Mesenchymal stem cell therapy for Crohn's perianal fistula-a real-world experience.

AIM: Remission rates of medically and surgically treated complex perianal fistulas in Crohn's disease are low. Recently, trials have demonstrated the potential for long-term remission with local injection of allogeneic adipose-derived mesenchymal stem cells (darvadstrocel). Our aim was to analyse outcomes from our real-world experience with this new treatment. METHODS: All patients with Crohn's disease suffering complex perianal fistulas who consecutively underwent administration of darvadstrocel at two centres were followed up and evaluated. Patients were assessed for clinical remission, response, failure, and any complications during follow-up. The results of all patients with a minimum of 3 months' follow-up are presented. RESULTS: Thirty-three patients with Crohn's disease and complex perianal fistulas were included. Of these, 20 (61%) experienced clinical remission that was maintained for a mean follow-up of 14 (3-32) months. A total of 24 of 33 (73%) experienced at least 3 months of clinical remission, with four later having recurrence (3-12 months). Among the remaining nine patients who did not experience clinical remission, two (6%) had partial remission (such as one of two fistulas closing), two (6%) showed signs of response but not remission, and five (15%) showed no signs of healing. The mean time to maintained clinical remission was 6 weeks (range 2 weeks to 6 months), and there were no severe adverse events. CONCLUSION: In this real-world experience, treatment of Crohn's disease complex perianal fistulas with darvadstrocel had a 61% success rate for maintained clinical remission.

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.

Cannabis Improves Clinical Outcomes and Quality of Life in Patients With Chronic Pouchitis.

Many patients with ulcerative colitis after ileoanal pouch anastomosis report improvement of pouchitis with the use of cannabis. Nine patients with chronic pouchitis used 1 g/d of cannabis: 7 patients were male with average age 51 ± 16 years. Average partial pouchitis disease activity index were 11 (range 8-17), 6 (range 5-8), and 5 (range 4-8); endoscopic subscores were 7 .3 ± 2.3, 6 ± 1.1, and 4.4 ± 0.9; average bowel movements per day were 14 (range 8-20), 8 (range 2-13), and 10 (range 13-8); and quality of life increased from 72 ± 1 to 90 ± 16 and 97 ± 10 (P = 0.001) before cannabis treatment and after 8-12 and 52 weeks, respectively. No adverse events were reported.

Do inflammatory bowel disease patient preferences from treatment outcomes differ by ethnicity and gender? A cross-sectional observational study.

BACKGROUND: Inflammatory bowel disease (IBD) patients' expectations of treatment outcomes may differ by ethnicity. AIM: To investigate treatment preferences of Jewish and Arabs patients. METHODS: This prospective survey ranked outcomes treatment preferences among Arab IBD patients, based on the 10 IBD-disk items compared to historical data of Jews. An anonymous questionnaire in either Arabic or Hebrew was distributed among IBD patients. Patients were required to rank 10 statements describing different aspects of IBD according to their importance to the patients as treatment goals. Answers were compared to the answers of a historical group of Jewish patients. RESULTS: IBD-disk items of 121 Arabs were compared to 240 Jewish patients. The Jewish patients included more females, [151 (62.9%) vs 52 (43.3%); P < 0.001], higher education level (P = 0.02), more urban residence [188 (78.3%) vs 54 (45.4%); P < 0.001], less unemployment [52 (21.7%) vs 41 (33.9%); P = 0.012], higher income level (P < 0.001), and more in a partnership [162 (67.8%) vs 55 (45.4%); P < 0.001]. Expectations regarding disease symptoms: abdominal pain, energy, and regular defecation ranked highest for both groups. Arabs gave significantly lower rankings (range 4.29-6.69) than Jewish patients (range 6.25-9.03) regarding all items, except for body image. Compared to Arab women, Jewish women attached higher priority to abdominal pain, energy, education/work, sleep, and joint pain. Multivariable regression analysis revealed that higher patient preferences were associated with Jewish ethnicity (OR 4.77; 95%CI 2.36-9.61, P < 0.001) and disease activity. The more active the disease, the greater the odds ratio for higher ranking of the questionnaire items (1-2 attacks per year: OR 2.13; 95%CI 1.02-4.45, P = 0.043; and primarily active disease: OR 5.29; 95%CI 2.30-12.18, P < 0.001). Factors inversely associated with higher patient preference were male gender (OR 0.5; 95%CI 0.271-0.935, P = 0.030), UC (OR 0.444; 95%CI 0.241-0.819, P = 0.009), and above average income level (OR 0.267; 95%CI: 0.124-0.577, P = 0.001). CONCLUSION: The highest priority for treatment outcomes was symptom relief., Patients preferences were impacted by ethnicity, gender, and socio-economic disparity. Understanding patients' priorities may improve communication and enable a personalized approach.

Mesenteric panniculitis is associated with cardiovascular risk-factors: A case-control study.

BACKGROUND: This study evaluated the prevalence of cardiovascular risk-factors in patients with mesenteric panniculitis. AIMS: To determine whether cardiovascular risk-factors and mesenteric panniculitis are associated. METHODS: Retrospective, matched case-control study of patients referred to Meir Medical Center, Israel, 2014-2019, who underwent computerized tomography scan, were diagnosed mesenteric panniculitis by radiologic criteria. They were compared to two, matched case-control groups: hospitalized patients without mesenteric panniculitis and the general population based on Israeli Ministry of Health surveys. Patients with active malignancy, IBD or significant intra-abdominal morbidity were excluded. RESULTS: Of 376 patients with mesenteric panniculitis diagnosed by computerized tomography, 187 were included. Compared to hospital patients, they had higher incidence of dyslipidemia (77.5%/56.7%), hypertension (52.4%/40.6%), obesity (body mass index>30) (60.4%/30.5%) and nonalcoholic fatty liver disease (42.2%/16.6%). Similar differences were observed compared to the general population. In multivariable logistic regression, dyslipidemia, obesity, and nonalcoholic fatty liver disease were independent predictors for mesenteric panniculitis. CONCLUSIONS: Patients with mesenteric panniculitis have more cardiovascular risk-factors compared to a case-control group and to the general population. This suggests that mesenteric panniculitis is clinically significant and may be part of the metabolic morbidity burden. This association should be further explored.

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.

Adherence, Safety, and Effectiveness of Medical Cannabis and Epidemiological Characteristics of the Patient Population: A Prospective Study.

BACKGROUND: Despite the absence of rigorous prospective studies, there has been an increase in the use of cannabis-based medicinal products. During the study period, the use of medical cannabis in Israel was tightly regulated by national policy. Through a prospective study of approximately 10,000 patients, we aimed to characterize the medical cannabis patient population as well as to identify treatment adherence, safety, and effectiveness. METHODS AND FINDINGS: In this study of prescribed medical cannabis patients, adherence, safety, and effectiveness were assessed at 6 months. Treatment adherence was assessed by the proportion of patients purchasing the medication out of the total number of patients (excluding deceased cases and patients transferred to another cannabis clinic). Safety was assessed by the frequency of the side-effects, while effectiveness was defined as at least moderate improvement in the patient condition without treatment cessation or serious side-effects. The most frequent primary indications requiring therapy were cancer (49.1%), followed by non-specific pain (29.3%). The average age was 54.6 ± 20.9 years, 51.1% males; 30.2% of the patients reported prior experience with cannabis. During the study follow-up, 1,938 patients died (19.4%) and 1,735 stopped treatment (17.3%). Common side-effects, reported by 1,675 patients (34.2%), were: dizziness (8.2%), dry mouth (6.7%), increased appetite (4.7%), sleepiness (4.4%), and psychoactive effect (4.3%). Overall, 70.6% patients had treatment success at 6 months. Multivariable logistic regression analysis revealed that the following factors were associated with treatment success: cigarette smoking, prior experience with cannabis, active driving, working, and a young age. The main limitation of this study was the lack of data on safety and effectiveness of the treatment for patients who refused to undergo medical assessment even at baseline or died within the first 6 months. CONCLUSIONS: We observed that supervised medical-cannabis treatment is associated with high adherence, improvement in quality of life, and a decrease in pain level with a low incidence of serious adverse events.

Short-term effectiveness and safety of tofacitinib in ulcerative colitis - real world data from tertiary medical centers in Israel.

BACKGROUND: We sought to define the effectiveness and safety of tofacitinib in a real-world (RW) cohort of Israeli patients with moderate to severe ulcerative colitis (UC). METHODS: This was a multi-center retrospective observational cohort study (2019-2020) to assess the effectiveness and safety of tofacitinib induction and maintenance therapy up to 26 weeks. Clinical response and remission were defined as a reduction in Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) of ≥3 points, and SCCAI ≤2 or a PMS ≤1, respectively. RESULTS: We included 73 patients, 47% male; median age 26 years [IQR: 19.5-39.5], disease duration 7 years [IQR: 2.5-14.5], follow-up 7.1 months [IQR: 3-12], 91% biologics-experienced, and 74% ≥ 2-biologics. Half of patients used concomitant corticosteroids (CS). Overall, 56.1% discontinued therapy due to either lack of response and/or adverse events (AEs), median time to discontinuation - 9.7 months [IQR 3.4-16]. Overall, response, remission, and CS-free-remission were achieved in 47.6%, 20.6%, and 17.5% of patients, respectively. At early maintenance (week 26), response, remission, and CS-free-remission were achieved in 65%, 22.5%, and 20% of patients, respectively. At week 26, tofacitinib 10 mg BID was still used in 43%. Seventeen patients (23.2%) had an adverse event including herpes zoster- 2.7%, hospitalization- 12.3%, and colectomy- 2.7%. CONCLUSIONS: Tofacitinib was effective in achieving CS-free-remission in about 1/5 of highly biologics -experienced patients with UC. Despite a considerable proportion of patients maintained on tofacitinib 10 mg bid, it was well tolerated and safe. Earlier positioning of tofacitinib in the therapeutic algorithm may result in improved outcomes.

Important relation between self-efficacy, sense of coherence, illness perceptions, depression and anxiety in patients with inflammatory bowel disease.

INTRODUCTION: Anxiety and depression are common disturbances in patients with inflammatory bowel diseases (IBD), and were found to impact the disease course. Illness perceptions (IPs), self-efficacy (SE) and sense of coherence (SOC) are important psychological functions, used by the individual to cope with his chronic disease. AIMS: to investigate the association of IP, SE and SOC on anxiety and depression among patients with IBD. PATIENTS AND METHODS: Patients filled questionnaires including: demographic, socioeconomic and clinical features. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. IP, SE and SOC were assessed using the Brief Illness perception Questionnaire, IBD-SE and SOC scales. RESULTS: The study sample consisted of 299 patients with IBD, median age 34.15, 63% females, 70.9% had Crohn's disease, filled the questionnaires. In the multivariate analysis, lower results in IP, SE and SOC were found to be associated with significantly increase anxiety (OR 8.35, p<0.001; OR 4.18, p=0.001; OR 4.67, p<0.001, respectively) and depression (OR 15.8, p=0.001; OR 10.99, p=0.029; OR 6.12, p=0.014. CONCLUSIONS: Anxiety and depression are associated with IP, SE and SOC in patients with IBD. Clinicians should be aware of this impact, recognise their patients' psychological abilities to cope with the disease and improve those abilities, when needed, in order to achieve a better coping with the disease and to prevent the development of anxiety and depression.

Endocannabinoid Levels in Ulcerative Colitis Patients Correlate With Clinical Parameters and Are Affected by Cannabis Consumption.

Background: Inflammatory bowel diseases (IBDs) are chronic, idiopathic, inflammatory, gastrointestinal disorders. The endocannabinoid system may have a role in the pathogenesis of IBD. We aimed to assess whether cannabis treatment influences endocannabinoids (eCBs) level and clinical symptoms of IBD patients. Methods: Blood samples and biopsies were taken from IBD patients treated by either cannabis or placebo for 8 weeks. Immunohistochemistry for N-acyl-phosphatidylethanolamine-selective phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH) expression was done on colon biopsies, and sample levels of anandamide (AEA), eCB2-arachidonylglycerol (2-AG), arachidonic acid (AA), palmitoylethanolamine (PEA), and oleoylethanolamine (OEA) were measured in patient's sera before and after cannabis treatment. Caco-2 cells were cultured with extracts of cannabis with/without tetrahydrocannabinol (THC) and their proteins extracted, and Western blotting for NAPE-PLD and FAAH expression was done. Results: Thirteen patients with Crohn's disease (CD) and nine patients with ulcerative colitis (UC) were treated with cannabis. Seventeen patients with CD and 10 with UC served as placebo groups. In all CD patients, the levels of eCBs remained unaltered during the treatment period. In UC patients treated with placebo, but not in those treated with cannabis, the levels of PEA, AEA, and AA decreased significantly. The percent reduction in bowel movements was negatively correlated with changes observed in the circulating AEA and OEA, whereas improvement in quality of life was positively correlated with the levels of 2-AG. In the biopsies from UC patients, FAAH levels increased over the study period. In Caco-2 cells, both cannabis extracts increased NAPE-PLD levels but reduced FAAH expression levels. Conclusion: Our study supports the notion that cannabis use affects eCB "tone" in UC patients and may have beneficial effects on disease symptoms in UC patients.

The inflammatory bowel disease disk application: A platform to assess patients' priorities and expectations from treatment.

OBJECTIVE: Inflammatory bowel disease (IBD) significantly impacts on patients' well-being. Patients' preferences for treatment outcomes do not necessarily fit physicians' goals. We aimed to investigate patients' priorities and expectations from treatment. METHODS: A questionnaire based on the IBD Disk application was distributed to patients through social media. Patient's preferences were assessed by grading the 10 IBD Disk items on a Likert-type scale from 1 to 10. A cluster analysis was used to classify patients into homogeneous subgroups according to their preferred items, using the K-means method. RESULTS: Among the 224 patients, 69.2% had Crohn's disease (CD). Their mean age was (38.9 ± 14.9) years and 62.9% were female. More CD patients compared with those with ulcerative colitis were treated with biologics compared with those with ulcerative colitis (71.0% vs 39.1%, P < 0.001). Most IBD Disk items ranked high in patients' preferences for treatment outcomes. Their leading preference was reducing abdominal pain, which was more prominent in CD patients, followed by regulating defecation and energy. Least important were interpersonal interactions, sexual functions, and body image. Patients were categorized into three clusters. Cluster 3 patients gave lower scores to most items and were characterized by tertiary education (P = 0.001), higher income (P < 0.001), less active disease (P = 0.02), and higher prevalence of successful treatment (P = 0.04). CONCLUSIONS: Patients' preferences for treatment outcomes are influenced by higher education, higher income, rural-dwelling, and disease activity. Better understanding of individual patient's preferences and the factors that affect them might bridge the gap between patients' and physicians' priorities to achieve better teamwork in controlling disease outcomes.

Oral CBD-rich Cannabis Induces Clinical but Not Endoscopic Response in Patients with Crohn's Disease, a Randomised Controlled Trial.

AIMS: Despite reports that medical cannabis improves symptoms in Crohn's disease [CD], controlled studies evaluating disease response are lacking. This study assessed the effect of cannabidiol [CBD]-rich cannabis oil for induction of remission in CD. METHODS: In a double-blind, randomised, placebo-controlled, single-centre trial, patients received orally either cannabis oil containing160/40 mg/ml cannabidiol/tetrahydrocannabinol [CBD/THC] or placebo for 8 weeks. Disease parameters, including the CD activity index [CDAI], and simple endoscopic score for CD [SES-CD], were assessed before and after treatment. In a subgroup of patients, blood samples were collected for CBD and THC plasma levels. RESULTS: The study included 56 patients, age 34.5 ± 11 years, men/women 30/26 [54/46%],30 in cannabis and 26 in placebo groups. CDAI at recruitment and after 8 weeks was 282 (interquartile range [IQR] 243-342) and 166 [IQR 82-226], and 264 [IQR 234-320] and 237 [IQR 121-271] [p <0.05] in the cannabis and placebo groups, respectively. Median quality of life [QOL] score improved from 74 for both groups at baseline to 91 [IQR 85-102] and 75 [IQR 69-88] after 8 weeks in the cannabis and placebo groups, respectively [p = 0.004]. SES-CD was 10 [IQR 7-14] and 11 [IQR7-14], and 7 [4-14] and 8 [IQR 4-12] [p = 0.75] before and after treatment, in the cannabis and placebo groups, respectively. Inflammatory markers (C-reactive protein [CRP], calprotectin) remained unchanged. CONCLUSIONS: Eight weeks of CBD-rich cannabis treatment induced significant clinical and QOL improvement without significant changes in inflammatory parameters or endoscopic scores. The oral CBD-rich cannabis extract was well absorbed. Until further studies are available, cannabis treatment in Crohn's disease should be used only in the context of clinical trials.

Cannabis is associated with clinical but not endoscopic remission in ulcerative colitis: A randomized controlled trial.

BACKGROUND: Cannabis is often used by patients with ulcerative colitis, but controlled studies are few. We aimed to assess the effect of cannabis in improving clinical and inflammatory outcomes in ulcerative colitis patients. METHODS: In a double-blind, randomized, placebo-controlled trial, patients received either cigarettes containing 0.5 g of dried cannabis flowers with80mgTetrahydrocannabinol (THC)or placebo cigarettes for 8 weeks. Parameters of disease including Lichtiger disease activity index, C reactive protein (CRP), calprotectin, Mayo endoscopic score and quality of life (QOL) were assessed before, during and after treatment. RESULTS: The study included 32 patients. Mean age was 30 years, 14 (43%) females. Lichtiger index improved in the cannabis group from 10.9 (IQR 9-14) to5 (IQR 1-7), (p<0.000), and in the placebo group from 11 (IQR 9-13) to 8 (IQR 7-10)(p = 0.15, p between groups 0.001). QOL improved in the cannabis group from 77±4 to 98±20 (p = 0.000) but not in the placebo group (78±3 at week 0 and 78±17 at week 8;p = 0.459; p between groups 0.007). Mayo endoscopic score changed in the cannabis group from 2.13±1 to 1.25±2 (p = 0.015) and in the placebo group from 2.15±1to 1.69±1 (p = 0.367, p between groups 0.17). CONCLUSION: Short term treatment with THC rich cannabis induced clinical remission and improved quality of life in patients with mild to moderately active ulcerative colitis. However, these beneficial clinical effects were not associated with significant anti-inflammatory improvement in the Mayo endoscopic score or laboratory markers for inflammation.(clinicaltrials.gov NCT01040910).

Physician adherence to societal guidelines following colonoscopy with polypectomy.

BACKGROUND: Colorectal cancer is a significant cause of mortality and morbidity in western countries. Polypectomy reduces the incidence and mortality of colorectal cancer. Following polypectomy, recommendations regarding the frequency and duration of surveillance rely mostly on features of the resected polyps and are summarized in various gastroenterological societal guidelines. In this study, we aimed to delineate the accuracy of current post-polypectomy surveillance recommendations and to check whether active intervention would lead to an improvement in accuracy and consistency with societal guidelines. METHODS: We prospectively collected polypectomy reports over a 3-month period in 2 tertiary medical centers. We then performed an intervention that included: 1) presentation of results from 1st phase; 2) re-affirming the guidelines in a departmental meeting; 3) addition of a dedicated reporting form for post-polypectomy surveillance recommendations in the patients' electronic medical file. Finally, we conducted a second prospective collection of post-polypectomy recommendations, over a second 3-month period. RESULTS: Prior to the intervention, 76% of the colonoscopies with polypectomy had a recommendation for surveillance, compared to 85% after the intervention (P=0.003). Prior to the intervention, 65% of patients received a recommendation consistent with societal guidelines, compared with 78% after the intervention (P=0.001). CONCLUSION: Intervention, including re-affirmation of the current guidelines and creation of a dedicated reporting platform, significantly increases the number of follow-up recommendations after polypectomy and their consistency with societal guidelines.

Role of Cannabis and Its Derivatives in Gastrointestinal and Hepatic Disease.

Medical and recreational cannabis use has increased dramatically over the last decade, resulting from mainstream cultural acceptance and legalization in several countries worldwide. Cannabis and its derivatives affect many gastrointestinal processes via the endocannabinoid system (ECS). The ECS influences gastrointestinal homeostasis through anti-inflammatory, anti-nociceptive, and anti-secretory effects. Some gastrointestinal disorders might therefore be treated with cannabinoids. Despite numerous studies in cell lines and animals, few human studies have evaluated the therapeutic effects of cannabinoids. Cannabis' schedule 1 drug status has limited its availability in research; cannabis has been legalized only recently, in some states, for medicinal and/or recreational use. Cannabinoids can alleviate chemotherapy-induced nausea and emesis and chronic pain. Studies have demonstrated the important roles of the ECS in metabolism, obesity, and nonalcoholic fatty liver disease and the anti-inflammatory effects of cannabis have been investigated in patients with inflammatory bowel diseases. Despite its potential benefits, undesired or even detrimental effects of cannabis can limit its use. Side effects such as cannabinoid hyperemesis syndrome affect some users. We review the ECS and the effects of cannabis and its derivatives on gastrointestinal and hepatic function in health and disease.

Cannabinoid receptor 2 agonist promotes parameters implicated in mucosal healing in patients with inflammatory bowel disease.

BACKGROUND: Cannabis benefits patients with inflammatory bowel disease (IBD). Cannabinoid receptors are expressed in gut immune cells and in epithelial cells of inflamed guts. Mucosal healing (MH) requires epithelial layer restoration. OBJECTIVE: To analyze the effects of CB2 agonist on parameters implicated in gut inflammation and MH. METHODS: Mucosal samples from areas of inflamed/uninflamed colon from 16 patients with IBD were cultured without/with cannabinoid receptor 2 (CB2) agonist (JWH-133, 10 µM, 6 hours (hr)), and analyzed for epithelial/stromal cell proliferation, apoptosis (secretome matrix metalloproteinase 9 (MMP9) activity, which impairs epithelial permeability) and interleukin-8 (IL-8) levels (n = 5-9). In addition, Caco-2 (colon carcinoma epithelial cells) were cultured with biopsy secretomes (48 hr), and analyzed for phenotype and protein markers of proliferation (proliferating cell nuclear antigen), autophagy (LC3IIB) and permeability (Zonula occludens-1) (n = 4-6). RESULTS: Uninflamed tissue had higher epithelial proliferation (Ki67: 50%↑, p < 0.05), and reduced secretome MMP9 activity and IL-8 levels (>50%↓, p < 0.05) compared to inflamed tissue. Treatment with CB2 agonist had no effect on epithelial apoptosis, but increased epithelial Ki67 expression (25%), and reduced secretome MMP9 and IL-8 levels in inflamed biopsies. Secretomes of CB2-treated biopsies increased Caco-2 number, migration, proliferating cell nuclear antigen and LC3IIB expression (all, p < 0.05), but had no effect on ZO-1. CONCLUSION: Using ex vivo and in vitro human models, we demonstrated that manipulating the cannabinoid system affects colon cells and secretome characteristics that facilitate MH in IBD.

An overview of cannabis based treatment in Crohn's disease.

Introduction: Cannabis use among inflammatory bowel disease (IBD) patients is common. There are many studies of various laboratory models demonstrating the anti-inflammatory effect of cannabis, but their translation to human disease is still lacking.Areas covered: The cannabis plant contains many cannabinoids, that activate the endocannabinoid system. The two most abundant phytocannabinoids are the psychoactive Tetrahydrocannabinol (THC), and the (mostly) anti-inflammatory cannabidiol (CBD). Approximately 15% of IBD patients use cannabis to ameliorate disease symptoms. Unfortunately, so far there are only three small placebo controlled study regarding the use of cannabis in active Crohns disease, combining altogether 93 subjects. Two of the studies showed significant clinical improvement but no improvement in markers of inflammation.Expert opinion: Cannabis seems to have a therapeutic potential in IBD. This potential must not be neglected; however, cannabis research is still at a very early stage. The complexity of the plant and the diversity of different cannabis chemovars create an inherent difficulty in cannabis research. We need more studies investigating the effect of the various cannabis compounds. These effects can then be investigated in randomized placebo controlled clinical trials to fully explore the potential of cannabis treatment in IBD.

Risk of metachronous neoplasia on surveillance colonoscopy among young and older patients after polypectomy.

BACKGROUND AND AIMS: Few reports address the appropriate colonoscopy surveillance interval for individuals <50-years-old. We compared the risk of metachronous neoplasia among young (<50 years), adult (50-74 years) and older (≥75 y) age groups. METHODS: This was a single center retrospective cohort study. Eligible subjects underwent their first colonoscopy with polypectomy between 2005 and 2014 and had at least one surveillance colonoscopy 3-5 years later. Patients (N = 495) were stratified at baseline into low-risk adenoma (LRA) and advanced adenoma groups. Study outcomes were overall and high-risk neoplasia at surveillance colonoscopy. RESULTS: In the baseline LRA-group (N = 201), the 5-year risk of metachronous high-risk neoplasia was 12.5%, 15.2% and 22.5% (P = 0.426) in the young, adult and older age groups, respectively. In the baseline advanced adenoma group (N = 294), the 3-year risk of metachronous high-risk neoplasia was 13.3%, 14.8% and 25.3% (P = 0.041), respectively. In multivariate analysis, the only risk factor for metachronous high-risk neoplasia was older age (OR 1.876, CI 1.087-3.238; P = 0.024). CONCLUSIONS: Considering the comparable risk of metachronous high-risk neoplasia in young and adult patients, surveillance recommendations after polypectomy should not differ. Since this risk is higher among older people, more frequent surveillance schedule can be considered for this age group but should be individualized.

Cannabis for the Treatment of Inflammatory Bowel Disease: A True Medicine or a False Promise?

Cannabis is the most widely used recreational drug worldwide and is used by some patients with inflammatory bowel disease (IBD) to ameliorate their disease. Whereas epidemiological studies indicate that as many as 15% of IBD patients use cannabis, studies inspecting cannabis use in IBD are few and small. We have conducted several studies looking at the use of cannabis in IBD. In Crohn's disease, we demonstrated that cannabis reduces the Crohn's disease activity index (CDAI) by >100 points (on a scale of 0-450).Two small studies in ulcerative colitis showed a marginal benefit. However, no improvement was observed in inflammatory markers or in endoscopic score in either disease. Many questions regarding cannabis use in IBD remain unanswered. For example, cannabis is a complex plant containing many ingredients, and the synergism or antagonism between them likely plays a role in the relative efficacy of various cannabis strains. The optimal doses and mode of consumption are not determined, and the most common form of consumption, i.e. smoking, is unacceptable for delivering medical treatment. Cannabis is a psychotropic drug, and the consequences of long-term use are unknown. Despite all these limitations, public opinion regards cannabis as a harmless drug with substantial medical efficacy. In Israel, the number of licenses issued for the medical use of cannabis is rising rapidly, as are the acknowledged indications for such use, but good-quality evidence for the effectiveness of cannabis is still lacking. Further studies investigating the medical use of cannabis are urgently needed.