The Mediterranean diet (MED) is increasingly recommended for patients with inflammatory bowel disease (IBD), yet evidence on its clinical impact and its effect on inflammatory markers remains limited. This study aimed to test the feasibility and effectiveness of a microbiota-targeted MED-based nutritional education program (IBDMED), in patients with early Crohn’s disease (CD) in Israel (ISR) and India (IND). Patients with early mild-to-moderate CD, and inflammatory phenotype (B1), were randomized to either the IBDMED program or a local standard-of-care dietary counseling (control). The IBDMED program included personalized dietary consultations with dietitians, a mobile application providing MED guidance, online support, and the use of wearables to monitor lifestyle parameters. Clinical outcomes [Harvey-Bradshaw Index (HBI)], quality of life (QoL) measures (s-IBDQ, IBD-Control), fecal calprotectin (FC), and changes in microbiome composition, were assessed before and after the 8-week intervention (NCT05536544). A total of 78 patients completed the 8-week intervention (ISR = 42; IND = 36). The median age was 34 years [IQR 25-42] and median BMI was 23.2 kg/m2 [IQR 20.5-26.7]. Overall, HBI improved from 2 [IQR 1-4.5] to 1 [1-3.5] in the IBDMED group (p = 0.02), with greater improvement in the ISR cohort from 4 [3-7] to 2 [0-4] (p = 0.004), compared with no significant changes in controls. Among patients with active disease (baseline HBI≥5), clinical remission was achieved in 8/10 (80%) in the IBDMED group compared with 4/10 (40%) in controls. Baseline QoL scores were higher in the IND cohort and improved overall in both ISR and IND, with significant improvement in the s-IBDQ in the IBDMED group and in the IBD-Control in both groups (p < 0.05). FC significantly decreased in the IBDMED group from 221 [126-400] to 136 [27-266] µg/g (p = 0.0019), while remaining comparable in controls. FC response, defined as a 50% reduction in patients with baseline levels >100 µg/g, was observed in 15/30 (50%) in the IBDMED group and 11/26 (42.3%) in controls. Reduction in FC was associated with increased IBDMED adherence score (p < 0.05). Preliminary microbial analysis revealed that clinical improvement was associated with increased microbial diversity, driven by increased relative abundances of butyrate producers. The IBDMED program is feasible and leads to clinical, QoL and inflammatory improvements in patients with early CD. These may be mediated by positive microbial changes and highlight the potential role of a microbiota-targeted and culturally adapted MED programs across different geographic populations, in modulating inflammation in patients with CD. Conflict of interest: Dr. Godny, Lihi: Grant: Helmsley Charitable Trust Raghunathan, Nalini: None Reshef, Leah: No conflict of interest Elial-Fatal, Sarine: None Shakhman, Shelly: No conflicts Fathima, Sana: None Pfeffer-Gik, Tamar: Altman Health Janssen Strauss group Kutukov, Lena: No conflict of interest Friedenberg, Adi: No conflict of interest Pauker, Maor: No conflict of interest Rabinowitz, Keren: No conflict of interest Barkan, Revital: Grant: Research grants from Pfizer and Abbvie Sharar Fischler, Tali: No conflict of interest Lichtenstein, Lev: No conflict of interest Mor, Michal Zehava: No conflict of interest Sehayek-Shabat, Vered: No conflict of interest Peleg, Idit: No conflict of interest Tamir-Degabli, Natalie: No conflict of interest Glusman-Bendersky, Ahinoam: No conflict of interest Kornowski Cohen, Maya: No conflict of interest Reiss Mintz, Hilla: No conflict of interest Odeh, Safwat: No conflict of interest Mekala, Dhanush: No conflict of interest Gunala, Nikhil: No conflict of interest Kalpakam, Kripa: No conflict of interest Thakur, Manisha: No conflict of interest P, Ambica: No conflict of interest Ollech, Jacob: No conflict of interest Snir, Yifat: No conflict of interest Broytman, Yelena: No conflict of interest Avni Biron, Irit: No conflict of interest Banai Eran, Hagar: No conflict of interest Yanai, Henit: Grant: Pfizer, ISF Personal Fees: AbbVie, Janssen, Pfizer, Takeda, Bristol Myers Squibb, and Elly Lilli. Gophna, Uri: No conflict of interest Banerjee, Rupa: RB has received grants/research support from Asian Healthcare Foundation, and the Leona M and Harry B Helmsley Charitable Trust Advisory board fees from Abbott, AstraZeneca, Abbvie, Cadila, Cipla, Dr Reddy Labs, Eli Lilly, Emcure, Ferring Pharma, Hetero Drugs, Janssen, MSN Labs, Mankind Pharma, Menarini, Micro Labs, Pfizer, Sun Pharmaceuticals, Takeda Pharmaceuticals, Torrent, Waterley, and Zydus. Dotan, Iris: Grant: The Leona M. and Harry B. Helmsley Charitable Trust, Altman Research, Pfizer, BMS Personal Fees: Pfizer, Falk, Ferring, Abbvie, Janssen, Celltrion, Takeda, Celgene/BMS, Gilead, Galapagos, Materia Prima, Sandoz, Sublimity, Sangamo, Spyre, Eli-Lilly, Harp Diagnostics, Gutreat, Astra Zeneca

Vaccines are pivotal for control of the coronavirus disease (COVID-19) pandemic. Patients with inflammatory bowel diseases (IBDs) treated with antitumor necrosis factor (TNF)-α have lower serologic response after two COVID-19 vaccine doses. Data regarding a third vaccine dose are scarce. An Israeli multicenter prospective observational study recruited 319 subjects: 220 with IBD (79 treated with anti-TNFα) and 99 healthy control (HC) participants. All patients received two mRNA-BNT162b2 vaccines (Pfizer/BioNTech), 80% of whom received a third vaccine dose. Evaluation included disease activity, anti-spike (S) and nucleocapsid (N) antibody levels, anti-TNFα drug levels, and adverse events (AEs). All participants showed significant serologic response one month after receiving a third dose. However, three months later, the anti-S levels decreased significantly in patients treated with anti-TNFα compared with the non-anti-TNFα and HC groups. A correlation between serologic response to the third vaccine dose and anti-TNF drug levels was not found. No significant AE or IBD exacerbation was observed. Importantly, lower serologic response after the third vaccine dose predicted infection. A third dose of BNT162b2 is effective and safe in patients with IBD. Lower serologic response predicted infection, even in seropositive subjects. Lower serologic responses and their rapid decline suggest a fourth vaccine dose in this patient population.

Abstract Background Vaccines are pivotal for control of the ongoing coronavirus disease (COVID-19) pandemic. Patients with inflammatory bowel diseases (IBD) treated with anti-tumor necrosis factor (TNF)-α have lower serologic response after two COVID-19 vaccine doses. Data regarding a 3rd vaccine are scarce. Methods Aim: To assess immune responses to, and safety of COVID-19 vaccines in patients with IBD, stratified according to therapy, and compared to healthy controls (HC). Subjects were recruited before the 1st vaccine (BNT162b2, Pfizer) and prospectively evaluated after the 2nd and 3rd vaccine doses. Evaluation included: disease activity, anti-spike (S) and nucleocapsid (N), anti-TNFα drug levels and adverse events (AE) Results Of 198 subjects having the 3rd vaccine dose, 125 had IBD: average age: 39.1±14.8 years; 40.8% females; 82- Crohn’s disease (CD), 33 ulcerative colitis (UC), 6 pouch, 3 IBD-U. There were 73 HC: average age 39.4±12.5 years, 69.9% females. Among patients with IBD: 51 and 74 (40.8%, 59.2%)) were treated or not with anti-TNFα, respectively. A month after the 3rd vaccine dose IBD activity was comparable in all patients regardless of treatment, and no increase in C-reactive protein or white blood cells was observed. Higher but not significant AE rate was registered in all subjects after the 3rd compared to 2nd vaccine dose (81% vs. 76%, respectively). AE rate in IBD and HC was comparable. No serious AE detected. There was a significant increase in anti-S levels one month after compared to pre 3rd vaccine dose in all participants. Furthermore, increase was 2-3 folds higher than that observed one month after the 2nd dose. Importantly, patients treated with anti-TNFα compared to non-anti-TNFα treated had significantly lower responses: 9219 (6347-13390) vs 16955 (13721-20951) (GMC (95%CI)), p<0.05. Serologic response did not correlate with anti-TNFα drug levels, antibodies or interval between drug and vaccine administration. During extended follow-up post 3rd dose, we found that lower serologic response predicts infection over time. Conclusion This prospective study shows that a 3rd dose of BNT162b2 vaccine is effective and safe in patients with IBD. Furthermore, patients treated with anti-TNFα had significantly lower serologic responses compared to anti-TNFα untreated ones. Lack of correlation between anti-TNFα drug levels and immune responses suggests there is no need to modify vaccination timing relatively to anti-TNFα administration. The significantly steeper increase in anti-S levels between 2nd and 3rd doses, suggests the 3rd dose is crucial in anti-TNFα treated patients, specifically due to the fact that higher serologic response predicts better defense from infection.

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.

had undetectable antibodies (three on tacrolimus and one on renal dialysis).One had breakthrough COVID-19 infection (S-titer=13u/mL).Patients receiving IS had significantly lower titers (mean log) for both vaccines, compared to those without IS overall (Fig 1A).Patients receiving IS had lower proportions with Anti-S Total Ab above 100U/mL, 300 U/ mL, 500U/ml and 1000U/mL at all timepoints up to 6 months post-second dose (Fig 1B).Patients on IS had significant titer decay (Fig 1C ,n=42, EDC 1.8%/day, p=0.012, t ½ ≈38 days) and was significantly faster (D-slope p<0.05) than those not on IS (n=74, p=0.058,EDC 0.05%/day, t ½ ≈153 days).Among anti-TNF monotherapy patients (Fig 1D ), there was faster decay in BNT162b2 (n=25, EDC 2.4%/day, p=0.002, t ½ ≈28 days) compared to mRNA-1273 (n=10, EDC 0.9%/day, p=0.188, t ½ ≈76 days), with near-significant D-slope (p=0.109).Conclusions: While IBD patients initially exhibit robust responses to SARS-CoV-2 vaccination, far fewer patients on IS achieve high titers.Titers decay faster in those on anti-TNF agents, and data suggests this decay is more pronounced with BNT162b2. Su1488

Abstract Background While vaccines against COVID-19 are effective in healthy individuals, we reported significantly lower serologic responses to BNT162b2 in patients with inflammatory bowel diseases (IBD) treated with anti-tumor necrosis factor (TNF) α agents. As this was apparent already, 4 weeks post vaccination, vaccine longevity is concerning. Aim: to assess long-term serologic responses to BNT162b2 in patients with IBD stratified according to medical treatment. Methods A prospective, observational multi-center Israeli study. Patients with IBD (anti-TNFα treated versus non-anti-TNFα treated) and healthy controls (HC) were followed from before the, 1st BNT162b2 dose until, 6 months after vaccination. COVID-19 spike (S) and nucleocapsid (N) antibodies (Abs) concentrations were analyzed by ELISA, followed by neutralization studies. Specific anti-receptor binding domain (RBD) memory B-cells response, serologic responses against variants of concern (VOCs), Beta, Gamma and Delta, immunoglobulin levels and lymphocyte cell subsets were evaluated as well. Safety was assessed using questionnaires, clinical and laboratory data. Results Of, 193 subjects, 130 had IBD (45 and, 85 in the anti-TNFα and non-anti-TNFα groups, respectively), 63 HC. Serologic response assessed, 176 (median) days (IQR, 166–186) and compared to, 4 weeks after, 1st dose significantly declined in all three groups, but was lowest in the anti-TNFα group:, 6 months anti-S Abs titer geometric means:, 193 (95%CI:, 128–292), 703 (520–951), and, 1253 (1023–1534) in anti-TNFα, non- anti-TNFα and HC groups, respectively, p<0.001, Figure, 1. This was further supported by neutralization and inhibition studies. Importantly, significantly decreased memory B-cell response towards RBD was detected only in the anti-TNFα group, with the most significant reduction in response to Beta VOC (p<0.0008 and p<0.0001, vs. non-anti-TNFα and HC, respectively). Older age was an additional predictor of lower serologic response. Immunoglobulin levels and lymphocyte cell subsets were comparable between the study groups. Infection rate reflected by anti-N Abs was ~1% in all groups. Safety was comparable in all groups. Conclusion The, 6-months serologic response to BNT162b2 vaccine, evaluated prospectively, decreased in all subjects, most prominently in patients with IBD treated with anti-TNFα. Importantly, the latter also had the sharpest decline in serologies, the lowest functional activity and lowest RBD specific memory B-cells. Older age is an additional predictor of decreased serologic response. Altogether, waning of COVID-19 serologic and functional response over, 6 months, specifically in patients with IBD treated with anti-TNFα, supports the need for an early third vaccine dose.

Background Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor-necrosis-factor (TNF)α biologics are at high risk for vaccine preventable infections. Their ability to mount adequate vaccine responses is unclear. Aim To assess serologic responses to mRNA-COVID-19 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared to healthy controls (HC). Methods Prospective, controlled, multi-center Israeli study. Subjects enrolled received two BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibodies levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinaly. Results Overall 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non-anti-TNFα), and 73 HC. After the first vaccine dose all HC were seropositive, while ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared to non-anti-TNFα treated patients, and HC (both P<.001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared to non-anti-TNFα treated patients, and HC (P<.03; P<.0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. Conclusions In this prospective study in patients with IBD stratified according to treatment all patients mounted serologic response to two doses of BNT162b2. However, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.

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.

AbstractBackgroundPatients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics are at high risk for vaccine preventable infections. Their ability to mount adequate vaccine responses is unclear.Aimto assess immune responses to mRNA-COVID-19 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared to healthy controls (HC).MethodsProspective, controlled, multi-center Israeli study. Subjects enrolled received two BNT162b2 (Pfizer/BioNTech) doses. Anti-spike (S) antibodies levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinaly.ResultsOverall 258 subjects: 185 IBD (67 treated with anti-TNFα), and 73 HC. After the first vaccine dose all HC were seropositive, while some patients with IBD, regardless of treatment, remained seronegative. After the second dose all subjects were seropositive, however anti-S levels were significantly lower in anti-TNFα treated compared to untreated patients, and HC (p<0.001; p<0.001, respectively). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared to untreated patients, and HC (p<0.03; p<0.0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-S levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity did not change in response to BNT162b2.ConclusionsIn this prospective study in patients with IBD stratified according to treatment all patients mounted an immune response to two doses of BNT162b2. However, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine immune response longevity in this group may be limited, vaccine booster dose should be considered.

SARS-CoV-2 pandemic has revolutionized and reshaped the way of thinking in the worldwide gastroenterology community regarding improving our personal protective equipment (PPE). This is especially important to reduce the risk of nosocomial COVID-19 transmission during the performance of elective and urgent endoscopies1ASGEGuidance for resuming GI endoscopy and practice operations after the COVID-19 Pandemic.2020Google Scholar,2Gralnek I, Hassan C, Beilenhoff U, et al. ESGE and ESGENA position statement on gastrointestinal endoscopy and COVID-19: an update on guidance during the post-lockdown phase and selected results from a membership surveyhttps://eref.thieme.de/ejournals/1438-8812_AAM#/10.1055-a-1213-5761. Endoscopy.Google Scholar and to reduce the psychological stress which endoscopy personnel experience.3Moraveji S. Thaker A.M. Muthusamy V.R. Banerjee S. Protocols, personal protective equipment utilization and psychological/financial stressors within endoscopy units in mid-pandemic: a large survey of hospital-based and ambulatory endoscopy centers in the US.Gastroenterology. 2020; Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar,4Rex D.K. Vemulapalli K.C. Lahr R.E. McHenry L. Sherman S. Al-Haddad M. Endoscopy staff are concerned about acquiring COVID-19 infection when resuming elective endoscopy.Gastroenterology. 2020; Google Scholar During the lockdown phase, deferred routine gastrointestinal endoscopies have resulted in decreased gastric and colorectal cancer diagnosis, presumably causing the upshifting of cancer stage by 6 months.5Lui T.K.L. Leung K. Guo C.G. Tsui V.W.M. Wu J.T. Leung W.K. Impacts of the coronavirus 2019 pandemic on gastrointestinal endoscopy volume and diagnosis of gastric and colorectal cancers: a population-based study.Gastroenterology. 2020; Google Scholar Hence, most of us have come out to a simple conclusion: SARS-CoV-2 infection might be our perennial unwanted risky "companion" for the next years. Ethically, we cannot afford to keep rejecting the performance of ordinary endoscopic procedures. Accordingly, our group, as others6Canelli R. Connor C.W. Gonzalez M. Nozari A. Ortega R. Barrier enclosure during endotracheal intubation.New Eng J Med. 2020; Crossref Scopus (396) Google Scholar,7Kobara H. Nishiyama N. Masaki T. Shielding for patients using a single-use vinyl-box under continuous aerosol suction to minimize SARS-CoV-2 transmission during emergency endoscopy.Digest Endoscopy. 2020; Crossref PubMed Scopus (17) Google Scholar have been working on the design of a special "droplets containing box", aiming to reduce drastically the gastroenterologist's exposure to nasopharyngeal droplets generated during gastroscopy. For this purpose, herein, we summarize our experience with a simple dedicated gastroscopy box. The box was made of a transparent Perspex and can be re-used, following official guidelines8Centers for Disease Control and Prevention. Coronavirus disease 2019 (COVID-19): cleaning and disinfection for community facilities. https://www.cdc.gov/coronavirus/2019-ncov/community/organizations/cleaning-disinfection.html.Google Scholar for cleaning and disinfection. It was tested on a simulator (GI-BRONCH Mentor™ 3D systems, formerly Simbionix). Due-to the physical structure of the simulator, the gastroscopy-box was positioned with its opening un-evenly placed regarding the simulator's mannequin mouth as shown in Fig. 1. The simulator's various modules were used to test the feasibility of performing gastroscopy with or without the box: Upper GI endoscopy Cases 1–5 were carried out with the box and then without it. EndoBubble module: this module consists of a tunnel (lumen) in which the endoscopist should navigate the scope and pop balloons. After two warm-up runs without the box, three consecutive runs were carried out without and with the box on level 1, and then three consecutive runs with and without the box on level 2 of the module. EndoBasket module: this module consists of a tunnel (lumen) in which the endoscopist navigate through this lumen, catches balls and puts them in a basket. After a warm-up run, three consecutive runs on level 1 were performed without the box, followed by three runs with the box. The metrics of gastroscopy simulations are summarized in Tables 1, 2a, 2b, 3. While these metrics are not validated as quality measures for gastroscopy and lack the specific ability for calculating any statistical differences, we think that our study clearly demonstrates gastroscopy through the gastroscopy-box is completely feasible.Table 1Box Vs Un-box gastroscopy simulations.Box EGDUn-Box EGDRun no.total time (sec)EOS*EOS: efficiency of screening. (%)EOS*EOS: efficiency of screening./sec ratioRun no.total time (sec)efficiency of screening (EOS) (%)EOS/sec ratio1168890.521149960.642219760.342203730.353303910.303273890.324252910.364212780.365274960.355261960.36 EOS: efficiency of screening. Open table in a new tab Table 2aBox Vs Un-box EndoBubble module simulations.EndoBubble module, level 1- BoxEndoBubble module, level 1- No boxRun no.total time (sec)number of wall hitsaverage time between balloon pops (sec)Run no.total time (sec)number of wall hitsaverage time between balloon pops (sec)162121682324802252023560234812 Open table in a new tab Table 2b EndoBubble module, level 2- BoxEndoBubble module, level 2- No BoxRun no.total time (sec)number of wall hitsaverage time between balloon pops (sec)Successful balloon pops ratio (%)Run no.total time (sec)number of wall hitsaverage time between balloon pops (sec)Successful balloon pops ratio (%)1891372.5199236528102802960377.539102853910277.5 Open table in a new tab Table 3Box Vs Un-box EndoBasket module simulations.EndoBasket module, level 1- BoxRun no.total time (sec)number of wall hits1st ball was located after (sec)1st ball was placed in its basket after (sec)2nd ball was located after (sec)2nd ball was placed in its basket after (sec)3rd ball was located after (sec)3rd ball was placed in its basket after (sec)15007922314046264012173143566034804722343944EndoBasket module, level 1- No BoxRun no.total time (sec)number of wall hits1st ball was located after (sec)1st ball was placed in its basket after (sec)2nd ball was located after (sec)2nd ball was placed in its basket after (sec)3rd ball was located after (sec)3rd ball was placed in its basket after (sec)149069233541462450472131374135604722374751 Open table in a new tab Testing of the efficacy of shielding from droplets was tested on a mannequin (Laerdal airway management trainer). A fluorescent dye (Glo Germ gel) detected by ultra-violet (UV) light simulated a patient's droplets. Five milliliters of fluorescent material diluted in ten milliliters of tap water was sprayed through the mannequin mouth. The endoscopist was positioned as for performing a gastroscopy and the mannequin was turned on its left side. The fluorescent color droplets were detected by UV light. Three positions were tested: With the box, the mannequin mouth is below the level of the box opening; With the box, the mannequin mouth is in the same level of the box opening and Without the box. When the gastroscopy-box opening was placed unevenly in regard to the simulator's mannequin mouth, the droplets were noted to be glowing inside the gastroscopy-box and on the scope. Only a few drops were detected on the hand holding the scope (shown in Fig. 2a). On the contrary, placing the opening of the gastroscopy-box evenly with the mannequin mouth resulted in droplet's contamination of the scope, the holding hand and the gown (shown in Fig. 2b). As expected, gastroscopy without the dedicated gastroscopy-box resulted in massive droplets contamination of the scope, the holding hand, the gown, and the bed (shown in Fig. 2c). To summarize, we believe that the gastroscopy-box might provide an additional layer of protection for endoscopy unit staff and its use should be further investigated. The authors have no conflicts of interest to declare. The authors are gratefully thankful for Eran Naron and Golan Landsberg from hp Indigo for their contribution to this work. The ethics committee of Samson-Assuta University Hospital waived the need for approval and consent. The gastroscopy-box was generously donated by hp IndigoLtd, Israel.

Abstract Background Biologic treatments are inherently associated with an increased risk of infections, and recipients are intuitively considered at-risk for a more severe course of COVID-19. However, the actual risks are not fully described, neither are the appropriate adjustments needed to mitigate such risks. Methods Nation-wide registry was set up by Israeli IBD Section, to characterize course of COVID-19 in IBD patients who contacted SARS-CoV-2 infection while on biologics. We prospectively collected demographic and clinical data, and analyzed COVID-19 outcomes with regard to the specific treatments. Results Between Apr and Oct 2020, 144 patients with an established IBD diagnosis and confirmed COVID-19 were enrolled at 20 IBD referral centers. The majority of patients was under the age of 40 (113, 78%), 9 (6%) were younger than 18, only 4 patients (3%) over the age of 70. 94 patients received biologics, as monotherapy (76, 52.8%), combined with immunomodulators (9, 10%) or concomitant corticosteroids (9, 10%). 37 patients (26%) were reported with moderate and severe COVID-19 course, third of them (13) on biologics. 24 patents (17%) were admitted for hospitalization, the rest managed in home setting (114, 79%) and hotels converted into makeshift healthcare facilities (6, 4%). Fifteen patients (10%) required non-invasive ventilation and oxygen support, 3 patients (2%) went on mechanical ventilation. All patients recovered uneventfully, with no mortalities reported. Age was the most significant factor associated with moderate and severe disease. We found no correlation between bowel disease activity and the severity of COVID-19 course. The rate of serious COVID-19 for the 94 patients who had received biologics was significantly lower than that of 50 patients who were not treated with biologics (13/94 vs 24/50; RR 0.29 [95% CI, 0.161–0.515]; p < 0.0001). On adjusting for age, gender, comorbidities, IBD phenotype and activity, the surprising ameliorating effect associated with biologics was profound and significant (OR, 0.082 [95% CI 0.009-0.621], p =0.013) in all age categories. Conclusion Our results are reassuring and encouraging, and do not suggest that therapeutic immune suppression renders IBD patients particularly vulnerable for more severe course of the COVID-19. Adjusted odds for severe COVID-19 course actually decreased significantly in patients treated with biologics. It could be speculated that cytokine inhibition may mitigate progression of the infection to a devastating hyperinflammatory state. Continuing necessary maintenance immune suppression seems to be appropriate and safe approach, despite the COVID-19 pandemic.

Characterisation of gut immune signature may help in better understanding of pathogenesis of inflammatory bowel diseases (IBD), and assist in individualisation of anti-inflammatory treatment. We compared phenotypic characteristics of gut-dedicated α4β7 integrin-expressing circulating (peripheral) T-lymphocytes to those expressed by T-lymphocytes allocated in intestinal mucosa. A time-of-flight mass spectrometry (CyTOF) was used to perform comprehensive immunophenotypic analysis of both the circulating and the mucosal lymphocytes, sampled from patients with IBD. We assessed a large array of signature cytokines, transcription factors and membrane markers to assign T cells into Th1, Th17, Th2 and Treg cell subpopulations, calculated subset composition of T-cell populations, and compared the compositions observed in T cells resident in mucosa to that of α4β7-positive circulating T-lymphocytes, in a given patient. Characterisation of Gut-dedicated (α4β7+) circulating CD4+ lymphocytes. Cytokines, transcription factors and membrane markers. Cytokines, transcription factors and membrane markers. We used Wilcoxon sign-rank test to examine the correlation between the compositions in the peripheral/mucosal sample pairs. We calculated correlation coefficients to rule out a possibility of within-the-sample interrelations between the subsets, to make sure it does not confound the results. Nine peripheral blood / mucosal sample pairs were tested. We found no correlation between the compositions of α4β7-expressing circulating T-lymphocytes and the mucosal T-lymphocytes. In a single patient (#7), a correlation was observed between the mucosal “signature” and that of the total (but not the α4β7-expressing) circulating T-lymphocytes (p = 0.0286). Intra-sample interrelation between the subpopulations was noticed in 3/9 patients (patient 1, Th1-Th17, r = 0.9997, p = 0.0148; Th17-Treg, r = 1, p = 0.0061; patient 5, Th1-Treg, r = 0.9981, p = 0.0391; patient 7, Th2-Th17, r = 0.9988, p = 0.0309). Subset composition of circulating α4β7-positive T-lymphocytes poorly correlates with the phenotype signatures expressed by T-lymphocytes resident in intestinal mucosa. The finding may suggest that the circulating T cells of different phenotypes may home to gut mucosa in dissimilar manners, perhaps with additional factors determining preferential homing of the specific pro-inflammatory and regulatory subpopulations. This may potentially explain the bell-shaped dose-response curve observed with several anti-integrin and anti-addressin therapeutic antibodies.

BACKGROUND AND THE STUDY AIM:Crohn's disease (CD) is a chronic inflammatory disorder defined as a transmural inflammation of the bowel wall, affecting the small and large intestine. The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity. We extended the Niv score to the colon and have a comprehensive view of the whole intestine.METHODS:We evaluated 3 parameters of intestinal pathology: A, Inflammation; B, Extent of disease; C, Presence of strictures. The scoring formula is as follows: CEDCAIic=(A1×B1+C1)+(A2×B2+C2)+(A3×B3+C3)+(A4×B4+C4) (1=proximal small bowel, 2=distal small bowel, 3=right colon, 4=left colon).RESULTS:The median CECDAIic score was 15.5 (range, 0 to 42), and the mean±SD score was 17.2±11.5. The CECDAIic scores per patient were similar among the 5 observers. Kendall's coefficient of concordance was high and significant for almost all the parameters examined except for strictures in the proximal small bowel and distal colon. Nevertheless, the coefficients for the small bowel and for the whole intestine were high, 0.85 and 0.77, P<0.0001, respectively.CONCLUSIONS:We established a new score, the CECDAIic of the small-bowel and colonic CD. We offer this easy, user-friendly score for use in randomized controlled trials and in the clinical follow-up of CD patients.

INTRODUCTION:Crohn's disease impairs patients' perception of health and has a negative impact on health-related quality of life. Although it is apparent that uncertainty is a significant factor that decreases quality of life, it has never been studied in patients with Crohn's disease. The objective of the present study was to examine the association between level of certainty, self-epistemic authority, Internet information gathering habits, and health-related quality of life.METHODS:A cross-sectional study of 105 Crohn's disease patients was conducted. Data were collected using a questionnaire composed of five parts: (1) demographic and clinical information; (2) health-related quality of life; (3) level of certainty; (4) self-epistemic authority; and (5) Internet information gathering habits regarding Crohn's disease.RESULTS:A significant positive correlation was demonstrated between levels of certainty and health-related quality of life. Self-epistemic authority correlated positively with certainty, while information gathering via the Internet was related to decreased certainty. Multiple regression analysis for factors associated with health-related quality of life showed a positive association with the level of certainty, while negative associations were found between Internet information seeking and disease activity with the quality of life.CONCLUSION:Level of certainty proved an important variable associated with health-related quality of life in Crohn's disease patients. Improving patients' self-epistemic authority can increase certainty and, thus, improve health-related quality of life.

Background . To investigate the association between 18F-FDG (Fluorodeoxyglucose) PET (positron emission tomography)/MRE (magnetic resonance enterography) metrics with the inflammatory biomarkers fecal calprotectin and C-reactive protein (CRP) in patients with Crohn’s disease (CD). Methods . This prospective pilot study was institutional review board (IRB) approved with informed consent obtained. Consecutive CD patients were referred to 18F-FDG PET/MRE. Patients in whom colonoscopy was performed and CRP and fecal calprotectin levels were measured were included. CRP and fecal calprotectin were regarded as positive for inflammation if they were greater than 0.5 mg/dl and 150 mcg/g, respectively. Correlation of quantitative variables was performed using the Pearson’s correlation coefficient. Receiver operating characteristic (ROC) curves were drawn and the area under the curve (AUC) was calculated to evaluate the accuracy of PET and MRE metrics in determining the presence of inflammation evaluated by calprotectin and CRP levels. Results . Analysis of 21 patients (16 women and 5 men, 43±18 years) was performed. Magnetic resonance index of activity (MaRIA) score had an AUC of 0.63 associated with fecal calprotectin and CRP. Adding apparent diffusion coefficient (ADC) and metabolic inflammatory volume (MIV) to MaRIA score resulted in an AUC of 0.92 with a cutoff value of 447 resulting in 83% and 100% sensitivity and specificity, respectively. Conclusion . The addition of ADC and MIV to the MaRIA score increases the accuracy for discrimination of disease activity in patients with CD. Trial registration number is 2015062.

Background: IBD specialists often find it difficult to make treatment plans for Crohn's disease (CD) patients, due to both inflammatory and fibrotic components of diseased bowel segments. It is essential to estimate the extent, dominance, depth and overall clinical implications of these. We have preliminarily evaluated a novel imaging method, FDG-PET MRenterography (PET-MRe) and its correlation with the commonly used biomarkers. Methods: In this exploratory study, 41 patients who were referred for colonoscopy for suspicion of CD, or evaluation of active CD, with a known prior diagnosis, underwent PET-MRe within 8 weeks of the endoscopic evaluation. A SES-CD was obtained at colonoscopy, CRP and fecal calprotectin (FC) were also measured. Imaging results were divided into: no, short-segment (<10cm) or long-segmental (>10cm) inflammation. The study was approved by the local IRB. Correlations were made between the extent of inflammation obtained by PET-MRe and the other parameters using the SAS 9.4 system, by Chi-Square and Wilcoxon tests. Univariate and multivariate analyses were performed per the above parameters. Results: 34 patients had terminal ileal (TI) disease and 7 had no evidence of inflammation. There was good correlation between active inflammation demonstrated in the terminal ileum by PET-MRe and FC >150, p<0.0008. Increased CRP levels and SES-CD score, showed a trend correlating with the extent of inflammation obtained from imaging, with median values of 0.69, 0.76 and 1.35 for CRP (p=0.26), and SES-CD scores of 1, 4.5 and 5.5 (p=0.32), when compared to non-inflamed, short segment and long segment of inflamed terminal ileum, respectively. Conclusions: This is a preliminary report of our pilot cohort of CD patients assessed by a novel imaging technique which will further enable the 3-dimensional evaluation of the burden of inflammation in CD patients. The transmural nature of this disease necessitates a modality that incorporates deep tissues uptake of FDG. We intend to further investigate the composite score that will express this.

Background: Data regarding the association between H. pylori carriage and a decreased risk of inflammatory bowel disease (IBD) are conflicting, as socioeconomic status (SES) is inversely related to both conditions, and could hypothetically confound the results. We aimed to assess whether this association exists independently of SES. Methods: We analyzed socioeconomic and medical information of 262,977 adult patients who consecutively performed urea breath tests (UBT) in Clalit Health Services at set intervals from 2007 to 2014. Figure 1. Study flow. IBD diagnosis and demographic, prescription and smoking status data and were extracted from HMO electronic database, and synchronized with detailed government-source socioeconomic information. Results: Out of the 262,977 subjects included, 2,240 (0.9%) had been diagnosed with IBD. The overall rate of H. pylori carriage among IBD vs. none-IBD subjects in the low, medium and high SES groups was 60.2% vs. 70.3%, 58.3% vs. 62.0% and 46.6% vs. 51.3%, accordingly; p<0.001 for each group. In multivariate analysis, H. pylori carriage was inversely associated with the diagnosis of IBD (OR 0.80; 95% CI 0.73–0.87; p<0.001). This effect was independent of socioeconomic confounders, and evident for all SES. Figure 2. Inverse association between H. pylori and IBD is independent of SES. Conclusions: Among a cohort of more than a quarter-million adult patients who performed a UBT, H. pylori carriage is inversely associated with a diagnosis of IBD, independently of socioeconomic confounders. Subjects carrying H. pylori may be less susceptible to develop IBD. Further studies are needed to explore the precise cause-and-effect relationship of this association.

Abstract Background: Pouchitis is a common complication in patients undergoing restorative proctocolectomy for ulcerative colitis. Therapeutic attempts include manipulations of pouch flora composition. In this systematic review, we aimed to score the evidence supporting the use of probiotics and prebiotics in pouchitis patients, to clarify the place of these treatments in current therapeutic regimens. Methods: We conducted extensive electronic searches of the PubMed and SCOPUS databases, from their earliest records through Nov 2016, for MESH terms “probiotics” and “pouchitis”. Results: The electronic search retrieved 20 citations [1–20]. Six published RCTs [2,3,9,10,13,14] and a RCT presented as an abstract [12] evaluated clinical, endoscopic end/or histological effect of probiotics as a primary outcome; other reports ranged in level of evidence between meta-analyses [16–19] (4), open-labeled trials [1,4–8,11,15] (8) and letters [20] (1). Conclusions: Prevention of onset of pouchitis/Primary prevention. Three studies examined the ability of various probiotic regimens to prevent the onset of pouchitis after the restorative proctocolectomy [1–3]. Primary preventive effect of VSL#3 was indicated by a single RCT, with calculated effect ratio of 1.50 [1.02, 2.21] [16]. Table 1. Use of probiotics for prevention of onset of pouchitis Study No. of patients Duration (months) probiotic strain Strain Control Pouchitis-free survival Gosselink (2004) 117 36 LGG No treatment (historical control) 93% vs. 71% (p=0.011) Gionchetti (2003) [2] 40 12 VSL#3 Placebo 90% vs. 60% (p<0.05) Yasueda (2015) [3] 17 24 Clostridium butyricum Placebo 89% vs. 50% (NS) Treatment of acute episode. Seven – mostly open-labeled and uncontrolled – trials examined the use of probiotics for treatment of acute pouchitis episode [4–10]. Efficacy of probiotics in acute episodes of pouchitis needs to be proved in randomized controlled trials. Table 2. Use of probiotics for treatment of active pouchitis Study No. of patients Duration (months) Strain Control Outcome Gionchetti et al. (2007) [4] 23 1 VSL#3 Open-labeled; uncontrolled 69% remission rate Laake et al. (2005) [5] 51 (10 with active disease) 1 Cultura® fermented milk product Open-labeled; uncontrolled Symptomatic and endoscopic improvement in patients with active disease Laake et al. (1999) [21] Cultura® fermented milk product Open-labeled; uncontrolled Symptomatic improvement Laake et al. (2003) [7] 10 ½ month Cultura® fermented milk product Open-labeled; uncontrolled Endoscopic improvement Laake et al. (2004) [8] 41 UC + 10 FAP 1 Cultura® fermented milk product Open-labeled; uncontrolled Symptomatic remission and endoscopic improvement Tomasz et al. (2014) [9] 43 (14 with active disease) 9 Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. Bulgaricus, Bifidobacterium bifidus Placebo 43% remission rate vs 0% on placebo Kuisma (2003) [10] 20 3 LGG Placebo No benefit Seven studies aimed to determine the efficacy of probiotic strains in preventing recurrences in patients with previous episode/s of pouchitis [4,9,11–15]. Probiotic mixture VSL#3 effectively prevents relapses after successful antibiotic treatment of active inflammation, with calculated effect ratio of 20.24 [4.28, 95.81] [16]. Side effects may affect the adherence of the patients with the long-term treatment [15,16]. Table 3. Use of probiotics for prevention of recurrences of pouchitis Study No. of patients Duration (months) Probiotic strain Control Outcome Pronio (2008) [11] 31 12 VSL#3 No treatment Small reduction of PDAI scores Brown (2004) [12] (abstract) 17 6 Bifidobacterium longum BB-536 Placebo Pouchitis-free survival 86% vs. 60% on placebo (NS); small reduction of PDAI scores Tomasz et al. (2014) [9] 43 9 Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. Bulgaricus, Bifidobacterium bifidus Placebo 43% in remission vs 0% on placebo Gionchetti et al. (2007) [4] 16 6 VSL#3 Open-labeled; uncontrolled 69% remission rate Gionchetti (2000) [13] 40 9 VSL#3 Placebo Pouchitis-free survival 85% vs. 0% on placebo (P<0.001) Mimura (2004) [14] 36 12 VSL#3 Placebo Pouchitis-free survival 85% vs. 6% on placebo (P<0.0001) Shen (2005) [15] 31 8 VLS#3 (self administration) Open-labeled compliance trial 80% non-adherence; 74% self-reported recurrence of symptoms References: [1] Gosselink, M.P., et al., Delay of the first onset of pouchitis by oral intake of the probiotic strain Lactobacillus rhamnosus G.G. Dis Colon Rectum, 2004. 47(6): p. 876–84. [2] Gionchetti, P., et al., Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology, 2003. 124(5): p. 1202–9. [3] Yasueda, A., et al., The effect of Clostridium butyricum MIYAIRI on the prevention of pouchitis and alteration of the microbiota profile in patients with ulcerative colitis. Surg Today, 2015. [4] Gionchetti, P., et al., High-dose probiotics for the treatment of active pouchitis. Dis Colon Rectum, 2007. 50(12): p. 2075–82. [5] Laake, K.O., et al., Outcome of four weeks' intervention with probiotics on symptoms and endoscopic appearance after surgical reconstruction with a J-configurated ileal-pouch-analanastomosis in ulcerative colitis. Scand J Gastroenterol, 2005. 40(1): p. 43–51. [6] Laake, K.O., et al., Influence of fermented milk on clinical state, fecal bacterial count and biochemical characteristics in patients with Ileo-Pouch-Anal-Anastomosis. Microb Ecol Health Dis, 1999. 11: p. 211–7. [7] Laake, K.O., et al., Assessment of mucosal inflammation and circulation in response to probiotics in patients operated with ileal pouch anal anastomosis for ulcerative colitis. Scand J Gastroenterol, 2003. 38(4): p. 409–14. [8] Laake, K.O., et al., Assessment of mucosal inflammation and blood flow in response to four weeks' intervention with probiotics in patients operated with a J-configurated ileal-pouchanal-anastomosis (IPAA). Scand J Gastroenterol, 2004. 39(12): p. 1228–35. [9] Tomasz, B., et al., Long-term use of probiotics Lactobacillus and Bifidobacterium has a prophylactic effect on the occurrence and severity of pouchitis: a randomized prospective study. Biomed Res Int, 2014. 2014: p. 208064. [10] Kuisma, J., et al., Effect of Lactobacillus rhamnosus GG on ileal pouch inflammation and microbial flora. Aliment Pharmacol Ther, 2003. 17(4): p.509–15. [11] Pronio, A., et al., Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells. Inflamm Bowel Dis, 2008. 14(5): p. 662–8. [12] Brown, S.J., et al., Bifidobacterium longum BB-536 and prevention of acute pouchitis. Gastroenterology, 2004. 126(4 Suppl 2): p. S465. [13] Gionchetti, P., et al., Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology, 2000. 119(2): p. 305–9. [14] Mimura, T., et al., Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut, 2004. 53(1): p. 108–14. [15] Shen, B., et al., Maintenance therapy with a probiotic in antibiotic-dependent pouchitis: experience in clinical practice. Aliment Pharmacol Ther, 2005. 22(8): p. 721–8. [16] Singh, S., et al., Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis. Cochrane Database Syst Rev, 2015. 11: p. CD001176. [17] Shen, J., Z.X. Zuo, and A.P. Mao, Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, Crohn's disease, and pouchitis: meta-analysis of randomized controlled trials. Inflamm Bowel Dis, 2014. 20(1): p. 21–35. [18] Elahi, B., et al., On the benefit of probiotics in the management of pouchitis in patients underwent ileal pouch anal anastomosis: a meta-analysis of controlled clinical trials. Dig Dis Sci, 2008. 53(5): p. 1278–84. [19] Holubar, S.D., et al., Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis. Cochrane Database Syst Rev, 2010(6): p. CD001176. [20] Kuzela, L., M. Kascak, and A. Vavrecka, Induction and maintenance of remission with nonpathogenic Escherichia coli in patients with pouchitis. Am J Gastroenterol, 2001. 96(11): p. 3218–9.

BACKGROUND:Vedolizumab (VDZ) is an anti-integrin monoclonal antibody effective in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to examine the "real world" efficacy and safety of VDZ in a large national patient cohort.METHODS:Patients with inflammatory bowel disease treated with VDZ were prospectively followed for 14 weeks. Patients who completed the induction protocol (week 0/2/6/14) or discontinued the treatment before week 14 for adverse events (AEs) or primary nonresponse were included. The primary outcome was induction of clinical remission at week 14; secondary outcomes included clinical response and corticosteroid-free clinical remission.RESULTS:A total of 204 patients (CD-130, UC-69, inflammatory bowel disease-unclassified-5) from 8 centers in Israel were included. Fifteen (7.4%) of the patients were anti-tumor necrosis factor naive and 46 (35.4%) had a previous surgery. For patients with CD, 69/130 (53.1%) responded to treatment; 45 (34.6%) achieved clinical remission; and 38 (29.2%) achieved corticosteroid-free remission at week 14. Fourteen (10.7%) patients discontinued VDZ before week 14 due to primary nonresponse or AEs. For UC, 32/74 (43.2%) responded to treatment; 20 (28.4%) achieved clinical remission, and 18 (24.3%) achieved corticosteroid-free remission at week 14. Fifteen (20.3%) patients with UC did not complete the induction due to primary nonresponse or AEs. AEs were reported by 29 (14.2%) patients (CD and UC combined), most common being nasopharyngitis and skin eruptions.CONCLUSIONS:In a large real-world Israeli cohort of anti-tumor necrosis factor-experienced patients with inflammatory bowel disease, VDZ was effective and safe in induction of clinical remission and steroid-free clinical remission.