Tongue squamous cell carcinoma metastasis to percutaneous endoscopic gastrostomy site: A case report of an unusual cause of gastrointestinal bleeding.

Percutaneous endoscopic gastrostomy tubes are often placed in patients with head and neck malignancy for long-term nutritional support. Though rare, head and neck squamous cell carcinoma can metastasize to the percutaneous endoscopic gastrostomy tube site and may initially present as a developing mass or as bleeding at the percutaneous endoscopic gastrostomy site. Patients with head and neck squamous cell carcinoma should be evaluated diligently before and after percutaneous endoscopic gastrostomy placement in order to avoid this rare but life-threatening complication. We present a case of tongue squamous cell carcinoma that metastasized to the percutaneous endoscopic gastrostomy tube site causing gastrointestinal bleeding.

Refractory gastric ulcer bleeding responsive to long-term octreotide.

Upper gastrointestinal tract bleeding is a common condition that can cause hemodynamic instability and death if left untreated. Endoscopic hemostasis is often successful; however, some patients may develop refractory bleeding. Pharmacologic management with octreotide is beneficial in patients with variceal bleeding and has been shown in some studies to be effective in refractory bleeding due to angiodysplasia. There is a paucity of literature regarding the usage of long-term octreotide in refractory bleeding secondary to a peptic ulcer. We present a case of a bleeding gastric ulcer that was refractory to endoscopic management but responsive to long-term octreotide therapy.

Soaring rates of alcohol-related hepatitis in the latter phase of the COVID-19 pandemic: A new normal?

Background: Studies have reported that the COVID-19 pandemic has led to an increase in alcohol consumption and alcohol-associated health problems in the general population. Our previous study documented a rise in severe alcohol-related hepatitis cases requiring inpatient admission in our hospital system in the early pandemic (2019 vs. 2020). This study assesses the rates of severe alcohol-related hepatitis in the latter part of the pandemic (2021). Methods: We performed a retrospective chart review via an electronic medical record to evaluate the number of cases of alcohol-related hepatitis in patients presenting to three community hospitals in Fresno, California, between 2019 (pre-pandemic) and 2021. A total of 547 patients were included in the study. We compared the demographics, clinical course, and outcomes of patients with alcohol-related hepatitis pre-pandemic (2019), early pandemic (2020), and during the later phase of the pandemic (2021). Results: The number of cases increased from 131 in 2019 to 201 in 2020 and 215 in 2021 (53% and 64% increase, respectively). The number of young patients (age <40 years) increased from 30 in 2019 to 61 in 2020 and 71 in 2021 (103% and 136% increase, respectively) (p = 0.13). The number of admissions of women increased from 24 in 2019 to 55 in 2020 and 67 in 2021 (129% and 179% increase, respectively) (p = 0.026). Deaths during hospitalization increased from 20 in 2019 to 26 in 2021 (p = 0.674). The number of rehospitalizations within 3 months increased 4.5 times from 18 in 2019 to 80 in 2021 (p < 0.001). Conclusion: Our study revealed that the admissions for alcohol-related hepatitis remained significantly above the pre-pandemic levels through the end of 2021. We believe this sustained increase in cases of alcohol-related hepatitis in our hospital system reflects a much larger national problem. Alcohol-related hepatitis is associated with significant morbidity, mortality, and societal cost. Urgent public health interventions are needed at a national level to prevent this rise in cases from becoming a new normal.

The Pandemic Within the Pandemic: Unprecedented Rise in Alcohol-related Hepatitis During the COVID-19 Pandemic.

BACKGROUND AND AIM: The third leading preventable cause of death in the United States is excessive alcohol consumption. Our study sought to assess the impact of the coronavirus disease 2019 (COVID-19) on hospitalizations for alcohol-related hepatitis at a community hospital system. We hypothesized an increase in cases of alcohol-related hepatitis requiring inpatient management, mirroring the strain on economic and societal norms imposed by the COVID-19 pandemic. APPROACH/RESULTS: We performed a retrospective chart review to study the incidence of alcohol-related hepatitis in patients presenting to 3 community hospitals in Fresno, California, before and during the COVID-19. Data including patient demographics, markers of disease severity, and clinical course were extracted from electronic medical records for 329 patients included in the study. There was a 51% increase in the overall incidence of alcohol-related hepatitis requiring hospitalization between 2019 and 2020 (P=0.003) and 69% increase (P<0.001) after implementation of the stay-at-home orders. In addition, 94% (P=0.028) increase in rehospitalizations was noted in 2020 (P=0.028), a 100% increase in patients under the age of 40 (P=0.0028), as well as a trend towards a 125% increase (P=0.06) of female patients admitted with this diagnosis during the COVID-19 pandemic. CONCLUSIONS: Our study revealed drastic increases in severe alcohol-related hepatitis requiring inpatient management, specifically in patients under the age of 40 and in women during the COVID-19 pandemic. Given the high morbidity and mortality associated with severe alcohol-related hepatitis, these findings have far-reaching and lasting implications for our already strained health care system extending beyond the COVID-19 pandemic timeframe. Urgent public health interventions are needed to combat the rising misuse of alcohol and its consequences.

Relapse From Deep Remission After Therapeutic De-escalation in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: We conducted a systematic review and meta-analysis evaluating the relapse rate after therapeutic de-escalation in inflammatory bowel disease [IBD] patients who achieved deep remission [DR]. METHODS: We searched MEDLINE, EMBASE, and major gastroenterology conferences up to July 2019 for studies reporting relapse in adult patients with DR who subsequently underwent therapeutic de-escalation. Eligible studies defined DR as at least a combination of clinical remission and mucosal healing/endoscopic remission. The primary outcome was cumulative 1-year and 2-year relapse rates after therapeutic de-escalation. Secondary outcomes were relapse rates in ulcerative colitis [UC] and Crohn's disease [CD], relapse after anti-tumour necrosis factor-α [anti-TNFα] de-escalation, and the rate of disease response recapture following re-escalation. RESULTS: Thirteen studies encompassing 837 patients were identified. The cumulative relapse rate after therapeutic de-escalation was 28.7% within 1 year [12 studies], and 38.4% within 2 years [eight studies]. Relapse rates within 1 year and 2 years were comparable between UC [five studies; 25.4% and 37.4%] and CD [seven studies; 34.1% and 39.9%]. Ten studies reported de-escalation of anti-TNFα, of which 29.8% patients relapsed within 1 year and 41.4% within 2 years. Response recapture following re-escalation [eight studies] was 75.4%. CONCLUSIONS: Despite achieving deep remission, therapeutic de-escalation in this patient population is associated with significant relapse risk within 1 year and 2 years. This risk is more pronounced in patients requiring anti-TNFα for management, likely because of more severe disease. Similar rates of relapse were reported among UC and CD within these time periods. These findings suggest that combined clinical and endoscopic remission should not be an impetus to consider therapeutic de-escalation.

The IBD-associated long noncoding RNA IFNG-AS1 regulates the balance between inflammatory and anti-inflammatory cytokine production after T-cell stimulation.

The inflammatory bowel diseases (IBD) are a complex set of chronic gastrointestinal inflammatory conditions arising from the interplay of genetic and environmental factors. This study focuses on noncoding RNA transcripts as potential mediators of IBD pathophysiology. One particular gene, interferon γ-antisense 1 (IFNG-AS1), has been consistently observed to be elevated in the intestinal mucosa of patients with actively inflamed IBD versus healthy controls. This study builds on these observations, demonstrating that the second splice variant is specifically altered, and this alteration even stratifies within inflamed patients. With the use of a CRISPR-based overexpression system, IFNG-AS1 was selectively overexpressed directly from its genomic loci in T cells. An unbiased mRNA array on these cells identified a large increase in many inflammatory cytokines and a decrease in anti-inflammatory cytokines after IFNG-AS1 overexpression. Media from T cells overexpressing IFNG-AS1 elicited an inflammatory signaling cascade in primary human peripheral blood mononuclear cells, suggesting the potential functional importance of IFNG-AS1 in IBD pathophysiology. The significance of these results is amplified by studies suggesting that a single-nucleotide polymorphism in IFNG-AS1, rs7134599, was associated with both subtypes of patients with IBD independently of race.NEW & NOTEWORTHY Long noncoding RNAs are an emerging field of inflammatory bowel disease (IBD) research. This study mechanistically analyzes the role of a commonly upregulated gene in IBD and shows IFNG-AS1 as a mediator of an inflammatory signaling cascade.

Identification of functional missense single-nucleotide polymorphisms in TNFAIP3 in a predominantly Hispanic population.

Background: Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) is a multifunctional ubiquitin binding and editing enzyme that regulates inflammation. Genetic studies have implicated polymorphisms within the TNFAIP3 locus to the development of numerous immune-related diseases. This study evaluated the frequencies of single nucleotide polymorphism (SNPs) within the exonic regions of the TNFAIP3 gene and an associated point mutation from the Illumina array among a predominantly Hispanic cohort. Methods: Genomic DNA was obtained from 721 participants and sequencing of all TNFAIP3 exons and an intergenic point mutation (rs6920220) was performed. In vitro functional assessment was performed by transfecting mutated TNFAIP3 constructs into TNFAIP3 knockout cells containing the NF-kB luciferase reporter and stimulating with TNFα. Comparative statistics were performed with Student's t-test for continuous variables and Chi-squared test for categorical variables. Results: Sequencing revealed two missense SNPs, rs146534657:A>G and rs2230926:T>G, both within exon 3 of TNFAIP3, which encodes the protein's deubiquitinating enzymatic domain. Frequencies of all three point mutations differed significantly across racial groups (χ2-test, P=0.014 to P<0.001). Compared to Caucasians, rs146534657:A>G was overrepresented among Hispanics (odds ratio (OR) [95% CI] 4.05 [1.24-13.18]), and rs2230926:T>G was more prevalent among African Americans (OR [95% CI] 3.65 [1.58-8.43]). In vitro assays confirm rs146534657:A>G and rs2230926:T>G decrease the ability of TNFAIP3 to abrogate NF-κB activation by 2-fold (P<0.01) and 1.7-fold (P<0.01), respectively. Conclusions: This study reports the frequency of rs146534657:A>G among Hispanics and is the first to evaluate its potential physiologic impact, establishing a basis for future research as a potential biomarker among this population.