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Purpose: The purpose of this study was to assess the effect of training with a personal, portable laparoscopic endo-trainer (PLET) on residents' laparoscopic skills., Methods: The study took place at a tertiary-care academic university hospital in Switzerland. All participants were randomized to either a home- or hospital-based PLET training group, and surgical skill performance was assessed using five laparoscopic exercises. 24 surgical residents, 13 females and 11 males, were enrolled at any training stage. Nine residents completed the assessments. Endpoints consisted of subjective and objective assessment ratings as well as exercise time and qualitative data up to 12 weeks. The primary outcome was the difference in exercise time and secondary outcomes included performance scores as well as qualitative data., Results: The hospital-based training group performed exercises number 1, 3 and 4 faster at 12 weeks than at baseline (p = .003, < 0.001 and 0.024). Surgical skill performance was not statistically significantly different in any of the endpoints between the hospital- and home-based training groups at 12 weeks. Both the subjective and objective assessment ratings significantly improved in the hospital-based training group between baseline and 12 weeks (p = .006 and 0.003, respectively). There was no statistically significant improvement in exercise time as well as subjective and objective assessment ratings over time in the home-based training group. The qualitative data suggested that participants who were randomized to the hospital-based training group wished to have the PLET at home and vice versa. Several participants across groups lacked motivation because of their workload or time constraints, though most believed the COVID-19 pandemic had no influence on their motivation or the time they had for training., Conclusion: The PLET enhances laparoscopic surgical skills over time in a hospital-based training setting. In order to understand and optimize motivational factors, further research is needed., Trial Registration: This trial was retrospectively registered on clinicaltrials.gov (NCT06301230)., (© 2024. The Author(s).)

Ionic liquids (ILs) have gained considerable attention due to their versatile and designable properties. ILs show great potential as antibacterial agents, but understanding the mechanism of attack on bacterial cells is essential to ensure the optimal design of IL-based biocides. The final aim is to achieve maximum efficacy while minimising toxicity and preventing resistance development in target organisms. In this study, we examined a dose-response analysis of ILs' antimicrobial activity against two pathogenic bacteria with different Gram types in terms of molecular responses on a cellular level using Fourier-transform infrared (FTIR) spectroscopy. In total, 18 ILs with different antimicrobial active motifs were evaluated on the Gram-negative enteropathogenic Escherichia coli (EPEC) and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). The results showed that most ILs impact bacterial proteins with increasing concentration but have a minimal effect on cellular membranes. Dose-response spectral analysis revealed a distinct ante-mortem response against certain ILs for MRSA but not for EPEC. We found that at sub-lethal concentrations, MRSA actively changed their membrane composition to counteract the damaging effect induced by the ILs. This suggests a new adaptive mechanism of Gram-positive bacteria against ILs and demonstrates the need for a better understanding before using such substances as novel antimicrobials.

Background: The most frequent complication of total thyroidectomy remains hypocalcemia due to low postoperative levels of serum intact parathyroid hormone (iPTH). The purpose of this study was to investigate the role of decreased iPTH at the end of surgery in predicting hypocalcemia. In addition, we examined the percentage decrease of iPTH as potential indicator of hypocalcemia., Methods: We retrospectively collected the data of patients who underwent total thyroidectomy for benign and malignant diseases at our institution between 2010 and 2022. The iPTH level was measured before and at the end of surgery, and serum calcium levels on the first postoperative day. Demographic, clinical, and biochemical characteristics of patients with low iPTH were compared with patients with normal iPTH levels using ANOVA for continuous variables and χ2-tests for categorical variables. Multivariable logistic regression analysis evaluated the association of iPTH at the end of surgery and the relative reduction of iPTH with postoperative hypocalcemia., Results: The mean age of the 607 patients in this study was 55.6 years, and the female-to-male ratio was 5:1. Goiter was the most common indication for surgery (N = 382, 62.9%), followed by Graves' disease (N = 135, 22.2%). The mean preoperative iPTH was 49.0 pg/ml, while the mean postoperative iPTH was 29.3 pg/ml. A total of 197 patients (32.5%) had an iPTH level below normal, 77 patients (39%), had iPTH levels of 10-15.0 pg/ml and 120 patients (61%) of < 10.0 pg/ml at the end of surgery. Among all patients, 124 (20.4%) developed hypocalcemia on the first postoperative day. The mean percentage of decrease of iPTH was highest among patients with iPTH < 10 pg/ml (76.9%, p < 0.01); this group of patients had also the highest rate of postoperative hypocalcemia on day one (45.0% vs. 26.0% vs 12.2%, p < 0.01)., Conclusions: Measurement of iPTH at the end of total thyroidectomy predicts patients who are at risk for postoperative hypocalcemia. The combination of low serum iPTH with a decrease in iPTH level of ≥ 50% may improve prediction of hypocalcemia compared to iPTH levels alone allowing for early calcium substitution in these patients at high risk of developing postoperative hypocalcemia., (© 2023. The Author(s).)

Lameness is an important health and welfare issue that causes considerable economic losses in dairy herds. The objective of this study was to investigate whether the hind feet position score (HFPS) can be used as an auxiliary trait for genetic evaluation of lameness. The HFPS is evaluated by visual scoring of the position of both the hind-digits to the mid-line of the cow's body. The higher the heel height of the lateral claw, the higher is the HFPS, and the higher is the risk for development of lameness. In total, 3,478 records from 1,064 Fleckvieh cows from 35 farms were obtained between September 1, 2021, and March 5, 2022. Data collection was carried out by the regional milk recording organizations. Hind feet position was scored visually by trained personnel during routine milk performance testing in the milking parlor using a 3-class scoring system: score 1 = 0° to <17° indicating a balanced heel height of both the medial and the lateral claw; score 2 = angle of 17° to 24°; score 3 = angle of >24°. After all cows had been milked, locomotion scoring was performed for each animal using a 5-class scoring system with locomotion scores ranging between 1 (normal) and 5 (severely lame). Using HFPS, sensitivity and specificity were 69.5% and 66.8%, respectively, for detecting lameness defined by locomotion score ≥2. For genetic analyses, a bivariate linear animal model was fitted with fixed effects of herd, parity, lactation stage, and classifier, and random effects of animal and permanent environment. Heritabilities for HFPS and locomotion score were 0.07 and 0.10, respectively, and the genetic correlation between the 2 traits studied was 0.80. These results suggest that the HFPS could be used for genetic evaluations to reduce lameness incidence in dairy cattle., (© 2023.)

This study aimed to develop a tool to detect mildly lame cows by combining already existing data from sensors, AMSs, and routinely recorded animal and farm data. For this purpose, ten dairy farms were visited every 30-42 days from January 2020 to May 2021. Locomotion scores (LCS, from one for nonlame to five for severely lame) and body condition scores (BCS) were assessed at each visit, resulting in a total of 594 recorded animals. A questionnaire about farm management and husbandry was completed for the inclusion of potential risk factors. A lameness incidence risk (LCS ≥ 2) was calculated and varied widely between farms with a range from 27.07 to 65.52%. Moreover, the impact of lameness on the derived sensor parameters was inspected and showed no significant impact of lameness on total rumination time. Behavioral patterns for eating, low activity, and medium activity differed significantly in lame cows compared to nonlame cows. Finally, random forest models for lameness detection were fit by including different combinations of influencing variables. The results of these models were compared according to accuracy, sensitivity, and specificity. The best performing model achieved an accuracy of 0.75 with a sensitivity of 0.72 and specificity of 0.78. These approaches with routinely available data and sensor data can deliver promising results for early lameness detection in dairy cattle. While experimental automated lameness detection systems have achieved improved predictive results, the benefit of this presented approach is that it uses results from existing, routinely recorded, and therefore widely available data.

Overexpression of MYC is a genuine cancer driver in lymphomas and related to poor prognosis. However, therapeutic targeting of the transcription factor MYC remains challenging. Here, we show that inhibition of the histone deacetylase 6 (HDAC6) using the HDAC6 inhibitor Marbostat-100 (M-100) reduces oncogenic MYC levels and prevents lymphomagenesis in a mouse model of MYC-induced aggressive B-cell lymphoma. M-100 specifically alters protein-protein interactions by switching the acetylation state of HDAC6 substrates, such as tubulin. Tubulin facilitates nuclear import of MYC, and MYC-dependent B-cell lymphoma cells rely on continuous import of MYC due to its high turn-over. Acetylation of tubulin impairs this mechanism and enables proteasomal degradation of MYC. M-100 targets almost exclusively B-cell lymphoma cells with high levels of MYC whereas non-tumor cells are not affected. M-100 induces massive apoptosis in human and murine MYC-overexpressing B-cell lymphoma cells. We identified the heat-shock protein DNAJA3 as an interactor of tubulin in an acetylation-dependent manner and overexpression of DNAJA3 resulted in a pronounced degradation of MYC. We propose a mechanism by which DNAJA3 associates with hyperacetylated tubulin in the cytoplasm to control MYC turnover. Taken together, our data demonstrate a beneficial role of HDAC6 inhibition in MYC-dependent B-cell lymphoma., (© 2022. The Author(s).)

We present two patients with right lower quadrant pain during the 36th week of pregnancy. In both cases, the challenges in diagnosing acute appendicitis in late pregnancy is underlined by misleading imaging results, revealing fluid in the lower abdomen, suggesting an appendicitis. Surgery was performed. Pre- and intraoperative gynecological examinations showed no signs of fetal distress. In patient 1, surgery revealed a torsion and necrosis of the right ovary and a 7-cm cyst of the fallopian tube. Open ovariectomy and appendectomy were performed. In patient 2, we saw a perforated appendicitis and cloudy ascites. Histology after appendectomy showed spots of endometriosis and serositis infiltrating into the appendix with signs of perforation at the tip. Patient 1 recovered after a short period of bowel paralysis. Patient 2 needed Caesarean section due to severe deceleration in the cardiotocograph and irregular uterine contractions. The newborn was kept in the neonatal ICU for 10 days., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2022.)

Introduction and Importance: Abdominal pain in the right upper quadrant is very common for patients to present in the emergency department. Finding the correct diagnosis seems straightforward in most cases but can be challenging., Case Presentation: We present the case of a 75-year-old male with a rare differential diagnosis for right upper quadrant and back pain, initially diagnosed as symptomatic cholelithiasis. After referral to an abdominal surgeon, detailed history taking prior to planned cholecystectomy revealed a record of back pain due to spinal degeneration and fusion surgery, as well as a bulb of the right abdominal wall with hypesthesia in a dermatomal area in the right upper quadrant. Considering these "new" facts, a spinal surgeon was consulted and a foraminal disc hernia of the thoracic vertebrae 11/12 was identified as the cause of symptoms. Instead of the initially planned cholecystectomy, a right-sided facetectomy Th11/12, sequestrectomy and unilateral transpedicular stabilization to decompress the nerve root was successfully performed., Clinical Discussion: Although, symptomatic cholelithiasis is one of the most common diagnoses for patients presenting with right upper quadrant pain in the presence of gallstones, other differential diagnoses have to be considered. Thoracic disc herniations can present with atypical symptoms that mimic other non-spinal causes and may pose a diagnostic challenge, sometimes even leading to unnecessary surgery., Conclusion: This case highlights a rare differential diagnosis for one of the most common diseases seen by emergency physicians. It emphasizes the risk of working under time pressure, especially in an emergency setting, which may lead to premature diagnostic error and treatment, endangering patient's care and safety., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

While benchmarking is already used for the assessment of performance gaps in cattle herd management and welfare concerns, its application to quantifying claw health performance is relatively new. The goal here was to establish a benchmarking system for claw health in Austrian dairy cattle. We used electronically registered claw health data of cows from 512 dairy herds documented by professional hoof trimmers, culling data from the same herds, and locomotion scores taken at regular milk performance testings in 99 dairy herds during 2020. Mean, median and the 10th, 25th, 75th, and 90th percentiles of the incidences of risk of lameness, 13 common claw lesions, and the annual culling risk directly related to claw and limb disorders were used as key performance indicators. Only validated data sets were used and participating trimmers and locomotion scorers had to pass interobserver reliability tests with weighted Cohen's kappa values ≥ 0.61 indicating substantial interobserver agreement. This claw health benchmarking system is intended to be used henceforth in the transnational cattle data network (RDV) by all participating farmers and is also available for veterinarians and consultants, with the agreement of respective farmers.

Listeria monocytogenes is an environmentally adapted saprophyte that can change into a human and animal bacterial pathogen with zoonotic potential through several regulatory systems. In this review, the focus is on the occurrence of Listeria sensu stricto and sensu lato in different ecological niches, the detection methods, and their analytical limitations. It also highlights the occurrence of L. monocytogenes genotypes in the environment (soil, water, and wildlife), reflects on the molecular determinants of L. monocytogenes for the saprophytic lifestyle and the potential for antibiotic resistance. In particular, the strain-specific properties with which some genotypes circulate in wastewater, surface water, soil, wildlife, and agricultural environments are of particular interest for the continuously updating risk analysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lourenco, Linke, Wagner and Stessl.)

Background: Rapid weight loss after bariatric surgery is a risk factor for gallstone formation. There are different strategies regarding its management in bariatric patients, including prophylactic cholecystectomy (CCE) in all patients, concomitant CCE only in symptomatic patients, or concomitant CCE in all patients with known gallstones. We present the safety and long-term results of the last concept., Method: Retrospective single-center analysis of a prospective database on perioperative and long-term results of patients with laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) over a 15-year period. The minimal follow-up was 24 months. Concomitant CCE was intended for all patients with gallstones detected by preoperative sonography., Setting: Academic teaching hospital in Switzerland., Results: After exclusion of patients with a history of CCE (11.5%), a total of 1174 patients (69.6% LRYGB, 30.4% LSG) were included in the final analysis. Preoperative gallbladder pathology was detected in 21.2% of patients, of whom 98.4%, or 20.9% of the total patients, received a concomitant CCE. The additional procedure prolonged the average operation time by 38 minutes (not significant) and did not increase the complication rate compared with bariatric procedure without CCE (3.7% versus 5.7%, P = .26). No complication was directly linked to the CCE. Postoperative symptomatic gallbladder disease was observed in 9.3% of patients (LRYGB 7.0% versus LSG 2.3%, P = .15), with 19.8% of those patients initially presenting with a complication., Conclusion: The concept of concomitant CCE in primary bariatric patients with gallstones was feasible and safe. Nevertheless, 9.3% of primary gallstone-free patients developed postoperative symptomatic gallbladder disease and required subsequent CCE despite routine ursodeoxycholic acid prophylaxis., (Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Disorders of the eye leading to visual impairment are a major issue that affects millions of people. On the other side ocular toxicities were described for e.g. molecularly targeted therapies in oncology and may hamper their development. Current ocular model systems feature a number of limitations affecting human-relevance and availability. To find new options for pharmacological treatment and assess mechanisms of toxicity, hence, novel complex model systems that are human-relevant and readily available are urgently required. Here, we report the development of a human immunocompetent Choroid-on-Chip (CoC), a human cell-based in vitro model of the choroid layer of the eye integrating melanocytes and microvascular endothelial cells, covered by a layer of retinal pigmented epithelial cells. Immunocompetence is achieved by perfusion of peripheral immune cells. We demonstrate controlled immune cell recruitment into the stromal compartments through a vascular monolayer and in vivo-like cytokine release profiles. To investigate applicability for both efficacy testing of immunosuppressive compounds as well as safety profiling of immunoactivating antibodies, we exposed the CoCs to cyclosporine and tested CD3 bispecific antibodies., (© 2022. The Author(s).)

Terpenes constitute one of the largest groups of secondary metabolites that are used, for example, as food-additives, fragrances or pharmaceuticals. Due to the formation of an intracytoplasmic membrane system and an efficient intrinsic tetraterpene pathway, the phototrophic α-proteobacterium Rhodobacter capsulatus offers favorable properties for the production of hydrophobic terpenes. However, research efforts have largely focused on sesquiterpene production. Recently, we have developed modular tools allowing to engineer the biosynthesis of terpene precursors. These tools were now applied to boost the biosynthesis of the diterpene casbene, the triterpene squalene and the tetraterpene β-carotene in R. capsulatus SB1003. Selected enzymes of the intrinsic isoprenoid pathway and the heterologous mevalonate (MVA) pathway were co-expressed together with the respective terpene synthases in various combinations. Remarkably, co-expression of genes ispA, idi and dxs enhanced the synthesis of casbene and β-carotene. In contrast, co-expression of precursor biosynthetic genes with the squalene synthase from Arabidopsis thaliana reduced squalene titers. Therefore, we further employed four alternative pro- and eukaryotic squalene synthases. Here, the synthase from Methylococcus capsulatus enabled highest product levels of 90 mg/L squalene upon co-expression with ispA. In summary, we demonstrate the applicability of R. capsulatus for the heterologous production of diverse terpene classes and provide relevant insights for further development of such platforms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Insufficient weight loss or secondary weight regain with or without recurrence of comorbidity can occur years after laparoscopic Roux en Y gastric bypass (LRYGB). In selected patients, increasing restriction or adding malabsorption may be a surgical option after conservative measures failed., Objectives: Evaluation of short and long term results of revisional surgery for insufficient weight loss or weight regain after LRYGB., Setting: Tertiary hospital., Methods: Retrospective analysis of prospectively collected data from a cohort of 1150 LRYGB patients. Included were patients, who underwent revisional bariatric surgery after LRYGB for insufficient weight loss with a follow-up of minimal 1 year., Results: Fifty-four patients were included in the analysis. After an interdisciplinary evaluation, patients with insufficient weight loss, signs of dumping syndrome, and lacking restriction were offered a nonadjustable band around the pouch (banded group, n = 34) and patients with sufficient restriction, excellent compliance, and adherence were offered a revision to laparoscopic biliopancreatic diversion (BPD group, n = 20). The revisional procedure was performed 3.3 ± 2.3 years after LRYGB in the banded-group and after 6.4 ± 4.3 years in the BPD group (P = .001). Mean body mass index at the time of the primary bariatric procedure was 41.7 ± 6.2 kg/m 2 in the banded group and 45.2 ± 8.2 kg/m 2 in the BPD group (P = .08); minimal body mass index between both operations was 29.1 ± 4.7 kg/m 2 in the banded group and 36.5 ± 9.4 kg/m 2 in the BPD group, and, at the time of revisional surgery, 31.4 ± 5.5 kg/m 2 in the banded group and 40.8 ± 6.7 kg/m 2 in the BPD group (P = .0001). The mean body mass index difference 1 year after revisional surgery was 1.3 ± 3.0 kg/m 2 in the banded group and 6.7 ± 4.5 kg/m 2 in the BPD group (P = .01). In the banded group, 11 patients (32.4%) needed removal of the band, 4 patients (11.8%) needed an adjustment, and 4 patients (11.8%) were later converted to BPD. In the BPD group, 2 (10.0%) patients needed revision for severe protein malabsorption., Conclusions: Insufficient weight loss or secondary weight regain after LRYGB is a rare indication for revisional surgery. Banded bypass has modest results for additional weight loss but can help patients suffering from dumping. In very carefully selected cases, BPD can achieve additional weight loss with acceptable complication rate but higher risk for reoperation. Future "adjuvant medical treatments," such as glucagon-like peptide 1 analogues and other pharmacologic treatment options could be an alternative for achieving additional weight loss and better metabolic response., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: After laparoscopic Roux-en-Y gastric bypass (RYGB), approximately 10-35% of patients with morbid obesity regain weight after an initial good result or fail to achieve a sufficient amount of weight loss. Patients in which conservative measures are not successful may potentially benefit from revisional surgery., Objective: To evaluate the effect of a non-adjustable ring placed around the gastric pouch in patients with insufficient weight loss or weight regain after RYGB., Setting: Four specialized bariatric hospitals in The Netherlands, Germany, and Switzerland., Methods: From 2011 to 2017, 79 patients underwent revisional surgery using a non-adjustable silicone ring because of insufficient results after RYGB. Data on weight loss and complications up to 2 years after revisional surgery was collected and analyzed retrospectively., Results: A follow-up percentage of 86% after 1 year and 61% after 2 years was achieved. In 75% of patients, further weight regain was prevented. Percentage total body weight loss improved by 7 to 26% 1 year after revisional surgery and remained stable during 2 years of follow-up. The additional weight loss effect of placing a non-adjustable ring was more pronounced in patients with an initial good result after primary RYGB. Eighteen (23%) rings were removed, most often due to dysphagia., Conclusion: Especially for patients who experience weight regain after initial good weight loss, placing a non-adjustable silicone ring around the gastric pouch results in modest improvements in weight loss. To prevent the risk of ring removal due to dysphagia, surgeons should take notice not to place the ring too tight around the gastric pouch during revisional surgery.

Introduction: The mean prevalence of thyroid nodules in adults is about 20% and increases with age. Most of the thyroid nodules are benign, and are rarely malignant. However, malignancy can often only be conclusively determined after resection. Therefore, it is essential that the surgical technique should be free of complications. Despite all published minimally invasive techniques, the open procedure via a Kocher incision is still standard and commonly used in a teaching setting. This standardised technique is presented step-by-step in the video., Indication: Sonographic and MIBI-scintigraphic possibly malignant solitary node in the right thyroid lobe., Procedure: Hemithyreoidectomy with neuromonitoring of recurrent laryngeal nerve., Conclusion: Hemithyroidectomy is an adequate primary therapy for a solitary possibly malignant thyroid nodule. Intraoperative neuromonitoring to identify and protect the recurrent laryngeal nerve, visualisation and protection of the parathyroid glands without compromising blood circulation and careful hemostasis are the main pillars of low risk surgery of the thyroid., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Cytokines are mediators of inflammatory processes in the course of inflammatory bowel disease (IBD) and participate in the bone metabolism. Interleukin 6 (IL-6) initiates osteoclastogenesis by modulating the activity of soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin., Objectives: The aim of the study was to evaluate bone mineral density (BMD) by densitometry and the concentration of interleukin 6, osteoprotegerin (OPG) and sRANKL protein (sRANKL) by ELISA in patients with IBD in relation to the control group; to assess the relationship between IL-6, OPG, sRANKL and BMD; and to assess the impact of disease duration and number hospitalization on BMD., Material and Methods: The studied group included 37 patients with Crohn's disease (I - CD), 37 patients with ulcerative colitis (II - UC) and 37 healthy subjects - control group (III - CG)., Results: The prevalence of osteoporosis and osteopenia was as follows: in I - CD, 18.92% and 32.43% in L2-L4; 13.51% and 35.13% in the neck, and in II - UC, 2.7% and 37.84% in L2-L4; 2.7%, and 29.73% in the femoral neck. The concentration of IL-6 correlated negatively with T-scores in the neck for the whole group, and in group I - CD, there was a significant positive correlation between serum OPG and IL-6., Conclusions: The incidence of osteopenia and osteoporosis in patients with IBD is high and increases with the duration of the disease and the number of hospitalizations. Patients with CD are at a higher risk of skeletal pathology than patients with UC. IL-6 can modulate bone mineral density in the femoral neck especially in the course of CD.

Gastrointestinal tract conditions are frequently associated with low bone mineral density and increased risk of fractures due to osteoporosis, the latter concerning particularly inflammatory bowel disease (IBD) patients. One of the candidate genes involved in osteoporosis is the transforming growth factor beta-1 (TGFB1) whose polymorphisms may be responsible for the development of this disease. The aim of this study was to analyse the frequency of TGFB1 polymorphic variants and determine the association between the c.29T>C TGFB1 polymorphism, and bone mineral density and fractures in IBD patients. The study subjects included 198 IBD patients [100 suffering from Crohn's disease (CD) and 98 from ulcerative colitis (UC)] and 41 healthy volunteers as a control group. Densitometric bone measurements were obtained using dual energy X-ray absorptiometry. The TGFB1 genotyping was conducted using restriction fragments length polymorphism. We conducted an analysis of genotype distribution's concordance with Hardy-Weinberg equilibrium. We found statistically significant differences in lumbar spine (L2-L4) and femoral neck BMD and T-scores between CD, UC and control subgroups. The distribution of TGFB1 polymorphic variants among CD and UC patients was concordant with Hardy-Weinberg equilibrium. There were no statistically significant differences in densitometric parameters (lumbar spine and femoral neck BMD, T-score, and Z-score) between carriers of different TGFB1 polymorphisms among IBD (CD and UC) patients nor among controls. We have found no statistically significant differences in the prevalence of low-energy fractures between groups of different TGFB1 polymorphic variant carriers. The allele dose effect, recessive effect and dominant effect analysis did not show an association between low-energy fractures and the TGFB1 polymorphisms among CD and UC patients. We have not observed an association between the c.29T>C TGFB1 polymorphic variant and the bone mineral density within the cancellous and cortical bones (L2-L4 and femoral neck, respectively), or the occurrence of fractures among the IBD patients and their family members.

Aim: To evaluate whether repeated serum measurements of trefoil factor-3 (TFF-3) can reliably reflect mucosal healing (MH) in Crohn's disease (CD) patients treated with anti-tumor necrosis factor-α (anti-TNF-α) antibodies., Methods: Serum TFF-3 was measured before and after anti-TNF-α induction therapy in 30 CD patients. The results were related to clinical, biochemical and endoscopic parameters. MH was defined as a ≥ 50% decrease in Simple Endoscopic Score for Crohn's disease (SES-CD)., Results: SES-CD correlated significantly with CD clinical activity and several standard biochemical parameters (albumin, leukocyte and platelet counts, C-reactive protein, erythrocyte sedimentation rate, fibrinogen). In contrast, SES-CD did not correlate with TFF-3 ( P = 0.54). Moreover, TFF-3 levels did not change significantly after therapy irrespectively of whether the patients achieved MH or not. Likewise, TFF-3 did not correlate with changes in fecal calprotectin, which has been proposed as another biochemical marker of mucosal damage in CD., Conclusion: Serum TFF-3 is not a convenient and reliable surrogate marker of MH during therapy with TNF-α antagonists in CD.

Osteoporosis is more frequent in inflammatory bowel disease (IBD) patients. A reduction in bone mineral mass in these individuals is caused not only by inflammatory processes in the bowel, because osteoporosis occurs already in very young IBD patients and in newly diagnosed individuals who have not yet undergone any pharmacological treatment. One of individual determinants of the bone turnover parameters is osteoprotegerin (OPG) encoded by the TNFRSF11B gene. The c.-223C > T polymorphism in this gene has been extensively studied in post-menopausal osteoporosis patients. However, no such studies exist for osteoporosis related to IBD. The aim of our study was to determine whether the c.-223C > T (rs2073617) polymorphism in the 5'UTR region of the gene encoding osteoprotegerin is a functional polymorphism which may change the gene expression and resulting OPG levels, and so be associated with osteopenia and osteoporosis, and impaired bone metabolism in Crohn's disease and ulcerative colitis patients. Our study included 198 IBD patients and 41 healthy controls. Lumbar spine and femoral neck bone mineral density, T-score, Z-score as well as OPG, RANKL, vitamin D, calcium and interleukin 4 and 10 concentrations were determined for all study subjects. Genotyping of the TNFRSF11B polymorphic site was performed by restriction fragment length polymorphism technique. Statistical analyses were conducted using Statistica software. Odds ratios, 95 % confidence intervals, and P values were calculated using the HWE calculator. Our results did not allow determining an unequivocal association between the polymorphic variants of the TNFRSF11B 5'UTR region and a susceptibility to osteoporosis in IBD patients. We have shown, however, that the c.-223T allele was twice as more frequent in Crohn's disease (CD) patients than among controls (OR = 1.99, P value = 0.009). Interestingly, average osteoprotegerin levels in CD patients did not significantly differ from those in controls, whereas in ulcerative colitis patients, OPG levels were significantly lower. We have concluded that low OPG levels may be associated with osteoporosis in ulcerative colitis, but it is not correlated with the c.-223C > T polymorphism in the TNFRSF11B gene. In CD patients, in turn, we observed increased RANKL levels. Our observations confirm different pathogeneses of Crohn's disease and ulcerative colitis as well as different molecular backgrounds of osteoporosis associated with these two diseases., Competing Interests: Iwona Krela-Kaźmierczak, Marta Kaczmarek-Ryś, Aleksandra Szymczak, Michał Michalak, Marzena Skrzypczak-Zielińska, Natalia Drwęska-Matelska, Michalina Marcinkowska, Piotr Eder, Lilianna Łykowska-Szuber, Ewa Wysocka, Krzysztof Linke and Ryszard Słomski have declare that they have no conflict of interest. Ethical Approval The study was approved by the Bioethical Committee of the University of Medical Sciences in Poznań, Poland, under Resolution No. 92/09. Informed consent was obtained from every participant. Human and Animal Rights and Informed Consent All followed procedures were in accordance with the ethical standards of the responsible committee on human experimentation (Bioethical Committee of the University of Medical Sciences in Poznań, Poland, Resolution No. 92/09). Informed consent was obtained from all individual participants included in the study.

Background: Soluble tumour necrosis factor-α (sTNF-α) has been reported to increase in the course of anti-TNF-α therapy for rheumatoid and skin diseases., Aims: To assess changes in sTNF-α and clinical efficacy of anti-TNF-α agents in Crohn's disease (CD)., Methods: Sixty-four patients on infliximab or adalimumab were analyzed. Clinical outcomes were assessed by using CD Activity Index after the induction therapy and at week 52. sTNF-α was measured before and after the induction therapy with high-sensitivity immunoassay., Results: In the majority of patients, sTNF-α increased significantly. Those with the greatest increase were more likely to experience long-term response, were more often treated with infliximab, had less frequently isolated small bowel CD, and tended to have sTNF-α levels at baseline that correlated with C-reactive protein., Conclusions: Neutralization of sTNF-α does not seem to be critical for the efficacy of anti-TNF-α therapy in CD. Paradoxically - an increase in sTNF-α may reflect an ongoing process that is beneficial for the clinical outcome., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The mechanisms of action of antitumor necrosis factor α (anti-TNF-α) antibodies in the therapy of inflammatory bowel disease (IBD) are not completely understood. Binding of antibodies to transmembrane TNF-α seems to be crucial for the induction of several cellular responses, including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and reverse signaling. However, these processes alone do not fully explain the diversity of responses to anti-TNF-α therapy seen in different patients. Thus, the present review aimed to discuss the current role of anti-TNF-α antibodies in treatment algorithms for IBD as well as the current knowledge on the mechanisms of action of these antibodies, particularly the less well known aspects of anti-TNF-α blockade. We also discussed a complex role of particular macrophage subpopulations, T regulatory cells, and intestinal endothelial cells, as well as presented new data on the clinical relevance of anti-inflammatory responses attributed to the Fc region of anti-TNF-α antibodies.

Large, deep full-thickness skin wounds from high-graded burns or trauma are not able to reepithelialize sufficiently, resulting in scar formation, mobility limitations, and cosmetic deformities. In this study, in vitro-constructed tissue replacements are needed. Furthermore, such full-skin equivalents would be helpful as in vivo-like test systems for toxicity, cosmetic, and pharmaceutical testing. Up to date, no skin equivalent is available containing the underlying subcutaneous fatty tissue. In this study, we composed a full-skin equivalent and evaluated three different media for the coculture of mature adipocytes, fibroblasts, and keratinocytes. Therefore, adipocyte medium was supplemented with ascorbyl-2-phosphate and calcium chloride, which are important for successful epidermal stratification (Air medium). This medium was further supplemented with two commercially available factor combinations often used for the in vitro culture of keratinocytes (Air-HKGS and Air-KGM medium). We showed that in all media, keratinocytes differentiated successfully to build a stratified epidermal layer and expressed cytokeratin 10 and 14. Perilipin A-positive adipocytes could be found in all tissue models for up to 14 days, whereas adipocytes in the Air-HKGS and Air-KGM medium seemed to be smaller. Adipocytes in all tissue models were able to release adipocyte-specific factors, whereas the supplementation of keratinocyte-specific factors had a slightly negative effect on adipocyte functionality. The permeability of the epidermis of all models was comparable since they were able to withstand a deep penetration of cytotoxic Triton X in the same manner. Taken together, we were able to compose functional three-layered full-skin equivalents by using the Air medium.

Objective: The combination of clinical remission and mucosal healing represents a major goal of different treatment strategies for ulcerative colitis (UC). This study aimed to assess which of the endoscopic indices used to evaluate mucosal changes in UC are correlated with clinical indices currently used to determine disease activity, as well as which of the endoscopic indices are correlated with the Geboes Index used for histological evaluation. It also aimed to find correlations between the currently used clinical activity indices and the histological Geboes Index., Methods: A group of 49 patients with a confirmed diagnosis of UC and a group of 52 individuals without a diagnosis of gastrointestinal disease, who constituted the control group, were investigated. All patients were evaluated by colonoscopy, and the severity of mucosal changes was scored in terms of nine different endoscopic indices commonly used in both pharmacological trials and clinical practice. Evaluation was also carried out using clinical and histological indices. Endoscopic indices used for UC were then correlated with different clinical and histological indices to find the strongest correlations., Results and Conclusion: A high correlation was demonstrated between three of the 11 evaluated clinical indices - Improvement Based on Individual Symptom Scores, Ulcerative Colitis Disease Activity Index, and Schroeder Index - and all nine endoscopic indices - Ulcerative Colitis Endoscopic Index of Severity, Baron Score, Schroeder Index, Feagan Index, Powell-Tuck Index, Rachmilewitz Index, Sutherland Index, Lofberg Index, and Lemman Index. Improvement Based on Individual Symptom Scores was the index with the highest correlation with all the endoscopic indices used for UC. The above indices are recommended for clinical evaluation of UC activity. The Ulcerative Colitis Endoscopic Index of Severity was moderately correlated with a histological index, and it is therefore recommended for routine endoscopic mucosal evaluation in patients with UC.

In order to better understand pathogenicity of Helicobacter pylori, particularly in the context of its carcinogenic activity, we analysed expression of virulence genes: cagA, virB/D complex (virB4, virB7, virB8, virB9, virB10, virB11, virD4) and vacA in strains of the pathogen originating from persons with gastric diseases. The studies were conducted on 42 strains of H. pylori isolated from patients with histological diagnosis of non-atrophic gastritis-NAG (group 1, including subgroup 1 containing cagA+ isolates and subgroup 2 containing cagA- strains), multifocal atrophic gastritis-MAG (group 2) and gastric adenocarcinoma-GC (group 3). Expression of H. pylori genes was studied using microarray technology. In group 1, in all strains of H. pylori cagA+ (subgroup 1) high expression of the gene as well as of virB/D was disclosed, accompanied by moderate expression of vacA. In strains of subgroup 2 a moderate expression of vacA was detected. All strains in groups 2 and 3 carried cagA gene but they differed in its expression: a high expression was detected in isolates of group 2 and its hyperexpression in strains of group 3 (hypervirulent strains). In both groups high expression of virB/D and vacA was disclosed. Our results indicate that chronic active gastritis may be induced by both cagA+ strains of H. pylori, manifesting high expression of virB/D complex but moderate activity of vacA, and cagA- strains with moderate expression of vacA gene. On the other hand, in progression of gastric pathology and carcinogenesis linked to H. pylori a significant role was played by hypervirulent strains, manifesting a very high expression of cagA and high activity of virB/D and vacA genes.

M ethotrexate (MTX) as an immunomodulatory drug has numerous applications in autoimmune diseases. Autoimmune patomechanism is one of the factors responsible for development of inflammatory bowel diseases (IBD). MTX is an alternative therapy in the treatment of IBD. Over the past several years clinical trials has confirmed the efficacy of MTX in the treatment of Crohn's disease (CD). Data concerning use of MTX in ulcerative colitis (UC) are not as numerous as in the CD. Currently, MTX is recommended for the induction treatment and maintenance therapy in CD patients, especially in steroid-dependent patients, disease refractory to corticosteroids, no improvement after treatment with azathioprine and 6-mercaptopurine, or in case of intolerance to these drugs. Preferred route of administration in the treatment of CD is parenteral supply. Contraception is indicated during MTX treatment since it's teratogenic.

Introduction: Monitoring the response to biological treatment in Crohn's disease (CD) is a very important element of the therapeutic optimisation., Aim: To evaluate the usefulness of measuring calprotectin, lactoferrin, and myeloperoxidase in stool as markers of long-term clinical and endoscopic response to anti-tumour necrosis factor α (anti-TNF) treatment in CD., Material and Methods: The studied group consisted of 35 CD patients treated with anti-TNF-α antibodies. Clinical activity was evaluated using Crohn's Disease Activity Index (CDAI), and the exacerbation of endoscopic changes was evaluated using a Simple Endoscopic Score for Crohn's Disease (SES-CD). The concentration of calprotectin, lactoferrin, and myeloperoxidase was measured using the ELISA method. All measurements were performed three times - before, after 3 months, and after a year of therapy., Results: During anti-TNF treatment the concentrations of all measured faecal markers decreased significantly in relation to baseline values. We observed a significant correlation at all time-points: before the therapy, after 3 months, and 12 months after starting the therapy, between the concentration of calprotectin and SES-CD, calprotectin and CDAI, as well as between lactoferrin and SES-CD, and lactoferrin and CDAI. Myeloperoxidase correlated with both SES-CD and CDAI only after 1 year of treatment., Conclusions: Faecal calprotectin and lactoferrin are valuable markers of clinical and endoscopic activity of CD in patients treated with anti-TNF antibodies. They are useful in monitoring the response to treatment. The usefulness of myeloperoxidase in this respect remains controversial., Competing Interests: The authors declare no conflict of interest.

Secondary osteoporosis occurs as an isolated pathology or co-exists with types I and II osteoporosis. The gastroenterologist may come across osteoporosis or osteopenia in a patient with a gastrointestinal disease. This is often a young patient in whom investigations should be carried out and appropriate treatment initiated, aimed at preventing bone fractures and the formation of the best peak bone mass. Osteoporosis occurs in patients with the following conditions: Crohn's disease, ulcerative colitis, celiac disease, post gastrectomy patients, patients with short bowel syndrome, chronic hepatitis and cirrhosis, treated with steroids (steroid-induced osteoporosis) and patients using proton pump inhibitors chronically (state of achlorhydria). It is therefore necessary to approve a list of risk factors of secondary osteoporosis, the presence of which would be an indication for screening for osteoporosis, including a DXA study and the development of a separate algorithm for the therapeutic management of secondary osteoporosis accompanying gastrointestinal diseases, especially in premenopausal young women and young men, because there are currently no registered drugs with proven antifracture activity for this group of patients.

Introduction: Objective assessment of Crohn's disease (CD) activity in patients treated with anti-tumour necrosis factor (anti-TNF) antibodies is crucial for the prediction of its long-term results. Mucosal healing estimated endoscopically has a strong predictive value; however, only combined assessment together with transmural healing in magnetic resonance enterography (MRE) gives full information about the whole spectrum of inflammatory lesions in CD., Aim: To assess the usefulness of intestinal healing phenomenon in CD, defined as improvement both in endoscopy and MRE, after anti-TNF induction therapy, in predicting long-term results of 1-year treatment., Material and Methods: Twenty-six patients with ileocolonic CD were enrolled into the study. In this group a parallel assessment of disease activity was estimated before and after induction doses of anti-TNF antibodies with ileocolonoscopy and MRE by using appropriate scores. Subsequently the patients were treated until 12 months and then followed-up. The associations between intestinal healing (assessed in MRE and endoscopy), and mucosal and transmural healing with long-term results of 1-year anti-TNF therapy were analysed statistically., Results: The median time of follow-up was 29 months (interquartile range - IQR: 14-46). Intestinal healing was significantly associated with favourable therapeutic outcomes ( p = 0.02) and had 75% (IQR: 35-97%) sensitivity and 72% (IQR: 46-90%) specificity in predicting long-term remission. Other parameters were not useful (transmural healing) or their usefulness was of borderline significance (mucosal healing)., Conclusions: Dynamic assessment of intestinal healing is an accurate method in predicting long-term outcomes in CD patients responding to 1-year anti-TNF therapy., Competing Interests: The authors declare no conflict of interest.

Background. Assessment of endoscopic activity of Crohn's disease (CD) is of growing importance both in clinical practice and in clinical trials. The study aimed to assess which of the endoscopic indices used for evaluation of mucosal changes correlates with the currently used clinical indices for determination of disease activity and with the results of histopathological examination. Study. A group of 71 patients with CD and 52 individuals without a diagnosis of GI tract disease as a control group were investigated, considering clinical and histological severity of the disease and the severity of inflammatory changes in the bowel. Evaluation was conducted with the use of clinical, endoscopic, and histopathological indices. Endoscopic indices were then correlated with different clinical and histopathological indices with the aim of finding the strongest correlations. Results and Conclusions. Correlation between the clinical disease activity and the severity of endoscopic lesions in CD was shown in this study to be poor. The results also indicate that the optimal endoscopic index used in the diagnostic stage and in the assessment of treatment effects in CD is Simple Endoscopic Score for Crohn's Disease (SES-CD).

Introduction: Immune-mediated angiogenesis may play an important role in the pathogenesis of inflammatory lesions in Crohn's disease (CD). The study aimed to assess the influence of anti-tumour necrosis factor (anti-TNF) therapy on the angiogenesis in relation to microscopic and endoscopic healing in CD patients., Material and Methods: Colonic tissue samples from 17 CD patients were taken during colonoscopy before and after anti-TNF therapy. Endoscopic and microscopic severities were estimated using validated scores. Immunohistochemical expression of CD31 and vascular endothelial growth factor (VEGF) were assessed in parallel., Results: The expression of CD31 and VEGF decreased significantly after the anti-TNF therapy in parallel to endoscopic improvement; however, the microscopic activity did not change significantly. There was a correlation between the change in CD31 and VEGF expression (p = 0.01; r = 0.6), as well as endoscopic healing (p = 0.04; r = 0.4). CD31 immunoexpression correlated with the number of poly- and mononuclear cells in the infiltrates in the mucosal lamina propria before the therapy (p = 0.02; r = 0.5)., Conclusions: We suggest that modulation of vascular proliferation can be a novel option to increase the efficacy of biological therapy in CD.

Introduction: Crohn's disease (CD) promotes the development of osteopaenia/osteoporosis, the cytokine background of which is not fully known., Aim: Evaluation of bone mineral density (BMD), the prevalence of osteopaenia and osteoporosis, and the determination of the levels of selected interleukins (IL), osteoprotegerin (OPG), and s-RANKL proteins in patients with CD in relation to a control group and assessment of the relationship between the tested cytokines, OPG, s-RANKL, and BMD., Material and Methods: Thirty-seven CD patients and 37 healthy volunteers (control group) were enrolled into the study. Densitometry of the lumbar spine (L2-L4) and of the femoral neck using the DXA technique was carried out. Serum levels of: IL-13, IL-4, IL-17, IL-1β, OPG, and s-RANKL were determined using the ELISA method. Progression-of-disease questionnaires were collected., Results: The prevalence of osteoporosis and osteopaenia in the CD group was: 18.92% and 32.43% in L2-L4; 13.51% and 35.13% in the neck, respectively. The IL-13 and IL-1β concentrations were significantly higher and OPG was significantly lower in CD patients when compared to controls. In the case of all subjects: IL-13 correlated negatively with the BMD of the neck, IL-17 correlated negatively with the Z-score of L2-L4, and OPG correlated negatively with the IL-13. In the case of CD patients, IL-4 correlated negatively with the BMD of L2-L4., Conclusions: The incidence of osteopaenia and osteoporosis in Polish CD patients is high. IL-13, IL-1β, and IL-4 seem to be connected with the pathology of decreased BMD in CD. It can be hypothesised that IL-13 may lower BMD by modulating OPG.

Introduction: The aim of this study was to assess the potential mechanisms providing resistance to apoptosis of lamina propria lymphocytes (LPL) directlyin intestinal tissues from patients with Crohn's disease (CD)., Material and Methods: Fifty CD patients were enrolled in the study. The control group consisted of healthy patients who underwent surveillance colonoscopy after endoscopic polypectomy. Each CD patient underwent colonoscopy with tissue sampling from inflamed areas of the colon with the assessment of immunohistochemical expression of active caspase 3, Fas, tumour necrosis factor receptor 1 (TNFR1), Bcl-2, Bax, CD4 and CD8. This was compared with healthy intestinal mucosa., Results: The expression of active caspase 3 was significantly lower in LPL in CD (0.4 ±0.3 vs. 2.8 ±1.5; p = 0.0002). A statistically significant increase of CD4 and CD8 positive cells was noted in CD (2.3 ±0.5 vs. 1.2 ±0.2, p < 0.0001; 2.1 ±0.3 vs. 1.1 ±0.3, p < 0.0001, respectively). It was associated with a significant increase of the Bcl-2 (6.7 ±2.7 vs. 2.9 ±0.8; p < 0.0001) and a decrease of the Bax protein expression (3.4 ±2.1 vs. 5.5 ±1.8; p < 0.0001) in CD. The expression of Fas and TNFR1 did not differ between the study groups., Conclusions: LPL in CD are resistant to apoptosis when compared with physiological conditions. This is probably due to an imbalance in Bcl-2 family proteins. TNFR1-related pathway is probably not involved in disturbances of LPL apoptosis in CD.

Down-regulation of immune-mediated angiogenesis seems to be an important mechanism in anti-tumor necrosis factor α (anti-TNFα) therapy for Crohn's disease (CD). However, it remains to be established whether the baseline pro-angiogenic activity as reflected by the level of vascular endothelial growth factor (VEGF) could be of predictive value for successful clinical outcome of such treatment. Here, the levels of serum VEGF and other crucial angiogenesis-regulating peptides were assessed before and after induction anti-TNFα therapy in CD patients, and in age- and sex-matched healthy controls. Clinical, endoscopic, and biochemical activity of CD was estimated in parallel. CD patients were divided into two subgroups, depending on baseline VEGF levels: a "low-VEGF" subgroup with VEGF levels similar to those detected in healthy people, and a "high-VEGF" subgroup with VEGF levels significantly increased. VEGF levels were found to significantly correlate with CD clinical activity. Compared to the "low-VEGF" subgroup, the reduction in CD clinical activity as assessed by Crohn's Disease Activity Index was significantly greater in "high-VEGF" patients both in absolute numbers, and as a percentage of pre-treatment values. Accordingly, the fraction of patients who did not respond adequately to treatment was significantly greater in the "low-VEGF" group. These data indicate that VEGF may serve as an additional marker of CD activity and that baseline VEGF levels can be helpful in predicting the efficacy of anti-TNFα therapy.

Etiological factors of bone metabolism disorders in inflammatory bowel diseases have been the subject of interest of many researchers. One of the questions often raised is vitamin D deficiency. Calcitriol acts on cells, tissues and organs through a vitamin D receptor. The result of this action is the multi-directional effect of vitamin D. The reasons for vitamin D deficiency are: decreased exposure to sunlight, inadequate diet, inflammatory lesions of the intestinal mucosa and post-gastrointestinal resection states. This leads not only to osteomalacia but also to osteoporosis. Of significance may be the effect of vitamin D on the course of the disease itself, through modulation of the inflammatory mechanisms. It is also necessary to pay attention to the role of vitamin D in skeletal pathology in patients with inflammatory bowel diseases and thus take measures aimed at preventing and treating these disorders through the supplementation of vitamin D.

Purpose: Magnetic resonance enterography (MRE) is a useful tool in assessing the transmural and extraintestinal lesions in Crohn's disease (CD). However, the influence of anti-tumor necrosis factor (anti-TNF) therapy on MRE features of CD severity remains unknown. The purpose of the study was to assess the short- and long-term changes in MRE features of CD activity in relation to CD clinical course in patients treated with anti-TNF antibodies., Methods: The influence on the most important parameters of CD activity seen in MRE was assessed retrospectively using a validated score. Patients were treated with anti-TNF agents and the clinical, laboratory, and MRE CD activity was estimated at baseline, after the induction therapy and after 1 year of treatment., Results: 71 patients were enrolled in a study. The change in CD clinical activity correlated significantly with fluctuations in MRE activity score (P < 0.0001, r = 0.5 for induction; P = 0.004, r = 0.7 for maintenance anti-TNF therapy, respectively). Bowel wall thickening, mesenteric lymphadenopathy, and fat wrapping with vascular proliferation were MRE parameters which changed significantly both after the induction and maintenance treatment in patients responding to the therapy. The change in MRE activity score was mostly pronounced during the first 3 months of treatment, when compared to the continuation of the therapy till week 52-54 (-6 points vs. -2 points, respectively; P = 0.0008)., Conclusions: Transmural and extraintestinal healing seen in MRE correlates with changes in CD clinical activity during anti-TNF therapy, thus MRE seems to be a useful tool in monitoring the efficacy of biological agents.

Background: Diagnosis and monitoring of Crohn's disease (CD) is difficult and time-consuming. In recent years, diagnostic usefulness of fecal calprotectin has been proven. However, data on the utility of other fecal markers are scarce., Aims: To evaluate the usefulness of fecal lactoferrin (FL) in the assessment of CD activity., Methods: The group consisted of 101 CD patients (median age: 30 years, IQR: 24-37). FL was measured in a single stool sample by using the immunoenzymatic methods. The clinical activity of the disease was evaluated by using the Crohn's Disease Activity Index (CDAI). Depending on the location of the disease, either a colonoscopy or magnetic resonance enterography was performed or both in order to evaluate the disease activity by using appropriate endoscopic and enterographic scores., Results: Median FL concentration was 84.14 (IQR: 36.4-302.9) μg/ml and it correlated with C-reactive protein concentration (p=0.0000001, r=0.5), CDAI (p=0.002, r=0.3) and colonic Simple Endoscopic Score for Crohn's Disease (SES-CD) (p=0.000004, r=0.5). Assuming endoscopic remission in the large intestine with colonic SES-CD≤3 points, a ROC curve showed that FL concentration of 145.82 μg/ml had 84.6% sensitivity and 60.5% specificity in discriminating CD patients with endoscopically active and inactive disease [AUC: 0.676 (95% CI: 0.531-0.8), (p=0.0347)]. The positive predictive value for this concentration was 42% and negative predictive value -92%., Conclusions: FL is a sensitive marker of CD activity and it reliably reflects the mucosal inflammatory lesions in large intestine. Thus, it can be helpful in diagnostics and monitoring of CD., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Increasing resistance to drugs represents a serious problem in treatment of infections with Helicobacter pylori, providing cause of frequent therapeutic failures. Present study aimed at analysis of changes in resistance of H. pylori to antibiotics in West Poland within the recent 15 years. 108 strains of H. pylori were analysed, isolated from gastric mucosa of adult patients. Group 1 involved 66 strains isolated in years of 1998/1999. Group 2 comprised 42 isolates obtained in years of 2013/2014. Susceptibility to amoxicillin (AMX), clarithromycin (CL), tetracycline (TC) and metronidazole (MTZ) was determined by E-test (AB Biodisc). All strains on both studied groups were susceptible to AMX. In group 1 all strains proved to be susceptible to TC, while 9% and 36% of tested strains were resistant to CL and MTZ, respectively. By contrast, in group 2, 31% and 83% of strains were resistant to CL and MTZ, respectively. In parallel, 14% strains were found to be resistant to TC (according to EUCAST interpretations). In West Poland, within recent 15 years a dramatic increase was noted in H. pylori strains resistant to metronidazole. In parallel, a significant increase was noted in proportion of strains resistant to clarithromycin.

The aim of the study was to assess the role of magnetic resonance enterography (MRE) in predicting one-year efficacy of anti-tumor necrosis factor antibodies--infliximab (IFX), adalimumab (ADA) in Crohn's disease (CD) patients primarily responding to therapy. We performed retrospective analysis among 61 CD patients who had undergone a successful IFX/ADA induction therapy and were treated with maintenance doses. All patients underwent MRE at week 0. We assessed which MRE features were predictive for steroid-free remission at week 52, and which were associated with a secondary loss of response. 44 patients were in steroid-free remission at week 52, 17--were secondary non-responders. The ROC curve showed that bowel thickening with contrast enhancement analyzed together at week 0 were associated with steroid-free remission at week 52 (p = 0.01; AUC 0.67). Bowel stenosis with or without prestenotic dilatation [OR 5.8 (95% CI 1.4-25) and 2.4 (95% CI 1.2 - 5) respectively; p = 0.01] and the presence of intra-abdominal fistulas [OR 1.4 (95% CI 1.1-2); p=0.004] were related to secondary non-response. A high baseline inflammatory activity detected by MRE predicts one-year response in CD after IFX/ADA. In case of bowel stenosis, intra-abdominal fistulas, other therapeutic options should be considered.

Introduction: There are data suggesting that the diagnostic usefulness of faecal calprotectin (FC) may vary depending on the Crohn's disease (CD) location. The aim of the study was to compare the diagnostic usefulness of FC in CD patients with different disease locations., Material and Methods: We prospectively enrolled 120 CD patients in the study. Disease activity was assessed by using Crohn's Disease Activity Index (CDAI), biochemical markers, and endoscopic and radiographic methods. Faecal calprotectin concentration was assessed in single stool samples by using the ELISA method., Results: Among all patients, 54 (45%) had ileocolonic CD location, 44 (36.5%) had isolated small bowel location, and 22 (18.5%) had colonic CD location. FC correlated significantly with C-reactive protein concentration and endoscopic and radiographic activity among patients with isolated small bowel CD (p = 0.03, r = 0.32; p < 0.0001, r = 0.78; p = 0.03, r = 0.35; respectively) and with C-reactive protein and endoscopic activity in isolated colonic CD (p = 0.0009, r = 0.7; p = 0.0002, r = 0.78; respectively). CDAI and inflammatory biochemical markers did not correlate with endoscopic and radiographic assessment in small bowel CD. In patients with ileocolonic CD, FC correlated significantly with endoscopy (p = 0.006, r = 0.5), radiographic assessment (p = 0.04, r = 0.3), CDAI (p = 0.0006, r = 0.5) and the majority of biochemical markers., Conclusions: Faecal calprotectin is a useful diagnostic marker in all CD patients. Although its usefulness in small bowel CD seems to be the lowest, it should be utilized particularly in this disease location because of the lack of other reliable, non-invasive diagnostic methods.

Objective: A case of agomelatine-induced hepatotoxicity is described in a 47-year female patient who has received the drug, 25 mg/day, for 4 months, for the treatment of depression., Methods: The patient was admitted to the Department of Gastroenterology because of fatigue and nausea, with concomitant elevation of alanine aminotransferase (ALT), 550 U/L, and asparagine aminotransferase (AST), 300 U/L., Results: Liver biopsy showed diffuse lymphocyte infiltration in the dilated portal spaces without lesion of hepatic lobules. Several weeks after stopping agomelatine, the liver enzymes returned to normal. Subsequently, small gallstones in common bile duct were detected and removed by the endoscopic sphincterotomy., Conclusions: It is hypothesized that choledocholithiasis could theoretically increase a risk of developing agomelatine-induced hepatotoxicity in this patient. Any pre-existing liver disease should be a contraindication for treatment with agomelatine.

In the presented studies p53 and bcl-2 proteins expression were evaluated in samples of gastric carcinomas in patients with Helicobacter pylori or EBV or without H. pylori/EBV infection. The studies were conducted on 64 adult patients with gastric adenocarcinomas: 16 patients with H. pylori (cagA+)-positivity (group 1), 14 with EBV-positive tumours (group 2), 12 with H. pylori/EBV-positive tumours (group 3) and 22 patients with H. pylori/EBV-negative tumours (group 4). H. pylori presence in gastric tumour specimens was detected using Giemsa staining and bacterial culture technique. Moreover, cagA gene was detected using PCR. EBV infection was detected based on EBER presence in the tissue by RNA in situ hybridization. Expressions of p53 and bcl-2 proteins were analysed using immunohistochemistry. Expression of p53 was noted in 14 (84%) patients from group 1, 8 (57%) patients from group 2, 7 (58%) patients from group 3, and 19 (86%) patients from group 4, whereas expression of bcl-2 was noted in 12 (75%) patients from group 1, in 10 (71%) patients from group 2, 9 (75%) patients from group 3, and 6 (27%) patients from group 4. The obtained results allow the conclusion, that H. pylori (cagA+)-associated development of the gastric adenocarcinoma is determined by abnormalities in the p53 protein function and overexpression of anti-apoptotic bcl-2 protein, whereas EBV-associated adenocarcinomas seem to be related with apoptosis resistance associated with bcl-2 overexpression.

Background: CD21 is a 145 kDa membrane glycoprotein expressed mainly on B-cells and follicular dendritic cells. It is involved in activation, survival and proliferation of B-cells. CD21 can be cleaved to give soluble CD21 (sCD21), which is constantly shed in healthy people whereas the level of sCD21 is low in patients suffering from various autoimmune diseases., Methods: Blood was collected from 12 healthy donors into Heparin, EDTA and gel-separation tubes. Furthermore, plasma from 6 healthy donors was combined and EDTA or EGTA was subsequently added to analyze its influence on sCD21 levels measured by ELISA., Results: Differences in sCD21 levels were observed dependent on blood collection tubes used. sCD21 levels measured by ELISA were significantly higher if heparin/gel containing tubes were used compared to EDTA blood collection tubes. Upon addition of EDTA/EGTA to plasma drawn using Heparin blood collection tubes, sCD21 levels decrease to amounts found in EDTA-containing blood collection tubes suggesting calcium as the responsible factor rather than magnesium., Conclusions: EDTA influences sCD21 levels determined by ELISA and therefore sCD21 measurements should be carried out using one type of blood collection tube throughout the experiment/medical examination.

This paper complements the previously published Guidelines of the Working Group of the Polish Society of Gastroenterology and former National Consultant in Gastroenterology regarding the management of patients with Crohn's disease and ulcerative colitis. Attention was focused on the new pharmaceutical recently registered for inflammatory bowel disease treatment.

The etiology of inflammatory bowel disease (IBD) is still not fully understood. Angiogenesis is one of the crucial phenomena sustaining chronic inflammation in the gastrointestinal tract. It has been also shown that the most potent anti-inflammatory drugs--anti-tumor necrosis factor alpha antibodies down-regulate intestinal angiogenesis, what is believed to contribute to their therapeutic efficacy. There are many proteins engaged in gastrointestinal angiogenesis, including pro-inflammatory cytokines, vascular growth factors, and adhesion molecules. Several of them are considered to be promising molecular targets for new drugs--monoclonal antibodies or fusion proteins. Here, we review new data highlighting the key role of proteins that regulate immune-mediated angiogenesis in IBD, like vascular endothelial growth factor, hypoxia inducible factor, angiopoietins, or basic fibroblast growth factor. We present the molecular mechanisms regulating the pathological proangiogenic activity in inflammatory conditions in IBD. We also discuss how new anti-cytokine regimens affect the function of angiogenesis-related proteins.

Background and Objective: Irritable Bowel Syndrome (IBS) has a substantial impact on health-related quality of life (HR-QoL) but high-quality data pre- and post-treatment using the IBS-Quality of Life (IBS-QOL) measure are limited. The objective of this study was to evaluate the changes from baseline of the IBS-QOL scores, symptom scores and health economic data in IBS patients, after 4 and 8 weeks of treatment with mebeverine hydrochloride or pinaverium bromide., Methods: This was a prospective observational cohort study in patients with IBS, diagnosed using the Rome III criteria in four countries (Poland, Egypt, Mexico and China)., Results: A total of 607 patients were enrolled. At baseline, the IBS-QOL total scores were 52.0 in Poland, 48.9 in Egypt, 51.9 in Mexico, 76.4 in China and 56.4 overall. Increases in IBS-QOL total score were statistically significant at Weeks 4 and 8 overall and in each country (overall: 11.8 at Week 4, 24.3 at Week 8; p < 0.001). Improvements were shown in all IBS-QOL subscales and scores. Symptoms and health economic outcomes were improved. Furthermore, the favourable safety profile of these treatments was confirmed in this study., Conclusions: This study demonstrated that IBS patients have a substantially reduced HR-QoL and that treatment with mebeverine hydrochloride or pinaverium bromide improved HR-QoL.

Soil and water are suggested to represent pivotal niches for the transmission of Listeria monocytogenes to plant material, animals, and the food chain. In the present study, 467 soil and 68 water samples were collected in 12 distinct geological and ecological sites in Austria from 2007 to 2009. Listeria was present in 30% and 26% of the investigated soil and water samples, respectively. Generally, the most dominant species in soil and water samples were Listeria seeligeri, L. innocua, and L. ivanovii. The human- and animal-pathogenic L. monocytogenes was isolated exclusively from 6% soil samples in regions A (mountainous region) and B (meadow). Distinct ecological preferences were observed for L. seeligeri and L. ivanovii, which were more often isolated from wildlife reserve region C (Lake Neusiedl) and from sites in proximity to wild and domestic ruminants (region A). The higher L. monocytogenes detection and antibiotic resistance rates in regions A and B could be explained by the proximity to agricultural land and urban environment. L. monocytogenes multilocus sequence typing corroborated this evidence since sequence type 37 (ST37), ST91, ST101, and ST517 were repeatedly isolated from regions A and B over several months. A higher L. monocytogenes detection and strain variability was observed during flooding of the river Schwarza (region A) and Danube (region B) in September 2007, indicating dispersion via watercourses., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)