Proximate Cause Of Death Research Articles

In Defense of Normothermic Regional Perfusion.

Normothermic regional perfusion (NRP) is a relatively new approach to procuring organs for transplantation. After circulatory death is declared, perfusion is restored to either the thoracoabdominal organs (in TA-NRP) or abdominal organs alone (in A-NRP) using extracorporeal membrane oxygenation. Simultaneously, surgeons clamp the cerebral arteries, causing a fatal brain injury. Critics claim that clamping the arteries is the proximate cause of death in violation of the dead donor rule and that the procedure is therefore unethical. We disagree. This account does not consider the myriad other factors that contribute to the death of the donor, including the presence of a fatal medical condition, the decision to withdraw life support, and the physician's actions in withdrawing life support and administering medication that may hasten death. Instead, we claim that physicians play a causative role in many of the events that lead to a patient's death and that these actions are often ethically and legally justified. We advance an "all things considered" view according to which TA-NRP may be considered ethically acceptable insofar as it avoids suffering and respects the wishes of the patient to improve the lives of others through organ donation. We conclude with a series of critical questions related to the practice of NRP and call for the development of national consensus on this issue in the United States.

Mortality in adults with sickle cell disease: Results from the sickle cell disease implementation consortium (SCDIC) registry.

The cause of death in people affected by sickle cell disease (SCD) is often challenging to define as prior studies have used retrospective or administrative data for analysis. We used a prospective longitudinal registry to assess mortality and clinical co-morbidities among subjects enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. At enrollment, we collected the following data: patient-reported demographics, SCD phenotype, baseline laboratory values, comorbidities, and current medications. Subjects were followed for a median of 4.7 years before the present analysis. The relationship of clinical co-morbidities (at time of enrollment) to mortality was determined using survival analysis, adjusting for SCD phenotype and gender. There was a total of 2439 people with SCD enrolled in the SCDIC registry. One hundred and twenty-eight participants (5%) died during the observation period (2017-2022). Six people died from trauma and were excluded from further analysis. Proximate cause of death was unwitnessed in 17% of the deaths, but commonest causes of death include cardiac (18%), acute chest or respiratory failure (11%), sudden unexplained death (8%). Enrollment characteristics of the individuals who died (n = 122) were compared to those of survivors (n = 2317). Several co-morbidities at enrollment increased the odds of death on univariate analysis. All co-morbidities were included in a multivariable model. After backward elimination, iron overload, pulmonary hypertension, and depression, remained statistically significant predictors of the risk of death. SCD reduces life expectancy. Improved comprehensive and supportive care to prevent end-organ damage and address comorbidities is needed for this population.

Do Not Turn a Blind Eye on Forensic Biochemistry: Using Vitreous Electrolytes to Reveal Renal Insufficiency as Cause of Death.

In both medical and forensic autopsy, the kidneys may be overlooked grossly and histologically. As both acute and chronic kidney dysfunction have major implications on morbidity and mortality, it is essential to consider the kidneys as a pathologic source for both immediate and proximate cause of death. For decades, vitreous humor has been used as a measure of postmortem electrolyte analysis to help understand ionic disturbances carried over from the antemortem period. Renal insufficiency from both acute and chronic kidney dysfunction can be ascertained from vitreous investigations and should be a consideration for cause of death. Here, we present 4 cases in which vitreous analysis was used to determine the cause of death. In highlighting these cases, we support the use of biochemical testing in autopsy while demonstrating how it can help elucidate an often overlooked means of mortality. Importantly, it can help with the formulation of clinicopathologic correlations between antemortem and postmortem findings.

How do mechanical circulatory support patients die? Autopsy findings for left-ventricular assist device/total artificial heart nonsurvivors

Although life saving for end-stage heart failure patients, permanent mechanical circulatory support (MCS) is often the proximate cause of death in those that do not survive to transplant. Autopsy remains the gold standard for diagnosing causes of death and a vital tool for better understanding underlying pathology of nonsurvivors. The aim of this study was to determine the frequency and outcomes of autopsy investigations and compare these with premortem clinical assessment. The autopsy findings and medical records of all patients who underwent left ventricular assist device (LVAD) or total artificial heart (TAH) insertion between June 1994 and April 2022 as a bridge to transplant, but subsequently died pre-heart transplantation were reviewed. A total of 203 patients had a LVAD or TAH implanted during the study period. Seventy-eight patients (M=59, F=19) died prior to transplantation (age 55 [14] years, INTERMACS=2). Autopsies were conducted in 26 of 78 patients (33%). Three were limited studies. The leading contributor to cause of death was respiratory (14/26), either nosocomial infection or associated with multiorgan failure. Intracranial hemorrhage was the second most common cause of death (8/26). There was a major discrepancy rate of 17% and a minor discrepancy rate of 43%. Autopsy study added a total of 14 additional contributors of death beyond clinical assessment alone (Graphical Abstract). Over an observational period of 26years, the frequency of autopsy was low. To improve LVAD/TAH patient survival to transplant, better understanding as to cause of death is required. Patients with MCS have complex physiology and are at high risk of infection and bleeding complications.

Bing Neel Syndrome: A Rare Contributing Factor of Psychosis and Suicidality.

Suicide rapidly increased in the United States by 30% from 2000 to 2020, accounting for more than 800,000 deaths ( Neurosci Res Program Bull . 1972; 10: 384-8). Studies have shown that there are a multitude of underlying issues, including mental illness, that elevate an individual's risk of dying by suicide ( CDC WONDER: Underlying cause of death, 1999-2019 . Atlanta, GA: US Department of Health and Human Services, CDC; 2020). Presented here is a case of Bing Neel syndrome (BNS) found in a 69-year-old man who died by suicide by jumping off a 135' bridge. His medical history was significant for traumatic brain injury, Waldenstrom macroglobulinemia (WM), major depressive disorder, suicidal ideation, and anxiety. Bing Neel syndrome is a rare central nervous system complication of WM. His wife reported an abrupt mental deterioration starting 5 years before his death, characterized by paranoia, depression, and insomnia. He had been a high-functioning university professor. His decline culminated with the loss of independence in his activities of daily living. At autopsy, it was found that he experienced blunt force injuries related to the fall, causing his death. A neuropathologic examination revealed a brisk and fulminant clonal CD20 + /immunoglobulin M+ lymphocytic infiltrate, involving all sampled regions of his brain, consistent with WM. This workup was critical to obtaining an accurate pathologic diagnosis of BNS and understanding his full clinical status before death. Although BNS was not the proximate cause of death, this diagnosis aided the death investigation as a causal factor in his suicidality and was vital to providing his family closure.

1204: THE CONTRIBUTION OF COVID-19 TO SEPSIS-RELATED MORTALITY IN THE UNITED STATES

Introduction: COVID-19-related organ dysfunction is increasingly recognized as sepsis, & sepsis has been reported as the most common proximate cause of death among COVD-19 patients in autopsy studies. Thus, the COVID-19 pandemic is expected to affect substantially the epidemiology of sepsis. However, the contribution of COVID-19 to sepsis-related mortality in the United States (US) is unknown. Methods: We used the CDC WONDER Multiple Cause of Death database to identify decedents with a diagnosis of sepsis during 2015-2019 and with diagnoses of COVID-19, sepsis, or both during 2020. Sepsis was identified using previously reported ICD-10 code-based taxonomy. COVID-19 was identified by ICD-10 code U071. Negative binomial regression was used on the 2015-2019 data to forecast the number of sepsis-related deaths in 2020. We then compared the number of observed vs expected sepsis-related deaths in 2020. In addition, we examined the reporting of a diagnosis of COVID-19 among decedents with sepsis and the proportion of a diagnosis of sepsis among those with COVID-19. The latter analyses were then repeated across the Department of Health and Human Services (HHS) Regions. Results: In 2020, there were 242,630 sepsis-related deaths, 384,536 COVID-19-related deaths, & 35,057 deaths with both diagnoses. The expected number of sepsis-related deaths for 2020 was 207,175 (95% CI 205,929-208,429), with the ratio of observed to expected deaths 1.17 (95%CI 1.16-1.18). COVID-19-related deaths comprised 15.0% of all observed sepsis-related deaths, ranging from 8.1% (HHS Region 10) to 18.2% (HHS Region 2). A diagnosis of sepsis was reported in 9.1% of all COVID-19-related deaths, varying from 6.6% (HHS Region 2) to 12.5% (HHS Region 9). Conclusions: Sepsis-related mortality was reported in less than 1 in 10 COVID-19-related deaths in the US during 2020, with the frequency of sepsis diagnoses varying nearly 2-fold across HHS regions. Although the number of COVID-19-related deaths far exceeded sepsis-related mortality, the contribution of the former to the latter, based on death certificates, was relatively minor. Our findings suggest substantial underdocumentation and possibly underrecognition of sepsis among COVID-19 decedents, likely contributing to varying coding practices during the first year of the pandemic.

What accounts for the high mortality of anorexia nervosa?

The exact medical complications, leading to the well-known high risk of death in patients with anorexia nervosa (AN), remain elusive. Such deaths are often abrupt with no satisfactory explanation. Suspected causes include cardiac QTc prolongation and, in turn, torsade de pointes (TdP). Psychotropic medications often prescribed to these patients are linked to QTc prolongation. AN is also presumed to cause heart failure due to malnutrition with increased susceptibility to QTc prolongation, and TdP, resulting in sudden cardiac death. Recent literature, however, is conflicting, and the likely cause of death may involve other cardiac abnormalities, such as low heart rate, abnormal heart rate variability, or increased QT dispersion. With an ongoing gap in research explaining the high mortality rate in AN, a compelling need to define the exact proximate causes of death in these patients remains. Because low serum potassium is the most common trigger for TdP, we postulate the early signal of sudden cardiac death, especially in patients with AN who purge, is hypokalemia. We also speculate that hypoglycemia could be a major factor in the sudden death of patients with AN as well as bradycardia or sinus arrest. A path forward to elucidate potential causes is offered.

Time to specialty care and mortality after cardiac arrest.

Out of hospital cardiac arrest (OHCA) patients are often transported to the closest emergency department (ED) or cardiac center for initial stabilization and may be transferred for further care. We investigated the effects of delay to transfer on in hospital mortality at a receiving facility. We included OHCA patients transported from the ED by a single critical care transport service to a quaternary care facility between 2010 and 2018. We calculated dwell time as time from arrest to critical care transport team contact. We abstracted demographics, arrest characteristics, and interventions started prior to transport arrival. For the primary analysis, we used logistic regression to determine the association of dwell time and in-hospital mortality. As secondary outcomes we investigated for associations of dwell time and mortality within 24h of arrival, proximate cause of death among decedents, arterial pH and lactate on arrival, sum of worst SOFA subscales within 24h of arrival, and rearrest during interfacility transport. We included 572 OHCA patients transported from an outside ED to our facility. Median dwell time was 113 (IQR=85-159) minutes. Measured in 30min epochs, increasing dwell time was not associated with in-hospital mortality, 24-h mortality, cause of death and initial pH, but was associated with lower 24-h SOFA score (p=0.01) and lower initial lactate (p=0.03). Rearrest during transport was rare (n=29, 5%). Dwell time was associated with lower probability of rearrest during transport (OR=0.847, (95% CI 0.68-1.01), p=0.07). Dwell time was not associated with in-hospital mortality. Rapid transport may be associated with risk of rearrest. Prospective data are needed to clarify optimal patient stabilization and transport strategies.

INVESTIGATION OF SARCOCYSTIS SPP. INFECTION IN FREE-RANGING AMERICAN BLACK BEARS (URSUS AMERICANUS) AND GRIZZLY BEARS (URSUS ARCTOS HORRIBILIS) IN BRITISH COLUMBIA, CANADA.

Sarcocystis spp. are protozoan parasites that cause a spectrum of lesions in various hosts. Hepatic sarcocystosis and encephalitis have been described in captive American black bears (Ursus americanus) and polar bears (Ursus maritimus), and in a free-ranging grizzly bear (Ursus arctos horribilis), but have not previously been reported in free-ranging American black bears. This study aimed to characterize the presence and lesions associated with Sarcocystis spp. in free-ranging bears in British Columbia, Canada from samples submitted to the provincial diagnostic laboratory. From 2007 to 2019, 102 free-ranging American black bear and grizzly bear tissues were examined postmortem for sarcocystosis using histopathology and follow-up molecular diagnostics. Sarcocystosis was confirmed in 41 (40%) free-ranging bears including 39 American black bears and two grizzly bears. Microscopic lesions included multifocal necrotizing hepatitis, nonsuppurative encephalitis, and/or intramuscular sarcocysts with or without associated inflammation. Sarcocystosis was considered the cause of death in eight (20%) of these bears, exclusively in cubs of the year (<1 yr old). Sarcocystis canis was identified in 22/32 (69%) cases where molecular characterization was performed and was the etiologic agent associated with bears that died of sarcocystosis. Confirmed cases were distributed widely across British Columbia. While there was an alternate proximate cause of death in the other confirmed bears, sarcocystosis may have contributed. Age was a significant risk factor, with yearlings presenting more often with fulminant lesions; however, there was a sampling bias toward juvenile bear submissions due to size and ease of transport. Further research is needed to understand the disease epidemiology and significance to population health.

Focused Cardiac Ultrasound Findings in Children Presenting With Shock to a Tertiary Care Hospital in Rwanda.

Shock remains a leading proximate cause of death in children. Children in sub-Saharan African (SSA) countries present with shock from a wide range of pathologies. Routine physiologic parameters may not reflect underlying physiology. No previous work has systematically described ultrasound findings in children with shock in an SSA country. We set out to perform focused cardiac ultrasound (FOCUS) on children with shock in Rwanda and describe the findings in this pilot study. In a prospective descriptive study, we trained pediatric residents to perform FOCUS on children presenting with shock to an urban tertiary care pediatric emergency department in Kigali, Rwanda. Images were transmitted via cellphone network and reviewed by experts. Primary outcome was expert's description of the FOCUS findings. Secondary outcomes included mortality at 48-hour, change in assessment and treatment after FOCUS, and agreement of FOCUS findings between residents and experts. Between January 2020 and April 2020, 25 subjects were enrolled by 8 residents. Eleven of 25 (44%) were newly diagnosed with acquired or congenital heart disease. The 48-hour mortality rate was higher in this group compared with those without heart disease (8 of 11 vs 1 of 14). The resident reported changing assessment and treatment based on FOCUS findings in 60% of patients (15 of 25). There was good to excellent agreements between residents and FOCUS experts on left ventricle function, pericardial effusion, and intravascular volume. In children presenting with signs and symptoms of shock in SSA, one could perform a screening FOCUS to distinguish between hypovolemic and cardiogenic shock.

Editors' Note: Cause of Death in Spontaneous Intracerebral Hemorrhage Survivors: Multistate Longitudinal Study

Using administrative claims data from 3 US states, Dr. Kuohn et al. report the long-term mortality rate of survivors with spontaneous intracerebral hemorrhage (ICH). Using an original population of 104,000 patients who were screened for eligibility, 72,432 survivors of the index hospitalization were followed for a median of 4 years. The 1-year risk of death or discharge to hospice was 9.5% (95% CI 9.2%–9.7%), with the most common proximate causes of death being infection (34%) or subsequent intracranial hemorrhage (13%). The median time from ICH to death was 10 months (IQR 2–31 months). Dr. Llamas-Nieves and colleagues highlight the importance of confounders such as diabetes, which was independently associated with death as shown in the multivariable regression model (HR 1.22, 95% CI 1.17–1.27), as this may be an important mediator of death because of infectious causes. The investigators acknowledge that diabetes contributes to death in the overall population; however, it was not independently associated with death due to infection (OR 1.16, 95% CI 0.86–1.55). The authors posit that diabetes (as well as age, post-ICH disability, and other comorbidities) are important contributors to the development of later infection, but it remains unclear why diabetes is not an independent modifier of death risk among patients who develop infection. Using administrative claims data from 3 US states, Dr. Kuohn et al. report the long-term mortality rate of survivors with spontaneous intracerebral hemorrhage (ICH). Using an original population of 104,000 patients who were screened for eligibility, 72,432 survivors of the index hospitalization were followed for a median of 4 years. The 1-year risk of death or discharge to hospice was 9.5% (95% CI 9.2%–9.7%), with the most common proximate causes of death being infection (34%) or subsequent intracranial hemorrhage (13%). The median time from ICH to death was 10 months (IQR 2–31 months). Dr. Llamas-Nieves and colleagues highlight the importance of confounders such as diabetes, which was independently associated with death as shown in the multivariable regression model (HR 1.22, 95% CI 1.17–1.27), as this may be an important mediator of death because of infectious causes. The investigators acknowledge that diabetes contributes to death in the overall population; however, it was not independently associated with death due to infection (OR 1.16, 95% CI 0.86–1.55). The authors posit that diabetes (as well as age, post-ICH disability, and other comorbidities) are important contributors to the development of later infection, but it remains unclear why diabetes is not an independent modifier of death risk among patients who develop infection.

Investigation of Algal Toxins in a Multispecies Seabird Die-Off in the Bering and Chukchi Seas.

Between 2014 and 2017, widespread seabird mortality events were documented annually in the Bering and Chukchi seas, concurrent with dramatic reductions of sea ice, warmer than average ocean temperatures, and rapid shifts in marine ecosystems. Among other changes in the marine environment, harmful algal blooms (HABs) that produce the neurotoxins saxitoxin (STX) and domoic acid (DA) have been identified as a growing concern in this region. Although STX and DA have been documented in Alaska (US) for decades, current projections suggest that the incidence of HABs is likely to increase with climate warming and may pose a threat to marine birds and other wildlife. In 2017, a multispecies die-off consisting of primarily Northern Fulmars (Fulmarus glacialis) and Short-tailed Shearwaters (Ardenna tenuirostris) occurred in the Bering and Chukchi seas. To evaluate whether algal toxins may have contributed to bird mortality, we tested carcasses collected from multiple locations in western and northern Alaska for STX and DA. We did not detect DA in any samples, but STX was present in 60% of all individuals tested and in 88% of Northern Fulmars. Toxin concentrations in Northern Fulmars were within the range of those reported from other STX-induced bird die-offs, suggesting that STX may have contributed to mortalities. However, direct neurotoxic action by STX could not be confirmed and starvation appeared to be the proximate cause of death among birds examined in this study.

Acquired brain injuries: neurophysiology in early prognosis and rehabilitation pathway

Despite advances in intensive care medicine and neurosurgical procedures, the mortality and long-term disability rates for serious traumatic and non-traumatic brain injuries remain high. With improvements in intensive care, the most common proximate cause of death in comatose patients following acquired brain injury is represented the withdrawal of life-sustaining therapies (ABI). This procedure, however, raises serious ethical concerns, as current approaches in the prediction of consciousness recovery and functional independence lack accuracy. The prediction of neurological outcome after severe ABI at the individual patient level is variable and challenging. Current prognostication models applied in severe traumatic brain injury and the post-cardiac arrest population perform reasonably well in predicting the neurological outcomes in low- and high-severity patients but do not allow for accurate outcome predictions in patients with intermediate severity. The current review highlights new clinical and instrumental prognostication develop-ments, with a particular focus on the prediction of consciousness recovery. In particular, recent research has leveraged neurophysiological techniques (electroencephalogram and somatosensory evoked potentials) to build a strategy for recovery prediction. In addition, we underline the relevance of instrumental motor assessments because motor impairment may affect the reliable evaluation of the effective consciousness level or may hamper patients’ complete functional recovery.

The Postmortem Interpretation of Cardiac Genetic Variants of Unknown Significance in Sudden Death in the Young: A Case Report and Review of the Literature.

Sudden cardiac death (SCD) in adolescents and young adults is a major traumatic event for families and communities. In these cases, it is not uncommon to have a negative autopsy with structurally and histologically normal heart. Such SCD cases are generally attributed to channelopathies, which include long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. Our understanding of the causes for SCDs has changed significantly with the advancements in molecular and genetic studies, where many mutations are now known to be associated with certain channelopathies. Postmortem analysis provides great value in informing decision-making with regard to screening tests and prophylactic measures that should be taken to prevent sudden death in first degree relatives of the decedent. As this is a rapidly advancing field, our ability to identify genetic mutations has surpassed our ability to interpret them. This led to a unique challenge in genetic testing called variants of unknown significance (VUS). VUSs present a diagnostic dilemma and uncertainty for clinicians and patients with regard to next steps. Caution should be exercised when interpreting VUSs since misinterpretation can result in mismanagement of patients and their families. A case of a young adult man with drowning as his proximate cause of death is presented in circumstances where cardiac genetic testing was indicated and undertaken. Eight VUSs in genes implicated in inheritable cardiac dysfunction were identified and the interpretation of VUSs in this scenario is discussed.

Development and validation of a risk factor-based system to predict short-term survival in adult hospitalized patients with COVID-19: a multicenter, retrospective, cohort study

BackgroundCoronavirus disease 2019 (COVID-19) has become a public health emergency of global concern. We aimed to explore the risk factors of 14-day and 28-day mortality and develop a model for predicting 14-day and 28-day survival probability among adult hospitalized patients with COVID-19.MethodsIn this multicenter, retrospective, cohort study, we examined 828 hospitalized patients with confirmed COVID-19 hospitalized in Wuhan Union Hospital and Central Hospital of Wuhan between January 12 and February 9, 2020. Among the 828 patients, 516 and 186 consecutive patients admitted in Wuhan Union Hospital were enrolled in the training cohort and the validation cohort, respectively. A total of 126 patients hospitalized in Central Hospital of Wuhan were enrolled in a second external validation cohort. Demographic, clinical, radiographic, and laboratory measures; treatment; proximate causes of death; and 14-day and 28-day mortality are described. Patients’ data were collected by reviewing the medical records, and their 14-day and 28-day outcomes were followed up.ResultsOf the 828 patients, 146 deaths were recorded until May 18, 2020. In the training set, multivariate Cox regression indicated that older age, lactate dehydrogenase level over 360 U/L, neutrophil-to-lymphocyte ratio higher than 8.0, and direct bilirubin higher than 5.0 μmol/L were independent predictors of 28-day mortality. Nomogram scoring systems for predicting the 14-day and 28-day survival probability of patients with COVID-19 were developed and exhibited strong discrimination and calibration power in the two external validation cohorts (C-index, 0.878 and 0.839).ConclusionOlder age, high lactate dehydrogenase level, evaluated neutrophil-to-lymphocyte ratio, and high direct bilirubin level were independent predictors of 28-day mortality in adult hospitalized patients with confirmed COVID-19. The nomogram system based on the four factors revealed good discrimination and calibration, suggesting good clinical utility.

Evaluation of an investigative model in dairy herds with high calf perinatal mortality rates in Switzerland

The objective of this study was to evaluate an investigative model which encompassed the risk factors, incidence, timing and causes of perinatal mortality (PM) (0–48 h) on high risk dairy farms (PM of >5% in the previous year) in Switzerland. This pilot-study was carried out on 47 predominantly Holstein PM calves from 21 dairy farms, between September 2016 and January 2018.Gross pathological examinations of calves and placentae as well as histopathological examinations of internal organs and placental tissue were performed. Further investigations included microbiological examinations: broad-spectrum bacterial and fungal culture, detection of Chlamydia abortus, Coxiella burnetii, pathogenic Leptospira spp. and Neospora caninum by real-time PCR (qPCR) and of bovine viral diarrhoea virus (BVDV) by Ag-ELISA. Maternal blood samples were used for serology of bovine herpesvirus 1 (BHV-1), Brucella abortus, Chlamydia abortus, Coxiella burnetii and nine pathogenic leptospiral serovars and the evaluation of trace element status. A questionnaire was completed with the farmer, which included general farm characteristics and case-related data. Inbreeding coefficients (IC) were calculated for pure-bred matings.At the farm-level, the PM rate was 10.0% (5.3–28.2%) and at the cow-level, 11.5%. These values, from high-risk farms, were approximately five-times higher than the contemporary national bovine PM rate (2.3%) in Switzerland. The risk factors associated with these high PM rates were the self-selection of high risk herds, the high proportion of primiparae in these herds (45%) and the evidence of widespread pathogenic infections on these farms (exposure: 67% of herds, 53% of dams; infection: 57% of herds, 45% of calves). The majority (68.1%) of calves died intrapartum. The most commonly diagnosed initiating/ultimate cause of death (UCOD) was infection (34%) of which Coxiella burnetii was the most frequently detected pathogen, by antigen. The most frequently diagnosed proximate cause of death (PCOD) was asphyxia (44.7%), though multiple PCOD was also common (21.3%). This study was the first detailed investigation of bovine PM in Switzerland. Infectious causes were diagnosed more frequently than expected. While the findings from these high PM Swiss herds may have limited external validity, the investigative model adopted and the detailed research methodologies employed can be replicated and re-evaluated, respectively, in future studies on PM internationally.

Lethal methemoglobinemia in the invasive brown treesnake after acetaminophen ingestion

The invasive brown treesnake (Boiga irregularis) has extirpated much of Guam’s native birdlife and poses significant threats to other parts of the western Pacific. Acetaminophen (APAP) is a proven lethal oral toxicant in reptiles but the physiological mechanism is unknown. The effects of a lethal APAP oral dose on methemoglobin (MetHb, non-oxygen carrying form) levels and other blood parameters were examined in brown treesnakes. Co-oximetry was used to measure MetHb (%) and other hemoglobin species. Assessment of red blood cell integrity, white blood cell differential counts, and plasma biochemical analyses were conducted to evaluate tissue damage, stress, and liver function. Changes in oxygen carrying capacity were noted in APAP-treated snakes indicated by a 50–60% increase in methemoglobin levels and a 40% decrease in oxyhemoglobin (oxygen-carrying form) levels compared to controls. APAP-treated snakes had decreased lymphocyte and increased monocyte counts while also having increased levels of blood analytes associate with impaired liver function and muscle damage. The proximate cause of death in APAP-treated snakes was likely acute methemoglobinemia and respiratory failure due to severe hypoxia with no observed signs of distress or pain. An orally-ingested lethal dose of APAP appears to be a humane method for lethal control of this species.

Mesenchymal stem cells (hMSC) exosomes couple the RV/PA during Pulmonary fibrosis (PF)

Background & Aim Right ventricular (RV) failure is the proximate cause of death in patients with PF and pulmonary hypertension (PAH). Subsequently, we developed an experimental model in which Bleomycin induces PF, PAH, and RV dysfunction in C57BL/6 mice. Here we hypothesize that hMSCs or their secretory activity (exosomes) protect the coupling of the RV to the PA and modulate pathogenic mechanisms during bleomycin induced PAH. Methods, Results & Conclusion We intravenously administered hMSC (500,000 cells), exosomes (20 micrograms/mouse) 30 and 35 days after the recurrent (12 doses) instillation of bleomycin (20 mg/Kg) into C57BL/6 mice. Subsequently, we performed hemodynamic evaluations (spontaneously breathing mice) to assess the effect of these interventions on the RV function and PA pressure of bleomycin treated mice. We also evaluated the effects of MSCs and exosomes on RV ATP and ROS generation, and VEGF signaling, implicated in PF and PAH. Compared to control, bleomycin treatment induced significant increases in RV systolic (20±3 vs 32±1mmHg) and diastolic pressures (3±1vs 8±1 mmHg), and depressed RV EF (60 vs 30%) 60 days after bleomycin injection. These changes were significantly (p Bleomycin exposure induces PAH and RV dysfunction in C57BL/6 mice. This RV dysfunction is associated with significant increases in RV mitochondrial ROS production, reduced ATP generation, and altered VEGF signaling. These hemodynamic and metabolic responses in the RV of bleomycin treated mice are ameliorated by the intravenous administration hMSCs or exosomes.

How Do Mechanical Circulatory Support Patients Die? Autopsy Findings for Bridge to Transplant LVAD/TAH Patients Who Do Not Survive to Transplant

Purpose Despite being life saving for end-stage heart failure patients, permanent mechanical circulatory support (MCS) is often the proximate cause of death in those that do not make it to transplant. Autopsy is the gold standard for causes of mortality, and is a vital tool for better understanding of pathology in this patient cohort. The aim of this study was to determine the frequency and outcomes of autopsy investigations over the course of a MCS program in a single center. Methods The autopsy findings of all patients who had a left ventricular assist device (LVAD) and total artificial heart (TAH) inserted between June 1994 and December 2016 as a bridge to transplant but subsequently died on pump were reviewed. Results A total of 187 patients had an LVAD or TAH implanted during the study. The cohort who died on pump (n=59; M=45, F=14) had an average age at implant of 53 ± 14 yrs, average INTERMACS score of 2, and average time on pump of 325 ± 316 days. Autopsies were conducted in 24/59 (41%) of patients. At autopsy, 8 patients had infection sited as cause of/contributing to the cause of death, one with purulent material obstructing the function of the pump. Six had explant swabs available. These were positive for MRSA, candida glabrata, pseudomonas fluorescens, scedosporium in 4 patients respectively, and 3/6 had positive explant swabs for pseudomonas aeruginosa. Lung injury was common, with 4 patients having acute respiratory distress syndrome, and 5 patients with diffuse alveolar damage. Four patients had intracranial hemorrhage, 2 patients had other bleeding (small bowel, haemopericardium), 1 patient had pump thrombus, 1 active myocarditis, and there was 1 accidental disconnection of the driveline. Conclusion Over an observational period of 22 years, the frequency of autopsies ordered was low. In order to keep patients alive to transplant, clinicians require a better understanding of causes of death. Patients with mechanical circulatory support have complex physiology and are at high risk of infection and bleeding complications.

Preliminary experience with point-of-care EEG in post-cardiac arrest patients

ObjectiveAbnormal electroencephalography (EEG) patterns are common after resuscitation from cardiac arrest and have clinical and prognostic importance. Bedside continuous EEGs are not available in many institutions. We tested the feasibility of using a point-of-care system for EEG acquisition. MethodsWe prospectively enrolled a convenience sample of post-cardiac arrest patients between 9/2015–1/2017. Upon hospital arrival, a limited EEG montage was applied. We tested both continuous EEG (cEEG) and this point-of-care EEG (eEEG). A board-certified epileptologist and a board-certified neurointensivist jointly reviewed all EEGs. Cohen’s kappa coefficient evaluated agreement between eEEG and cEEG and Fisher’s exact test evaluated their associations with survival to hospital discharge and proximate cause of death. ResultsWe studied 95 comatose post-cardiac arrest patients. Mean age was 59 (SD17) years. Most (61%) were male, few (N = 22; 23%) demonstrated shockable rhythms, and PCAC IV illness severity was present in 58 (61%). eEEG was interpretable in 57 (60%) subjects. The most common eEEG interpretations were: continuous (21%), generalized suppression (14%), burst-suppression (12%) and burst-suppression with identical bursts (10%). Seizures were detected in 2 eEEG subjects (2%). No patient with seizure or burst-suppression with identical bursts survived. cEEG demonstrated generalized suppression (31%), burst-suppression with identical bursts (27%), continuous (18%) and seizure (4%). The eEEG and cEEG demonstrated fair agreement (kappa = 0.27). Neither eEEG nor cEEG was associated with survival (p = 0.19; p = 0.11) or proximate cause of death (p = 0.14; p = 0.8) ConclusionseEEG is feasible, although artifact often precludes interpretation. eEEG is fairly associated with cEEG and may facilitate post-cardiac arrest care.