Utility of Lille Score in Predicting 30-Day Survival in Steroid-Treated Alcohol-Associated Hepatitis.

BACKGROUND/AIMS: In alcohol-associated hepatitis (AH), the Lille score is used to assess futility of steroids. However, the ability of the Lille score to predict 30-day survival in AH is not well-defined. Our aim is to compare the utility of the Lille score in predicting 30-day survival in those with AH treated with steroids. METHODS: Retrospective chart review of 882 patients hospitalized with AH from January 1st, 2012 through December 30th, 2019 was performed. Of these, 201 patients with severe AH met the threshold to receive steroids. Those with data to calculate Lille score < 0.45 on day 4 (n = 29) or 7 (n = 89) who continued steroids were compared to 83 patients with Lille scores ≥ 0.45 on day 4 (n = 18) or 7 (n = 65) who stopped steroids. The primary outcome was 30-day survival. For comparison, a contemporaneous matched control group was also analyzed of 110 patients who were hospitalized with severe AH, but did not receive steroids. RESULTS: In patients with Lille score < 0.45, survival was higher at 30-day when compared to those with Lille score ≥ 0.45 (94.9% vs. 80.72%; p = 0.002). The sensitivity, specificity, positive predictive value and negative predictive value of Lille score (< 0.45) to predict 30-day survival was 95%, 19%, 63%, and 73%, respectively. CONCLUSIONS: In severe AH, those with Lille score < 0.45 at day 4 or 7 have improved 30-day survival compared to those with Lille score ≥ 0.45. In those receiving steroids, Lille score has excellent sensitivity to predict 30-day survival but poor specificity.

Outcomes of Cancer Patients with COVID-19: The Virginia Commonwealth University Experience.

PURPOSE: The cancer population is significantly impacted by coronavirus disease 2019 (COVID-19) due to inherent risks of infection imposed by malignancy and therapeutic agents. Evaluating risk factors in this group will lead to improved guidelines for the treatment of malignancy in the setting of a COVID-19 pandemic. PATIENTS AND METHODS: This retrospective study reviewed 295 inpatient cancer patients positive for COVID-19 between February 2020 and December 2021 to determine specific risk factors of mortality and associated complications. Various patient characteristics were collected to evaluate outcomes in patient death, oxygen requirement, ventilatory support, and increased length of stay. RESULTS: 31 (10.5%) of 295 patients died due to COVID-19. Of those that died, the majority had hematologic cancer (48.4%). There was no difference in the odds of death among the cancer groups. Those vaccinated had a reduced risk of death (OR 0.04, CI 0-0.23). Patients with lung cancer (OR 3.69, CI 1.13-12.31), obesity (OR 3.27, CI 1.18-9.27), CHF (OR 2.68, CI 1.07-6.89) were more likely to require ventilation. Those treated with hormonal therapy had higher odds of having a prolonged admission (OR 5.04, CI 1.17-2.53). Otherwise, cancer therapy had no significant difference in any outcome. CONCLUSION: The mortality rate of cancer patients was 10.5%, lower than in other studies. Vaccinations had mortality benefits, but no effect on hypoxia, ventilator use, or LOS. Delaying cancer therapy during peak infection is likely not necessary based on the results of this study. With improved knowledge in the risks of infection and the utility of personalized precautions, both providers and patients can better prepare for another potential wave of COVID-19.

Venetoclax with decitabine or azacitidine in relapsed or refractory acute myeloid leukemia.

Relapsed or refractory acute myeloid leukemia (AML) is associated with poor outcomes and resistance to therapy. The addition of venetoclax, a BCL-2 antagonist, to lower-intensity therapies results in improved survival in the first-line setting compared to monotherapy with a hypomethylating agent or low-dose cytarabine. Despite this, much remains unknown about the performance of venetoclax with a hypomethylating agent following the first-line setting. Additionally, while the ELN 2022 guidelines appear to improve the prognostication of AML, clarification is needed to determine how the revision applies to lower-intensity strategies. To investigate this, we retrospectively analyzed the performance of venetoclax with decitabine or azacitidine in relapsed or refractory AML under the ELN 2022 guidelines. We demonstrated that the ELN 2022 revision is not optimized for lower-intensity venetoclax-based strategies. To refine the prognostication schema, we showed significantly improved response and survival benefits for patients with mutated NPM1 and IDH. Relatively, patients with mutated NRAS, KRAS, and FLT3-ITD were associated with inferior response and survival. Furthermore, there is an unmet clinical need for tools to improve the selection of lower-intensity therapy candidates with borderline functional status. Using an incremental survival computation method, we discovered that a CCI score threshold of 5 distinguishes patients at an elevated risk of death. Together, these novel findings highlight areas of refinement to improve survival in relapsed or refractory AML.

Assessing the clinical utility of major indices for nonalcoholic fatty liver disease in East Asian populations.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease. The growing prevalence of NAFLD is strongly associated with the high incidence of metabolic syndrome. NAFLD affects as much as 19% of the US population with a disproportionate impact on minority racial groups such as Asian Americans. If not promptly managed, NAFLD may progress to more feared complications. Liver indices for NAFLD screening have been proposed but were often developed using study populations with different anthropometrics than patients of East Asian descent. This review compares the accuracy of five indices for NAFLD screening in Asian cohorts. The Fatty Liver Index performed well in multiple large-scale community studies, although other indices may be more suited for specific patient cohorts. This is important, as the utilization of liver indices could accelerate screening for NAFLD for early management and to reduce liver disease-related health disparities among Asian Americans.

Mechanisms regulating the loss of Tregs in HUPO mice that develop spontaneous inflammatory arthritis.

T regulatory cells (Tregs) are a potential therapeutic target in many autoimmune diseases including rheumatoid arthritis (RA). The mechanisms responsible for the maintenance of Tregs in chronic inflammatory conditions such as RA are poorly understood. We employed our mouse model of RA in which, the following deletion of Flice-like inhibitory protein in CD11c+ cells, CD11c-FLIP-KO (HUPO) mice develop spontaneous, progressive, erosive arthritis, with reduced Tregs, and the adoptive transfer of Tregs ameliorates the arthritis. HUPO thymic Treg development was normal, but peripheral of Treg Foxp3 was diminished mediated by reduction of dendritic cells and interleukin-2 (IL-2). During chronic inflammatory arthritis Tregs fail to maintain Foxp3, leading to non-apoptotic cell death and conversion to CD4+CD25+Foxp3- cells. Treatment with IL-2 increased Tregs and ameliorated the arthritis. In summary, reduced dendritic cells and IL-2 in the milieu of chronic inflammation, contribute to Treg instability, promoting HUPO arthritis progression, and suggesting a therapeutic approach in RA.

Venetoclax with decitabine or azacitidine in the first-line treatment of acute myeloid leukemia.

Treatment paradigms for acute myeloid leukemia (AML) have evolved at a rapid pace in recent years. The combination of venetoclax with a hypomethylating agent prolonged survival in clinical trials when compared to hypomethylating agent monotherapy. However, little is known about the performance of venetoclax-based regimens outside of clinical trials, given conflicting safety and efficacy data. Even less is known about the impact of the hypomethylating agent backbone. In this study, we demonstrate that decitabine-venetoclax is associated with a significantly higher rate of grade three or higher thrombocytopenia, but lower rates of lymphocytopenia compared to azacitidine-venetoclax. There was no difference in response or survival across ELN 2017 cytogenetic risk categories in the overall cohort. Significantly more patients succumb to relapsed or refractory disease than death from any other cause. We demonstrated that a Charlson comorbidity index score threshold of seven identifies exceptionally high-risk patients, providing evidence for clinical use to reduce the risk of early treatment-related mortality. Lastly, we provide evidence that measurable residual disease negativity and an IDH mutation predict a significant survival benefit outside clinical trials. Taken together, these data illuminate the real-world performance of venetoclax and decitabine or azacitidine in the treatment of AML.