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ABSTRACT Objective This study investigates the role of Sialic acid-binding Immunoglobulin-Like Lectin-9 (SIGLEC9), a novel immune checkpoint, in Cervical Cancer (CC) and its interaction with immune cells in the tumor microenvironment. Methods SIGLEC9 expression in CC was analyzed using the TNM plot, TCGA, and Human Protein Atlas databases, alongside its correlation with tumor stage. The relationship between SIGLEC9 expression and immune cell infiltration was explored using TCGA and TISIDB databases. Single-cell analysis focused on SIGLEC9 in macrophages. Protein interactions were assessed through the String, IntAct, BioGRID, and Mentha databases. MUC1 expression was validated via GEO and GEPIA databases. Immunohistochemical staining, western blot, immunofluorescence, and flow cytometry were used for verification. The prognostic significance of SIGLEC9 and SIGLEC9+ Tumor-Associated Macrophages (TAMs) was evaluated. Results SIGLEC9 was found to be significantly upregulated in CC, with higher levels correlating with poor prognosis. It was expressed in macrophages and T-cells, and elevated SIGLEC9+ TAMs were linked to reduced overall survival. Conclusion SIGLEC9 plays a crucial role in the progression and prognosis of cervical cancer through its interaction with TAMs and T-cells. These findings highlight SIGLEC9 as a potential target for new immunotherapies in CC.

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ABSTRACT Introduction Over 90% of Head and Neck Cancers are Squamous Cell Carcinoma (HNSCC). HNSCC patients with no evidence of disease after treatment completion usually present a high frequency of late treatment-related toxicities. Here, we aimed to evaluate the prevalence of cachexia among head and neck squamous cell carcinoma patients treated with cisplatin-based chemoradiation with curative intent and presenting no evidence of disease. We hypothesize that even patients post long-term follow-up and curative-intention treatment present a high frequency of cancer cachexia. Materials and methods This cross-sectional observational study included 120 patients with HNSCC who had previously received definitive or adjuvant chemoradiation. Eligible patients were in regular follow-up for at least 2-years, with no evidence of disease. We assessed clinical characteristics, body composition, muscle strength, nutritional status, and blood tests. The primary outcome was the prevalence of cachexia, and the secondary outcome was an association between cachexia and self-reported dysphagia. Results Using two different diagnostic criteria (Fearon and Evans criteria), we found that 20.7% and 8.6% of patients presented cancer cachexia after more than two years of follow-up after curative chemoradiation treatment. As expected, cachectic patients presented lower mid-arm muscle circumference, with dysphagia in 73%. In addition, in cachectic patients diagnosed according to Evans's cancer cachexia criteria, we found lower muscle strength levels. There is no association between dysphagia and cancer cachexia, regardless of the diagnostic criteria. Conclusion In long-term follow-up, head and neck squamous cell carcinoma patients with no evidence of disease frequently present with cachexia after curative chemoradiation.

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ABSTRACT Objective Arteriovenous Fistula (AVF) is the preferred vascular access for patients with Chronic Kidney Disease Stage G5 (CKDG5). Normal AVF function is an important prerequisite for hemodialysis, and there are few reports of studies predicting the factors affecting dysfunctional AVF. The aim of this study was to investigate the expression of Chitosanase-3-Like protein-1 (CHI3L1) in AVFs from patients with end-stage renal disease and to analyze the potential mechanism of its role in AVF dysfunction. Methods CKDG5 patients who underwent AVF surgery at our institution from January 2020 to September 2023 were prospectively collected. The general clinical data and laboratory data were collected in detail, and the occurrence of postoperative dysfunctional AVF was recorded. Then, the optimal diagnostic threshold of serum CHI3L1 was observed by the Receiver Operating Characteristic (ROC) curve. Kaplan-Meier survival curve and Log-rank test were used for survival analysis. Multi-factor backward logic analysis was used to screen baseline clinical factors and construct prediction Model 1. Subsequently, serum CHI3L1 was combined with baseline clinical factors to construct Prediction Model 2. The predictive value of the two models was evaluated by the ROC curve and the Area Under the Curve (AUC). Results A total of 152 CKDG5 patients who underwent AVF surgery were continuously included. They were divided into a normal AVF group (n = 64) and a dysfunctional AVF group (n = 88). Gender, age, body mass index, primary disease, diameter of cephalic vein, diameter of radial artery, follow-up time, and levels of Ca, K, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, white blood cell count, platelets, fasting blood glucose, and hemoglobin in both groups were not statistically significant between the two groups (p > 0.05). Systolic blood pressure, diastolic blood pressure, parathyroid hormone, serum albumin, and CHI3L1 were increased, whereas serum phosphorus level was decreased in CKDG5 patients with dysfunctional AVF (p < 0.05). The AUC of serum CHI3L1 was 0.797 (95% CI 0.728‒0.866, p < 0.001), the optimal cut-off value was 148.0 ng/mL, the sensitivity was 62.5%, and the specificity was 84.38%. The primary fluency rate in the high serum CHI3L1 level group was significantly lower than that in the low serum CHI3L1 level group (p < 0.001). Multifactorial logistic regression analysis showed that elevated serum CHI3L1 was an independent risk factor for postoperative dysfunctional AVF. The predictive value of the CHI3L1-containing predictive Model 2 was higher, with a net benefit at threshold probabilities of 0.2‒0.9 for its clinical decision curve. Conclusion This study proposes a risk prediction model of serum CHI3L1 combined with clinical risk factors, which can be utilized to make a preliminary prediction of the risk of dysfunctional AVF more easily, and thereafter to identify and intervene in high-risk patients early.

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ABSTRACT Objective To evaluate and monitor, through electrophysiological assessment of hearing, the integrity of the peripheral and central auditory pathways in infants with Peri-intraventricular hemorrhage and/or Periventricular Leukomalacia (PIVH/PVL) who stayed in a Neonatal Intensive Care Unit (NICU), aiming to verify the occurrence of possible neural dysfunctions in this system. Material and methods This prospective longitudinal study evaluated preterm Newborns (NBs) and infants at the time of hospital discharge and after 3- and 6-months. The Study Group (SG) had 12 females and 11 males, with gestational age between 25- and 33-weeks, and a mean gestational age of 29.82-weeks at birth. The Control Group (CG) had 26 healthy NBs, distributed in 13 females and 13 males, with gestational age between 27- and 33-weeks and a mean of 30.67-weeks of gestational age at birth. All participants underwent Auditory Brainstem Response (ABR) and Cortical Auditory Evoked Potentials (CAEP) P1, N1, P2, at the time of hospital discharge, and 3- and 6-months after discharge. Each group’s results were compared using statistical tests. Results Evolutionary study of mean ABR and CAEP latencies in infants in the study and control group showed a similar pattern over the six months after hospital discharge. Conclusion The comparison of brainstem and cortical potentials showed that auditory function is symmetrical in the peripheral and central portions of the auditory pathway in both groups. The maturation of the ABR and CAEP waves in both groups developed in a very similar way over the six months after hospital discharge.

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ABSTRACT Objective Evaluate the prognostic of the sarcomatous component (homologous vs heterologous). Methods This retrospective study evaluated patients with FIGO I‒IVA Uterine Carcinosarcoma (UCS) treated at a single cancer center. The endpoints were Overall Survival (OS) and Disease-Free Survival (DFS) according to the sarcomatous component. The Kaplan-Meier was used for survival analyses. Hazard Ratio (HR) and 95% Confidence Interval (95% CI) were calculated using Cox regression. Results 61 patients with localized/locally advanced disease (34 homologous vs. 27 heterologous) were included. The most common pathological subtype was Rhabdomyosarcoma (60%) in the heterologous and endometrial stromal sarcoma (95%) in the homologous group. All patients underwent surgery. Adjuvant Chemotherapy (CT) was indicated for approximately 70%. A difference was observed between patients who did not complete adjuvant CT: 32.0% vs. 57.9% in homologous and heterologous groups, respectively (p = 0.03). The main reason for this was recurrence during treatment. Comparing homologous vs. heterologous group, median DFS was 143.2 months vs. 18.0 months (HR = 3.72, 95% CI 1.73‒8.02; p = 0.001) and median OS was 143.2 months vs. 34.4 months (HR = 2.79, 95% CI 1.27‒6.13; p = 0.001), respectively. Heterologous subtype (HR = 4.34, 95% CI 1.59‒11.85, p = 0.004) and FIGO stage III (HR = 3.33, 95% CI 1.18–9.39, p = 0.023) were associated with inferior DFS and OS, while completing adjuvant CT (HR = 0.22, 95% CI 0.07‒0.69, p = 0.009) was associated with superior outcomes. Conclusions The sarcomatous component has a relevant prognostic impact in localized/locally advanced UCS. The heterologous component was associated with a worse DFS and OS. Other negative prognostic factors were FIGO stage III and not completing adjuvant CT.

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ABSTRACT Objective Population-specific Cephalic Index (CI) classifications are lacking for Malaysian subadults. This study aimed to develop a new CI classification and determine the prevalence of deformational brachycephaly using Computed Tomography (CT) images. Methods A total of 520 CT images from subadults aged 0- to 20-years were included in the study. Two cranial measurements were obtained: the maximum Cephalic Length (CL) and the maximum Cephalic Width (CW), derived from axial CT images. The CI was subsequently calculated using the formula: CW/CL × 100. In addition, a simple linear regression analysis was performed to evaluate the relationship between CI and age. Results The modified CI ranges for the Malaysian subadult population were defined as follows: dolichocephalic ≤ 78.8, mesocephalic 78.9–89.0, brachycephalic 89.1–94.0, and hyperbrachycephalic ≥ 94.1. The predictive equation derived was y = 87.08–0.47x +0.01×2 (y = CI and x = Age in years). A significant negative correlation was found between age and CI (r = -0.101, p < 0.001), with the index decreasing by approximately 0.026 per year. This indicates a natural trend towards a less brachycephalic head shape with maturation. Conclusion This new, population-specific classification provides an essential reference tool for clinicians and researchers to accurately detect, manage, and treat cranial deformities in Malaysian subadults, with significant applications in pediatrics, anthropology, and forensic medicine.

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ABSTRACT Objective To assess whether electrocardiographic markers of Global Electrical Heterogeneity (GEH) improve the identification of patients requiring tertiary care, either alone or combined with an explainable machine learning model, compared with standard ECG features and clinical risk factors in a real-world tertiary cardiology population. Methods Patients were forwarded to a specific evaluation in a cardiology-specialized hospital performed an ECG and data collection. A series of follow-up attendances occurred in periods of 6-months, 12-months and 15-months to check for cardiovascular-related events (mortality or new nonfatal cardiovascular events (Stroke, MI, PCI, CS), as identified during 1-year phone follow-ups. The first attendance ECG was measured by a specialist and processed in order to obtain the Global Electric Heterogeneity (GEH) using the Kors Matriz. The ECG measurements, GEH parameters, and risk factors were combined for training multiple instances of XGBoost decision tree models. Each instance was optimized for the AUCPR, and the instance with the highest AUC was chosen as representative of the model. The importance of each parameter for the winner tree model was compared to better understand the improvement from using GEH parameters. Results GEH parameters were statistically significant in this population (p < 0.001), particularly the QRST angle and SVG magnitude. The combined model integrating GEH, standard ECG features, and clinical risk factors achieved the best performance, with a sensitivity of 94.1 %, specificity of 30.8 %, AUC of 67.6 %, and F2 score of 0.62. SVG feature importance and SHAP analyses were consistent with the statistical findings, indicating that the model's decision patterns align with clinically relevant information and reinforce the role of GEH features. The modeling approach was carefully designed to prevent overfitting, ensure generalizability, and facilitate implementation through its decision tree architecture. Conclusion VCG-derived features may improve the identification of patients requiring tertiary care, either alone or integrated into an explainable and robust machine learning model trained on real-world data. Its clinical value will ultimately depend on prospective validation and seamless integration within existing care pathways.

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ABSTRACT Objective To evaluate the risk factors associated with the presence of Painful Subcutaneous Edema (PSE) in children and adolescents with Immunoglobulin A Vasculitis (IgAV). Methods A multicenter study evaluated 686 patients (≤ 18 years-old) at first 3-months after diagnosis. IgAV patients with PSE were compared to those without PSE. Results PSE was found in 219/686 (31.9 %). The sites were lower limbs 192/215 (89.3 %) and upper limbs 85/215 (39.5 %). Persistent PSE (≥ 6-weeks of duration) was found in 4/215 (2 %), and recurrent PSE was found in 7/217 (3 %). The median age at diagnosis was significantly lower in PSE patients compared to those without [5.0 (3.4) vs. 6.3 (4.3) years, p = 0.001]. Increased CRP was significantly higher in IgAV with PSE compared to without PSE (52.6 % vs. 41.1 %, p = 0.03), likewise thrombocytosis (> 400.000 mm3) (43.8 % vs. 35.1 %, p = 0.04). Although associated with higher inflammatory markers, PSE was not linked to more severe outcomes. Logistic regression demonstrated that age at diagnosis was inversely associated with PSE (OR = 0.986; 95 % CI 0.981‒0.992; p < 0.001). Conclusion PSE occurred in approximately one-third-of IgAV patients at disease onset and was diagnosed predominantly at an early age, with a more inflammatory presentation at onset. However, in spite of the higher levels of inflammatory markers, PSE was not linked to more severe outcomes.

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ABSTRACT Background Fibromyalgia (FM) is a chronic, non-inflammatory syndrome characterized by widespread body pain, fatigue, sleep disturbances, impaired cognitive function and anxiety. Peripheral and central sensitization are thought to cause chronic pain in this disorder, which impairs quality of life. No specific laboratory test, radiographic method, or biomarker has been identified for diagnosis. As its physiopathology is not fully understood, no specific treatment has been identified. At this stage, studies are needed to facilitate diagnosis and guide treatment. Methods Eighty-nine women with FM and 36 healthy controls were enrolled in this cross-sectional, case-controlled, single-centre study. FM-related measurements (number of tender points, myalgic score, pain Visual Analogue Scale [VAS]) were recorded. All participants underwent an analysis of trapezius muscle thickness and elasticity. Skin and subcutaneous tissue thickness, and hypodermis thickness were measured by using B-mode Ultrasonography (USG) and tension (compression) Sonoelastography (SEL). Results Skin thickness was lower in FM patients than in healthy controls (p < 0.01). Both trapezius muscle thickness and elastography scores were higher in the FM group compared to controls (p < 0.05 and p < 0.001, respectively). A significant correlation was found between VAS score and elastography scores (r = 0.661, p < 0.001); however, there was no significant correlation between VAS score and trapezius or skin thickness. Conclusion Patients with FM have lower skin thickness and higher trapezius muscle thickness and elastography scores than healthy controls. The thinner skin thickness in FM compared to controls may represent a potentially important factor in the pathophysiological mechanism of peripheral sensitization.

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ABSTRACT Objective: Given the current lack of diagnostic markers with high sensitivity and specificity, the diagnosis and treatment of Recurrent Spontaneous Abortion (RSA) have always presented significant difficulties. To analyze the relationship between hsa_circ_0005075 and RSA and conduct a preliminary exploration of its mechanism. Methods: Fifty-eight RSA patients admitted to the studied hospital from March 2022 to January 2024 (research group) and 52 normal pregnant women (control group) were selected as the research subjects. Peripheral blood hsa_circ_0005075 expression was detected to determine the difference between the two groups. In addition, the evaluation value of hsa_circ_0005075 for RSA, miscarriage, and adverse pregnancy outcomes was analyzed through Receiver Operating Characteristic (ROC) curves. Furthermore, human placental Trophoblast Cells (TBCs) HTR8/SVneowere purchased and transfected with abnormal hsa_circ_0005075 expression sequences to identify changes in HTR8/SVneoproliferation, invasion, and apoptosis, and alterations in Wnt/β-catenin pathway expression. Results: hsa_circ_0005075 was higher in the research group than in the control group (4.00 ± 0.93 vs. 2.78 ± 0.94, p < 0.05). ROC curves indicated the excellent diagnostic effect of hsa_circ_0005075 on the occurrence of RSA (Area Under Curve [AUC = 0.820]), miscarriage (AUC = 0.744), and adverse pregnancy outcomes (AUC = 0.726). In vitro, increasing hsa_circ_0005075 inhibited HTR8/SVneogrowth, decreased cell clones and cell invasion number, increased apoptosis, shortened the G0/G1 phase, and activated the Wnt/β-catenin pathway; the opposite results were observed after silencing hsa_circ_0005075 expression. Mechanistically, gain and loss-offunction experiments revealed that hsa_circ_0005075 acts as a negative regulator of trophoblast proliferation, invasion, and cell cycle progression, and induces apoptosis by suppressing the Wnt/β-catenin signaling pathway. Conclusions: The present findings identify hsa_circ_0005075 as a promising circulating biomarker for RSA and demonstrate that it contributes to RSA pathogenesis by impairing trophoblast function through inhibition of the Wnt/β-catenin pathway, suggesting its potential as a therapeutic target.

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Abstract Context The rapid aging of the Brazilian population in recent decades has strained the healthcare system. A lack of chronic patient absorption in primary care has led to overloaded emergency departments, which handle preventable decompensation and care that could be managed at home. Objectives To identify the demand for patients eligible for Palliative Care (PC), among patients in four Emergency Departments (ED) in a metropolitan region in Brazil. Methods This observational, cross-sectional study involved four emergency departments: two public university hospitals and two private hospitals. Patient data on gender, age, visit reasons, and comorbidities were collected, along with the Supportive and Palliative Care Indicators Tool (SPCIT-BR™), Palliative Performance Scale (PPS) assessments, and opioid use information. Results Of the 270 patients, 101 (37.4 %) were eligible for PC. Of these eligible patients, the median age was 70-years, 54.5 % were male and public EDs had 9-fold higher odds of palliative care eligibility. Age, dyspnea, and fever predicted palliative care eligibility. Conclusions The present findings demonstrate the necessity of further implementation of palliative care programs, particularly in the public health system. Such integration could lead to a decrease in unnecessary ED visits and home-based care that reflects patient wishes.

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Abstract Background A diagnostic nomogram for predicting tubulointerstitial lesions (T1/2) in IgA Nephropathy (IgAN), developed in Guangzhou (GZ) using estimated Glomerular Filtration Rate (eGFR) and Urinary Protein Excretion (UPE), demonstrated high accuracy (AUC = 0.92) but lacked external validation. Methods The authors externally validated the nomogram in an independent cohort from Kunming (KM, n = 387; median altitude: 1,891 m), including a high-altitude subgroup (> 2,000 m, n = 155). Model performance was evaluated using Receiver Operating Characteristic (ROC) curves, calibration plots, and Decision Curve Analysis (DCA). Both creatinine-based eGFR (eGFRcr) and Creatinine-Cystatin C-based eGFR (eGFRcr-cys), each combined with UPE, were assessed. Results The nomogram achieved nearly identical AUCs of 0.80 in the overall KM cohort for both eGFRcr-UPE (95% CI: 0.75-0.85) and eGFRcr-cys-UPE (95% CI: 0.74-0.85), demonstrating strong generalizability across eGFR formulas. In the high-altitude subgroup, performance significantly improved (AUC = 0.89; 95% CI: 0.83-0.95) for both models. Conclusion External validation demonstrates that the nomogram combining eGFR and UPE is feasible for non-invasive prediction of T1/2 lesions, with comparable performance between eGFRcr and eGFRcr-cys. The improved accuracy observed at high altitude suggests altitude-related influences that merit further study. Prospective studies are needed to determine its prognostic value for clinical outcomes such as CKD progression and treatment response.

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Abstract Objectives Interleukin-8 (IL-8) is a key cytokine regulating immunity and inflammation, and its genetic polymorphisms have been increasingly linked to cancer susceptibility. However, findings on the role of specific IL-8 polymorphisms across different cancers remain inconsistent, necessitating a comprehensive meta-analysis. Methods The authors systematically searched Embase, PubMed, Chinese databases, Google Scholar, and Web of Science up to June 25, 2023. A total of 104 case-control studies (26,029 cases and 31,577 controls) were included in a high-powered meta-analysis. Summary Odds Ratios (ORs) with 95% Confidence Intervals (95% CIs) were calculated using Stata. Additionally, the authors performed an ELISA-based validation study to measure serum IL-8 levels in Prostate Cancer (PCa) patients grouped by genotype. Results The +2767 polymorphism was associated with a significant reduction in overall cancer risk. The +781 polymorphism increased cancer risk specifically in Caucasian populations. In contrast, the -251 polymorphism demonstrated a strong pan-cancer risk association, particularly in Mixed/Asian ethnicities, gastric cancer, lung cancer, and hospital-based studies. Mechanistically, patients with the -251 AA/AC genotypes had elevated serum IL-8 levels, which were linked to more aggressive PCa pathogenesis. Conclusion This pioneering meta-analysis identifies the IL-8 -251 polymorphism as a high-risk biomarker and +2767 as a protective variant. By functionally validating that the -251 risk allele promotes PCa progression via IL-8 overexpression, the present study establishes IL-8 genotyping as a potential tool for ethnic-specific risk stratification and prognostic prediction, with broad implications for precision oncology.

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Abstract Objective To explore the associations of Physical Activity (PA) and sleep with functional disability among older adults. Method A total of 1927 participants were enrolled from the China Health and Retirement Longitudinal Study (CHARLS) between 2015 and 2020. Activities of Daily Living (ADL) were used to assess functional status. Sleep consisted of nighttime sleep (healthy sleep, or unhealthy sleep) and daytime nap sleeping (extended, moderate, short, or none), and PA was classified as sufficient or insufficient. Effects of sleep and PA on ADL Disability (ADLD) among the elderly were examined using logistic regression analysis, with Odds Ratios (ORs) and 95% Confidence Intervals (95% CIs) calculated. Results After a follow-up of 5-years, healthy nighttime sleep was linked to a decreased odds of ADLD (OR = 0.77, 95% CI: 0.60‒0.98). In participants with sufficient PA, healthy nighttime sleep was linked to the odds of ADLD (OR = 0.68, 95% CI: 0.52‒0.90). No multiplicative interaction of PA and nighttime sleeping was found. Moreover, the association between healthy nighttime sleep and decreased risk of ADLD was consistent in females (OR = 0.64, 95% CI: 0.45‒0.91) and those with complications (OR = 0.63, 95%CI: 0.46‒0.87). Conclusion Healthy nighttime sleep may be beneficial for preventing ADLD in older people. The benefits of sufficient PA with healthy sleep on reducing the risk of ADLD remain uncertain.

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Abstract Objectives The authors hypothesized that establishing a one-stop clinic for the management of Developmental Dysplasia of the Hip (DDH) at our institution would enhance screening procedures, referral processes, patient compliance, early diagnosis, and timely treatment for this condition. To inform clinical practice, the authors conducted a collaborative development of flowcharts for evidence-based patient care protocols, based on the Graf method and patient journey optimization. Methods A weekly DDH clinic was established in a tertiary/quaternary public teaching hospital in Brazil, integrating pediatrics, radiology, and orthopedics. Flowcharts were collaboratively designed during ten interdisciplinary meetings. As a pilot study, the authors included an initial cohort involved in an observational retrospective study during the period from October 2023 to December 2024. Results A novel system of grouping Graf types and subtypes was presented, accompanied by a treatment algorithm and phased therapeutic approach, based on the underlying hip pathology and immediate therapeutic requirements to promote hip centralization and acetabular development. A total of 98 infants were examined at the clinic during the specified period, with 22 receiving non-surgical treatment utilizing the Pavlik harness. Conclusion The establishment of a one-stop DDH clinic demonstrated a successful interdisciplinary approach, contributing to early diagnosis and effective treatment of DDH. The collaborative development of flowcharts facilitated the standardization of patient management protocols. Continued refinement of screening procedures and data collection methods is necessary to optimize care and inform future research on DDH management.

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Abstract Introduction Obinutuzumab, a type II anti‐CD20 monoclonal antibody used for treating B-cell hematologic malignancies, improves outcomes and prolongs progression-free survival. However, its use is linked to adverse reactions that vary by gender. This study aims to assess adverse event signals related to Obinutuzumab using FAERS data, thereby providing safety insights for clinical application. Methods FAERS data from Q4 2013 to Q4 2024 were processed in R with duplicate reports removed. Drug names were standardized using Medex UIMA 1.3.8, and adverse events were classified according to MedDRA v26.1. The disproportionality analysis was conducted using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods to evaluate adverse reaction signals related to Obinutuzumab. A stratified analysis by gender was performed to enhance the accuracy of data interpretation. Results A total of 14,450,774 case reports, 70,790,109 drug cases, and 41,401,915 REAC records were collected. The results showed that although the proportion of male patients in overall adverse event reports was higher, female patients exhibited significantly higher ROR and PRR in systemic adverse reactions such as blood and lymphatic system disorders, suggesting that women may face greater risks. At the Preferred Term (PT) level, strong signals were observed for common adverse events such as myelosuppression and febrile neutropenia. Additionally, abnormal signals for pure red cell aplasia and enteroviral meningitis were prominent only in females. Conclusion Obinutuzumab is associated with significant adverse event risks, notably higher in females, highlighting the need for enhanced safety monitoring and further exploration of gender-specific mechanisms in adverse event development.

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Abstract Aim To characterize the epidemiology, clinicopathological features, and renal outcomes in patients with Monoclonal Gammopathy of Renal Significance (MGRS). Methods The authors conducted a retrospective analysis of all renal biopsy-confirmed MGRS cases diagnosed between 2010‒2020, with histopathological review by two independent pathologists. Post-hoc power analysis confirmed adequate statistical power (92 %). Results Among 124 histologically confirmed MGRS cases (median age 64.0-years, IQR 52.5‒68.0), renal amyloidosis predominated (75.8 %), followed by monoclonal immunoglobulin deposition disease (MIDD, 10.5 %), cryoglobulinemic GN (4.8 %), proliferative GN with monoclonal Ig deposits (PGNMID, 2.4 %), light chain proximal tubulopathy (3.2 %), and C3 glomerulopathy with monoclonal gammopathy (1.6 %). Amyloidosis patients primarily presented with nephrotic syndrome (77.7 %), while fewer exhibited acute kidney injury (3.2 %), chronic kidney disease (16.1 %), or ESRD (6.7 %). Compared to other MGRS subtypes, amyloidosis patients demonstrated significantly lower anemia rates (p < 0.001), higher LDH (p = 0.035), preserved eGFR (p < 0.001), greater proteinuria (p = 0.037), and hypoalbuminemia (p < 0.001). The renal response rates were 26.1 % (Amyloidosis-Associated MGRS, MGRS-A) versus 33.3 % (Non-Amyloidosis MGRS, MGRS-NA), while hematologic responses were 8.7 % versus 0 %, respectively. Both hematologic (p = 0.007) and renal responses (p = 0.009) correlated with improved survival. MGRS-A showed inferior renal survival (p = 0.05). Multivariate analysis identified hypotension (p = 0.005), elevated creatinine (p = 0.002), and cardiac involvement (p = 0.022) as independent predictors of ESKD, while age (p < 0.001) and cardiac involvement (p < 0.001) predicted mortality. Conclusion MGRS represents a clinically significant cause of kidney injury in monoclonal gammopathy patients, with amyloidosis being the predominant etiology. MGRS-A portends a worse prognosis than MGRS-NA. Therapeutic responses in both hematologic and renal parameters predict survival benefits. Age and cardiac involvement emerge as key prognostic markers for both renal and patient survival.

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Abstract Context Down Syndrome (DS) is the main genetic cause of Intellectual Disability (ID) and is characterized by the presence of several medical comorbidities. Among these, Obstructive Sleep Apnea (OSA) stands out, with a prevalence much higher than that of the general population. The clinical impact of OSA in subjects without DS described in the literature includes increased cardiovascular, metabolic and neurocognitive risk. However, among the adult population with DS, these associations are poorly described. Objectives To evaluate the presence and characterize OSA in adults with DS and its association with body composition, metabolic profile, functional and cognitive performance. Methods This cross-sectional study included 34 persons with DS aged 18 years or over. The measurements were: anthropometry, complete Polysomnography in the Sleep laboratory (PSG), neuropsychological assessment using the Abbreviated Wechsler Intelligence Scale and NEUPSILIN Brief Assessment Instrument, biochemical assessments, and functionality scales (Barthel and Lawton). There were 30 representative PSG. Subjects with and without OSA were compared regarding clinical, anthropometric, functional (n = 30), and cognitive (n = 20) variables. Sleep changes were correlated with the variables under study. Results The frequency of OSA (apnea-hypopnea index ≥ 5 events/h) was 63 %. As compared to no OSA, OSA was associated with male sex (p = 0.001), greater cervical circumference (34 vs. 40 cm, p < 0.001), greater deposition of abdominal fat (82 vs. 92 cm, p = 0.049), higher average levels systolic blood pressure (p = 0.03), higher frequency of altered fasting blood glucose or glycated hemoglobin equal to or greater than 5.7 % (p = 0.03) and low HDL cholesterol (p = 0.004). OSA was associated with worse performance in episodic and semantic verbal memory (p = 0.02). Conclusion Adults with DS have a high frequency of OSA, which may be related to metabolic profile and worse memory performance.

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Abstract Objective Advanced prostate cancer (PCa) remains a leading cause of cancer-related mortality in men. While Prostate-Specific Antigen (PSA)-based early screening has demonstrated mortality reduction, its diagnostic accuracy remains limited. This study aimed to evaluate the potential of serum transducin (beta)-like-1 X-linked Receptor-1 (TBL1XR1) and Microfibrillar-Associated Protein-5 (MFAP5) as novel diagnostic biomarkers for supplementing PSA-based detection. Method Through bioinformatic analysis, TBL1XR1 and MFAP5 were identified as candidate markers, with their expression validated using reverse transcription-quantitative polymerase chain reaction. Diagnostic performance was assessed via Receiver Operating Characteristic (ROC) curve analysis, while Pearson correlation coefficients evaluated biomarker associations. Results Serum TBL1XR1 and MFAP5 levels were elevated in PCa patients, both exhibiting positive correlations with PSA concentrations. Individual AUC values reached 0.8197 (TBL1XR1) and 0.8139 (MFAP5). The free PSA (fPSA)/total PSA (tPSA) ratio showed decreased values in PCa cases, demonstrating superior diagnostic utility compared to total PSA alone. A combined panel of TBL1XR1, MFAP5, and PSA achieved an AUC of 0.939 with a Youden index of 0.756. Conclusions TBL1XR1 and MFAP5 have the potential for PCa diagnosis. The synergistic application of TBL1XR1, MFAP5, and PSA significantly enhances diagnostic accuracy. These findings indicate that serum TBL1XR1 and MFAP5 represent promising diagnostic markers for PCa. The combination of serum TBL1XR1 and MFAP5 with PSA for diagnosis may potentially reduce unnecessary biopsies in clinical practice.

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Abstract Objective This study aimed to explore the efficacy and safety of lenvatinib and sorafenib as first-line treatments for hepatocellular carcinoma. Method The authors searched PubMed, Web of Science, Cochrane, CNKI, Wanfang, and other databases and compared the clinical efficacy of lenvatinib and sorafenib as first-line treatments for hepatocellular carcinoma. Two participants screened the literature, collated the data, and evaluated the literature according to the inclusion and exclusion criteria. RevMan 5.4 software was used for meta-analysis of the included studies. Results Ten studies were included in the meta-analysis. The results of the meta-analysis showed that, in terms of efficacy, compared with sorafenib, lenvatinib prolongs PFS in patients with hepatocellular carcinoma (HR = 85.50, 95 % CI: 38.53‒189.73, p < 0.00001) and OS (HR = 36.73, 95 % CI: 20.28-66.52, p < 0.00001), and the differences were statistically significant. In terms of safety, the risk of toxicities in the lenvatinib group at any level of gastrointestinal toxicities, metabolism/nutrition toxicities, hematological toxicities, Renal/Urinary, Vascular toxicities, and endocrine toxicities was significantly higher in the lenvatinib group than in the sorafenib group. The risks of metabolism/nutrition toxicities, renal/urinary toxicities, and vascular toxicities above grade III were significantly higher than those in the sorafenib group. The Skin/Subcutaneous Tissue toxicities of any grade and above were significantly lower than those in the sorafenib group. Conclusions As a first-line treatment for hepatocellular carcinoma, lenvatinib can prolong PFS and OS and improve the clinical benefit rate and quality of life of patients. The increased risk of specific adverse events with lenvatinib requires diligent clinical oversight.

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Abstract Introduction Preimplantation Genetic Testing (PGT-A) has been increasingly used in IVF to improve embryo selection. However, its clinical utility in patients with a good prognosis remains debated. There is a lack of robust scientific evidence about the benefits of preimplantation genetic testing Next-Generation Sequencing (NGS) on the clinical pregnancy and live birth rates in good-prognosis IVF patients undergoing elective Single Embryo Transfer (eSET) testing. Objective To compare the clinical pregnancy rate after IVF treatment in patients with a good prognosis between groups that receive the transfer of a single embryo with or without pre-implantation genetic embryo analysis. Methods This work was a prospective randomized clinical study that evaluated 206 patients to compare the clinical pregnancy rate after the first elective transfer of an embryo, associated or not with pre-implantation genetic embryo analysis using Next-Generation Sequencing (NGS). Patients were randomized into groups: SET group ‒ patients undergoing the transfer of a single embryo (eSET, elective Single Embryo Transfer) without embryo genetic analysis (SET group, n = 103); and NGS + SET group ‒ patients undergoing eSET with embryo genetic analysis (NGS + SET group, n = 103). Results The clinical pregnancy rate after the first transfer was similar between the two groups (SET: 76.7 % and NGS + SET: 79.6 %; p = 0.613). There was also no statistical difference in live birth rates or abortion rates between the groups analyzed. Conclusion This clinical trial suggests no significant improvement in the embryo genetic analysis in IVF treatments for infertile couples with a good prognosis

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Abstract Background Knee osteoarthritis is a degenerative joint condition characterized by the progressive degeneration of knee cartilage. Acupuncture therapy, as an alternative treatment, has shown significant efficacy in managing joint disorders. In the current study, the effects of four acupuncture strategies in treating knee osteoarthritis were compared and analyzed. Methods 123 cases diagnosed with knee osteoarthritis were included in the current study at the First People's Hospital of Jiujiang City from May 2022 to May 2023. The patients received different acupuncture strategies, including traditional acupuncture, electroacupuncture, warm acupuncture, and fire acupuncture. Then the information regarding the treatment effects on physical function and inflammatory cytokines was collected and analyzed. Results The data showed that all four treatment strategies could improve the life quality of the patients, but the effects of electroacupuncture were stronger. The effects of warm acupuncture and fire acupuncture were weaker than electroacupuncture, but were stronger than traditional acupuncture. Regarding the effects on knee physical function and inflammatory indicators, electroacupuncture also showed better treatment effects than the other three treatments. The overall efficacy in treating knee osteoarthritis was comparable between different treating strategies, even though the effects of different acupuncture strategies on detailed items might be different. Conclusions Collectively, the current study demonstrated that all the acupuncture strategies could improve the physical function and reduce pain in the knee, thereby improving the life quality of patients, with electroacupuncture showing the strongest effects on certain detecting items.

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Abstract Purpose Sepsis remains a major cause of mortality in ICU patients, requiring accurate prognostic tools for optimal management. This study aimed to develop and validate an interpretable machine learning-based nomogram for predicting in-hospital mortality in sepsis patients to guide clinical decision-making. Methods This retrospective cohort study included 407 adult sepsis patients from ICU admissions between January 2019 and December 2024. Patients were randomly divided into training (n = 284) and validation (n = 123) cohorts. A LASSO-based multivariate logistic regression was applied to construct a predictive nomogram. Results Seven independent predictors emerged for in-hospital mortality: age, abdominal infection, vasopressor requirement, WBC, BNP, APACHE II score, and mechanical ventilation support. The nomogram showed strong discrimination with an AUC of 0.900 in the training cohort and 0.796 in the validation cohort. Calibration curves, decision curve analysis, and SHAP interpretation confirmed good model performance and clinical utility. Conclusions The novel machine learning-based nomogram provides a practical, interpretable risk assessment tool for early mortality prediction, potentially improving patient outcomes through enhanced clinical understanding and timely interventions in critically ill sepsis patients.

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Abstract Background Venous Thromboembolism (VTE) is a major global health concern, with Vena Cava Filters (VCFs) serving as an alternative to anticoagulation in high-risk patients. Brazil’s VCF trends remain understudied, particularly in its dual public-private healthcare system. This database study allows a broad overview of the Brazilian healthcare landscape. Methods This cross-sectional nationwide analysis used Brazilian public (SUS/TabNet) and private (ANS/D-TISS) healthcare databases (2015-2023) to assess VCF placement rates, regional disparities, and in-hospital mortality. Data included 21,630 procedures, analyzed via generalized linear models (Gamma/Poisson distributions). Results The private system performed 57% of VCFs (12,323) despite covering only 25% of the population, with a 4.25-fold higher procedure rate per capita than the public system (29.45 vs. 6.42 per-million). Women accounted for 57.8% of recipients. The Southeast region dominated (70% private, 40.5% public), while the North and Midwest had the lowest rates. Mortality rates were comparable (public 6.7% vs. private 7.4%, p = 0.066), peaking during COVID-19. Procedure volumes rose 140% over 9-years, contrasting with declining U.S. trends post-FDA restrictions. Conclusions Brazil’s VCF use reflects systemic disparities, with private-system overrepresentation and regional gaps. This study enables unprecedented insights into large-scale VCF implementation across diverse healthcare subsystems.

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Abstract Background Neurofibromatosis type 1 is a systemic genetic disease with manifestations that include neurocognitive alterations. The disease's characteristics influence various areas of the lives of affected individuals, regardless of their place of residence. Objectives This study compares the experiences of a small group of patients with type 1 neurofibromatosis in two public hospitals in Brazil and Portugal. Methods This is an exploratory, cross-sectional, and descriptive study. Patients of legal age or those responsible for underage patients were included in a health service in the Clinical Hospital of the State University of Campinas in Brazil and the Clinical Academic Center of Coimbra in Portugal. They answered an online form about quality of life and access to health. Results 18 participants were included, 13 Brazilians and 5 Portuguese. Most were female and had a mean age at diagnosis of 8.2-years. The mean age of Brazilians was 9.1-years for the first consultation with a geneticist and 15.5-years among Portuguese. The average number of professionals accessed was 4.5 among Brazilians and 3.8 among Portuguese. Limitations Small sample size, restricted temporal aspect, convenience bias of participants with internet access, and self-declaration of data by participants. Conclusions Both Brazilians and Portuguese participants with neurofibromatosis type 1 presented similar difficulties regarding access to health. The differences found between the participants from both countries focus on access to medical geneticists and their health literacy. Expanding studies would help identify care priorities related to the specificities of NF1 that could improve the quality of life of affected individuals.

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Abstract Background This study examines the therapeutic effects of resveratrol, known for its antioxidant and anti-inflammatory properties, in mitigating the harmful effects of isoflurane, an inhalation anesthetic, on testicular tissues in mice. Methods Sixty adult male C57BL/6 mice were grouped into six categories: control (normal saline), isoflurane only (1.5% for 1-hour/day), low-dose Resveratrol (RSV, 50 mg/kg/day), high-dose RSV (100 mg/kg/day), isoflurane combined with low-dose RSV, and isoflurane combined with high-dose RSV. After 35-days, the mice were euthanized, and their testes were harvested for stereological analysis and the assessment of antioxidant and apoptotic markers. Results Exposure to isoflurane resulted in decreased seminiferous tubule volume and length, along with increased interstitial tissue volume of the testis. Co-treatment with resveratrol, especially at higher doses, mitigated these changes. Additionally, resveratrol modulated the expression of the apoptotic genes Bcl2l1, Bax, and Caspase-3, and enhanced the expression of antioxidant genes GPX1, Sod1, and catalase in mice that received isoflurane. Conclusions The findings suggest that resveratrol effectively counters isoflurane-induced damage in testicular structures and gene expression, enhancing tubular integrity and antioxidant defense. This indicates a potential therapeutic approach to protect against isoflurane-induced testicular toxicity.

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Abstract Objective This pilot study aimed to investigate the effects of a 12-week Zumba training program on Thyroid-Stimulating Hormone (TSH), Free Thyroxine (FT4), lipid profile, and anthropometric parameters in overweight and obese postmenopausal women. Methods Twenty-two women (aged 44‒60 years) were randomly assigned to a Zumba training group (ZG; n = 11) or a control group (CG; n = 11). The ZG participated in 60-min Zumba sessions three times per week for 12-weeks, while the CG maintained their usual lifestyle. Before and after the intervention, participants underwent assessments of body composition, blood pressure, and circulating levels of TSH, FT4, Total Cholesterol (TC), and Triglycerides (TG). Results Following the intervention, the ZG showed significant reductions in TSH (p = 0.001; Cohen’s d (d) = 0.90), TG levels (p = 0.043; d = 0.75), body fat percentage, body mass index, waist and hip circumference, and both systolic and diastolic blood pressure (all p < 0.05). No significant changes were observed for FT4 and TC levels. No notable changes were recorded in the CG. Conclusions The 12-week Zumba program can serve as a feasible and enjoyable strategy for promoting physical activity in overweight and obese postmenopausal women, leading to improvements in thyroid function, TG levels, body composition, and blood pressure. These preliminary findings support the potential of Zumba for enhancing cardiometabolic health during menopause, though larger, long-term trials are needed to confirm these effects and investigate their durability.

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Abstract Background The GALAD model integrates serological biomarkers (AFP, AFP-L3%, DCP) with demographic factors to estimate the presence of Hepatocellular Carcinoma (HCC). However, its applicability in Chinese populations with HBV-related HCC remains underexplored. This study validated the clinical utility of GALAD in this specific population. Methods A retrospective cohort study enrolled 217 HBV-related HCC patients, 210 patients with benign Liver disease without cirrhosis, 247 Cirrhosis patients, and 220 healthy controls. Serum levels of AFP, AFP-L3%, and DCP were measured. Receiver Operating Characteristic (ROC) curve analysis assessed diagnostic performance, and the Hosmer-Lemeshow test evaluated model calibration. Serum levels of AFP, AFP-L3%, and DCP were measured. Receiver Operating Characteristic (ROC) curve analysis assessed diagnostic performance, and the Hosmer-Lemeshow test evaluated model calibration. Results GALAD demonstrated superior diagnostic performance, with an Area Under the Curve (AUC) of 0.942. At an optimal cutoff of 1.89, sensitivity and specificity were 89.91 % and 81.51 %, respectively. The model showed excellent calibration (χ2 = 8.934, p > 0.05), confirming its reliability for Chinese HBV-related HCC patients. Conclusion The GALAD model outperforms individual biomarkers in diagnosing HBV-related HCC in the Chinese population, highlighting its potential utility in clinical practice. This cost-effective tool holds particular promise for the tertiary prevention of HBV-related HCC, especially in resource-limited settings.

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Abstract Background One-Lung Ventilation (OLV), though essential for thoracic surgery, triggers inflammation and oxidative stress that may lead to Acute Lung Injury (ALI). Remote Ischemic Preconditioning (RIPC) is a simple, non-invasive intervention that may activate protective pathways and reduce ischemia-reperfusion injury. This randomized controlled trial assessed whether limb RIPC attenuates OLV-induced lung injury during thoracoscopic lobectomy. Methods Fifty-four patients undergoing thoracoscopic lobectomy with OLV were randomized to the RIPC (n = 27) or Control (NC, n = 27) group. RIPC consisted of five cycles of 5-min ischemia and 5-min reperfusion using a lower limb tourniquet before OLV. Blood samples were collected at T0 (post-induction), T1 (30-min after OLV), T2 (90-min after OLV), and T3 (30-min after resumption two-lung ventilation). The primary endpoint was plasma CC16. Secondary endpoints included IL-6, MDA, arterial blood gases, Intraoperative Oxygenation Indices (OI, RI, A-aDO2, a/A), and hospital stay. Results Plasma CC16, IL-6, and MDA levels were significantly lower in the RIPC group from T1 to T3 (all p < 0.001). In contrast, oxygenation indices, blood gas parameters, and hospital stay did not differ significantly between groups (all p > 0.05). Conclusions Limb RIPC effectively reduced systemic markers of lung injury (CC16), inflammation and oxidative stress during OLV but not in short-term improvements in oxygenation or clinical recovery. These findings suggest that RIPC confers molecular protection, with potential functional benefits requiring longer follow-up or evaluation in high-risk populations. Larger multicenter trials are warranted.

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Abstract Background Temporomandibular Disorder (TMD) often causes chronic orofacial pain and functional limitations, with conventional treatments providing suboptimal results. Phytocannabinoids such as Δ9-Tetrahydrocannabinol (Δ9-THC) and Cannabidiol (CBD) have analgesic and anti-inflammatory properties, but evidence in TMD is scarce. Objective To evaluate the efficacy of Δ9-THC/CBD therapy in reducing pain and improving mandibular function in TMD patients. Methods Twenty adults with chronic myofascial pain (DC/TMD diagnosis) participated in a blinded, crossover, non-randomized study. Participants underwent two consecutive 90-day phases: placebo followed by Δ9-THC/CBD therapy (1:1 ratio, starting with a dose of 2 mg/day in the first week, gradually adjusting an increase of 2 mg/week until reaching 10 mg/day in the fifth week, sublingually), without washout. Outcomes included pain intensity (VAS), muscle sensitivity (algometry), mandibular function (mouth opening, protrusion, laterality) and pain sensitivity (allodynia/hyperalgesia). Data were analyzed using linear mixed models for repeated measures. Results Δ9-THC/CBD improved all outcomes versus baseline and post-placebo (p < 0.001; Cohen’s d > 0.8). Mouth opening increased from 45.9 mm to 49.9 mm; VAS pain decreased from 7.35 to 3.50. Functional pain dropped by ∼90%, with near elimination of allodynia and hyperalgesia. Placebo effects were minimal. Conclusion Δ9-THC/CBD therapy provided substantial analgesic and functional benefits in TMD patients, supporting its potential as a therapeutic alternative. Larger randomized studies are recommended to validate these findings and explore underlying mechanisms.

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Abstract Objective Whether Totally Laparoscopic Gastrectomy (TLG) is beneficial for patients with gastric cancer remains not fully understood. This study was to evaluate the advantages of Totally Laparoscopic Gastrectomy (TLG) for treating Gastric Cancer (GC). Methods From January 2019 to December 2021, 380 patients with gastric cancer were included into this study (190 per group). The outcomes of interest, including postoperative recovery, inflammation, and oncological results, were compared between the two groups. Results The patient baselines between the two groups were comparable. The TLG group had lower risks of wound infection (p = 0.02) and total complications (p = 0.03) compared to LAG. The TLG group exhibited significantly shorter operative time (median: 215 vs. 240 min, p < 0.001), less intraoperative blood loss (median: 50 vs. 100 mL, p < 0.001), shorter time to first flatus (median: 3 vs. 4 days, p < 0.001), and reduced length of postoperative hospital stay (p < 0.001). Furthermore, patients in the TLG group exhibited lower White Blood Cell (WBC) counts on POD 1 compared to patients in the LAG group (mean 11.74 vs. 12.75 × 10^9/L; p = 0.003). Multivariate logistic regression analysis revealed that TLG was an independent predictor of shorter postoperative hospitalization (OR (95% CI): 0.54 (0.30‒0.95), p = 0.03). Interestingly, the TLG group had more lymph nodes harvested than the LAG group (median (range): 23 (2‒88) vs. 23 (2‒88), p < 0.001). Conclusions This study demonstrates that TLG has a lower risk of complications and faster postoperative recovery, thus TLG is superior to LAG for the treatment of gastric cancer.

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Abstract Background and aim Accumulating evidence suggests maturity onset diabetes of the young (MODY) caused by GCK gene mutations (GCK-MODY) is often misdiagnosed as Gestational Diabetes Mellitus (GDM) in pregnant women. This study investigated the prevalence and diagnostic value of GCK gene mutations in Chinese GDM patients. Methods A retrospective analysis was conducted on 3394 pregnant women undergoing prenatal care or delivery at Beijing Jishuitan Hospital between April and December 2019. GDM was diagnosed in 474 women (14.0%) using the International Association of Diabetes and Pregnancy Study Groups (IADPSG, 2010) criteria via a 75 g Oral Glucose Tolerance Test (OGTT). Among these, 177 GDM patients with fasting blood glucose ≥5.1 mmoL/L underwent targeted GCK gene sequencing. Results Targeted sequencing identified eight rare GCK variants in nine individuals. None of the variant carriers met definitive diagnostic criteria for GCK-MODY. The prevalence of rare GCK variants in the screened GDM subgroup was 1.9% (9/474). Conclusion The low prevalence (1.9%) of rare GCK variants and absence of confirmed GCK-MODY cases indicate limited utility of fasting glucose-based screening for GCK-MODY in Chinese GDM populations. These findings highlight challenges in distinguishing GCK-MODY from GDM through conventional glucose thresholds.

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Abstract Objectives This study investigated the Eustachian Tube Dysfunction (ETD) prevalence and its influencing factors in Chronic Rhinosinusitis (CRS) patients undergoing Functional Endoscopic Sinus Surgery (FESS), based on postoperative histopathological subtypes. The findings may aid in the diagnosis and individualized management of CRS with comorbid ETD. Method This study included 92 patients who underwent FESS surgery for CRS and were hospitalized in the Otolaryngology Head and Neck Surgery Department of Zhengzhou University People's Hospital from January 2024 to May 2024. According to the postoperative pathological results, the patients were divided into the Chronic Rhinosinusitis without Nasal Polyps (CRSsNP) group and the Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) group. The CRSwNP group was further divided into an Eosinophilic Chronic Rhinosinusitis with Nasal Polyps (EosCRSwNP) subgroup. General information, imaging examination data, 7-item symptom score scale for eustachian tube dysfunction (Eustachian Tube Dysfunction Questionnaire-7, ETDQ-7), and eustachian tube pressure score (Eustachian Tube Score, ETS) of all included patients were collected. The prevalence of ETD in patients with different pathological types of CRS, the influencing factors of eustachian tube function in preoperative CRS patients, and the consistency of the two eustachian tube function detection methods and the test efficacy of the two eustachian tube function detection methods were analyzed. Results Correlations & Risk Factors: CRSwNP: Serum total IgE moderately correlated with preop ETDQ-7 (ρ = 0.497, p = 0.001). EosCRSwNP: Age (γ = 0.534, p < 0.01) and IgE (ρ = 0.506, p < 0.05) strongly correlated with ETDQ-7. IgE was an independent risk factor (OR = 1.010). Using the ETDQ-7 score and ETS score as the main diagnostic methods for ETD indicates that there is no statistically significant difference in the prevalence of ETD among the three groups of patients (CRSsNP, CRSwNP, and EosCRSwNP) (p > 0.05). Two types of examination methods were used to test the preoperative eustachian tube function of patients with different pathological types of CRS. The consistency degree of the results of the ETDQ-7 score and the ETS score was different. Among them, the patients in the EosCRSwNP group had the highest score, while those in the CRSsNP group had the lowest score (CRSsNP group: κ = 0.396, p < 0.01; CRSwNP group: κ = 0.421, p < 0.01; EosCRSwNP group: κ = 0.563, p < 0.01). Conclusion ETD Incidence & Correlation: ETD occurrence in CRS varies slightly by subtype but remains comparable overall. CRSwNP patients show a significant association between ETD symptoms and serum total IgE levels. The ETDQ-7 score and the ETS score, as subjective and objective methods for evaluating the function of the eustachian tube, have good consistency in results and can relatively accurately assess the eustachian tube function of patients with CRS.

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Abstract Introduction The effects of acute physical exercise on executive functions remain controversial, partly due to inconsistencies in how exercise intensity is measured. This study investigated the impact of moderate and vigorous aerobic exercise on three core components of executive function: inhibitory control, working memory, and cognitive flexibility. Exercise intensity was rigorously defined using a combination of heart rate reserve, ventilatory thresholds, and rate of perceived exertion. Method Twenty-six physically active adults completed three separate sessions in a randomized order: Rest (REST), Moderate-intensity exercise (MOD), and Vigorous-Intensity exercise (VIG). Cognitive performance was assessed during each condition using the Go/No-Go test (inhibitory control), the 2-back test (working memory), and the Multitasking test (cognitive flexibility). Results Inhibitory control improved significantly during exercise. Response Times (RT) on the Go/No-Go test were reduced in both MOD (p = 0.038) and VIG (p = 0.003) compared with REST, without changes in accuracy. In contrast, working memory and cognitive flexibility showed no significant differences across conditions. Conclusions Acute moderate and vigorous aerobic exercise, up to the second ventilatory threshold, selectively enhances inhibitory control by reducing RT, with no detectable effects on working memory or cognitive flexibility. By integrating multiple physiological and perceptual markers of intensity, this study provides a rigorous evaluation of the acute cognitive effects of aerobic exercise.

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Abstract Objective To explore the role of circular RNA derived from RERE (circ-RERE) in regulating Programmed Death-Ligand-1 (PD-L1) expression and microRNA-128-3p (miR-128-3p)/Zinc finger e-box Binding homeobox-1 (ZEB1) axis in Acute Myeloid Leukemia (AML). Methods AML cell viability, proliferation, apoptosis, the ratio of microtubule-associated protein 1A/1B-Light Chain 3-phosphatidylethanolamine conjugate (LC3-II) to free LC3 (LC3-I) (LC3-II/LC3-I), and PD-L1 expression, as well as CD8+ T-cell cytotoxicity, were correspondingly analyzed. The targeting relationship between miR-128-3p and circ-RERE or ZEB1 was verified. Results As detected, suppressing circ-RERE or overexpressing miR-128-3p significantly blocked the proliferation, migration, invasion, and autophagy of AML cells, promoted cell apoptosis, suppressed PD-L1 expression, and increased CD8+ T-cell cytotoxicity. circ-RERE competed with miR-128-3p to regulate ZEB1. Forced expression of ZEB1 did a reversal of circ-RERE suppression-induced effects. Conclusion In a word, circ-RERE promotes autophagy and immune escape in AML by regulating PD-L1 expression through the miR-128-3p/ZEB1 axis, which may provide a new target for AML therapy.

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Abstract Objective “Treat-to-close” strategy in the treatment of patients with Atrial Septal Defects (ASD) combined with severe Pulmonary Hypertension (PAH). This study explored the long-term survival of patients undergoing the “treat-to-close” strategy and the characteristics of the applicable population. Methods A total of 141 ASD-PAH patients were collected. Patients were classified as “Occlusion Group” (OG) and “Conservative Treatment Group” (CTG) depending on the suitability of ASD occlusion after drug treatment. The baseline characteristics and long-term follow-up outcomes of the two groups were recorded. Results Patients in the OG underwent 5 (3.8) months of Pulmonary Artery-targeted Drug Therapy (PADT) before ASD occlusion. OG patients had better long-term survival (p = 0.043). Pulmonary Vascular Resistance (PVR): Area Under the Curve (AUC) 0.813 (0.726‒0.899, p < 0.001), Pulmonary Arterial Oxygen Saturation (PASO2): AUC = 0.794 (95% CI: 0.682‒0.904 p < 0.001), Pulmonary Artery Systolic Pressure (PASP): AUC = 0.808 (95% Confidence Interval [95% CI]: 0.733‒0.883 p < 0.001) and PASO2 combined with PASP: 0.918 (95% CI: 0.854‒0.979 p < 0.001) contribute to the screening of drug-sensitive populations. Conclusions The treat-to-close strategy significantly improves long-term patient survival. Initial intraoperative indications can help screen the beneficiary population. Larger-scale prospective studies are needed to validate the present findings.

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Abstract Background This study aimed to evaluate the provision of mammograms and cervical biopsies in Brazil’s public and private healthcare sectors and the availability of gynecologists and obstetricians. Methods This ecological study included specialists in gynecology and obstetrics, as well as data on mammograms and cervical biopsy procedures performed in 2024 through the Brazilian Unified Health System (SUS) and private health insurance plans. For each state, ratios of specialist availability and the rate of procedures per 100,000 women were calculated. Sensitivity analysis was performed to calculate the ratio of procedures in women of different age groups, and Spearman’s correlation coefficient was used to assess the association between specialist availability and the rate of procedures performed. Results In 2024, health insurance plans performed 15,510.88 mammograms per 100,000 women, almost triple the SUS rate (5,733.93). The private sector performed 426.28 cervical biopsies per 100,000 women, while the public sector conducted only 85.24. The total provision of mammograms varied from 12,691.29 per 100,000 women in São Paulo to 2,702.91 in Pará. For cervical biopsies, the provision ranged from 348.94 per 100,000 women in São Paulo to 21.18 in Roraima. Correlation analysis showed a positive association between specialist availability and procedure volume (mammograms: r = 0.74; biopsies: r = 0.39; p < 0.001), which remained consistent after sensitivity analysis. Conclusion Separate indicators for procedure provision and specialist availability effectively identified regional disparities. These findings can guide policymakers in reducing inequalities in access to early breast and cervical cancer diagnosis.

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Abstract Background Pressure Injuries (PIs) are frequent, preventable complications in Intensive Care Units (ICUs), leading to morbidity, mortality, and increased healthcare costs. Alternating Pressure Air Mattresses (APAMs) have been proposed to reduce PI incidence, but real-world data remain scarce. Objectives To assess the effectiveness and cost-efficiency of APAMs in preventing PIs among critically ill patients. Methods This retrospective cohort study was conducted in a 10-bed tertiary ICU, comparing patients before and after APAM implementation. Multivariate logistic regression identified independent PI risk factors, and a cost-effectiveness model was developed using Number Needed to Treat (NNT) and treatment costs. Results APAM use reduced overall PI risk by 33% (RR = 0.67; 95% CI 0.45-0.98) and Stage III-IV ulcer risk by 84% (RR = 0.16; 95% CI 0.05-0.53). The NNT was 23, corresponding to net savings of USD 121,750 over five years for a 10-bed ICU, with cost recovery achieved within 4.3-months. Length of Stay (LOS) and prolonged mechanical ventilation independently increased PI risk by 19% and 13% per day, respectively. APAMs’ benefit was attenuated in patients with extended LOS and ventilation. Sepsis and respiratory failure increased PI risk in univariate analysis but lost significance after adjustment, indicating mediation by LOS and ventilation. APAMs eliminated the need for negative pressure wound therapy in this cohort. Conclusions APAMs significantly reduced severe PI incidence and treatment requirements in critically ill patients, demonstrating cost-effectiveness. Their protective effect was limited in patients with prolonged ICU stay or ventilation. Multicenter randomized trials are warranted, especially in diabetic and septic populations.

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Abstract Objective Diabetes, hypertension, and obesity are common traditional risk factors for Chronic Kidney Disease (CKD). In this population-based longitudinal study, the authors identified risk factors associated with CKD development. Method A total of 6,238 Korean adults aged 40- to 69-years without baseline CKD were included. Among them, 4,057 participants with baseline estimated Glomerular Filtration Rate (eGFR) measurements were analyzed. Logistic regression models were used to evaluate significant predictors of CKD. Results Over a 10-year follow-up period, CKD developed in 354 subjects (8.7 %). Leptin levels were significantly higher in participants who developed CKD compared to those who did not (8.89 ± 8.00 vs. 6.44 ± 5.52, p < 0.001). After adjusting for confounding factors, logistic regression analysis indicated that participants in the highest quartile of muscle mass were 2.314-times more likely to develop CKD compared to those in the lowest quartile (Odds Ratio [OR = 2.314]; 95 % Confidence Interval [95 % CI: 1.372-3.902]; p = 0.014). In multivariable-adjusted models, the OR for incident CKD when comparing the lowest to the highest quartiles of body fat was 2.166 in men; however, the significance disappeared after adjusting for eGFR. Among women, higher leptin levels and lower adiponectin levels were independently associated with incident CKD (p = 0.003 and p = 0.038, respectively), regardless of traditional CKD risk factors. Furthermore, compared to subjects without CKD, those with metabolic syndrome had an OR (95 % CI) of 5.256 (2.813-9.820) for incident CKD after controlling for confounding factors. Conclusion These findings suggest that muscle mass and body fat may serve as better predictors of incident CKD.

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Abstract Purpose To evaluate the prevalence of Irritable Bowel Syndrome (IBS) and its related sociodemographic, nociceptive, neuropathic, nociplastic, psychosocial, and systemic factors in patients with Chronic Pelvic Pain (CPP). Materials and methods This observational, prospective, and analytical study was conducted at a Pelvic Pain Outpatient Clinic between August 2021 and March 2022 with patients diagnosed with CPP. The following instruments were applied: IBS was diagnosed using the Rome IV criteria, the Questionnaire for Chronic Pelvic Pain Assessment (QCPPA) of the International Pelvic Pain Society (IPPS), the Depression, Anxiety and Stress Scale (DASS-21), the Douleur Neuropathique 4 questionnaire (DN4), and the Central Sensitization Inventory (CSI). Results In this study, 111 women with CPP were evaluated. The prevalence of IBS was 53.15%. Patients with IBS showed significantly higher frequencies of myofascial pain (p < 0.001), neuropathic pain (p = 0.026), and central sensitization (p = 0.010). Binary logistic regression identified myofascial pain (OR = 7.614; 95% CI: 2.12-22.88; p = 0.001) as an independent predictor of IBS, while infertility showed a protective association with IBS, with an adjusted odds ratio of 0.209 (95% CI: 0.048-0.915; p = 0.038). Conclusion Women with CPP have a high prevalence of IBS. In addition to the association with classic factors, this study also observed a significant association with neuropathic pain and pain centralization. A significant association with myofascial syndrome was observed, which appeared as a strong predictor of IBS in the adjusted model.

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Abstract Objectives To contribute to the organizational culture and interdisciplinary connections to surpass frontiers created by evolving specialization that put professionals as well as processes apart. In addition, we preserved and stimulated local established professional skills. Methods The authors worked by listening to organizational demands as well as demands of colleagues at work in a network organizational non-mandatory working weekly forums through videoconferences. Forums were devoted to specific scenarios, such as surgical center facilities, outpatient clinics, hybrid rooms, clinical directors, multidisciplinary leadership, intensive care units’ leadership, and institutional life. Mandatory (by local regulation) subcommittee forums occurred every two weeks. Participants of the meetings were in their working place. Every leadership would be present at most in two forums each week; participation might rotate between local leaderships. Results 200 interdisciplinary nonmandatory working forums were carried out in 2024; number of invites ranged between 52 (hybrid room) and 131 (clinical units’ leadership), participations ranged between 718 (hybrid room) and 791 (clinical units leadership) and mean participation ranged between 17.4 (range 11‒25; standard deviation 3.21) and 20.1 (range 11‒27; standard deviation 3.40). Hundred six mandatory forums were carried out in 2024; the number of invites ranged between 10 (subcommittee of pharmacology) and 19 (review of mortality); mean participation ranged between 9 (range 5‒12; standard deviation 2.16) and 11.7 (range 6‒15; standard deviation 2.24). Specific practical initiatives were born from these forums. Conclusions The authors consider that interdisciplinary connectivity was participative to a shared understanding of processes and associated requirements.

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Abstract Background The COVID-19 economic impact on health institutions has been discussed since the beginning of the pandemic, and the repercussions in different spheres were enormous. The economic evaluation in health became necessary as a management tool. Objective To describe and compare the hospitalization costs in Intensive Care Units (ICUs) and the patients' clinical and demographic variables, before and during the COVID-19 pandemic. Data sources and study setting Partial economic evaluation of patients admitted to four ICUs, in a Brazilian reference center, in two periods: pre-pandemic (03/30/19 ‒ 06/30/19) and pandemic (03/30/20 ‒ 06/30/20). Study design Observational cohort study. Data collection/Extraction methods Micro and macro costing methodology; clinical and demographic variables were considered for the comparative analysis. Results In 2019, 521 hospitalizations were analyzed. Patients were predominantly male (61%), between 31- and 60-years old (48.2%) and of white race (75.4%). In 2020, 610 hospitalizations were analyzed: 60.3% male, 51.6% > 60-years old and 65.2% white race. All ICUs had an increase in deaths (2019: average of 26.9%; 2020: average of 48.8%). The average total hospitalization costs and the average patient-day cost in 2019 was US$ 6051.01 and US$ 787.48, respectively; in 2020, US$ 19,492.73 and US$ 1542.74. Human resources was the component with the highest cost (2019: 51.6%; 2020: 78.2%). Patients who require additional therapeutic procedures had a higher average cost in 2020. Conclusion During COVID, patients were older (> 60-years), a higher percentage of patients identified as mixed race, the death rate was significantly higher, and the length of stay was significantly higher, resulting in the outcome “discharge”. The COVID cost was significantly higher. The main cost component was human resources, mainly during the COVID pandemic. Additional therapeutic procedures were associated with higher costs.

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Abstract Background Testosterone plays a crucial role in cognitive development and behavioral differences between sexes. However, it remains unclear whether age-related testosterone decline affects cognitive function in elderly men. Objective To determine whether serum steroid levels influence cognitive function in elderly males. Methods Sixty men with a mean age of 73.5 ± 5.9 years were evaluated. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE), administered by a single trained examiner. To rule out the influence of depression on MMSE, the Geriatric Depression Scale (GDS) was applied. Age, BMI, education level, serum Total Testosterone (TT), Free Testosterone (FT), Estradiol (E2), and sex hormone-binding globulin levels were measured and correlated with total and subdomain MMSE scores and GDS scores. Nonparametric tests and multivariable regression analyses were performed. Results Age was negatively correlated with TT (r = -0.36; p = 0.003), and TT was inversely associated with BMI (r = -0.45; p < 0.001). BMI was negatively correlated with total MMSE scores (r = -0.30; p = 0.010). TT and E2 levels showed no significant associations with overall MMSE, except for a positive correlation between TT and the Spatial Orientation subdomain (r = 0.26; p = 0.040). TT and FT were both negatively correlated with GDS scores (r = -0.32; p = 0.010; and r = -0.27; p = 0.030, respectively). After adjustment, only education years remained independently associated with MMSE (β = 0.374, p = 0.013). Conclusions Although lower serum testosterone levels were associated with depressive symptoms, no significant correlation was found with global cognitive performance; an interesting finding was the impact of years of education on MMSE score.

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Abstract Genomic studies support the role of Prostaglandin E2 (PGE2) in the pathogenesis of primary Hypertrophic Osteoarthropathy (HOA), with mutations in the 15-hydroxyprostaglandin dehydrogenase encoding gene resulting in increased PGE2 levels. The aim of this study was to analyse the clinical characteristics, comorbidities, and potential role of PGE2 in primary and secondary forms of HOA and/or digital clubbing. Methods Twenty-two patients (14 men/8 women) aged 15- to 78-years (50.8 ± 14.7) diagnosed with clubbing and/or HOA attended the Rheumatology Department for over 15-years. The authors reviewed the clinical characteristics of the patients, including associated comorbidities, image findings, Bone Turnover Markers (BTM), serum and urinary levels of PGE2, treatment, and the clinical evolution of these subjects. Results Most patients presented associated clinical conditions for HOA and/or clubbing, with only one, the youngest (15-years old), having primary HOA. Pulmonary disorders constituted the most frequent associated condition. All the subjects evaluated (18/22) presented increased urinary PGE2 levels, with most also presenting increased serum PGE2 values. BTM were assessed in most subjects (21/22), showing increased values in most (15/21), particularly in PINP and CTX. Eight patients were treated with selective inhibitors of Cyclooxygenase-2 (COX-2), improving their symptoms. Conclusions All subjects with primary or secondary HOA and/or clubbing of the series presented increased PGE2 values, particularly in urine, supporting the role of this mediator in the etiopathogenesis of this disorder. When the treatment of the associated condition is not possible, the use of COX-2 seems to be an effective symptomatic therapeutic approach in this entity.

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Abstract Objective This prospective cohort study describes clinical, laboratory factors and virological factors associated with in-hospital mortality among 227 Intensive Care Unit (ICU) patients with SARS-CoV-2 infection admitted in Brazil during the pre-vaccination, pre-Omicron phase of the pandemic (September 2020 to March 2021). Methods Clinical and laboratory data were extracted from medical records, and viral load was quantified by RT-qPCR Cycle threshold (Ct) values. Independent predictors of mortality were evaluated using multivariable Cox proportional hazards regression, and survival was analyzed with Kaplan-Meier curves. Results Non-survivors were significantly older (p < 0.001) and more likely to have hypertension (p = 0.014) and chronic respiratory disease (p = 0.042). At admission, they exhibited higher leukocyte counts (p = 0.001), D-dimer (p = 0.028), and creatinine levels (p = 0.001), as well as more frequent tracheal intubation (p < 0.001). During hospitalization, non-survivors showed persistently elevated leukocyte counts and developed more complications, including acute kidney injury, septic shock, and cardiac arrest (p < 0.001). Viral load was higher in non-survivors (p = 0.026) and among those requiring intubation (p = 0.042) or with cardiovascular disease (p = 0.016). In the multivariable Cox model, only creatinine at admission remained independently associated with mortality (HR = 1.18; 95% CI: 1.00-1.39; p = 0.049). Survival analysis showed reduced survival among patients aged ≥ 65-years (p = 0.004) and those with chronic respiratory disease (p = 0.029). Conclusions This study integrates clinical, laboratory, and viral load data to detail the early COVID-19 severity and mortality patterns in a Brazilian ICU.

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Abstract Objective Chronic Pelvic Pain (CPP) presents significant diagnostic challenges, often involving multiple pathologies, including endometriosis and pelvic venous disorders. This study examined the prevalence of endometriosis among women with confirmed pelvic varicosities. Methods The authors performed a retrospective analysis of 52 women with CPP and pelvic varicosities who underwent multiparametric magnetic resonance venography between January 2019 and December 2023. All images were reviewed by a single experienced radiologist, blinded to clinical data and vascular findings, to identify radiological signs of endometriosis. Results Among the 52 women, 32 exhibited radiological findings consistent with endometriosis, corresponding to a prevalence of 61.5% (95% CI: 47.0%-74.5%). Conclusion This study demonstrates a high prevalence of endometriosis among women with pelvic varicosities. Multiparametric MRI proved effective as a non-invasive diagnostic modality capable of identifying both vascular and gynecologic abnormalities in a single session, supporting integrated assessment approaches for women with CPP. Limitations include the retrospective design and the lack of histological confirmation of endometriosis.

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Abstract Introduction Burn injuries are a significant global health concern, with an estimated 8.4 million cases annually. Although specific cost data from Brazil are limited, international reports estimate an average burn-related hospitalization cost of USD 88,218. Educational tools for populations are desirable to prevent burn injury. Thus, the authors designed a gamified model to promote burn education and prevention among Brazilian students. Methods The intervention was conducted in four public schools, three High Schools (HS) and one Vocational School (VS). Students first completed a 21-question online pre-test assessing their baseline knowledge. A 20-minute lecture followed, covering burn classification and prevention. Students then participated in an interactive online trivia game (Burn Game) designed to reinforce learning. Finally, they completed the same test as a post-intervention assessment. Results A total of 134 students participated (73 from VS, 61 from HS), with a mean age of 18.6 ± 4.9 years; 73.13% were female. Post-test scores improved significantly across the participants, with 132 students showing higher scores. The overall mean score difference was 7.16-points (95% CI: 6.47-7.86; p < 0.001). Subgroup analysis revealed gains in both VS (MD = 6.08; 95% CI: 5.33-6.83) and HS students (MD = 8.46; 95% CI: 7.41-9.51), with HS students showing the greatest improvement. Conclusion The present study suggests that gamified teaching indeed contributed to significantly increasing students' knowledge about burn prevention and classification.

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Abstract Background Intra-Abdominal Hypertension (IAH) is reported to be frequent after liver transplantation. Nonetheless, the evolution of surgical techniques improved postoperative care in the last decades, which could lead to a lower incidence of Intra-abdominal hypertension. Methods The authors prospectively studied 104 patients. The intra-abdominal pressure and abdominal perfusion pressure were measured at the end of surgery and every 6 hours until 72 hours, and patients were divided into two groups: with (IAH+) or without (IAH-) IAH. Outcomes analyzed were death, renal function, reoperation, need for vasopressors, mechanical ventilation, hemodialysis, and graft function measured by indocyanine green. Results The incidence of Intra-abdominal hypertension was 14.4%, with no abdominal compartment syndrome cases. After 48 hours, 60% of the IAH+ group was on mechanical ventilation versus 26.7% in the IAH- group (p = 0.016). The prevalence of dialysis at the end of the first postoperative week was higher in the IAH+ group (31.3% vs. 10.8%, p = 0.047). Both groups had similar indocyanine green clearance on the third and seventh postoperative days. Reoperation rates (12.4% vs. 20%), need for retransplant (10.1% vs. 13.3%), and death (14% vs. 18.2%) were similar in IAH- and IAH+ groups, respectively. The number of blood products transfused (OR = 1.18) and body mass index (OR = 1.10) were associated with the development of intra-abdominal hypertension, while intraoperative ascites (OR = 0.19) was a protective factor. Conclusions Intra-abdominal hypertension was present in 14.4% of liver transplant patients, and IAH was linked to a greater need for mechanical ventilation and hemodialysis but not to more reoperations, transplants, or deaths.

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Abstract Objective This study aimed to compare the comparative protective effects of Melatonin (Mel) and Glutathione (GSH) against Carboplatin (CARB)-induced ovarian toxicity in rats, with a focus on folliculogenesis, oxidative stress, inflammation, and apoptosis. Methods Female Wistar rats were allocated into six groups: Control, GSH, Mel, CARB, GSH+CARB, and Mel+CARB. Mel and GSH were administered intraperitoneally for 7 days before CARB injection. Ovarian tissues were subjected to histopathological and morphometric analyses, while serum oxidative stress markers (MDA, SOD, CAT, GSH-Px), proinflammatory cytokines (TNF-α, IL-6), and AMH levels were quantified. Caspase-3 and NF-κB expressions were evaluated immunohistochemically. Results CARB caused severe ovarian injury characterized by marked follicular depletion, stromal edema, hemorrhage, inflammation, fibrosis, and a significant reduction in preantral and Graafian follicles, with a concomitant increase in atretic follicles (p < 0.01). Both Mel and GSH pre-treatment markedly reduced histological damage, restored follicular counts, improved antioxidant status, and suppressed inflammatory and apoptotic responses. Melatonin tended to exert stronger protective effects on certain parameters, particularly in preserving AMH levels, attenuating fibrosis, and reducing Caspase-3 and NF-κB expression, although the differences between Mel+CARB and GSH+CARB groups were not statistically significant in all comparisons. Conclusion Pre-treatment with melatonin or glutathione effectively mitigated CARB-induced ovarian toxicity by modulating oxidative stress, inflammation, and apoptosis. Melatonin appeared to provide relatively greater protection in some parameters, but without consistent statistical superiority over glutathione. These results underscore the potential of antioxidant-based strategies for fertility preservation during chemotherapy. Further studies with larger sample sizes and direct comparative analyses are warranted to clarify relative efficacy and confirm translational relevance.

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Abstract Objective To investigate which factors mediate the association between doctors’ communication behaviours and patients’ satisfaction with care and trust placed in their doctors. Methods Qualitative descriptive study conducted in a tertiary teaching hospital in São Paulo, Brazil, with 60 patients enrolled in the preoperative risk assessment clinic. They underwent a semi-structured interview, which was analysed using a reflexive thematic analysis approach. Results Patients' satisfaction with care and trust placed in their doctors were analysed. The main themes identified as mediating factors were doctors' competencies, patients subjectiveness, and healthcare context. Conclusion Better understanding the mediators involved in the association between communication and patients’ satisfaction and trust allows the creation of specific educational actions targeted at doctors. Innovation We use a qualitative approach to identify mediating factors and shed light on how what happens in the “doctor’s office” can mediate the connection between communication, satisfaction and trust.

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Abstract Objective Obesity is a major independent risk factor for chronic kidney disease. High-Intensity Interval Training (HIIT) is recognized as an interesting therapeutic strategy in managing obesity and related disorders. However, there is still a lack of knowledge about its impact on kidney function. The study aimed to evaluate the impact of the HIIT program on kidney function and erythrocyte parameters in overweight/obese women. Methods Thirty-three overweight/obese young women (age, 17.0 ± 1.15 yrs.; body mass index, 33.3 ± 4.77 kg/m2) were allocated into HIIT (n = 17) or control (n = 16) groups. The HIIT program was performed 3 times a week for nine weeks. Body composition parameters, blood creatinine, blood urea, estimated Glomerular Filtration Rate (eGFR), serum electrolytes (i.e., sodium, potassium, chloride, calcium, phosphorus, and magnesium), and red blood cell parameters (i.e., red blood cell count, hematocrit, hemoglobin and mean corpuscular volume) were collected before the start and after the completion of the training. Results Nine weeks of HIIT significantly improved (p < 0.01) body mass index, body fat, and waist circumference, but the auhtors found no statistically significant changes in blood creatinine, urea, eGFR, and red blood cell parameters (p > 0.05). No variable changed in the control group. Conclusions HIIT improved body composition; however, no significant changes in renal function parameters were detected in this underpowered study.

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Abstract Objective To address the critical challenge of efficiently and ethically managing surgical waiting lists in digital health systems by developing a decision support framework based on biopsychosocial prioritization. Methods The authors integrate the Analytic Hierarchy Process (AHP) with K-Means clustering to create a hybrid decision support model that prioritizes patients using multidimensional biopsychosocial variables. The model was applied in the otolaryngology (ENT) unit of a high-complexity public hospital in Chile. Expert-informed weightings guided the AHP process, while K-Means clustering enabled data-driven segmentation into clinically coherent patient groups. Results The proposed methodology significantly outperformed traditional chronological scheduling approaches. Specifically, it achieved a 27 % reduction in mean clinical risk, a 41 % decrease in urgent hospitalizations, a 32 % reduction in urgent bed days, and more than 12-days of acceleration in access for high-priority patients. Contribution While the AHP-clustering hybrid is established in prior literature, our contribution lies in operationalizing it with ethical safeguards and real-world validation within a high complexity ENT unit. Conclusion Our hybrid AHP and K-Means approach offers a transparent, scalable, and interpretable decision support tool for surgical prioritization. It aligns with the goals of digital health transformation by improving the fairness, efficiency, and responsiveness of healthcare delivery.

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Abstract Background In this meta-analysis, the authors aimed to provide a comprehensive overview of the benefits of exercise and its potential implications in the management of atrial fibrillation. Method The authors conducted searches in PubMed, MEDLINE, EMBASE, and Cochrane databases using the terms “atrial fibrillation”, “exercise”, “cardiac rehabilitation”, or “physical activity”. The endpoints included the 6-Minute Walk Test (6MWT), maximal Oxygen uptake (VO2max) measured by Cardiopulmonary Exercise Testing (CPET), maximal power measured by CPET, resting Heart Rate (HR), Left Ventricular Ejection Fraction (LVEF), data from the 36-Item Short Form Survey Instrument (SF-36), and AF recurrence post-ablation. Results The present analysis included 11 randomized control trials published in the past 15-years, involving a total of 1251 patients. The pooled analysis showed significant increases in VO2max, 6MWT, and maximal power in AF patients post-exercise (-3.05, 95 % CI: [-4.79, -1.3], I2 = 84 %, p < 0.0001; -42.07, 95 % CI: [-56.22, -27.93], I2 = 0 %, p < 0.00001; -16.39, 95 % CI: [-20.76, -12.01], I2 = 72 %, p < 0.00001, respectively). Sensitivity analysis results remained consistent but significantly reduced heterogeneity. The authors found that the recurrence rate was significantly lower in patients who exercised (RR = 0.76, 95 % CI: [0.62, 0.95], I2 = 0 %, p = 0.01). Quality of life was assessed using the SF-36 scale, which includes eight domains. The pooled results are as follows: physical function (WMD = -6.46, 95 % CI: [-10.48, -2.44], I2 = 52 %, p = 0.002), role physical (WMD = -13.02, 95 % CI: [-16.68, -9.36], I2 = 32 %, p < 0.00001), general health (WMD = -7.80, 95 % CI: [-12.35, -3.25], I2 = 62 %, p = 0.0008), bodily pain (WMD = -3.54, 95 % CI: [-6.82, -0.26], I2 = 0 %, p = 0.03), vitality (WMD = -8.34, 95 % CI: [-14.31, -2.36], I2 = 74 %, p = 0.006), social function (WMD = -6.44, 95 % CI: [-12.17, -0.72], I2 = 71 %, p = 0.03), role emotional (WMD = -12.18, 95 % CI: [-16.46, -7.90], I2 = 0 %, p < 0.00001), and mental health(WMD = -6.79, 95 % CI: [-11.69, -1.88], I2 = 72 %, p = 0.007). Sensitivity analysis resulted in consistent outcomes with heterogeneity reduced to 0 % for all domains. Conclusion The present study found that exercise rehabilitation benefits patients with atrial fibrillation. Exercise can improve quality of life and possibly reduce recurrence. While it enhances cardiorespiratory fitness (VO2max, 6MWT, maximal power), it does not significantly improve ejection fraction or heart rate.

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Abstract Background Abdominal Aortic Calcification (AAC) is closely associated with visceral adiposity. The authors aimed to investigate the relationship between a Body Shape Index (ABSI) and AAC. Methods Data were obtained from the 2013‒2014 cycle of the National Health and Nutrition Examination Survey (NHANES). Weighted multivariable regression, tests for trends, subgroup analysis, and smooth curves were used to explore the association between ABSI and AAC scores, as well as Severe Abdominal Aortic Calcification (SAAC). Receiver Operating Characteristic (ROC) curves were plotted to compare the predictive abilities of ABSI, Weight-adjusted Waist Index (WWI), Body Mass Index (BMI), Waist-to-Height Ratio (WHtR), and Waist Circumference (WC) for AAC and SAAC. Results A total of 2741 individuals were included in the present study. The weighted incidence of AAC was 29.12%, and SAAC was 7.94%. After fully adjusting for covariates, each one-unit increase in ABSI was associated with a 0.42-point increase in the AAC score (95% CI: 0.29, 0.63), and the risk of SAAC increased by 37% (95% CI: 1.12, 1.77). Smooth curves showed a nonlinear positive correlation between ABSI and AAC scores, as well as SAAC. No dependence was observed in the subgroup analysis. ROC analysis showed that ABSI was a stronger predictor than WWI, BMI, WHtR, and WC. Conclusions ABSI has a positive correlation with AAC scores and SAAC. However, prospective studies are required to validate the present results.

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Abstract Background Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive lung disorder characterized by limited therapeutic options. Thus, identifying new therapeutic targets for IPF is imperative. Methods The authors employed 2 large-scale circulating proteomic and IPF GWAS (Ncase = 2189, Ncontrol = 407,609) to conduct proteome-wide Mendelian randomization meta-analysis. Subsequently, the authors utilized Summary Mendelian Randomization analysis and Bayesian colocalization to enhance the screening of proteins. Lastly, MR analysis of protein-protein level ratio, two-step MR method, enrichment analysis, Protein-Protein Interaction (PPI), and druggability assessment were applied to explore the potential mechanisms of candidate proteins. Results Through proteome-wide Mendelian randomization analysis and multiple validations, the authors identified 3 plasma proteins significantly associated with IPF. With strong evidence of colocalization and consistent support from SMR analysis, the gene-predicted MASP1 was correlated with decreased IPF risk (ORmeta = 0.46, 95% CImeta: 0.22‒0.99, Pmeta = 0.0478, PPH4 = 0.92). With suggestive colocalization support (PPH4 = 0.50), the levels of S100A11 were inversely related to IPF risk, with odds ratios of 0.53 (95% CIMR1 0.34-0.83, PMR1 = 0.0053). Conversely, the gene-predicted WFIKKN2 was associated with an increased risk of IPF (ORmeta = 1.31, 95% CImeta 1.15-1.48, Pmeta = 2.48E-05, PPH4 = 0.50). Their association was further supported by SMR analysis. Moreover, MR analysis of protein level ratio, mediator MR analysis, enrichment, and PPI network provided insights into the potential drug development based on the proteins. Conclusions Our proteome-wide Mendelian Randomization analysis highlighted MASP1, S100A11, and WFIKKN2 as potential targets for further clinical investigation in IPF. The specific mechanisms by which these proteins influence IPF pathogenesis require further elucidation through continued research.

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Abstract Objective The better survival of preterm infants in recent years raises concerns about the risk of Intraventricular Hemorrhage (IVH). The authors investigated the incidence, risk factors, severity, and mortality of IVH in Very Low Birth Weight (VLBW) infants, comparing those < 1000 g with those weighing 1000 g ‒ 1499 g. Methods This is a cohort of VLBW infants admitted from 2009‒2018. All neonates with gestational age between 24‒36 weeks, weighing from 400 g to 1499 g, and who underwent cranial ultrasound in the first 72-hours of life were included. Independent variables were maternal, gestational, birth, and neonatal data. Outcomes were IVH (all grades) and severe IVH (grades 3 and 4) in preterm infants < 1000 g and in those ≥ 1000 g. Results A total of 724 VLBW infants were studied, 37% of these weighing < 1000 g. The incidence of IVH was 32% and was more frequent in those < 1000 g (50.5%) compared with those ≥ 1000 g (21.5%). In preterm infants < 1000 g, gestational age and patent ductus arteriosus were associated with IVH, and severe IVH. In the group ≥ 1000 g, IVH was associated with preeclampsia, first-minute Apgar, use of vasoactive drugs and surfactant. The mortality of preterm infants with IVH was 35%; in severe cases, it reached 64.5% in those < 1000 g and 41% in those ≥ 1000 g. Conclusions IVH is frequent and severe, with a high mortality rate in VLBW infants, especially in those < 1000 g. Several risk factors for IVH are potentially preventable and most of them reflect the role of hemodynamic instability in the occurrence of IVH. These results can guide obstetricians and neonatologists in the implementation of good care practices.

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Abstract Objectives Evaluate the performance of diagnostic measures (sensitivity and specificity) of the Intrinsic Capacity (IC) construct by domain and by age group. Study design 164 elderly individuals were assessed in the 5 domains of IC (cognition, psychological, vitality, locomotion, and sensory) and for Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), frailty, and urinary incontinence. One-way ANOVA, t-test, or Mann-Whitney test were used for quantitative variables, and chi-square test for qualitative variables. The sensitivity and specificity were evaluated using the ROC curve. Results Decline in IC was older, worse ADL, IADL, and mental function, low gait speed, higher depression scores, frailty, and urinary incontinence. The full version and the cognitive, psychological, locomotion, and sensory domains demonstrated moderate performance, while the vitality showed poor performance. The age-stratified analysis indicated that among participants aged 60-69 years, the cognitive, vitality, locomotion, and sensory domains showed poor performance, while the psychological domain demonstrated good performance. In the 70-79-year group, all domains showed moderate performance. In individuals aged ≥ 80-years, the cognitive, psychological, vitality, and locomotion domains demonstrated moderate performance, whereas the sensory domain showed good performance. Conclusions Full IC construct and most domains showed moderate performance, with the exception of vitality (poor performance). When analyzed by domain and age group, performance varied across domains, ranging from poor to moderate, with the sensory domain showing the best results in the oldest group. Furthermore, the intrinsic capacity construct remains a useful screening approach for identifying older adults at risk of frailty.

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Abstract Background Despite significant advancements in immunotherapy for advanced esophageal cancer, there remains a critical need for reliable biomarkers to predict long-term clinical outcomes. The C-PLAN index, a novel composite score integrating C-Reactive Protein (CRP), lymphocyte dynamics, nutritional risk, and the Neutrophil-to-Lymphocyte Ratio (NLR), was developed to serve as a potential prognostic tool in this setting. Methods This study included 228 patients with advanced esophageal cancer who received PD-1/PD-L1 inhibitors between January 2018 and March 2023. Patients were stratified into low-risk (score ≤ 2), Medium-risk (score 3-4), or high-risk (score ≥ 5) groups based on the C-PLAN index. Clinical outcomes, including Overall Survival (OS) and Progression-Free Survival (PFS), were assessed over a 24-month follow-up period. Nonlinear associations between the C-PLAN index and OS/PFS were evaluated using restricted cubic splines. Cox proportional hazards models identified independent prognostic factors for OS, while time-dependent Receiver Operating Characteristic (ROC) curves compared the predictive accuracy of the C-PLAN index with that of NLR. Results Of the 228 patients enrolled, 189 were included in the final analysis. Significant differences in baseline characteristics were observed across risk groups: low-risk patients exhibited higher Body Mass Index (BMI) and albumin levels, whereas high-risk patients had larger tumor sizes, elevated CRP, Lactate Dehydrogenase (LDH), NLR, and C-PLAN scores. The median PFS was significantly longer in the low-risk group compared with intermediate- and high-risk groups (p < 0.001). A significant nonlinear relationship between the C-PLAN index and both OS and PFS was observed (p for nonlinearity < 0.001). Multivariable analysis identified NLR, poorly differentiated histology, and the C-PLAN index as independent predictors of mortality. Time-dependent ROC analyses revealed that the C-PLAN index demonstrated superior predictive accuracy compared to NLR at both 12-months (Area Under the Curve [AUC], 0.710 vs. 0.496) and 24-months (AUC, 0.897 vs. 0.740). Conclusion The C-PLAN index provides a robust and clinically meaningful prognostic tool for patients with advanced esophageal cancer treated with immune checkpoint inhibitors. Its superior predictive performance compared to traditional markers such as NLR highlights its potential utility in risk stratification and guiding treatment decisions.

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Abstract The amputation of a limb directly impacts functioning. The lack of standardization in the assessment of lower-limb amputees complicates the identification of actual impairments. The Timed Up and Go (TUG) test has been validated and used in these individuals' clinical practice. The authors compared the performance of lower-limb amputees with that of healthy volunteers and identified the factors involved in performing the test and, consequently, in the patient´s functioning ability. Lower limb amputee individuals referred to the Institute of Physical Medicine and Rehabilitation of the Hospital das Clínicas of the Faculty of Medicine at the University of São Paulo (IMREA-HCFMUSP) were included, as well as healthy volunteers, between August 2020 and July 2022. Statistical data were analyzed using Stata 14, with a significance level set at α < 0.05. The results indicate that TUG times were statistically different between the groups, which can be explained by factors such as age, mobility measured by the Amputee Mobility Predictor Questionnaire (AMP), and prosthetic use. The TUG test can be standardized in clinical practice for amputee patients, and identifying the factors influencing its values supports the structuring of rehabilitation for lower-limb amputations.

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Abstract Background Direct-Acting Antivirals (DAAs) are effective in 95% of patients, but concerns about potential cardiotoxicity and decreased Warfarin Sensitivity (WS) need further investigation. The study aimed to evaluate the safety and effectiveness of sofosbuvir-based therapy in patients with significant heart diseases, considering potential drug interactions and their impact on cardiac function. Methods The study involved 100 patients with HCV genotype 4, including 40 with ischemic heart disease, 20 with prosthetic valve replacement, 20 with NYHA class I‒II heart failure, and 20 with systemic hypertension. All received sofosbuvir-based antiviral therapy and underwent routine laboratory tests, N-Terminal B-type Natriuretic Peptide (NT-Pro BNP), abdominal ultrasound, and echocardiography at baseline and three months post-treatment. Results Ninety-six patients achieved SVR, resulting in improved cardiac ejection fraction (EF) from 53.2 ± 8.8% to 56.2 ± 6.9% (p = 0.000) and reduced left atrial volume (LAV) from 43.2 ± 4.2 to 41.7 ± 3.9 mm (p = 0.008). Liver stiffness also improved (p = 0.013), and no disabling symptoms were reported. MAPSE increased from 8.4 ± 2.4 mm to 9.5 ± 2.5 mm, and interventricular septum thickness (IVT) decreased from 12.5 ± 1.8 mm to 10.9 ± 1.3 mm (p = 0.001 and P = 0.000, respectively). The warfarin dose needed to be increased to optimize INR after SVR, but this adjustment did not affect WS (p = 0.16). Conclusion Sofosbuvir-based antiviral therapy was well tolerated and demonstrated a reassuring cardiac safety profile in HCV patients with pre-existing heart disease, with no major arrhythmias or adverse cardiac events observed during or after therapy.

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Abstract Introduction Organ preservation at low temperatures has been described since Alexis Carrel's time in 1912. Since then, organs have been stored in a mixture of frozen saline solution and liquid, with a temperature of around 4 °C. Studies suggest higher temperatures may preserve mitochondrial function, allowing for an extended ischemia time. Various systems are commercially available, each with different preservation principles. This study aims to analyze the underlying parameters of each device. Materials and methods A systematic review was conducted using the following databases: PubMed, Embase, and Cochrane Library, searching for clinical trials and observational studies evaluating the use of thermal boxes for lung preservation devices in transplantation. The assessed outcomes were Primary Graft Dysfunction (PGD), ventilation time, length of hospital stay, rejection rate, and survival rate. Results The search yielded six studies selected based on title and abstract, including 519 lung transplant cases. The preservation systems evaluated were LUNGguard and MYTEMPF. Our studies assessed LUNGguard, with a total of 298 patients. This system maintained an average temperature of 6 °C (4° to 8 °C), and 51 patients developed grade 3 PGD within 72 h. The mean ventilation time was 25.2 h (25 to 25.5 h), and ICU stay ranged from 8 to 9 days. Rejection was observed in 3 out of 18 patients, and hospital survival was reported in 221 out of 231 patients. MYTEMP 65 HC was evaluated in one study with 70 patients, of whom 4 developed grade 3 PGD within 72 h. The mean ventilation time was 49 h, and the length of hospital stay was 25 days. Kaplan-Meier estimated survival was 94 % (HR = 0.65; 95 % CI 0.26 to 1.6). Discussion/conclusion Preservation systems show different performances in lung preservation devices for transplantation. Across available studies, LUNGguard has been reported to maintain temperature stability with corresponding survival findings. Across studies of MYTEMP, lower grade 3 PGD rates have been reported, together with longer ventilation and hospitalization durations, and the device is described as non-transport. Other devices exist on the market, but their data remains unpublished. In summary, ongoing clinical studies with these and other preservation devices are expected to provide new evidence in the near future. As additional data become available, an updated systematic review will help clarify their comparative performance and guide clinical practice.

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Abstract Background Sarcopenia, characterized by progressive loss of skeletal muscle mass and strength with pathophysiological changes that may originate in early life, and the Cardiometabolic Index (CMI) ‒ a reliable marker for lipid metabolic dysfunction and central adiposity ‒ have associations that are insufficiently studied. This study aimed to investigate the association between CMI and sarcopenia in U.S. adults aged 20-59 and to evaluate the predictive value of CMI for sarcopenia. Methods Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011-2018, which initially encompassed 39,156 participants, the authors applied age-based screening and exclusion of cases with missing data, resulting in a final analytical cohort of 4784 participants for statistical analysis. Sarcopenia was defined per the Foundation for the National Institutes of Health (FNIH) criteria: Appendicular Lean Mass (ALM) adjusted for BMI < 0.512 in men and < 0.461 in women. CMI was calculated as [triglycerides (mg/dL) / high-density lipoprotein cholesterol (mg/dL)] × [waist circumference (cm) / height (m)] / body mass index (kg/m2). Multivariate logistic regression, subgroup analysis (sex, age, race and clinical conditions), Generalized Additive Models (GAM), piecewise regression, Propensity Score Matching (PSM), Inverse Probability Weighting (IPW), and Receiver Operating Characteristic (ROC) curves were employed. Analyses were adjusted for three categories of confounders: sociodemographic factors, behavioral factors, and clinical factors. Results Among the 4784 participants, 425 (8.88%) had sarcopenia. Descriptive analysis showed that the median CMI of sarcopenia participants was higher (0.82 vs. 0.43; p < 0.001) compared with non-sarcopenia participants, and they had unfavorable demographic/clinical characteristics (e.g., older age, higher prevalence of diabetes). In the full sample, after adjusting for all confounding factors, Elevated CMI correlated with an increased odds of presenting sarcopenia (Odds Ratio [OR = 1.39], 95% CI = 1.05-1.91, p = 0.005). The multi-dimensional model incorporating CMI demonstrated superior predictive ability (AUC = 0.819). GAM revealed a non-linear association with a threshold of 0.899, which was strongest in males, individuals aged 20-39 years, non-Hispanic Blacks, those with hypertension, and non-obese or non-diabetic individuals. Conclusion Cardiometabolic Index (CMI) has a non-linear positive association with sarcopenia in U.S. young and middle-aged adults, with a threshold of 0.899. The multi-dimensional predictive model incorporating CMI demonstrates superior performance in assessing odds of presenting sarcopenia compared to traditional anthropometric indicators, indicating its potential as a novel clinical biomarker for such evaluations.

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Abstract Purpose This research aimed to examine the impact of M2 Macrophages-derived exosomes (M2-exo) on the osteogenic differentiation of Periodontal Ligament Stem Cells (PDLSCs). Methods Human monocytes THP-1 were used to induce the M1 and M2 polarization. The PDLSCs were co-cultured with M1 and M2 type THP-1, and subjected to M2-exo treatment, respectively. The osteogenic differentiation of PDLSCs was analyzed through ALP and ARS staining. The mRNA expression of biomarkers of M1 and M2 macrophages, OPN, Runx2, ALP and CCL18 was evaluated by RT-qPCR assay. Results The findings suggested that M1 type THP-1 inhibited the steogenic differentiation of PDLSCs and M2 type THP-1 promoted it. M2-exo also promoted steogenic differentiation of PDLSCs and increased the OPN, Runx2 and ALP mRNA levels. Furthermore, CCL18 levels were increased in M2 type THP-1 and M2-exo treated PDLSCs. After CCL18 knockdown, the role of M2-exo in PDLSCs was reversed. Conclusion In conclusion, this study confirmed that M2-exo derived exosomes facilitated PDLSCs' osteogenic differentiation through secreting CCL18.

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Abstract Background Accumulating evidence suggests an association between Ankylosing Spondylitis (AS) and Cardiovascular Disease (CVD), yet the causal effects of AS on different CVD types remain unclear. This study aimed to determine the associations between AS and CVD using two-sample Mendelian Randomization (MR) analysis. Methods The genetically predicted causal relationships between AS and six common cardiovascular and cerebrovascular diseases (hypertension, atrial fibrillation, acute myocardial infarction, coronary atherosclerosis, angina, and heart failure) were evaluated using MR analysis. Data originated from Genome-Wide Association Studies (GWAS). Single Nucleotide Polymorphisms (SNPs; p < 5 × 10-8, r2 < 0.01) were selected as Instrumental Variables (IVs) for MR analysis. The primary outcome for causal inference was the Inverse Variance-Weighted (IVW) method, complemented by other methods (MR Egger, weighted median, simple mode, weighted mode). All results were presented as Odds Ratios (ORs). Heterogeneity and pleiotropy analyses were performed to ensure result stability and reliability. Results MR results provided positive causal evidence for AS on hypertension (OR = 1.0143; 95% CI: 1.0038‒1.0248, p = 7.269 × 10-3) and heart failure (OR = 1.0128; 95% CI: 1.0037‒1.0217, p = 5.76 × 10-3). Conversely, none of the IVW methods indicated causal effects for AS on the other four diseases. Sensitivity analyses supported the robustness of the results. Conclusion This study indicates that ankylosing spondylitis has positive causal effects on hypertension and heart failure.

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Abstract Background This study aims to evaluate the association between SII and the prevalence of MetS in the female population of the United States, utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2013-2018. Methods The study analyzed data from 6140 participants. The association between SII and MetS was investigated using both univariate and multivariable analyses. Additionally, the relationship between SII and all-cause as well as cardiovascular mortality was assessed through Cox proportional hazards regression models. Results MetS was prevalent in 37.52% of the study population. Participants diagnosed with MetS showed higher SII scores compared to those without MetS. There was a nonlinear “J”-shaped dose-response relationship between increased SII levels and increased all-cause mortality in the MetS population. The same trend of relationship between SII levels and cardiovascular mortality was observed in people aged 60-years and older in the MetS population. Conclusion The results of this study suggest that there is a significant association between elevated SII and the presence of MetS, and that systemic inflammation indicated by SII may contribute to the development and progression of MetS and its associated complications. Further studies are warranted to elucidate the underlying mechanisms between SII and MetS and to evaluate the clinical utility of SII in risk stratification and management strategies.

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Abstract Background Uterus transplantation is an emerging treatment for absolute uterine factor infertility. While surgically complex, the procedure also presents unique challenges for anesthetic management, particularly in living-donor scenarios, where two major operations proceed in close succession with partial temporal overlap. The authors report the anesthetic management and challenges of the first successful living-donor uterus transplantation in Latin America. Case presentation A 34-year-old female recipient with Mayer-Rokitansky-Küster-Hauser syndrome and her 31-year-old sister, with two previous vaginal births, as the living-donor. The donor's anesthesia was challenging due to the prolonged surgical time, requiring extended general anesthesia with extended mechanical ventilation and continuous invasive monitoring. Another key challenge was managing the donor's significant postoperative pain, necessitating a robust multimodal approach. The recipient's anesthetic course focused on maintaining hemodynamic stability, normothermia, and appropriate fluid balance during major fluid shifts, vascular clamping, and graft reperfusion. Both patients remained hemodynamically stable without vasopressor support throughout their respective procedures. Conclusion This landmark case demonstrates that successful living-donor uterus transplantation is feasible in a new clinical setting but underscores the critical importance of a specialized, proactive anesthetic strategy. Anesthesiologists must be prepared for prolonged surgical times, control postoperative pain in the donor, and complex hemodynamic management in the recipient. A multidisciplinary approach, psychological support, and comprehensive strategies to minimize perioperative discomfort for the donor, are crucial for optimizing outcomes for both donor and recipient.

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Abstract Objective To evaluate the efficacy and safety of combinations of oral midazolam and esketamine for pediatric preoperative sedation. Intervention Children aged 1‒6-years undergoing elective surgery were assigned to Group A (0.62 mg/kg midazolam and 2.05 mg/kg esketamine), Group B (0.41 mg/kg midazolam and 4.1 mg/kg esketamine), and Group C (0.21 mg/kg midazolam and 6.16 mg/kg esketamine). The combination was administered orally before anesthesia induction. Outcomes Primary outcome was sedation success, defined as a modified Ramsay sedation score ≥3a, low parent-child separation anxiety, and acceptance of the face mask for inhalation induction. Secondary outcomes included parental satisfaction, occurrence of Adverse Events (AE), and recovery times. Results The sedation success rate in Group B was 71.8%, which was significantly higher than Group A (53.5%, p < 0.05) but not Group C (68.2%, p > 0.05). There was no difference in the sedation success rate between Group A and Group C (p > 0.05). The overall incidence rate of AE in Group C was 25.90%, which was significantly higher than that in Group A (2.30%) and Group B (4.70%) (p < 0.05). No significant differences in sedation success rates were observed between genders within each group (p > 0.05). Conclusion The combination of 0.41 mg/kg midazolam and 4.1 mg/kg esketamine provided the most effective sedation with the fewest adverse events in pediatric patients. This regimen may reduce rescue sedation needs and improve perioperative flow. Trial registration http://www.chictr.org.cn (ChiCTR2400080633; date of first registration: February 4th, 2024).

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Abstract Introduction Hospitalization can generate stress and anxiety and lead to depression. Music therapy has been used in hospital environments to promote patient well-being. However, scarce research has examined heterogeneous groups using the single-session format. This controlled clinical trial aimed to compare the effects of three methods of single-session music therapy on reducing anxiety and depression in hospitalized adult patients with diverse endocrine disorders. Method Participants (n = 222) were non-randomly distributed into three experimental music therapy groups (compositional, songwriting, and receptive) and a control group. The instruments used were the Hospital Anxiety and Depression Scale (HADS; pre-and post-test). Results The experimental groups presented a statistically significant decrease in the HADS scores (p < 0.05) compared with the control group. Participants in the experimental groups reported an enhancement in well-being. Discussion Single-session music therapy interventions, mainly the receptive method, had a positive impact on reducing anxiety and depression in a heterogeneous group of hospitalized adult patients with endocrinopathies.

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Abstract Background Regular assessment of exercise tolerance is essential for managing COPD, nevertheless, the standard 6-Minute Walk Test (6MWT) is difficult to perform outside clinical settings. This study aimed to develop and validate a smartphone-based digital 1-Minute Sit-to-Stand Test (1MSTST) to estimate 6-Minute Walking Distance (6MWD) by integrating data from the phone's Inertial Motion Unit (IMU) with advanced machine learning algorithms, offering a convenient alternative for remote functional assessment. Methods The enrolled COPD patients completed the smartphone-based digital 1MSTST and 6MWT with a minimum 15-minute rest period between the two tests. Accelerometer and gyroscope data were recorded by a smartphone throughout the 1MSTST. Systolic and Diastolic Blood Pressure (SBP, DBP), Heart Rate (HR) and Pulse Oxygen Saturation (SpO2) were measured before and after the 1MSTST and 6MWT. The authors used a smartphone-based dataset of 66 subjects and algorithms such as Extreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), Support Vector Machine (SVM), Linear Regression (LR) and Random Forest (RF) to estimate the prediction of digital 1MSTST to 6MWD. The correlation between the features extracted from digital 1MSTST and the 6MWD was analyzed. Results A total of 66 patients with stable COPD were enrolled to build the predictive model for 6MWD. The change of HR and SBP after 1MSTST was higher than that of 6MWT (paired t-test, ΔHR: p < 0.0001, ΔSBP: p < 0.0001) with no significant difference in the change of DBP and SpO2 (paired t-test, ΔDBP: p = 0.974, ΔSpO2: p = 0.072). Pearson correlation analysis identified the top seven features that were strongly correlated with 6MWD. The RF machine learning model had the best performance to predict the 6MWD (R-square = 0.86, MAE = 24.3). Bland-Altman analysis indicates that the RF model provides a bias of -0.61 ± 31.04 and that the limits of agreement (95%, 1.96 SD) range from -60.22 to 61.45. Conclusions The smartphone-based digital 1MSTST, combined with machine learning, can accurately estimate 6MWD. The significance of this study lies in proposing a novel assessment paradigm that may serve as a practical tool for remote monitoring of exercise capacity in COPD management.

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Abstract This study describes the implementation of an interdisciplinary model within the COVID-19 cohort at Hospital das Clínicas, Universidade de São Paulo (HCFMUSP). Among 1957 survivors, 749 attended the first follow-up (6‒11 months), revealing that 83% reported persistent symptoms ‒ mainly fatigue, dizziness, pain, and dyspnea ‒ highlighting the need for extended monitoring. A four-year program involving 22 study groups was established to characterize symptom frequency, severity and disability, explore clinical and sociodemographic associations, and evaluate the potential for recovery through multidisciplinary approaches. A dedicated team coordinated recruitment, teleconsultations, in-person assessments and database management. Of 749 patients, 523 completed teleconsultations, 433 attended the first visit, and 367 the second. The implementation demonstrated that interdisciplinary research enhances patient engagement, reduces fragmentation, and supports efficient and high-quality research in complex human-based studies.

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Abstract Objective To assess the feasibility and performance of a robotic telesurgery platform operating within the Brazilian Unified Health System (SUS) infrastructure in a dry lab environment under wired and private 5 G network conditions. Methods Over three consecutive days, robotic surgeons performed three standardized dry lab tasks from a remote console at PROMIN‒FMUSP, with the robotic unit at HU-USP. Sessions were conducted using either a wired or a private 5 G network. Performance outcomes included task success and completion time. Connectivity metrics ‒ latency, jitter and packet loss ‒ were recorded; and per-participant mean values were used in descriptive analyses. Surgeons completed post-session assessments of perceived safety, usability, and mental workload. Results Twenty-eight robotic surgeons completed dry lab sessions (23 wired, 5 private 5 G). Task success was 100% for Task 1, 82.1% for Task 2, and 89.3% for Task 3; all failures occurred in wired sessions. Median completion times were 26 s (Task 1), 4.5 min (Task 2), and 8.5 min (Task 3). Median latency and jitter were significantly higher in 5 G than in wired sessions (latency: 32.4 vs. 12.0 ms; jitter: 30.8 vs. 6.8 ms). Median packet loss was low under both conditions (0.0% in 5 G; 0.09% in wired). Most surgeons rated the system as safe (78.6% assigned the maximum safety score) and considered it suitable for high-complexity procedures (67.9%). Conclusion Robotic telesurgery within SUS infrastructure was feasible in a simulated environment. Although the private 5 G network exhibited higher latency and jitter than the wired connection, the task completion and usability were preserved, supporting further evaluation in controlled clinical settings.

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Abstract Background Ovarian cancer is a leading cause of mortality among women globally. This study aimed to evaluate the diagnostic value of CA-125, HE4, and the ROMA index in identifying ovarian cancer in patients in Bangladesh. Methods This case-control study was conducted at the National Institute of Cancer Research and Hospital (NICRH) in 50 patients with histologically confirmed epithelial ovarian cancer, 25 patients with benign ovarian diseases, and 25 healthy controls. Women with prior chemotherapy or hormonal therapy, non-epithelial ovarian cancer, bilateral oophorectomy, pregnancy, or serious systemic illness were excluded. Serum CA-125 and HE4 levels were measured using Chemiluminescence Immunoassay (CLIA), and the ROMA index was calculated. Receiver Operating Characteristic (ROC) analysis was performed to assess diagnostic performance. Results The mean ages of participants were 52.5-years for ovarian cancer patients, 38.2-years for those with benign diseases, and 45.0-years for healthy controls. The median serum levels of HE4, CA-125, and ROMA index were significantly higher in ovarian cancer patients compared to controls. ROC analysis revealed AUCs of 0.95 for ROMA, 0.92 for HE4, and 0.88 for CA-125 in differentiating cancer from healthy controls, and 0.93 for ROMA, 0.94 for HE4, and 0.60 for CA-125 in differentiating cancer from benign ovarian diseases. ROMA and HE4 significantly distinguished ovarian cancer from benign conditions (p < 0.001), while CA-125 did not (p = 0.165). Conclusion In this study, the ROMA index appeared to perform better than HE4 and CA-125, though findings should be interpreted cautiously, considering the limited statistical power.

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Abstract Objectives This study examines the challenges related to pharmacological outcomes in Fibromyalgia (FM), a multifaceted syndrome characterized by widespread pain, cognitive impairment, and fatigue. It aims to evaluate medication use patterns, identify potential drug-drug interactions, assess adherence to clinical guidelines, and determine how these pharmacological factors may contribute to symptoms often described as fibro-fog and influence overall health and well-being. Methods This cross-sectional study analyzed medication usage and potential drug interactions in women with FM. Tools such as CheckTheMeds® and the CRIDECO Anticholinergic Load Scale were employed to assess the pharmacological appropriateness of treatments in alignment with clinical guidelines and to quantify anticholinergic burden. Results A total of 881 medication alerts were reviewed, corresponding to 108 women with FM (mean age: 54.06 ± 8.43). Pain management medications accounted for 72.94% of the total medications prescribed. The analysis revealed a significant anticholinergic burden in 50.93% of the patients. Conclusions Pharmacological reviews are essential in the management of FM, as they enhance treatment safety, minimize risks such as CNS depression and excessive anticholinergic burden. Optimizing medication regimens may indirectly influence symptoms commonly reported in fibromyalgia, including those often referred to as fibro-fog, while supporting safer and more individualized treatment strategies.

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Abstract Objective To compare outcomes of short-course versus longer-course antibiotic regimens in mechanically ventilated adult patients with sepsis due to pneumonia. Methods The authors performed a retrospective cohort study using the MIMIC-IV database (2008-2022), identifying 2590 adults meeting Sepsis-3 criteria with a primary diagnosis of pneumonia requiring invasive mechanical ventilation. Patients were stratified by antibiotic duration (short: 2‒7 days; long: 8‒14 days). Demographics, comorbidities, severity (SOFA score, PaO2/FiO2 ratio), and microbiology were extracted. The primary outcome was 90-day all-cause mortality. The authors used Kaplan-Meier analysis, multivariable Cox proportional hazards models, and subgroup analyses to assess the effect of treatment duration. Results The study found that overall 90-day mortality did not differ significantly (short-course ∼41.3% vs. long-course ∼41.2%; p = 0.98). Subgroup analyses indicated that in patients > 65-years, those with severe hypoxemia (low PaO2/FiO2), on RRT, or infected with Staphylococcus aureus or Pseudomonas aeruginosa, shorter therapy was associated with higher mortality rates (p < 0.05). Conversely, younger or less severely ill patients showed no significant effect of duration. These findings may reflect residual confounding. Conclusions In this observational cohort, shorter antibiotic courses were not associated with increased 90‑day mortality after adjustment. Given potential confounding and limited recurrence data, subgroup signals are hypothesis‑generating and require confirmation in randomized trials.

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Abstract Objective This study aimed to develop and validate a machine learning model integrating multi-omics and radiomics data to improve diagnostic accuracy and identify potential biomarkers for Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD). Methods A total of 278 patients with RA were enrolled across two cohorts. Cohort 1 (63 RA-nonILD, 46 RA-ILD) provided clinical data, chest CT images, plasma, and PBMC samples for non-targeted metabolomics, transcriptomics, and 4D DIA proteomics. Cohort 1 was split in a 6:4 ratio into training and validation sets. Machine-learning algorithms (RF, LASSO, SVM) and a Transformer model were used to screen biomarkers. Diagnostic models were constructed using LASSO, RF, LightGBM, and CatBoost. A combined imaging-clinical logistic regression model was developed and externally validated in cohort 2 (102 RA-nonILD, 67 RA-ILD). Associations between key biomarkers, inflammation, lung function, and CT severity were examined, and pathways related to the radiomic feature Kurtosis were explored. Results Nine radiomic features, five metabolites, two proteins, and eight genes were identified as key biomarkers. The metabolomics-based CatBoost model showed the best single-omics performance (AUC = 0.982). The multi-omics integration model outperformed all single-omics models. The imaging-clinical model demonstrated strong diagnostic accuracy in both internal (AUC = 0.963) and external validation (AUC = 0.913), and a nomogram was constructed for clinical risk assessment. Key biomarkers correlated with inflammatory indicators and lung-function decline, and high-Kurtosis-associated genes were enriched in pro-fibrotic pathways. Conclusion Integrating multi-omics and radiomics with machine learning yields a robust diagnostic strategy for RA-ILD. The imaging-clinical nomogram provides a practical tool for risk assessment, and identified biomarkers reflect disease severity and progression.

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Abstract Background This study compared the clinical and radiological outcomes of Onlay and Inlay Lower Trapezius Tendon (LTT) transfer techniques in managing posterosuperior Functional Irreparable Rotator Cuff Tears (FIRCTs). Methods This retrospective comparative study included patients who underwent Onlay and Inlay LTT transfer. The inclusion criteria were FIRCTs defined by tendon retraction to the glenoid, fatty infiltration > 2 grade according to Goutallier, and with a positive External Rotation (ER) lag sign. Patients with irreparable subscapularis, dysfunctional deltoid, advanced glenohumeral osteoarthritis, cuff tear arthropathy, and revision surgeries were excluded. Outcomes measures included the active Range Of Motion (ROM), Acromiohumeral Distance (AHD), American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE) score and Constant score. Results The study included 39 patients (21 Onlay and 18 Inlay LTT) with at least 2-year follow-up. Both groups achieved significant improvement in active forward elevation from 118.6 ± 57.6° to 145.7 ± 18° in the Onlay group (p = 0.046) and 112.2 ± 49.2° to 140.6 ± 30.6° in the Inlay group (p = 0.046). The ER improved from 31 ± 21.2°to 44.3 ± 16° in the Onlay (p = 0.027) and 29.4 ± 27.1° to 45 ± 16.9° in the Inlay group (p = 0.046). The postoperative AHD was better in the Onlay group (7.3 ± 2.5 vs. 4.8 ± 3.2 mm, p = 0.001). The ASES, SANE, and Constant scores all improved significantly at final follow-up (all p < 0.001) in both groups and reached the Minimal Clinically Important Difference. Conclusion Both the onlay and Inlay techniques of LTT transfer effectively improved shoulder function in patients with irreparable posterosuperior rotator cuff tears. The Onlay technique resulted in better AHD at final follow-up.

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Abstract Introduction Rheumatoid Arthritis (RA) is a chronic inflammatory disease often linked to Interstitial Lung Disease (ILD). Slit guidance Ligand-3 (Slit3), a member of the axon guidance molecule superfamily, mediates a series of biological activities, including the regulation of the inflammatory response and fibrosis. This study explored Slit3’s clinical significance as a serum biomarker for RA-ILD. Methods Between November 2022 and April 2024, patients diagnosed with RA were included in the Foshan First People's Hospital. The clinical data of patients were collected from hospital records, and the serum level of Slit3 was measured using an enzyme-linked immunosorbent assay. Logistic regression was employed to determine odds ratios for Slit3 and other indicators associated with the development of RA-ILD. Results In total, 232 patients were included. Patients with RA in the high Slit3 subgroup were older, were more likely to be positive for rheumatoid factor and anti-cyclic citrullinated peptide antibody, and had higher levels of erythrocyte sedimentation rate and C-reactive protein. They also showed higher Disease Activity Scores (DAS28-CRP, DAS28-ESR, SDAI) as well as elevated pro-inflammatory cytokine interleukin-6. Notably, logistic regression analysis indicated that the elevated serum level of Slit3 was an independent predictor of RA-ILD. Conclusions Elevated serum level of Slit3 was associated with higher disease activity and served as an independent risk factor of RA-ILD. Slit3 may hold promise as a useful serum biomarker and therapeutic target for RA-ILD.

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Abstract Objective This study aimed to develop and validate a nomogram model integrating 5-Hydroxytryptamine (5-HT) and oxidative stress markers to predict the efficacy of flunarizine hydrochloride in treating vertigo. Methods A retrospective study included 244 vertigo patients treated with flunarizine hydrochloride from September 2022 to December 2024. Patients were divided into training (70%) and validation (30%) sets. Clinical data, 5-HT levels, and oxidative stress indicators (Superoxide Dismutase [SOD], Malondialdehyde [MDA], Glutathione Peroxidase [GSH-Px]) were collected and analyzed. The influencing factors of treatment efficacy were screened using univariate and multivariate logistic regression. Least Absolute Shrinkage and Selection Operator (LASSO) regression was implemented using the R 'glmnet' package with 10-fold cross-validation. A nomogram model was constructed by integrating the independent influencing factors of treatment efficacy. Model performance was assessed via calibration curves, Consistency index (C-index), Decision Curve Analysis (DCA), and Receiver Operating Characteristic (ROC) curve. Results There were 176 cases in the effective group and 68 cases in the ineffective group. Age, 5-HT, SOD, MDA, and GSH-Px were identified as independent predictors of treatment efficacy (p < 0.05). After variable selection via LASSO regression, the reduced nomogram demonstrated strong discriminative ability, with C-indexes of 0.862 (in the training set) and 0.874 (in the validation set), and average absolute errors of 0.144 and 0.138, respectively. Hosmer-Lemeshow tests confirmed good fit of the model (training: χ² = 9.061, p = 0.337; validation: χ² = 8.034, p = 0.430). ROC analysis yielded Area Under the Curve (AUC) values of 0.861 (95% CI: 0.797-0.925) and 0.870 (95% CI: 0.798-0.973) for training and validation sets, with sensitivity/specificity values of 0.892/0.711 and 1.000/0.650, respectively. Conclusion The simplified nomogram incorporating age and oxidative stress markers demonstrates robust predictive accuracy while enhancing clinical feasibility. Actionable thresholds were established, such that patients with a score > 70-points should be considered for alternative therapies due to a high predicted risk of treatment non-response.

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Abstract Background Mounting evidence suggests that diet-induced inflammation may modulate the risk of Latent Tuberculosis Infection (LTBI). However, the reported association between the Dietary Inflammatory Index (DII) and LTBI remains inconsistent, and potential confounding factors such as country of birth have not been fully elucidated in previous studies. Objective This study aimed to evaluate the confounding effect of country of birth on the apparent association between DII and LTBI, using data from the National Health and Nutrition Examination Survey (NHANES). A key hypothesis was tested that the observed relationship between DII and LTBI could be explained by the stratification of nativity status. Methods A cross-sectional analysis was conducted on 3892 eligible participants from NHANES with no missing values for core variables. Comprehensive variables were collected, including core indicators DII,LTBI status, and active tuberculosis status defined in accordance with the diagnostic criteria specified in the NHANES operational guidelines), demographic characteristics (country of birth, age, gender, ethnicity, household size), socioeconomic factors (educational attainment, Poverty Income Ratio [PIR], marital status), and health-related covariates (Body Mass Index [BMI], smoking habits, alcohol intake, Hypertension [HPT], Diabetes Mellitus [DM]). Logistic regression models, smooth curve fitting, and stratified analyses by country of birth (US-born vs. non-US-born) were applied to quantify the association between DII and LTBI, with sequential adjustment for potential confounders. Results The DII values of the participants ranged from -4.63 (highly anti-inflammatory diet) to 5.47 (highly pro-inflammatory diet), with a mean of 1.40±1.91, indicating a slight pro-inflammatory dietary tendency overall. LTBI prevalence varied by TB classification, and TB-positive groups showed significantly higher active tuberculosis rates than the TB-negative group. In the initial multivariate logistic regression model, adjusted for demographic, socioeconomic, and health-related factors (excluding country of birth), a significant inverse association was observed between DII and LTBI (OR = 0.93, 95 % CI 0.88-0.98, p = 0.011). However, this association was attenuated to non-significance after further adjustment for country of birth (OR = 0.96, 95 % CI 0.90-1.01). Stratified analyses confirmed the lack of a significant association between DII and LTBI in both US-born (OR = 0.95, 95 % CI 0.88-1.04) and non-US-born (OR = 0.96, 95 % CI 0.88-1.03) subgroups, with all interaction p-values > 0.05. Additionally, the initial linear dose-response relationship between DII and LTBI was no longer maintained after controlling for country of birth. The authors acknowledge that the country of birth variable is a relatively crude indicator, and residual confounding may persist in the current analysis. Conclusions In this nationally representative sample, the initially observed inverse association between DII and LTBI was not sustained after adjusting for country of birth, indicating that nativity status is a critical confounder of the apparent DII-LTBI relationship. The findings highlight that the previously reported protective effect of an anti-inflammatory diet against LTBI may be attributable to the confounding influence of country of birth rather than a direct causal effect. Future epidemiological studies investigating diet-infection relationships should rigorously assess and control for country of birth as a potential confounding factor, and explore more refined indicators to reduce residual confounding.

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Abstract Background COVID-19 can lead to enduring long-term effects, particularly in severe cases requiring hospitalization. This study contrasts Normal lung Patterns (NP) with Restrictive lung Disease (RD) regarding the evolution of physical performance and functionality post-COVID-19 hospitalization. Methods This is a prospective cohort study. Individuals post-COVID-19 were evaluated at 1- and 12-months post-discharge. Data collection included analysis of lung function, physical performance, functionality, and clinical data. Results Of the 185 participants initially assessed, 62 attended the final evaluation. At 1 month post-discharge, 57 (92%) had been admitted to the ICU and 47 (76%) exhibited RD. After 12-months, RD decreased to 20 (32%). Both groups showed improved Sit-to-Stand repetitions (p = 0.002). A substantial percentage (28%) of participants with RD experienced functional impairments at one month, with a notable proportion maintaining these limitations after one year (15%). Conclusions Almost half of individuals with RD (43%) still exhibited this pulmonary alteration after one year (RD 20/47). Additionally, RD participants demonstrated decreased physical performance at one month (15%), with only a fraction (5%) showing improvement after one year. Finally, these results pointed out the necessity of long-term follow-up regarding the recovery trajectory of post-COVID patients. Furthermore, there is a clear need to offer specific rehabilitation focusing on pulmonary, physical performance and functionality.

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Abstract Background Older adults hospitalized with Community-Acquired Pneumonia (CAP) frequently experience early secondary cardiovascular events. The authors quantified risk factors and the incremental value of frailty and cardiac biomarkers beyond the Pneumonia Severity Index (PSI). Methods The authors ran a single-center, prospective cohort of adults ≥65-years with CAP admitted between January and December 2024. The primary endpoint was any in-hospital SCE (acute heart failure, MI/ACS per Fourth Universal Definition, new atrial fibrillation/flutter, ischemic stroke/TIA, or cardiovascular death). Prespecified predictors were prior cardiovascular disease, PSI, Clinical Frailty Scale (CFS), High-Sensitivity Troponin (hs-cTn), and NT-proBNP. Penalized multivariable logistic regression estimated adjusted odds ratios, 30- and 90-day outcomes were used to cause-specific Cox and Fine-Gray models. Results Among 172 patients (median age 77; 46% women), in-hospital SCEs occurred in 27.9% patients (48 out of 172 patients with 65 total component events; 95% CI 21.7-35.0), and 68.8% occurred within 72 h. Specifically, heart failure was 18.0%, new atrial fibrillation was 9.9%, MI was 5.8%, and cardiovascular death was 2.9%. In multivariable analysis, CFS ≥ 5 (Aor = 2.07, 95% CI 1.03-4.17), abnormal hs-cTn (aOR = 2.52, 1.25-5.06), and NT-proBNP per doubling (aOR = 1.38, 1.12-1.71) independently predicted SCEs. Discrimination improved from AUC 0.68 (PSI) to 0.73 with CFS and 0.79 with biomarkers (optimism-corrected 0.77), with NRI +0.18 and decision-curve net benefit at 10%-25% thresholds. Cumulative SCE incidence was 33.7% at 30-days and 37.8% at 90-days. Fine-Gray results were consistent. Conclusions SCEs were common and occurred early after admission. Adding frailty and cardiac biomarkers to PSI improved risk stratification and may help high-risk patients receive closer monitoring. External validation is needed before its clinical application.

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Abstract Introduction Aging has a significant impact on health, leading to changes in body composition and physical functionality in older adults. Objective Given the relevance of this topic, the aim of this study was to analyze the effects of vitamin D supplementation combined with physical exercise over a 12-week period on body composition and metabolic profile in elderly women. Methods The study followed a clinical approach, employing a randomized, double-blind, placebo-controlled trial, in accordance with the guidelines established by the Consolidated Standards of Reporting Trials (CONSORT), conducted at the Movement Studies Laboratory in São Paulo, Brazil. Analyses were performed using an intention-to-treat approach with random effects regression models. The study sample consisted of 46 elderly individuals, divided into two groups with 23 participants each. The experimental group received vitamin D3 supplementation at a dose of 49,000 IU/week, while the placebo group received seven capsules of the same size, volume, and color, containing lactose but no vitamin D3. Results After analyzing the results, it was observed that the groups were homogeneous in terms of age (p = 0.7658) and BMI (p = 0.5904). The results showed differences in 25-OH vitamin D levels (p < 0.001) between the groups over time. Conclusion In conclusion, vitamin D supplementation successfully increased serum levels but failed to provide additional benefits for muscle mass or metabolic markers compared to resistance training alone.

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Abstract Introduction Critical Velocity (CV) is widely used to assess aerobic performance in endurance sports. Studies have compared protocols for CV determination in elite athletes. However, knowledge on the influence of the assessment protocol on CV and sex-based differences on metabolic responses at critical swimming velocity is limited. Objective This study aims to compare different protocols for determining CV in swimming among male and female triathletes and to compare sex-based differences in the metabolic and perceived exertion responses after swimming 750 m at CV estimated by the three-parameter model. Methods Highly trained amateur triathletes (12 men, 35.7 ± 11.0 years; 10 women, 38.1 ± 6.0 years) performed maximal swimming tests (50, 100, 200, and 400 m) to estimate Critical Velocity (CV). Each completed a 750 m swim at the CV determined by the three-parameter protocol (100-200-400 m), with monitoring of metabolic responses (lactate level and heart rate) and pain, dyspnea, and subjective perceived exertion. Results The four-distance protocol yielded the highest CV in both sexes, whereas the protocol based on 92% of the 400 m time produced the lowest values (p < 0.001). After the 750 m swim, men showed higher ratings of perceived exertion (p = 0.005), pain (p < 0.001), dyspnea (p < 0.001), and blood lactate concentration (p < 0.001) than women. Conclusion The protocol used to determine CV significantly influences estimated values. Importantly, all findings related to physiological and perceptual responses during the 750 m swim are specific to the CV determined by the three-parameter protocol and should not be generalized to other CV determination methods. Under this protocol, CV may be associated with an exercise intensity approaching the severe domain; however, this interpretation should be made with caution.

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Abstract Background Hypertensive heart disease with heart failure is a severe cardiovascular condition with high mortality rates. The relationship between the Lactate Dehydrogenase to Albumin Ratio (LAR) and mortality in these patients remains unclear. Methods The authors analyzed 3019 patients with hypertensive heart failure using data from the MIMIC-IV database. Cox regression models were used to assess the association between LAR and mortality, with adjustments for various covariates. Restricted cubic spline analysis was employed to evaluate the threshold effect of LAR on mortality. Kaplan-Meier survival curves and subgroup analyses further explored the impact of LAR. Results LAR was significantly associated with increased mortality across all time points: hospital mortality (HR = 4.86, 95% CI 4.12 to 5.73; p < 0.001), 30-day mortality (HR = 4.16, 95% CI 3.56 to 4.87; p < 0.001), 90-day mortality (HR = 3.56, 95% CI 3.08 to 4.12; p < 0.001), and 365-day mortality (HR = 2.91, 95% CI 2.54 to 3.33; p < 0.001). These associations remained significant after multivariable adjustments. The Cox regression model with restricted cubic spline analysis revealed a threshold effect of LAR on mortality, with turning points at 1.662 for hospital mortality, 2.393 for 30-day mortality, 2.407 for 90-day mortality, and 2.406 for 365-day mortality (all p < 0.001 for non-linear tests). Kaplan-Meier survival curves showed significant differences in survival across LAR quartiles for all mortality outcomes (all p < 0.001). Conclusion The LAR is significantly associated with mortality in critically ill patients, with a clear threshold effect. LAR may serve as a potential prognostic marker for identifying high-risk patients.

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Abstract Background Population-based studies exploring the association between sarcopenia, possible sarcopenia and Knee Osteoarthritis (KOA) ‒ particularly including the intermediate state of possible sarcopenia ‒ remain limited. The authors aimed to explore both cross-sectional and longitudinal associations between possible sarcopenia, sarcopenia, and KOA in a large cohort of Chinese adults. Methods The authors utilized data from the China Health and Retirement Longitudinal Study. After applying the exclusion criteria, a total of 5018 participants aged 45-years or older were included and followed from 2011 to 2015. Sarcopenia status was classified as non-sarcopenia, possible sarcopenia, or sarcopenia according to the Asian Working Group for Sarcopenia. Logistic regression was used to assess the associations between sarcopenia status and KOA, including associations with changes in sarcopenia status over follow-up. Results Sarcopenia and possible sarcopenia demonstrated a significant positive association with KOA, exhibiting an Odds Ratio (OR) of 1.37 (95% CI: 1.02‒1.83) and an OR of 1.55 (95% CI: 1.26‒1.91), respectively. Participants who newly developed sarcopenia had an increased likelihood of developing KOA than those who remained non-sarcopenic, with an OR of 1.72 (95% CI: 1.27‒2.32). The incidence of KOA differed significantly among the non-sarcopenia, possible sarcopenia, and sarcopenia groups, with rates of 10.0% in the non-sarcopenia group, 17.8% in the possible sarcopenia group, and 16.1% in the sarcopenia group (p-value < 0.01). Conclusions Sarcopenia and possible sarcopenia were associated with the occurrence of KOA. Individuals who newly developed sarcopenia or possible sarcopenia were at a higher risk of developing KOA during the four-year follow-up.

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Abstract Background Carpal Tunnel Syndrome (CTS) is a common entrapment neuropathy leading to pain and functional impairment. While smoking has been proposed as a modifiable risk factor, evidence from observational studies remains inconsistent due to potential confounding and reverse causality. Method The authors performed a two-sample Mendelian Randomization (MR) analysis to assess the causal relationship. Genetic instruments for five smoking phenotypes were derived from large-scale Genome-Wide Association Studies (GWAS). Summary-level data for CTS were obtained from the FinnGen Consortium (n = 480,201). The Inverse Variance Weighted (IVW) method was the primary analysis, supplemented by four other MR methods and a suite of sensitivity analyses to assess robustness and pleiotropy. Results Genetically predicted smoking propensity was associated with a higher risk of CTS. Specifically, genetic predisposition to smoking initiation (ORMR-IVW = 1.53; 95% CI 1.33-1.76; p < 0.001) and heavier cigarette consumption (ORMR-IVW = 1.52; 95% CI: 1.31-1.77; p < 0.001) significantly increased CTS risk. The estimate for current smoking was particularly strong (ORMR-IVW=3.96; 95% CI 2.20-7.12; p < 0.001). Sensitivity analyses were largely consistent, though some heterogeneity and potential pleiotropy were detected for specific phenotypes. Conclusions This MR study supports a causal role of smoking in the development of CTS. These findings underscore the importance of smoking cessation as a potential preventive measure against CTS and should be integrated into patient counseling and public health strategies.

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Abstract Objective Pancreatic Cancer (PC) is a highly aggressive malignancy with a dismal prognosis, primarily due to late-stage diagnosis and limited therapeutic options. This study aimed to identify potential biomarkers involved in PC progression and immune microenvironment modulation. Methods RNA sequencing data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were integrated to identify differentially expressed genes. Mendelian Randomization (MR) analysis was conducted to assess causal associations between candidate genes and PC risk. Immune cell infiltration was evaluated using the CIBERSORT algorithm, and mediation analysis explored the role of immune cells in PC progression. Validation was performed using RT-qPCR and immunohistochemistry in clinical tissue samples. Results CLIC3 and MST1R were significantly overexpressed in PC tissues and associated with advanced tumor stages. MR analysis confirmed their causal relationship with PC, with Odds Ratios of 2.36 (95% CI: 1.58-3.51) for CLIC3 and 1.30 (95% CI: 1.06-1.60) for MST1R. High expression of these genes correlated with increased M0 macrophages and decreased CD8⁺ T cells, CD4⁺ T-cells, and naïve B-cells, suggesting immune dysregulation. Mediation analysis emphasized the pivotal role of CD8⁺ cytotoxic T-cells in PC progression. Moreover, CLIC3 and MST1R were closely associated with immune checkpoint molecules CD276 and NT5E. Conclusions CLIC3 and MST1R are overexpressed and causally implicated in pancreatic cancer development and immune modulation. They represent promising biomarkers and potential therapeutic targets for precision immunotherapy in PC.

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Abstract Background The causal relationship between circulating blood cells and Osteoarthritis (OA) remains unclear. This study aimed to explore this potential relationship using a two-sample Mendelian Randomization (MR) approach. Methods Data from large-scale GWAS (Blood Cell Consortium and GWAS Catalog) were analyzed using two-sample MR methods, with Inverse Variance Weighting as the primary approach. A Bonferroni correction was applied for multiple testing for the two primary traits. Robustness was assessed through comprehensive sensitivity analyses for heterogeneity and pleiotropy. Results After Bonferroni correction, Genetically Predicted Hemoglobin (HGB) showed a weak genetic association consistent with a potential causal pathway for OA risk (OR = 1.004, 95% CI 1.001-1.007, p = 0.018). The association for Neutrophil (NEU) count was not statistically significant. While sensitivity analyses did not detect directional pleiotropy, significant heterogeneity was observed for the genetic instruments. Conclusion This exploratory study provides preliminary genetic evidence for a statistically significant but clinically negligible MR estimate of hemoglobin in OA pathogenesis. The clinical and biological significance of this minuscule effect remains uncertain. The findings should be interpreted as hypothesis-generating, highlighting the need for further research rather than establishing a definitive causal link.

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Abstract Objective To investigate the correlations among seven emotions, Traditional Chinese Medicine (TCM) syndromes, and serum levels of Interleukin-6 (IL-6) and Interferon-gamma (IFN-γ) in patients with primary lung cancer. Methods In this prospective cohort study, 331 newly diagnosed, treatment-naïve lung cancer patients were enrolled. TCM syndrome differentiation was independently performed by two blinded senior physicians. Patients were categorized into four syndrome types: Lung Qi Stagnation with Phlegm and Blood Stasis (n = 95), Qi and Yin Deficiency (n = 127), Spleen Deficiency with Phlegm-Dampness (n = 36), and Yin Deficiency with Phlegm-Heat (n = 73). Emotional states were assessed using the “TCM Seven Emotions Scale”. Serum IL-6 and IFN-γ levels were measured via ELISA. Results Specific emotions were predominantly associated with particular TCM syndromes (all p < 0.05). The Lung Stagnation with Phlegm and Blood Stasis group showed higher IL-6 levels, while the Qi and Yin Deficiency group had lower IFN-γ levels compared to other syndromes (p < 0.05). Crucially, Spearman's correlation analysis revealed a significant positive correlation between the total emotion score and serum IL-6 level (rs = 0.325, p < 0.001), and a significant negative correlation with IFN-γ level (rs = -0.391, p < 0.001). Conclusion The seven emotions exhibit syndrome-specific expression patterns in lung cancer patients. Significant correlations were found between emotional states and the inflammatory markers IL-6 and IFN-γ, suggesting a potential integrative link between psychological state, TCM diagnosis, and systemic inflammation, which may inform clinical approaches.

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Abstract Background The prevalence of diabetes‑associated Lower Urinary Tract Symptoms (LUTS) is relatively low, and there are limited clinical studies on its associated factors. The present study proposed to investigate the predictive value of various inflammatory indices in patients with diabetes‑associated LUTS. Methods Utilizing data from the National Health and Nutrition Examination Survey 2005‒2008, patients were categorized into four groups: normal group, Diabetes Mellitus (DM) group, LUTS group, and diabetes‑associated LUTS group. Inflammatory indices included C-Reactive Protein (CRP), White Blood Cell (WBC) count, Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Systemic Inflammation Response Index (SIRI), and Systemic Inflammation Index (SII). Multivariate logistic regression and Restricted Cubic Splines (RCS) were employed to evaluate the relationship between inflammatory indices and diabetes‑associated LUTS. Results A total of 5680 participants were included in the final analysis, comprising 3779 females and 1901 males. The prevalence of diabetes‑associated LUTS was 6.9% in females and 2.2% in males. Diabetes-associated LUTS was associated with older age, lower educational level, hypertension, congestive heart failure, coronary heart disease, emphysema, and higher body mass index and inflammatory indices. Furthermore, multivariate logistic regression analysis revealed that WBC count was a significant factor for both female and male diabetes‑associated LUTS patients, with higher WBC levels correlating with increased diabetes‑associated LUTS risk (females: adjusted Odds Ratio [OR] = 1.115 [1.032‒1.205], p = 0.006; males: OR = 1.207 [1.083‒1.345], p = 0.001). RCS revealed a positive association between WBC count and diabetes‑associated LUTS in female and male participants. Conclusion Inflammatory markers such as CRP and WBC count were higher in the diabetes‑associated LUTS group compared to the other three groups. WBC count is an associated factor for diabetes‑associated LUTS, and incorporating WBC count into clinical assessments can aid in identifying diabetes‑associated LUTS patients, thereby facilitating targeted interventions.

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Abstract Aims To investigate the clinical characteristics of patients with first-episode acute appendicitis and explore the value of CT imaging grading combined with inflammatory markers in evaluating the cure and relapse of conservative treatment. Methods A retrospective cohort study was conducted to collect the clinical data of 482 patients with acute appendicitis diagnosed in the Emergency Department of the Second Affiliated Hospital of Fujian Medical University from October 2021 to February 2024. The imaging features of these patients were evaluated using Computed Tomography (CT) scans. Descriptive analysis, chi-square test, ordinal logistic regression model, Kaplan-Meier curve, and COX regression analysis were used to analyze the data. Results Elevated levels of Procalcitonin (PCT) and C-Reactive Protein (CRP) were associated with higher CT grades. Acute appendicitis patients with higher CT grades had a poor prognosis with antibiotic treatment. CT grade was a predictor of the prognosis of antibiotic treatment, and a high CT grade was an independent risk factor for relapse. Conclusion CT grade combined with inflammatory markers (PCT and CRP) can effectively predict the prognosis of conservative treatment for acute appendicitis, and CT grade can be used to predict the risk of relapse.

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Abstract Objective To evaluate the association between lipid profile, statin use, metabolic syndrome, and clinic. Prostate Enlargement (PE) in adult men attending a urology outpatient clinic. Methods A cross-sectional study was conducted among 1117 men aged 40-years or older. Prostate volume was measured by ultrasonography; a volume ≥ 40 mL was considered the threshold for enlargement. Independent variables included lipid fractions, prescription-based statin use, and components of metabolic syndrome. Multivariate logistic regression models were applied, adjusted for age, hypertension, and medication exposure. Results The median age was 63-years (IQR: 55-71), and the median prostate volume was 34.0 mL (IQR: 26.0-48.0). Statin use was identified in 36.5% of the sample, and the prevalence of PE was 38.9%. Age was the only factor independently associated with PE (OR = 1.07; 95% CI: 1.05-1.09; p < 0.001). Metabolic syndrome was associated with PE in crude analysis; however, this association lost statistical significance after adjustment for potential confounders. Conclusion Age was the only independent determinant of prostate enlargement in this metabolically controlled cohort. Lipid parameters and prescription-based statin use showed no adjusted association with prostate volume; however, the lack of detailed statin exposure data warrants cautious interpretation of these findings.

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Abstract Objective The causal relationship between thyroid dysfunction and osteomyelitis was unclear. The authors used two-sample Mendelian Randomization (MR) methods to investigate the potential causal effects of hyperthyroidism and hypothyroidism on the risk of osteomyelitis. Method The authors obtained summary-level data from large-scale genome-wide association studies for hyperthyroidism, hypothyroidism, and osteomyelitis for individuals of European ancestry. The causal analysis between thyroid dysfunction and osteomyelitis was carried out using Univariable MR (UVMR). Subsequently, Multivariable MR (MVMR) was performed to adjust for potential confounding from years of schooling, smoking initiation, and body mass index. A range of sensitivity analyses, including reverse MR, was conducted to test the robustness of the results. Results In univariable analysis, genetically predicted hyperthyroidism (Odds Ratio [OR = 1.21], 95% Confidence Interval [95% CI 1.071‒1.374], p = 0.002) and hypothyroidism (OR = 1.140, 95% CI 1.035‒1.255, p = 0.0078) were both associated with an increased risk of osteomyelitis. After adjusting for confounders in the MVMR analysis, the association for hyperthyroidism was attenuated to non-significance (OR = 1.07, 95% CI 0.95‒1.21, p = 0.28). In contrast, the causal effect of hypothyroidism on osteomyelitis remained robust (OR = 1.15, 95% CI 1.03‒1.29, p = 0.02). Reverse MR analyses showed no evidence that osteomyelitis was a cause of either hyperthyroidism or hypothyroidism. Conclusion This study provided genetic evidence supporting a causal effect of hypothyroidism on an increased risk of osteomyelitis. This finding provides evidence-based recommendations for closely monitoring patients with hypothyroidism to prevent the onset of osteomyelitis.

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Abstract Background Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS), a common sleep-related breathing disorder, is closely associated with an increased risk of cardiovascular and metabolic comorbidities. Polysomnography, the diagnostic gold standard, is costly and environmentally sensitive. This study explored the diagnostic potential of miR-1180-3p and its role in Chronic Intermittent Hypoxia (CIH)-induced vascular injury. Methods Serum miR-1180-3p and CERS1 levels were measured in 112 OSAHS patients and 88 controls via qRT-PCR. Correlations with PSG parameters (LSpO₂, AHI, TS90%) were analyzed. In vitro, HUVECs were exposed to CIH, and miR-1180-3p effects on cell viability, apoptosis, and oxidative stress (MDA, SOD, GSH-Px) were assessed. TargetScan and dual-luciferase assays validated miR-1180-3p-CERS1 binding. Evaluating miR-1180-3p/CERS1 axis regulation of OSAHS pathogenesis via co-inhibition experiments. Results A significant upregulation of miR-1180-3p was detected in OSAHS patients (p < 0.001). miR-1180-3p served as an independent risk factor for OSAHS (OR = 5.405, 95% CI 2.247‒13.001) and held diagnostic value (AUC = 0.882). miR-1180-3p correlated negatively with LSpO2 (r = -0.705) but positively with AHI (r = 0.676) and TS90% (r = 0.774), with correlations persisting across mild, moderate, and severe OSAHS subgroups. In CIH-treated HUVECs, miR-1180-3p inhibition restored cell viability, reduced apoptosis, and alleviated oxidative stress. CERS1 was confirmed as a direct target, and its silencing reversed miR-1180-3p inhibition-mediated protection. Conclusion miR-1180-3p was a novel diagnostic biomarker for OSAHS. By targeting CERS1, miR-1180-3p exacerbated CIH-induced damage to HUVECs, thereby regulating the pathological progression of OSAHS.

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Abstract Objective Adipose tissue is used in several specialties to obtain Adipose-derived Stem Cells (ASC) and fat derivatives. Several studies analyze protocols for harvesting fat tissues. However, these studies showed inconclusive data regarding cell viability and function. Thus, the objective of this study was to analyze protocols regarding cell viability, identify the best method, and test cell differentiation and proliferation when using the chosen methods. Methods This study harvested lipoaspirate products from three healthy women undergoing aesthetic procedures. The first analysis corresponds to the viability of fat tissue liposuction products for the washing process. The second analyzes the effect of anesthetic drugs, and the third analyzes the cytotoxicity of the fraction process. After testing all these steps, the authors prepared the fat tissue using the best method chosen after the first analysis to test cell differentiation (adipogenesis, osteogenesis, and chondrogenesis) and proliferation. Results The analysis showed that saline solution 0.9% was the washing solution that induced less cell death. Regarding anesthetic and vasoconstrictor drugs, lidocaine, ropivacaine, and epinephrine caused similar levels of cell death, but sodium bicarbonate increased cell proliferation. The number of passages through a 2.4 mm Luer-to-Luer transfer device did not influence cell viability. The proliferation and differentiation of ASC in adipocytes, osteoblasts, and chondrocytes were preserved using saline solution 0.9% and 20 × passages for fat fractioning. Conclusions The findings of this study provide preliminary in vitro evidence that may improve future investigations on the fat harvesting process.

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Abstract Background Lactate has been proven to be an important metabolite involved in tumor initiation, progression, and tumor microenvironment, affecting patient prognosis. The role of lactate metabolism-related genes in liver cancer is unclear. Methods The authors identified lactate metabolism-related genes from five key pathways and scored their relevance. Genetic and clinical data from TCGA-LIHC and validation cohorts (GSE54236, ICGC, and GSE116174) were analyzed to confirm survival associations. Sodium lactate rescue experiments were performed on ASPDH-overexpressing cells to investigate the role of lactate. In vivo xenograft models verified ASPDH’s effects on tumor growth and NF-κB/PD-L1 signaling. Results From 320 lactate metabolism-related genes, four core genes were identified: LPCAT1, TMEM220-AS1, ASPDH, and LECT2. Low ASPDH expression correlated with poorer survival across multiple datasets. PD-L1 ROC analysis showed high diagnostic efficacy (AUC = 0.8). ASPDH knockdown enhanced proliferation, colony formation, migration, and invasion, while overexpression had opposite effects. Sodium lactate rescue experiments further demonstrated that exogenous lactate partially restored cell proliferation, migration, and invasion abilities suppressed by ASPDH overexpression, along with increased nuclear p65 and PD-L1 expression, confirming lactate's role in mediating ASPDH-regulated NF-κB pathway activity and PD-L1 expression. GSEA linked ASPDH to PD-L1 expression and checkpoint pathways. In vivo, ASPDH overexpression suppressed tumor growth, decreased nuclear p65 and PD-L1, and increased cytoplasmic p65, alongside reduced lactate secretion and NF-κB/PD-L1 modulation. Conclusion ASPDH inhibits liver cancer cell proliferation, migration, and invasion by downregulating lactate secretion and suppressing the NF-κB/PD-L1 signaling pathway.

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Abstract Background Allergic Rhinitis (AR) represents a widespread chronic inflammatory condition, with especially prevalence observed in children and urban populations. Aim This study primarily explored the expression of miR-628-3p in AR and its functional implications on the inflammatory response, and elucidated the underlying molecular mechanisms through which miR-628-3p regulates AR. Methods RT-qPCR analysis quantified miR-628-3p expression in AR patient serum and cell models. The biological functionality of the cells was assessed using the CCK-8 assay and flow cytometry. Inflammatory cytokine levels were measured via ELISA. Bioinformatic prediction and dual-luciferase reporter assays were employed to validate miR-628-3p targets. Results miR-628-3p expression was upregulated in the serum and cell samples of AR compared to healthy controls. miR-628-3p can target and bind to the downstream CELF2. Downregulation of miR-628-3p reduced apoptosis in AR cells and suppressed levels of inflammatory factors, while transfection of si-CELF2 reversed the protective ability of miR-628-3p inhibitor on AR cells. Conclusions Knockdown of miR-628-3p may contribute to the pathogenesis of AR by mediating CELF2 to reduce the apoptosis and inflammatory response of AR cells, suggesting its potential protective role against AR-related cellular damage.

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Abstract Background BOS172722, a selective TTK inhibitor, shows promise for Breast Cancer (BC) treatment. The role of gut microbiota as a potential mediator in this process has not been established. This Mendelian Randomization (MR) study investigated the causal effect of TTK inhibition on BC and conducted an exploratory analysis of potential mediation by gut microbiota. Methods A two-step, two-sample drug target MR analysis used IEU Open GWAS project datasets. The inverse-variance-weighted method estimated causal effects, with sensitivity tests confirming robustness. False Discovery Rate (FDR) correction was applied to analyses for all microbial taxa. Results Genetically predicted TTK inhibition significantly reduced BC risk (OR = 0.667, 95 % CI 0.543-0.819; FDR-adjusted p < 0.001). In secondary analyses, initial uncorrected results indicated nominal associations between TTK inhibition and 20 gut microbial taxa, and between 6 taxa and BC risk. However, none of these microbiota-related associations remained statistically significant after FDR correction (all q-values >0.1). An exploratory mediation analysis on Genus Anaerostipes id.1991, which showed the strongest nominal signals (TTK inhibition on Anaerostipes: uncorrected p = 0.003; Anaerostipes on BC: uncorrected p = 0.025), was performed for hypothesis generation only; no statistically significant mediation was observed. Conclusion This study provides robust genetic evidence that TTK inhibition is causally associated with a decreased risk of breast cancer. The exploratory analysis of gut microbiota as a mediator did not yield statistically significant results after correction for multiple testing. The potential role of specific microbes, such as Genus Anaerostipes, remains inconclusive and requires further dedicated investigation.

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Abstract Purpose Ultrasonography is a non-invasive, radiation-free, and cost-effective imaging modality for evaluating the Temporomandibular Joint (TMJ) and Masticatory Muscles (MM). Despite its clinical potential, a standardized quantitative ultrasound protocol for assessing masticatory system asymmetry in Temporomandibular Disorders (TMD) is lacking. This pilot study aimed to evaluate the feasibility of a standardized ultrasound protocol for the quantitative assessment of masticatory system asymmetry and to explore its preliminary associations with TMD-related symptoms. Materials and methods Fifteen young adult participants (aged 19-26 years) underwent bilateral ultrasound examination of the masticatory muscles (masseter, temporalis, lateral pterygoid, and sternocleidomastoid muscles) and TMJ structures, including interarticular spaces and articular components. Measurements were performed by trained examiners using standardized anatomical landmarks. Asymmetry was quantified using percentage difference indices and aggregated into a composite anatomical asymmetry score. Proposed asymmetry reference values were applied for descriptive purposes only, and all statistical analyses were conducted on an exploratory, hypothesis-generating basis. Results The composite anatomical asymmetry index differed from symmetry (mean ± SD: 18.45% ± 17.13%). An association was observed between anatomical asymmetry and joint sounds (crepitation) (Spearman’s ρ = 0.88), while pain showed a lower-magnitude association (ρ = 0.51). Conclusion This pilot study demonstrates the feasibility of a standardized ultrasound-based protocol for the quantitative assessment of masticatory system asymmetry. The findings are exploratory and intended to support methodological development and hypothesis generation. Further validation in larger, blinded study populations is warranted.

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Abstract Objectives Functional Threshold Power (FTP) is widely used for performance evaluation and training prescription in endurance sports. Although FTP is strongly associated with power at the Respiratory Compensation Point (RCP), its interchangeability remains debated. This study examined the relationship and agreement between FTP and RCP in amateur triathletes and tested whether sex influences this relationship. Methods Forty-nine amateur triathletes (male and female) participated. Each athlete completed a maximal cardiorespiratory cycling test and an FTP test, separated by at least 72 h. Linear regression models were used to test the association between FTP and RCP. A regression model including the interaction term (FTP × sex), equivalent to an ANCOVA framework, was applied to assess sex effects on the FTP-RCP relationship. Agreement between methods was assessed using Bland-Altman analysis. Two-way analysis of variance (ANOVA) was performed to examine the effects of sex, test type, and their interaction on absolute power (W), power relative to total body mass, and power relative to lean mass. Results FTP and RCP were strongly correlated (r = 0.916; p < 0.001). The interaction term FTP × sex was not significant (β = -0.135, p = 0.524), indicating that the regression slopes do not differ between males and females. Thus, the relationship between FTP and RCP was statistically similar across sexes. However, Bland-Altman analysis revealed wide limits of agreement, indicating poor interchangeability between FTP and RCP at the individual level. Conclusions FTP is strongly associated with RCP, and the relationship is independent of sex. Despite this association, FTP and RCP are not interchangeable measures. Caution is warranted when using FTP as a direct surrogate for RCP in training prescription and performance assessment.

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Abstract Introduction Hepatitis C (HCV) is an important cause of global morbidity and mortality and can progress to cirrhosis and hepatocellular carcinoma. Vertical transmission occurs in around 5%‒6% of cases, increasing in pregnant women with a high viral load or co-infection with HIV. Although universal screening is recommended by international guidelines, its implementation in Brazil is uneven. This study estimated the seroprevalence of anti-HCV antibodies among pregnant women attending public maternity hospitals in Paraná and compared the results with national data. Material and methods This was an observational, descriptive, and cross-sectional population-based study to assess seroprevalence. The study included 1202 pregnant women aged between 16 and 49, treated in 14 public maternity hospitals in Paraná, in different regions of the state. Anti-HCV screening was carried out by ELISA, and reactive cases were confirmed by viral load (PCR). Sociodemographic and obstetric data and risk factors were obtained from questionnaires and medical records. Results Nine participants tested positive for anti-HCV antibodies, corresponding to a seroprevalence of 0.75% (95% CI 0.34%‒1.40%). This seroprevalence falls within the range reported in previous Brazilian cross-sectional studies of pregnant women (0.06%-2.66%). No active infection was identified, as all reactive samples were HCV RNA-negative. More than half were unaware of their previous infection. No significant associations with traditional risk factors were observed. Discussion The low anti-HCV seroprevalence and the absence of detectable viremia indicate a minimal risk of vertical transmission in the cohort studied. These findings are consistent with low endemicity settings and support the role of prenatal screening in identifying previously undiagnosed infection and enabling linkage to postpartum care. The studies reviewed showed substantial heterogeneity in prevalence estimates, reflecting differences in population characteristics, sample sizes, study periods, and methodologies. The under-representation of rural areas and the exclusion of illiterate women may have led to an underestimation of seroprevalence and should be considered when interpreting the results. Therefore, the findings are primarily generalizable to literate pregnant women attending public maternity hospitals in urban and peri‑urban áreas.

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ABSTRACT Video capsule endoscopy and balloon-assisted enteroscopy have changed the management of small bowel lesions. Both methods allow for the examination of the entire small bowel, and balloon-assisted enteroscopy enables therapeutic interventions. Due to the heterogeneous distribution of medical resources across Brazilian states, small bowel endoscopic procedures, though well established in developed countries, have been implemented in a different fashion in Brazil. Objective This study aimed to present the results of a Brazilian consensus voting about the major indications for small bowel endoscopy for diagnostic and therapeutic procedures. Methods A group of ten members of the small bowel endoscopy committee from the Brazilian Society of Digestive Endoscopy elaborated statements about pre, intra, and post-procedure considerations, diagnostic and therapeutic indications, and complications. An expert panel of 46 endoscopists specialized in small bowel endoscopy across the country revised and discussed each statement and voted utilizing the Delphi methodology. If a minimum threshold of 80% agreement was achieved, the statement was included in the document as a recommendation. Results A total of 45 statements were elaborated by the expert panel. All statements were appreciated by the specialists and approved with an 80% (or greater) agreement using the Delphi consensus. Conclusions An expert group approved the First Brazilian consensus in small bowel endoscopy utilizing the Delphi methodology, producing a list of 45 statements and recommendations about diagnostic and therapeutic procedures. This consensus may assist the management and decision-making process in patients with small bowel diseases.

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Abstract Objective To develop a signature of Diabetes-Related Genes (DRGs) using data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to predict the prognosis of Breast Cancer (BRCA) patients and identify potential therapeutic targets. Methods A list of DRGs was sourced from the GeneCard database. Analyses of differential expression and consensus clustering were conducted to identify DRGs, and Cox regression and Least Absolute Shrinkage and Selection Operator (Lasso) regression were used to construct prognostic risk signatures based on DRGs. High- and low-risk groups were classified using median risk scores, and nomogram plots were created to visualize prognostic signatures. The relationship between immune infiltration, chemotherapeutic agents, and risk scores was evaluated, along with the expression of DRGs in individual immune cells. Results A total of 1231 RNA-seq samples (cancer: 1118, paraneoplastic: 113), 1046 clinical data, and 965 DRGs were obtained from the databases. Differential expression and consensus clustering analyses identified 224 differentially expressed DRGs. Cox regression and Lasso regression analyses led to the establishment of a prognostic signature based on 8 DRGs. Kaplan-Meier curves demonstrated that patients in the low-risk group had a significantly better prognosis compared to those in the high-risk group (p < 0.001). The calibrated curves of the nomogram at 1-, 2-, 3-, and 5-years all aligned with the diagonal, indicating that our nomogram has high predictive performance. Immune infiltration analysis showed significant correlations between our constructed signature and the relative abundance of immune cells (p < 0.05). Single-cell data analysis revealed that DRGs were predominantly expressed in CD4+ conventional T-cells and regulatory T-cells. Conclusion This study has successfully developed a prognostic signature for DRGs, which can be utilized as an efficient tool for risk stratification and prognostic prediction in BRCA patients. Additionally, this research offers a novel basis for investigating potential immunotherapy targets for BRCA patients.

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Abstract Objective To explore the application value of fecal Syndecan-2 gene Methylation (mSDC2) detection, combined detection of serum Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 72-4 (CA72-4) in screening of Colorectal Cancer (CRC) and precancerous lesions. Methods A total of 196 participants were enrolled in this case-control study from March to December 2023, including 65 with CRC, 38 with advanced adenomas, 33 with non-advanced adenomas, and 60 controls. The sensitivity, specificity, and Odds Ratios (OR) for serum CEA, CA72-4, and fecal mSDC2 were evaluated. Results The sensitivity of fecal mSDC2 for CRC was 86.2% (56/65), with a specificity of 96.7% (58/60), with an OR of 28.9 (95% CI 8.6-97.2, p < 0.001). The sensitivity in advanced adenomas was 34.2% (13/38). Serum CEA had a sensitivity of 56.9% (37/65) and a specificity of 96.7% (58/60) for CRC, with an OR of 5.7 (95% CI 2.0-16.4, p < 0.001). Combined detection of CEA and CA72-4 had a sensitivity of 69.2% (45/65) and a specificity of 81.6% (49/60). The triple combination (mSDC2 + CEA + CA72-4) achieved a sensitivity of 96.9% (63/65) and a specificity of 78.3% (47/60) in the CRC, and a sensitivity of 50% (19/38) for advanced adenomas. The combined detection had higher sensitivity than single detection, with statistically significant differences compared to serum-based detection (p < 0.001). Conclusion Combining fecal mSDC2 with serum CEA and CA72-4 increased sensitivity for CRC detection in this single-center study, at the cost of reduced specificity. Validation in larger, screening-intended cohorts with predefined thresholds is warranted.

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Abstract Objectives This study set out to determine whether early use of Terlipressin (TP) as an adjunct to Norepinephrine (NE) could improve clinical outcomes in patients with septic shock. Material and Methods In this prospective, randomized trial, 104 patients with septic shock were assigned to three groups receiving TP at different NE thresholds: Low-dose (L, ≥ 0.25 μg/kg/min), Mid-dose (M, ≥ 0.5 μg/kg/min), and High-dose (H, ≥ 0.75 μg/kg/min). Primary outcomes included 28-day mortality and vasopressor-free days. Secondary outcomes encompassed hemodynamic parameters, organ function recovery, inflammatory markers, and adverse events. Results No significant difference was observed in 28-day mortality among groups (L: 42.86 %, M: 47.06 %, H: 51.43 %; p = 0.328). However, the L group exhibited significantly more vasopressor-free days (defined as days alive and free of all vasopressor support for ≥ 24 consecutive hours within the first 7-days after randomization; median 4.2, IQR 2.1-5.3) than the M (3.1-days) and H groups (2.3-days; p < 0.01). Key secondary outcomes showed superior hemodynamic stabilization in the L group, with shorter time to target MAP (4.2 vs. 5.6-6.5 h, p < 0.05) and accelerated lactate clearance (p < 0.01). Organ function recovery was significantly enhanced in the L group, demonstrated by reduced CRRT duration (3.5 vs. 6.8-7.5 days, p < 0.001), improved renal and hepatic function, higher platelet counts (215 vs. 130-165 × 10⁹/L, p < 0.001), and more rapid inflammatory resolution (Procalcitonin and CRP reduction, all p < 0.05). Adverse events were significantly lower in the L group (p < 0.001). Conclusions Early low-dose TP adjunctive therapy reduces NE dependence, enhances hemodynamic stability, promotes multi-organ function recovery, and improves safety profile in septic shock, without significantly affecting 28-day mortality. These findings support its role as a beneficial adjunct vasopressor when initiated at lower NE doses.

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Abstract Objectives To determine whether Rheumatoid Arthritis (RA) is associated with an increased risk of incident Sudden Sensorineural Hearing Loss (SSNHL). Methods The authors conducted a nationwide, propensity-score-matched cohort study using Taiwan’s Longitudinal Health Insurance Database (2000-2015). Adults with incident RA (n = 45,425) were matched 1:4 to those without RA controls (n = 181,700). The primary outcome was incident SSNHL (ICD-9-CM 389.10). Time-to-event analyses used Kaplan-Meier curves with log-rank tests and multivariable Cox regression. Landmark sensitivity analyses excluded SSNHL events within the first 1- and, separately, 5-years of follow-up. Results SSNHL occurred in 169/45,425 (0.37%) RA patients and 462/181,700 (0.25%) controls. RA was associated with a higher SSNHL risk (adjusted hazard ratio 2.695, 95% CI 2.248-3.231; p < 0.001). Kaplan-Meier and log-rank tests showed greater cumulative incidence in the RA cohort (p < 0.001). In landmark sensitivity analyses excluding events within the first 1- and 5-years, the association remained significant (Year 1: 34 vs. 45, p = 0.007; Year 5: 105 vs. 172, p < 0.001), indicating that the excess risk was not driven by very early events. Conclusions The present study revealed a high frequency of SSNHL in patients with RA, which highlights the importance of heightened clinical vigilance and prompt audiologic evaluation for hearing-related symptoms in this population.

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Abstract Background and objective Seoul Virus (SEOV), a zoonotic hantavirus, is a major cause of Hemorrhagic Fever with Renal Syndrome (HFRS) and represents a global health challenge. With no licensed vaccines or specific antivirals available, this study aimed to design a glycoprotein-based multi-epitope vaccine against SEOV using immunoinformatics approaches. Materials and methods MHC-I and MHC-II epitopes were predicted via the Immune Epitope Database (IEDB) and screened for antigenicity, non-allergenicity, and non-toxicity. Four constructs were designed, with V2 selected as the best candidate. Structural modeling was performed using AlphaFold3 and validated with Ramachandran analysis. Molecular docking with Toll-like receptor-4, molecular dynamics simulations, and immune simulations were conducted to evaluate stability and immunogenicity. Results The V2 construct demonstrated high antigenicity (0.683) and broad population coverage (95.94%). Structural validation confirmed 95.6% of residues in favored regions. Docking revealed strong binding to Toll-like receptor-4, and dynamics confirmed stability through RMSD, RMSF, Rg, PCA, DCCM, and FEL analysis. Immune simulations predicted robust responses, including high IgG1 titers. Codon optimization (GC content 56.62%) and cloning confirmed expression potential. Conclusions The V2 construct exhibits stability, strong immunogenicity, and broad population coverage, supporting its potential as a vaccine candidate against SEOV. Experimental validation in vitro and in vivo is required to confirm efficacy and safety.

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Abstract Background Bacterial infections can negatively impact post-liver transplant morbidity and mortality, and the impact of incipient spontaneous bacterial peritonitis or bacterascites from intraoperative ascitic fluid is unknown. The present study’s objectives were to analyse the risk factors for post-liver transplant infection and survival within 30-days after transplant. Methods This is a single-center retrospective cohort study of liver transplant patients from 2010‒2017, whose ascitic fluid collected during transplant was sent for analysis. Survival analysis using the Kaplan-Meier method and Cox regression in the multivariate analysis was used to determine risk factors for post-transplant infection and survival. Results Of 297 patients, 22 had intraoperative SBP, 40 had bacterascites, and 235 had a normal ascitic fluid. 67% were male, median age 53-years, and median MELD score of 24. In multivariate analysis, there was no association between the presence of SBP or the presence of bacterascites and the occurrence of infection or death, and although it was not clinically significant, there was a trend towards worse survival in the bacterascites group. Patients undergoing post-transplant reoperation (OR = 2.28, 95% CI 1.12-4.60, p = 0.022), post-transplant MDR colonization (OR = 4.39, 95% CI 2.61-7.39, p < 0.001), and post-transplant dialysis (OR = 2.20, 95% CI 1.31-3.69, p = 0.003) had a higher rate of infection in the first 30-days after transplantation; pre-transplant MDR colonization, early graft dysfunction and low body mass index were independent predictors of worse survival. Conclusions Intraoperative SBP and bacterascites that received targeted treatment did not impact infections nor survival rates up to 30-days after liver transplant, while most episodes were treated. In this population of severe patients with ascites, patients undergoing reoperation, post-transplant MDR colonization and post-transplant dialysis were at higher risk of infection.

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Abstract Introduction During the Coronavirus Disease (COVID-19) pandemic, public and healthcare workers were recommended to use Personal Protective Equipment (PPE) to prevent the spread of infection. With the increased use of different types of respiratory protection, including facemasks and PPE, cardiovascular parameters are expected to vary within physiological levels. Objective This study aimed to evaluate the variations in cardiovascular parameters on wearing facemasks or full-body PPE while performing the 6-Minute Walk Test (6-MWT), a standardized physical exercise. Methods This quasi-experimental study involved 99 healthy young adults aged 18-24 years with a normal mean BMI. The participants were randomly selected into a control and two experimental groups (wearing a facemask, or full-body PPE). Measurements of Heart Rate (HR), Blood Pressure (BP), and Oxygen Saturation (SpO2%) were performed before and after 6-MWT. The data were analyzed using paired t-tests for comparison of parameters and repeated measures ANOVA for a Group × Time (Pretest/Posttest) interaction between the groups, where p-value < 0.05 was considered statistically significant. Results Based on paired t-tests, heart rate and blood pressure showed a significant difference between pretest and posttest in each group. Mixed-model ANOVA revealed no significant Group × Time interactions for any cardiovascular parameter, indicating that the physiological response to the 6-MWT was similar regardless of PPE worn. A significant difference in 6-minute walk distance was observed between the facemask group and full-body PPE group. Conclusion In this cohort, no significant effects of Group × Time interaction were observed for SpO2%, HR, and BP on wearing different PPE and performing 6-MWT, a submaximal physical activity.

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Abstract Background Diet plays a key role in regulating the gut microbiota. This study aimed to investigate the association between the Dietary Index of the Gut Microbiome (DI-GM) ‒ a score designed to reflect the potential of a diet to support a healthy gut microbiota ‒ and different types of arthritis, an area where systematic studies remain scarce. Methods Data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 were analyzed using multivariable logistic regression, Restricted Cubic Spline (RCS) regression, and subgroup analyses to assess associations between DI-GM and Osteoarthritis (OA) and Rheumatoid Arthritis (RA). Results A total of 6168 participants were included, among whom 506 had Osteoarthritis (OA) and 303 had Rheumatoid Arthritis (RA). Multivariable analyses showed no significant association between DI-GM and OA (p > 0.05), but significant inverse associations with RA across models (ORs 0.74, 0.64, and 0.74; all p < 0.05). Restricted cubic spline analysis detected no significant nonlinear relationships for either outcome. Subgroup analyses suggested potential associations within certain populations. Conclusion This cross-sectional study found an inverse association between the diet-based DI-GM score and RA, but no significant association with OA. Given the limitations of the cross-sectional design, the observed association is equally compatible with dietary changes resulting from RA diagnosis and management (reverse causality). As this study did not measure the gut microbiota, the role of the microbiome as a mediator remains speculative. Therefore, these results require confirmation in prospective studies that can account for reverse causation and directly assess the gut microbiome.

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Abstract Introduction Vitamin D deficiency has been associated with increased Coronary Artery Disease (CAD) risk, potentially through its associations with lipid metabolism, particularly HDL-C. This study investigates the mediating role of HDL-C in the relationship between serum vitamin D and the severity of CAD. Methods In this cross-sectional study, 1015 participants undergoing elective angiography were enrolled from the Nutrition Heshmat Registry (NUTHER). Serum 25(OH)D levels were categorized as very low (< 12 ng/mL), low (12-20 ng/mL), marginal (20-30 ng/mL), and normal (≥ 30 ng/mL). CAD severity was quantified using the Gensini score, with severe CAD defined as a score ≥ 60. Logistic regression, restricted cubic spline analysis, and mediation models were employed to assess associations and potential mediation effects of HDL-C. Results Participants with normal vitamin D levels (serum 25(OH)D ≥ 30 ng/mL) had 39% lower odds (adjusted OR = 0.61, 95% CI 0.40-0.93, P for trend = 0.017) of severe CAD compared to those with very low levels. A dose-response analysis confirmed a linear inverse association between 25(OH)D and CAD severity (P for overall = 0.0160). Mediation analysis revealed that HDL-C accounted for 18.1% (95% CI 11.8%, 44.0%) of the total effect of vitamin D on CAD severity, while LDL-C, total cholesterol, and triglycerides showed negligible mediation. Conclusion Higher serum vitamin D levels are associated with lower CAD severity, partially mediated by HDL-C. These findings suggest that adequate levels of both vitamin D and HDL-C may be associated with a lower severity of CAD. Further research, including randomized trials, is needed to confirm these associations and explore clinical implications.

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Abstract Background Venous outflow is a key determinant of immune and metabolic homeostasis following intestinal transplantation. In living-donor settings, maintaining physiologic portal drainage may attenuate systemic inflammation and support local defense mechanisms during early reperfusion. This study investigated the molecular and histological effects of portal versus systemic venous drainage in a swine model of living-donor intestinal transplantation. Methods Twenty-two swine intestinal transplants were assigned to portal (n = 12) or caval (n = 10) drainage. Grafts were preserved in Custodiol® (HTK), implanted orthotopically, and sampled two hours after reperfusion. Intestinal and hepatic tissues underwent qRT-PCR analysis of inflammatory, apoptotic, endothelial, and oxidative-stress pathways. Histological injury was scored (0-3). Groups were compared using the Mann-Whitney U test with Bonferroni and FDR adjustment. Results Histopathological alterations were mild and comparable between groups in both intestinal and hepatic tissues, with no significant differences across epithelial, vascular, inflammatory, or necrotic parameters. In intestinal samples, IL-1α (fold-change = 6.76; p = 0.013) and IFN-γ (fold-change = 2.10; p = 0.023) exhibited higher early expression in portal-drainage grafts, although neither signal remained statistically significant after multiple-testing correction. The remaining markers showed broadly overlapping distributions. In the liver, CD8 demonstrated the largest numerical difference (fold-change = 0.48; p = 0.044), but no hepatic target reached significance after adjustment. Conclusions Portal and caval drainage produced comparable early histological injury and only subtle molecular variation. Although not significant after adjustment, these early transcriptional shifts suggest potential immunometabolic effects of venous outflow configuration and represent exploratory, hypothesis-generating findings that warrant further study.

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Abstract Purpose This retrospective study investigated the impact of Allergic Rhinitis (AR) patients receiving Allergen-specific Immunotherapy (AIT) on Coronavirus Disease 2019 (COVID-19) infection, clinical characteristics, and prognosis. Methods This was a single-center, retrospective cohort study that included patients with AR who received subcutaneous desensitization with Aloege or sublingual desensitization from 10 December to 31 March 2023 at Changsha The Second Xiangya Hospital, China. Results The investigation comprised 761 outpatients, including 336 individuals with allergic rhinitis who underwent AIT and 425 healthy subjects. Patients with AR who received AIT treatment showed a significantly lower risk of COVID-19 infection in the multivariate analysis (OR=0.48, p = 0.005). The probability of developing hyposmia after contracting COVID-19 was reduced in the experimental cohort compared to the control cohort (OR = 0.39, 95 % CI 0.27‒0.57, p < 0.001). Additionally, the test group experienced a reduction in sore throat (OR = 0.32, 95 % CI 0.22‒0.47, p < 0.001) and a shorter duration of systemic symptoms (OR = 0.49, 95 % CI 0.34‒0.7, p < 0.001) following COVID-19 infection. Furthermore, it was discovered that the impact on quality of life after COVID-19 infection was significantly different between the two groups, with the test group exhibiting a higher quality of life compared to the control group (p < 0.001). Conclusion During a concentrated or sudden outbreak of COVID-19, patients with AR who received AIT had a lower proportion of hyposmia than the healthy population, and the severity of sore throat and its impact on quality of life were relatively mild.

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Abstract Objectives To evaluate the diagnostic performance of multiparametric Magnetic Resonance Imaging (MRI) and Ultrasound (US) for detecting Acute Immune Rejection (AIR) after kidney transplantation through a systematic review and meta-analysis. Methods Five electronic databases were systematically searched up to May 30, 2025. Eligible studies included kidney transplant recipients assessed with noninvasive imaging for AIR and reporting diagnostic accuracy. Two reviewers independently performed study selection, data extraction, and quality assessment using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Given the heterogeneity of imaging modalities, MRI and US studies were analyzed separately, and subgroup analyses and meta-regression were performed to explore sources of heterogeneity. Results Eighteen studies (1140 cases; 494 AIR and 646 non-AIR) were included. For MRI, the pooled sensitivity, specificity, and Area Under the Curve (AUC) were 0.89, 0.91, and 0.96, respectively. For US, the pooled sensitivity, specificity, and AUC were 0.79, 0.89, and 0.90, respectively. Substantial between-study heterogeneity was observed. Meta-regression and subgroup analyses suggested that heterogeneity was associated with reference standard and imaging timing. Conclusion MRI and US demonstrate promising accuracy for detecting AIR after kidney transplantation. However, the available evidence remains limited in scale, and substantial heterogeneity exists across studies. Therefore, MRI and US should be considered adjunctive tools rather than replacements for histopathological biopsy. Further large-scale, prospective studies are required to validate their clinical utility.

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Abstract Objective Medulloblastoma (MB) is one of the most prevalent solid brain tumors in the pediatric population. Although hundreds of Differentially Expressed Genes (DEGs) have been identified as diagnostic molecules and therapeutic targets for Medulloblastoma (MB), the function of metabolism-associated genes in the pathophysiological mechanisms of MB remains unclear. Methods The Gene Expression Omnibus (GEO) provided five datasets that contain mRNA expression profiles and clinical information. In detail, 599 MB samples extracted from GSE85217 were set as the training set (n = 400) and test set (n = 199). For validation, 74 samples from GSE37418, 8 scRNA-seq samples, and 37 RNA-seq samples were used. Nonnegative matrix factorization clustering was conducted, leading to the identification of four MB subclasses (C1, C2, C3, and C4) in both the training and test sets. Results C1 and C3 are metabolically active, and C2 involves metabolic hypoactivity; C4 did not exhibit obvious metabolic characteristics. Next, GSE50161, GSE74195, and GSE86574 were used to identify DEGs, and a 17-gene metabolism-associated signature for prognosis prediction was established. The authors performed transcriptome and single-cell sequencing on medulloblastoma bulk specimens to further validate metabolic subclasses and the prognosis prediction model at the transcriptome and cellular level. Conclusion The present study classifies Medulloblastoma (MB) based on metabolic signatures, supplementing existing subtype characterization from a metabolic perspective. The authors provide preliminary insights into MB’s metabolic hallmarks and a potential reference for developing multimolecule-based personalized therapies and prognostic tools ‒ with the caveat that the 17-gene signature requires additional multi-center validation to confirm clinical utility.

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Abstract Background Intracerebral Hemorrhage (ICH) entails high morbidity and rapid clinical deterioration; early risk stratification is critical. Although inflammatory biomarkers correlate with Hematoma Expansion (HE) and outcomes, their incremental value over existing models is uncertain. Methods The authors retrospectively included consecutive acute ICH admissions to Tongji Hospital (2012‒2024). An inflammatory score (0‒9) was derived from the first post-admission blood draw (on admission or next morning), all within 24 h of admission, using neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, systemic immune-inflammation index (neutrophil × platelet/lymphocyte), lactate dehydrogenase, and high-sensitivity C-reactive protein. HE was defined as > 6 mL or > 33% on 24‒48 h follow-up Computed Tomography (CT). 90-day outcomes were poor function (modified Rankin Scale [mRS] score 4‒6) and mortality. Multivariable models used multiple imputation. Results HE analyses included 1047 patients with baseline and 24‒48 h follow-up CT; 298 (28.5%) had HE. Outcome analyses included 953 patients (94-lacked 90-day follow-up); 399 (41.9%) had mRS 4‒6 and 120 (12.6%) died. The score was independently associated with HE (adjusted Odds Ratio 1.18), poor function (1.27), and mortality (1.30). Adding the score increased the area under the receiver operating characteristic curve (AUC) for HE (0.681 to 0.709; ΔAUC = 0.029; p = 0.007), poor function (0.826 to 0.842; ΔAUC = 0.016; p = 0.014), and mortality (0.815 to 0.838; ΔAUC = 0.022; p = 0.036). Sensitivity analyses, including a ≤ 6 h landmark analysis, inverse probability weighting (IPW) for follow-up availability, and complete-case analyses, yielded similar effects. Conclusion An admission laboratory-based inflammatory score provides independent, incremental prognostic value for HE and 90-day outcomes after ICH. Registration-URL http://www.chictr.org.cn. Unique identifier: ChiCTR-ROC-2,000039365.

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Abstract Background The Triglyceride-Glucose Index (TyG) has emerged as a convenient surrogate marker of insulin resistance and has been linked to various metabolic disorders. However, its relationship with Acute Pancreatitis (AP) in adult critically ill patients remains unclear. Methods The authors analyzed 2,588 adult critically ill patients from the MIMIC database. Participants were stratified by median TyG and TyG-BMI indices. Logistic regression, restricted cubic spline, and subgroup analyses evaluated associations with AP risk. ROC curves assessed predictive performance. Results High TyG and TyG-BMI groups exhibited greater metabolic derangements, longer ICU/hospital stays, and higher comorbidity burden. AP patients (9.4%) had elevated TyG levels (9.9 vs. 8.7, p < 0.001). Both indices were independently associated with AP risk in continuous, IQR, and quartile analyses (TyG: OR per IQR = 2.08, 95% CI 1.75-2.48; TyG-BMI: OR per IQR = 1.34, 95% CI 1.12-1.58). TyG showed linear dose-response, whereas TyG-BMI exhibited nonlinear associations. Associations were consistent across subgroups. ROC analysis indicated superior predictive ability for TyG (AUC = 0.809) versus TyG-BMI (AUC = 0.787, p = 0.00227). Conclusion Both TyG and TyG‑BMI indices are independent predictors of acute pancreatitis, with TyG demonstrating a statistically higher but modestly improved discriminative performance.

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Abstract Objective Regular exercise reduces the risk of obesity, but the impact of endurance exercise on skeletal muscle metabolic processes remains incompletely understood. This study investigated the effects of endurance exercise on the transcriptome and metabolome of skeletal muscle in obese mice. Method Transcriptomic and metabolomic profiling of skeletal muscle samples was performed across experimental groups to identify differentially expressed genes and differential metabolites. Functional enrichment of DEGs and metabolites was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Integrated pathway-level analysis was conducted using iPath 3.0. Results Integrated transcriptomic and metabolomic analysis indicated that endurance exercise altered lipid metabolism, amino acid metabolism, and nucleotide metabolism pathways in the skeletal muscle of obese mice. Specifically, endurance exercise downregulated the expression of lipid metabolism-related gene Acot2, amino acid metabolism-related gene Nos2, and carbohydrate metabolism-related genes Itpkb and Inpp4b. Furthermore, endurance exercise decreased the levels of palmitic acid, arachidonate, phosphatidylcholine, acetylcholine, hypoxanthine, urea, and acetyl-CoA. Conclusions Endurance exercise positively impacts skeletal muscle metabolic health in obese mice through coordinated regulation of multiple metabolic pathways and reduction of specific metabolites

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Abstract Objectives To describe procedural and early outcomes following laser-cut Stent-Assisted Coil Embolization (SACE) for Basilar Apex Aneurysms (BAAs) at a single institution. Methods The authors conducted a retrospective review of 43 consecutive patients with BAAs (both ruptured and unruptured) who underwent laser-cut SACE between September 2019 and April 2023. Outcomes included procedural success (defined as successful stent deployment and coil embolization without procedural abandonment or device malfunction), immediate and 6-month angiographic occlusion status (Raymond classification), periprocedural complications, and 3-month clinical status (modified Rankin Scale, mRS). Treatment strategies (single-stent vs. Y-configuration) and stent types (Enterprise vs. Atlas) were selected per operator discretion. Results The procedural success rate was 100%. Immediate post-procedural angiography showed complete occlusion (Raymond I) in 81.4% (35/43) and neck remnant (Raymond II) in 18.6% (8/43). The periprocedural complication rate was 9.3% (4/43), including two thromboembolic events (4.7%), one fatal brain herniation, and one other non-specified complication. Among 42 surviving patients, 88.1% (37/42) had an mRS score ≤ 2 at 3-months. Six-month angiographic follow-up, available for 37 patients (86.0%), revealed complete occlusion in 97.3% (36/37) and neck remnant in 2.7% (1/37). Subgroup analyses comparing single-stent (n = 38) and Y-stent (n = 5) techniques, as well as Enterprise (n = 21) and Atlas (n = 17) stents in single-SACE, showed no statistically significant differences in occlusion rates or clinical outcomes, though these analyses were underpowered. Conclusion In this single-center, retrospective experience of patients with saccular BAAs, laser-cut SACE for BAAs was associated with high procedural success and favorable early angiographic and clinical outcomes.

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Abstract Introduction The vaccination against COVID-19 is being carried out, and observing the aging process and changes in the face of the pandemic in the older adults, studies are needed to better understand these changes. The purpose of this study was to compare immune response, inflammation, physical-functional performance, and gait at one and nine months after the fourth dose of the COVID-19 vaccine between physically active and insufficiently active older adults. Methods Prospective cohort study. Thirty older adults were evaluated and divided into two groups: the Experimental Group ‒ physically active (EG, n = 15) and the Control Group ‒ insufficiently active (CG, n = 15). Assessments were baseline, one and nine months, post-vaccination and regular exercise practice. Main Outcome Measures: Immunological and inflammatory markers and physical-functional variables: questionnaires (FRAQ, Baecke), physical tests (Step Test, Floor Transfer Test, Timed Up and Go, six-minute walk test, hand grip strength), and gait analysis using a pressure platform. Results The EG showed increased IgA and decreased IgG levels over time. Regarding inflammation, EG demonstrated modulation of the inflammatory response, characterized by increased IL-10 levels, significant changes in IL-12p70 and IP-10 concentrations, and improved pro-/anti-inflammatory cytokine ratios (e.g., IL-6/IL-10), indicating a more regulated immune profile. Additionally, EG improved physical performance in the Step Test, Floor Transfer Test, and six-minute walking test, along with reduced plantar load in the midfoot and rearfoot regions. In contrast, the CG showed reductions in IL-10 and IP-10 levels over time, without consistent improvement in inflammatory modulation or physical-functional performance. In inter-group comparisons at nine months, EG exhibited higher IL-10 levels and a more favorable pro-/anti-inflammatory balance compared with CG, suggesting a controlled and effective immune activation following vaccination. Conclusion The practice of regular physical exercise was associated with more favorable immune, inflammatory, physical-functional, and gait outcomes at one and nine months after the fourth dose of the COVID-19 vaccine in physically active older adults compared with insufficiently active peers. These findings suggest that long-term regular physical exercise was associated with modulation of the immune-inflammatory profile, marked by a balanced increase in both Th1-associated cytokines (IL-12p70, IP-10) and the regulatory cytokine IL-10 and increased IgA levels and a reduction in IgG over time, suggesting a controlled and effective immune activation following vaccination against COVID-19 and regular exercise practice compared with CG (insufficiently active) and better physical-functional performance with reduction plantar overloading during gait.

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Abstract Objective Traditional biochemical testing is limited by fixed sites, specialized equipment, and long turnaround times, severely reducing patient compliance with regular monitoring. To address the demands of routine lipid management, this study developed a simple, rapid and low-cost method for Total Cholesterol (TC) detection that enables high-throughput parallel processing of multiple samples. Method This method synchronously identifies the RGB values of multiple pixels in an image through a mobile phone camera. All experiment procedures were strictly followed according to the guidelines of the National Committee for Clinical Laboratory Standards. Multiple performance indicators of the device were evaluated, and the results were compared for consistency with those from a fully automated clinical biochemical analyzer. Results The TC concentration showed the strongest quantitative correlation with the green channel intensity (G-value). This method was preliminarily validated on a prototype smartphone. Both its detection precision and accuracy met clinical standards. The method demonstrated satisfactory linearity over 1.19-8.49 mmoL/L, and its analytical results for the limited samples in this study were highly consistent with those obtained from the automatic biochemical analyzer. Conclusions Integrating low cost and high efficiency, this novel method has great application potential in indoor settings within primary healthcare institutions and resource-limited remote areas.

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Abstract Study design Experimental study about hyperprolactinemia on the Epiphyseal Growth Plate (EGP). Objectives Evaluated the EGP of the lactating female with hyperprolactinemia induced by metoclopramide and of the physiological lactating female. Methods Ten (10) females received 0.2 mL of saline solution at 0.9% (control group, CTR), and ten (10) females received 200 µg/day of metoclopramide (experimental, HPRL). Treatments lasted for 79 consecutive days (50 days of induction of HPRL, 19 days of gestation, and 10 days of breastfeeding). On the 79th day, the lactating female mice were euthanized and the knees were removed and fixed in 10% formaldehyde for 24 hours and decalcified bone for immuno-histochemistry (TUNEL and Ki67) analysis, and use Masson's trichrome. Data were statistically analyzed by the Mann-Whitney test (p < 0.05). Results Apoptosis of chondrocytes was higher in the EGP (femur and tibiae) of the lactating female-HPRL compared to the EGP (femur and tibiae) of the lactating female-CTR (p < 0.05). Cell proliferation of chondrocytes was significantly higher in the EGP in the femur compared to the EGP in the femur of lactating females-CTR (p < 0.05), however, the EGP in the tibiae (HPRL vs. CTR) was not significant, p > 0.05. Conclusions The present study revealed excess cell death (TUNEL) of chondrocytes, consisting of 2-fold in the EGP of the femur and 4-fold in the EGP of the tibiae of a lactating female with hyperprolactinemia induced by metoclopramide, with greater involvement of the tibiae in relation to the femur, which is a fact that can lead to an imbalance between chondrogenesis and osteogenesis.

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Abstract Objective To investigate the effects of Laparoscopic Sleeve Gastrectomy (LSG) on the safety profile and metabolic parameter improvement in adolescents (10‒17 years-old) with grade IV obesity (BMI ≥ 50 kg/m2). Methods From May 2023 to September 2024, a total of 60 adolescent patients with grade IV obesity who underwent LSG at the Department of Bariatric and Metabolic Diseases, The First Hospital of Hebei Medical University, were enrolled as the initial study cohort. Observations and statistics were collected on surgical-related complications, body weight, (Body Mass Index) BMI, glucose metabolism indicators, lipid metabolism indicators, liver function, and nutritional status to analyze the safety and efficacy of the procedure. Results A total of 60 adolescent patients successfully underwent LSG without conversion to open surgery or perioperative mortality. During postoperative follow-up, only 31 patients completed regular assessments with complete data available for analysis. There were no perioperative period complications such as postoperative hemorrhage or gastric leak. Follow-up assessments at 3-months, 6-months, and 1-year postoperatively revealed significant improvements (p < 0.05) in the following parameters: body weight .[preoperative (154.1 ± 19.3) kg, 1-year postoperative (97.8 ± 13.6) kg], BMI .[preoperative (51.9 ± 3.8) kg/m2, 1-year postoperative (30.2 ± 1.4) kg/m2], uric acid .[preoperative (491.5 ± 92.4) μmoL/L, 1-year postoperative (376.8 ± 23.6) μmoL/L], liver function, blood lipids, glycated hemoglobin, and fasting insulin .[preoperative (57.9 ± 17.6) μIU/L, 1-year postoperative (15.5 ± 6.2) μIU/L] Preoperatively, 12 patients had hypertension, 8 had type 2 diabetes mellitus, 4 had Polycystic Ovary Syndrome (PCOS), and 10 had Non-Alcoholic Fatty Liver Disease (NAFLD). At 1-year after surgery, all patients with hypertension and type 2 diabetes mellitus achieved remission criteria. In addition, imaging findings and liver function improved significantly in 7 of the 10 patients with fatty liver disease, and clinical manifestations improved in 3 of the 4 patients with polycystic ovary syndrome. Concurrently, a declining trend (p < 0.05) was observed postoperatively in hemoglobin, trace elements (calcium, iron), and vitamins (Vitamin D, Vitamin B12), although all values remained within the normal range. Conclusion LSG is a safe and effective procedure for improving metabolic disorders in adolescent patients with grade IV obesity, with confirmed short-term efficacy. However, the widespread declining trend in postoperative nutritional indicators underscores that systematic nutritional monitoring and intervention must be a core component of postoperative management in clinical practice to achieve long-term health benefits.

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Abstract COVID-19 remains the most devastating and challenging viral disease in human history Objective This study explores the biochemical and host microRNA (miRNA) response to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and explores how DE miRNAs alter molecular pathways to identify potential prognostic and therapeutic biomarkers. Methods Biochemical profiling on automated chemistry analyzers and circulating miRNA profiling by Next Generation Sequencing were performed in moderate (ward) and severe (ICU) patients of COVID-19. miRNA Differential Expression (DE) was analyzed in ICU vs. Control and Ward vs. Control Groups. Statistical comparison of biochemical variables amongst ICU, Ward, and Control groups was done on SPSS by applying the Kruskal-Wallis test; p-value < 0.05 was considered significant. miRNA DE analysis was performed with the help of a bioinformatics tool, DESeq2. A False Discovery Rate (FDR) adjusted p-value < 0.05 was considered to be significant. Results Most biochemical parameters were significantly and proportionately altered with respect to the severity of the disease. Patients showed compromised renal, hepatic, and cardiac function, as well as deranged blood pictures and elevated inflammatory markers (CRP, IL-6, LDH, and Ferritin). miRNA Differential Expression (DE) when analyzed in both study groups, 102 DE miRNAs were found in the ICU vs. Control group, of which miR-423-5p was significantly upregulated, and miR-744-5p was significantly downregulated. Whereas, in the Ward vs. control group, out of 91 DE miRNAs, only miR-486-5p was observed to be significantly upregulated. Gene targets of these three miRNAs were further explored along with their cellular pathways. Literature suggests that these affected cellular pathways converge on the stimulation of the NF-κB pathway. Biochemical evaluation of COVID-19 cases reveals major disease severity predictors like raised inflammatory markers CRP, IL-6, LDH, elevated organ function tests and deranged hematological profiles. Conclusion Three differentially expressed miRNAs were observed that might be involved in the activation of NF-κB, which acts as a major modulator of inflammation in response to SARS-CoV-2 infection. The miRNA findings are preliminary and hypothesis-generating, only requiring independent validation e.g., qPCR in a larger cohort. The probable theragnostic potential of these miRNAs may be clinically explored further by the use of miRNA mimics or miRNA inhibitors that may change the adversity associated with this virus altogether.

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Abstract Objective Aggressive early hydration is the cornerstone of Acute Pancreatitis (AP) care, but the optimal fluid-balance strategy and its impact on long-term survival remain unclear. The authors therefore tested whether first-week fluid accumulation affects 90-day mortality. Methods Retrospective cohort study of 1142 AP patients admitted to the Intensive Care Unit (ICU) within the MIMIC-IV database. Daily fluid intake/output were extracted for the first 7-days; patients were classified as cumulative positive (n = 842) or negative (n = 300) balance by Day-7. The authors used Cox regression, Propensity Score Matching (PSM), and multiple sensitivity analyses to evaluate the association between fluid balance and 90-day mortality. Results Overall 90-day mortality was 19.3%. Mortality was higher in the positive balance group. Multivariable Cox regression showed an adjusted hazard ratio (HR = 1.54 [1.06-2.22], p = 0.022); the corresponding E-value was 2.45. After PSM, the association persisted. IPTW yielded a similar point estimate (HR = 1.51, 95% CI 1.01-2.25, p = 0.115). Landmark analyses excluding early deaths confirmed the finding. RCS revealed a non-linear relationship, suggesting both highly positive and negative balances are associated with increased mortality. Conclusion A positive cumulative fluid balance at Day-7 is associated with increased 90‑day mortality in ICU patients with AP. This association may partially reflect the higher severity of the underlying disease process in the group with positive cumulative fluid balance on Day-7, rather than a direct causal effect. Despite this limitation, the present findings support an individualized, biphasic fluid strategy: early adequate resuscitation followed by goal‑directed de‑escalation.

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Abstract Objective To report the first clinical application of robotic telesurgery within the Brazilian Unified Health System (SUS) infrastructure, evaluating feasibility, safety, and stakeholder perceptions in a consecutive case series. Methods Five consecutive robotic telesurgeries across four surgical specialties were performed using the Toumai/MicroPort platform. The remote surgeon operated from the console at PROMIN-FMUSP, while the robotic unit and patient were located at HU-USP, approximately 5 km away. All procedures used a wired network connection. A structured safety protocol with predefined conversion triggers and a standby bedside surgeon was applied. Outcomes included procedural completion, network latency, intraoperative events, and 30-day postoperative outcomes. Post-procedure structured interviews captured perceptions from the remote surgeon, bedside surgeon, and anesthesia team using Likert scales and the NASA-TLX adapted instrument. Results Four of five procedures were completed entirely via remote console. One case (radical prostatectomy) required conversion to local surgeon control due to a local cable disconnection at the patient site near the end of the procedure (the network connection itself was preserved); the bedside surgeon completed the remaining approximately 10 min without adverse consequences. Surgical specialties included thoracic surgery (two cases), urology, head and neck surgery, and gynecology. Median operative time was 165 min (range 106‒240). Console-reported latency was approximately 12 ms in each case. No intraoperative adverse events occurred. All remote surgeons rated perceived safety at the maximum score. Bedside surgeons and anesthesiologists uniformly considered the model safe, although saturation of most perception scores at the maximum value limited inter-case discrimination. One patient (Case 2, head and neck) had a Clavien-Dindo grade II complication (edema and pain requiring one additional day of hospitalization). No readmissions, reoperations, or mortality occurred within 30 days. Conclusion The first clinical application of robotic telesurgery within SUS proved technically feasible across four surgical specialties in five consecutive low-to-medium complexity cases, with no major adverse events at 30-days. The single conversion was managed safely by the standby bedside surgeon, consistent with the intended behavior of the structured safety protocol. These initial findings ‒ limited by the small sample and absence of a control group ‒ support the continued, progressive evaluation of telesurgery within Brazil's public health system.

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Abstract Objective The rapid advancement of Large Language Models (LLMs) has generated interest in their application to medical education, particularly for high-stakes assessments like the USMLE. This study aims to evaluate the performance of DeepSeek-R1, a state-of-the-art LLM developed in China, compared to OpenAI models, to assess its feasibility for medical education and assessment. Methods The authors evaluated the performance of five models, including DeepSeek-R1, DeepSeek-V3, and three OpenAI models (GPT-4 Omni, OpenAI o3-mini, OpenAI o1 pro), on 321 text-based USMLE-style questions. Accuracy rates were calculated, and statistical comparisons were performed using Chi-Square tests with Bonferroni correction. Results DeepSeek-R1 achieved the highest overall accuracy of 92.5% (95% CI 89.1%‒94.9%), significantly outperforming the OpenAI models (all 78.8%, p < 0.0001). DeepSeek-R1 also surpassed the reported average human examinee performance across all USMLE steps. The inter-model consensus between DeepSeek-R1 and OpenAI o1 pro yielded 94.9% accuracy, indicating high reliability for straightforward queries. Furthermore, in discordant cases, DeepSeek-R1 demonstrated superior capability with 82.8% accuracy compared to 14.1%‒28.1% for the OpenAI models (p < 0.0001). Conclusion DeepSeek-R1 emerges as a compelling candidate in the AI-driven healthcare landscape, demonstrating superior accuracy and reasoning capabilities. However, its current limitation in multimodal data processing underscores the need for further innovation. These findings provide valuable insights for educators and policymakers regarding the integration of non-Western LLMs into medical assessment.

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Abstract Objective Large population-based studies that could identify risk factors associated with sepsis mortality are scarce, but could be helpful in clinical risk assessments. With this study, the authors aimed to examine possible risk factors for sepsis mortality. Methods The authors conducted an open nationwide cohort study, including 157,143 individuals aged ≥ 18-years diagnosed with (first event) sepsis (1998-2018). The outcome was 30-day all-cause mortality following sepsis. The predictors were sociodemographic factors, the Charlson Comorbidity Index, severe mental disorders, pyelonephritis and influenza/pneumonia diagnosis within 30-days before sepsis. Logistic regression models were used to calculate Odds Ratios (OR) and 95% Confidence Intervals (95% CI). Results The overall 30-day mortality proportion was 17.9%, and 30.5% among those aged ≥ 85-years. In the full model, several sociodemographic factors were associated with mortality. For example, individuals aged ≥ 85-years had higher mortality (OR = 13.02, 95% CI 11.50-14.74) compared to those aged 18-44 years. Mortality was also higher among individuals with low educational level (1.09, 1.05-1.13), with low family income (1.17, 1.14-1.21), living outside large cities (1.09, 1.06-1.12), and not being married/cohabiting (1.17, 1.14-1.21), whereas individuals not born in Sweden (0.93, 0.89-0.98) had slightly lower mortality, compared to their respective reference category. Pyelonephritis was associated with lower mortality (0.25, 0.22-0.28) compared with no preceding diagnosis, whereas influenza/pneumonia had no significant association with mortality (1.06, 0.99-1.13). Conclusion These findings can be used to increase the awareness of potential risk factors for sepsis mortality in all settings where patients with sepsis are treated and subsequently followed.

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Abstract Background This multicenter cohort study investigated the association between neonatal Respiratory Distress Syndrome (RDS) and wheezing in preschool-aged preterm infants. Methods A total of 525 children born at < 32-weeks’ gestation were enrolled from three tertiary hospitals in Southwest China and classified into RDS (n = 275) and non-RDS (n = 250) groups. Current wheezing (≥ 1 parental-reported episode in the past year) outcomes were assessed using the International Study on Asthma and Allergy in Childhood (ISAAC) questionnaire at 3-6 years of age. Results The RDS group showed a significantly higher incidence of current wheezing (11.3% vs. 5.6%; aOR = 2.45, 95% CI 1.20-4.98). Subgroup analyses revealed particularly elevated risks among females, infants born at 28⁺⁰-29⁺⁶ weeks, those with birth weights of 1000-1499g, non-IVF conceptions, those with bronchopulmonary dysplasia, and those with < 14-days of oxygen therapy. Sensitivity analyses supported the robustness of these findings. Conclusions The study indicates that RDS is an independent risk factor for wheezing in preterm preschoolers and highlights the need for targeted respiratory monitoring in this population.

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Abstract Objective The research focuses on understanding how GSDMD and Caspase-1, key regulators of pyroptosis, influence postoperative recurrence in Endometrial Polyps (EPs) and examines whether a combined biomarker can effectively predict recurrence likelihood. Methods 264 EP patients (stratified post-surgery into dydrogesterone-treated and control groups) and 132 healthy women were included. Peripheral blood GSDMD-N, Caspase-1, and estrogen concentrations were quantified. Follow-up assessments at one-year post-operation were conducted to examine associations between these pyroptotic markers and clinical outcomes. Results Increases in GSDMD-N and Caspase-1 were observed in EP patients versus healthy subjects (p < 0.05). A diagnostic AUC of 0.781 was determined for the joint model. Pyroptosis markers correlated positively with FSH//E2 and negatively with P (p < 0.05). Recurrent post-surgery cases had higher GSDMD-N/Caspase-1 than non-recurrent ones (p < 0.05); the predictive AUC of the combined model for recurrence reached 0.727. Conclusion Post-EP recurrence correlates with GSDMD/Caspase-1 levels, and integrating these markers enhances recurrence risk assessment.

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ABSTRACT Objective: To assess the diagnostic and prognostic accuracy of C-Reactive Protein (CRP) in adult patients with suspected or confirmed sepsis. Methods: A systematic review and meta-analysis were conducted using the Medline, Embase, and Google Scholar databases, without language or time restrictions. Studies involving adults at risk for, suspected of, or diagnosed with sepsis who underwent CRP measurement and reported diagnostic or prognostic accuracy data were eligible. Both cross-sectional and cohort studies were included. Risk of bias was evaluated with the QUADAS-2 tool, and the quality of evidence was graded using the GRADE approach. Results: A total of 3599 records were screened, and 22 studies (13,083 patients) met the inclusion criteria, 16 assessing diagnostic accuracy and 6 evaluating prognostic value. In the diagnostic meta-analysis, the pooled sensitivity was 83 % (95 % CI 75 %–89 %) and specificity was 56 % (95 % CI 41 %–69 %), with high heterogeneity (I2 = 80.1 %) and a false-positive rate of 44.3 % (95 % CI 30.9 %‒58.6 %). In the prognostic analysis for mortality, the pooled sensitivity was 81 % (95 % CI 70 %–89 %) and the specificity was 77 % (95 % CI 64 %–86 %), with high heterogeneity (I2 = 65.9 %) and a false-positive rate of 22.8 % (95 % CI 13.6 %–35.6 %). Most studies presented a moderate to high risk of bias, and the overall quality of the evidence was rated as low. Conclusions: Current evidence reveals high diagnostic uncertainty and limited prognostic accuracy of CRP in adults with sepsis. The low specificity and high error rates restrict the clinical utility of CRP for diagnostic or prognostic decision-making in sepsis management.

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Abstract Breast cancer remains a major health concern for women because of its prevalence and high morbidity and mortality rates. Metastasis represents the most severe prognosis, and many studies have been conducted to understand the mechanisms involved in cell migration and the factors influencing this process. Objectives To evaluate the effects of melatonin on breast cancer cells through a systematic literature review. Method Systematic review of the literature was carried out through PubMed, Embase and Web of Science as scientific search platforms using Population, Intervention, Comparison, and Outcome (PICO) with the keywords (P) “rat” or “murine”; (I) “melatonin’’, “pineal’’ and “indolamine’’; (C) “breast cancer model’’, “mammary cancer model’’ and “breast tissue’’ and (O) “proliferation” and “cell migration.” The inclusion criteria were full-text, open-access articles in Portuguese, English, or Spanish that focused on the antioxidant and proapoptotic actions of melatonin on breast cancer cells. The exclusion criteria were articles published >20-years ago, those with missing methodological information, and those not describing the dosage and specificity of the research product used. The findings of each included study were structured in tables with details about the sample size, dose of melatonin, and route of administration. The quality of evidence was assessed using the Cochrane risk-of-bias tool. This study was registered in PROSPERO (n° CRD42025635531). Results A total of 257 articles were selected from the databases; 25 were read in full, resulting in 10 articles selected for this systematic review, with a total population of 756 animals studied. From the studies analyzed, six showed a reduction in tumors in correlation with the apoptosis process. This review shows that melatonin can inhibit tumorigenesis in three studies with the lowest risk of bias, which reinforces the oncostatic action of melatonin. However, several studies have combined other substances to evaluate their oncostatic action, making it difficult to infer the mechanisms involved. Further studies are necessary to elucidate the mechanisms through which melatonin acts in mammary carcinogenesis. Conclusion The literature shows that in animal models of breast tumors, high doses of melatonin can induce tumor reduction by cell death through apoptosis. However, further studies are required to understand the mechanisms by which this hormone acts in mammary carcinogenesis.

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Abstract Background/Aims Zenker's Diverticulum (ZD) is a pharyngoesophageal pulsion diverticulum traditionally managed with open surgical or endoscopic (rigid and flexible) techniques. Zenker’s Peroral Endoscopic Myotomy (Z-POEM) has recently emerged as a minimally invasive alternative demonstrating promising efficacy and safety. This narrative review aims to synthesize current evidence regarding the technical evolution of Z-POEM, its indications, procedural nuances, long-term outcomes, cost-effectiveness, and future directions. Methods A structured narrative review was conducted in accordance with SANRA guidelines to assess the technical modifications, clinical outcomes, and complications of Zenker’s Per-Oral Endoscopic Myotomy (Z-POEM). Relevant literature published between January 2016 and September 2025 was systematically searched across PubMed, Scopus, and EMBASE, supplemented by manual citation tracing. Eligible studies included clinical trials, cohorts, observational reports, and technical notes focusing on Z-POEM or its variants. Data extraction and synthesis were performed independently by two reviewers, with findings organized into thematic domains comprising procedural techniques, efficacy, safety, adverse events, recurrence, and follow-up. Results Proper patient selection is critical for technical success. Factors such as diverticulum size, symptom severity, and anatomical features guide the optimal technique. Long-term studies report sustained clinical success exceeding 85% over 30‒40 months. Repeat Z-POEM procedures have shown high efficacy in managing recurrence. Comparative data indicate Z-POEM achieves superior clinical outcomes compared with flexible endoscopic septotomy, with comparable safety and procedure times. Conclusions Z-POEM demonstrates high safety and efficacy, though long-term durability may favor Z-POEM in larger or fibrotic diverticula. Further research should focus on cost-effectiveness, technique standardization, and long-term comparative outcomes to refine patient selection criteria and consolidate Z-POEM as a first-line therapy for ZD.

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Abstract Objective To compare the specificity and sensitivity between self-collection and collection performed by healthcare professionals in testing High-risk oncogenic Human Papillomavirus (HrHPV) to detect high-grade uterine cervical lesions. Methods A systematic review was conducted following PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Meta-analysis was conducted on STATA-14SE using random effects models for the aggregated values of sensitivity and specificity of studies that evaluated self-collection and collection by healthcare professionals. This review is registered on PROSPERO under CRD42022347731. Results This study included 17 articles. Regarding the sensitivity of the collection method, self-collection was superior to professional collection in 2 studies, inferior in 8, equivalent in 1, and variable depending on the sample storage medium, HPV DNA analysis method, or CIN grade assessed in 3. The specificity between the methods was higher with self-collection in 5 studies, lower in 5 others, equivalent in 1, not evaluated in 1, and variable depending on the HPV DNA detection method in 2 articles. The results of the meta-analysis of studies that evaluated the sensitivity and specificity of devices used for HPV detection between self-collection and health-professionals collection showed significant differences of sensitivity favorable to the health-professionals (SMD = -0.540; 95% CI -0.595 ‒ -0.486; p < 0.001). The evaluation of the sensitivity and specificity of the type of lesion between self-collection and health professionals’ collection showed significant differences in sensitivity, favorable to the health professionals (SMD = -0.872; 95% CI -1.392 ‒ -0.351; p = 0.001). Conclusion In conclusion, while specificity is comparable, this meta-analysis demonstrates that self-collected samples have significantly lower sensitivity for detecting HR-HPV and high-grade cervical lesions compared to clinician-collected samples. This suggests that self-sampling, in its current form, may be best utilized with complementary triage strategies or in settings where its logistical advantages outweigh the modest reduction in sensitivity for increasing screening coverage.

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Abstract Objective To perform a meta-analysis evaluating thiamine’s efficacy for sepsis and septic shock to support its clinical use. Methods The meta-analysis of randomized controlled studies on patients with sepsis and septic shock evaluated the efficacy of intravenous thiamine. Articles were retrieved from online databases. Qualities of included studies were assessed. Results Nine studies enrolling 520 patients were included. Regarding bias risk assessment of studies, two articles were classified as low risk, three were categorized as raising some concerns, and four were identified as high risk. Patients in the thiamine group were significantly associated with decreased proportion of Renal Replacement Therapy (RRT, Odds Ratio [OR = 0.26], p = 0.0007), decreased 24 h lactate level (Mean Difference [MD = -0.35], p = 0.004), and larger 24 h SOFA score change (MD = 1.15, p < 0.00001). No statistical significance was detected in short-time mortality (OR = 0.78, p = 0.18) and 24 h lactate change (MD = 0.09, p = 0.36) between the two groups. In the thiamine-deficient subgroup (2 studies, 51 patients), exploratory analysis indicated a potential short-term mortality reduction with thiamine (OR = 0.18, p = 0.01), though limited by the small sample size. Conclusion This meta-analysis preliminarily suggested that thiamine may exert a potential role in improving organ dysfunction among patients with sepsis and septic shock. No significant benefit of thiamine in reducing short-term mortality was observed. It is important to note that the total number of patients included in this meta-analysis is relatively small, which limits the statistical power and external validity of the results.

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Abstract Prioritizing patients on elective surgical waiting lists is one of the strategies to reduce waiting times for care, improve Health-Related Quality of Life (HRQoL), and optimize clinical resources. According to the World Health Organization (WHO) recommendations, including biopsychosocial factors in the Clinical Priority Assessment Criteria (CPAC) is critical for an equitable and efficient allocation of surgical treatments. Long waiting lists, decreased Health-Related Quality of life (HRQoL), lack of capacity of health care facilities, and lack of policies to improve these problems negatively affect the population worldwide. This article presents a systematic literature review to identify biopsychosocial factors that can be used for prioritizing patients on surgical waiting lists. 71 articles were studied, finding that the most frequently mentioned biopsychosocial factors are pain and/or discomfort, followed by patient age, disease severity, comorbidities, expected complications after the procedure, ability to work and/or study, efficacy of the procedure and/or expected improvement, time on the waiting list, ability to participate in family/social activities, impact on the disease if surgery is delayed, need for a caregiver, effect on the procedure if surgery is delayed, composition and size of the surgical team, being a caregiver, length of hospital stay, urgency of the procedure, among others. These findings reinforce the importance of a comprehensive assessment of the patient and the environment to improve clinical outcomes and equity in access to surgical interventions by integrating the patient and physician perspectives in pursuit of better outcomes.

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Abstract Background “Chemobrain”, or chemotherapy-related cognitive impairment, is a well-documented clinical phenomenon. While neuroinflammation has been proposed as a key underlying mechanism, a comprehensive mapping of the knowledge structure and evolution of this specific research domain is lacking. Methods The authors conducted a bibliometric analysis to quantitatively and visually characterize the scholarly literature on neuroinflammation and chemobrain. A total of 923 relevant publications from the Web of Science Core Collection (1994‒2023) were analyzed using VOSviewer. Results The analysis reveals a rapidly growing field, with a significant increase in publications and thematic focus on terms like cytokines, microglia, and oxidative stress in recent years. This shift signifies a move from purely descriptive studies toward mechanistic inquiry. While the United States has historically been the dominant contributor, China has emerged as a leading force in the past decade, indicating a global expansion of research interest. Conclusion This study provides the first holistic overview of the neuroinflammation and chemobrain research landscape, delineating its thematic evolution and collaborative networks. The findings underscore that neuroinflammation remains a highly active, yet not fully elucidated, mechanistic hypothesis driving the field. A key limitation is the bibliometric nature of the study, which reflects terminological and publication trends rather than direct biological validation. Future research should focus on integrating multi-omics data and conducting longitudinal clinical studies to substantiate these mechanistic links.

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Abstract Objective In this research, we conducted a systematic review of artificial intelligence techniques used for the diagnosis of lung cancer. Methods A systematic search of Web of Science, PubMed, Scopus, Epistemonikos, Cochrane, Medline, and Embase databases was carried out, containing the literature published up to June 2025. Prediction model risk of bias assessment tool (PROBAST) was used to evaluate the risk of bias and applicability of the diagnostic model studies included in the current research. Results 204 studies were included. The included articles utilized various AI techniques, including CNN (Convolutional Neural Network), SVM (Support Vector Machine), RF (Random Forest), KNN (K-Nearest Neighbor), PM-DL (Pattern Matching combined with Deep Learning), ANN (Artificial Neural Network), DNN (Deep Neural Network), CDNs (Convolutional Dense Networks), DLS (Deep Learning System), LSTM (Long Short-Term Memory), NNE (Neural Network Ensemble), and LDA (Linear Discriminant Analysis). The CNN model appears to be the most commonly used model in the papers. It was observed that applying deep learning models to preprocessed and augmented medical images led to improved performance metrics, including AUC, sensitivity, and accuracy. The accuracy of artificial intelligence techniques ranged from 68.4 to 100, while the sensitivity varied from 50.0 to 100. The specificity of the artificial intelligence techniques ranged from 50.0 to 100. The AUC of the artificial intelligence techniques ranged from 61.0 % to 100 %, while the recall varied from 75.0 to 99.82. Conclusion This research accentuates the potential of artificial intelligence techniques in the diagnosis and detection of lung cancer, with diverse levels of diagnostic accuracy. Additional research is required to optimize these artificial intelligence techniques, as well as to ascertain their clinical relevance and appropriateness in real-world clinical applicability.

Resumo em Inglês:

Abstract Background and methods Recurrent fever is a complex clinical presentation that poses significant diagnostic challenges, particularly when no clear etiology emerges despite extensive investigation. This integrative narrative review provides a comprehensive overview of recurrent fever and proposes a practical diagnostic flowchart focused on the most frequent etiologies, with particular emphasis on the Latin American and Brazilian contexts. Literature from MEDLINE/PubMed, LILACS, and SciELO was reviewed to summarize evidence on epidemiology, differential diagnosis, and diagnostic strategies. Results Recurrent fever may arise from infectious diseases, autoimmune or autoinflammatory disorders, malignancies, metabolic or occupational conditions, drug-induced etiologies, and factitious causes. Infections, notably tuberculosis, malaria, leishmaniasis, and endocarditis, remain leading contributors in developing countries. Non-infectious causes such as rheumatologic conditions, neoplasms, and inborn errors of immunity must also be considered, especially in persistent or unexplained cases. A structured, tiered approach to diagnosis is recommended, beginning with basic laboratory and imaging studies, progressing to targeted invasive procedures and advanced modalities such as 18F-FDG PET/CT, and, when appropriate, genomic sequencing. The flowchart proposed in this review emphasizes clinical history, frequent reassessment, and the judicious use of diagnostic resources to balance cost-effectiveness and diagnostic yield. Moreover, distinguishing between inflammatory and non-inflammatory patterns, as well as identifying the newly described Syndrome of Undifferentiated Recurrent Fever (SURF), may guide further evaluation. Ultimately, recurrent fever requires a systematic and multidisciplinary approach. Incorporating epidemiological context and advances in molecular and imaging technologies may improve diagnostic accuracy and patient outcomes.

Resumo em Inglês:

Abstract Background Accurate assessment of Submucosal (SM) invasion in gastric neoplasms is vital for curative endoscopic management, yet conventional endoscopy remains moderately accurate and operator dependent. Whether AI can deliver reliable, generalizable depth prediction is unknown. Aim This investigation establishes the diagnostic capability of AI-driven endoscopic systems for identifying SM invasion. Methods: A PRISMA-DTA systematic review and meta-analysis identified studies that used machine-learning or deep-learning models applied to endoscopic imaging with histopathology as the reference standard. Validation-set 2 × 2 data were pooled using hierarchical models to estimate sensitivity, specificity, and AUC, and heterogeneity was assessed through subgroup analyses. Results Eight studies were included in the systematic review; seven studies provided sufficient data (including ten cohorts for the meta-analysis). AI systems demonstrated a pooled sensitivity of 0.75 (95% CI 0.69-0.81) and a specificity of 0.84 (95% CI 0.79-0.87). Discriminatory ability was high (AUC = 0.87, 95% CI 0.84-0.90), providing a conservative, transportable estimate of performance based on validation cohorts. Heterogeneity was substantial. Externally validated models showed lower sensitivity than internally validated models (0.72 vs. 0.79; p < 0.001), revealing overfitting. Korean cohorts demonstrated higher specificity than studies from other regions (0.87 vs. 0.79; p < 0.001). Fagan's analysis showed that a positive AI result increased post-test probability from 25% to 61%, while a negative result reduced it to 9%. Conclusions AI-assisted endoscopic assessment establishes a high-accuracy framework for identifying SM invasion and opens the door to more consistent treatment selection in early gastric cancer. International external validation and unified invasion definitions remain essential for dependable clinical use.