Alcoholic liver disease (ALD), comprising a spectrum of diseases ranging from alcoholic fatty liver disease (AFLD) to advanced ALD (including alcoholic hepatitis, cirrhosis, and cirrhosis complications), 1 is a leading cause of mortality in the United States, with nearly 250 000 deaths attributed to ALD in 2010. 2,3 Overall US clinical burden of ALD remains unclear, perhaps because of lack of a definitive standard for identifying ALD. This study focused on the specific, more well-defined subset of AFLD to estimate national prevalence among US adults.

OBJECTIVES: Alcoholic liver disease (ALD) prevalence, particularly the subset with advanced liver disease, is not well defined. Herein, we aim to provide a comprehensive assessment of ALD epidemiology across the spectrum of disease severity and across different settings using 3 unique US databases. METHODS: We performed a retrospective, observational study of US adults with ALD using 2001–2016 National Health and Nutrition Examination Survey (NHANES), 2007–2014 Nationwide Inpatient Sample (NIS), and 2007–2017 United Network for Organ Sharing (UNOS) registry. ALD in the NHANES was defined using clinical laboratory data and self-reported alcohol use, among which fibrosis-4 score of >2.67 defined stage ≥3 fibrosis. Alcoholic cirrhosis (AC) in the NIS was identified using International Classification of Diseases, Ninth Revision codes. ALD in the UNOS was identified using UNOS coding. RESULTS: From 2001–2002 to 2015–2016, the overall weighted ALD prevalence was stable from 8.8% to 8.1% (P = 0.102), whereas the proportion of ALD with stage ≥3 fibrosis increased from 2.2% (95% CI: 0.4–4.0) to 6.6% (95% CI: 2.0–9.9; P = 0.007) (NHANES). From 2007 to 2014, the number of hospitalizations among patients with AC per 1,000 increased by 32.8%, and the proportion of hospitalizations among the patients with AC with ≥3 cirrhosis complications increased from 11.6% in 2007 to 25.8% in 2014 (P trend < 0.0001) (NIS). From 2007 to 2017, the total number of adults with ALD listed for liver transplant increased by 63.4% and the proportion with concurrent hepatocellular carcinoma increased by 178% (UNOS). DISCUSSION: Among these 3 US databases, consistent observations of increasing ALD severity emphasize the urgent need for greater awareness about the consequences of unhealthy alcohol use and interventions aimed specifically at addressing alcohol use disorders.

Background: Immune checkpoint inhibitors (ICIs) are monoclonal antibodies used to activate the immune system against tumor cells. Despite therapeutic benefits, ICIs have the potential to cause immune-related adverse events such as myocarditis, a rare but serious side effect with up to 50% mortality in affected patients. Histologically, patients with ICI myocarditis have lymphocytic infiltrates in the heart, implicating T cell–mediated mechanisms. However, the precise pathological immune subsets and molecular changes in ICI myocarditis are unknown. Methods: To identify immune subset(s) associated with ICI myocarditis, we performed time-of-flight mass cytometry on peripheral blood mononuclear cells from 52 individuals: 29 patients with autoimmune adverse events (immune-related adverse events) on ICI, including 8 patients with ICI myocarditis, and 23 healthy control subjects. We also used multiomics single-cell technology to immunophenotype 30 patients/control subjects using single-cell RNA sequencing, single-cell T-cell receptor sequencing, and cellular indexing of transcriptomes and epitopes by sequencing with feature barcoding for surface marker expression confirmation. To correlate between the blood and the heart, we performed single-cell RNA sequencing/T-cell receptor sequencing/cellular indexing of transcriptomes and epitopes by sequencing on MRL/Pdcd1 −/− (Murphy Roths large/programmed death-1–deficient) mice with spontaneous myocarditis. Results: Using these complementary approaches, we found an expansion of cytotoxic CD8 + T effector cells re-expressing CD45RA (Temra CD8 + cells) in patients with ICI myocarditis compared with control subjects. T-cell receptor sequencing demonstrated that these CD8 + Temra cells were clonally expanded in patients with myocarditis compared with control subjects. Transcriptomic analysis of these Temra CD8 + clones confirmed a highly activated and cytotoxic phenotype. Longitudinal study demonstrated progression of these Temra CD8 + cells into an exhausted phenotype 2 months after treatment with glucocorticoids. Differential expression analysis demonstrated elevated expression levels of proinflammatory chemokines (CCL5/CCL4/CCL4L2) in the clonally expanded Temra CD8 + cells, and ligand receptor analysis demonstrated their interactions with innate immune cells, including monocytes/macrophages, dendritic cells, and neutrophils, as well as the absence of key anti-inflammatory signals. To complement the human study, we performed single-cell RNA sequencing/T-cell receptor sequencing/cellular indexing of transcriptomes and epitopes by sequencing in Pdcd1 −/− mice with spontaneous myocarditis and found analogous expansions of cytotoxic clonal effector CD8 + cells in both blood and hearts of such mice compared with controls. Conclusions: Clonal cytotoxic Temra CD8 + cells are significantly increased in the blood of patients with ICI myocarditis, corresponding to an analogous increase in effector cytotoxic CD8 + cells in the blood/hearts of Pdcd1 −/− mice with myocarditis. These expanded effector CD8 + cells have unique transcriptional changes, including upregulation of chemokines CCL5/CCL4/CCL4L2, which may serve as attractive diagnostic/therapeutic targets for reducing life-threatening cardiac immune-related adverse events in ICI-treated patients with cancer.

Objective Topical intranasal anticholinergics are commonly prescribed for the relief of chronic rhinitis and associated symptoms, warranting thorough assessment of the supporting evidence. The present study aimed to evaluate the safety and efficacy of anticholinergic nasal sprays in the management of allergic and non‐allergic rhinitis symptom severity and duration. Methods A search encompassing the Cochrane Library, PubMed/MEDLINE, and Scopus databases was conducted. Primary studies describing rhinorrhea, nasal congestion, and/or postnasal drip outcomes in rhinitis patients treated with an anticholinergic spray were included for review. Results The search yielded 1,029 unique abstracts, of which 12 studies (n = 2,024) met inclusion criteria for qualitative synthesis and 9 (n = 1,920) for meta‐analysis. Median follow‐up was 4 weeks and ipratropium bromide was the most extensively trialed anticholinergic. Compared to placebo, anticholinergic treatment was demonstrated to significantly reduce rhinorrhea severity scores (standardized mean difference [95% CI] = −0.77 [−1.20, −0.35]; −0.43 [−0.72, −0.13]) and duration (−0.62 [−0.95, −0.30]; −0.29 [−0.47, −0.10]) in allergic and non‐allergic rhinitis patients respectively. Benefit was less consistent for nasal congestion, postnasal drip, and sneezing symptoms. Reported adverse effects included nasal mucosa dryness or irritation, epistaxis, headaches, and pharyngitis, though comparison to placebo found significantly greater risk for epistaxis only (risk ratio [95% CI] = 2.19 [1.22, 3.93]). Conclusion Albeit treating other symptoms with less benefit, anticholinergic nasal sprays appear to be safe and efficacious in reducing rhinorrhea severity and duration in both rhinitis etiologies. This evidence supports their continued use in the treatment of rhinitis‐associated rhinorrhea. Level of Evidence 1 Laryngoscope, 133:722–731, 2023

No abstract

aged 18 to 59 years (Figure) (adjusted prevalence ratio [PR], 0.63 [95% CI, 0.44-0.90]; P= .009 for trend). This decline was not heterogeneous by age (P = .41 for interaction). Prevalence of nonvaccine-type oral HPV infections remained unchanged in unvaccinated men aged 18 to 59 years (8.6% in 2009-2010 vs 8.4% in 2015-2016; adjusted PR, 1.02 [95% CI, 0.79-1.33]; P = .66 for trend).In unvaccinated women aged 18 to 59 years, oral HPV prevalence remained unchanged for vaccine types (0.6% in 2009-2010 vs 0.5% in 2015-2016 adjusted PR, 0.96 [95% CI, 0.23-3.98]; P = .79 for trend) and for nonvaccine types (2.6% in 2009-2010 vs 3.3% in 2015-2016 adjusted PR, 1.29 [95% CI, 0.71-2.35]; P = .58 for trend) (Figure).

No abstract