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BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

Perioperative terlipressin (Tp) during living donor liver transplantation (LDLT) has been shown to reduce intraoperative portal pressures and improve renal function. Its role and safety profile have never been evaluated in a double-blind randomized controlled trial (RCT). The aim was to evaluate the hemodynamic effects, clinical benefits, and safety of perioperative Tp infusion in adult LDLT. This was a single-center double-blind RCT. Consenting adults with chronic liver disease and low risk of posttransplant renal dysfunction undergoing their first LDLT were randomized. The study group (terlipressin group [TpG]) received an initial bolus of Tp during surgery followed by a Tp infusion for 72 hours in the postoperative period. The placebo group (PbG) received a saline infusion. The primary endpoint was portal pressure after arterial reperfusion. Multiple intraoperative and postoperative variables served as secondary endpoints. A total of 41 patients were enrolled in the trial (TpG, 21; PbG, 20). There were no significant differences in intraoperative portal pressures, blood loss, fluid requirement, vasopressor requirement, or urine output. Peak intraoperative and end of surgery lactate levels were significantly higher in the Tp group. There was no difference in postoperative liver function tests. Incidence of acute kidney injury as assessed by Risk, Injury, Failure, Loss, and End-Stage Kidney Disease criteria was lower in the Tp group (27% versus 60%; P = 0.04). The TpG had less postoperative ascites, a lower need for percutaneous interventions, and a shorter hospital stay. Incidence of bradycardia requiring pharmacological intervention and withdrawal from study was significantly higher in the TpG. In conclusion, this study has not demonstrated a reduction in postreperfusion portal pressure with Tp. However, Tp infusion reduced postoperative ascitic drain output resulting in less frequent percutaneous interventions and reduced hospital stay. Intraoperative hyperlactatemia and symptomatic bradycardia are major concerns. Its use should be restricted to patients with high-volume ascites, and it needs close monitoring during drug infusion. Liver Transplantation 23 1007-1014 2017 AASLD.

Purpose Acute hemorrhagic leukoencephalitis (AHLE) is a rare and severe form of acute disseminated encephalomyelitis (ADEM). Only a few reports of AHLE in coronavirus disease 2019 (COVID-19) patients have been described to date. We report a case of COVID-19-related AHLE along with a literature review describing salient clinical and imaging characteristics. Methods A literature search was performed on Medline (2020-present), PubMed, Cochrane Library, CINAHL, and Google scholar on 28 January 2021 for all articles published using MeSH terms “COVID-19” or “SARS-CoV-2” with “Acute hemorrhagic leukoencephalitis” or “Acute hemorrhagic encephalitis.” Relevant case reports and case series describing clinical and imaging features of AHLE associated with SARS-CoV-2 infection were included, data compiled, and critically reviewed. Results Acute onset encephalopathy and rapidly deteriorating neurological status is the common clinical presentation in AHLE. CSF analysis reveals elevated proteins and lymphocytic pleocytosis. Typical neuroimaging features include multifocal, variable-sized, poorly defined cerebral white matter lesions with cortical sparing. Involvement of the brainstem, cerebellar peduncles, and deep grey matter can also occur, although rarely. Lesions are hyperintense on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) images, hypointense on T1W images, and show microhemorrhages, variable diffusion restriction, and post-contrast enhancement. Extensive microhemorrhages, brainstem involvement, and gross hemorrhage often portend a poor prognosis. Conclusion Heightened awareness about the clinical and imaging presentation of COVID-19-related AHLE can positively alter the outcome in a select few by enabling early diagnosis and aggressive management.

In living donor liver transplantation, optimal graft size is estimated from values like graft volume/standard liver volume and graft/recipient body weight ratio but the final functional hepatic mass is influenced by other donor and recipient factors. Grafts with insufficient functional hepatic mass can produce a life-threatening condition with rapidly progressive liver failure called small-for-size syndrome (SFSS). Diagnosis of SFSS requires careful surveillance for signs of inadequate hepatocellular function, residual portal hypertension, and systemic inflammation that suggest rapidly progressive liver failure. Early diagnosis, symptom control, and addressing the cause of SFSS may prevent the need for retransplantation. With increased attention to avoiding donor risk, intensivists will be confronted with more SFSS recipients. In this review, we aim to outline a systematic approach to the medical management of patients with SFSS by providing a concise synopsis of general supportive care-neurological, cardiovascular, and renal support, mechanical ventilation, nutritional support, infection control, and tailored immunosuppression-with an aim to avoid end-organ damage or death and a review of current interventions including liver support devices, portal flow modulating drugs, and other experimental interventions that aim to preserve existing hepatic mass and improve conditions for hepatic regeneration. We examine evidence for SFSS interventions to provide the reader with information that may assist in clinical decision making. Points of controversy in care are purposefully highlighted to identify areas where additional experimental work is still needed. A full understanding of the pathophysiology of SFSS and measures to support liver regeneration will guide effective management.