Aspiration-related deaths in 57 consecutive patients: autopsy study.
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ABSTRACT:
SUBMITTER: Hu X
PROVIDER: S-EPMC4116222 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:IntroductionThe COVID-19 pandemic is an international emergency with an extreme socioeconomic impact and a high mortality and disease burden. The COVID-19 outbreak is neither fully understood nor fully pictured. Autopsy studies can help understand the pathogenesis of COVID-19 and has already resulted in better treatment of patients. Structured and systematic autopsy of COVID-19-related deaths will enhance the mapping of pathophysiological pathways, not possible in the living. Furthermore, it provides an opportunity to envision factors translationally for the purpose of disease prevention in this and future pandemics. This is the protocol for an autopsy study that offers an umbrella for deep and diverse investigations of COVID-19-related deaths, including a systematic investigation of 'long' COVID-19 by means of extensive and systematic tissue sampling.Methods and analysisA COVID-19-specific autopsy algorithm has been created to cover all cases undergoing clinical or forensic autopsy in Denmark. The algorithm describes advanced tissue sampling and a translational analytical follow-up for deep phenotyping. The translational approach covers registry data, postmortem imaging, gross autopsy findings, microscopic organ changes, postmortem toxicology, postmortem biochemical investigation, microbiological profiling and immunological status at the time of death, and future research projects covering genetics and epigenetics on an organ level.Ethics and disseminationThis study has been approved by the Regional Ethics Committee of the Region of Greater Copenhagen (No: H-20078436) and the Danish Data Protection Agency (No: 2002-54-1080). Next of kin gave informed consent to research. The study results will be published in peer-reviewed journals.Trial registration numberThis study is purely observational and, as such, does not meet the criteria of the International Committee of Medical Journal Editors for clinical trials; thus, there is no need for registration in a database of research trials, such as clinical trials. To facilitate cooperation in research, provide transparency on case recruitment for publications to come and to avoid unnecessary duplicate work, we nevertheless wish to publish our protocol.
| S-EPMC8406463 | biostudies-literature
Project description:ImportancePostmortem genetic testing of young individuals with sudden death has previously identified pathogenic gene variants. However, prior studies primarily considered highly penetrant monogenic variants, often without detailed decedent and family clinical information.ObjectiveTo assess genotype and phenotype risk in a diverse cohort of young decedents with sudden death and their families.Design, setting, and participantsPathological and whole-genome sequence analysis was conducted in a cohort referred from a national network of medical examiners. Cases were accrued prospectively from May 2015 to March 2019 across 24 US states. Analysis began September 2016 and ended November 2020.ExposuresEvaluation of autopsy and clinical data integrated with whole-genome sequence data and family member evaluation.ResultsA total of 103 decedents (mean [SD] age at death, 23.7 [11.9] years; age range, 1-44 years), their surviving family members, and 140 sex- and genetic ancestry-matched controls were analyzed. Among 103 decedents, autopsy and clinical data review categorized 36 decedents with postmortem diagnoses, 23 decedents with findings of uncertain significance, and 44 with sudden unexplained death. Pathogenic/likely pathogenic (P/LP) genetic variants in arrhythmia or cardiomyopathy genes were identified in 13 decedents (12.6%). A multivariable analysis including decedent phenotype, ancestry, and sex demonstrated that younger decedents had a higher burden of P/LP variants and select variants of uncertain significance (effect size, -1.64; P = .001). These select, curated variants of uncertain significance in cardiac genes were more common in decedents than controls (83 of 103 decedents [86%] vs 100 of 140 controls [71%]; P = .005), and decedents harbored more rare cardiac variants than controls (2.3 variants per individual vs 1.8 in controls; P = .006). Genetic testing of 31 parent-decedent trios and 14 parent-decedent dyads revealed 8 transmitted P/LP variants and 1 de novo P/LP variant. Incomplete penetrance was present in 6 of 8 parents who transmitted a P/LP variant.Conclusions and relevanceWhole-genome sequencing effectively identified P/LP variants in cases of sudden death in young individuals, implicating both arrhythmia and cardiomyopathy genes. Genomic analyses and familial phenotype association suggest potentially additive, oligogenic risk mechanisms for sudden death in this cohort.
| S-EPMC8358810 | biostudies-literature
Project description:BackgroundAccurate cause of death data are essential to guide health policy. However, mortality surveillance is limited in many low-income countries. In such settings, verbal autopsy (VA) is increasingly used to provide population-level cause of death data. VAs are now widely interpreted using the automated algorithms SmartVA and InterVA. Here we use conventional autopsy as the gold standard to validate SmartVA methodology.MethodsThis study included adult deaths from natural causes in São Paulo and Recife for which conventional autopsy was indicated. VA was conducted with a relative of the deceased using an amended version of the SmartVA instrument to suit the local context. Causes of death from VA were produced using the SmartVA-Analyze program. Physician coded verbal autopsy (PCVA), conducted on the same questionnaires, and Global Burden of Disease Study data were used as additional comparators. Cause of death data were grouped into 10 broad causes for the validation due to the real-world utility of VA lying in identifying broad population cause of death patterns.FindingsThe study included 2,060 deaths in São Paulo and 1,079 in Recife. The cause specific mortality fractions (CSMFs) estimated using SmartVA were broadly similar to conventional autopsy for: cardiovascular diseases (46.8% vs 54.0%, respectively), cancers (10.6% vs 11.4%), infections (7.0% vs 10.4%) and chronic respiratory disease (4.1% vs 3.7%), causes accounting for 76.1% of the autopsy dataset. The SmartVA CSMF estimates were lower than autopsy for "Other NCDs" (7.8% vs 14.6%) and higher for diabetes (13.0% vs 6.6%). CSMF accuracy of SmartVA compared to autopsy was 84.5%. CSMF accuracy for PCVA was 93.0%.InterpretationThe results suggest that SmartVA can, with reasonable accuracy, predict the broad cause of death groups important to assess a population's epidemiological transition. VA remains a useful tool for understanding causes of death where medical certification is not possible.
| S-EPMC9904092 | biostudies-literature
Project description:BACKGROUND:Conventional definitions of sudden cardiac death (SCD) presume cardiac cause. We studied the World Health Organization-defined SCDs autopsied in the POST SCD study (Postmortem Systematic Investigation of SCD) to determine whether premortem characteristics could identify autopsy-defined sudden arrhythmic death (SAD) among presumed SCDs. METHODS:Between January 2, 2011, and January 4, 2016, we prospectively identified all 615 World Health Organization-defined SCDs (144 witnessed) 18 to 90 years in San Francisco County for medical record review and autopsy via medical examiner surveillance. Autopsy-defined SADs had no extracardiac or acute heart failure cause of death. We used 2 nested sets of premortem predictors-an emergency medical system set and a comprehensive set adding medical record data-to develop Least Absolute Selection and Shrinkage Operator models of SAD among witnessed and unwitnessed cohorts. RESULTS:Of 615 presumed SCDs, 348 (57%) were autopsy-defined SAD. For witnessed cases, the emergency medical system model (area under the receiver operator curve 0.75 [0.67-0.82]) included presenting rhythm of ventricular tachycardia/fibrillation and pulseless electrical activity, while the comprehensive (area under the receiver operator curve 0.78 [0.70-0.84]) added depression. If only ventricular tachycardia/fibrillation witnessed cases (n=48) were classified as SAD, sensitivity was 0.46 (0.36-0.57), and specificity was 0.90 (0.79-0.97). For unwitnessed cases, the emergency medical system model (area under the receiver operator curve 0.68 [0.64-0.73]) included black race, male sex, age, and time since last seen normal, while the comprehensive (area under the receiver operator curve 0.75 [0.71-0.79]) added use of β-blockers, antidepressants, QT-prolonging drugs, opiates, illicit drugs, and dyslipidemia. If only unwitnessed cases <1 hour (n=59) were classified as SAD, sensitivity was 0.18 (0.13-0.22) and specificity was 0.95 (0.90-0.97). CONCLUSIONS:Our models identify premortem characteristics that can better specify autopsy-defined SAD among presumed SCDs and suggest the World Health Organization definition can be improved by restricting witnessed SCDs to ventricular tachycardia/fibrillation or nonpulseless electrical activity rhythms and unwitnessed cases to <1 hour since last normal, at the cost of sensitivity.
| S-EPMC6738572 | biostudies-literature
Project description:BackgroundRegistration of the fact of death is almost complete in the city of Chennai and not so in the rural Villupuram district in Tamilnadu, India. The cause of death is often inadequately recorded on the death certificate in developing countries like India. A special verbal autopsy (VA) study of 48,000 adult (aged >or= 25 yrs) deaths in the city of Chennai (urban) during 1995-97 and 32,000 in rural Villupuram during 1997-98 was conducted to arrive at the probable underlying cause of death to estimate cause specific mortality.MethodsA ten day training on writing verbal autopsy (VA) report for adult deaths was given to non-medical graduates with at least 15 years of formal education. They interviewed surviving spouse/close associates of the deceased to write a verbal autopsy report in local language (Tamil) on the complaints, symptoms, signs, duration and treatment details of illness prior to death. Each report was reviewed centrally by two physicians independently. Random re-interviewing of 5% of the VA reports was done to check the reliability and reproducibility of the VA report. The validity of VA diagnosis was assessed only for cancer deaths.ResultsVerbal autopsy reduced the proportion of deaths attributed to unspecified and unknown causes from 54% to 23% (p < 0.0001) in urban and from 41% to 26% (p < 0.0001) in rural areas in Tamilnadu for adult deaths (>or= 25). The sensitivity of VA to identify cancer was 95% in the age group 25-69.ConclusionA ten day training programme to write verbal autopsy report with adequate feed back sessions and random sampling of 5% of the verbal autopsy reports for re-interview worked very well in Tamilnadu, to arrive at the probable underlying cause of death reliably for deaths in early adult life or middle age (25-69 years) and less reliably for older ages (70+). Thus VA is practicable for deaths in early adult life or middle age and is of more limited value in old age.
| S-EPMC535898 | biostudies-literature
Project description:BackgroundThe purpose of the work was to assess the contribution to diagnosis and/or treatment (CDT) of bone marrow aspiration (BMA) in the critically ill patient.MethodsThe retrospective study included 193 patients. On the basis of BMA findings, contribution to diagnosis was defined by one of four previously unestablished diagnoses (maturation arrest of granulocyte precursors, hemophagocytic lymphohistiocytosis, hematological malignancy, marrow infiltration with cancer cells) and to treatment as the initiation or withdrawal of a specific treatment including the decision to forgo life-sustaining treatment (DFLST).ResultsA CDT of BMA was observed in 40/193 patients (20.7%). BMA contributed to diagnosis in 37 cases (granulocyte precursor maturation arrest, N?=?10; hemophagocytic lymphohistiocytosis, N?=?12; hematological malignancy, N?=?15) and to treatment in 14, including three DFLSTs. In multivariate analysis, the factors associated with a CDT were hematological malignancy, cancer or non-malignant hematological abnormality known on admission, indication for BMA excluding isolated thrombocytopenia, higher pre-BMA HScore (calculated prior to BMA), and higher SOFA score with or without platelet-count SOFA subscore. In the 160 patients without hematological malignancy or cancer known on admission, non-malignant hematological abnormality known on admission, indication for BMA excluding isolated thrombocytopenia, higher pre-BMA HScore, and higher SOFA score calculated with or without platelet-count SOFA subscore were independently associated with a CDT of BMA.ConclusionBMA can have a significant CDT in ICU patients with or without a known hematological malignancy or cancer on admission. An HScore calculated before BMA can be a valuable tool for predicting a CDT of BMA.
| S-EPMC5715543 | biostudies-literature
Project description:BackgroundLymphotoxin-alpha (LTA) is a pro-inflammatory cytokine with anti-tumor activity. The objective of this study was to determine whether LTA polymorphisms influence the presence of cancer.MethodsLTA polymorphisms C804A (rs1041981, T60N) and T495C (rs2229094, C13R) were determined in 1,536 consecutive autopsy cases and were registered in the Japanese single-nucleotide polymorphisms (SNPs) for geriatric research (JG-SNP) Internet database. Tumors were systematically reviewed, pathologically confirmed, and assessed in relation to LTA genotype.ResultsThe study population consisted of 827 males and 709 females, with a mean age of 80 years. Altogether, we studied 606 subjects without cancer and 930 subjects with cancer of the stomach (n = 183), lung (n = 164), colon or rectum (n = 143), or other sites. The presence of cancer was higher in males than in females. The C804A and T495C polymorphisms were associated with cancer in males (CA + AA: CC, adjusted OR = 0.72, 95% CI = 0.53 - 0.99; TC + CC: TT, adjusted OR = 1.45, 95% CI = 1.04 - 2.02; respectively) but not in females. In males, the C804A polymorphism was associated with lung cancer (CA + AA: CC, adjusted OR = 0.60, 95% CI = 0.37 - 0.97), whereas the T495C polymorphism was associated with gastric cancer (TC + CC: TT, adjusted OR = 1.68, 95% CI = 1.06 - 2.65).ConclusionWe found some evidence of an association between LTA polymorphisms and cancer risk in elderly Japanese men. Further studies in larger populations should examine this hypothesis.
| S-EPMC2527017 | biostudies-literature
Project description:Mortality statistics by age, sex and cause are the foundation of basic health data required for health status assessment, epidemiological research and formation of health policy. Close to half the deaths in Malaysia occur outside a health facility, are not attended by medical personnel, and are given a lay opinion as to the cause of death, leading to poor quality of data from vital registration. Verbal autopsy (VA) is a very useful tool in diagnosing broad causes of deaths for events that occur outside health facilities. This article reports the development of the VA methods and our principal finding from a validation study.A cross sectional study on nationally representative sample deaths that occurred in Malaysia during 2013 was used. A VA questionnaire suitable for local use was developed. Trained field interviewers visited the family members of the deceased at their homes and conducted face to face interviews with the next of kin. Completed questionnaires were reviewed by trained physicians who assigned multiple and underlying causes. Reference diagnoses for validation were obtained from review of medical records (MR) available for a sample of the overall study deaths.Corresponding MR diagnosis with matched sample of the VA diagnosis were available in 2172 cases for the validation study. Sensitivity scores were good (>75%) for transport accidents and certain cancers. Moderate sensitivity (50% - 75%) was obtained for ischaemic heart disease (64%) and cerebrovascular disease (72%). The validation sample for deaths due to major causes such as ischaemic heart disease, pneumonia, breast cancer and transport accidents show low cause-specific mortality fraction (CSMF) changes. The scores obtained for the top 10 leading site-specific cancers ranged from average to good.We can conclude that VA is suitable for implementation for deaths outside the health facilities in Malaysia. This would reduce ill-defined mortality causes in vital registration data, and yield more accurate national mortality statistics.
| S-EPMC5553780 | biostudies-other
Project description:AimsForensic autopsies are important for the investigation of deaths with a legal or public-health interest, as well as being a source for cause-of-death statistics. The aim of this study was to investigate the use of forensic autopsies in Norway, with a special emphasis on geographical variation.MethodsData from the Norwegian Cause of Death Registry for the years 1996-2017 included 920,232 deaths and 37,398 forensic autopsies. We used logistic regression to identify factors that were associated with the proportion of forensic autopsies, grouped according to the registered cause of death. Explanatory variables were age and sex, place of death, police district, population size and urbanity level of the municipality and distance to the autopsy facility.ResultsThe proportion of deaths undergoing forensic autopsy was 4.1%, with the highest being homicides (96.6%) and the lowest being deaths from natural causes (1.7%). Variation between police districts was 0.9-7.8%, and the span persisted during the study period. The most important explanatory variables across the strata were place of death (there were few autopsies of deaths in health-care facilities), police district and age of the deceased. Distance to the autopsy facility, sex, population size and the level of urbanity had only a minor influence. The variation between police districts was not fully accounted for by the other investigated factors.Conclusions
| S-EPMC9152604 | biostudies-literature
Project description:BackgroundPublic objection to autopsy has led to a search for minimally invasive alternatives. Imaging has potential, but its accuracy is unknown. We aimed to identify the accuracy of post-mortem CT and MRI compared with full autopsy in a large series of adult deaths.MethodsThis study was undertaken at two UK centres in Manchester and Oxford between April, 2006, and November, 2008. We used whole-body CT and MRI followed by full autopsy to investigate a series of adult deaths that were reported to the coroner. CT and MRI scans were reported independently, each by two radiologists who were masked to the autopsy findings. All four radiologists then produced a consensus report based on both techniques, recorded their confidence in cause of death, and identified whether autopsy was needed.FindingsWe assessed 182 unselected cases. The major discrepancy rate between cause of death identified by radiology and autopsy was 32% (95% CI 26-40) for CT, 43% (36-50) for MRI, and 30% (24-37) for the consensus radiology report; 10% (3-17) lower for CT than for MRI. Radiologists indicated that autopsy was not needed in 62 (34%; 95% CI 28-41) of 182 cases for CT reports, 76 (42%; 35-49) of 182 cases for MRI reports, and 88 (48%; 41-56) of 182 cases for consensus reports. Of these cases, the major discrepancy rate compared with autopsy was 16% (95% CI 9-27), 21% (13-32), and 16% (10-25), respectively, which is significantly lower (p<0·0001) than for cases with no definite cause of death. The most common imaging errors in identification of cause of death were ischaemic heart disease (n=27), pulmonary embolism (11), pneumonia (13), and intra-abdominal lesions (16).InterpretationWe found that, compared with traditional autopsy, CT was a more accurate imaging technique than MRI for providing a cause of death. The error rate when radiologists provided a confident cause of death was similar to that for clinical death certificates, and could therefore be acceptable for medicolegal purposes. However, common causes of sudden death are frequently missed on CT and MRI, and, unless these weaknesses are addressed, systematic errors in mortality statistics would result if imaging were to replace conventional autopsy.FundingPolicy Research Programme, Department of Health, UK.
| S-EPMC3262166 | biostudies-literature