Prebiotic Treatment in Patients with Nonalcoholic Fatty Liver Disease (NAFLD)-A Randomized Pilot Trial.

Several studies show that gut microbiotas in patients with nonalcoholic fatty liver disease (NAFLD) differ from those in a healthy population, suggesting that this alteration plays a role in NAFLD pathogenesis. We investigated whether prebiotic administration affects liver fat content and/or liver-related and metabolic parameters. Patients with NAFLD and metabolic syndrome (age: 50 ± 11; 79% men) were randomized to receive either 16 g/day of prebiotic (ITFs-inulin-type fructans) (n = 8) or placebo (maltodextrin) (n = 11) for 12 weeks. Patients were instructed to maintain a stable weight throughout the study. Liver fat content (measured by H1MRS), fecal microbiota, and metabolic, inflammatory, and liver parameters were determined before and after intervention. Fecal samples from patients who received the prebiotic had an increased content of Bifidobacterium (p = 0.025), which was not observed with the placebo. However, the baseline and end-of-study liver fat contents did not change significantly in the prebiotic and placebo groups, neither did the liver function tests' metabolic and inflammatory mediators, including fibroblast growth factor-19 and lipopolysaccharide-binding protein. Body weight remained stable in both groups. These findings suggest that prebiotic treatment without weight reduction is insufficient to improve NAFLD.

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.

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).

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.

Cholecystectomy and Biliary Sphincterotomy Increase Fecal Bile Loss and Improve Lipid Profile in Dyslipidemia.

BACKGROUND AND AIMS: Bile is the only significant pathway for cholesterol elimination. Cholecystectomy (CS) increases fecal bile acid loss, and endoscopic biliary sphincterotomy (ES) is thought to have a similar effect. We speculated that a combined effect of ES + CS would further enhance fecal bile acid loss, potentially causing lipid profile changes in these patients. METHODS: Fecal bile acids and sterols were determined using gas chromatography in cohorts of post-CS + ES, post-CS and in healthy controls. The effect of ES + CS on blood lipid profile was assessed retrospectively in a single-center cohort of post-CS + ES patients, using a computerized database. Parameters of interest included demographics, medical history, and lipid profiles. RESULTS: Fecal primary bile acid concentrations were increased after CS + ES compared to CS and controls (cholic acid [CA] 1.4 ng/mg vs. 0.26 ng/mg, p = 0.02 vs. 0.23 ng/mg, p = 0.004, chenodeoxycholic acid [CDCA] 1.92 ng/mg vs. 0.39 ng/mg, p = 0.02 vs. 0.23 ng/mg, p = 0.01, respectively). Fecal cholesterol excretion was similar in all three groups. Baseline serum lipid profile and subsequent changes following CS + ES were correlated. In patients with baseline hypercholesterolemia (total cholesterol (TC) > 200 mg/dl), TC levels decreased by 28.5 mg/dl, and LDL levels decreased by 21.5 mg/dl. The effect was more pronounced in those with TC > 200 mg/dl, despite of statin intake. In patients with hypertriglyceridemia [triglycerides (TG) > 200 mg/dl], TG decreased by 67.8 mg/dl following ES + CS. Among patients without dyslipidemia or dyslipidemia with adequate response to statins, the effect of ES + CS on lipid profile was minor. CONCLUSIONS: Fecal bile acid loss increases following CS + ES. The effect on blood lipid profile depends on baseline TC and TG levels. Lipid profile is improved in dyslipidemic patients, while the impact of CS + ES is minimal on the normolipemic population.

Fecal microbiome signatures of pancreatic cancer patients.

Pancreatic cancer (PC) is a leading cause of cancer-related death in developed countries, and since most patients have incurable disease at the time of diagnosis, developing a screening method for early detection is of high priority. Due to its metabolic importance, alterations in pancreatic functions may affect the composition of the gut microbiota, potentially yielding biomarkers for PC. However, the usefulness of these biomarkers may be limited if they are specific for advanced stages of disease, which may involve comorbidities such as biliary obstruction or diabetes. In this study we analyzed the fecal microbiota of 30 patients with pancreatic adenocarcinoma, 6 patients with pre-cancerous lesions, 13 healthy subjects and 16 with non-alcoholic fatty liver disease, using amplicon sequencing of the bacterial 16S rRNA gene. Fourteen bacterial features discriminated between PC and controls, and several were shared with findings from a recent Chinese cohort. A Random Forest model based on the microbiota classified PC and control samples with an AUC of 82.5%. However, inter-subject variability was high, and only a small part of the PC-associated microbial signals were also observed in patients with pre-cancerous pancreatic lesions, implying that microbiome-based early detection of such lesions will be challenging.

Medical cannabis for inflammatory bowel disease: real-life experience of mode of consumption and assessment of side-effects.

OBJECTIVE: Use of medical cannabis for improving symptoms of inflammatory bowel disease is increasing. However, reports on long-term outcomes are lacking. This prospective, observational study assessed the effects of licensed cannabis use among patients with inflammatory bowel disease. METHODS: Dose and mode of consumption, adverse events, use of other medications, and long-term effects were evaluated among 127 patients with inflammatory bowel disease using legalized medical cannabis. Blood count, albumin, and C-reactive protein were assessed before, 1 month, and at least 1 year after medical cannabis therapy was initiated. Questionnaires on disease activity, patient function, and signs of addiction were completed by patients and by a significant family member to assess its effects. RESULTS: The average dose used was 31 ± 15 g/month. The average Harvey-Bradshaw index improved from 14 ± 6.7 to 7 ± 4.7 (P < 0.001) during a median follow-up of 44 months (interquartile range, 24-56 months). There was a slight, but statistically significant, average weight gain of 2 kg within 1 year of cannabis use. The need for other medications was significantly reduced. Employment among patients increased from 65 to 74% (P < 0.05). We conclude that the majority of inflammatory bowel disease patients using cannabis are satisfied with a dose of 30 g/month. We did not observe negative effects of cannabis use on the patients' social or occupational status. CONCLUSIONS: Cannabis use by inflammatory bowel disease patients can induce clinical improvement and is associated with reduced use of medication and slight weight gain. Most patients respond well to a dose of 30 g/month, or 21 mg Δ9-tetra- hydrocannabinol (THC) and 170 mg Cannabidiol (CBD) per day.

A novel gallbladder umbrella stent (the Shai™ Stent) for prevention of stone migration and impaction: results on feasibility and short-term safety in a porcine model.

BACKGROUND AND AIMS: Cholelithiasis is the most common biliary tract disorder. Surgery is the treatment of choice for symptomatic gallstones. Aims of this study were to investigate the feasibility and short-term safety of a new endoscopic procedure with a specially designed Nitinol gallbladder stent for blockage of gallstone migration, the Shai™ Stent. The Shai stent is designed to enable free bile flow, which will be supposed to prevent recurrent attacks. METHODS: The Shai™ Stent was inserted into the gallbladder during a standard ERCP procedure using a conventional metal stent delivery system. The aim of the present study was to investigate the feasibility and safety of insertion and deployment and removal of the stent into the gallbladder of pigs. In addition, the short-term safety of the stent was evaluated. RESULTS: Fifteen stents were placed in the gallbladder of 15 pigs. Mean procedure time was 25 min (15-37). The maximum follow-up before sacrifice was 42 days. The stent in 1 pig had migrated at the 42 days follow-up but there were no macroscopic changes in its gallbladder or other organs. The stent remained in place in the remaining 12 pigs at autopsy, and the gallbladder and bile ducts were macroscopically normal. Stent removal was easily done in two pigs immediately after placement. CONCLUSIONS: Correct placement and removal of the Shai™ Stent in the gallbladder is safe and feasible in pigs. Further clinical trials are warranted to confirm these results and to effectively evaluate the capability of this stent as an innovative biotechnology to block gallstones from migration and impaction.

Diabetes Mellitus and Age are Risk Factors of Interval Colon Cancer: A Case-Control Study.

BACKGROUND AND AIMS: Interval colorectal cancer (CRC) is largely related to a poor endoscopic performance or different biology in the development of the polyp. However, patient-related factors were less investigated for their association with interval cancer. We thus evaluated tumor and patient characteristics as predictors of interval cancer in a population from Israel. METHODS: In this retrospective study, patients that were diagnosed with colon cancer in our institution and had 2 colonoscopies were included. Demographic parameters and tumor characteristics were compared between 84 cases with interval cancer, occurring 1-10 years after a negative colonoscopy, and 983 patients with primary CRC. In addition, patient-related features, including diabetes and diverticulosis, were compared between 51 patients with interval cancer after negative colonoscopy and 255 controls with no cancer and a previous negative colonoscopy. RESULTS: Compared to "positive" controls with primary cancer, patients with interval cancer were older (age 71.3 vs. 67.6, p = 0.003), had proximal tumor location (57 vs. 34%, p < 0.001) and non-advanced (0-2) tumor staging (78.5 vs. 64.8%, p = 0.014). Compared with -"negative" healthy controls, cases with interval cancer had only higher prevalence of diabetes (31 vs. 15%, p = 0.002). No significant differences were seen between patients with interval cancer occurring < 3 years and after 3-10 years. CONCLUSIONS: Patients with Interval cancer tend to be older and have diabetes. These patient groups should be more carefully or more frequently screened for pre-malignant lesions.

Risk of metachronous advanced lesions after resection of diminutive and small, non-advanced adenomas.

BACKGROUND AND AIMS: Current post-polypectomy surveillance interval guidelines do not discriminate between 1-2 diminutive (1-5mm) and small (6-9mm) non-advanced adenomas. This study compared the risk for metachronous advanced lesions in these groups. METHODS: Patients with 1-2 diminutive, non-advanced adenomas and no further advanced lesions, and patients with no polyps at baseline colonoscopy were retrospectively analyzed to determine the rate of metachronous advanced lesions. These were defined as the combined rate of colon cancer, advanced adenoma and ≥ 3 non-advanced adenomas at surveillance colonoscopy. Polyp size was measured either subjectively by the endoscopist or by pathology-based measurements. RESULTS: Among patients with diminutive (n = 395) and small polyps (n = 110), advanced lesions were found in 68 patients (17.2%) and 16 patients (14.5%), respectively (P = 0.53), during a mean follow-up of 4.3 ± 0.9 years. In contrast, advanced lesions were observed in 33 patients (6.6%) in the no polyp group (n = 505), significantly lower than diminutive (P = 0.000) and small polyp groups (P = 0.002), despite a mean follow-up duration of 6.1 ± 1.9 years. The rate of metachronous advanced lesions was also similar between patients with 1-3mm polyps (16%) versus 7-9mm polyps (15.8%). CONCLUSIONS: Our findings suggest that among patients who underwent polypectomy of up to 2 non-advanced adenomas, those with diminutive and small polyps have the same risk of metachronous advanced lesions; thus, supporting uniform recommendations for surveillance colonoscopy for these lesions.

The Relationship between Gender, Severity of Disease, Treatment Type, and Employment Outcome in Patients with Inflammatory Bowel Disease in Israel.

Introduction: Since individuals with IBD typically experience symptoms during their prime years of employment, it raises the question about IBD impact on employment status. Most studies concentrated on absenteeism from work with varying results in different populations. However, absenteeism reflects only one dimension of the ability to work and does not expose the problem of inability to hold a full-time job. Aims: To evaluate the influence of IBD on unemployment and working hours in Israel. Secondary aims were to investigate the correlation between working hours and the type of medical treatment and the impact of severity of disease. Patients and Methods: Demographic data, employment status, number of weekly working hours, and disease parameters. The data was compared to that of the general Israeli population extracted from the website of the Central Bureau of Statistics. Results: 242 IBD patients were interviewed. Patients median age was 37.04(IQR 30.23-44.68) years and 88 (36.4%) were men and 154 (63.6%) women. Diagnosis of CD was established in 167 (69%) patients and UC in 65 (26.9%). There was no significant reduction in employment rates or working hours among the IBD patients comparing to the general population. Immunosuppressive or biologic treatment did not influence employment status. The unemployed patients had higher disease severity (median 7.33, IQR 5-10.66) compared to employed patients (median 6, IQR 3.66-7.66; p=0.003). Conclusions: Although IBD patients in Israel do not have higher unemployment, those with severe disease have lower proportion of employment.

Identification of Synergistic Interaction Between Cannabis-Derived Compounds for Cytotoxic Activity in Colorectal Cancer Cell Lines and Colon Polyps That Induces Apoptosis-Related Cell Death and Distinct Gene Expression.

Introduction: Colorectal cancer remains the third most common cancer diagnosis and fourth leading cause of cancer-related mortality worldwide. Purified cannabinoids have been reported to prevent proliferation, metastasis, and induce apoptosis in a variety of cancer cell types. However, the active compounds from Cannabis sativa flowers and their interactions remain elusive. Research Aim: This study was aimed to specify the cytotoxic effect of C. sativa-derived extracts on colon cancer cells and adenomatous polyps by identification of active compound(s) and characterization of their interaction. Materials and Methods: Ethanol extracts of C. sativa were analyzed by high-performance liquid chromatography and gas chromatograph/mass spectrometry and their cytotoxic activity was determined using alamarBlue-based assay (Resazurin) and tetrazolium dye-based assay (XTT) on cancer and normal colon cell lines and on dysplastic adenomatous polyp cells. Annexin V Assay and fluorescence-activated cell sorting (FACS) were used to determine apoptosis and cell cycle, and RNA sequencing was used to determine gene expression. Results: The unheated cannabis extracts (C2F), fraction 7 (F7), and fraction 3 (F3) had cytotoxic activity on colon cancer cells, but reduced activity on normal colon cell lines. Moreover, synergistic interaction was found between F7 and F3 and the latter contains mainly cannabigerolic acid. The F7 and F7+F3 cytotoxic activity involved cell apoptosis and cell cycle arrest in S or G0/G1 phases, respectively. RNA profiling identified 2283 differentially expressed genes in F7+F3 treatment, among them genes related to the Wnt signaling pathway and apoptosis-related genes. Moreover, F7, F3, and F7+F3 treatments induced cell death of polyp cells. Conclusions:C. sativa compounds interact synergistically for cytotoxic activity against colon cancer cells and induce cell cycle arrest, apoptotic cell death, and distinct gene expression. F3, F7, and F7+F3 are also active on adenomatous polyps, suggesting possible future therapeutic value.

Primary sclerosing cholangitis is associated with abnormalities in CFTR.

BACKGROUND: The etiology of primary sclerosing cholangitis (PSC) is unknown. PSC and Cystic Fibrosis related liver disease have common features: chronic inflammation, biliary damage and similar cholangiographic findings. It is unknown whether or not PSC is related to cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. We hypothesize that a sub-group of PSC patients may be a "single-organ" presentation of CF. METHODS: Patients with PSC underwent nasal potential difference (NPD) measurement, sweat chloride measurement and complete CFTR sequencing by new generation sequencing. RESULTS: 6/32 patients aged 46 ±â€¯13 yrs. had CFTR causing mutations on one allele and 19 had CFTR polymorphisms; 6/23 tested had abnormal and 21 had intermediate sweat tests; 4/32 patients had abnormal NPD. One patient had chronic pancreatitis and was infertile. CONCLUSIONS: 19% of PSC patients had features of CFTR related disorder, 19% carry CFTR mutations and 50% had CFTR polymorphisms. In some patients, PSC may be a single organ presentation of CF or a CFTR-related disorder.

Revealing the Puzzle of Nonadherence in IBD-Assembling the Pieces.

Background: Adherence is generally associated with improved treatment outcomes in inflammatory bowel disease (IBD) patients. Different components of the patient profile have an impact on patient adherence. Capturing nonadherent patients by identifying modifiable risk factors in daily practice still remains a challenge. The objective of this study was to identify modifiable and nonmodifiable risk factors for nonadherence in IBD patients. Methods: Patients filled out questionnaires including demographic, clinical, and socioeconomic information and accessibility to gastrointestinal services. Psychological features were assessed using the Sense of Coherence, Hospital Anxiety and Depression Scale, IBD-Self Efficacy, and Brief Illness Perception (BIPQ) questionnaires. Adherence to treatment was evaluated using the Morisky score. Results: The study included 311 patients: 62.4% females, median age 34.78 years, 70.4% Crohn's disease (CD). Multivariate analysis was done in 3 sections: demographic and disease characteristics, communication with medical staff, and psychological aspects; all included sex and disease type. Ulcerative colitis (UC) patients were less adherent (odds ratio [OR], 1.792; OR, 1.915; OR, 1.748; respectively). Females were less adherent in 2 sections (OR, 1.841; OR, 1.751; respectively). Employment (OR, 2.449), low score in on the BIPQ-understanding of disease (OR, 0.881), and poor communication with the gastroenterologist (OR, 1.798) were also predictors of low adherence. Conclusions: Nonmodifiable characteristics such as female sex and UC are associated with low adherence. Good communication with the treating physician and understanding the disease are modifiable factors associated with high adherence. Early intervention might improve patients' adherence.

Telomere Length, Aggregates, and Capture in Cirrhosis.

BACKGROUND: Shortened telomeres were found in patients with cirrhosis, probably reflecting chronic liver injury, continuous regeneration, and destruction of hepatic nodules. OBJECTIVES: To test whether telomere shortening is a general marker of cirrhosis, independent of disease etiology. METHODS: We evaluated telomere length in patients with cryptogenic cirrhosis (largely a late sequela of steatohepatitis) compared to patients with cirrhosis caused by chronic hepatitis B and C (HBV/HCV). We also evaluated telomere aggregates, a sensitive parameter of telomere dysfunction and genetic instability. We analyzed peripheral lymphocytes from 25 patients with cryptogenic cirrhosis, 15 patients with cirrhosis due to chronic viral hepatitis, and 20 age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization. Aggregate size was divided into three fusion groups of 2-5, 6-10, and 11-15 telomeres, relative to the size of a single telomere. RESULTS: Shorter telomere length was found in patients with cirrhosis from all three etiologies (mean 121.3 ± 24.1) compared to controls (mean 63.5 ± 23.5). In contrast, there was significantly more fusion of > 5 telomeres only in the HBV/HCV cirrhosis group compared to healthy controls (P = 0.023), but not in the cryptogenic cirrhosis group. CONCLUSIONS: While shortened telomeres in peripheral lymphocytes are a general marker of liver cirrhosis, telomere aggregates may signify a more sensitive genetic instability parameter for the diverse, etiology-based malignant potential of cirrhosis. This finding is in agreement with the well-known higher tendency toward developing hepatocellular carcinoma with cirrhosis caused by chronic hepatitis relative to steatohepatitis.

Anti-Inflammatory Activity in Colon Models Is Derived from Δ9-Tetrahydrocannabinolic Acid That Interacts with Additional Compounds in Cannabis Extracts.

Introduction: Inflammatory bowel diseases (IBDs) include Crohn's disease, and ulcerative colitis. Cannabis sativa preparations have beneficial effects for IBD patients. However, C. sativa extracts contain hundreds of compounds. Although there is much knowledge of the activity of different cannabinoids and their receptor agonists or antagonists, the cytotoxic and anti-inflammatory activity of whole C. sativa extracts has never been characterized in detail with in vitro and ex vivo colon models. Material and Methods: The anti-inflammatory activity of C. sativa extracts was studied on three lines of epithelial cells and on colon tissue. C. sativa flowers were extracted with ethanol, enzyme-linked immunosorbent assay was used to determine the level of interleukin-8 in colon cells and tissue biopsies, chemical analysis was performed using high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance and gene expression was determined by quantitative real-time PCR. Results: The anti-inflammatory activity of Cannabis extracts derives from D9-tetrahydrocannabinolic acid (THCA) present in fraction 7 (F7) of the extract. However, all fractions of C. sativa at a certain combination of concentrations have a significant increased cytotoxic activity. GPR55 receptor antagonist significantly reduces the anti-inflammatory activity of F7, whereas cannabinoid type 2 receptor antagonist significantly increases HCT116 cell proliferation. Also, cannabidiol (CBD) shows dose dependent cytotoxic activity, whereas anti-inflammatory activity was found only for the low concentration of CBD, and in a bell-shaped rather than dose-dependent manner. Activity of the extract and active fraction was verified on colon tissues taken from IBD patients, and was shown to suppress cyclooxygenase-2 (COX2) and metalloproteinase-9 (MMP9) gene expression in both cell culture and colon tissue. Conclusions: It is suggested that the anti-inflammatory activity of Cannabis extracts on colon epithelial cells derives from a fraction of the extract that contains THCA, and is mediated, at least partially, via GPR55 receptor. The cytotoxic activity of the C. sativa extract was increased by combining all fractions at a certain combination of concentrations and was partially affected by CB2 receptor antagonist that increased cell proliferation. It is suggested that in a nonpsychoactive treatment for IBD, THCA should be used rather than CBD.

Surveillance after positive colonoscopy based on adenoma characteristics.

BACKGROUND: Patients with adenomatous polyps are at increased risk for developing colorectal cancer based on the characteristics and number of polyps, but less is known about the individual and combined contribution of these factors. This study aimed to better characterize the risk of advanced adenoma and cancer in patients with positive baseline colonoscopy. METHODS: Patients who had polyps at baseline colonoscopy were included in this retrospective cohort study (N=1165) and were categorized into 6 groups: (1) 1-2 non-advanced adenomas (NAA's), (2) ≥3 NAA's, (3) advanced tubular adenoma, (4) small tubulovillous adenoma (TVA), (5) large TVA and (6) multiple advanced adenomas (MAA's). Findings at surveillance colonoscopy were documented in each group. RESULTS: The combined incidence of advanced adenoma, ≥3 NAA's, and colorectal cancer at surveillance colonoscopy was significantly higher in the baseline large TVA (29.2%) than small TVA groups (13.5%, P<0.001), as well as in the MAA's group (44.1%) compared with large TVA group (P=0.02). The incidence of colorectal cancer, however, was not significantly different between the groups. CONCLUSIONS: The size of the polyp and the number of advanced lesions are more important than its histology for predicting the risk of high-risk metachronous lesions at follow-up.