Curcumin-QingDai Combination for Patients With Active Ulcerative Colitis: A Randomized, Double-Blinded, Placebo-Controlled Trial.

BACKGROUND & AIMS: We evaluated the efficacy of herbal combination of curcumin-QingDai (CurQD) in active ulcerative colitis (UC). METHODS: Part I was an open-label trial of CurQD in patients with active UC, defined by a Simple Clinical Colitis Activity Index score of 5 or higher and a Mayo endoscopic subscore of 2 or higher. Part II was a placebo-controlled trial conducted in Israel and Greece, randomizing active UC patients at a 2:1 ratio to enteric-coated CurQD 3 g/d or placebo for 8 weeks. The co-primary outcome was clinical response (reduction in the Simple Clinical Colitis Activity Index of ≥3 points) and an objective response (Mayo endoscopic subscore improvement of ≥1 or a 50% fecal calprotectin reduction). Responding patients continued either maintenance curcumin or placebo alone for an additional 8 weeks. Aryl-hydrocarbon receptor activation was assessed by cytochrome P450 1A1 (CYP1A1) mucosal expression. RESULTS: In part I, 7 of 10 patients responded and 3 of 10 achieved clinical remission. Of 42 patients in part II, the week 8 co-primary outcome was achieved in 43% and 8% of CurQD and placebo patients, respectively (P = .033). Clinical response was observed in 85.7% vs 30.7% (P < .001), clinical remission in 14 of 28 (50%) vs 1 of 13 (8%; P = .01), a 50% calprotectin reduction in 46.4% vs 15.4% (P = .08), and endoscopic improvement in 75% vs 20% (P = .036) in the CurQD and placebo groups, respectively. Adverse events were comparable between groups. By week 16, curcumin-maintained clinical response, clinical remission, and clinical biomarker response rates were 93%, 80%, and 40%, respectively. CurQD uniquely up-regulated mucosal CYP1A1 expression, which was not observed among patients receiving placebo, mesalamine, or biologics. CONCLUSIONS: In this placebo-controlled trial, CurQD was effective for inducing response and remission in active UC patients. The aryl-hydrocarbon receptor pathway may merit further study as a potential UC treatment target. CLINICALTRIALS: gov ID: NCT03720002.

The Effect of the Crohn's Disease Exclusion Diet on Patients With Pouch Inflammation: An Interventional Pilot Study.

Restorative proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice for patients with ulcerative colitis.1 Unfortunately, pouch inflammation (ie, pouchitis) is reported in up to 72% of pouch patients.1,2.

Higher Maintenance Adalimumab Trough Levels are Associated With Achievement of Advanced Remission Targets in Patients With Inflammatory Bowel Disease.

BACKGROUND: Biomarker normalization and endoscopic remission are superior to clinical remission in achieving improved long-term clinical outcomes in patients with inflammatory bowel diseases. GOAL: To study whether higher maintenance adalimumab levels are associated with clinical remission, biomarker normalization, and endoscopic remission. STUDY: Data were collected retrospectively from the patients' medical records. We defined clinical remission as a Harvey Bradshaw Index ≤5 or a partial Mayo score ≤2 for Crohn's disease (CD) and ulcerative colitis (UC), respectively, biomarker normalization as a C-reactive protein <0.5 mg/dL and/or calprotectin <250 (mg/kg), endoscopic remission as a (simple endoscopic score-CD) ≤3/4 for ileal/extensive CD, respectively, or an endoscopic Mayo score ≤1 for UC, and deep remission as the combination of clinical and endoscopic remission with normal biomarkers. RESULTS: Ninety-seven patients were included (82 CD and 15 UC). Patients who achieved clinical remission, biomarker normalization, or endoscopic remission had higher serum trough adalimumab levels compared with patients not in remission [mean (M)±standard error (SE)=8.98±0.78 vs. 5.92±0.96 µg/mL; P=0.016, 9.38±0.85 vs. 5.48±0.87 µg/mL; P=0.002; 9.13±0.88 vs. 6.02±0.77 µg/mL; P=0.019, respectively]. Receiver-operating curve analysis showed that an adalimumab level of ≥8.25 µg/mL was associated with deep remission (sensitivity 84%, specificity 70%, area under the curve 0.775; P<0.001). CONCLUSION: Clinical remission, biomarker normalization, and endoscopic remission are positively associated with adalimumab trough levels. Adalimumab level of ≥8.25 µg/mL is associated with deep remission. This study provides additional data to guide therapeutic drug monitoring with adalimumab.

A watchful waiting approach for newly diagnosed Crohn's disease patients with an inflammatory phenotype.

BACKGROUND: An early treat-to-target approach in Crohn's disease (CD) patients is recommended to avoid complications. However, CD may not always progress despite lack of treatment, thus exposing some patients to unnecessary side effects. We aimed to examine whether newly diagnosed CD patients with an inflammatory phenotype can benefit from a watchful waiting approach. METHODS: This retrospective cohort study followed CD patients with an inflammatory phenotype who were diagnosed between 2010 and 2015 and followed for at least 1 year. A watchful waiting approach was defined as maintenance therapy with 5-ASA medication only or no treatment during the first year of diagnosis or longer. Disease complications were defined as need for surgery or change in disease phenotype. RESULTS: Eighty-six patients were included and followed-up for 57.0 ± 29.0 months. Thirty-seven patients were managed with a watchful waiting approach and 49 with an early therapeutic intervention. The majority of patients (83.8%) in the watchful waiting group did not develop disease complications. In this group, there was no difference in clinical disease severity (stools per day, 2.7 ± 1.7 vs 3.3 ± 1.0, P = 0.39; abdominal pain, 74.2 vs 50.0%, P = 0.24) between those who did not develop complications and those who did. Smoking was associated with a complicated course (multivariate analysis: OR = 1.98, 95% CI 1.06-3.71, P = 0.03). CONCLUSIONS: A watchful waiting approach of newly diagnosed CD patients with an inflammatory phenotype may be a feasible option, with low long-term complication rate specifically in nonsmoking patients.

Efficacy and Follow-up of Segmental or Subtotal Colectomy in Patients With Colitis-Associated Neoplasia.

The historical approach to neoplasia in the setting of chronic colitis was to perform a total proctocolectomy. Recent consensus and society guidelines1-3 suggest that when dysplastic lesions can be removed endoscopically, continued surveillance is appropriate. This is based on improvements in optical technologies and the low risk of metachronous colorectal carcinoma in these patients.4-6 We hypothesized that if a lesion was completely removed surgically and followed up endoscopically, metachronous colorectal carcinoma would be a rare occurrence. Thus, segmental resection may be offered as a definitive surgery in patients with chronic colitis and localized colorectal neoplasia in whom endoscopic resection is not feasible. Retention of the distal colon/rectum is expected to result in an overall improved quality of life compared with permanent ileostomy or an ileoanal J-pouch. Here, we report our experience and follow-up evaluation of segmental resections for preoperative neoplasia in patients with Crohn's disease (CD) or ulcerative colitis (UC).

Higher Thioguanine Nucleotide Metabolite Levels are Associated With Better Long-term Outcomes in Patients With Inflammatory Bowel Diseases.

GOALS: The aim of this study was to assess whether sustained 6-thioguaninenucleotide (6-TGN) levels were associated with improved long-term outcomes in patients with inflammatory bowel diseases (IBD). BACKGROUND: Cross-sectional data have shown that thiopurine metabolites are correlated with clinical efficacy in patient receiving thiopurines for IBD but the role for serial measurements through treatment course is unclear. STUDY: We conducted a retrospective cohort study including patients with IBD on thiopurine monotherapy and had serial 6-TGN levels measured. Predictive variables included demographics, disease phenotype, 6-TGN levels (nadir, median, and peak levels). The primary outcome was the development of a disease relapse. The secondary outcome was the need for IBD surgery. RESULTS: Two hundred eighteen 6-TGN samples from 87 patients were analyzed. Nadir and median 6-TGN levels were significantly higher in patients who did not relapse [185 and 233 pmol per 8×10 red blood cells (RBCs)] as compared with levels in patients who did relapse (150 and 167 pmol per 8×10 RBCs, P=0.025) but there was no significant difference in peak 6-TGN level. When adjusted for confounding factors, a nadir 6-TGN level ≥161 and a median 6-TGN level ≥264 were associated with a significant decrease in the rate of disease exacerbation (hazard ratio: 0.5; 95% confidence interval, 0.26-0.87; P=0.016 and hazard ratio: 0.4; 95% confidence interval, 0.2-0.82; P=0.14). CONCLUSIONS: Serial thiopurine metabolite level assessments and dose adjustment aiming to maintain higher 6-TGN levels may be helpful to improve long-term outcomes in patients with IBD.

Dilemmas for guardians of advanced dementia patients regarding tube feeding.

Background: advanced dementia is an incurable illness, its last stage marked by inability to eat. Tube feeding was deemed a helpful solution at this stage, but in recent years its inefficiency has been proved, and it is no longer practiced in many countries around the world. In Israel, however, the procedure is still accepted. In the gastroenterology department at the Bnai Zion Medical Center, a serious interaction is ongoing with patients' legal guardians, where detailed information is given about the inefficiency of the tube procedure. Nevertheless, the great majority of guardians choose to have it performed. Purpose: to probe the considerations underlying the decision for gastrostomy, despite the data and the recommendations. Method: qualitative research, including participant observation at the clinic and in-depth interviews with guardians. Findings: the families of most patients did not discuss end-of-life issues with them. The overwhelming preference for using the technology was interpreted as life-saving, in contrast to comfort feeding, which was deemed euthanasia. The reasons given for the decision to tube feed were drawn from a range of outlooks: religion, the patient's earlier survival capacity, and pragmatic considerations involving relations with nursing home staff. Conclusion: study of the decision-making process of advanced dementia patients' guardians sheds light on the layers of meaning of the Israeli discourse regarding end-of-life issues.

Correction to: Risk Factors for Clostridium difficile Isolation in Inflammatory Bowel Disease: A Prospective Study.

The original version of the article unfortunately contained an error in a percentage value in Results section of Abstract.

Risk Factors for Clostridium difficile Isolation in Inflammatory Bowel Disease: A Prospective Study.

INTRODUCTION: Clostridium difficile is the most commonly isolated stool pathogen in inflammatory bowel disease (IBD). Traditional risk factors for C. difficile may not exist in patients with IBD, and no prior studies have assessed the risk factors for the isolation of C. difficile in both symptomatic and asymptomatic IBD outpatients. METHODS: We prospectively recruited consecutive IBD patients presenting to our outpatient clinic between April 2015 and February 2016. We excluded patients with a diverting ostomy or ileoanal pouch. Demographics, healthcare exposures, medical therapies and disease activity were recorded from medical charts or surveys. A rectal swab was performed from which toxigenic culture and PCR analysis for the presence of toxin and fluorescent PCR ribotyping were performed. The primary outcome of interest was isolation of toxigenic C. difficile. RESULTS: A total of 190 patients were enrolled in this prospective study including 137 (72%) with Crohn's disease and 53 (28%) with ulcerative colitis. At the time of enrollment, 69 (36%) had clinically active disease. Sixteen (8.4%) patients had toxigenic C. difficile isolated on rectal swab at enrollment and four (2.1%) patients had non-toxigenic C. difficile cultured. Mixed infection with more than one toxigenic isolate was present in 5/16 (31.3%) individuals. Patients with CD with a toxin positive isolate were more likely to have a history of CDI in the past 12 months (40 vs. 11.02%, p = 0.027) and an emergency department visit in the past 12 weeks (50 vs. 20.63%, p = 0.048). In UC, individuals with isolation of C. difficile were more likely to be hospitalized within the past 12 months (66.6 vs. 8.51%, p = 0.003). C. difficile isolation at the time of presentation was not associated with a subsequent disease relapse over a 6-month period in CD (p = 0.557) or UC (p = 0.131). CONCLUSION: Healthcare exposures remain a significant risk factor for C. difficile isolation in the IBD population; however, this was not associated with relapse of disease. Further studies assessing the clinical significance of C. difficile isolation is warranted in IBD.

Prospective Observational Evaluation of the Time-Dependency of Adalimumab Immunogenicity and Drug Concentration in Ulcerative Colitis Patients: the POETIC II Study.

BACKGROUND AND AIMS: Home self-injection of the human anti-tumour necrosis alpha [anti-TNFα] monoclonal adalimumab complicates prospective serial-sampling studies. Although a recent study examined adalimumab levels and immunogenicity in Crohn's disease [CD] patients, prospective real-world data from ulcerative colitis [UC] patients are lacking. METHODS: A three-monthly home-visit programme from induction was established prospectively for UC patients. Clinical scores were determined at each visit, and sera were obtained for assessment of drug and anti-adalimumab antibody levels. Calprotectin was measured using a smartphone-based app. This cohort was compared to a parallel prospective cohort of adalimumab-treated CD patients [POETIC1]. RESULTS: Fifty UC patients starting adalimumab [median follow-up 28 weeks] were compared to 98 adalimumab-treated CD patients [median follow-up 44 weeks]. Only 11/50 UC patients [22%] continued treatment to the end of the follow-up compared with 50/98 [51%] CD patients (odds ratio [OR] = 0.27, p = 0.001). Loss of response was significantly more common in UC patients [OR = 3.2, p = 0.001]. Seventeen patients [34%] in the UC cohort developed anti-adalimumab antibodies, 9/17 [52.9%] as early as week 2. There was no difference between patient cohorts in the overall development of anti-adalimumab antibodies [34% vs 30.6%, respectively, OR = 1.67, p = 0.67], nor was there a difference in early immunogenicity [OR = 1.39, p = 0.35]. There was no difference in low drug levels [<3 µg/mL] between the two cohorts [OR = 0.87, p = 0.83]. CONCLUSIONS: Loss of response to adalimumab therapy was significantly more common in the UC compared to the CD cohort and was driven by a higher rate of non-immunogenic, pharmacodynamic parameters.

Fecal transplantation for ulcerative colitis from diet conditioned donors followed by dietary intervention results in favorable gut microbial profile compared to fecal transplantation alone.

BACKGROUND AND AIMS: Several fecal microbial transplantation (FMT) approaches for ulcerative colitis (UC) have been investigated with conflicting results. We have recently published the clinical outcomes from the CRAFT-UC Trial using FMT with the UC Exclusion Diet (UCED), compared with FMT alone. Here we aimed to compare the two FMT strategies in terms of microbial profile and function. METHODS: Subjects recruited to the CRAFT-UC study with available pre- and post-intervention fecal samples were included. Donors received diet conditioning for 14 days based on the UCED principles. Group-1 received single FMT by colonoscopy (Day 1) and enemas (Days 2 and 14) without donors' dietary conditioning (N=11). Group-2 received FMT but with donors' dietary pre-conditioning and UCED for the patients (N=10). Fecal samples were assessed by DNA shotgun metagenomic sequencing. RESULTS: Following diet conditioning, donors had depletion in metabolic pathways involved in sulfur-containing amino acids biosynthesis. Only Group-2 showed significant shifts towards the donors' microbial composition (ADONIS: R2=0.15, p=0.008) and significant increased Eubacterium_sp_AF228LB post-intervention (ß-coefficient 2.66, 95%CI 2.1-3.3, q<0.05) which was inversely correlated with fecal calprotectin (rho=-0.52, p=0.035). Moreover, pathways involved in gut inflammation and barrier function including branched chain amino acids were enriched post intervention in Group-2 and were significantly inversely correlated with fecal calprotectin. CONCLUSION: FMT from diet conditioned donors followed by the UCED led to microbial alterations associated with favorable microbial profile which correlated with decreased fecal calprotectin. Our findings support further exploration of additive benefit of dietary intervention for both donors and patients undergoing FMT as a potential treatment of UC.

Medical Cannabis Increases Appetite but Not Body Weight in Patients with Inflammatory Bowel Diseases.

We aimed to elucidate the effect of Medical Cannabis (MC) on appetite and nutritional status among patients with inflammatory bowel disease (IBD). A case series of patients with IBD were initiating treatment with MC for disease-related symptoms, at the IBD clinic of a tertiary referral medical center. Patients' demographics, anthropometrics, medical history and treatment and MC use were systematically recorded. An appetite and food frequency questionnaire (SNAQ and FFQ) were filled before, and at 3 and 6 months of treatment. Patients with IBD initiating MC were enrolled (n = 149, age 39.0 ± 14.1 years, 42.3% female), and 33.6% (n = 50) were treated for improvement of nutritional status. A modest increase in appetite after 3 months was detected among all patients enrolled (Pv = 0.08), but there were no significant differences in energy or macronutrient intake, and in patients' body mass index (BMI). A significant appetite improvement after 3 months was detected among 34.0% (n = 17) of patients, but this was not associated with increased caloric intake or BMI at 3 or 6 months. Among patients without increased appetite after 3 months of MC therapy, BMI decreased at 6 months (24.1 ± 3.7 vs. 23.4 ± 3.6, Pv = 0.010). MC may be a potential strategy to improve appetite among some patients with IBD, but not caloric intake or BMI.

Crohn's Disease Exclusion Diet for the Treatment of Crohn's Disease: Real-World Experience from a Tertiary Center.

The Crohn's Disease (CD) exclusion diet (CDED) has been shown to induce remission in pediatric and adult patients with CD. In this retrospective cohort study, we describe our real-world experience with the CDED at the inflammatory bowel disease (IBD) unit of the Tel Aviv Medical Center between 2018-2021. CD patients with multiple clinical presentations and disease phenotypes who initiated the diet were included. Indications for treatment, medical and nutritional data were collected from dietician clinic visits and medical records. Clinical and biomarker responses were determined. The CDED was recommended to 220 CD patients. Seventy-two patients were included in the analysis for a clinically active disease (n = 48) or for remission maintenance (n = 24). Among patients with a clinically active disease, 62.5% of patients achieved clinical remission at week 6 and at week 12. A positive association between high adherence to the CDED and clinical remission at week 12 was observed (adjusted OR = 7.6, 95% CI 1.07-55.2, p = 0.043). Among patients treated for remission maintenance, remission at week 12 was maintained among 83.3% of patients. We conclude that the CDED may be a promising intervention for multiple CD presentations and indications. These findings should be further validated in larger, prospective, controlled studies.

Early Initiation of Adalimumab Significantly Diminishes Postoperative Crohn's Disease Endoscopic Recurrence and Is Superior to 6-Mercaptopurine Therapy: An Open-Label, Randomized Controlled Study.

Postoperative recurrence (POR) is the rule in patients with Crohn's disease (CD), mitigated with prophylactic therapy. The evidence for therapeutic choice and timing of intervention is lacking. We aimed to compare the rates of POR in patients treated early with prophylactic 6-mercaptopurine (6-MP) or adalimumab. We conducted a prospective single-center randomized open-label clinical study in which patients in surgical remission following their first ileocecectomy were randomized to receive early treatment with 6-MP or adalimumab. Patients were followed up clinically every 3 months and underwent endoscopy at weeks 32 and 58 postoperatively. The primary endpoint was endoscopic recurrence (ePOR) at 1 year (week 58), defined as a Rutgeerts score ≥ i2. We enrolled 35 patients (25 males, mean age 35 ± 1.4 years, median disease duration 5 ± 6.1 years) following ileocecectomy. Of these, seven (20%) were current smokers and nine (26%) biologics-experienced. Patients allocated to adalimumab had significantly less ePOR than patients treated with 6MP at week 32 (21% vs. 69%, p = 0.004) and 58 (47% vs. 75%), (p = 0.03, HR = 0.39, 95% CI = 0.16-0.93). POR was associated with an increased diameter of the resected small bowel surgical specimen, lower baseline body mass index (BMI), increased week 18 fecal calprotectin, increased week 18 serum alanine aminotransferase and decreased week 18 hemoglobin level. Adalimumab was more effective than 6-MP in preventing ePOR. Increased operative small bowel diameter and lower postoperative BMI were associated with ePOR. At eighteen weeks, serum hemoglobin, ALT and fecal calprotectin levels were predictive of endoscopic disease recurrence. (ClinicalTrials.gov ID NCT01629628).

Real-world experience with Curcumin-QingDai combination for patients with active ulcerative colitis: A retrospective multicentre cohort study.

BACKGROUND: Curcumin and QingDai (QD, Indigo) have been shown to be effective for treating active ulcerative colitis (UC). AIM: To evaluate the real-world experience with the Curcumin-QingDai (CurQD) herbal combination to induce remission in active UC. METHODS: A retrospec-tive multicentre adult cohort study from five tertiary academic centres (2018-2022). Active UC was defined as a Simple Clinical Colitis Activity Index (SCCAI) ≥ 3. Patients were induced by CurQD. The primary outcome was clinical remission at weeks 8-12, defined as SCCAI ≤2 and a decrease ≥3 points from baseline. Secondary outcomes were clinical response (SCCAI decrease ≥3 points), corticosteroid-free remission, faecal calprotectin (FC) response (reduction ≥50%), FC normalisation (FC ≤100 µg/g for patients with FC ≥300 µg/g at baseline), and safety. All outcomes were analysed for patients who were maintaining stable treatment. RESULTS: Eighty-eight patients were included; 50% were biologics/small molecules experienced, and 36.5% received ≥2 biologics/small molecules. Clinical remission was achieved in 41 (46.5%), and clinical response in 53 (60.2%). Median SCCAI decreased from 7 (IQR:5-9) to 2 (IQR:1-3); p < 0.0001. Of the 26 patients on corticosteroids at baseline, seven achieved corticosteroid-free remission. Among 43 biologics/small molecules experienced patients, clinical remission was achieved in 39.5% and clinical response in 58.1%. FC normalisation and response were achieved in 17/29 and 27/33, respectively. Median FC decreased from 1000 µg/g (IQR:392-2772) at baseline to 75 µg/g (IQR:12-136) at the end of inductions (n = 30 patients with paired samples); p < 0.0001. No overt safety signals emerged. CONCLUSION: In this real-world cohort, CurQD effectively induced clinical and biomarker remission in patients with active UC, including patients who were biologics/small molecules experienced.

Assessment of patients' understanding of inflammatory bowel diseases: Development and validation of a questionnaire.

BACKGROUND: Educating patients regarding thier inflammatory bowel disease (IBD) is important for their empowerment and disease management. We aimed to develop a questionnaire to evaluate patient understanding and knowledge of IBD. METHODS: We have developed the Understanding IBD Questionnaires (U-IBDQ), consisting of multiple-choice questions in two versions [for Crohn's disease (CD) and ulcerative colitis (UC)]. The questionnaires were tested for content and face validity, readability, responsiveness and reliability. Convergent validity was assessed by correlating the U-IBDQ score with physician's subjective assessment scores. Discriminant validity was assessed by comparison to healthy controls (HC), patients with chronic gastrointestinal (GI) conditions other than IBD, and to GI nurses. Multivariate analysis was performed to determine factors associated with a high level of disease understanding. RESULTS: The study population consisted of IBD patients (n = 106), HC (n = 35), chronic GI disease patients (n = 38) and GI nurses (n = 19). Mean U-IBDQ score among IBD patients was 56.5 ± 21.9, similar for CD and UC patients (P = 0.941), but significantly higher than that of HC and chronic GI disease patients and lower than that of GI nurses (P < 0.001), supporting its discriminant validity. The U-IBDQ score correlated with physician's subjective score (r = 0.747, P < 0.001) and was found to be reliable (intra-class correlation coefficient = 0.867 P < 0.001). Independent factors associated with high U-IBDQ scores included academic education (OR = 1.21, 95% CI 1.10-1.33, P < 0.001), biologic therapy experience (OR = 1.24, 95% CI 1.01-1.53, P = 0.046), and IBD diagnosis at <21 years of age (OR = 2.97, 95% CI 1.05-8.87, P = 0.050). CONCLUSIONS: The U-IBDQ is a validated, reliable and short, self-reported questionnaire that can be used for assessing understanding of disease pathophysiology and treatment by IBD patients.

The Crohn's disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn's disease (CDED-AD): an open-label, pilot, randomised trial.

BACKGROUND: The Crohn's disease exclusion diet (CDED) with partial enteral nutrition is effective for induction of remission in children with mild-to-moderate Crohn's disease. We aimed to assess the CDED in adults with Crohn's disease. METHODS: We did an open-label, pilot randomised trial at three medical centres in Israel. Eligible patients were biologic naive adults aged 18-55 years with mild-to-moderate Crohn's disease (defined by a Harvey-Bradshaw Index score of 5-14 points), a maximal disease duration of 5 years, with active disease on colonoscopy, or imaging with elevated inflammatory markers (C-reactive protein >5 mg/L or faecal calprotectin concentration >200 µ/g). Patients were randomly assigned (1:1) to CDED plus partial enteral nutrition or CDED alone for 24 weeks. Randomisation was via block randomisation (block sizes of six) using sealed, numbered, and opaque envelopes. Patients and investigators were aware of which group patients were assigned to due to the nature of the different interventions. The primary endpoint was clinical remission, defined as a Harvey-Bradshaw Index score of less than 5 at week 6. The primary endpoint was assessed in the intention-to-treat (ITT) population, which included all patients who used the dietary therapy for at least 48 h. We report results of the final analysis. This trial is registered with ClinicalTrials.gov, NCT02231814. FINDINGS: Between Jan 12, 2017, and May 11, 2020, 91 patients were screened, of whom 44 were randomly assigned to the CDED plus partial enteral nutrition group (n=20) or CDED alone group (n=24). 19 patients in the CDED plus partial enteral nutrition group and 21 patients in the CDED alone group received the allocated intervention for at least 48 h and thus were included in the ITT analysis. At week 6, 13 (68%) of 19 patients in the CDED plus partial enteral nutrition group and 12 (57%) of 21 patients in the CDED group had achieved clinical remission (p=0·4618). Among the 25 patients in remission at week 6, 20 (80%) were in sustained remission at week 24 (12 patients in the CDED plus partial enteral nutrition group and eight in the CDED alone group). 14 (35%) of 40 patients were in endoscopic remission at week 24 (eight patients in the CDED plus partial enteral nutrition group and six in the CDED alone group). No serious adverse events or treatment-related adverse events were reported in either group. INTERPRETATION: CDED with or without partial enteral nutrition was effective for induction and maintenance of remission in adults with mild-to-moderate biologic naive Crohn's disease and might lead to endoscopic remission. These data suggest that CDED could be used for mild-to-moderate active Crohn's disease and should be assessed in a powered randomised controlled trial. FUNDING: Azrieli Foundation and Nestle Health Science.

Use of Faecal Transplantation with a Novel Diet for Mild to Moderate Active Ulcerative Colitis: The CRAFT UC Randomised Controlled Trial.

BACKGROUND: We evaluated whether integration of novel diets for donors and patients, in addition to faecal transplantation [FT], could increase FT remission rate in refractory ulcerative colitis [UC]. METHODS: This was a blinded, randomised, controlled trial in adults with active UC, defined by a simple clinical colitis activity index [SCCAI] of ≥5 and ≤11 and endoscopic Mayo score 2-3, refractory to medication. Group 1 received free diet and single donor standard FT by colonoscopy on Day 1and rectal enemas on Days 2 and 14 without dietary conditioning of the donor. Group 2 received FT as above but with dietary pre-conditioning of the donor for 14 days and a UC Exclusion Diet [UCED] for the patients. Group 3 received the UCED alone. The primary endpoint was Week 8 clinical steroid-free remission, defined as SCCAI <3. RESULTS: Of 96 planned patients, 62 were enrolled. Remission Week 8 Group 1 was 2/17 [11.8%], Group 2 was 4/19 [21.1%], Group 3 was 6/15 [40%] [non-significant]. Endoscopic remission Group 1 was 2/17 [12%], Group 2 was 3/19 [16%], Group 3 was 4/15 [27%] [Group 1 vs 3 p = 0.38]. Mucosal healing [Mayo 0] was achieved only in Group 3 [3/15, 20%] vs 0/36 FT patients [p = 0.022]. Exacerbation of disease occurred in 3/17 [17.6%] of Group 1, 4/19 [21.1%] of Group 2, and 1/15 [6.7%] of Group 3 [Group 2 vs 3, p = 0.35]. CONCLUSIONS: UCED alone appeared to achieve higher clinical remission and mucosal healing than single donor FT with or without diet. The study was stopped for futility by a safety monitoring board.

COVID-19 in Patients with Inflammatory Bowel Disease: The Israeli Experience.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory bowel diseases (IBD) affecting millions of people worldwide. IBD therapies, designed for continuous immune suppression, often render patients more susceptible to infections. The effect of the immune suppression on the risk of coronavirus disease-19 (COVID-19) is not fully determined yet. OBJECTIVE: To describe COVID-19 characteristics and outcomes and to evaluate the association between IBD phenotypes, infection outcomes and immunomodulatory therapies. METHODS: In this multi-center study, we prospectively followed IBD patients with proven COVID-19. De-identified data from medical charts were collected including age, gender, IBD type, IBD clinical activity, IBD treatments, comorbidities, symptoms and outcomes of COVID-19. A multivariable regression model was used to examine the effect of immunosuppressant drugs on the risk of infection by COVID-19 and the outcomes. RESULTS: Of 144 IBD patients, 104 (72%) were CD and 40 (28%) were UC. Mean age was 32.2 ± 12.6 years. No mortalities were reported. In total, 94 patients (65.3%) received biologic therapy. Of them, 51 (54%) at escalated doses, 10 (11%) in combination with immunomodulators and 9 (10%) with concomitant corticosteroids. Disease location, behavior and activity did not correlate with the severity of COVID-19. Biologics as monotherapy or with immunomodulators or corticosteroids were not associated with more severe infection. On the contrary, patients receiving biologics had significantly milder infection course (p = 0.001) and were less likely to be hospitalized (p = 0.001). Treatment was postponed in 34.7% of patients until recovery from COVID-19, without consequent exacerbation. CONCLUSION: We did not witness aggravated COVID-19 outcomes in patients with IBD. Patients treated with biologics had a favorable outcome.

Risk Factors for Malnutrition among IBD Patients.

(1) Background: Malnutrition is a highly prevalent complication in patients with inflammatory bowel diseases (IBD). It is strongly associated with poor clinical outcomes and quality of life. Screening for malnutrition risk is recommended routinely; however, current malnutrition screening tools do not incorporate IBD specific characteristics and may be less adequate for screening these patients. Therefore, we aimed to identify IBD-related risk factors for development of malnutrition. (2) Methods: A retrospective case-control study among IBD patients attending the IBD clinic of the Tel-Aviv Medical Center for ≥2 consecutive physician consultations per year during 2017-2020. Cases who had normal nutritional status and developed malnutrition between visits were compared to matched controls who maintained normal nutritional status. Detailed information was gathered from medical files, including: demographics, disease phenotype, characteristics and activity, diet altering symptoms and comorbidities, medical and surgical history, annual healthcare utility, nutritional intake and the Malnutrition Universal Screening Tool (MUST) score. Univariate and multivariate analyses were used to identify malnutrition risk factors. The independent risk factors identified were summed up to calculate the IBD malnutrition risk score (IBD-MR). (3) Results: Data of 1596 IBD patients met the initial criteria for the study. Of these, 59 patients developed malnutrition and were defined as cases (n = 59) and matched to controls (n = 59). The interval between the physician consultations was 6.2 ± 3.0 months, during which cases lost 5.3 ± 2.3 kg of body weight and controls gained 0.2 ± 2.3 kg (p < 0.001). Cases and controls did not differ in demographics, disease duration, disease phenotype or medical history. Independent IBD-related malnutrition risk factors were: 18.5 ≤ BMI ≤ 22 kg/m2 (OR = 4.71, 95%CI 1.13-19.54), high annual healthcare utility (OR = 5.67, 95%CI 1.02-31.30) and endoscopic disease activity (OR = 5.49, 95%CI 1.28-23.56). The IBD-MR was positively associated with malnutrition development independently of the MUST score (OR = 7.39, 95%CI 2.60-20.94). Among patients with low MUST scores determined during the index visit, identification of ≥2 IBD-MR factors was strongly associated with malnutrition development (OR = 8.65, 95%CI 2.21-33.82, p = 0.002). (4) Conclusions: We identified IBD-related risk factors for malnutrition, highlighting the need for a disease-specific malnutrition screening tool, which may increase malnutrition risk detection.