The Effects of Gluten-free Diet on Body Mass Indexes in Adults with Celiac Disease: A Systematic Review and Meta-analysis of Observational Studies.

GOALS AND BACKGROUND: Gluten-free diet (GFD) includes a higher intake of sugars and fats. Previous studies have investigated its effect on body mass index (BMI) in celiac disease (CD) patients but had contradictive conclusions. Thus, we conducted a systematic review and meta-analysis examining the effect of GFD on BMI in CD patients. STUDY: Systematically, we conducted literature research using Medline, Scopus, and Embase, and we identified 1565 potential studies/abstracts. Only studies of patients with CD under a GFD with recorded BMI before and after dietary intervention were included. Subgroup analyses based on study design and BMI categories were performed. We calculated the pooled odds ratios (ORs) and 95% confidence intervals (Cls) for the number of patients in each BMI group according to the World Health Organization (WHO) definitions after GFD using fixed and random effect meta-analysis. RESULTS: The analysis included 10 studies and 38 sub-studies/data sets, which encompassed 2450 patients from 5 countries. We found nonsignificant odds for changing the BMI group (pooled OR 0.972, 95% CI: 0.858-1.101, P=0.65) after GFD. However, looking specifically at BMI subgroups, we found higher odds for BMI category change after GFD in underweight patients (OR 0.588, 95% CI: 0.479-0.723, P <0.001), and overweight patients,25

Dysplasia detection rates under a surveillance program in a tertiary referral center for inflammatory bowel diseases: Real-world data.

BACKGROUND AND AIMS: Surveillance colonoscopies are crucial for high-risk patients with inflammatory bowel diseases (IBD) to detect colorectal carcinoma (CRC). However, there is no established quality metric for dysplasia detection rate (DDR) in IBD surveillance. This study assessed the DDR in a dedicated surveillance program at a tertiary referral center for IBD. METHODS: Consecutive patients with quiescent colitis were enrolled in a cross-sectional study evaluating DDR. High-definition colonoscopy with dye chromoendoscopy (DCE) was performed by a specialized operator. Advanced dysplasia (AD) was defined as low-grade dysplasia ≥ 10 mm, high-grade dysplasia, or colorectal cancer. Risk factors for dysplasia detection were analyzed. RESULTS: In total, 119 patients underwent 151 procedures, identifying 206 lesions, of which 40 dysplastic with seven AD . Per-lesion and per-procedure DDR were 19.4 % and 20.5 %, respectively. The per-procedure AD detection rate (ADDR) was 4.6 %. A Kudo pit pattern of II-V had a sensitivity of 92.5 % for dysplasia detection but a false positive rate of 64.8 % (p < 0.001). Age at diagnosis and at index colonoscopy and past or indefinite dysplasia were associated with per-procedure dysplasia detection. CONCLUSIONS: In a real-world setting, a dedicated surveillance program achieved a high DDR. We suggest that optimal DDR in high-risk IBD patients be defined and implemented as a standardized quality measure for surveillance programs.

A decision-making model for prediction of a stable disease course in chronic hepatitis B patients.

Patients with chronic hepatitis B (CHB) are regularly monitored for HBV DNA and liver enzymes in order to assess disease progression and the need for antiviral therapy. Identifying patients with a stable course of disease can potentially prolong the intervals between visits, withhold unnecessary tests and save money. Accordingly, we aimed to find predictors for a stable disease course in patients with CHB. 579 patients with CHB, who were followed in a tertiary referral center between January 2004-December 2018, were retrospectively analyzed. Patients with low and steady viral load titer (< 2000 IU/ml) and normal ALT levels (< 40 IU/ml) in 6 consecutive clinic encounters were considered to have a stable course of CHB. A stepwise multivariate logistic regression analysis and a decision tree model were used to identify predictors of a stable disease course. Following exclusion of ineligible patients, a total of 220 patients were included in the final analysis. 64/220 patients had a stable disease course. Patients with a stable disease were older (62.99 ± 12.36 Vs. 54.07 ± 13.64, p < 0.001) with a higher percentage of women (53% vs. 38%) and had lower baseline levels of AST, ALT and viral load (VL). In a multivariate analysis, age (OR 0.94, 95% CI 0.91-0.98), baseline ALT (OR 1.06, 95% CI 1.01-1.1) and VL (OR 1.05 95% CI 1.02-1.08), were significantly associated with a stable disease. In a decision tree model, patients 46-67 years old, with baseline VL < 149 IU/mL and ALT < 40 IU/mL had the best probability (91%) for a stable disease course over 4.4 ± 2.2 years. We conclude that integrating patients' age with baseline VL and ALT can predict a stable disease course in patients with CHB off treatment.

Multi-focal dysplasia is associated with high recurrence rates after successful ablation of dysplastic Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) might recur after complete eradication of intestinal metaplasia (CEIM). We investigated  factors associated with recurrence of BE after successful Radiofrequency ablation (RFA). METHODS: A longitudinal study of BE patients with dysplasia treated with RFA from 2014 to 2021 in two large referral centers. Recurrence was identified in histologic specimens. Factors associated with post-RFA recurrence were analyzed using Cox regression analysis. RESULTS: A total of 728 patients with BE were identified, 118 had underwent RFA, and 113 had sufficient follow up time. Mean age was 63.7 (±11.7) years, 73.5% were males, 59.3% had long segment of BE, and 30.1% had multifocal dysplasia. During 340.8 patient-years of follow-up, 15 patients (13.3%) had recurrence of BE, which represent an incidence rate of 4.41% per patient-year. Incidence rate of recurrence with dysplasia was 1.17% per patient-year. Multifocal dysplasia, number of RFA sessions, and endoscopic resection before RFA were associated with risk of recurrence in univariate analysis. However, in cox regression analysis only multifocal dysplasia (HR 10.99; 95% CI 2.83-22.62, p = 0.001) was associated with post-RFA recurrence. CONCLUSION: Total recurrence rates after CEIM are low, and multifocal dysplasia before the ablative therapy is significantly associated with BE recurrence after CEIM. Patients with multifocal dysplasia should be monitored rigorously after successful ablation.

Gastric cancer risk in the elderly is associated with omeprazole use and inversely associated with aspirin use.

BACKGROUND: The association between long-term omeprazole use and gastric cancer (GC) risk is controversial. The aim of this study was to investigate the incidence of GC in elderly community-dwelling omeprazole chronic users with/without aspirin compared to non-users. METHODS: The registry of a large health management organization was searched for all community-dwelling members aged ≥65 years from January 2002 to December 2016. Data on demographics, background parameters, and chronic omeprazole and aspirin use (>11 prescriptions/year) were retrieved. Those diagnosed with new-onset GC during the study period (from January 2003) were identified. RESULTS: Of 51 405 subjects who met the inclusion criteria, 197 were diagnosed with GC during a mean follow-up period of 8.74 ±â€…4.16 years. This group accounted for 0.7% of PPI chronic users (72/11 008) and 0.3% (125/40 397) of nonusers (P < 0.001). GC risk was directly associated with omeprazole chronic use [hazard ratio (HR) 2.03, 95% confidence interval (CI): 1.51-2.73, P < 0.001] and inversely associated with aspirin chronic use (HR 0.55, 95% CI: 0.40-0.75, P < 0.001). Each year of omeprazole use increased GC risk by 9%, and each year of aspirin use decreased GC risk by 10% among omeprazole chronic users. The lowest rate of GC was found in omeprazole nonusers/ aspirin chronic users, and the highest, in omeprazole chronic users/aspirin nonusers. CONCLUSION: Higher GC rate was associated with omeprazole chronic use and inversely associated with aspirin chronic use relative to omeprazole nonuse in community-dwelling elderly.

Autoimmune Pancreatitis in Patients with Inflammatory Bowel Disease: A Real-World Multicentre Collaborative ECCO CONFER Study.

BACKGROUND: Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and predictors of complicated AIP course have rarely been reported. METHODS: An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD. RESULTS: We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35 ±â€…16 years]. The majority of Crohn's disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR] = 1.05, p = 0.008), whereas family history of IBD [OR = 0.1, p = 0.03], and CD diagnosis [OR = 0.2, p = 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred. CONCLUSIONS: In this large international cohort of patients with concomitant AIP-IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP course.

Seattle Protocol Is More Effective in Detection of Dysplasia Compared to Technology-Assisted Targeted Biopsies in Patients with Barrett's Esophagus.

BACKGROUND AND AIMS: With the development of narrow-band imaging (NBI) in the endoscopic evaluation of patients with Barrett's esophagus (BE), the role of random biopsies according to the Seattle protocol (SP) has been questioned. We aim to compare the utility of advanced imaging to SP in patients with BE. METHODS: A prospective cohort of patients with proven BE was retrospectively analyzed. All biopsies were reviewed by an expert GI pathologist. Advanced imaging was tandemly used with SP in each endoscopic procedure. RESULTS: A total of 155 out of 340 patients (45.5%) with BE were diagnosed with dysplasia during a median follow-up of 4.7 years (IQR 3.4-6.1 years) and were part of the statistical analysis. A total of 82 patients had a diagnosis of dysplasia at presentation, whereas 84 patients developed dysplasia during follow up. A total of 67 out of 82 patients with dysplasia at presentation (81.7%), and 65 out of 84 patients that were diagnosed with dysplasia during follow-up (77.4%) were diagnosed using SP. In addition, whereas all the events of EAC were diagnosed using targeted biopsies, 57.1% of the events of HGD and 86.3% of LGD were diagnosed using SP. CONCLUSION: Our findings demonstrate the significance of SP in the detection of low- and high-grade dysplasia in patients with BE. SP should remain the mainstay of endoscopic surveillance in this population.

Predictors of poor outcome following liver biopsy for the investigation of new hepatic space occupying lesion/s.

BACKGROUND: Ultrasound-guided percutaneous liver biopsy (UPLB) is currently performed mainly to determine if new hepatic space occupying lesions (SOL) represent benign, primary malignant, or metastatic disease. This study sought to investigate the outcome of UPLB in this setting. METHODS: In a retrospective study, patients with a new hepatic SOL who underwent UPLB during 1/2006-12/2016 were included and followed to 12/2018. Clinical data and pathology reports were reviewed. Mortality within 60 days and no change in patients' management following UPLB were defined as medically futile. RESULTS: Included 140 patients, 50% male, mean age 68.8 ± 11.5 years; 112 patients died, all of malignant disease. 32 patients (23%) died within 60 days of UPLB. Median post-UPLB survival was 151 days. Survival was significantly shorter in patients with >1 hepatic lesion (n = 108) or an extrahepatic malignant lesion (n = 77) (p = 0.0082, p = 0.0301, respectively). On Cox Proportional Hazards analysis, significant predictors of mortality within 60 days of UPLB were: age as a continuous variable, (HR 1.070, 95% CI 1.011-1.131, p = 0.018), serum albumin <2.9 g/dL, (HR 4.822 95% CI 1.335-17.425, p = 0.016) and serum LDH >1500 U/L (HR 9.443, 95% CI 3.404-26.197, p < 0.0001). CONCLUSIONS: In patients with these features or with disseminated disease, liver biopsy should be carefully reconsidered.

Ondansetron Use During Pregnancy: Birth Defects and Obstetric Outcomes.

Ondansetron is a widely administered medication for nausea and vomiting of pregnancy. Further examination of its teratogenic capacity is necessary. This study examines the association between ondansetron treatment during pregnancy and birth defects and adverse obstetric outcomes. Patient data were extracted from Clalit Health Services, Israel. A propensity-score analysis was performed matching those exposed to ondansetron with those who were not. Findings identified 774 women exposed to ondansetron, matched 1:1 with unexposed control patients. No significant differences were found between the groups for: cleft palate, cardiovascular congenital abnormalities, spina bifida occulta, preterm delivery, or small for gestational age. Ondansetron may be a useful and safe alternative as treatment for women who suffer from hyperemesis gravidarum and do not respond to other antiemetic drugs. Notwithstanding, additional prospectively designed research is needed to establish the safety of ondansetron treatment during pregnancy.

An alternative pathway to plant cold tolerance in the absence of vacuolar invertase activity.

To cope with cold stress, plants have developed antioxidation strategies combined with osmoprotection by sugars. In potato (Solanum tuberosum) tubers, which are swollen stems, exposure to cold stress induces starch degradation and sucrose synthesis. Vacuolar acid invertase (VInv) activity is a significant part of the cold-induced sweetening (CIS) response, by rapidly cleaving sucrose into hexoses and increasing osmoprotection. To discover alternative plant tissue pathways for coping with cold stress, we produced VInv-knockout lines in two cultivars. Genome editing of VInv in 'Désirée' and 'Brooke' was done using stable and transient expression of CRISPR/Cas9 components, respectively. After storage at 4°C, sugar analysis indicated that the knockout lines showed low levels of CIS and maintained low acid invertase activity in storage. Surprisingly, the tuber parenchyma of vinv lines exhibited significantly reduced lipid peroxidation and reduced H2 O2 levels. Furthermore, whole plants of vinv lines exposed to cold stress without irrigation showed normal vigor, in contrast to WT plants, which wilted. Transcriptome analysis of vinv lines revealed upregulation of an osmoprotectant pathway and ethylene-related genes during cold temperature exposure. Accordingly, higher expression of antioxidant-related genes was detected after exposure to short and long cold storage. Sugar measurements showed an elevation of an alternative pathway in the absence of VInv activity, raising the raffinose pathway with increasing levels of myo-inositol content as a cold tolerance response.

Development and validation of a prediction model for histologic progression in patients with nondysplastic Barrett's esophagus.

OBJECTIVES: Patients with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). We developed a model to predict histologic progression in patients with nondysplastic BE (NDBE). METHODS: A longitudinal study in three referral centers was performed between January 2010 and December 2019. As progression to low-grade dysplasia (LGD) can be considered an indication for ablative therapy, the study end-point was histopathologic progression to LGD, high-grade dysplasia, or EAC at 3 years after diagnosis. We used logistic regression to create the model. Seventy percent of the cohort were used to stem the model and the remaining 30% for internal validation. RESULTS: A total of 542 patients were included, 69.4% of whom were male, mean age 62.2 years. Long-segment BE at index endoscopy was diagnosed in 20.8% of the patients. After a mean follow-up of 6.7 years, 133 patients (24.5%) had histologic progression. Our model identified a neutrophil-to-lymphocyte ratio (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.77-2.32, P < 0.001), BE length (OR 1.22, 95% CI 1.09-1.36, P < 0.001), age (OR 1.03, 95% CI 1.02-1.05, P = 0.02), smoking (OR 1.66, 95% CI 1.09-2.75, P = 0.04), and renal failure (OR 1.51, 95% CI 0.93-2.43, P = 0.07) as predictors of histologic progression at 3 years. The areas under the receiver operating characteristic curves of this model were 0.88 and 0.76 in the training and validation cohorts, respectively. CONCLUSION: This novel, internally validated model may predict histologic progression, even in patients with NDBE who generally have low rates of progression over time, and may contribute to enhanced patient selection for more intense surveillance programs.

Video Capsule Endoscopy after Bariatric Surgery: A Tertiary Referral Center Experience.

BACKGROUND AND AIM: Minimal data are available regarding the performance of video capsule endoscopy (VCE) in patients who underwent bariatric surgery. We aimed to report indications, feasibility, and safety of VCE performed after bariatric surgery, specifically focusing on diagnosis rates of Crohn's disease (CD) in this population. METHODS: A retrospective analysis of all VCE procedures was performed between January 2015 and December 2019. All patients who underwent bariatric surgery prior to VCE were included. Indication for VCE, ingestion methods, completion rates, retention rates, and endoscopic findings were recorded. RESULTS: A total of 1,255 patients underwent VCE examination during the study period, of which 31 (2.5%) underwent bariatric surgery prior to VCE. The most common bariatric surgery was laparoscopic sleeve gastrectomy (16 patients, 51.6%), and the most common indication for VCE was evaluation of iron deficiency anemia (14 patients, 45.1%). The majority of patients ingested the capsule independently, without endoscopic assistance (20, 64.5%). Although a patency capsule was not used in our cohort, no events of capsule retention were documented. Mean transit time was 4.32 h. Only 4 events of incomplete examination were recorded. Over a median follow-up of 27.5 months (IQR 13.0-34.2), 10 patients (31.2%) had a final diagnosis of CD with a median Lewis score of 225 (IQR 135-900). CONCLUSION: VCE is a feasible and safe procedure after bariatric surgery. Oral ingestion does not carry risk of retention. It is an effective means of diagnosis of small-bowel CD in this population.

Steatosis, HBV-related HCC, cirrhosis, and HBsAg seroclearance: A systematic review and meta-analysis.

BACKGROUND AND AIMS: NAFLD and chronic hepatitis B (CHB) infection are common etiologies of HCC. The impact of hepatic steatosis on HCC in CHB, as well as its relationship with the development of cirrhosis, fibrosis, and HBsAg seroclearance, remains controversial. APPROACH AND RESULTS: Data from observational studies were collected through PubMed, EMBASE, and the Cochrane Library from inception to February 1, 2022. Outcomes of interest included the association of hepatic steatosis with HCC, cirrhosis, advanced fibrosis, and HBsAg seroclearance, expressed in terms of pooled ORs. Additional subgroup and sensitivity analyses were performed to validate the robustness of findings. A total of 34 studies with 68,268 patients with CHB were included. Hepatic steatosis was associated with higher odds of HCC (OR, 1.59; 95% CI, 1.12-2.26; I2  = 72.5%), with the association remaining consistent in Asia (OR, 1.56; 95% CI, 1.08-2.25), studies with a median follow-up duration of ≥5 years (OR, 2.82; 95% CI, 1.57-5.08), exclusion of alcohol use (OR, 1.71; 95% CI, 1.01-2.91), and biopsy-proven steatosis (OR, 2.86; 95% CI, 1.61-5.06), although no significant association was noted among nucleos(t)ide analogue-treated patients (OR, 1.05; 95% CI, 0.62-1.77). Steatosis was associated with the development of cirrhosis (OR, 1.52; 95% CI, 1.07-2.16; I2  = 0%) and HBsAg seroclearance (OR, 2.22; 95% CI, 1.58-3.10; I2  = 49.0%). CONCLUSIONS: Hepatic steatosis was associated with an increased risk of HCC and cirrhosis among patients with CHB but with a higher chance of achieving a functional cure, highlighting the importance of identifying concomitant steatosis in CHB.

Newly Diagnosed Crohn's Disease Patients in India and Israel Display Distinct Presentations and Serological Markers: Insights from Prospective Cohorts.

Background: Crohn's disease (CD) incidence is rising in India. However, features of newly diagnosed patients with CD in this population are largely unknown. The Indo-Israeli IBD GastroEnterology paRtnership (TiiiGER) aimed to investigate differences in presentation among patients with newly diagnosed CD in India and Israel, and to explore phenotype−serotype correlations. Methods: A prospective observational cohort study of consecutive adults (>18 years) conducted in two large referral centers in India and Israel (2014−2018). Clinical data, an antiglycan serological panel, and 20 CD-associated genetic variants were analyzed. Outcomes: complicated phenotype at diagnosis and early complicated course (hospitalizations/surgeries) within 2 years of diagnosis. Results: We included 260 patients (104, Indian (65.4%, male; age, 37.8); 156 Israeli (49.4%, male; 31.8, age)). Median lag time from symptoms onset to diagnosis was 10.5 (IQR 3−38) vs. 3 (IQR 1−8) months in Indian vs. Israeli patients (p < 0.001). Complicated phenotype at diagnosis was observed in 48% of Indian and 30% of Israeli patients (p = 0.003). Complicated phenotype was associated with higher anti-Saccharomyces cerevisiae antibody (ASCA) seropositivity rate among Israeli patients (p < 0.001), but not among Indian patients. Antiglycan serology did not correlate with the tested genetic variants. Early complicated course occurred in 28 (18%) Israeli and 13 (12.5%) Indian patients. The time from diagnosis to complication was comparable (log rank p = 0.152). Antiglycan serology did not correlate with a complicated early course in either cohort. Conclusions: There are significant differences in patients presenting with newly diagnosed CD in India and Israel, including phenotype and distinct biomarkers at diagnosis. These differences suggest different genetic and environmental disease modifiers.

Incidence of Colorectal Adenomas After Bariatric Surgery: Pre-operative Super Morbid Obesity Is Independently Associated with Increased Risk.

PURPOSE: The impact of pre-bariatric surgery BMI on the incidence of colorectal adenomas in the post-operative period is unknown. Here we aim to evaluate the incidence of colorectal adenomas after bariatric surgery and to assess super morbid obesity (SMO) as a risk factor for post-operative colorectal adenomas. MATERIALS AND METHODS: An inception cohort of 1639 patients that underwent bariatric surgery between 2011 and 2019 in a referral center was retrospectively analyzed. SMO was defined as BMI > 50.0 kg/m2. Cox regression analysis was performed to assess the influence of pre-operative BMI on the primary outcome. RESULTS: A total 381 patients (23.2% of the cohort) underwent colonoscopy and included in the analysis. Mean age was 51.1 years (± 10.6) with mean BMI of 42.2 kg/m2 (± 6.2), and 49 patients (12.9%) had SMO. Median time to colonoscopy was 3.5 years. One hundred nine patients (28.6%) had colorectal polyps, and 38/109 (34.8%) had advanced adenoma. Two patients had colorectal cancer (CRC). Pre-procedural SMO was associated with diagnosis of colorectal polyp (HR 2.4, 95% CI 1.5-3.9, p < 0.001) and advanced adenomas (HR 4.2, 95% CI 2.0-8.9, p < 0.001) upon adjustment to previously reported risk factors of CRC. CONCLUSION: Pre-procedural SMO is associated with increased risk of colorectal adenomas after bariatric surgery compared to obese and morbidly obese individuals. Pre-operative BMI should be incorporated into post-operative screening plan in this population.

Effectiveness of Ustekinumab Dose Escalation in Patients With Crohn's Disease.

BACKGROUND & AIMS: A subset of patients with Crohn's disease (CD) do not respond to ustekinumab at the standard dose of 90 mg every 8 weeks. Little is known about the efficacy of shortening the interval between doses. METHODS: We performed a retrospective study to determine the effectiveness of ustekinumab dose interval shortening, collecting data from 506 patients with CD who received subcutaneous ustekinumab 90 mg every 8 weeks at a single center. We obtained data from 110 patients who initially received subcutaneous ustekinumab 90 mg every 8 weeks and then had their interval shortened to every 4 weeks. Harvey Bradshaw Index (HBI) scores before and after the dose interval shortening was available for 78 patients in the cohort (71%), levels of C-reactive protein (CRP) for 60 patients (55%), and levels of fecal calprotectin for 8 patients (7%). RESULTS: Following dose interval shortening, the patients' median HBI decreased from 4.5 to 3 (P = .002), the median level of CRP decreased from 8 mg/L to 3 mg/L (P = .031), and median level of fecal calprotectin decreased from 378 µg/g to 157 µg/g (P = .57). Among patients who had an HBI >4, a level of CRP ≥5mg/dL, a level of fecal calprotectin >250ug/g, or endoscopic evidence for disease activity before dose interval shortening, after the dose interval was shortened, 28% achieved clinical remission (an HBI score ≤4), 22% had a normal level of CRP (<5 mg/dL), 50% had reduced levels of fecal calprotectin, and 36% achieved endoscopic remission. CONCLUSIONS: Shortening the ustekinumab 90 mg dose interval to 4 weeks for patients with CD who did not respond to doses every 8 weeks improved clinical and biological indices of disease activity. Patients who lose response to the standard dose of ustekinumab might benefit from dose interval shortening, which was effective and safe.

Neutrophil to lymphocyte ratio and risk of neoplastic progression in patients with Barrett's esophagus.

BACKGROUND: Patient's with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). Neutrophil to lymphocyte ratio (NLR) was found to be a predictor of poor prognosis in patients with EAC; however, its performance in premalignant esophageal lesions is vague. We aimed to evaluate the utility of NLR as a predictor of histologic progression in patients with BE. METHODS : A prospective cohort of patients with proven BE in a tertiary referral center was retrospectively analyzed. All biopsies were reviewed by an expert gastrointestinal pathologist. The discriminatory capacity of NLR was evaluated by area under the receiver operating characteristic (AUC) curve analysis and Cox regression analysis. RESULTS: 324 patients (mean age 62.3 years, 241 [74.4 %] males) were included in the final analysis. Overall, 13 patients demonstrated histologic progression to neoplasia over a mean follow-up of 3.7 years (progression risk 1.0 % per year). The AUC of NLR for progression to high grade dysplasia (HGD) or EAC was 0.88 (95 % confidence interval [CI] 0.83 - 0.96), and baseline NLR was associated with a 3-fold increase of progression to HGD and EAC during follow-up (hazard ratio [HR] 3.2, 95 %CI 1.5 - 5.8; P < 0.001). Notably, in a subgroup analysis of patients with nondysplastic BE (NDBE) at presentation, NLR was also a risk factor for histologic progression (HR 2.4, 95 %CI 1.7 - 3.4; P < 0.001). CONCLUSION: NLR predicted histologic progression in patients with BE. Patients with NDBE and NLR above 2.4 can be considered for specific surveillance programs with shorter intervals between sessions.

Use of proton pump inhibitors is associated with lower rates of first-time ischemic stroke in community-dwelling elderly.

AIM: Data on cardiovascular outcomes in elderly using proton pump inhibitors (PPI) are scant. We aimed to test the association between PPI use and the occurrence of first-time ischemic stroke (FTIS) among elderly. METHODS: The electronic database of a centrally located district branch of a large health maintenance organization in Israel was retrospectively screened (2002-2016) for community-dwelling individuals (≥65-95 years) for demographics and co-morbidities. Follow-up was until FTIS, death or end of study. Findings were analyzed by PPI use and occurrence of FTIS. RESULTS: 29,639 subjects (without history of stroke and use of antiplatelet aggregation drugs) mean age of 82.2 ± 5.5 years (range: 65-95 years, 38% male) were analyzed: 8,600 (29%) used PPIs. Mean follow up was 10.58 years (SD ± 5.44). Similar total and annual occurrence rates of FTIS were depicted in PPI users and non-users (20.9% vs. 21% and 2% vs. 2.1%, respectively). On a Cox regression analysis, upon adjustment for age, gender and cardiovascular disease related risk factors, PPI use was significantly associated with lower rates of FTIS (HR 0.73, 95% C.I. 0.69-0.77, p < 0.001). The risk for FTIS was significantly lower in subjects using PPI at any dose and for any time period compared to non-users (HR 0.9, 95% C.I. 0.85-0.96 for 7-48 yearly prescriptions and HR 0.51, 95% C.I. 0.46-0.55 for ≥49 yearly prescriptions). CONCLUSIONS: PPI use was associated with lower rates of FTIS in community-dwelling elders. Prospective large-scale studies are needed to fully elucidate the effect of PPI in this aging population.

Efficacy of biosimilar infliximab CT-P13 among inpatients with severe steroid-refractory colitis.

INTRODUCTION: In this study, we evaluate the efficacy and safety of the biosimilar infliximab, CT-P13, in the treatment of inpatients with severe steroid-refractory colitis. METHODS: A retrospective cohort study of adult colitis patients (UC or isolated Crohn's colitis) admitted to the University of Chicago inflammatory bowel disease inpatient service between January 2018 and December 2018 for management of severe colitis refractory to IV steroids who received CT-P13 were included in the study. Patients diagnosed with active small bowel Crohn's disease were excluded. CT-P13 was given as a single infusion of 5 to 10 mg/kg. A comprehensive review of their electronic medical records was performed, and demographic, clinical, laboratory, and endoscopic data were extracted. The primary endpoint was colectomy-free survival. RESULTS: Twenty-one patients with severe steroid-resistant colitis were included. Twelve patients had ulcerative colitis, seven patients had a diagnosis of indeterminate colitis, and two patients had a diagnosis of Crohn's colitis. The median age was 32.2 years. The median disease duration was 4.3 years, and the median follow-up time was 5.9 months. Patients had a median CRP of 23. All patients had moderate to severe disease on endoscopy. Colectomy-free survival was 76% at 3 months and 70% at 6 months. No severe adverse events were reported in this patient cohort. CONCLUSION: A significant proportion of patients with severe colitis failing IV steroids responded to induction therapy with CT-P13. Colectomy-free survival rates were similar to previous randomized trials using originator infliximab as induction therapy in severe steroid-refractory colitis.

Association Between Fibrosis Stage and Outcomes of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Biopsy-confirmed liver fibrosis is a prognostic factor for patients with nonalcoholic fatty liver disease (NAFLD). We performed a systematic review to quantify the prognostic value of fibrosis stage in patients with NAFLD and the subgroup of patients with nonalcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate endpoint. METHODS: We searched the MEDLINE, Embase, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver-related clinical events and outcomes in adults with NAFLD or NASH. We collected data on mortality (all cause and liver related) and morbidity (cirrhosis, liver cancer, and all liver-related events) by stage of fibrosis, determined by biopsy, for patients with NAFLD or NASH. Using fibrosis stage 0 as a reference population, we calculated fibrosis stage-specific relative risk (RR) and 95% confidence interval (CI) values for mortality and morbidities. We performed fixed-effect and random-effect model meta-analyses. Metaregression was used to examine associations among study design (prospective vs retrospective cohort), overall risk of bias (medium or high), and mean duration of follow-up (in years). RESULTS: Our meta-analysis included 13 studies, comprising 4428 patients with NAFLD; 2875 of these were reported to have NASH. Compared with no fibrosis (stage 0), unadjusted risk increased with increasing stage of fibrosis (stage 0 vs 4): all-cause mortality RR, 3.42 (95% CI, 2.63-4.46); liver-related mortality RR, 11.13 (95% CI, 4.15-29.84); liver transplant RR, 5.42 (95% CI, 1.05-27.89); and liver-related events RR, 12.78 (95% CI, 6.85-23.85). The magnitude of RR did not differ significantly after adjustment for confounders, including age or sex in the subgroup of NAFLD patients with NASH. Three studies examined the effects of increasing fibrosis on quality of life had inconsistent findings. CONCLUSIONS: In a systematic review and meta-analysis, we found biopsy-confirmed fibrosis to be associated with risk of mortality and liver-related morbidity in patients with NAFLD, with and without adjustment for confounding factors and in patients with reported NASH. Further studies are needed to assess the association between fibrosis stage and patient quality of life and establish that change in liver fibrosis stage is a valid endpoint for use in clinical trials.