Precision medicine: Externally validated explainable AI support tool for predicting sustainability of infliximab and vedolizumab in ulcerative colitis.

OBJECTIVE: Drug sustainability (DS), a surrogate marker for drug efficacy, is important, especially when aiming for precision medicine. However, it lacks reliable prediction methods. AIMS: To develop and externally validate a web-based artificial intelligence(AI)-derived tool for predicting DS of infliximab and vedolizumab in patients with moderate-to-severe Ulcerative Colitis (UC). METHODS: Data from three Israeli centers included infliximab or vedolizumab patients treated for >54 weeks. Sustainability meant no corticosteroids, hospitalizations or surgeries. Machine learning techniques predicted >54-week and overall DS using baseline clinical data. RESULTS: The model was developed using data from 246 patients from Rabin Medical Center and externally validated on 67 patients from Rambam Health Care Campus and Sheba Medical Center. No significant difference in DS was observed across the datasets. Most patients were biologic-naïve and primarily treated with vedolizumab. The model performed well, with an area under the ROC curve of 0.86, and showed good accuracy (65.5 %-76.9 %) across the test sets. CONCLUSIONS: The study introduces a novel, AI-based tool for predicting >54-week DS of infliximab and vedolizumab in moderate-to-severe UC, using baseline parameters. This can aid clinical decision-making in the framework of precision medicine, promising to optimize disease management while maintaining physician autonomy.

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

Vedolizumab Is Associated with Longer Drug Sustainability Compared to Infliximab in Moderate-to-Severe Ulcerative Colitis: Long-Term Real-World Cohort Data.

BACKGROUND AND AIM: Drug sustainability (DS) is a surrogate marker for treatment efficacy. We aimed to compare the DS of two main biologics used to treat moderate-to-severe ulcerative colitis (UC), infliximab (IFX) and vedolizumab (VDZ), in a real-world setting. METHODS: We conducted a retrospective cohort study at a tertiary medical center in Israel. We included patients treated between 1 December 2017 and 1 May 2021, who were followed for up to 300 weeks. DS was defined as corticosteroid-, surgical-, and hospitalization-free treatment. RESULTS: 217 patients with UC were included. VDZ had a significantly longer median DS of 265.6 weeks compared to IFX's 106.5 weeks (p = 0.001) in treatment-naïve patients, even when adjusting for disease severity (HR 0.55 95 CI 0.3-0.98, p = 0.042). In treatment-experienced patients, DS was comparable between IFX and VDZ (p = 0.593). CONCLUSIONS: VDZ showed significantly longer DS in treatment-naïve patients with UC compared to IFX, also when adjusted for disease severity. There was no difference in DS between VDZ and IFX in treatment-experienced patients and patients switching from one drug to another. VDZ may be a suitable first-line treatment for biologic-naïve patients with moderate-to-severe UC.

The use of artificial intelligence to identify subjects with a positive FOBT predicted to be non-compliant with both colonoscopy and harbor cancer.

BACKGROUND: Subjects with a positive Fecal Occult Blood Test (FOBT) that are non-compliant with colonoscopy are at increased risk for colorectal cancer (CRC). Yet, in clinical practice, many remain non-compliant. AIMS: To evaluate whether machine learning models (ML) can identify subjects with a positive FOBT predicted to be both non-compliant with colonoscopy within six months and harbor CRC (defined as the "target population"). METHODS: We trained and validated ML models based on extensive administrative and laboratory data about subjects with a positive FOBT between 2011 and 2013 within Clalit Health that were followed for cancer diagnosis up to 2018. RESULTS: Out of 25,219 included subjects, 9,979(39.6%) were non-compliant with colonoscopy, and 202(0.8%) were both non-compliant and harbored cancer. Using ML, we reduced the number of subjects needed to engage from 25,219 to either 971 (3.85%) to identify 25.8%(52/202) of the target population, reducing the number needed to treat (NNT) from 124.8 to 19.4 or to 4,010(15,8%) to identify 55.0%(52/202) of the target population, NNT = 39.7. CONCLUSION: Machine learning technology may help healthcare organizations to identify subjects with a positive FOBT predicted to be both non-compliant with colonoscopy and harbor cancer from the first day of a positive FOBT with improved efficiency.

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.

Significant Differences in IBD Care and Education across Europe: Results of the Pan-European VIPER Survey.

BACKGROUND: Inflammatory bowel disease (IBD) care and education might differ around Europe. Therefore, we conducted this European Variation In IBD PracticE suRvey (VIPER) to investigate potential differences between countries. METHODS: This trainee-initiated survey, run through SurveyMonkey®, consisted of 47 questions inquiring basic demographics, IBD training, and clinical care. Results were compared according to gross domestic product (GDP) per capita, for which countries were divided into 2 groups (low/high income, according to the World Bank). RESULTS: The online survey was completed by 1,285 participants from 40 European countries, with a majority of specialists (65.3%) working in academic institutions (50.4%). Significant differences in IBD-specific training (55.9% vs. 38.4%), as well as availability of IBD units (58.4% vs. 39.7%) and multidisciplinary meetings (73.2% vs. 40.1%), were observed between respondees from high and low GDP countries (p < 0.0001). In high GDP countries, IBD nurses are more common (85.9% vs. 36.0%), also mirrored by more nurse-led IBD clinics (40.6% vs. 13.7%; p < 0.0001). IBD dieticians (33.4% vs. 16.5%) and psychologists (16.8% vs. 7.5%) are mainly present in high GDP countries (p < 0.0001). In the current COVID era, telemedicine is available in 73.2% versus 54.1% of the high/low GDP countries, respectively (p < 0.0001). Treat-to-target approaches are implemented everywhere (85.0%), though access to biologicals and small molecules differs significantly. CONCLUSION: Much variability in IBD practice exists across Europe, with marked differences between high and low GDP countries. Further work is required to help address some of these inequalities, aiming to improve and standardize IBD care and training across Europe.

Specialized Emergency Department Assessment and Multidisciplinary Intervention After Discharge Improve Management of Patients With Inflammatory Bowel Diseases.

GOAL: The aim was to assess proactive specialized inflammatory bowel diseases (IBD) emergency department (ED) consultation and multidisciplinary IBD team (IBD-MDT) intervention on IBD-related patient outcomes after discharge. BACKGROUND: Despite advances in patient care, IBD-related ED visits have increased and substantially contribute to the IBD burden. METHODS: Consecutive patients with IBD (below 50 y) who visited the ED during November 2017 to April 2018 (intervention group) were compared with patients with IBD that visited the same ED during 2014 to 2017 (standard-care group). The primary outcomes were hospitalization and ED revisits at 30, 90, and 180 days. RESULTS: The intervention group (45 patients, mean age 32.43±8.6 y, 57.8% male) and the standard-care group (237 patients) had comparable baseline characteristics, including age, sex, and IBD type, and similar rates of hospital admissions from the ED (46.7% vs. 38.8%, P=0.32). The intervention group more frequently underwent computed tomography (40% vs. 8%, P<0.001) and surgical interventions (13.3% vs. 0.8%, P<0.001) within the same hospital admission, compared with the standard-care group. In the intervention group, 24 patients were discharged from the ED, of whom 17 patients visited the IBD clinic (median 5 d postdischarge) and the majority were referred to ambulatory IBD-MDT services (dietitian: 46.7%, psychologist: 6.7%, advanced endoscopist: 8.9%, and proctology services: 6.7%). The intervention group had significantly fewer ED revisits than the standard-care group (30 d: 4.4% vs. 19.8%, P=0.013; 90 d: 4.4% vs. 35.9%, P<0.001; 180 d: 6.7% vs. 43%, P<0.001). CONCLUSION: Proactive specialized ED assessments and IBD-MDT interventions after a hospital discharge were preferable; they significantly reduced the ED revisit rate for at least 6 months.

Machine learning for selecting patients with Crohn's disease for abdominopelvic computed tomography in the emergency department.

BACKGROUND: Patients with Crohn's disease (CD) frequently undergo abdominopelvic computed tomography (APCT) in the emergency department (ED). It's essential to diagnose clinically actionable findings (CAF) as they may need immediate intervention, frequently surgical. However, repeated APCT's includes increased ionizing radiation exposure. Guidance regarding APCT performance is mostly clinical and empiric. AIMS: We used a machine learning (ML) approach for predicting CAF on APCT in the ED. METHODS: We performed a retrospective cohort study of patients with CD who presented to the ED and underwent APCT. CAF were defined as bowel obstruction, perforation, intra-abdominal abscess or complicated fistula. ML was used to predict the probability of having CAF on APCT, using routine clinical variables. RESULTS: Of 101 admissions included, 44 (43.5%) had CAF on APCT. ML successfully identified patients at low (NPV 91.6%, CI-95% 90.6-92.5) and high (PPV 92.8%, CI-95%, 92.3-93.2) risk for CAF (AUROC = 0.774), using beats-per-minute, mean arterial pressure, neutrophil-to-lymphocyte ratio and sex. This allowed the construction of a risk stratification scheme according to patients' probability for CAF on APCT. CONCLUSION: We present a novel artificial intelligence-based approach, utilizing readily available clinical variables to better select patients with CD in the ED for APCT. This might reduce the number of APCTs performed, avoiding related hazards while ensuring high-risk patients undergo APCT.

Oscillospira and related bacteria - From metagenomic species to metabolic features.

Oscillospira is an under-studied anaerobic bacterial genus from Clostridial cluster IV that has resisted cultivation for over a century since the first time it was observed. In recent years its 16S rRNA gene was identified in several human gut microbiota studies where it was often associated with interesting traits, especially leanness. However, very little is known about its metabolism or physiology. Here we used nearly complete genomes derived from shot-gun metagenomic data from the human gut to analyze Oscillospira and related bacteria. We used sequence similarity, gene neighbourhood information and manual metabolic pathway curation to decipher key metabolic features of this intriguing bacterial genus. We infer that Oscillospira species are butyrate producers, and at least some of them have the ability to utilize glucuronate, a common animal-derived sugar that is both produced by the human host and consumed by that host in diets rich in animal products. These findings could help explain diet-related inter-individual variation in faecal Oscillospira levels as well as the observation that the presence of this genus is reduced in diseases that involve inflammation.

Hyperemesis gravidarum in northern Israel: a retrospective epidemiological study.

BACKGROUND: Hyperemesis gravidarum (HG) is characterized by severe intractable nausea and vomiting in pregnancy leading to electrolyte imbalance, ketonuria, and weight loss. The cause is unknown. This study sought to investigate the prevalence and characteristics of HG in the Western Galilee in two ethnic populations and to estimate its economic burden. METHODS: Data on ethnicity, age, gestational age, number of pregnancies, and length of hospitalization were collected from the medical files of all women with HG admitted to the Galilee Medical Center in 2010-2013. Findings were compared between Arabs and Jews. Prevalence was assessed relative to total number of births. Economic burden was assessed by cost of hospitalization and work days lost. RESULTS: The cohort included 184 women, 124 Arabic (67.4 %) and 60 Jewish (32.6 %). There were 13,630 births at the medical center during the study period, for a calculated prevalence of HG of 1.2 %. There was no difference in the relative proportions of Arabs and Jews between the cohort and the total women giving birth at our center. Mean patient age was 27.2 years, gestational age 9.3 weeks, parity 2.35. Mean age was significantly higher in the Jewish group. There were no significant between-group differences in the other clinical parameters. Mean number of hospitalization days was 2.24 days, and of additional rest days prescribed, 4.62. The calculated annual cost of HG was 452,943.42 NIS (120,144.14 USD), crudely extrapolated to a nationwide cost of 15-20 million NIS (5,300,000 USD). CONCLUSION: The prevalence and characteristics of HG are similar in the Arabic and Jewish populations of northern Israel. Mean gestational age at admission for HG was lower in our study than earlier ones, probably owing to the universal health care provided by law in Israel. HG prevalence was twice that reported previously in southern Israel but still within the range observed in other world regions. The socioeconomic differences between Arabs and Jews in the Galilee are smaller than elsewhere in Israel, suggesting a multifactorial etiology of HG. HG poses a major economic burden which should be considered when planning health policies. Further studies of this issue are warranted.

Oscillospira: a Central, Enigmatic Component of the Human Gut Microbiota.

Oscillospira is an enigmatic bacterial genus that has never been cultured, but is constantly detected by 16S rRNA gene surveys of the human microbiome. Here we summarize recent evidence that Oscillospira is positively associated with leanness and health, speculate about its physiology, and argue its potential importance for human health.