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Pulmonary Co-Infections Detected Premortem Underestimate Postmortem Findings in a COVID-19 Autopsy Case Series.

ABSTRACT: Bacterial and fungal co-infections are reported complications of coronavirus disease 2019 (COVID-19) in critically ill patients but may go unrecognized premortem due to diagnostic limitations. We compared the premortem with the postmortem detection of pulmonary co-infections in 55 fatal COVID-19 cases from March 2020 to March 2021. The concordance in the premortem versus the postmortem diagnoses and the pathogen identification were evaluated. Premortem pulmonary co-infections were extracted from medical charts while applying standard diagnostic definitions. Postmortem co-infection was defined by compatible lung histopathology with or without the detection of an organism in tissue by bacterial or fungal staining, or polymerase chain reaction (PCR) with broad-range bacterial and fungal primers. Pulmonary co-infection was detected premortem in significantly fewer cases (15/55, 27%) than were detected postmortem (36/55, 65%; p < 0.0001). Among cases in which co-infection was detected postmortem by histopathology, an organism was identified in 27/36 (75%) of cases. Pseudomonas, Enterobacterales, and Staphylococcus aureus were the most frequently identified bacteria both premortem and postmortem. Invasive pulmonary fungal infection was detected in five cases postmortem, but in no cases premortem. According to the univariate analyses, the patients with undiagnosed pulmonary co-infection had significantly shorter hospital (p = 0.0012) and intensive care unit (p = 0.0006) stays and significantly fewer extra-pulmonary infections (p = 0.0021). Bacterial and fungal pulmonary co-infection are under-recognized complications in critically ill patients with COVID-19.

SUBMITTER: Platt AP

PROVIDER: S-EPMC10383307 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Pulmonary Co-Infections Detected Premortem Underestimate Postmortem Findings in a COVID-19 Autopsy Case Series.

Platt Andrew P AP Bradley Benjamin T BT Nasir Nadia N Stein Sydney R SR Ramelli Sabrina C SC Ramos-Benitez Marcos J MJ Dickey James M JM Purcell Madeleine M Singireddy Shreya S Hays Nicole N Wu Jocelyn J Raja Katherine K Curto Ryan R Salipante Stephen J SJ Chisholm Claire C Carnes Stephanie S Marshall Desiree A DA Cookson Brad T BT Vannella Kevin M KM Madathil Ronson J RJ Soherwardi Shahabuddin S McCurdy Michael T MT Saharia Kapil K KK Rabin Joseph J Nih Covid-Autopsy Consortium Grazioli Alison A Kleiner David E DE Hewitt Stephen M SM Lieberman Joshua A JA Chertow Daniel S DS

Pathogens (Basel, Switzerland) 20230712 7

Bacterial and fungal co-infections are reported complications of coronavirus disease 2019 (COVID-19) in critically ill patients but may go unrecognized premortem due to diagnostic limitations. We compared the premortem with the postmortem detection of pulmonary co-infections in 55 fatal COVID-19 cases from March 2020 to March 2021. The concordance in the premortem versus the postmortem diagnoses and the pathogen identification were evaluated. Premortem pulmonary co-infections were extracted from ...[more]

PMID: 37513779

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Project description:South Asia accounts for the majority of the world's suicide deaths, but typical psychiatric or surveillance-based research approaches are limited due to incomplete vital surveillance. Despite rich anthropological scholarship in the region, such work has not been used to address public health gaps in surveillance and nor inform prevention programs designed based on surveillance data. Our goal was to leverage useful strategies from both public health and anthropological approaches to provide rich narrative reconstructions of suicide events, told by family members or loved ones of the deceased, to further contextualize the circumstances of suicide. Specifically, we sought to untangle socio-cultural and structural patterns in suicide cases to better inform systems-level surveillance strategies and salient community-level suicide prevention opportunities. Using a mixed-methods psychological autopsy approach for cross-cultural research (MPAC) in both urban and rural Nepal, 39 suicide deaths were examined. MPAC was used to document antecedent events, characteristics of persons completing suicide, and perceived drivers of each suicide. Patterns across suicide cases include (1) lack of education (72% of cases); (2) life stressors such as poverty (54%), violence (61.1%), migrant labor (33% of men), and family disputes often resulting in isolation or shame (56.4%); (3) family histories of suicidal behavior (62%), with the majority involving an immediate family member; (4) gender differences: female suicides were attributed to hopeless situations, such as spousal abuse, with high degrees of social stigma. In contrast, male suicides were most commonly associated with drinking and resulted from internalized stigma, such as financial failure or an inability to provide for their family; (5) justifications for suicide were attributions to 'fate' and personality characteristics such as 'stubbornness' and 'egoism'; (5) power dynamics and available agency precluded some families from disputing the death as a suicide and also had implications for the condemnation or justification of particular suicides. Importantly, only 1 out of 3 men and 1 out of 6 women had any communication to family members about suicidal ideation prior to completion. Findings illustrate the importance of MPAC methods for capturing cultural narratives evoked after completed suicides, recognizing culturally salient warning signs, and identifying potential barriers to disclosure and justice seeking by families. These findings elucidate how suicide narratives are structured by family members and reveal public health opportunities for creating or supplementing mortality surveillance, intervening in higher risk populations such as survivors of suicide, and encouraging disclosure.

Project description:IntroductionCyanobacterial blooms produce toxins that may become aerosolized, increasing health risks through inhalation exposures. Health related effects on the lower respiratory tract caused by these toxins are becoming better understood. However, nasal exposures to cyanotoxins remain understudied, especially for those with neurotoxic potential. Here, we present a case series study evaluating exposure to β-N-methylamino-l-alanine (BMAA), a cyanobacterial toxin linked to neurodegenerative disease, in postmortem olfactory tissues of individuals with varying stages of Alzheimer's disease (AD).MethodsOlfactory bulb (Ob) tissues were collected during autopsies performed between 2014 and 2017 from six South Florida brain donors (ages 47-78) with residences less than 140 m from a freshwater body. A triple quadrupole tandem mass spectrometry (UHPLC-MS/MS) method validated according to peer AOAC International guidelines was used to detect BMAA and two BMAA isomers: 2,4-diaminobutyric acid (2,4-DAB) and N-(2-aminoethyl)glycine (AEG). Quantitative PCR was performed on the contralateral Ob to evaluate the relative expression of genes related to proinflammatory cytokines (IL-6 & IL-18), apoptotic pathways (CASP1 & BCL2), and mitochondrial stress (IRF1 & PINK1). Immunohistochemistry was also performed on the adjacent olfactory tract (Ot) to evaluate co-occurring neuropathology with BMAA tissue concentration.ResultsBMAA was detected in the Ob of all cases at a median concentration of 30.4 ng/g (Range <LLOQ - 488.4 ng/g). Structural isomers were also detected with median concentrations of 28.8 ng/g (AEG) and 103.6 ng/g (2,4-DAB). In addition, we found that cases with BMAA tissue concentrations above the <LLOQ also displayed increased expression of IL-6 (3.3-fold), CASP1 (1.7-fold), and IRF1 (1.6-fold). Reactive microglial, astrogliosis, myelinopathy, and neuronopathy of axonal processes in the Ot were also observed in cases with higher BMAA tissue concentrations.ConclusionOur study demonstrates that the cyanobacterial toxin BMAA can be detected in the olfactory pathway, a window to the brain, and its presence may increase the occurrence of proinflammatory cytokines, reactive glia, and toxicity to axonal processes. Further studies will be needed to evaluate BMAA's toxicity via this route of exposure and factors that increase susceptibility.

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Project description:Methoxyacetylfentanyl is one of many fentanyl analogs available as new psychoactive substances. It have been encountered in both the European Union and the United States, and existing literature suggest that methoxyacetylfentanyl is around 3- to 5-fold less potent than fentanyl. The aim of the present work was to combine case information with blood concentrations and abundance of urinary metabolites to investigate the importance of these parameters for toxicological interpretation. Quantification of methoxyacetylfentanyl in femoral blood was performed by LC--MS-MS and urinary metabolites were analyzed by LC--QTOF-MS with and without hydrolysis with β-glucuronidase/arylsulfatase. For confirmation of identified metabolites, methoxyacetylfentanyl was incubated with hepatocytes for up to 5 hours and analyzed with the same method as the urine samples. In eleven postmortem cases (27 to 41 years old and including one female) methoxyacetylfentanyl was reported in femoral blood. The cause of death was intoxication by methoxyacetylfentanyl alone or in combination with other drugs in all but one case, where death was attributed to acute complications of an underlying heart disease but with possible contribution from methoxyacetylfentanyl. In total, 27 urinary metabolites were found, including eight glucuronides. Major biotransformations were O-demethylation, dealkylation to form the nor-metabolite, mono- and dihydroxylations of the phenethyl moiety, as well as combinations thereof. The most abundant metabolites in hydrolyzed urine included O-desmethyl-, O-desmethyl-phenethyl-hydroxy-, O-desmethyl-phenethyl-hydroxymethoxy- and nor-methoxyacetylfentanyl. Differences in the abundance of methoxyacetylfentanyl and its major metabolites could be interpreted to indicate fatal intoxications in abstinent or chronic users. We postulate that urinary concentrations of methoxyacetylfentanyl and two metabolites, in combination with the methoxyacetylfentanyl concentration in femoral blood, might be good indicators of the time between administration and death as well as prior use.

Project description:ObjectivesTo determine the diagnostic accuracy of postmortem magnetic resonance imaging (PM-MRI) and postmortem ultrasound (PM-US) for perinatal autopsy in the same patient cohort, and to determine whether PM-US can provide the same anatomical information as PM-MRI.MethodsIn this prospective, 5-year (July 2014-July 2019) single-center study, we performed 1.5-T PM-MRI and PM-US in an unselected cohort of perinatal deaths. The diagnostic accuracies of both modalities were calculated, using autopsy as the reference standard. As a secondary objective, the concordance rates between the two imaging modalities for the overall main diagnosis and for five anatomical regions (brain, spine, thorax, heart and abdomen) were calculated.ResultsDuring the study period, 136 cases underwent both PM-US and PM-MRI, of which 88 (64.7%) also underwent autopsy. There was no significant difference in the rates of concordance with autopsy between the two modalities for overall diagnosis (PM-US, 86.4% (95% CI, 77.7-92.0%) vs PM-MRI, 88.6% (95% CI, 80.3-93.7%)) or in the sensitivities and specificities for individual anatomical regions. There were more non-diagnostic PM-US than PM-MRI examinations for the brain (22.8% vs 3.7%) and heart (14.7% vs 5.1%). If an 'imaging-only' autopsy had been performed, PM-US would have achieved the same diagnosis as 1.5-T PM-MRI in 86.8% (95% CI, 80.0-91.5%) of cases, with the highest rates of agreement being for spine (99.3% (95% CI, 95.9-99.9%)) and cardiac (97.3% (95% CI, 92.4-99.1%)) findings and the lowest being for brain diagnoses (85.2% (95% CI, 76.9-90.8%)).ConclusionAlthough there were fewer non-diagnostic cases using PM-MRI than for PM-US, the high concordance rate for overall diagnosis suggests that PM-US could be used for triaging cases when PM-MRI access is limited or unavailable. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Dataset Information

Pulmonary Co-Infections Detected Premortem Underestimate Postmortem Findings in a COVID-19 Autopsy Case Series.

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Pulmonary Co-Infections Detected Premortem Underestimate Postmortem Findings in a COVID-19 Autopsy Case Series.

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