Fewer emergency department alarms is associated with reduced use of medications for acute agitation.

Background And Objectives: Patient monitoring systems provide critical information but often produce loud, frequent alarms that worsen patient agitation and stress. This may increase the use of physical and chemical restraints with implications for patient morbidity and autonomy. This study analyzes how augmenting alarm thresholds affects the proportion of alarm-free time and the frequency of medications administered to treat acute agitation.

Alcohol-induced extracellular ASC specks perpetuate liver inflammation and damage in alcohol-associated hepatitis even after alcohol cessation.

Background Aims: Prolonged systemic inflammation contributes to poor clinical outcomes in severe alcohol-associated hepatitis (AH) even after the cessation of alcohol use. However, mechanisms leading to this persistent inflammation remain to be understood.

Approach Results: We show that while chronic alcohol induces nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in the liver, alcohol binge results not only in NLRP3 inflammasome activation but also in increased circulating extracellular apoptosis-associated speck-like protein containing a caspase recruitment domain (ex-ASC) specks and hepatic ASC aggregates both in patients with AH and in mouse models of AH.

Granulocyte colony-stimulating factor attenuates liver damage by M2 macrophage polarization and hepatocyte proliferation in alcoholic hepatitis in mice.

Massive inflammation and liver failure are main contributors to the high mortality in alcohol-associated hepatitis (AH). In recent clinical trials, granulocyte colony-stimulating factor (G-CSF) therapy improved liver function and survival in patients with AH. However, the mechanisms of G-CSF-mediated beneficial effects in AH remain elusive.

A Case of Bleeding During Infection With COVID-19.

Dr. Patrick Lowe: Our case today is that of a 47-year-old woman who was referred to our emergency department (ED) due to bloody urine, dark tarry stools, red spots on her skin, and bruising throughout her body. Fourteen days prior to presentation, she began exhibiting intermittent fevers, headache, shortness of breath, and a dry cough, and she tested positive for SARS-CoV-2 (the virus that causes COVID-19 pneumonia).

Stabilization of Metastatic Uterine Leiomyosarcoma Using Pembrolizumab.

The estimated 5-year survival rate for patients with stage IV uterine leiomyosarcoma is 29%, with a median survival of <1 year. This report describes a patient with stage IVB leiomyosarcoma who experienced stable disease for 15 months on pembrolizumab. A woman aged 62 years, gravida 2 para 2, with postmenopausal bleeding and a necrotic uterine fibroid underwent a dilation and curettage and was diagnosed with uterine leiomyosarcoma.

Inhibition of the Inflammasome Signaling Cascade Reduces Alcohol Consumption in Female But Not Male Mice.

Background: Alcohol use disorder is a significant societal and medical burden that is associated with both organ pathology and addiction. Excessive alcohol use results in neuroinflammation characterized by activation of the inflammasome, a multiprotein complex, and IL-1β increase in the brain. Recent studies suggest that inflammation could contribute to alcohol addiction.

Dysregulated Autophagy and Lysosome Function Are Linked to Exosome Production by Micro-RNA 155 in Alcoholic Liver Disease.

Cellular homeostais, that is normally maintained through autophagy, is disrupted in alcoholic liver disease (ALD). Because autophagy and exosome biogenesis share common elements, we hypothesized that increased exosome production in ALD may be linked to disruption of autophagic function. We found impaired autophagy both in ALD and alcoholic hepatitis (AH) mouse models and human livers with ALD as indicated by increased hepatic p62 and LC3-II levels.

Biomarkers of Macrophage Activation and Immune Danger Signals Predict Clinical Outcomes in Alcoholic Hepatitis.

Although mortality due to acute alcoholic hepatitis (AH) correlates with Model for End-Stage Liver Disease (MELD) scores, biomarkers are critically needed to manage this disease. Increases in inflammatory markers and macrophage activation are associated with acute AH and could be potential biomarkers of clinical events and/or mortality. We enrolled 89 clinically diagnosed AH patients in four US academic medical centers.

Macrophage-Specific Hypoxia-Inducible Factor-1α Contributes to Impaired Autophagic Flux in Nonalcoholic Steatohepatitis.

Inflammatory cell activation drives diverse cellular programming during hepatic diseases. Hypoxia-inducible factors (HIFs) have recently been identified as important regulators of immunity and inflammation. In nonalcoholic steatohepatitis (NASH), HIF-1α is upregulated in hepatocytes, where it induces steatosis; however, the role of HIF-1α in macrophages under metabolic stress has not been explored.

MicroRNA 122, Regulated by GRLH2, Protects Livers of Mice and Patients From Ethanol-Induced Liver Disease.

Background & Aims: Chronic, excessive alcohol consumption leads to alcoholic liver disease (ALD) characterized by steatosis, inflammation, and eventually cirrhosis. The hepatocyte specific microRNA 122 (MIR122) regulates hepatocyte differentiation and metabolism. We investigated whether an alcohol-induced decrease in level of MIR122 contributes to development of ALD.

Alcohol-induced miR-155 and HDAC11 inhibit negative regulators of the TLR4 pathway and lead to increased LPS responsiveness of Kupffer cells in alcoholic liver disease.

Inflammation promotes the progression of alcoholic liver disease. Alcohol sensitizes KCs to gut-derived endotoxin (LPS); however, signaling pathways that perpetuate inflammation in alcoholic liver disease are only partially understood. We found that chronic alcohol feeding in mice induced miR-155, an inflammatory miRNA in isolated KCs.

Correction: Alcohol-related changes in the intestinal microbiome influence neutrophil infiltration, inflammation and steatosis in early alcoholic hepatitis in mice.

[This corrects the article DOI: 10.1371/journal.pone.

Inhibition of spleen tyrosine kinase activation ameliorates inflammation, cell death, and steatosis in alcoholic liver disease.

Unlabelled: The spectrum of alcoholic liver disease (ALD) is a major cause of mortality with limited therapies available. Because alcohol targets numerous signaling pathways in hepatocytes and in immune cells, the identification of a master regulatory target that modulates multiple signaling processes is attractive. In this report, we assessed the role of spleen tyrosine kinase (SYK), a nonreceptor tyrosine kinase, which has a central modulatory role in multiple proinflammatory signaling pathways involved in the pathomechanism of ALD.

Adult mouse model of early hepatocellular carcinoma promoted by alcoholic liver disease.

Aim: To establish a mouse model of alcohol-driven hepatocellular carcinoma (HCC) that develops in livers with alcoholic liver disease (ALD).

Methods: Adult C57BL/6 male mice received multiple doses of chemical carcinogen diethyl nitrosamine (DEN) followed by 7 wk of 4% Lieber-DeCarli diet. Serum alanine aminotransferase (ALT), alpha fetoprotein (AFP) and liver Cyp2e1 were assessed.

Human ovarian tissue cortex surrounding benign and malignant lesions.

Objective: To quantify the number of follicles in patients with ovarian pathologies, benign and malignant, in pregnant and nonpregnant states and to determine how the presence of ovarian masses and BRCA status affects follicular counts.

Materials And Methods: Slides from 134 reproductive-aged women undergoing oophorectomy were examined using light microscopy by 3 independent counters blinded to the diagnosis. In all, 20 patients had cancer, 69 had benign conditions, and 35 patients were BRCA+ or had a strong family history of breast and/or ovarian cancer.

Characterization of FUS mutations in amyotrophic lateral sclerosis using RNA-Seq.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting in severe muscle weakness and eventual death by respiratory failure. Although little is known about its pathogenesis, mutations in fused in sarcoma/translated in liposarcoma (FUS) are causative for familial ALS. FUS is a multifunctional protein that is involved in many aspects of RNA processing.

Phase II clinical trial of bevacizumab with albumin-bound paclitaxel in patients with recurrent, platinum-resistant primary epithelial ovarian or primary peritoneal carcinoma.

Objective: We examined the safety and efficacy of combining bevacizumab with albumin-bound (ab-) paclitaxel to treat patients with recurrent, platinum-resistant primary epithelial ovarian or peritoneal carcinoma.

Methods: Patients had measurable disease per RECIST guidelines, progressing within 6 months after a prior course of platinum-based treatment. Patients received ab-paclitaxel 100mg/m(2) given by intravenous infusion over 30 min on days 1, 8, and 15 of a 28-day cycle with bevacizumab 10mg/kg given on days 1 and 15.