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Objectives Corner metaphyseal lesions (CMLs) are specific for child abuse but challenging to detect on radiographs. The accuracy of CT for CML detection is unknown. Our aim was to compare diagnostic accuracy for CML detection on post-mortem skeletal surveys (PMSS, plain radiography) versus post-mortem CT (PMCT). Methods A 10-year retrospective review was performed at a children’s hospital for patients having PMSS, PMCT and histopathological correlation (reference standard) for suspected CMLs. Twenty-four radiologists independently reported the presence or absence of CMLs in all cases in a blinded randomised cross-over design across two rounds. Logistic regression models were used to compare accuracy between modalities. Results Twenty CMLs were reviewed for each of the 10 subjects (200 metaphyses in all). Among them, 20 CMLs were confirmed by bone histopathology. Sensitivity for these CMLs was significantly higher for PMSS (69.6%, 95% CI 61.7 to 76.7) than PMCT (60.5%, 95% CI 51.9 to 68.6). Using PMSS for detection of CMLs would yield one extra correct diagnosis for every 11.1 (95% CI 6.6 to 37.0) fractured bones. In contrast, specificity was higher on PMCT (92.7%, 95% CI 90.3 to 94.5) than PMSS (90.5%, 95% CI 87.6 to 92.8) with an absolute difference of 2.2% (95% CI 1.0 to 3.4, p  < 0.001). More fractures were reported collectively by readers on PMSS (785) than on PMCT (640). Conclusion PMSS remains preferable to PMCT for CML evaluation. Any investigation of suspected abuse or unexplained deaths should include radiographs of the limbs to exclude CMLs. Clinical relevance statement In order to avoid missing evidence that could indicate child abuse as a contributory cause for death in children, radiographs of the limbs should be performed to exclude CMLs, even if a PMCT is being acquired. Key Points • Corner metaphyseal lesions (CMLs) are indicative for abuse, but challenging to detect. Skeletal surveys (i.e. radiographs) are standard practice; however, accuracy of CT is unknown. • Sensitivity for CML detection on radiographs is significantly higher than CT. • Investigation of unexplained paediatric deaths should include radiographs to exclude CMLs even if CT is also being performed.

Background Verbal autopsy (VA) has been proposed to determine the cause of death (COD) distributions in settings where most deaths occur without medical attention or certification. We develop performance criteria for VA-based COD systems and apply these to the Registrar General of India’s ongoing, nationally-representative Indian Million Death Study (MDS). Methods Performance criteria include a low ill-defined proportion of deaths before old age; reproducibility, including consistency of COD distributions with independent resampling; differences in COD distribution of hospital, home, urban or rural deaths; age-, sex- and time-specific plausibility of specific diseases; stability and repeatability of dual physician coding; and the ability of the mortality classification system to capture a wide range of conditions. Results The introduction of the MDS in India reduced the proportion of ill-defined deaths before age 70 years from 13% to 4%. The cause-specific mortality fractions (CSMFs) at ages 5 to 69 years for independently resampled deaths and the MDS were very similar across 19 disease categories. By contrast, CSMFs at these ages differed between hospital and home deaths and between urban and rural deaths. Thus, reliance mostly on urban or hospital data can distort national estimates of CODs. Age-, sex- and time-specific patterns for various diseases were plausible. Initial physician agreement on COD occurred about two-thirds of the time. The MDS COD classification system was able to capture more eligible records than alternative classification systems. By these metrics, the Indian MDS performs well for deaths prior to age 70 years. The key implication for low- and middle-income countries where medical certification of death remains uncommon is to implement COD surveys that randomly sample all deaths, use simple but high-quality field work with built-in resampling, and use electronic rather than paper systems to expedite field work and coding. Conclusions Simple criteria can evaluate the performance of VA-based COD systems. Despite the misclassification of VA, the MDS demonstrates that national surveys of CODs using VA are an order of magnitude better than the limited COD data previously available.

Background Verbal autopsies with physician assignment of cause of death (COD) are commonly used in settings where medical certification of deaths is uncommon. It remains unanswered if automated algorithms can replace physician assignment. Methods We randomized verbal autopsy interviews for deaths in 117 villages in rural India to either physician or automated COD assignment. Twenty-four trained lay (non-medical) surveyors applied the allocated method using a laptop-based electronic system. Two of 25 physicians were allocated randomly to independently code the deaths in the physician assignment arm. Six algorithms (Naïve Bayes Classifier (NBC), King-Lu, InSilicoVA, InSilicoVA-NT, InterVA-4, and SmartVA) coded each death in the automated arm. The primary outcome was concordance with the COD distribution in the standard physician-assigned arm. Four thousand six hundred fifty-one (4651) deaths were allocated to physician (standard), and 4723 to automated arms. Results The two arms were nearly identical in demographics and key symptom patterns. The average concordances of automated algorithms with the standard were 62%, 56%, and 59% for adult, child, and neonatal deaths, respectively. Automated algorithms showed inconsistent results, even for causes that are relatively easy to identify such as road traffic injuries. Automated algorithms underestimated the number of cancer and suicide deaths in adults and overestimated other injuries in adults and children. Across all ages, average weighted concordance with the standard was 62% (range 79–45%) with the best to worst ranking automated algorithms being InterVA-4, InSilicoVA-NT, InSilicoVA, SmartVA, NBC, and King-Lu. Individual-level sensitivity for causes of adult deaths in the automated arm was low between the algorithms but high between two independent physicians in the physician arm. Conclusions While desirable, automated algorithms require further development and rigorous evaluation. Lay reporting of deaths paired with physician COD assignment of verbal autopsies, despite some limitations, remains a practicable method to document the patterns of mortality reliably for unattended deaths. Trial registration ClinicalTrials.gov , NCT02810366. Submitted on 11 April 2016.

Background Physician-coded verbal autopsy (PCVA) is the most widely used method to determine causes of death (CODs) in countries where medical certification of death is uncommon. Computer-coded verbal autopsy (CCVA) methods have been proposed as a faster and cheaper alternative to PCVA, though they have not been widely compared to PCVA or to each other. Methods We compared the performance of open-source random forest, open-source tariff method, InterVA-4, and the King-Lu method to PCVA on five datasets comprising over 24,000 verbal autopsies from low- and middle-income countries. Metrics to assess performance were positive predictive value and partial chance-corrected concordance at the individual level, and cause-specific mortality fraction accuracy and cause-specific mortality fraction error at the population level. Results The positive predictive value for the most probable COD predicted by the four CCVA methods averaged about 43% to 44% across the datasets. The average positive predictive value improved for the top three most probable CODs, with greater improvements for open-source random forest (69%) and open-source tariff method (68%) than for InterVA-4 (62%). The average partial chance-corrected concordance for the most probable COD predicted by the open-source random forest, open-source tariff method and InterVA-4 were 41%, 40% and 41%, respectively, with better results for the top three most probable CODs. Performance generally improved with larger datasets. At the population level, the King-Lu method had the highest average cause-specific mortality fraction accuracy across all five datasets (91%), followed by InterVA-4 (72% across three datasets), open-source random forest (71%) and open-source tariff method (54%). Conclusions On an individual level, no single method was able to replicate the physician assignment of COD more than about half the time. At the population level, the King-Lu method was the best method to estimate cause-specific mortality fractions, though it does not assign individual CODs. Future testing should focus on combining different computer-coded verbal autopsy tools, paired with PCVA strengths. This includes using open-source tools applied to larger and varied datasets (especially those including a random sample of deaths drawn from the population), so as to establish the performance for age- and sex-specific CODs.

Cause-of-death data derived from verbal autopsy (VA) are increasingly used for health planning, priority setting, monitoring and evaluation in countries with incomplete or no vital registration systems. In some regions of the world it is the only method available to obtain estimates on the distribution of causes of death. Currently, the VA method is routinely used at over 35 sites, mainly in Africa and Asia. In this paper, we present an overview of the VA process and the results of a review of VA tools and operating procedures used at demographic surveillance sites and sample vital registration systems. We asked for information from 36 field sites about field-operating procedures and reviewed 18 verbal autopsy questionnaires and 10 cause-of-death lists used in 13 countries. The format and content of VA questionnaires, field-operating procedures, cause-of-death lists and the procedures to derive causes of death from VA process varied substantially among sites. We discuss the consequences of using varied methods and conclude that the VA tools and procedures must be standardized and reliable in order to make accurate national and international comparisons of VA data. We also highlight further steps needed in the development of a standard VA process.

Rationale and objectivesIntroduction of post-mortem imaging has helped improve sudden unexpected death in infancy (SUDI) management in Europe. French guidelines were issued in 2007 to homogenise SUDI investigations including imaging. The aim of this study was to evaluate current imaging management of SUDI in France.Material and methodsBetween January 2022 and July 2022, all 35 SUDI French referral centres were invited to answer an e-mailed online survey including 29 questions divided into four different sections covering imaging practices for SUDI including radiology department organisation, imaging modalities performed, methods of reading, and current training resources. Partial responses were secondarily completed by a personal call to the SUDI imaging consultant. The current implementation of the 2007 recommendations was compared with a previous evaluation from 2015 and with current North American practices.ResultsThe participation rate of centres performing SUDI imaging was 100% (35/35). Imaging was systematically performed in 94.3% (33/35) of the centres: 74.3% (26/35) using radiography; 5.7% (2/35) using ultrasound; 94.3% (33/35) using computed tomography (CT), including 89% (31/35) whole-body CT and 5.7% (2/35) brain CT; and 20% (7/35) using magnetic resonance imaging (MRI). Two centres (5.7%, 2/35) did not systematically perform brain imaging. One (2.9%, 1/35) used ultrasound-guided biopsy. In comparison with 2015, rates of brain imaging increased by 25.4% (P=0.008). There was no significant difference in the number of forensic MRIs performed between France and North America (P=0.663).ConclusionDespite improvements since 2015, full compliance with French guidelines for SUDI investigations remains incomplete. The use of imaging, particularly CT and brain imaging, has increased. Further efforts are needed to standardise imaging practices for optimal SUDI investigations.

ObjectivesTo establish contrast-enhanced (CE) cadaver-specific post-mortem computed tomography (PMCT) in first-year gross anatomy teaching and quantitatively evaluate its learning benefit.Methods132 first-year medical students were included in this IRB-approved study and randomly assigned to an intervention group (n=59) provided with continuous access to CE and non-enhanced (NE) cadaver-specific PMCT-scans during the first-semester gross anatomy course, and a control group (n=73) that had only NE cadaver-specific PMCT data available. Four multiple-choice tests were carried out (15 questions each) subsequent to completion of the corresponding anatomy module: Head and neck anatomy, extremities, thorax, and abdomen. Median test results were compared in each module between the groups using the Wilcoxon rank-sum test. Additionally, participants of the intervention group answered a 15-item feedback-questionnaire.ResultsThe intervention group achieved significantly higher test scores in head and neck anatomy (median=12.0, IQR=10.0–13.0) versus the control group (median=10.5, IQR=9.0–12.0) (p<0.01). There were no significant differences in the comparison of other modules. CEPMCT was highly appreciated by undergraduate medical students.ConclusionsThe incorporation of contrast-enhanced cadaver-specific PMCT-scans in gross anatomy teaching was proven to be feasible in the framework of the medical curriculum and significantly improved the students’ learning performance in head and neck anatomy.Key Points• Cadaver-specific contrast-enhanced post-mortem CT (CEPMCT) is feasible in the medical curriculum.• CEPMCT yields significantly improved learning performance in head and neck anatomy (p<0.01).• CEPMCT is highly appreciated by medical students and used in tutor- or self-guided modes.

This paper presents autopsy findings of 3 COVID-19 patients randomly selected for post-mortem from two tertiary referral Polish hospitals. Analysis of macroscopic, histopathological findings with clinical features was performed. All 3 deceased patients were Caucasian males (average age 61 years, range from 56 to 68 years). Using real-time polymerase chain reaction assay, the patients were confirmed (antemortem) to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Two patients were obese, and 1 patient had type 2 diabetes mellitus. The medical history of 1 patient included hemorrhagic pancreatitis, gangrenous cholecystitis, Acinetobacter baumanii sepsis, and cholecystectomy. Pulmonary embolism was diagnosed in 2 patients. At autopsy, in 1 case, the lungs showed bilateral interstitial pneumonia with diffuse alveolar damage (DAD), while in another case, interstitial pulmonary lymphoid infiltrates and enlarged atypical pneumocytes were present but without DAD. Microthrombi in lung vessels and capillaries were observed in 2 cases. This study revealed thrombotic complications of COVID-19 and interstitial pneumonia with DAD presence as the main autopsy findings in patients with SARS-CoV-2 infection that was confirmed antemortem with molecular tests. Autopsy studies using tissue sections handled in accordance with SARS-CoV-2 biosafety guidelines are urgently needed, especially in the case of subjects who were below the age of 60.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer by providing new options in addition to existing therapies. However, peptide vaccination therapies still represent an attractive approach, because of the antigen specificity. We identified survivin 2B peptide (SVN‐2B), a 9‐mer antigenic peptide encoded by survivin, and an SVN‐2B peptide vaccine‐based phase II randomized clinical trial targeting unresectable and refractory pancreatic carcinoma was undertaken. The SVN‐2B peptide vaccine did not have any statistically significant clinical benefits in that study. Therefore, we undertook an autopsy study to analyze the immune status of the pancreatic cancer lesions at the histological level. Autopsies were carried out in 13 patients who had died of pancreatic cancer, including 7 who had received SVN‐2B peptide vaccination and 6 who had not, as negative controls. The expression of immune‐related molecules was analyzed by immunohistochemical staining. Cytotoxic T lymphocytes were analyzed by tetramer staining and enzyme‐linked immunospot assay. Histological analysis revealed dense infiltration of CD8+ T cells in some lesions in patients who had received the SVN‐2B peptide vaccine. A high rate of programmed cell death ligand 1 expression in cancer cells was observed in these cases, indicating that CTLs were induced by SVN‐2B peptide vaccination and had infiltrated the lesions. The lack of a significant antitumor effect was most likely attributable to the expression of immune checkpoint molecules. These findings suggest that the combination of a tumor‐specific peptide vaccine and an ICI might be a promising approach to the treatment of pancreatic carcinoma in the future. Autopsy analysis using pancreatic cancer cases with survivin 2B peptide vaccination revealed that numbers of CTLs were trapped in cancer stroma. This result indicates that inhibition of cancer stroma might be the next target for effective cancer immunotherapy.

In 2018, Pakistan had the world's highest neonatal mortality rate. Within Pakistan, most neonatal deaths occur in rural areas where access to health facilities is limited, and robust vital registration systems are lacking. To improve newborn survival, there is a need to better understand the causes of neonatal death in high burden settings and engage caregivers in the promotion of newborn health. To describe the causes of neonatal death in a rural area in Pakistan and to estimate the effect of an integrated neonatal care kit (iNCK) on cause-specific neonatal mortality. We analyzed data from a community-based, cluster-randomized controlled trial of 5286 neonates in Rahim Yar Khan (RYK), Punjab, Pakistan between April 2014 and August 2015. In intervention clusters, Lady Health Workers (LHW) delivered the iNCK and education on its use to pregnant women while control clusters received the local standard of care. The iNCK included interventions to prevent and identify signs of infection, identify low birthweight (LBW), and identify and manage hypothermia. Verbal autopsies were attempted for all deaths. The primary outcome was cause-specific neonatal mortality. Verbal autopsies were conducted for 84 (57%) of the 147 reported neonatal deaths. The leading causes of death were infection (44%), intrapartum-related complications (26%) and prematurity/LBW (20%). There were no significant differences in neonatal mortality due to prematurity/LBW (RR 0.43; 95% CI 0.15-1.24), infection (RR 1.10; 95% CI 0.58-2.10) or intrapartum-related complications (RR 1.04; 95% CI 0.0.45-2.41) among neonates who died in the intervention arm compared to those who died in the control arm. The major causes of neonatal deaths in RYK, Pakistan mirror the global landscape of neonatal deaths. The iNCK did not significantly reduce any cause-specific neonatal mortality.