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Novel strategies to treat ALD aim at targeting Kupffer cells. These interventions modulate Kupffer cell activation or macrophage polarization. Evidence from mouse models and early clinical studies in patients with ALD injury supports the notion that pathogenic macrophage subsets can be successfully translated into novel treatment options for patients with this disease.The rapid spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has resulted in an unprecedented public health crisis worldwide. Recent studies indicate that a hyperinflammatory syndrome induced by SARS-CoV-2 contributes to disease severity and mortality in COVID-19. In this review, an overview of the pathophysiology underlying the hyperinflammatory syndrome in severe COVID-19 is provided. The current evidence suggests that the hyperinflammatory syndrome results from a dysregulated host innate immune response. The gross and microscopic pathologic findings as well as the alterations in the cytokine milieu, macrophages/monocytes, natural killer cells, T cells, and neutrophils in severe COVID-19 are summarized. The data highlighted include the potential therapeutic approaches undergoing investigation to modulate the immune response and abrogate lung injury in severe COVID-19.The lacrimal gland is critical for maintaining the homeostasis of the ocular surface microenvironment through secreting aqueous tears in mammals. Many systemic diseases such as Sjögren syndrome, rheumatoid arthritis, and diabetes can alter the lacrimal gland function, eventually resulting in aqueous tear-deficient dry eye. Here, a high-fat diet (HFD) experimental mouse model was used to clarify how hyperlipidemia affects lacrimal gland function. Aqueous tear secretion fell about 50% after 1 month on a HFD. Lipid droplets accumulated in the matrix and acinar cells of the lacrimal gland after this period, along with changes in the lipid metabolism, changes in gene expression levels, and disruption of fatty acid oxidative activity. Immune cell infiltration and rises in the gene expression levels of the inflammation-related cytokines Il1β, Tnfα, Tsg6, Il10, Mmp2, and Mmp9 were found. HFD also induced mitochondrial hypermegasoma, increased apoptosis, and decreased lacrimal gland acinar cell proliferation. Replacement of the HFD with the standard diet partially reversed pathologic changes in the lacrimal gland. Similarly, supplementing the HFD with fenofibrate also partially reversed the inhibited tear secretion and reduced lipid accumulation, inflammation, and oxidative stress levels. The authors conclude that a HFD induces pathophysiological changes and functional decompensation of the lacrimal gland. Therefore, ingestion of a HFD may be a causative factor of dry eye disease.

Heart transplantation is limited by the supply of donor organs. Previous studies have associated female donor to male recipient with decreased posttransplant survival. We wanted to evaluate whether this risk can be mitigated using higher donor than recipient body mass index (BMI).

We performed a retrospective analysis of the Organ Procurement and Transplantation Network/United Network of Organ Sharing registry encompassing years 2005 to 2018 for all male adult recipients (>18 years of age) who underwent isolated heart transplantation with grafts from female donors. The association between donor and recipient BMI difference and recipient survival was evaluated using adjusted Cox proportional hazards modeling.

A total of 3788 male recipients who received female donor hearts met inclusion criteria for analysis. Maximally selected rank statistics identified donor minus recipient BMI of 1.5 kg/m

as a meaningful cutoff point in the analysis of recipient survival. Sunitinib Multivariable Cox proportional hazards an.

Patients with liver cirrhosis (LC) undergoing cardiac surgery (CS) face perioperative high mortality and morbidity, but extensive studies on this topic are lacking.

All adult patients with LC undergoing a CS procedure between 2000 and 2017 at 10 Italian Institutions were included in this retrospective cohort study. LC was classified according to preoperative Child-Turcotte-Pugh (CTP) score and Model for End-Stage Liver Disease (MELD) score. Early-term and medium-term outcomes analysis was performed in the overall population and according to CTP classes.

The study population included 144 patients (mean age 66 ± 9 years, 69% male). Ninety-eight, 20, and 26 patients were in CTP class A, in early CTP class B (MELD score <12), or advanced CTP class B (MELD score >12), respectively. The main LC etiologies were viral (43%) and alcoholic (36%). Liver-related clinical presentation (ascites, esophageal varices, and encephalopathy) and laboratory values (estimated glomerular filtration rate, serum albumin, aurther analysis are needed to better estimate the preoperative risk stratification of these patients.

CS outcomes in patients with LC are significantly affected in relation to the extent of preoperative liver dysfunction, but in early CTP classes, medium-term survival is acceptable. Further analysis are needed to better estimate the preoperative risk stratification of these patients.Although NO2, a major traffic related air pollutant, has been associated with onset of childhood asthma, young children may be more susceptible to traffic related air pollution exposure compared to other individuals. We linked data from National Longitudinal Survey of Children and Youths Cycle 1-5 (1994-2003) and the National Air Pollution Surveillance Program to determine the association between NO2 exposure and either early or late onset childhood asthma phenotypes. Children diagnosed with asthma from age 0-3 were defined as having early onset asthma. Children diagnosed with asthma from age 4-9 were defined as having late onset asthma. Mean NO2 exposure for each quartile was 6.31 ppb, 9.45 ppb, 11.83 ppb, and 17.9 ppb. Higher levels of NO2 exposure were more strongly associated with early childhood asthma (Quartile 3 OR 2.11, 95% CI 1.29, 3.44, Quartile 4 OR 2.16, 95% CI 1.27, 3.68) compared to the lowest level of NO2 exposure (Quartile 1). No such association was observed with risk of late childhood asthma onset.