Citations

A case of the Taussig-Bing complex with necropsy findings is reported. Of additional interest was the unusual occurrence of associated malformations of the aortic-arch system, including coarctation of the aorta and anomalous origin of the right subclavian artery proximal to the coarctation. A narrow patent ductus arteriosus was present and probably represented a temporary phase in the process of normal anatomic closure. A single coronary artery that divided into the two main coronary arteries shortly after its origin also was present. Origin of the anomalous right subclavian artery proximal to a zone of aortic coarctation is an extremely rare arrangement among malformations of the aortic-arch system.

Background In kidney transplantation, a contrast CT scan is obtained in the donor candidate to detect subclinical pathology in the kidney. Recent work from the Aging Kidney Anatomy study has characterized kidney, cortex, and medulla volumes using a manual image-processing tool. However, this technique is time consuming and impractical for clinical care, and thus, these measurements are not obtained during donor evaluations. This study proposes a fully automated segmentation approach for measuring kidney, cortex, and medulla volumes. Methods A total of 1930 contrast-enhanced CT exams with reference standard manual segmentations from one institution were used to develop the algorithm. A convolutional neural network model was trained ( n =1238) and validated ( n =306), and then evaluated in a hold-out test set of reference standard segmentations ( n =386). After the initial evaluation, the algorithm was further tested on datasets originating from two external sites ( n =1226). Results The automated model was found to perform on par with manual segmentation, with errors similar to interobserver variability with manual segmentation. Compared with the reference standard, the automated approach achieved a Dice similarity metric of 0.94 (right cortex), 0.90 (right medulla), 0.94 (left cortex), and 0.90 (left medulla) in the test set. Similar performance was observed when the algorithm was applied on the two external datasets. Conclusions A fully automated approach for measuring cortex and medullary volumes in CT images of the kidneys has been established. This method may prove useful for a wide range of clinical applications.

Background Sudden cardiac arrest is the leading mode of death in the United States. Epilepsy affects 1% of Americans; yet epidemiological data show a prevalence of 4% in cases of sudden cardiac arrest. Sudden unexpected death in epilepsy (SUDEP) may share features with sudden cardiac arrest. The objective of this study was to report autopsy and genomic findings in a large cohort of SUDEP cases. Methods and Results Mayo Clinic Sudden Death Registry containing cases (ages 0–90 years) of sudden unexpected and unexplained deaths 1960 to present was queried. Exome sequencing performed on decedent cases. From 13 687 cases of sudden death, 656 (4.8%) had a history of seizures, including 368 confirmed by electroencephalography, 96 classified as SUDEP, 58 as non‐SUDEP, and 214 as unknown (insufficient records). Mean age of death in SUDEP was 37 (±19.7) years; 56 (58.3%) were male; 65% of deaths occurred at night; 54% were found in bed; and 80.6% were prone. Autopsies were obtained in 83 cases; bystander coronary artery disease was frequently reported as cause of death; nonspecific fibrosis was seen in 32.6% of cases, in structurally normal hearts. There were 4 cases of Dravet syndrome with pathogenic variants in SCN1A gene. Using whole exome sequencing in 11 cases, 18 ultrarare nonsynonymous variants were identified in 6 cases including CACNB2, RYR2, CLNB, CACNA1H, and CLCN2 . Conclusions This study examined one of the largest single‐center US series of SUDEP cases. Several cases were reclassified as SUDEP, 15% had an ECG when alive, and 11 (11.4%) had blood for whole exome sequencing analysis. The most frequent antemortem genetic finding was pathogenic variants in SCN1A ; postmortem whole exome sequencing identified 18 ultrarare variants.

Abstract Despite the challenges of the pandemic, there has been substantial progress with coronavirus disease 2019 (COVID-19) therapies. Pivotal COVID-19 trials like SOLIDARITY, RECOVERY, and ACCT-1 were rapidly conducted and data disseminated to support effective therapies. However, critical shortcomings remain on trial conduct, dissemination and interpretation of study results, and regulatory guidance in pandemic settings. The lessons that we learned have implications for both the current pandemic and future emerging infectious diseases. There is a need for establishing and standardizing clinical meaningful outcomes in therapeutic trials and for targeting defined populations and phenotypes that will most benefit from specific therapies. Standardized processes should be established for rapid and critical data review and dissemination to ensure scientific integrity. Clarity around the evidence standards needed for issuance of both emergency use authorization (EUA) and biologic license application (BLA) should be established and an infrastructure for executing rapid trials in epidemic settings maintained.

Abstract Given the urgent need for treatments during the coronavirus disease 2019 pandemic, the US Food and Drug Administration issued emergency use authorizations (EUAs) for multiple therapies. In several instances, however, these EUAs were issued before sufficient evidence of a given therapy’s efficacy and safety were available, potentially promoting ineffective or even harmful therapies and undermining the generation of definitive evidence. We describe the strengths and weaknesses of the different therapeutic EUAs issued during this pandemic. We also contrast them to the vaccine EUAs and suggest a framework and criteria for an evidence-based, trustworthy, and publicly transparent therapeutic EUA process for future pandemics.

Background and Purpose: Less is known about the risk factors and outcomes associated with stroke in the current era of increasing heart transplantation (HT) being performed in older patients. The impact of immunosuppression on risk of stroke has not yet been previously studied. We aimed to determine the incidence, risk factors and outcomes of stroke after HT. Methods: We retrospectively analyzed the incidence of ischemic and hemorrhagic strokes and associated outcomes in all consecutive HT recipients transplanted between 1994 and 2016 at a single institution. Results: Of 529 patients who underwent HT, 57 (10.7%) developed stroke, 8.1% had an ischemic events and (2.6%) had a hemorrhagic stroke. Age at HT (adjusted hazard ratio [HR] 1.33; P =0.03) and diabetes (HR, 2.60; P =0.02) were associated with increased risk of ischemic events. Patients with stroke (any type) were more likely to have worse kidney function (HR, 1.81; P =0.02) whereas patients with ischemic events were more likely to undergo combined organ transplantation (HR, 2.01; P =0.05). Cytomegalovirus infection was found to be associated with increased risk of any stroke (HR, 2.09; P =0.02).Conversion from calcineurin inhibitor to sirolimus-based immunosuppression was not found to be associated with a significant change in stroke risk (HR, 1.39; P =0. 45) compared with calcineurin inhibitor maintenance therapy. Stroke of any type and ischemic events were independently associated with increased risk of death (HR, 1.90; P =0.001 and HR, 2.14; P <0.001, respectively). Conclusions: Stroke after HT is associated with increased mortality. Older age at HT, diabetes, renal dysfunction, and CMV infection were associated with greater risk of stroke.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a critical strategy to overcome the COVID-19 pandemic. Multiple SARS-CoV-2 vaccines have been developed in a rapid timeframe to combat the pandemic. While generally safe and effective, rare cases of venous thromboembolism (VTE) have been reported after two adenovirus-based vaccines, the AstraZeneca ChAdOx1 nCoV-19 vaccine and the Janssen Ad.26.COV2.S vaccine, as well as after the Pfizer-BioNTech BNT162b2 mRNA vaccine. Here, we present the case of a patient who developed acute pulmonary emboli (PE) shortly after his second dose of the Moderna mRNA-1273 SARS-CoV-2 vaccine. We report the results of an extensive thrombophilia workup that was normal except for the identification of positive lupus anticoagulant (LA) signals. It is our goal to contribute to the body of knowledge regarding SARS-CoV-2 vaccines and encourage vaccine adverse event reporting so that clinicians can have a full appreciation and awareness of the possible adverse events related to these critical vaccines.