Outcomes and risk factors for mortality in clostridioides difficile infection in patients with NAFLD and NASH.

INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH) and, ultimately, cirrhosis. Clostridioides difficile is the most common nosocomial cause of diarrhea and is associated with worse clinical outcomes in other liver diseases, including cirrhosis, but has not been extensively evaluated in concomitant NAFLD/NASH. MATERIALS AND METHODS: We conducted a retrospective cohort study using the National Inpatient Sample database from 2015 to 2017. Patients with a diagnosis of CDI, NAFLD, and NASH were identified using International Classification of Diseases (Tenth Revision) codes. The outcomes of our study include length of stay, hospitalization cost, mortality, and predictors of mortality. RESULTS: The CDI and NASH cohort had a higher degree of comorbidity burden and prevalence of peptic ulcer disease, congestive heart failure, diabetes mellitus, and cirrhosis. Patients with NASH and CDI had a significantly higher mortality rate compared to the CDI only cohort (mortality, 7.11 % vs. 6.36 %; P = 0.042). Patients with CDI and NASH were at increased risk for liver-related complications, acute kidney injury, and septic shock (P < 0.001) compared to patients with CDI only. Older age, intestinal complications, pneumonia, sepsis and septic shock, and liver failure conferred an increased risk of mortality among the CDI and NASH cohort. CONCLUSIONS: Patients with NASH had a higher rate of liver-related complications, progression to septic shock, and mortality rate following CDI infection compared to the CDI only cohort.

Bariatric Surgery Reduces Cancer Risk in Adults With Nonalcoholic Fatty Liver Disease and Severe Obesity.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and increased risk of cancer. The impacts of bariatric surgery on cancer risk in NAFLD patients are unknown. We investigated the effect of bariatric surgery on cancer risk in patients with NAFLD and severe obesity using the MarketScan database. METHODS: We conducted a retrospective cohort study of 18 to 64 years old newly diagnosed NAFLD patients with severe obesity between 2007 and 2017. We used Cox proportional hazard models to examine the association between bariatric surgery, modeled as a time-varying covariate, and the risks of any cancer and obesity-related cancer, while accounting for confounding using inverse probability of treatment weighting (IPTW). RESULTS: A total of 98,090 patients were included in the study, 33,435 (34.1%) received bariatric surgery. In those without surgery, 1898 incident cases of cancer occurred over 115,890.11 person-years of follow-up, compared with 925 cancer cases over 67,389.82 person-years among surgery patients (crude rate ratio, 0.84; 95% CI, 0.77- 0.91). The IPTW-adjusted risk of any cancer and obesity-related cancer was reduced by 18% (hazard ratio, 0.82; 95% CI, 0.76-0.89) and 25% (hazard ratio, 0.65; 95% CI, 0.56-0.75), respectively, in patients with versus without bariatric surgery. The adjusted risks of any cancer and obesity-related cancer were significantly lower in cirrhotic versus non-cirrhotic patients who underwent surgery. In cancer-specific models, bariatric surgery was associated with significant risk reductions for colorectal, pancreatic, endometrial, thyroid cancers, hepatocellular carcinoma, and multiple myeloma. CONCLUSION: Bariatric surgery was associated with significant reductions in the risks of any cancer and obesity-related cancer in NAFLD patients with severe obesity.

Drug-induced liver injury associated with antiseizure medications from the FDA Adverse Event Reporting System (FAERS).

PURPOSE: Treatment with antiseizure medications (ASMs) confers a risk of drug-induced liver injury (DILI), especially for older ASMs. We sought to quantify recent reports of DILI attributed to both older and newer generation ASMs and survey newly marketed ASMs for hepatotoxicity in a large post-marketing database. METHODS: We queried over 2.6 million adverse event reports made to the FDA Adverse Event Reporting System (FAERS) database between July 1, 2018 and March 31, 2020 for DILI due to ASMs commonly used in clinical practice. Patient characteristics and outcomes were assessed. We calculated the reporting odds ratio (ROR) of DILI for each individual ASM versus all non-ASM reports. RESULTS: A total of 2175 DILI cases were attributed to an ASM during the study period. 97.2% of these were designated as serious reactions, which include death, hospitalization, disability, and other life-threatening outcomes. A number of older and newer generation ASMs were associated with DILI, specifically: carbamazepine (ROR 2.92), phenobarbital (ROR 2.91), oxcarbazepine (ROR 2.58), phenytoin (ROR 2.40), valproate (ROR 2.22), lamotrigine (ROR 2.06), clobazam (ROR 1.67), levetiracetam (ROR 1.56), and diazepam (ROR 1.53). However, increased odds of DILI were not seen with zonisamide, perampanel, stiripentol, lacosamide, clonazepam, pregabalin, felbamate, eslicarbazepine, cannabidiol, topiramate, gabapentin, ethosuximide, brivaracetam, or primidone. Vigabatrin, tiagabine, and rufinamide all had zero reports of DILI. CONCLUSIONS: The majority of newer generation ASMs were not significantly associated with DILI. Future studies utilizing FAERS in conjunction with other data sources will be critical for the ongoing surveillance of DILI, particularly as newly marketed ASMs continue to enter into widespread clinical use.

The Microbiome and Hepatocellular Carcinoma.

The human microbiome is a vast and complex system encompassing all of the microbes and their genes that occupy the environmentally exposed surfaces of the human body. The gut microbiota and its associated microbiome play an integral role in mammalian metabolism and immune tolerance as well as in immunocompetence. Disruptions in the human gut microbiome are associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. The persistence of this inflammation has been shown to induce the accumulation of genetic and epigenetic changes leading to hepatocellular carcinoma (HCC). Therefore, the importance and prognostic influence of the gut microbiome on hepatocarcinogenesis has been increasingly studied in recent years. This review discusses the mechanisms by which imbalances in the gut microbiome disturb the gut-liver axis to impact hepatocarcinogenesis, including disruption of the intestinal barrier, changes in bile acid metabolism, and reduction in tumor-suppressing microRNA. Furthermore, this review summarizes recent advances in potential microbiome-based therapeutic opportunities in HCC.

Effect of Long-Term Mesalamine Therapy on Cancer-Associated Gene Expression in Colonic Mucosa of Patients with Ulcerative Colitis.

BACKGROUND: The role of 5-aminosalicylic acid (5-ASA or mesalamine) in the prevention of colorectal cancer in ulcerative colitis (UC) patients was reported, but the effect on molecular targets in UC colon mucosa is unknown. AIM: This observational study evaluates gene expression levels of 5-ASA targets using serial colon biopsy specimens from UC patients undergoing long-term 5-ASA therapy. METHODS: Transcript levels were compared between colonoscopic biopsy specimens collected from 62 patients at initial and final follow-up colonoscopy at 2-6 years. All patients had mild-to-moderate UC and were undergoing long-term 5-ASA maintenance. Stepwise multiple linear regression analyses were performed to correlate changes in transcript levels with therapeutic response (Mayo clinical score endoscopy and DAI and/or Nancy histopathology score) and nonclinical variables. RESULTS: The transcript levels of colorectal carcinogenesis-associated known 5-ASA target genes were significantly reduced after prolonged 5-ASA therapy (P < 0.005-0.03). Multiple linear regression models predicted significant association between transcript levels of Ki-67, NF-kB (p65), PPARγ, COX-2 and IL-8, CDC25A, and CXCL10 with duration of drug (5-ASA) exposure (P ≤ 0.05). Ki-67, NF-kB (p65), and CXCL10 transcripts were also correlated with reduced endoscopy sub-score (P ≤ 0.05). COX-2, IL-8, CDC25A, and TNF transcripts strongly correlated with DAI sub-scores (P ≤ 0.05). Only COX-2 and IL-8 transcript levels correlated (P ≤ 0.05) with Nancy histological score. CONCLUSION: This study provides molecular evidence of changes in carcinogenesis-related targets/pathways in colon tissue during long-term 5-ASA maintenance therapy that may contribute to the observed chemopreventive effects of 5-ASA in UC patients.

Barrett's metaplasia develops from cellular reprograming of esophageal squamous epithelium due to gastroesophageal reflux.

Gastroesophageal reflux disease (GERD) clinically predisposes to columnar Barrett's metaplasia (BM) in the distal esophagus. We demonstrate evidence supporting the cellular origin of BM from reprograming or transcommitment of resident normal esophageal squamous (NES) epithelial cells in response to acid and bile (A + B) exposure using an in vitro cell culture model. The hTERT-immortalized NES cell line NES-B10T was exposed 5 min/day to an A + B mixture for 30 wk. Morphological changes, mRNA, and protein expression levels for the inflammatory marker cyclooxygenase-2; the lineage-determining transcription factors TAp63 (squamous), CDX2, and SOX9 (both columnar); and the columnar lineage markers Villin, Muc-2, CK8, and mAb Das-1 (incomplete phenotype of intestinal metaplasia) were assessed every 10 wk. Markers of columnar lineage and inflammation increased progressively, while squamous lineage-determining transcriptional factors were significantly decreased both at the mRNA and/or protein level in the NES-B10T cells at/after A + B treatment for 30 wk. Distinct modifications in morphological features were only observed at/after 30 wk of A + B exposure. These changes acquired by the NES-B10T 30-wk cells were retained even after cessation of A + B exposure for at least 3 wk. This study provides evidence that chronic exposure to the physiological components of gastric refluxate leads to repression of the discernable squamous transcriptional factors and activation of latent columnar transcriptional factors. This reflects the alteration in lineage commitment of the precursor-like biphenotypic, NES-B10T cells in response to A + B exposure as the possible origin of BM from the resident NES cells.NEW & NOTEWORTHY This study provides evidence of the origins of Barrett's metaplasia from lineage transcommitment of resident esophageal cells after chronic exposure to gastroesophageal refluxate. The preterminal progenitor-like squamous cells alter their differentiation and develop biphenotypic characteristics, expressing markers of incomplete-type columnar metaplasia. Development of these biphenotypic precursors in vitro is a unique model to study pathogenesis of Barrett's metaplasia and esophageal adenocarcinoma.

The prevalence and impact of psychiatric comorbidities on hospitalized inflammatory bowel disease patients in the United States: insights from the National Inpatient Sample from 2009-2018.

Background: Patients with inflammatory bowel disease (IBD) are at increased risk of anxiety and mood disorders. This study examines the temporal trends and clinical impact of anxiety and mood disorder diagnoses in hospitalized IBD patients in the United States during a 10-year period. Methods: Using the National Inpatient Sample from 2009-2018, all IBD-related discharges in adults were analyzed. Primary outcomes were the prevalence and temporal trends of mood disorder and anxiety diagnoses for IBD-related admissions. The impact of the psychiatric comorbidities on clinical outcomes was also evaluated. Results: A total of 1,718,736 IBD-related discharged were identified. A diagnosis of anxiety or a mood disorder was found to have a prevalence of 16.44% and 18.97%, respectively, amongst IBD-related admissions. The prevalence of anxiety disorders amongst hospitalized IBD patients increased significantly (from 12.13% to 20.26%), whereas the prevalence of mood disorders did not (17.46% and 18.9%). IBD admissions with psychiatric comorbidities had lower rates of IBD-related complications or mortality during hospitalization compared to IBD admissions without comorbid psychiatric diagnoses. This population, however, was more likely to experience certain comorbidities such as Clostridioides difficile, pneumonia, and venous thromboembolism, as well as a longer hospitalization. Conclusions: The prevalence of comorbid anxiety among hospitalized IBD patients in the United States matches or exceeds the prevalence of anxiety in the general hospitalized population. Given its association with more in-hospital complications and a longer hospital stay, it is important to further understand how psychological screening and mental health services can improve the management of hospitalized IBD patients.

Surgery in Nonalcoholic Cirrhosis: Clinical Outcomes, Healthcare Utilization, and Cost Analysis.

BACKGROUND: Patients with cirrhosis are at increased risk of complications following surgery due to multiple factors, including portal hypertension and alterations in hemostasis. Improvements in perioperative management as well as risk stratification scores have helped improve outcomes, but gaps remain in our understanding of the cost and morbidity of cirrhotic patients who undergo surgery. METHODS: We conducted a case-control study using the IBM Electronic Health Record (EHR) MarketScan Commercial Claims (MSCC) database from January 1, 2007 to December 31, 2017. Nonalcoholic cirrhotic patients who underwent surgery were identified based on International Classification of Diseases, Ninth Revision (ICD-9)/Tenth Revision (ICD-10) codes for multiple surgical categories and matched with controls with cirrhosis who did not undergo surgery in this time period. A total of 115,512 patients were identified with cirrhosis, of whom 19,542 (16.92%) had surgery. Medical history and comorbidities were compiled, and outcomes in the six-month period following surgery were analyzed between matched groups. A cost analysis was performed based on claims data. RESULTS: Nonalcoholic cirrhotic patients who underwent surgery had a higher comorbidity index at baseline compared with controls (1.34 vs. 0.88, P<0.0001). Mortality was increased in the surgery group (4.68% vs. 2.38%, P<0.001) in the follow-up period. The surgical cohort had higher rates of adverse hepatic outcomes, including hepatic encephalopathy (5.00% vs. 2.50%, P<0.0001), spontaneous bacterial peritonitis (0.64% vs. 0.25%, P<0.001), and higher rates of septic shock (0.66% vs. 0.14%, P<0.001), intracerebral hemorrhage (0.49% vs. 0.04%, P<0.001), and acute hypoxemic respiratory failure (7.02% vs. 2.31%, P<0.001). Healthcare utilization analysis revealed increased total claims per patient in the surgical cohort (38.11 vs. 28.64, P<0.0001), higher inpatient admissions (6.05 vs. 2.35, P<0.0001), more outpatient visits (19.72 vs. 15.23, P<0.0001), and prescription claims per patient (11.76 vs. 10.61, P<0.0001) in the postsurgical period. The likelihood of at least one inpatient stay was higher in the surgical cohort (51.63% vs. 22.32%, P<0.0001), and inpatient stays were longer (4.99 days vs. 2.09 days, P<0.0001). The total cost of health services was significantly increased per patient in the postoperative period for patients undergoing surgery ($58,246 vs. $26,842, P<0.0001), largely due to increased inpatient costs ($34,446 vs. $10,789, P<0.0001). CONCLUSION: Nonalcoholic cirrhotics undergoing surgery experienced worse outcomes with respect to adverse hepatic events and complications, including septic shock and intracerebral hemorrhage. Claims and cost analysis showed a significant increase in health expenditure in the surgical group, largely due to the cost of more frequent and longer inpatient admissions.

Reduction in Gastrointestinal Cancers in Cirrhotic Patients Receiving Rifaximin vs Lactulose Only Therapy for Hepatic Encephalopathy.

Background Rifaximin and/or lactulose therapy is widely used in cirrhotic patients for the prevention and treatment of hepatic encephalopathy. The incidence of gastrointestinal cancers in these patients on lactulose, rifaximin, and/or combination therapy is unknown. We investigated the possible effect of lactulose and rifaximin on cancer risk in patients with cirrhosis using the MarketScan database. Methods A retrospective cohort study was conducted using the Truven Health MarketScan Commercial Claims databases from 2007-2017. An index date was defined for each participant as the earliest date of cirrhosis diagnosis. A baseline period for each participant was defined as the 12 months prior to the first medication date while the study follow-up period represented the period from the initiation of the medication to its cessation. ANOVA was used to compare all continuous measures of age and duration of medication. Wald Chi-square tests were performed to test the associations between the study groups. Results A total of 12,409 patients were included in our study. The rifaximin only cohort had the greatest reduction in risk of developing colon cancer, esophageal cancer, and stomach cancer compared to the other groups. Rifaximin reduced the risk of colon cancer and esophageal cancer by 59.42% and 70.37%, respectively, compared to patients taking lactulose only. Patients in the lactulose plus rifaximin cohort had the highest rate of development of pancreatic cancer (lactulose plus rifaximin vs rifaximin only vs lactulose only, 0.45% vs 0.24% vs 0.21%; P < 0.0001) and liver and intrahepatic bile duct cancers (11.73% vs 5.84% vs 5.49%; P < 0.0001). Conclusion Colon, esophageal, and gastric cancers had a marked incidence reduction in the rifaximin only cohort compared to the other cohorts studied.

Outcomes, Mortality, and Cost Burden of Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis.

BACKGROUND AND AIMS: Cirrhosis is associated with an increased risk of acute kidney injury (AKI) and hepatorenal syndrome (HRS). Healthcare utilization and cost burden of AKI and HRS in cirrhosis is unknown. We aimed to analyze the health care use and cost burden associated with AKI and HRS in patients with cirrhosis in the United States by using real-world claims data. METHODS: We conducted a case-control study using the Truven Health MarketScan Commercial Claims databases from 2007-2017. A total of 34,398 patients with cirrhosis with or without AKI and 4,364 patients with cirrhosis with or without HRS were identified using International Classification of Diseases, Ninth or Tenth Revision, codes and matched 1:1 by sociodemographic characteristics and comorbidities using propensity scores. Total and service-specific were quantified for the 12-months following versus the 12-months before the first date of AKI or HRS diagnosis and over 12-months following a randomly selected date for cirrhosis controls to capture entire disease burdens. RESULTS: The AKI and HRS group had a higher number of comorbidities and were associated with higher rates of readmission and mortality. The AKI and HRS groups had a significantly higher prevalence of ascites, spontaneous bacterial peritonitis (SBP), encephalopathy, gastrointestinal bleeding, septic shock, pulmonary edema, and respiratory failure. Compared to patients with cirrhosis only, AKI was associated with higher number of claims per person (AKI vs. cirrhosis only, 60.30 vs. 47.09; p<0.0001) and total annual median health care costs (AKI vs. cirrhosis only, $46,150 vs. $26,340; p<0.0001). Compared to patients with cirrhosis only, the HRS cohort was associated with a higher number of claims per person (HRS vs. cirrhosis only, 44.96 vs. 43.50; p<0.0009) and total annual median health care costs (HRS vs. cirrhosis only, $34,912 vs. $23,354; p<0.0001). Inpatient costs were higher than the control cohort for AKI (AKI vs. cirrhosis only, $72,720 vs. $29,111; p<0.0001) and HRS (HRS vs. cirrhosis only, $ 98,246 vs. $27,503; p<0.0001). Compared to the control cohort, AKI and HRS had a higher rate of inpatient admission, mean number of inpatient admissions, and mean total length of stay. CONCLUSIONS: AKI and HRS are associated with higher health care utilization and cost burden compared to cirrhosis alone, highlighting the importance for improved screening and treatment modalities.

Demographics and Outcomes Related to Wilson's Disease Patients: A Nationwide Inpatient Cohort Study.

Background and objective Wilson's disease (WD) is a rare autosomal recessive disease caused by mutations in the ATP7B gene, leading to impairment in copper excretion and subsequent accumulation primarily in the liver and brain. There is scarce data in the literature on the outcomes and cost burden of WD. In light of this, we aimed to assess outcomes, mortality rates, and costs associated with WD patients and their management in the United States (US). Methods We conducted a retrospective cohort study based on data in the National Inpatient Sample (NIS) database from 2007 to 2017. A total of 17,713 patients with a diagnosis of WD were identified using the International Classification of Diseases, Ninth or Tenth Revision (ICD-9/10) codes. Bivariate analyses were performed using t-tests for continuous variables and Pearson's chi-square tests for categorical variables, where two-sided p-values <0.05 were considered statistically significant. Results The majority of the 17,713 identified patients were female. The mean age of the WD cohort was 49 years. WD patients had a higher prevalence of Kayser-Fleischer rings, neuropsychiatric symptoms, and liver-related complications including acute hepatitis, liver failure, portal hypertension, and cirrhosis. Peptic ulcer disease, connective tissue disease, and hemolytic anemia were significantly more common in the WD cohort. Compared to the non-WD cohort, the WD cohort had a significantly higher mortality rate, longer length of stay (LOS), and increased hospitalization costs (p<0.0001). A higher proportion of patients who had undergone orthotopic liver transplantation (OLTx) were in the 18-34 and 35-44-year-old subgroups. On the contrary, the highest proportion of patients with WD who had not undergone OLTx were in the 55-89-year-old subgroup. WD patients who had undergone OLTx had a lower degree of comorbidities, decreased mortality rate, and shorter LOS (all p<0.0001) compared to WD patients who had not undergone OLTx. Conclusion Based on our findings, patients with WD had a higher LOS, mean hospitalization costs, and mortality rate compared to the non-WD cohort. Mortality rate and LOS were significantly lower in WD patients who had undergone OLTx.

Early-Onset Colorectal Cancer: Prevalence, Risk Factors, and Clinical Features Among Commercially Insured Adults in the United States.

BACKGROUND:  The incidence of colorectal cancer (CRC) in patients younger than 50 has been rising over the last several decades, accounting for up to 25% of total cases. Despite the screening age recently being lowered to 45, a significant proportion of cases would still arise at younger ages prior to screening. Nonfamilial early-onset CRC remains a particular concern. Identification of risk factors and clinical features in this age group is needed to improve detection. METHODS: In this retrospective cohort analysis using claims data from the Truven Health MarketScan® Commercial Claims insurance database from 2007 to 2017, patients were identified with colon and rectal cancer, compared across three age groups (ages 18-40, 40-50, and >50), and analyzed for risk factors and clinical features. RESULTS: Female sex was more prevalent in the younger age group compared to age >50 (54% and 51.9% vs. 49.6%), with little change noted between rectal cancer age groups by sex. A higher percentage of younger patients were in the obese age groups compared with older groups for colon cancer, particularly the morbidly obese with BMI >40 (24.94%, 25.75%, and 21.34% in the three age groups). Abdominal pain was a common presenting symptom identified in the age groups <50 compared with age >50 (25% and 19% vs. 14%), along with hematochezia, weight loss, and anemia. CONCLUSIONS: Morbid obesity and female sex may be important risk factors among patients with early-onset CRC. The presence of abdominal pain was more common among the early-onset CRC cohort.

Nonalcoholic Fatty Liver Disease in Lean/Nonobese and Obese Individuals: A Comprehensive Review on Prevalence, Pathogenesis, Clinical Outcomes, and Treatment.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, with an estimated prevalence of 25% globally. NAFLD is closely associated with metabolic syndrome, which are both becoming increasingly more common with increasing rates of insulin resistance, dyslipidemia, and hypertension. Although NAFLD is strongly associated with obesity, lean or nonobese NAFLD is a relatively new phenotype and occurs in patients without increased waist circumference and with or without visceral fat. Currently, there is limited literature comparing and illustrating the differences between lean/nonobese and obese NAFLD patients with regard to risk factors, pathophysiology, and clinical outcomes. In this review, we aim to define and further delineate different phenotypes of NAFLD and present a comprehensive review on the prevalence, incidence, risk factors, genetic predisposition, and pathophysiology. Furthermore, we discuss and compare the clinical outcomes, such as insulin resistance, dyslipidemia, hypertension, coronary artery disease, mortality, and progression to nonalcoholic steatohepatitis, among lean/nonobese and obese NAFLD patients. Finally, we summarize the most up to date current management of NAFLD, including lifestyle interventions, pharmacologic therapies, and surgical options.

The Spontaneous Regression of Primary Gastrointestinal Malignancies: An Observational Review.

The spontaneous regression or remission (SR) of cancer, often described as the partial or complete disappearance of a malignant tumor in the absence of all medical treatment and therapy, is a well-documented phenomenon. With efforts ongoing to establish cancer treatments that limit undesirable outcomes and adverse effects, these uncommon occurrences of SR carry significant implications for novel therapies and warrant further investigation. While several case studies have reported instances of SR in gastrointestinal (GI) malignancies, a comprehensive review of previous manifestations of SR in the GI tract remains lacking. The inclusion criteria for the rare phenomenon are also in need of an appropriate update that takes recent scientific advancements and emerging new medical technologies into account. Our analysis of 390 cases of SR in the GI tract focuses primarily on neoplasms of the hepatobiliary system and proposes an updated version of the older inclusion criteria for spontaneous regression.

Wilson's Disease: An Analysis of Health Care Use and Cost Burden of Commercially Insured Adults in the United States.

The economic and health care use burdens of Wilson's disease (WD) are unknown. In this study, we aimed to quantify this health care resource use and economic burden. We performed a retrospective case-control analysis of individuals in the Truven Health MarketScan Commercial Claims database (2007-2017). Using propensity scores, 424 WD cases were matched 1:1 to chronic liver disease (CLD) controls without WD. Total and service-specific parameters, expressed in monthly averages, were quantified for the 6-month pre-WD diagnosis versus the 12-month period after diagnosis. Wilcoxon signed-rank tests and McNemar tests were used to examine incremental differences in burden between cases and controls. Adjusted multivariable generalized linear regression models were used to compare health care burdens. Relative to the 6-month pre-WD diagnosis, the 12 months after diagnosis had more claims per patient (2.87 vs. 3.35; P < 0.0001) and increased per patient health care costs (US $2,089 vs. US $3,887; P < 0.0001). WD cases incurred US $1,908 more in total unadjusted costs compared to controls in the 12-month postindex date monthly averages. The increase in claims was primarily due to outpatient visits (1.62 vs. 1.82) and pharmaceutical claims (1.11 vs. 1.37). Cases also had higher health care costs for inpatient admissions (US $559 vs. US $1,264), outpatient visits (US $770 vs. US $1,037), and pharmaceutical claims (US $686 vs. US $1,489). Conclusion: WD is associated with significant health care cost and use burdens driven by increased inpatient admissions, outpatient visits, and pharmaceutical claims.

Association of Bariatric Surgery With Cardiovascular Outcomes in Adults With Severe Obesity and Nonalcoholic Fatty Liver Disease.

Importance: There are no approved treatments for nonalcoholic fatty liver disease (NAFLD) despite its association with obesity and increased risk of cardiovascular disease (CVD). Objective: To examine the association between bariatric surgery and CVD risk in individuals with severe obesity and NAFLD. Design, Setting, and Participants: This large, population-based retrospective cohort study obtained data from the MarketScan Commercial Claims and Encounters database from January 1, 2007, to December 31, 2017. Participants included insured adults aged 18 to 64 years with NAFLD and severe obesity (body mass index ≥40) without a history of bariatric surgery or CVD before NAFLD diagnosis. Baseline characteristics were balanced between individuals who underwent surgery (surgical group) and those who did not (nonsurgical group) using inverse probability of treatment weighting. Data were analyzed from March 2020 to April 2021. Exposures: Bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy, and other bariatric procedures) vs nonsurgical care. Main Outcomes and Measures: The main outcome was the incidence of cardiovascular events (primary or secondary composite CVD outcomes). The primary composite outcome included myocardial infarction, heart failure, or ischemic stroke, and the secondary composite outcome included secondary ischemic heart events, transient ischemic attack, secondary cerebrovascular events, arterial embolism and thrombosis, or atherosclerosis. Cox proportional hazards regression models with inverse probability treatment weighting were used to examine the associations between bariatric surgery, modeled as time varying, and all outcomes. Results: The study included 86 964 adults (mean [SD] age, 44.3 [10.9] years; 59 773 women [68.7%]). Of these individuals, 30 300 (34.8%) underwent bariatric surgery and 56 664 (65.2%) received nonsurgical care. All baseline covariates were balanced after applying inverse probability treatment weighting. In the surgical group, 1568 individuals experienced incident cardiovascular events compared with 7215 individuals in the nonsurgical group (incidence rate difference, 4.8 [95% CI, 4.5-5.0] per 100 person-years). At the end of the study, bariatric surgery was associated with a 49% lower risk of CVD (adjusted hazard ratio [aHR], 0.51; 95% CI, 0.48-0.54) compared with nonsurgical care. The risk of primary composite CVD outcomes was reduced by 47% (aHR, 0.53 [95% CI, 0.48-0.59), and the risk of secondary composite CVD outcomes decreased by 50% (aHR, 0.50; 95% CI, 0.46-0.53) in individuals with vs without surgery. Conclusions and Relevance: Results of this study suggest that, compared with nonsurgical care, bariatric surgery was associated with significant reduction in CVD risk in individuals with severe obesity and NAFLD.

Alterations of the fecal microbiota in relation to acute COVID-19 infection and recovery.

People with acute COVID-19 due to SARS-CoV-2 infection experience a range of symptoms, but major factors contributing to severe clinical outcomes remain to be understood. Emerging evidence suggests associations between the gut microbiome and the severity and progression of COVID-19. To better understand the host-microbiota interactions in acute COVID-19, we characterized the intestinal microbiome of patients with active SARS-CoV-2 infection in comparison to recovered patients and uninfected healthy controls. We performed 16S rRNA sequencing of stool samples collected between May 2020 and January 2021 from 20 COVID-19-positive patients, 20 COVID-19-recovered subjects and 20 healthy controls. COVID-19-positive patients had altered microbiome community characteristics compared to the recovered and control subjects, as assessed by both α- and ß-diversity differences. In COVID-19-positive patients, we observed depletion of Bacteroidaceae, Ruminococcaceae, and Lachnospiraceae, as well as decreased relative abundances of the genera Faecalibacterium, Adlercreutzia, and the Eubacterium brachy group. The enrichment of Prevotellaceae with COVID-19 infection continued after viral clearance; antibiotic use induced further gut microbiota perturbations in COVID-19-positive patients. In conclusion, we present evidence that acute COVID-19 induces gut microbiota dysbiosis with depletion of particular populations of commensal bacteria, a phenomenon heightened by antibiotic exposure, but the general effects do not persist post-recovery.

Evaluation of a U.S. National Cohort to Determine Utilization in Colectomy Rates for Ulcerative Colitis Among Ethnicities.

BACKGROUND: Colectomy is the curative management for ulcerative colitis (UC). Multiple studies have reported racial disparities for colectomy before the advent of anti-TNF alpha agents. The aim of this study was to describe racial and geographic differences in colectomy rates among hospitalized patients with UC after anti-TNF therapy was introduced. METHODS: We examined all patients discharged from the hospital between 2010 and 2014 with a primary diagnosis of UC or of complications of UC. The data were evaluated for race and colectomy rates among the hospitalized patients with UC. RESULTS: The unadjusted national colectomy rate among hospitalized patients with UC between 2010 and 2014 was 3.90 per 1000 hospitalization days (95% confidence interval, 3.72-4.08). The undajusted colectomy rates in African American (2.33 vs 4.35; P < 0.001) and Hispanic patients (3.99 vs 4.35; P ≤ 0.009) were considerably lower than those for White patients. After adjustment for confounders, the incidence rate ratio for African American as compared to White patients was 0.43 (95% confidence interval, 0.32-0.58; P < 0.001). Geographic region of the United States also showed significant variation in colectomy rates, with western regions having the highest rate (4.76 vs 3.20; P < 0.001). CONCLUSIONS: Racial and geographical disparities persist for the rate of colectomy among hospitalized patients with UC. The national database analysis reveals that colectomy rates for hospitalized African American and Hispanic patients were lower than those for White patients. Further studies are important to determine the social and biologic foundations of these disparities.

Effectiveness and safety of SARS-CoV-2 vaccine in Inflammatory Bowel Disease patients: a systematic review, meta-analysis and meta-regression.

INTRODUCTION: There are concerns regarding the effectiveness and safety of SARS-CoV-2 vaccine in inflammatory Bowel Disease (IBD) patients. This systematic review and meta-analysis comprehensively summarises the available literature regarding the safety and effectiveness of SARS-CoV-2 vaccine in IBD. METHODS: Three independent reviewers performed a comprehensive review of all original articles describing the response of SARS-CoV-2 vaccines in patients with IBD. Primary outcomes were (1) pooled seroconversion rate SARS-CoV-2 vaccination in IBD patients (2) comparison of breakthrough COVID-19 infection rate SARS-CoV-2 vaccination in IBD patients with control cohort and (3) pooled adverse event rate of SARS-CoV-2 vaccine. All outcomes were evaluated for one and two doses of SARS-CoV-2 vaccine. Meta-regression was performed. Probability of publication bias was assessed using funnel plots and with Egger's test. RESULTS: Twenty-one studies yielded a pooled seroconversion rate of 73.7% and 96.8% in IBD patients after one and two doses of SARS-CoV-2 vaccine respectively. Sub-group analysis revealed non-statistically significant differences between different immunosuppressive regimens for seroconversion. Meta-regression revealed that the vaccine type and study location independently influenced seroconversion rates. There was no statistically significant difference in breakthrough infection in IBD patients as compared to control after vaccination. CONCLUSION: In summary, the systematic review and meta-analysis suggest that SARS-CoV-2 vaccine is safe and effective in IBD patients.

Healthcare Utilization and Cost Burden of Porphyria in Commercially Insured Adults in the United States.

OBJECTIVES: The healthcare burden associated with porphyria remains unevaluated despite the associated increased risks of morbidity and mortality. We aimed to assess the healthcare utilization and cost burdens of porphyria in the United States (US) using real-world claims data. METHODS: We performed a case-control analysis of adults in the Truven Health MarketScan® Commercial Claims database (2010-2015). Using propensity scores, 2788 porphyria cases were matched 1:1 to porphyria-free controls with chronic liver disease. Total and service-specific parameters were quantified for the 12 months before porphyria diagnosis versus the 12 months after diagnosis and over the 12 months following a randomly selected date for controls. Wilcoxon signed rank tests and McNemar tests were used to examine incremental differences in burden between cases and controls. Adjusted multivariable generalized linear regression models were used to compare healthcare burdens for cases versus controls. RESULTS: Relative to the 12 months before porphyria diagnosis, the following 12 months had more claims per patient (35.94 vs 39.67; p < 0.0001) and increased per-patient healthcare costs (US$21,308 vs US$27,270; p < 0.0001). Porphyria cases incurred US$7839 more in total unadjusted costs compared with controls in the 12 months after index date. Compared with controls, cases also had more claims (39.67 vs 34.81), primarily due to inpatient admissions (1.80 vs 0.78) and outpatient visits (21.41 vs 17.98). Cases also had higher healthcare costs for inpatient admissions (US$8882 vs US$4674) and outpatient visits (US$12,378 vs US$9801). CONCLUSION: Porphyria is associated with significant healthcare costs and utilization burdens driven by increased inpatient admissions, outpatient visits, and pharmaceutical claims.