Validation and Update of the Lémann Index to Measure Cumulative Structural Bowel Damage in Crohn's Disease.

BACKGROUND & AIMS: The Lémann Index is a tool measuring cumulative structural bowel damage in Crohn's disease (CD). We reported on its validation and updating. METHODS: This was an international, multicenter, prospective, cross-sectional observational study. At each center, 10 inclusions, stratified by CD duration and location, were planned. For each patient, the digestive tract was divided into 4 organs, upper tract, small bowel, colon/rectum, anus, and subsequently into segments, explored systematically by magnetic resonance imaging and by endoscopies in relation to disease location. For each segment, investigators retrieved information on previous surgical procedures, identified predefined strictures and penetrating lesions of maximal severity (grades 1-3) at each organ investigational method (gastroenterologist and radiologist for magnetic resonance imaging), provided segmental damage evaluation ranging from 0.0 to 10.0 (complete resection). Organ resection-free cumulative damage evaluation was then calculated from the sum of segmental damages. Then investigators provided a 0-10 global damage evaluation from the 4-organ standardized cumulative damage evaluations. Simple linear regressions of investigator damage evaluations on their corresponding Lémann Index were studied, as well as calibration plots. Finally, updated Lémann Index was derived through multiple linear mixed models applied to combined development and validation samples. RESULTS: In 15 centers, 134 patients were included. Correlation coefficients between investigator damage evaluations and Lémann Indexes were >0.80. When analyzing data in 272 patients from both samples and 27 centers, the unbiased correlation estimates were 0.89, 0,97, 0,94, 0.81, and 0.91 for the 4 organs and globally, and stable when applied to one sample or the other. CONCLUSIONS: The updated Lémann Index is a well-established index to assess cumulative bowel damage in CD that can be used in epidemiological studies and disease modification trials.

The Accuracy of Serum Biomarkers in the Diagnosis of Steatosis, Fibrosis, and Inflammation in Patients with Nonalcoholic Fatty Liver Disease in Comparison to a Liver Biopsy.

Background and Objective: This study was conducted to evaluate the diagnostic performance of various biomarkers for steatosis, fibrosis, and inflammation in comparison to a liver biopsy (LB) in patients with nonalcoholic fatty liver disease (NAFLD). Materials and Methods: This was a cross-sectional study that included 135 patients with biopsy-proven NAFLD. Fatty liver index (FLI), hepatic steatosis index (HSI), cell death markers (CK-18 M30 and CK-18 M65), FIB-4 index, NAFLD fibrosis score (NFS), BARD, and AST to platelet ratio index (APRI) were calculated and analysed. Results: FLI, HSI scores, and the cell death biomarkers showed poor diagnostic accuracy for steatosis detection and quantification, with an area under the curve (AUC) of <0.70. The cell death biomarkers likewise did not perform well for the detection of nonalcoholic steatohepatitis (NASH) (AUC < 0.7). As for the fibrosis staging, only APRI and the cell death biomarkers had moderate accuracy (AUC > 0.7) for advanced fibrosis, whereas FIB-4, BARD, and NFS scores demonstrated poor performance (AUC < 0.70). However, a combination of FIB-4 and NFS with the cell death biomarkers had moderate accuracy for advanced (≥F3) fibrosis detection, with an AUC of >0.70. Conclusions: In this first study on Croatian patients with NAFLD, serum biomarkers demonstrated poor diagnostic performance for the noninvasive diagnosis of liver steatosis and NASH. APRI and the cell death biomarkers had only moderate accuracy for diagnosing advanced fibrosis, as did the combination of FIB-4 and NFS with the cell death biomarkers. Further studies regarding serum biomarkers for all NAFLD stages are needed.

Efficacy and Safety of Vedolizumab Subcutaneous Formulation in a Randomized Trial of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Maintenance treatment with vedolizumab, a monoclonal antibody that inhibits the gut-selective α4ß7 integrin, is administered intravenously. Some patients might prefer a subcutaneous formulation of vedolizumab for maintenance treatment. Subcutaneous vedolizumab was investigated as maintenance treatment in patients with moderately to severely active ulcerative colitis. METHODS: We performed a phase 3, double-blind, double-dummy trial at 141 sites in 29 countries from December 18, 2015 through August 21, 2018. Patients with moderately to severely active ulcerative colitis received open-label treatment with intravenous vedolizumab 300 mg at weeks 0 and 2. At week 6, patients with clinical response were randomly assigned maintenance treatment with subcutaneous vedolizumab 108 mg every 2 weeks, intravenous vedolizumab 300 mg every 8 weeks, or placebo. The primary end point was clinical remission at week 52, which was defined as a total Mayo score of ≤2 and no subscore >1. RESULTS: Among the randomized 216 patients, clinical remission at week 52 was achieved by 46.2%, 42.6%, and 14.3% of patients in the subcutaneous vedolizumab, intravenous vedolizumab, and placebo groups, respectively (subcutaneous vedolizumab vs placebo: Δ32.3%; 95% confidence interval, 19.7%-45.0%; P < .001). The subcutaneous vedolizumab group also had greater endoscopic improvement and durable clinical response at week 52 compared with placebo (both P < .001). The incidence of injection-site reactions was more frequent in patients given subcutaneous vedolizumab (10.4%) than intravenous vedolizumab (1.9%) or placebo (0%); these were not treatment limiting, most were mild, and none resulted in discontinuation. Subcutaneous and intravenous vedolizumab safety profiles were otherwise similar. CONCLUSIONS: Subcutaneous vedolizumab is effective as maintenance therapy in patients with moderately to severely active ulcerative colitis who had a clinical response to intravenous vedolizumab induction therapy. It has a favorable safety and tolerability profile. ClinicalTrials.gov ID: NCT02611830; EudraCT 2015-000480-14.

Prevalence, predictors and age-related sexual and erectile dysfunction in patients with inflammatory bowel disease: A tertiary centre experience.

INTRODUCTION: The impact of sexuality and quality of life (QOL) is one of the main concerns of IBD. Despite the obvious relevance of this problem, knowledge of the extent of sexual dysfunction (SD) in IBD is limited. Aim of this study was to assess the prevalence of SD and erectile dysfunction (ED), QOL their predictors, and their age-related dynamic in IBD patients. METHODS: In this cross-sectional study, 202 IBD patients [122 male, 80 female, 133 Crohn's disease (CD), 69 ulcerative colitis (UC)] fulfilled International Index of Erectile Function (IIEF) or Female Sexual Functioning Index (FSFI). QOL was assessed using IBDQ-32 through bowel, systemic, emotional and social domains. RESULTS: Prevalence of SD in men was 18%, ED 30.3% and SD in women 75%. Low QOL was present in 34.6% without gender difference (P = .253). In men, SD and ED were highest among 21-30 years and raising after 51 years of age. In women, SD was constantly highly prevalent, showing no decline over time. In multivariate analysis significant predictors of SD in men were CD phenotype, disease duration and emotional domain of IBDQ, of ED depression, emotional and bowel domain of IBDQ, and of SD in women emotional IBDQ domain. CONCLUSION: Quality of sex life is a serious concern among IBD patients and is age related. Components that play a role in sexual functioning in IBD require more clarification and further development of screening and treatment guidelines for SD to provide better care in the IBD population.

Relationship between coffee consumption, sleep duration and smoking status with elastographic parameters of liver steatosis and fibrosis; controlled attenuation parameter and liver stiffness measurements.

AIM: our aim was to explore the association between life habits and the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) as the surrogate markers of liver steatosis and fibrosis in a large cohort of non-alcoholic fatty liver disease (NAFLD) patients. METHODS: In this prospective, cross-sectional study we had analysed 1998 patients with diagnosed NAFLD. Sleeping duration was categorised in three groups: short (S) (<6 hours), moderate (M) (6-8 hours) and long (L) (>8 hours) sleep duration. Coffee drinking was categorized into no (0), moderate (1-2) and frequent (≥3) consumption (in cups/day). Smoking was categorised as yes versus no. RESULTS: Frequent coffee consumers had the lowest prevalence of obesity, hypertension, dyslipidaemia and diabetes. Furthermore, coffee non-consumers had highest values of hepatic enzymes, CAP and LSM. Moderate sleep duration was associated with lower values of CAP and LSM. Coffee consumption was associated with lower CAP in all the multivariate models (CAP unadjusted and model 1, 2 and 3), with largest effect in most frequent coffee consumers (≥3, model 3). Also, most frequent coffee consumers were associated with lower LSM in unadjusted model, model 1 and 2, while this was not the case for model 3 and those who consumed 1-2 cups of coffee per day. Reduced sleeping was confirmed as risk factor for elevated CAP in most of the models (unadjusted and model 1 and 2). Also, negative association of LSM was also confirmed in unadjusted model and model 2. Patients which slept 6-8 hours per day were mostly associated with lower CAP and LSM. Smoking status was not associated with CAP or LSM values. CONCLUSION: Coffee consumption has beneficial effect on CAP and LSM and this effect is dose dependent since and independent of a variety of relevant confounders. We have shown that moderate sleep duration has also beneficial effect on CAP and LSM.

Small intestinal bacterial overgrowth and non-alcoholic fatty liver disease diagnosed by transient elastography and liver biopsy.

BACKGROUND: We aimed to determine if there was a higher incidence of small intestinal bacterial overgrowth (SIBO) in non-alcoholic fatty liver disease (NAFLD) than in patients without NAFLD. Moreover, we assessed whether patients with significant fibrosis (SF) had a higher incidence of SIBO compared with patients with non-significant or no liver fibrosis. METHODS: NAFLD was diagnosed in 117 patients by using Fibroscan with a controlled attenuation parameter (CAP) as well as liver biopsy (LB). SIBO was defined by esophagogastroduodenoscopy with an aspiration of the descending duodenum. RESULTS: Patients with non-alcoholic steatohepatitis (NASH) and those with SF on LB had a significantly higher incidence of SIBO than patients without NASH and those without SF, respectively (P < .05). According to histological characteristics, there was a higher proportion of patients in the SIBO group with higher steatosis and fibrosis grade, lobular and portal inflammation, and ballooning grade (P < .001). In multivariate analysis, significant predictors associated with SF and NASH were type 2 diabetes mellitus (T2DM) and SIBO. Moreover, in multivariate analysis, significant predictors that were independently associated with SIBO were T2DM, fibrosis stage and ballooning grade (OR 8.80 (2.07-37.37), 2.50 (1.16-5.37) and 27.6 (6.41-119), respectively). The most commonly isolated were gram-negative bacteria, predominantly Escherichia coli and Klebsiella pneumoniae. CONCLUSION: In this relatively large population of patients, we used a gold standard for both SIBO (quantitative culture of duodenum's descending part aspirate) and NAFLD (LB), and we demonstrated that NASH patients and those with SF had a higher incidence of SIBO. Moreover, significant predictors independently associated with SIBO were T2DM, fibrosis stage and ballooning grade. Although TE is a well-investigated method for steatosis and fibrosis detection, in our study, independent predictors of SIBO were histological characteristics of NAFLD, while elastographic parameters did not reach statistical significance.

Intravenous supplementation type and volume are associated with 1-year outcome and major complications in patients with chronic intestinal failure.

BACKGROUND AND AIM: No marker to categorise the severity of chronic intestinal failure (CIF) has been developed. A 1-year international survey was carried out to investigate whether the European Society for Clinical Nutrition and Metabolism clinical classification of CIF, based on the type and volume of the intravenous supplementation (IVS), could be an indicator of CIF severity. METHODS: At baseline, participating home parenteral nutrition (HPN) centres enrolled all adults with ongoing CIF due to non-malignant disease; demographic data, body mass index, CIF mechanism, underlying disease, HPN duration and IVS category were recorded for each patient. The type of IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorised as <1, 1-2, 2-3 and >3 L/day. The severity of CIF was determined by patient outcome (still on HPN, weaned from HPN, deceased) and the occurrence of major HPN/CIF-related complications: intestinal failure-associated liver disease (IFALD), catheter-related venous thrombosis and catheter-related bloodstream infection (CRBSI). RESULTS: Fifty-one HPN centres included 2194 patients. The analysis showed that both IVS type and volume were independently associated with the odds of weaning from HPN (significantly higher for PN <1 L/day than for FE and all PN >1 L/day), patients' death (lower for FE, p=0.079), presence of IFALD cholestasis/liver failure and occurrence of CRBSI (significantly higher for PN 2-3 and PN >3 L/day). CONCLUSIONS: The type and volume of IVS required by patients with CIF could be indicators to categorise the severity of CIF in both clinical practice and research protocols.

Perioperative Probiotics or Synbiotics in Adults Undergoing Elective Abdominal Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To define the impact of perioperative treatment with probiotics or synbiotics on postoperative outcome in patients undergoing abdominal surgery. BACKGROUND: Postoperative surgical infection accounts for a third of all cases of sepsis, and is a leading cause of morbidity and mortality. Probiotics, prebiotics, and synbiotics (preparations that combine probiotics and prebiotics) are nutritional adjuncts that are emerging as novel therapeutic modalities for preventing surgical infections. However, current evidence on their effects is conflicting. METHODS: A comprehensive search of the PubMed, Embase, and WHO Global Index Medicus electronic databases was performed to identify randomized controlled trials evaluating probiotics or synbiotics in adult patients undergoing elective colorectal, upper gastrointestinal, transplant, or hepatopancreaticobiliary surgery. Bibliographies of studies were also searched. The primary outcome measure was incidence of postoperative infectious complications. Secondary outcomes included incidence of noninfectious complications, mortality, length of hospital stay, and any treatment-related adverse events. Quantitative pooling of the data was undertaken using a random effects model. RESULTS: A total of 34 randomized controlled trials reporting on 2723 participants were included. In the intervention arm, 1354 patients received prebiotic or symbiotic preparations, whereas 1369 patients in the control arm received placebo or standard care. Perioperative administration of either probiotics or synbiotics significantly reduced the risk of infectious complications following abdominal surgery [relative risk (RR) 0.56; 95% confidence interval (CI) 0.46-0.69; P < 0.00001, n = 2723, I = 42%]. Synbiotics showed greater effect on postoperative infections compared with probiotics alone (synbiotics RR: 0.46; 95% CI: 0.33-0.66; P < 0.0001, n = 1399, I = 53% probiotics RR: 0.65; 95% CI: 0.53-0.80; P < 0.0001, n = 1324, I = 18%). Synbiotics but not probiotics also led to a reduction in total length of stay (synbiotics weighted mean difference: -3.89; 95% CI: -6.60 to -1.18 days; P = 0.005, n = 535, I = 91% probiotics RR: -0.65; 95% CI: -2.03-0.72; P = 0.35, n = 294, I = 65%). There were no significant differences in mortality (RR: 0.98; 95% CI: 0.54-1.80; P = 0.96, n = 1729, I = 0%) or noninfectious complications between the intervention and control groups. The preparations were well tolerated with no significant adverse events reported. CONCLUSIONS: Probiotics and synbiotics are safe and effective nutritional adjuncts in reducing postoperative infective complications in elective abdominal surgery. The treatment effects are greatest with synbiotics.

Diagnosis of malnutrition in patients with gastrointestinal diseases: recent observations from a Global Leadership Initiative on Malnutrition perspective.

PURPOSE OF REVIEW: To review recent reports on techniques and tools for screening and diagnosis of malnutrition in gastrointestinal disease, in the light of the newly published definition of malnutrition by the Global Leadership Initiative on Malnutrition (GLIM). RECENT FINDINGS: In 2019, the GLIM concept of malnutrition was published advocating a two-step procedure; first, screening, and second confirmation of the diagnosis that requires a combination of phenotypic and etiologic criteria. Three studies in patients with gastrointestinal disorders so far published utilize the GLIM criteria. Otherwise, traditional tools, as Nutrition Risk Screening-2002, Malnutrition Universal Screening Tool or Subjective Global Assessment are used, and confirm that malnutrition is observed in a substantial number of patients with inflammatory bowel diseases (IBDs), serious liver disorders and various forms of pancreatitis. Common for these disorders is an extensive loss of muscle mass, which is one of the GLIM phenotypic criteria. Such patients often undergo abdominal computed tomography scans that enable psoas muscle mass at L3 or L4 level to be calculated. SUMMARY: The GLIM criteria for the diagnosis of malnutrition are feasible for IBD, liver and pancreas diseases. Pending studies expect to provide data on the clinical relevance to diagnose malnutrition by the GLIM concept.

Vitamin D for treatment of non-alcoholic fatty liver disease detected by transient elastography: A randomized, double-blind, placebo-controlled trial.

AIM: To evaluate the effects of vitamin D on transient elastography (TE, FibroScan) indices of liver steatosis (controlled attenuation parameter [CAP]) and fibrosis (liver stiffness measurement [LSM]) in adults with non-alcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: In this randomized (2:1), double-blind, single-centre, 12-month trial, patients with NAFLD were treated with vitamin D (1000 IU/day) (n = 201) or a matching placebo (n = 110). Two co-primary outcomes were changes in CAP and LSM after 360 days of treatment versus baseline. Two main secondary outcomes were CAP/LSM changes after 180 days of treatment. RESULTS: Both CAP and LSM gradually decreased in vitamin D-treated patients and slightly increased in the placebo arm. Vitamin D was superior to placebo for both primary outcomes (mean differences in CAP and LSM changes (-49.5 dB/m [95% CI -59.5 to -39.4] and -0.72 kPa [95% CI -1.43 to 0.00], respectively) and both secondary outcomes (-22.1 dB/m [-32.1 to -12.1] and -0.89 kPa [-1.61 to -0.17], respectively). Of a number of exploratory outcomes (change at 12 months vs. baseline), vitamin D reduced serum uric acid (-17.9 µmol/L [-30.6 to -5.2]), gamma-glutamyltransferase (-8.9 IU/L [-15.5 to -2.3)] and fasting serum insulin levels (-5.1 pmol/L [-9.3 to -0.8]) as well as the homeostatic model assessment of insulin resistance index (-1.6 [-3.1 to -0.2]) (false discovery rate [5%]-adjusted P-values between .0572 and .0952). CONCLUSION: Low-medium dose supplementation of vitamin D (1000 IU/day) over 12 months reduces TE indices of liver steatosis (CAP) and fibrosis (LSM) in NAFLD patients.

HIGH PREVALENCE OF UNTREATED AND UNDERTREATED VITAMIN D DEFICIENCY AND INSUFFICIENCY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE.

Inflammatory bowel disease (IBD) patients with vitamin D deficiency show an increased risk of hospital admission, surgery, and loss of response to biologic therapy while high vitamin D levels are identified as a protective factor. Our goal was to investigate the prevalence of untreated and undertreated vitamin D deficiency and factors associated with vitamin D deficiency. In this cross-sectional study, we measured serum vitamin D in a random sample of Caucasian IBD patients. Vitamin D deficiency was defined as <50 nmol/L and insufficiency as 50-75 nmol/L. Supplementation was defined as taking 800-2000 IU vitamin D daily. Untreated patients were defined as not taking supplementation and undertreated group as receiving supplementation but showing vitamin D deficiency or insufficiency despite treatment. Our study included 185 IBD patients, i.e. 126 (68.1%) with Crohn's disease (CD) and 59 (31.9%) with ulcerative colitis (UC). Overall, 108 (58.4%) patients had vitamin D deficiency and 60 (32.4%) patients vitamin D insufficiency. There were 16 (14.8%) and 11 (18.3%) treated patients in vitamin D deficiency and vitamin D insufficiency group, respectively. The rate of untreated patients was 81.7% (n=49) in vitamin D deficiency group and 85.2% (n=92) in vitamin D insufficiency group. Tumor necrosis factor alpha inhibitors were associated with higher serum vitamin D levels in CD and UC, and ileal involvement, ileal and ileocolonic resection with lower levels. In conclusion, not only is vitamin D deficiency common in IBD patients but the proportion of untreated and undertreated patients is considerably high. We suggest regular monitoring of vitamin D levels in IBD patients regardless of receiving vitamin D supplementation therapy.

The Mediterranean diet and its association with selected gut bacteria.

PURPOSE OF REVIEW: Mediterranean diet is often viewed in the context of impact on composition of gut microbiota and its consequences on prevention and treatment of various diseases. It is known how complex carbohydrates present in this type of dietary pattern are fermented by healthy gut microbiota, producing in turn short-chained fatty acids with purported benefits for human health, whereas other mechanisms and interactions play a role as well. RECENT FINDINGS: Recent research endeavors take a step further and demonstrate how exactly Mediterranean diet can affect the composition, activity, and diversity of intestinal microorganisms and their metabolomic profiles, and how these alterations can be linked to various chronic diseases. A change in the ratio of two dominant gut phyla (Firmicutes and Bacteroidetes) represents a hallmark feature of many diseases, which can be influenced by introducing dietary modifications. In addition, gut microbiota composition as a whole may serve as a marker of Mediterranean diet adherence. SUMMARY: Increasing our knowledge and awareness of diet-microbiota interdependence may result in specific and targeted dietary approaches for microbial modulation and subsequent disease risk reduction, with Mediterranean diet serving as a blueprint for healthy eating.

A Single Small Bowel Hemangioma Detected by Video Capsule Endoscopy in a Patient Presenting with Iron-deficiency Anemia - Two Case Reports.

Hemangioma of the small intestine is a rare vascular malformation which mostly presents as occult gastrointestinal bleeding and iron-deficiency anemia. Patients are often asymptomatic except of fatigue due to anemia. Hemangiomas can arise anywhere in the luminal gastrointestinal tract, with jejunum as the most commonly involved site. They are very hard to recognize mostly due to their localization. Video capsule endoscopy and balloon-assisted enteroscopy have very much improved preoperative diagnostics and made major contribution to establishing the diagnosis - which was very difficult in the past and almost all cases were diagnosed during or after the operation. Surgical resection is still the conventional treatment modality, although with the improvement of endoscopic therapeutic interventions (endoscopic mucosal resection, argon-plasma coagulation) there are more therapeutic possibilities.

LEUKOCYTAPHERESIS IN THE MANAGEMENT OF SEVERE STEROID-DEPENDENT ULCERATIVE COLITIS.

Ulcerative colitis (UC) is a multifactorial disease of unknown precise etiology and immunopathogenesis. Peripheral blood granulocytes and monocytes/macrophages are the major sources of cytokines, which regulate inflammation. Leukocytapheresis (LCAP) is a method where blood is processed by apheresis system that removes lymphocytes and plasma before being returned to the body. We report the first case in Croatia where we used LCAP in the treatment of a patient with severe steroid-dependent UC. After 12 LCAP procedures, good clinical response was obtained and there were no significant adverse side effects noticed. The patient remained in clinical remission over two years in which he underwent regular follow ups at outpatient clinic. Over a 10-year follow-up period after LCAP, the patient had only occasional clinical symptoms of disease activity. The clinical course was complicated with the development of metastatic colorectal carcinoma, which points to the importance of regular disease monitoring rather than the increased risk of malignant disease after LCAP. Patients with UC are a demanding group of patients that warrant the search for novel treatment strategies other than conventional pharmacological therapies. Although LCAP is still not a common treatment modality in our daily practice, data from recent studies suggest it to be an effective and safe procedure in the management of active UC patients.

Increased arterial stiffness - similar findings in patients with inflammatory bowel disease without prior hypertension or diabetes and in patients with well-controlled hypertension.

PURPOSE: Chronic inflammatory diseases are related with earlier onset of atherosclerosis. We hypothesized that inflammatory bowel disease patients with chronic, systemic inflammation have an increased arterial stiffness associated with the disease duration. Also, we wanted to compare arterial stiffness markers between inflammatory bowel disease and well-controlled hypertension patients. MATERIALS AND METHODS: A total of 89 inflammatory bowel disease patients (60 patients with Crohn's disease and 29 patients with ulcerative colitis, age range 20-64 years) without history of arterial hypertension or diabetes were enrolled and age matched with a control group of patients (73 patients, age range 25-69 years, 41 (56.1%) males) with known history of well-controlled arterial hypertension. We have used a noninvasive device that simultaneously measures brachial blood pressure and estimates PWV and AIx in inflammatory bowel disease and hypertension groups of patients. RESULTS: Patients with pathological PWV values were significantly older, had significantly longer duration of inflammatory bowel disease, higher values of serum cholesterol and HDL-cholesterol, and higher AIx (17.4% vs. 9.8%) (all p < .05). Higher PWV was associated with age and duration of inflammatory bowel disease in the linear regression model. PWV values were higher in hypertensive patients in the first two age quartiles while interestingly, in the last two quartiles, PWV was lower than in inflammatory bowel disease group of patients. CONCLUSIONS: Chronic subclinical inflammation is responsible for dyslipidemia and accelerated atherosclerosis which consequently alterates arterial elasticity. Inflammatory bowel disease and its duration should also be considered a risk factor for subclinical organ damage, as well as hypertension.

Association of polymorphic variants in serotonin re-uptake transporter gene with Crohn's disease: a retrospective case-control study.

AIM: To analyze the distribution of SLC6A4 gene polymorphisms in Crohn's disease (CD) patients and their association with the disease. METHODS: We evaluated the presence/absence of promoter (5-HTTLPR, rs25531) and intron 2 (STin2 VNTR) polymorphic variants of SLC6A4 gene in a retrospective case-control study including 192 CD patients and 157 healthy controls (HC). Genotyping was performed by polymerase chain reaction. The association of polymorphisms with CD and its clinical subtypes was analyzed using χ2 and Fisher exact test, binary logistic regression, and haplotype analysis. RESULTS: CD patients and healthy controls had similar sex (88 [45.8%] vs 84 [53.5%] women, respectively; P=0.154) and age (41.3±12.8 years vs 41.7±8.8 years, respectively, P=0.091) distribution. Significant differences were observed in the STin2 genotype and allele distribution between CD patients and healthy controls (P=0.003 and P=0.002, respectively) and between the corresponding female subgroups (P=0.004 and P=0.007, respectively), with a significant negative association of biallelic ss (STin2.9 and Stin2.10) STin2 genotype with CD (P=0.013, age- and sex-adjusted odds ratio [OR] 0.5, 95% confidence interval [CI] 0.29-0.86; women: P=0.006, age-adjusted OR 0.32, 95% CI 0.14-0.72) and a significantly higher S-STin2.12 (5-HTTLPR/rs25531: S-STin2: STin2.12) haplotype distribution in CD patients (P=0.004, OR 1.62, 95% CI 1.16-2.26). There was no significant association between 5-HTTLRP and rs25531 genotype or allele frequencies and CD and between any SLC6A4 polymorphic loci with clinical CD subtypes. CONCLUSION: STin2 VNTR polymorphism of SLC6A4 gene may contribute to CD pathogenesis.

The Role of Vitamin D in Inflammatory Bowel Disease - Assessing Therapeutic and Preventive Potential of Supplementation and Food Fortification.

Inflammatory bowel diseases are a group of chronic inflammatory conditions that affect gastrointestinal tract due to inapt and continuous immune activation in response to a myriad of predisposing factors (most notably genetics, environmental impact and gut microbiota composition). It has been shown that vitamin D status can also play a role in the disease pathogenesis, as its deficiency is commonly observed in two major forms of inflammatory bowel diseases - Crohn's disease and ulcerative colitis. Mounting evidence supports the concept of intricate relationship between gut dysbiosis and vitamin D metabolism, while suboptimal levels of this vitamin have been linked to increased clinical disease relapse rates, inadequate response to drugs, as well as decreased quality of life in patients with Crohn's disease and ulcerative colitis. Consequently, the pertinent question is whether increased vitamin D supplementation and (on a population level) food fortification may bring significant benefit to the affected individuals. In this short review we discuss the synthesis, functions, status and food sources of vitamin D, appraise biotechnological facets of vitamin D status analysis and food fortification, and concentrate on novel developments in the field that describe its influence on intestinal microbiota and inflammatory bowel disease.

Modulating Composition and Metabolic Activity of the Gut Microbiota in IBD Patients.

The healthy intestine represents a remarkable interface where sterile host tissues come in contact with gut microbiota, in a balanced state of homeostasis. The imbalance of gut homeostasis is associated with the onset of many severe pathological conditions, such as inflammatory bowel disease (IBD), a chronic gastrointestinal disorder increasing in incidence and severely influencing affected individuals. Despite the recent development of next generation sequencing and bioinformatics, the current scientific knowledge of specific triggers and diagnostic markers to improve interventional approaches in IBD is still scarce. In this review we present and discuss currently available and emerging therapeutic options in modulating composition and metabolic activity of gut microbiota in patients affected by IBD. Therapeutic approaches at the microbiota level, such as dietary interventions alone or with probiotics, prebiotics and synbiotics, administration of antibiotics, performing fecal microbiota transplantation (FMT) and the use of nematodes, all represent a promising opportunities towards establishing and maintaining of well-being as well as improving underlying IBD symptoms.

GUIDELINES FOR THE PREVENTION, DETECTION AND THERAPY OF VITAMIN D DEFICIENCY IN ADULTS.

It is estimated that over one billion of people around the globe have low serum values of vitamin D, therefore, we can consider vitamin D deficiency as a pandemic and public health problem. Geographic position of Croatia, especially the continental part of the country, is a risk factor for the development of deficiency of vitamin D in the population. The aim of these guidelines is to provide the clinicians with easy and comprehensive tool for prevention, detection and therapy of vitamin D deficienney in healthy population and various groups of patients. They were made as a result of collaboration of clinicians of different backgrounds who are dealing with patients at risk of vitamin D deficiency. These guidelines are evi- dence-based, according to GRADE-system (Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendation. The main conclusions address the recommended serum vitamin D values in the population which should be between 75 and 125 nmol/L and defining recommended preven- tive and therapeutic dosages of vitamin D in order to reach the adequate levels of serum vitamin D.

[ABNORMALITIES OF HEMOSTASIS IN PATIENTS WITH LIVER CIRRHOSIS].

Until the beginning of the 90ies, it was believed that patients with liver cirrhosis were auto-anticoagulated and thus protected from thromboembolic events. However, new discoveries have broken the longstanding paradigm. In deranged hepatic function there is a reduced synthesis of procoagulants and endogenous anticoagulants, however, extrahepatally synthesized hemostatic and fibrinolytic factors are disproportionately affected. In stable disease hemostatic system is "rebalanced'' but fragile, therefore, even a minimal stress can promote bleeding or thrombosis. Also, there are many concomitant factors, such as hemodynamic changes, other organ affection, namely kidney, and predisposition to infection, that shift the balance towards either bleeding or thrombosis. Conventional laboratory tests are not sufficient for evaluation of the bleeding risk, prothrombotic risk factors are not clearly identified, and safety profile of antithrombotic drugs is not precisely evaluated since cirrhotic patients are mainly excluded from big clinical trials. For all that is said, the diagnostic and therapeutic approach in this context is complex and requires teamwork of a hepatologist, hematologist and in a phase of operative treatment, the anesthesiologist. In this review article, we will discuss mechanisms of hemostatic and fibrinolytic abnormalities of liver cirrhosis, the incidence of thromboembolic events as well as prophylactic and therapeutic options in the setting of conservative treatment.