Major discrepancy between clinical diagnosis of death and anatomopathological findings in adolescents with chronic diseases during 18-years

Ribeiro, Maira P.; Duarte Neto, Amaro N.; Dolhnikoff, Marisa; Lindoso, Livia; Lourenco, Benito; Marques, Heloisa H.; Pereira, Maria F.B.; Cristofani, Lilian M.; Odone Filho, Vicente; Campos, Lucia M.A.; Sallum, Adriana M.E.; Carneiro-Sampaio, Magda; Delgado, Artur F.; Carvalho, Werther B.; Mauad, Thais; Silva, Clovis A.

doi:10.1016/j.clinsp.2023.100184

Brasil

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Original articles • Clinics 78 • 2023 • https://doi.org/10.1016/j.clinsp.2023.100184 linkcopy

Major discrepancy between clinical diagnosis of death and anatomopathological findings in adolescents with chronic diseases during 18-years

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objectives: To evaluate the inconsistency between clinical diagnosis of death and autopsy findings in adolescents with chronic diseases.

Methods: A cross-sectional study including a sample of adolescents’ autopsies who died in a pediatric and adolescent tertiary hospital over 18 consecutive years. During this period, there were n = 2912 deaths, and n = 581/2912(20%) occurred in adolescents. Of these, n = 85/581(15%) underwent autopsies and were analyzed. Further results were divided into two groups: Goldman classes I or II (high disagreement between main clinical diagnosis of death and anatomopathological findings, n = 26) and Goldman classes III, IV or V (low or no disagreement between these two parameters, n = 59).

Results: Median age at death (13.5 [10‒19] vs. 13 [10‒19] years, p = 0.495) and disease duration (22 [0‒164] vs. 20 [0‒200] months, p = 0.931), and frequencies for males (58% vs. 44%, p = 0.247) were similar between class I/II vs. class III/IV/V. The frequency of pneumonia (73% vs. 48%, p = 0.029), pulmonary abscess (12% vs. 0%, p = 0.026), as well as isolation of yeast (27% vs. 5%, p = 0.008), and virus (15% vs. 2%, p = 0.029) identified in the autopsy, were significantly higher in adolescents with Goldman class I/II compared to those with Goldman class III/IV/V. In contrast, cerebral edema was significantly lower in adolescents of the first group (4% vs. 25%, p = 0.018).

Conclusion: This study showed that 30% of the adolescents with chronic diseases had major discrepancies between clinical diagnosis of death and autopsy findings. Pneumonia, pulmonary abscess, as well as isolation of yeast and virus were more frequently identified at autopsy findings in the groups with major discrepancies.

Keywords: Autopsy; Death; Adolescent; Chronic diseases; Pneumonia; Yeast

HIGHLIGHTS

Evaluation of disagreement between clinical diagnosis of death and autopsy findings in adolescents with chronic diseases.

30% of the adolescents with chronic diseases had major discrepancies between clinical diagnosis of death and autopsy findings, mainly caused by infections.

Pneumonia, pulmonary abscess, as well as isolation of yeast and virus were identified at autopsy findings in the groups with major discrepancies.

Variables	Class I/II (n = 26)	Class III/IV/V (n = 59)	p
Demographic data
Age at death, years	13.5 (10‒19)	13 (10‒19)	0.495
Male sex	15 (58)	26 (44)	0.247
Residents out of the state of SP	3 (12)	8 (14)	1.000
Disease duration, months	22 (0‒164)	20 (0‒200)	0.931
Hospital admissions at PICU or ER
Period of last hospitalization, days	23 (0‒102)	9 (0‒99)	0.563
Number of previous hospitalizations	3.5 (1‒19)	3 (1‒32)	0.448
Death at PICU	18 (69)	44 (75)	0.609
Death at ER	6 (23)	7 (12)	0.204
Supportive measures at PICU or ER
Pediatric palliative care	0 (0)	3 (5)	0.550
Surgical procedures	8 (31)	20 (34)	1.000
Renal replacement therapy	7 (27)	14 (24)	0.789
Antibiotics therapy	23 (88)	55 (93)	0.670
Antifungal therapy	13 (50)	36 (61)	0.344
Vasoactive drugs	25 (96)	49 (83)	0.160
Albumin transfusion	10 (38)	22 (37)	1.000
Blood products transfusion	18 (69)	49 (83)	0.162
Invasive respiratory support	23 (88)	53 (90)	1,000
Central venous catheterization	0 (0)	0 (0)	NA
“Do-not-resuscitate order”	5 (19)	7 (12)	0.500

Autopsy findings	Class I/II (n = 26)	Class III/IV/V (n = 59)	p
Cerebral involvement	12 (46)	30 (51)	0.690
Meningoencephalitis	7 (27)	7 (12)	0.114
Cerebral hemorrhage	7 (27)	17 (29)	1.000
Cerebral herniation	2 (8)	3 (5)	0.639
Cerebral edema	1 (4)	15 (25)	0.018
Parenchyma ischemia	0 (0)	1 (2)	1.000
Heart involvement	10 (38)	27 (46)	0.532
Cardiomegaly	2 (8)	5 (8)	1.000
Left ventricle hypertrophy	0 (0)	1 (2)	1.000
Pericardial effusion	4 (15)	19 (32)	0.108
Myocarditis	6 (23)	5 (8)	0.084
Pericarditis	1 (4)	1 (2)	0.521
Myocardiosclerosis	1 (4)	1 (2)	0.521
Pulmonary involvement	23 (88)	56 (95)	0.364
Pneumonia	19 (73)	28 (47)	0.029
Pleural effusion	11 (42)	29 (49)	0.560
Pneumothorax	1 (4)	0 (0)	0.306
Hemothorax	1 (4)	1 (2)	0.521
Pulmonary abscess	3 (12)	0 (0)	0.026
Pulmonary hemorrhage	10 (38)	28 (47)	0.486
Pulmonary thromboembolism	2 (8)	2 (3)	0.583
Pulmonary edema	7 (27)	21 (36)	0,433
Pulmonary infarction	0 (0)	3 (5)	0.550
Pulmonary bronco aspiration	0 (0)	2 (3)	1.000
Tracheitis	0 (0)	2 (3)	1.000
Mediastinal mass	1 (4)	0 (0)	0.306
Hepatic and biliary involvements	13 (50)	29 (49)	1.000
Ascites	9 (35)	24 (41)	0.808
Hepatitis	7 (27)	11 (19)	0.389
Hepatic abscess	1 (4)	1 (2)	0,521
Cirrhosis	1 (4)	3 (5)	1.000
Pancreas involvement	6 (23)	14 (24)	0.948
Pancreatitis	6 (23)	14 (24)	0.948
Renal involvement	10 (38)	12 (20)	0.079
Pyelonephritis	5 (19)	5 (8)	0.155
Chronic nephropathy	5 (19)	6 (10)	0.299
Renal infarction	0 (0)	1 (2)	1.000
Genital organ alteration	2 (8)	1 (2)	0.220
Spleen involvement	11 (42)	26 (44)	0.880
Spleen necrosis	2 (8)	5 (8)	1.000
Splenitis	10 (38)	23 (39)	0.930

Autopsy findings	Class I/II (n = 26)	Class III/IV/V (n = 59)	p
Gastrointestinal involvement	17 (65)	34 (58)	0.501
Esophagus alterations	6 (23)	12 (20)	0.779
Hemorrhagic gastritis	7 (27)	18 (31)	0.738
Gastric ulcers	5 (19)	4 (7)	0.124
Colitis	8 (31)	12 (20)	0.482
Digestive hemorrhage	6 (23)	13 (22)	0.915
Peritonitis	2 (8)	2 (3)	0.583
Hemoperitoneum	1 (4)	0 (0)	0.306
Intestinal obstruction	0 (0)	2 (3)	1.000
Intestinal perforation	0 (0)	1 (2)	1.000
Other abnormalities	13 (50)	35 (59)	0.424
Muscles abnormalities	0 (0)	2 (3)	1.000
Joint abnormalities	2 (8)	2 (3)	0.583
Skin abnormalities	9 (35)	27 (46)	0.338
Genetic abnormalities	2 (8)	6 (10)	1.000
Malformations	0 (0)	5 (8)	0.317
Tumors	8 (31)	21 (36)	0.805
Tumor primary histogenesis
Acute myeloid leukemia	1 (4)	4 (7)	1.000
Acute lymphoblastic leukemia A	0 (0)	3 (5)	0.550
Acute lymphoblastic leukemia B	1 (4)	2 (3)	1.000
Others	6 (23)	12 (20)	0.779
Tumor primary site
Lymphohematopoietic	3 (12)	16 (27)	0.159
Armpit	0 (0)	1 (2)	1.000
Inferior limbs	0 (0)	3 (5)	0.550
Central nervous system tumor	1 (4)	0 (0)	0.306
Retro orbital	1 (4)	0 (0)	0.306
Skull	1 (4)	0 (0)	0.306
Mediastinum	1 (4)	0 (0)	0.306
Intestine	1 (4)	0 (0)	0.306
Colon	0 (0)	1 (2)	1.000
Localization of tumor
Central nervous system	2 (8)	3 (5)	0.639
Head and neck	1 (4)	2 (3)	1.000
Mediastinal	1 (4)	4 (7)	1.000
Cardiac	0 (0)	2 (3)	1.000
Pulmonary	2 (8)	4 (7)	1,000
Hepatic	2 (8)	8 (14)	0.717
Pancreatic	0 (0)	1 (2)	1.000
Bile ducts	0 (0)	1 (2)	1.000
Intestinal	0 (0)	4 (7)	0.308
Spleen	2 (8)	9 (15)	0.491
Kidney	0 (0)	4 (7)	0.308
Pelvis	0 (0)	1 (2)	1.000
Bone	3 (12)	7 (12)	1.000
Microorganism
Gram positive cocci	2 (8)	0 (0)	0.091
Gram negative cocci	1 (4)	0 (0)	0.306
Yeasts	7 (27)	3 (5)	0.008
Hyphomycetes	3 (12)	1 (2)	0.083
Protozoa	1 (4)	0 (0)	0.306
Virus	4 (15)	1 (2)	0.029

Patient	Age at death	Sex	Final clinical diagnosis (other relevant information of clinical history on medical records)	Final autopsy diagnosis^a a Final autopsy diagnosis is based on macroscopic and microscopic analyses.	Goldman class
1	11	M	Pneumonia (JIA, fever, vomiting, seizure)	Diffuse hemophagocytosis	I
2	12	F	Pneumonia and sepsis/septic shock (JIA)	Pneumonia/cytomegaloviruses	I
3	13	M	Bacterial peritonitis and sepsis/septic shock (hepatic cirrhosis)	Disseminated candidiasis	I
4	11	F	Sepsis/septic shock without a primary defined source of infection (medulloblastoma, cerebral herniation)	Pneumonia	II
5	11	M	Severe drug reaction (Stevens-Johnson syndrome after penicillin allergy)	Pneumonia	I
6	11	M	Intestinal sub occlusion and sepsis/septic shock without a primary defined source of infection (PNET, abdominal distension, hematemesis, dehydration)	Hemorrhagic shock by bowel perforation	I
7	16	F	Febrile neutropenia (AML)	Diffuse severe hemorrhage by coagulopathy	I
8	11	F	Sepsis/septic shock without a primary defined source of infection (congenital hepatic fibrosis)	Pneumonia due to Nocardia	I
9	16	M	Sepsis/septic shock without a primary defined source of infection (sclerosis cholangitis after liver transplantation)	Acute pancreatitis	I
10	18	F	Hypovolemic shock (cSLE, arterial hypertension)	Disseminated intravascular coagulation	I
11	14	M	Sepsis/septic shock without a primary defined source of infection (germ cell tumor, ARDS)	Pneumonia/cytomegaloviruses	II
12	19	F	Pericarditis and sepsis/septic shock without a primary defined source of infection (cSLE)	Invasive aspergillosis	I
13	18	M	Sepsis/septic shock without a primary defined source of infection (sclerosis cholangitis after liver transplantation, ARDS)	Aspiration pneumonia	I
14	11	F	Disseminated angiosarcoma and sepsis/septic shock without a primary defined source of infection (pancytopenia)	Cerebral hemorrhage	I
15	13	F	Pancytopenia, pneumonia and sepsis/septic shock (cSLE)	Invasive aspergillosis	II
16	14	M	Acute respiratory insufficiency (juvenile dermatomyositis, pulmonary hemosiderosis)	Pneumonia	I
17	14	F	Liver insufficiency and sepsis/septic shock without a primary defined source of infection (alpha 1-antitrypsin deficiency)	Invasive aspergillosis	I
18	11	M	Chronic diarrhea and sepsis/septic shock without a primary defined source of infection (HIV)	Cryptococcosis	I
19	12	M	Neurotoxoplasmosis and sepsis/septic shock without a primary defined source of infection (HIV)	Invasive aspergillosis	I
20	12	F	Sepsis/septic shock without a primary defined source of infection (ALL, and severe musculoskeletal pain)	Pneumonia/necrotising bacterial laryngitis	II
21	10	M	Cardiorespiratory arrest (HIV)	Pneumonia by Pneumocystis jirovecii	I
22	17	F	Sepsis/septic shock without a primary defined source of infection (cSLE, hypogammaglobinemia, fever, vomiting, headache)	Pneumonia	II
23	15	M	Sepsis/septic shock without a primary defined source of infection (epidermolysis bullosa)	Pneumonia/sigmoid volvulus	I
24	16	M	Sepsis/septic shock without a primary defined source of infection (cSLE, fever, vomiting, myalgia, seizure)	Pneumonia	II
25	14	M	Alveolar hemorrhage (medullary aplasia, fever, bronchoalveolar culture positive for Elizabethkingia meningoseptica)	Septic shock due to disseminated candidiasis	I
26	17	M	Diffuse hemorrhage (idiopathic thrombocytopenic purpura, fever, hypoxemia, disseminated petechial rash, meningeal signs)	Pneumonia/mediastinal abscess	I

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[TFN1] Results are presented in n (%), median (minimum-maximum); Class I, Missed major diagnosis with probable impact on survival and that accurate diagnosis would have changed management; Class II, Missed major diagnosis with no probable impact on survival and that accurate diagnosis would not have changed management; PICU, Pediatric Intensive Care Unit; ER, Emergency Room; NA, Not Applicable; SP, São Paulo.