A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitis.

Background: In trials conducted in India, recombinant granulocyte colony stimulating factor (GCSF) improved survival in alcohol-associated hepatitis (AH). The aim of this trial was to determine the safety and efficacy of pegfilgrastim, a long-acting recombinant GCSF, in patients with AH in the United States. Methods: This prospective, randomized, open label trial conducted between March 2017 and March 2020 randomized patients with a clinical diagnosis of AH and a Maddrey discriminant function score ≥32 to standard of care (SOC) or SOC+pegfilgrastim (0.6 mg subcutaneously) on Day 1 and Day 8 (clinicaltrials.gov NCT02776059). SOC was 28 days of either pentoxifylline or prednisolone, as determined by the patient's primary physician. The second injection of pegfilgrastim was not administered if the white blood cell count exceeded 30,000/mm3 on Day 8. Primary outcome was survival at Day 90. Secondary outcomes included the incidence of acute kidney injury (AKI), hepatorenal syndrome (HRS), hepatic encephalopathy, or infections. Findings: The study was terminated early due to COVID19 pandemic. Eighteen patients were randomized to SOC and 16 to SOC+pegfilgrastim. All patients received prednisolone as SOC. Nine patients failed to receive a second dose of pegfilgrastin due to WBC > 30,000/mm3 on Day 8. Survival at 90 days was similar in both groups (SOC: 0.83 [95% confidence interval [CI]: 0.57-0.94] vs. pegfilgrastim: 0.73 [95% CI: 0.44-0.89]; p > 0.05; CI for difference: -0.18-0.38). The incidences of AKI, HRS, hepatic encephalopathy, and infections were similar in both treatment arms and there were no serious adverse events attributed to pegfilgrastim. Interpretation: This phase II trial found no survival benefit at 90 days among subjects with AH who received pegfilgrastim+prednisolone compared with subjects receiving prednisolone alone. Funding: was provided by the United States National Institutes of Health and National Institute on Alcohol Abuse and Alcoholism U01-AA021886 and U01-AA021884.

Necrotising fasciitis in the COVID-19 era: A consequence of caution - A case series.

Necrotising fasciitis (NF) is a severe soft tissue infection that is associated with a high risk of morbidity and mortality. During the coronavirus disease 19 (COVID-19) pandemic, the population has been actively discouraged from presenting to emergency medical services unless absolutely necessary. While this was an important step in allowing for preservation of limited resources in a time of crisis, it may have resulted in immeasurable 'secondary victims' of the pandemic as patients with time-critical conditions delay hospital presentation. In this case series, we describe three patients that noted symptoms of soft tissue infection, but delayed seeking healthcare advice due to concerns regarding COVID-19 exposure. All three progressed to NF, requiring highly morbid wide surgical debridement and prolonged hospital admission, with a high risk of potential mortality. The findings of this series demonstrate the importance of consistently delivering appropriate and timely healthcare interventions to patients with non-COVID-19-related conditions. While efforts must be made to ensure preservation of valuable healthcare resources in a global pandemic, patients must also be empowered to seek timely care for non-COVID-19-related conditions even in this time of crisis.

Parsimonious machine learning models to predict resource use in cardiac surgery across a statewide collaborative.

Objective: We sought to several develop parsimonious machine learning models to predict resource utilization and clinical outcomes following cardiac operations using only preoperative factors. Methods: All patients undergoing coronary artery bypass grafting and/or valve operations were identified in the 2015-2021 University of California Cardiac Surgery Consortium repository. The primary end point of the study was length of stay (LOS). Secondary endpoints included 30-day mortality, acute kidney injury, reoperation, postoperative blood transfusion and duration of intensive care unit admission (ICU LOS). Linear regression, gradient boosted machines, random forest, extreme gradient boosting predictive models were developed. The coefficient of determination and area under the receiver operating characteristic (AUC) were used to compare models. Important predictors of increased resource use were identified using SHapley summary plots. Results: Compared with all other modeling strategies, gradient boosted machines demonstrated the greatest performance in the prediction of LOS (coefficient of determination, 0.42), ICU LOS (coefficient of determination, 0.23) and 30-day mortality (AUC, 0.69). Advancing age, reduced hematocrit, and multiple-valve procedures were associated with increased LOS and ICU LOS. Furthermore, the gradient boosted machine model best predicted acute kidney injury (AUC, 0.76), whereas random forest exhibited greatest discrimination in the prediction of postoperative transfusion (AUC, 0.73). We observed no difference in performance between modeling strategies for reoperation (AUC, 0.80). Conclusions: Our findings affirm the utility of machine learning in the estimation of resource use and clinical outcomes following cardiac operations. We identified several risk factors associated with increased resource use, which may be used to guide case scheduling in times of limited hospital capacity.

Invasive Pulmonary Aspergillosis and Tuberculosis Complicated by Hemophagocytic Lymphohistiocytosis - Sequelae of COVID-19 in a Liver Transplant Recipient.

Liver transplant recipients are at an increased risk of opportunistic infections due to the use of immunosuppression. Coronavirus disease of 2019 (COVID-19) increases the risk of these infections further due to associated immune dysfunction and the use of high-dose steroids. We present a case of a liver transplant recipient who developed disseminated tuberculosis and invasive pulmonary aspergillosis complicated by acquired hemophagocytic lymphohistiocytosis after recovering from severe COVID-19.

Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A State-of-the-Art Review.

The vast majority of patients (>99%) with severe acute respiratory syndrome coronavirus 2 survive immediate infection but remain at risk for persistent and/or delayed multisystem. This review of published reports through May 31, 2021, found that manifestations of postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) affect between 33% and 98% of coronavirus disease 2019 survivors and comprise a wide range of symptoms and complications in the pulmonary, cardiovascular, neurologic, psychiatric, gastrointestinal, renal, endocrine, and musculoskeletal systems in both adult and pediatric populations. Additional complications are likely to emerge and be identified over time. Although data on PASC risk factors and vulnerable populations are scarce, evidence points to a disproportionate impact on racial/ethnic minorities, older patients, patients with preexisting conditions, and rural residents. Concerted efforts by researchers, health systems, public health agencies, payers, and governments are urgently needed to better understand and mitigate the long-term effects of PASC on individual and population health.

The Good Treatment, the Bad Virus, and the Ugly Inflammation: Pathophysiology of Kidney Involvement During COVID-19.

Kidney involvement is a common complication during SARS-CoV-2 infection. Its association with poor outcomes, especially in critically ill patients, raises issues whether kidney involvement reflects multi-organ damage or if it is a specific feature of the infection. Based on observational studies, autopsy series, and on current understanding of the route of entry of the virus, this review will highlight the different types of kidney involvement during COVID-19 and put them in the perspective of the different pathophysiological hypotheses. Virus entry route through ACE2 ligation and TMPRSS2 coligation allows identifying potential viral targets in the kidney, including tubules, endothelial cells, and glomerulus. While reports have described damages of all these structures and virus kidney tropism has been identified in renal extracts in autopsy series, no direct viral infection has been found in the latter structures thus far on kidney biopsies. Notwithstanding the technical challenge of disclosing viral invasion within tissues and cells, viral direct cytopathogenic effect generally does not appear as the cause of the observed renal damage. Inflammation and altered hemodynamics, described as "viral sepsis," might rather be responsible for organ dysfunction, including kidneys. We shall place these various mechanisms into an integrated vision where the synergy between direct viral pathogenicity and systemic inflammation enhances renal damage. As SARS-CoV-2 inexorably continues its rampant spread, understanding the sequence of events in the kidneys might thus help inform improved therapeutic strategies, including antiviral drugs and immunomodulators.

Incidence and Risk Factors for Acute Kidney Injury and Its Effect on Mortality in Patients Hospitalized From COVID-19.

OBJECTIVE: To determine the incidence of and risk factors for the development of acute kidney injury (AKI) and investigate the association between AKI and mortality in patients hospitalized with coronavirus disease 2019 (COVID-19) infection. PATIENTS AND METHODS: This retrospective case series includes the first 370 patients consecutively hospitalized with confirmed COVID-19 illness between March 10, 2020, and May 13, 2020, at a 242-bed teaching hospital. To determine independent associations between demographic factors, comorbid conditions, and AKI incidence, multivariable logistic regression models were used to estimate odds ratios adjusted for clinical covariates. RESULTS: Median age of patients was 71 (interquartile range, 59-82) years and 44.3% (145 of 327) were women. Patients with AKI were significantly older with a higher comorbid condition burden and mortality rate (58.1% [104 0f 179] vs 19.6% [29 of 148]; P<.001) when compared with those without AKI. Increasing age, chronic kidney disease, hyperlipidemia, and being of African American descent showed higher odds of AKI. Patients with AKI had significantly higher odds of mortality when compared with patients without AKI, and this effect was proportional to the stage of AKI. Increasing age and acute respiratory distress syndrome also revealed higher adjusted odds of mortality. CONCLUSIONS: Acute kidney injury is a common complication among hospitalized patients with COVID-19 infection. We found significantly higher odds of AKI with increasing age and among patients with hyperlipidemia, those with chronic kidney disease, and among African Americans. We demonstrate an independent association between AKI and mortality with increasingly higher odds of mortality from progressively worsening renal failure in hospitalized patients with COVID-19 infection.

Cardiac Dysfunction and Shock in Pediatric Patients With COVID-19.

Coronavirus disease-2019 (COVID-19) has been reported to cause significant morbidity in adults, with reportedly a lesser impact on children. Cardiac dysfunction has only been described in adults thus far. We describe 3 cases of previously healthy children presenting with shock and COVID-19-related cardiac inflammation. (Level of Difficulty: Intermediate.).