Efficacy and Safety of Vedolizumab and Tumor Necrosis Factor Inhibitors in the Treatment of Steroid-refractory Microscopic Colitis: A Systematic Review and Meta-analysis.

BACKGROUND: Tumor necrosis factor (TNF-α) inhibitors and the α4ß7 integrin antagonist, vedolizumab, have been investigated as treatment options for patients with steroid-refractory microscopic colitis. AIMS: To evaluate the benefit of vedolizumab and TNF-α inhibitors in patients with steroid-refractory microscopic colitis. METHODS: Retrospective studies and case series involving patients with steroid-refractory MC who either received vedolizumab, adalimumab, or infliximab were eligible for inclusion. Pooled proportional meta-analyses were used to calculate the rate of clinical remission at induction, clinical response, maintenance of remission, histologic remission, and overall medication related adverse effects. Statistical analysis was performed in R using the metafor and meta packages. RESULTS: A total of 14 studies involving 164 patients were included. Pooled analysis showed a clinical remission rate of 63.5% [95% CI (0.483; 0.776), I2=43% P=0.08], 57.8% [95% CI (0.3895; 0.7571), I2=0%, P=0.7541], and 39.3% [95% CI (0.0814; 0.7492), I2=66%, P=0.02] for vedolizumab, infliximab, and adalimumab, respectively. The maintenance of remission rates were 65.9% [95% CI (0.389; 0.889), I2=67%, P=0.02], 45.3% [95% CI (0.1479; 0.7747), I2=0%, P=0.36] and 32.5% [95% CI (0.000; 0.8508), I2=53%, P=0.14] in patients who received vedolizumab, infliximab, and adalimumab, respectively. Rate of biological-related adverse events warranting discontinuation of therapy was 12.2%, 32.9%, and 23.0% for the vedolizumab, infliximab, and adalimumab groups, respectively. CONCLUSION: Vedolizumab and anti-TNF-α agents demonstrated a clinical benefit in the treatment of steroid-refractory microscopic colitis and with a tolerable safety profile. Future randomized controlled trials are needed to compare vedolizumab with TNF-α inhibitors and examine treatment effect on patients' quality of life.

Association between obstructive sleep apnea and gastroesophageal reflux disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: We aim to conduct a systematic review and determine the association between obstructive sleep apnea (OSA) and gastroesophageal reflux disease (GERD). METHODS: Literature search for eligible studies was performed across major databases. The main endpoint was to assess the association between GERD and OSA. Subgroup analyses were performed to determine this strength of the association stratified by the diagnostic tools used for OSA (nocturnal polysomnogram or Berlin questionnaire) and GERD (validated reflux questionnaire or esophagogastroduodenoscopy). We also compared sleep efficiency, apnea hypopnea index, oxygen desaturation index, and Epworth Sleepiness Scale in OSA patients with or without GERD. Results were pooled together using Reviewer Manager 5.4. RESULTS: Six studies involving 2950 patients with either GERD or OSA were included in the pooled analysis. Our findings suggest that there was a statistically significant unidirectional association between GERD and OSA (odds ratio [OR] = 1.53, P = 0.0001). Subgroup analyses redemonstrated an OSA-GERD association irrespective of the tools used for diagnosing either GERD or OSA (P = 0.24 and P = 0.82, respectively). Sensitivity analyses demonstrated the same association after controlling for gender (OR = 1.63), BMI (OR = 1.81), smoking (OR = 1.45), and alcohol consumption (OR = 1.79). In patients with OSA, there were no statistically significant differences between patients with or without GERD in terms of apnea hypopnea index (P = 0.30), sleep efficiency (P = 0.67), oxygen desaturation index (P = 0.39), and Epworth Sleepiness Scale (P = 0.07). CONCLUSION: There exists an association between OSA and GERD that is independent of the modalities used for screening or diagnosing both disorders. However, the presence of GERD did not affect the severity of OSA.

Combination Topical Epinephrine and Non-steroidal Inflammatory Drugs in the Prevention of Post-ERCP Pancreatitis: A Systematic Review.

BACKGROUND: The utility of combination rectal NSAID and topical epinephrine (EI) or rectal NSAID and normal saline (SI) sprayed on duodenal papilla in the prevention of post-ERCP pancreatitis (PEP) has been studied but results have been conflicting. AIMS: To evaluate the benefit of using combination prophylaxis in preventing PEP. METHODS: A literature search was performed using Scopus, PubMed/MEDLINE, and Cochrane databases in May 2021. Randomized controlled trials (RCTs) involving adults patients who underwent ERCP and received EI versus SI were eligible for inclusion. The pooled effect was expressed as odds ratio (OR) to assess the rate of PEP, severity of PEP, and specific adverse events. The results were pooled using Reviewer Manager 5.4 software. RESULTS: Six RCTs involving 4016 patients were included in the final analysis. The EI group did not demonstrate any significant benefit over SI group in preventing PEP (OR = 1.00, 95% CI [0.68, 1.45], P = 0.98), irrespective of gender or the epinephrine concentration used. The tests for subgroup differences were not statistically significant with P-values of 0.66 and 0.28, respectively. The addition of topical epinephrine to rectal NSAID did not improve the rate of moderate to severe PEP (OR = 0.94, P = 0.86) or PEP in high-risk patients (OR = 1.14, 95%, P = 0.73). The rates of infection, including cholangitis and sepsis (OR = 0.63, P = 0.07), gastrointestinal bleeding (OR = 1.25, P = 0.56) and procedure-related death (OR = 0.71, P = 0.59) were similar between both groups. CONCLUSION: The addition of topical epinephrine did not demonstrate any benefit over rectal NSAID alone in preventing PEP or reducing other procedure-related adverse events.

Efficacy of Fecal Microbiota Transplantation in the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.

BACKGROUND: Fecal microbiota transplantation (FMT) has been investigated as a treatment option for patients with inflammatory bowel disease with controversial results.We sought to perform a systematic review and meta-analysis to evaluate the benefit of FMT in patients with ulcerative colitis. METHODS: Double-blind randomized controlled trials (RCTs) including adult patients with active ulcerative colitis who received either FMT or placebo were eligible for inclusion. Outcomes of interest included the rate of combined clinical and endoscopic remission, endoscopic remission or response, clinical remission or response, and specific adverse events. The results were pooled together using Reviewer Manager 5.4 software. Publication bias was assessed using the Egger's test. RESULTS: Six RCTs involving 324 patients were included. Our findings demonstrate that compared with placebo, FMT has significant benefit in inducing combined clinical and endoscopic remission (odds ratio, 4.11; 95% confidence interval, 2.19-7.72; P < .0001). Subgroup analyses of influencing factors showed no differences between pooled or single stool donors (P = .71), fresh or frozen FMT (P = .35), and different routes or frequencies of delivery (P = .80 and .48, respectively). Pre-FMT antibiotics, bowel lavage, concomitant biologic therapy, and topical rectal therapy did not affect combined remission rates (P values of .47, .38, .28, and .40, respectively). Clinical remission or response and endoscopic remission or response were significantly higher in patients who received FMT compared with placebo (P < .05) without any differences in serious or specific adverse events. CONCLUSIONS: FMT demonstrated a clinical and endoscopic benefit in the short-term treatment of active ulcerative colitis, with a comparable safety profile to placebo. Future RCTs are required to standardize study protocols and examine data on maintenance therapy.

Our systematic review of double-blind randomized controlled trials demonstrates that fecal microbiota transplantation is effective in inducing short-term clinical and endoscopic remission in adult patients with active ulcerative colitis and with a similar safety profile as compared with placebo.

Effect of Hormonal Replacement Therapy on Gastroesophageal Reflux Disease and its Complications in Postmenopausal Women.

Female hormones and hormone replacement therapy (HRT) are thought to play a role in gastroesophageal reflux disease (GERD). Pregnancy, menopause, and HRT have all been reported as risk factors for GERD.1-6 It has been suggested that estrogen and progesterone confer their effect on the gastrointestinal tract by increasing nitric oxide synthesis, a muscle relaxant which decreases smooth muscle tone of the lower esophageal sphincter and esophageal body predisposing patients to gastroesophageal reflux.6-8 However, the exact mechanism that these hormones play in GERD remains to be elucidated because menopause, which is a risk factor for GERD, is associated with a decrease in estrogen and progesterone levels. Thus the exact relationship between the different hormonal therapies and GERD remains unclear. The aim of this study was to determine the role and possible risk that estrogen and progesterone HRT pose for the development of GERD in postmenopausal women. In addition, we aimed to assess the relationship between HRT in postmenopausal women and GERD complications, such as esophageal stricture and Barrett's esophagus.

Diagnostic Accuracy of the Proton Pump Inhibitor Test in Gastroesophageal Reflux Disease and Noncardiac Chest Pain: A Systematic Review and Meta-analysis.

BACKGROUND: Response to a trial of proton pump inhibitors (PPIs) is currently accepted as a first step in the management of gastroesophageal reflux disease (GERD). However, information on the diagnostic performance of the PPI test is limited. AIM: The aim of this study was to determine the diagnostic accuracy of the PPI test in GERD and noncardiac chest pain (NCCP) and to assess the test performance in erosive reflux disease (ERD) and nonerosive reflux disease (NERD). METHODS: Web of Science, Cochrane Controlled Register of Trials (CENTRAL), and MEDLINE were searched for studies reporting the diagnostic accuracy of the PPI test in adult patients with typical GERD and NCCP who underwent evaluation using an accepted reference standard, from January 1, 1950, through February 1, 2021. Subgroup analyses were performed, and the risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS: Nineteen studies (GERD=11, NCCP=8) involving 1691 patients were included. In GERD, the PPI test had 79% pooled sensitivity [95% confidence interval (CI), 72%-84%], and 45% pooled specificity (95% CI, 40%-49%). In NCCP, pooled sensitivity and specificity were 79% (95% CI, 69%-86%) and 79% (95% CI, 69%-86%), respectively. In ERD, the PPI test had 76% pooled sensitivity (95% CI, 66%-84%) and 30% pooled specificity (95% CI, 8%-67%). In NERD, the PPI test had 79% pooled sensitivity (95% CI, 70%-86%) and 50% pooled specificity (95% CI, 39%-61%). CONCLUSIONS: The PPI test was sensitive in GERD but with suboptimal specificity. The test performed better in GERD-related NCCP. Diagnostic accuracy was comparable in ERD and NERD.

Small Bowel Adenocarcinoma: a Nationwide Population-Based Study.

PURPOSE: Small intestinal cancers have a non-specific clinical presentation and hence a delayed diagnosis. The prevalence of small intestinal cancers is low, and there are no cost-effective methods of screening. This study aimed to identify clinical characteristics of duodenal and jejunal adenocarcinomas that can assist in the early detection and diagnosis of disease. METHODS: Duodenal adenocarcinoma and jejunal adenocarcinoma in Explorys database (1999-2019) were compared using odds ratio (OR) with 95% confidence intervals. Data on demographic characteristics, risk factors, clinical features, and treatment were collected. RESULTS: Out of a total of 8100 patients with a diagnosis of primary adenocarcinoma of the small intestine, 5110 are primary adenocarcinoma of duodenum (63%), and 600 are primary adenocarcinoma of jejunum (7.4%). Patients with jejunal adenocarcinoma when compared with patients with duodenal adenocarcinoma are more obese (OR, 1.36) and have a significantly higher prevalence of malignant neoplasm of colon (OR, 3.07), Crohn's disease (OR, 4.42), and celiac disease (OR, 2.48). Jejunal adenocarcinoma patients presented more frequently with intestinal obstruction (OR, 1.99), whereas duodenal adenocarcinoma patients more commonly presented with iron deficiency anemia (OR, 0.16). Patients with jejunal adenocarcinoma are less likely to undergo therapy with anti-neoplastic agents when compared with duodenal adenocarcinoma (OR, 0.81). There are no differences in patients undergoing surgical intervention or a combination of surgical intervention and antineoplastic therapy. CONCLUSIONS: Jejunal adenocarcinoma is more commonly associated with colorectal cancer, celiac disease, and Crohn's disease. They also had lower odds of requiring chemotherapeutic agents.

Quantifying risk factors for microscopic colitis: A nationwide, retrospective cohort study.

BACKGROUND: Microscopic colitis (MC) is associated with several risk factors; however, their relative risk has been variable and not thoroughly evaluated. We aimed to quantify the risk of medical comorbidities and medications associated with MC and treatment offered to these patients. METHODS: A population-based retrospective analysis in International Business Machines (IBM) Explorys (1999-2018), a pooled, de-identified database of 63 million patients in the USA, was performed. Odds ratios (OR) were calculated between MC and other diseases/medications. MC patients were also stratified by age to assess trends of MC in different age groups. RESULTS: A total of 1130 patients had MC in the database. Among medications, non-steroidal anti-inflammatory agents (OR, 20.2) and proton pump inhibitors (OR, 12.1) were associated with highest odds of MC. Among medical comorbidities, infectious gastroenteritis (OR, 26.6) and celiac disease (OR, 22.5) had the highest odds of being associated with MC. Tobacco smoking, psoriasis, Sjogren's syndrome, Clostridium difficile infection, and malabsorption syndromes all conferred odds greater than 10. CONCLUSION: Early identification of MC is critical for minimizing morbidity and mortality. Epidemiologic information can be integrated with current clinical algorithms to more rapidly identify patients at risk.

New-onset depression after colorectal cancer diagnosis: a population-based longitudinal study.

INTRODUCTION: To date, no large studies examining the temporal relationship between colorectal cancer (CRC) and the subsequent development of depressive disorders exist. We aimed to assess the incidence of depression post-colorectal cancer (CRC) diagnosis. METHODS: To conduct this longitudinal study, we searched the large US population-based database, Explorys (IBM), from January 1, 1999, to January 1, 2021. We investigated new-onset depression and its associated mortality as well as the role of the mental health provider post-CRC diagnosis. Confidence intervals were calculated for all outcomes and multivariate regression analysis was performed. RESULTS: Incident depression post-CRC diagnosis was 20.8 vs 8.9 per 100 person-years [OR 3.46, p < 0.0001] in the general population and conferred a 123% increased risk of all-cause mortality [P < 0.0001]. Male patients (OR: 1.89) were more likely to become depressed post-CRC diagnosis as compared to females. Moreover, the absolute number of male patients with post-CRC depression was significantly higher than that of females (68% vs 32%; P < 0.0001). In addition, depression after CRC was more common among Whites (OR: 1.68) and patients aged > 65 years (OR: 5.17). Referral to a mental health provider resulted in significantly lower all-cause mortality (3.6% vs 26.9%; p < 0.0001). DISCUSSION: Our findings advocate for initiating depression screening for high-risk patients post-CRC diagnosis and prompt mental health provider referral.

Impact of inflammatory bowel disease on hospital outcomes in acute ischemic stroke: a nationwide cohort study.

PURPOSE: Patients with inflammatory bowel disease (IBD) have an increased risk of venous thrombotic events. The impact IBD has on arterial thrombosis is not well characterized. We aimed to identify the impact of IBD on hospital outcomes in patients admitted for acute ischemic stroke (AIS). METHODS: This is a retrospective cohort study utilizing the 2017 National Inpatient Sample. We identified all adult patients with a principal diagnosis of AIS and compared those with a concurrent diagnosis of IBD to those without-subgrouped by ulcerative colitis (UC) and Crohn's disease (CD). Outcomes were mortality and healthcare usage among IBD patients with AIS. Multivariate analysis was used to control for confounders. Analyses were performed using STATA. RESULTS: Five hundred twenty-four thousand and forty-five patients were admitted for AIS in 2017; of them 2200 (0.41%) had a concurrent diagnosis of IBD. The presence of IBD did not significantly affect in-hospital mortality (4.09% vs. 4.01%) among patients admitted for AIS [OR 1.07 95% CI: 0.65-1.76], with similar findings upon subgroup analysis of UC [OR 0.91, 95% CI: 0.39-2.09] and CD [OR 1.17, 95% CI: 0.62-2.19]. Mean hospital length of stay and charges/costs in AIS were similar irrespective of IBD. CONCLUSIONS: UC and CD do not appear to be associated with a higher risk of mortality or increased healthcare usage in AIS. AIS risk assessment in patients with IBD is important but should be done in a similar fashion to the general population.

The incidence of COVID-19 in patients with metabolic syndrome and non-alcoholic steatohepatitis: A population-based study.

BACKGROUND: The novel coronavirus disease (COVID-19) emerged from China in 2019 and rapidly spread worldwide. Patients with metabolic comorbid conditions are more susceptible to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Metabolic syndrome is a constellation of interlinked metabolic risk factors that predispose patients to increased risk of complications. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and non-alcoholic steatohepatitis (NASH) is the aggressive form of NAFLD. OBJECTIVE: The aim of this study is to determine the relationship between metabolic syndrome components and the risk of COVID-19. METHODS: We reviewed data from a large commercial database (Explorys IBM) that aggregates electronic health records from 26 large nationwide healthcare systems. Using systemized nomenclature of clinical medical terms (SNOMED-CT), we identified adults with the diagnosis of metabolic syndrome and its individual components from 1999 to 2019. We included patients with the diagnosis of COVID-19 from December 2019 to May 2020. Comorbidities known to be associated with COVID-19 and metabolic syndrome such as obesity, diabetes mellitus, dyslipidemia, smoking, male gender, African American, and hypertension were collected. Univariable and multivariable analyses were performed to investigate whether metabolic syndrome or its individual components are independently associated with the risk of COVID-19. RESULTS: Out of 61.4 million active adult patients in the database, 8885 (0.01%) had documented COVID-19. The cumulative incidence of COVID-19 was higher if metabolic syndrome was the primary diagnosis (0.10% vs 0.01%, OR 7.00 [6.11-8.01]). The adjusted odds (aOR) of having COVID-19 was higher in patients if they were African Americans (aOR 7.45 [7.14-7.77]), hypertensive (aOR 2.53 [2.40-2.68]), obese (aOR 2.20 [2.10-2.32]), diabetic (aOR 1.41 [1.33-1.48]), hyperlipidemic (aOR 1.70 [1.56-1.74]), or diagnosed with NASH (aOR 4.93 [4.06-6.00]). There was a slight decrease in the adjusted odds of having COVID-19 in males as compared to females (aOR 0.88 [0.84-0.92]). CONCLUSION: The incidence of COVID-19 in patients with metabolic syndrome is high. Among all comorbid metabolic conditions, NASH had the strongest association with COVID-19.

Non-alcoholic steatohepatitis and the risk of myocardial infarction: A population-based national study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a systemic disease with bidirectional relationships with cardiovascular disease (CVD). Non-alcoholic steatohepatitis (NASH) is a more severe subtype of NAFLD. Patients with NASH exhibit more intra and extrahepatic inflammation, procoagulant imbalances and proatherogenic lipid profiles. Whether NASH increases the risk of ischemic heart disease is currently unclear. AIM: To investigate the relationship between acute myocardial infarction (MI) and NASH in a large cohort of subjects in the United States. METHODS: We reviewed data from a large commercial database (Explorys IBM) that aggregates electronic health records from 26 large nationwide healthcare systems. Using systemized nomenclature of clinical medical terms (SNOMED CT), we identified adult with the diagnosis of NASH from 1999-2019. We included patients with the diagnosis of acute MI from 2018-2019. Comorbidities known to be associated with NASH and MI such as obesity, diabetes mellitus, hyperlipidemia, smoking, male gender, and hypertension were collected. Univariable and multivariable analyses were performed to investigate whether NASH is independently associated with the risk of MI. RESULTS: Out of 55099280 patients, 43170 were diagnosed with NASH (0.08%) and 107000 (0.194%) had a MI within 2018-2019. After adjusting for traditional risk factors, NASH conferred greater odds of MI odds ratio (OR) 1.5 [95% confidence interval (CI): 1.40-1.62]. Hyperlipidemia had the strongest association with MI OR 8.39 (95%CI: 8.21-8.58) followed by hypertension OR 3.11 (95%CI: 3.05-3.17) and smoking OR 2.83 (95%CI: 2.79-2.87). NASH had a similar association with MI as the following traditional risk factors like age above 65 years OR 1.47 (95%CI: 1.45-1.49), male gender OR 1.53 (95%CI: 1.51-1.55) diabetes mellitus OR 1.89 (95%CI: 1.86-1.91). CONCLUSION: MI appears to be a prevalent disease in NASH. Patients with NASH may need early identification and aggressive cardiovascular risk modification.

FIB-4 Regression With Direct-Acting Antiviral Therapy in Patients With Hepatitis C Infection: A Safety-Net Hospital Experience.

Background: Liver fibrosis stage determines the risk of morbidity and mortality from chronic hepatitis C virus (HCV) infection. The majority of HCV-infected patients are underserved and have other comorbid conditions that lead to more progressive liver disease such as cirrhosis and hepatocellular carcinoma. Safety net hospitals are the prime location to treat these patients. Direct acting antiviral (DAA) agents are highly effective in virus eradication. Aim: We aimed to evaluate the effect of treatment with DAAs on FIB-4 index. Methods: We identified 343 patients who initiated HCV treatment with DAAs from 2016 to 2018 and achieved a sustained virologic response (SVR) in Metrohealth Medical Center, a safety net hospital system. We compared the severity of hepatic fibrosis before and 1 year after SVR was attained. We evaluated whether the presence of other comorbid conditions influenced liver fibrosis regression. All analyses were performed using SAS software. Results: There was a statistically significant drop in mean FIB-4 score from baseline to post-SVR (3.47 ± 2.84 vs. 2.28 ± 1.60, P < 0.001). One hundred seventeen patients had baseline FIB-4 scores ≥3.25, 56% had FIB-4 scores <3.25 after SVR. Alcohol use disorder was associated with a higher baseline FIB-4 score compared to low level drinking (3.85 ± 0.20 vs. 3.15 ± 0.16). These patients showed greater improvement in FIB-4 scores after treatment when compared to those without alcohol use disorder (1.44 ± 0.15 vs. 0.97 ± 0.13, P = 0.02). Conclusion: FIB-4 index is a useful non-invasive tool for monitoring fibrosis regression after antiviral therapy. Patients with a history of alcohol abuse had the greatest reduction in FIB-4 score post-SVR.

Endoscopic Management of Ganglioneuroma in the Stomach.

Ganglioneuromas are rare benign tumors of neuroblastic origin that can occur anywhere along the sympathetic chain. They are rarely found in the gastrointestinal tract and can appear as solitary polypoid lesions or diffuse as part of a familial syndrome. They are often asymptomatic but may present with nonspecific symptoms depending on their anatomic location. They have no special endoscopic appearance and are diagnosed by histology and immunohistochemistry staining. We present a case of solitary gastric ganglioneuroma treated successfully with endoscopic resection.

Isolated colonic neurofibroma, a rare tumor: A case report and review of literature.

BACKGROUND: Neurofibromas are tumors comprised of peripheral nerve sheath and connective tissue components. They can occur sporadically or as part of familial syndromes such as neurofibromatosis type 1. Isolated colonic neurofibroma without systemic manifestations is a rarely reported clinical entity. Here we present a case of a 51 years old male with an isolated colonic neurofibroma seen on a screening colonoscopy. CASE SUMMARY: Fifty-one years old male who was otherwise healthy without a significant family history of cancer underwent a screening colonoscopy and was found have a 2.3 cm × 1.4 cm lesion in the colon. Tissue biopsy revealed a spindle cell tumor. Magnetic resonance imaging of the pelvis was negative for adenopathy. He underwent an endoscopic ultrasound that showed an ill-defined avascular lesion of mixed echogenicity measuring 2.8 cm × 15.2 cm in the submucosa with no communication with muscularis mucosa or propria. Immunohistochemistry staining of the tumor was strongly positive for S100, with rare penetrating axons deep within the tumor. Tumor cells were negative for c-kit and desmin and had low Ki-67 index. These findings were consistent with a solitary colonic submucosal neurofibroma. A detailed history and physical examination did not reveal any evidence of extraintestinal neurofibromatosis. He underwent transanal surgical resection of the tumor. The patient tolerated the procedure well without any complications. CONCLUSION: While neurofibromas have been well described in literature, an isolated colonic neurofibroma is a rare pathological entity. Malignant transformation of neurofibromas has been reported in patients with neurofibromatosis syndromes. We report a case of isolated colonic neurofibroma and highlight the importance of resection due to the increased risk of tumorigenesis.