Early-Onset Invasive Pulmonary Aspergillosis in a Liver Transplant Patient: A Case Report.

Invasive pulmonary aspergillosis (IPA) in liver transplant patients remains rare but exceedingly fatal. The diagnostic challenges associated with this condition are compounded by its infrequent onset within the first two weeks following transplantation. Moreover, therapeutic management is complex due to the intricate drug interactions between triazole antifungals and calcineurin inhibitor immunosuppressants. We present the case of a 63-year-old male who underwent uncomplicated liver transplantation (LT) and developed early-onset IPA. Despite maximal efforts, the patient expired. This report aims to underscore the vital importance of timely diagnosis and therapy in preventing the insidious progression of invasive disease and subsequent mortality.

Comparing the demographics and laboratory biomarkers of the COVID-19 Omicron wave and the Alpha wave in a predominantly Afro-Caribbean patient population in New York City.

BACKGROUND: There is a knowledge gap of specific characteristics linked to disease severity of the different COVID-19 waves, especially in underserved populations. We compared the demographic and clinical factors associated with SARS-CoV-2-infected patients admitted to the intensive care unit (ICU) during the Omicron and Alpha waves. METHODS: An observational study comparing two COVID-19 waves was conducted in Brooklyn, NY. Twenty-seven ICU admitted patients with a positive COVID-19 test result during the period of November 1, 2021, to January 31, 2022, ("Omicron wave") were compared to 271 COVID-19 patients who received ICU consults during the Alpha wave, the period from March 28, 2020, to April 30, 2020. RESULTS: The Omicron wave had a 55.6% mortality rate compared to a 67.2% mortality rate in the Alpha wave. For the non-survivors, there were more females (66.7%) in the Omicron wave, while the trend was reversed in the Alpha wave (38.5%). Most of the patients seen were Black (> 85%) in both waves. A bivariate comparison of the two waves found that patients in the Omicron wave had overall significantly lower ALT levels (p = 0.03) and higher monocyte % (p = 0.005) compared to the patients in the Alpha wave. In the multivariate analysis, adjusting for age and sex, increasing levels of HCO3- were significantly associated with reduced mortality in the Omicron wave (OR: 0.698; 95% CI: 0.516 - 0.945; p = 0.02). Also, multivariable analyses using both waves combined found that neutrophil % was significantly associated with increased mortality (OR: 1.05; 95% CI: 1.02 - 1.09; p = 0.006) while lymphocyte % was significantly associated with reduced mortality (OR: 0.946; 95% CI: 0.904 - 0.990; p = 0.018). CONCLUSIONS: The COVID-19-positive ICU patients in the Omicron wave experienced less severe outcomes than those of the Alpha wave. In contrast to the Alpha variant, the Omicron variant exhibited enhanced infectivity and disease severity in females.

Procalcitonin Levels in COVID-19 Patients Are Strongly Associated with Mortality and ICU Acceptance in an Underserved, Inner City Population.

Background and Objectives: This study aimed to identify demographic and clinical factors at the time of critical care consultation associated with mortality or intensive care unit acceptance in a predominantly Afro-Caribbean population during the first wave of the COVID19 pandemic. Materials and Methods: This retrospective, single-center observational cohort study included 271 COVID19 patients who received a critical care consult between March 11 and April 30, 2020 during the first wave of the COVID19 pandemic at State University of New York Downstate Health Sciences University. Results: Of the 271 patients with critical care consults, 33% survived and 67% expired. At the bivariate level, age, blood urea nitrogen, and blood neutrophil percentage were significantly associated with mortality (mean age: survivors, 61.62 ± 1.50 vs. non-survivors, 68.98 ± 0.85, p < 0.001). There was also a significant association between neutrophil% and mortality in the univariate logistic regression model (quartile 4 vs. quartile 1: odd ratio 2.73, 95% confidence interval (1.28-5.82), p trend = 0.044). In the multivariate analyses, increasing levels of procalcitonin and C-reactive protein were significantly associated with mortality, adjusting for age, sex, and race/ethnicity (for procalcitonin quartile 4 vs. quartile 1: odds ratio 5.65, 95% confidence interval (2.14-14.9), p trend < 0.001). In contrast, higher platelet levels correlated with significantly decreased odds of mortality (quartile 4 vs. quartile 1, odds ratio 0.47, 95% CI (0.22-0.998), p trend = 0.010). Of these factors, only elevated procalcitonin levels were associated with intensive care unit acceptance. Conclusions: Procalcitonin showed the greatest magnitude of association with both death and likelihood of intensive care unit acceptance at the bivariate level. Our data suggests that procalcitonin reflects pneumonia severity during COVID-19 infection. Thus, it may help the intensivist identify those COVID19 patients who require intensive care unit level care.

SIRT7 deficiency suppresses inflammation, induces EndoMT, and increases vascular permeability in primary pulmonary endothelial cells.

Acute lung injury (ALI), a common condition in critically ill patients, has limited treatments and high mortality. Aging is a risk factor for ALI. Sirtuins (SIRTs), central regulators of the aging process, decrease during normal aging and in aging-related diseases. We recently showed decreased SIRT7 expression in lung tissues and fibroblasts from patients with pulmonary fibrosis compared to controls. To gain insight into aging-related mechanisms in ALI, we investigated the effects of SIRT7 depletion on lipopolysaccharide (LPS)-induced inflammatory responses and endothelial barrier permeability in human primary pulmonary endothelial cells. Silencing SIRT7 in pulmonary artery or microvascular endothelial cells attenuated LPS-induced increases in ICAM1, VCAM1, IL8, and IL6 and induced endomesenchymal transition (EndoMT) with decreases in VE-Cadherin and PECAM1 and increases in collagen, alpha-smooth muscle actin, TGFß receptor 1, and the transcription factor Snail. Loss of endothelial adhesion molecules was accompanied by increased F-actin stress fibers and increased endothelial barrier permeability. Together, these results show that an aging phenotype induced by SIRT7 deficiency promotes EndoMT with impaired inflammatory responses and dysfunction of the lung vascular barrier.