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BACKGROUND Subcutaneous administration of infliximab shows an increased benefit in terms of pharmacokinetics and pharmacodynamics effects compared to the intravenous infliximab. The practical question arises whether routine administration in refractory CD patients who have failed prior biological therapy will provide "biobetter" clinical efficacy. AIMS We propose a single center study designed to evaluate SC-IFX treatment outcomes in patients with active CD after the previous failures of other biologicals (TMAbs). Such a refractory CD cohort was chosen because there is currently insufficient appropriate medication therapy available for these patients and the identification of parameters predicting response to SC-IFX treatment could be of great benefit to some of them. PATIENTS & METHODS A total of 32 CD patients were included, with the median age of 34.5 years and median CD duration of 11 years; >90% of them with stricturing and/or penetrating disease behavior, >80% with ileocolic involvement, and about 40% with the active perianal disease. Eighteen of 32 patients (56%) have failed on ≥3 previous TMAbs, the rest on 2 previous TMAbs. Twenty (62.5%) of n = 32 have had IV-IFX in past; in this sub-cohort, 85% of patients have positive anti-IFX antibodies (ATI). In ATI-positive sub-cohort, induction of SC-IFX was realized with four 120 mg SC doses weekly. Two induction IV infusions of 5 mg/kg IFX were administered in 2-week intervals in ATI-negative sub-cohort. Maintenance treatment in whole cohort consisted of 120 mg SC IFX bi-weekly. RESULTS Of the 32 patients, 7 individuals have failed the treatment during the induction phase: one because of heart disease progression, and 6 patients due to delayed hypersensitivity reactions with systemic manifestation. In 25/32 patients who continued their treatment up to W14, the initial median Harvey-Bradshaw index (HBI) of 6 (min 1, max 28) did not decrease significantly within the 14 weeks of treatment (p=0.067). However, both the serum CRP level (p=0.039) and fecal calprotectin level (p=0.027) have shown significant decrease. Median trough IFX levels have increased from 6 μg/mL at W2 to 10 μg/mL at W14 (p CONCLUSIONS Our short-term experience with SC-IFX shows the treatment efficacy and tolerability in complicated CD patients after multiple TMAbs failures.The research gap in information about biobetters in patients with IBD must be filled and predictive factors for the response to SC-IFX must be found.

INTRODUCTION Despite significant impact biological treatment had on prospects of patients with ulcerative colitis, there is still a substantial proportion of patients with either secondary loss of response or primary non-response to multiple drugs. Beside dose optimization and selection of drugs with different mechanism of action, combination of two different targeted molecules has been proposed in cases where inflammatory activity cannot get under control. This case series provide promising results of vedolizumab in combination with tofacitinib in treatment resistent UC patients. METHODS Patients with complicated refractory or acute severe colitis, in whom combined treatment with vedolizumab and tofacitinib based on shared clinical decision was started, were included. Data on demographics, treatment details, persistence and disease activity including laboratory markers, clinical activity index (partial Mayo score) during regular visits every 2 months up to one year after treatment initiation were collected. Currently available data were analyzed at 6 months of treatment. Endoscopic disease activity before and 2-6 months after dual therapy start was evaluated. RESULTS In total, 21 ulcerative colitis patients who were started on vedolizumab and tofacitinib dual therapy between October 2020 and September 2022 were included. Tofacitinib dose was 10mg bid in all patients and all patients on vedolizumab maintenance treatment had intensified dosing regimen. Mean patients age was 36.4±8.1 years, 47.6% were males and 52.4% females. Mean disease duration at baseline was 7.5±5.8 years. All patients had advanced disease including 61.9% with extensive colitis and 38.1% with left-sided colitis. At least 2 previous biologics in monotherapy were used in 85.7% of patients. Mean pMayo score at baseline was 5.6±1.9 and decreased to 0.5±0.9 at 6 months (p=0.0020). Initial fecal calprotectin in the cohort was 1829±2520µg/g vs. 225±257µg/g at 6 months (p=0.0068) and mean CRP changed from 11.4±17.1 to 5.4±7.2mg/l (p=ns). Endoscopic Mayo score before dual treatment initiation averaged 2.8±0.5 indicating mostly severe disease activity and decreased to 1.4±1.2 during follow-up endoscopy (p=0.0005) with half of the patients having only no to mild activity (eMayo 0-1). Up to now, dual therapy had to be terminated in 7 patients – 4 patients failed on the treatment, 1 refused to continue with dual therapy, 1 patient experienced adverse event (liver lesion) and 1 was discontinued for reimbursement reasons. CONCLUSION In the presented small cohort of patients, however, with refractory and complicated ulcerative colitis in whom other modalities were depleted or colectomy was considered, combined vedolizumab and tofacitinib treatment has proven to be very efficient with half of the patients reaching mucosal healing after 6 months and without raising significant safety concerns.

INTRODUCTION Small bowel stricture is common in Crohn’s disease (CD), both de novo and after resection. With all standard treatments having high recurrence rates, CD patients would benefit greatly from a novel and highly durable non-surgical intervention. We report the first long-term study of longitudinal compression therapy (LCT) for the treatment of anastomotic strictures in an animal CD stricture model. LCT entails progressive endoluminal compression of stricture tissue between two flange-like device components. The goal is to gradually bring about necrosis of fibrotic tissue interposed between the two flanges while allowing remodeling with minimal iatrogenic inflammation around the periphery. METHODS Stable anastomotic strictures with hallmarks of CD small bowel strictures were created in 6 pigs, using an established method entailing ileocolonic anastomosis creation with a bypassed ileal segment to maintain patency of the gastrointestinal tract followed by serial injections of phenol/trinitrobenzenesulfonic acid at the anastomosis site. Instead of using LCT devices deployed wholly endoscopically, to best study stricture response to LCT in this model, we used devices with magnetic elements for compressive force generation and integrated ultraminiature sensor arrays for monitoring treatment progression; one 23 mm diameter device component was placed via a surgical enterotomy and a second was deployed endoscopically. Animals were followed for 9 weeks after LCT to gauge post-treatment stricture response. RESULTS LCT device placement was successful in all animals. Five animals reached the 9-week timepoint. One animal was sacrificed on day 12 due to urinary tract complications unrelated to the device. The initial therapeutic response took place over a 3-hour period after device placement, with LCT devices applying increasing force from 3 to 10 Newtons. In endoscopic assessments, widened lumens were noted, with openings 3.3-fold larger at 2 weeks and 3.7-fold larger at 9 weeks. In comparison, for endoscopic balloon dilation in the same animal stricture model, the openings were 2.3-fold larger at 2 weeks, declining to 1.9-fold at 9 weeks. Endoscopic and macroscopic evaluation after euthanasia demonstrated newly patent lumens after excision of stricture tissue, with healthy-appearing mucosa and no macroscopic findings of stricture. CONCLUSION Prior work by our group and others--in animal models and in a small number of treated patients--has provided favorable indications of efficacy of LCT for treating refractory strictures. To the best of our knowledge, this is the first study to include long-term follow-up of LCT in a validated animal model of Crohn’s stricture. This work provides strong preliminary support that LCT’s combination of resection and neo-epithelialization can durably resolve CD stricture. LCT clinical studies are planned as a next step. Design and operation of device systems for longitudinal compression therapy for small bowel stricture in Crohn’s. (a) Longitudinal compression therapy device systems incorporate a dual-flange design, with a mechanism for drawing the flanges together to longitudinally compress the stricture. For single-sided access, expanding flange designs can be used (inset, top left). The LCT device systems used in this study are pairs of discrete non-expanding flange components, with one flange component placed proximal to the strictured region via laparotomy; magnetic elements in the flange components supply the compressive force. This design facilitates incorporation of ultraminiature sensor arrays into the flange components for monitoring stricture response to treatment (inset bottom right). (b)-(d) Steps in longitudinal compressive therapy: (b) advancing the LCT device through the stricture; (c) stricture compression between distal flange and expanded proximal flanges; (d) completion of therapy. Representative result for LCT in the porcine model of Crohn’s small bowel stricture. (a) Before treatment, a length of bowel 15 mm long is badly strictured, with the lumen less than 10 mm at its narrowest point. (b) At 2 weeks after LCT treatment, the narrowest point is markedly larger. (c) At 9 weeks post LCT treatment—a time after which balloon dilated strictures tend to have recurred—the LCT treated stricture is even more open than at 2 weeks post, consistent with the LCT intervention having spurred healing instead of exacerbating fibrosis. Three-dimensional anatomy of strictured segments determined by impedance-based measurement (Endoflip, Medtronic).

Background: Antimicrobial coatings of central venous catheters (CVC) have the potential to reduce the risk of infectious complications. The aim of this study was to examine the efficacy of a catheter with a non-leaching antimicrobial coating against catheter colonization and bloodstream infections (BSI). Methods: The study was conducted in two centers using a prospective, randomized, double-blind and controlled design (680 intensive care patients; a protective CVC (Certofix® protect) or a standard CVC (Certofix®). Primary objectives were the rates of catheter colonization and BSI in the two groups. Other baseline demographics, APACHE II score, insertion site, location of CVC placement (ICU or theatre), indwelling time and length of ICU stay were comparable for both groups. Results: While the rate of catheter colonization between the coated and uncoated CVC (17.4% vs. 18.7%, P=0.7477) and the rate of microbiologically confirmed catheter associated infections were similar (1.4% vs. 1.9%, P=0.7521), the coated CVC showed a significantly lower incidence of BSI (2.0% vs. 6.5%, P=0.0081) and a significantly lower mean incidence of BSI per 1000 catheter days (3.2 vs. 8.3, P=0.0356). Conclusion: The non-leaching antibacterial coating of the protective catheter was effective in reducing the incidence of BSI but not the rate of catheter colonization. However, the incidence of BSI is a better surrogate marker for the risk of developing clinical signs of infection suggesting that use of the non-leaching protective catheter is effective in this regard. Trial number: ClinicalTrials.gov (ID: NCT00555282), https://clinicaltrials.gov/show/NCT00555282

Background Crohn’s disease (CD) and ulcerative colitis (UC) are two forms of inflammatory bowel disease (IBD), where gut but not skin dysbiosis is well recognized. Tumor-necrosis factor alpha (TNFα) blockers have been successful in IBD treatment, but up to a quarter of patients suffer from skin adverse events (SkAE), for which we do not have a tool to predict them. Therefore, we examined the skin microbiota composition of IBD patients at several body sites by 16S bacterial profiling. Moreover, we quantified 22 serum markers of inflammation and epithelial barrier disruption in the setting of anti-TNFα therapy and SkAE manifestation by ELISA. Results The skin microbiota signature of IBD patients differed markedly from healthy subjects. In particular, skin microbiota of CD patients differed significantly from that of UC and HC at the retroauricular crease. CD patients showed high abundance of Corynebacterium (ASV86) and lower abundance of Actinomyces (ASV28), Cutibacterium (ASV212), Lawsonella (ASV87), and other taxa compared to HC. UC patients showed higher abundance of Delftia (ASV1039) and Pseudomonas (ASV1183), and lower abundance of Actinomyces (ASV28), Streptococcus (ASV607), or Haemophilus (ASV1150) than HC. Although microbiome changes were correlated at the ASV level in CD and UC patients compared to HC, we identified some bacterial ASV’s that exhibited changes typical of individual IBD forms. Manifestation of SkAE during anti-TNFα therapy was associated with a specific microbiota profile on the skin, and with a decrease in serum levels of L-FABP and I-FABP. Conclusions The overall proinflammatory effect of IBD might predispose for altered skin microbiota composition, hence promoting SkAE manifestation during anti-TNFα therapy. We identified specific serum markers associated with the incidence of SkAE during anti-TNFα therapy, however, further studies are needed to shed light on the impact of microbiota in this matter. Combining sequencing technology with search for serum biomarkers has opened up new opportunities in studying SkAE related to anti-TNFα therapy. Early detection of changes in microbiota-host equilibrium may have beneficial consequences in revealing the pathogenesis of SkAE in IBD.

Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract that have been linked to microbiome dysbiosis and immune system dysregulation. We investigated the longitudinal effect of anti-TNF therapy on gut microbiota composition and specific immune response to commensals in IBD patients. The study included 52 patients tracked over 38 weeks of therapy and 37 healthy controls (HC). To characterize the diversity and composition of the gut microbiota, we used amplicon sequencing of the V3V4 region of 16S rRNA for the bacterial community and of the ITS1 region for the fungal community. We measured total antibody levels as well as specific antibodies against assorted gut commensals by ELISA. We found diversity differences between HC, Crohn’s disease, and ulcerative colitis patients. The bacterial community of patients with IBD was more similar to HC at the study endpoint, suggesting a beneficial shift in the microbiome in response to treatment. We identified factors such as disease severity, localization, and surgical intervention that significantly contribute to the observed changes in the gut bacteriome. Furthermore, we revealed increased IgM levels against specific gut commensals after anti-TNF treatment. In summary, this study, with its longitudinal design, brings insights into the course of anti-TNF therapy in patients with IBD and correlates the bacterial diversity with disease severity in patients with ulcerative colitis (UC).

INTRODUCTION Both primary strictures and secondary anastomotic strictures are common complications in patients with inflammatory bowel diseases (IBD), especially Crohn’s disease (CD). Balloon dilation has been the gold standard in the endoscopic treatment of these strictures. Endoscopic stricturotomy (ESt, Figure 1) represents a promising novel approach, however, the data published on this method so far has been limited to a small sample and few sites. METHODS All ESts performed in IBD patients between September 2018 and April 2021 in our tertiary IBD center were included. Data on demographics, disease characteristics, procedure details and outcomes were analyzed. Technical success was defined as an ability to pass the scope through the stricture following the procedure. Complications included perforation and immediate or delayed bleeding with the need of intervention or hospitalization. RESULTS In total, 92 procedures were performed in 67 patients (60 with Crohn’s disease, CD, and 7 with ulcerative colitis, UC) Among these 46.3% were males. Mean age was 43.9±12.5 years and mean disease duration was 14.6±9.7 years. Single ESt was done in 73.1% (49) of patients, while 26.9% (18) required multiple procedures. Most common location of stricture was surgical anastomosis site (82, 89.1%), while remaining 10 were located at anal canal (de novo stricture). Anastomotic strictures included ileo-colonic (64.1%), colo-colonic (9.8%), ileo-rectal (3.3%), and ileal pouch-anal (12.0%) anastomoses. Previous endoscopic balloon dilation (EBD) was attempted in 53.3% of the procedures, 27.2% of the analyzed procedures were preceded by earlier ESt. Technical success was achieved in 83 ESts (90.2%), complications occurred in four cases (all delayed bleeding, managed conservatively). After the mean follow-up time of 18.1±10.0 months, cumulative probability of reintervention (ESt, EBD or surgery) at 6 months was 30.2% (95% CI 15.6-46.2%), 40.3% (95% CI 25.5-54.6%) at 12 months and 48.8% (95% CI 34,0-62,1%) at 18 months (Figure 2). Time to reintervention was not significantly affected by previous intervention, age of the anastomosis, sex or age of the patients, concurrent therapy and specific ESt technique employed. CONCLUSION ESt is a novel endoscopic technique, which is both efficacious and safe to be performed in patients with IBD-related strictures.

Trust negotiation is a type of trust management model for establishing trust between entities by a mutual exchange of credentials. This approach was designed for online environments, where the attributes of users, such as skills, habits, behaviour and experience are unknown. Required criteria of trust negotiation must be supported by a trust negotiation model in order to provide a functional, adequately robust and efficient application. Such criteria were identified previously. In this paper we are presenting a model specification using a UML-based notation for the design of trust negotiation. This specification will become a part of the Software Development Life Cycle, which will provide developers a strong tool for incorporating trust and trust-related issues into the software they create. The specification defines components and their layout for the provision of the essential functionality of trust negotiation on one side as well as optional, additional features on the other side. The extra features make trust negotiation more robust, applicable for more scenarios and may provide a privacy protection functionality.

Trust negotiation represents a suitable approach for building trust in online environments, where the interacting entities are anonymous. It covers important criteria on security and privacy. In this work, we propose a method for implementing our model specification that handles trust negotiation. We define the structure of the trust negotiation module that is a standalone unit capable of negotiating on its own. It may be included to any software by its defined interfaces. We realise our method with a ride-sharing scenario and four trust negotiation strategies that we apply in order to validate our design and implementation. We propose a solution that is fully customisable based on different requirements. The proposal provides guidelines for developers in the process of including trust negotiation into their software.

INTRODUCTION Despite significant impact biological treatment had on prospects of patients with IBD, there is still a substantial proportion of patients with either secondary loss of response or primary non-response to therapy. Strategies to avert treatment failure include dose optimization, selection of drugs with different mechanism of action or recently combination of two different targeted molecules in cases where inflammatory activity is not under control. METHODS Patients failing on all available treatment modalities in whom surgery was not possible or was to be avoided and in whom combined treatment with two biological agents or biological agent and a small molecule was started were included. Data on demographics, treatment details, treatment persistence and disease activity including laboratory parameters and clinical activity indices - Harvey-Bradshaw for Crohn’s disease (CD) and partial Mayo score for ulcerative colitis (UC) were collected. Treatment response was evaluated using simple physician’s global assessment (PGA) as no, partial or full response. RESULTS In total, 25 patients were started on dual therapy between September 2020 and May 2021, 68% with CD and 32% with UC. Mean age of the cohort was 34.4±10.9 years, 56% were males and 44% females. Mean disease duration at baseline was 11.2±6.6 years. The follow-up continued until September 2021, median survival on therapy was 45.4 weeks and it was stopped in 40% of patients during the follow-up period. Reasons for termination included poor response, allergic reaction, unsatisfactory pharmacokinetics, advancement to surgery and denial by health insurance company. The included patients were complicated with low age of onset in CD (20.7±8.6 years), dominantly ileocolonic involvement (77%), 35% with proximal disease and 35% with perianal disease. Over 88% underwent abdominal surgery in the past. Two thirds of patients had extensive UC. Various combinations of drugs have been used with prevailing combination of ustekinumab (UST) and vedolizumab (VDZ) (41%) and UST with adalimumab (35%) in CD and VDZ with tofacitinib (63%) in UC. While in CD the overall clinical PGA response was poor with only 30% of patients at least partially responding at week 30, in UC 80% of patients were responders at week 30 (Figures 1 and 2). Apart from two infusion reactions, no other adverse events raising safety concerns occurred during the follow-up. Direct costs of the dual therapy were estimated to be 5-8 times higher as compared to the standard therapy with anti-TNF drug. CONCLUSIONS Dual therapy proved to be feasible option that can be employed without significant safety concerns in a carefully selected group of patients. Patients with colonic involvement seemed to benefit the most from the treatment, however, high incurred costs currently limit more widespread use of dual therapy in common clinical practice.

Background: Safety data of the ‘real life’ use of an infliximab biosimilar, CT-P13 in inflammatory bowel disease (IBD) are still lacking. Our aim was to assess the frequency and characteristics of infusion reactions during CT-P13 therapy in 13 Hungarian and 1 Czech IBD centres. Methods: Clinical and safety data was registered at fixed appointments. Trough levels and anti-drug antibody (ADA) concentration were measured by ELISA. Association between demographic, clinical, laboratory parameters and infusion reaction rates were evaluated statistically. Results: Three hundred and eighty-four IBD patients were included. Twenty-eight Hungarian IBD patients (9.6%) developed infusion reaction during the treatment, 64.3% of them was previously exposed to anti TNF therapy. No infusion reaction occurred in the Czech population. CT-P13 therapy had to be stopped in 17 patients who developed infusion reaction and was switched to adalimumab in 12 patients. However in 39.3% of patients developing infusion reaction CT-P13 therapy was continued with the use of premedication. Cumulative ADA positivity rates were 8.7%, 19.3%, and 28.0% at weeks 0, 14, and 30. Previous anti-TNF-alpha exposure (30% vs. 3.1%, p

This paper presents the results of a user study which quantifies the relative and absolute quality of example-based texture synthesis algorithms. In order to allow such evaluation, a list of texture properties is compiled, and a minimal representative set of textures is selected to cover these. Six texture synthesis methods are compared against each other and a reference on a selection of twelve textures by non-expert participants (N = 67). Results demonstrate certain algorithms successfully solve the problem of texture synthesis for certain textures, but there are no satisfactory results for other types of texture properties. The presented textures and results make it possible for future work to be subjectively compared, thus facilitating the development of future texture synthesis methods.

Background Telemedicine enables proper and immediate monitoring of the patient’s current health state, followed by well-timed and customised treatment. The aim of our study was to assess feasibility and safety of telemonitoring in Czech patients with inflammatory bowel disease (IBD). Furthermore, we wanted to evaluate the impact of telemonitoring on the number of outpatient′s visits and direct health-care cost. Methods We performed randomised controlled study including patients with IBD in stable remission on conventional therapy who were randomised either to telemonitoring (IBDA) or control (CTRL) group and were followed-up for 12 months. All IBDA patients had access to a specific web application which contained a set of questioners assessing disease activity and complications which were filled-in at least every 3 months. Evaluation of clinical activity was accompanied by measurement of faecal calprotectin (FC) at home using CalproSmart test. Individuals in the CTRL group were followed under the standard conditions as other outpatients. Results A total of 131 were included (42% males; 47% with Crohn′s disease) and randomised to IBDA (n = 94) or control group (n = 37). HBI/pMayo activity indexes were not significantly different at baseline (p = 0.636 and p = 0.853) and end of study (p = 0.517 and p = 0.890) in the two groups. Similarly, no significant difference in inflammatory markers (C-reactive protein, FC) was observed in either group (p>0.05). The occurrence of intercurrent infections (0.93 vs. 0.81 cases of infection/patient-year, p = 0.87) or the need for hospitalisations (1 vs. 0) was similar between the groups. The number of outpatient visits was significantly lower in the IBDA than in the CTRL group (median number in IBDA group 0, in the CTRL group 4.2 visits, respectively, p < 0.0001). Telemedicine led to a reduction in the direct annual health-care cost of patient follow-up by ~25% compared with the standard care. Conclusion Results of the first Czech IBD telemedicine study confirm the effectiveness and safety of the telemedicine approach, which led to a reduction in outpatient visits and savings in health-care costs while maintaining a high standard of health care. Acknowledgements: Supported by the IBD-Comfort Endowment Fund.

Simulation of power flow in machine tools is crucial for future development of energy efficient machines as well as for energy optimization of existing machines, production systems and manufacturing processes. This paper describes analytical approach for modelling of energy consumption of auxiliary units of the CNC machine with corresponding activity management, because these units are usually not included in current models. The developed model is then compared with the measurement of the real 3-axis machine to prove the accuracy of the model. Results show the need to calibrate the real consumption of each unit instead of theoretical value from the plate of the unit. Without this calibration, models can be inaccurate.

Background Ileocolonic resection is the most common surgery in Crohn’s disease (CD). However, stricture formation in the anastomosis is considered to be a frequent cause of significant morbidity in CD and a reason for reoperation. Endoscopic balloon dilatation (EBD) is an established modality for non-surgical treatment of strictures in CD, however, summary data from the Czech Republic are lacking. Methods All EBDs of CD anastomotic strictures performed in the 7 centres from the Czech Republic between January 1, 2013, and May 30, 2019, were included. Demographics, disease characteristics, concomitant medication and procedure outcomes were analysed. Technical success was defined as an ability to pass the endoscope through the site of the stricture following the procedure. Complications included perforation and bleeding with the need for intervention or hospitalisation. Kaplan–Meier and logistic regression analysis were performed. Results In total, 615 procedures performed in 282 patients, 52.1% males, were included. Mean age at the time of the first procedure was 41.9 ± 12.7 years and mean disease duration was 14.5 ± 8.4 years. Single dilatation was performed in 47.9% of patients, 52.1% requested repeated interventions (2–10, median 2). Cumulative probability of redilatation at 6 months, 1 year and 3 years was 20.2% (95% CI 14.8–26.2%), 31.8% (95% CI 26.5–37.2%) and 59.4% (95% CI 55.5–63.0%) respectively. Cumulative probability of a need for reoperation at 6 months, 1 year and 3 years was 4.4% (95% CI 0.5–16.9%), 8.2% (95% CI 2.3–19.3%) and 14.8% (95% CI 7.1–25.2%) respectively. Technical success was reached in 81.1% of procedures and relief of symptoms in 86.7%. The success of the procedure was dependent on the age of the patient (OR 0.98; 95% CI 0.96–0.99), smoking (OR 0.57; 95% CI 0.32–0.98) and concomitant immunosuppression use (OR 1.99; 95% CI 1.31–3.02). Complications occurred in 2.6% of the procedures. Reintervention until 6 months after the procedure was needed in 26.7% of cases, out of which repeated dilatation in 21.3% of cases and early surgery took place in 5.4% of cases. The technical success (OR 0.44; 95% CI 0.29–0.67) and repeated dilatation (OR 1.57; 95% CI 1.09–2.27) were significantly associated with the need for reintervention until 6 months. Conclusion In a large multicentric Czech cohort, the EBD in Crohn’s disease anastomotic strictures was proven to be safe and effective with results comparable to the available international data.

CT-P13, the first biosimilar monoclonal antibody to infliximab (IFX), has previously been confirmed to be efficacious in inducing mucosal healing in ulcerative colitis (UC) patients. The aim of this study was to evaluate the efficacy of CT-P13 therapy in maintaining mucosal healing in UC.CT-P13 trough levels, antibody positivity, serum inflammatory markers as CRP level, fecal calprotectin at weeks 14 and 54, concomitant steroid and azathioprine therapy at the time of induction therapy and at weeks 14 and 54, previous use of anti TNF drug and the need of dose intensification as possible predictive factors for mucosal healing at week 54 were evaluated in this prospective study.61 patients had already completed the 54-week treatment period. Mucosal healing was shown in 65.5 % and 62.1 %, complete mucosal healing was present in 31% and 38 % at week 14 and 54, respectively. The median values of CRP, leukocytes, thrombocytes, and albumin showed significant difference between baseline and week 54. Serum antibody positivity was proved in 6.5 % and 19.7 % of cases at week 14 and 54, respectively.Our study confirmed the long-term efficacy of CT-P13 therapy on mucosal healing in UC.

Discontinuation of anti-TNF therapy in patients with inflammatory bowel diseases (IBD) in remission remains a controversial issue. The aims of our study were to assess the proportion of patients who relapse after cessation of biological treatment, and to identify potential risk factors of disease relapse.Consecutive IBD patients who discontinued anti-TNF therapy in steroid-free clinical and endoscopic remission were prospectively followed. Multiple logistic regression and Cox proportional-hazards models were used to assess the predictors of disease relapse.Seventy-eight IBD patients (Crohn's disease, CD 61; ulcerative colitis, UC 17) were included and followed for a median of 30 months (range 7-47). A total of 32 (53%) CD patients and nine (53%) UC patients relapsed by the end of the follow-up with a median time to relapse of 8 months (range 1-25) in CD patients and 14 months (range 4-37) in UC patients, respectively. The cumulative probabilities of maintaining remission at 6, 12, and 24 months were 82%, 59%, and 51% in CD patients, and 77%, 77%, and 64% in UC patients, respectively. Survival of CD patients who were in deep remission (clinical and endoscopic healing; faecal calprotectin150 mg/kg; CRP ≤5 mg/l) was not better compared with those who did not fulfill these criteria. In multivariate models, only colonic CD protected patients from disease relapse.Approximately half of the IBD patients relapsed within 2 years after anti-TNF discontinuation. In CD patients, no difference between those who were or were not in deep remission was found. Colonic localization protected patients from relapse.

We give a complete classification of polynomial models for smooth real hypersurfaces of finite Catlin multitype in $\mathbb C^3$, which admit nonlinear infinitesimal CR automorphisms. As a consequence, we obtain a sharp 1-jet determination result for any smooth hypersurface with such model. The results also prove a conjecture of the first author about the origin of such nonlinear automorphisms (AIM list of problems, 2010). As another consequence, we describe all possible dimensions of the Lie algebra of infinitesimal CR automorphisms, which leads to a new "secondary" gap phenomenon.

We consider the fundamental invariant of a real hypersurface in C-N - its holomorphic symmetry group - and analyze its structure at a point of degenerate Levi form. Generalizing the Chern-Moser operator to hypersurfaces of finite multitype, we compute the Lie algebra of infinitesimal symmetries of the model and provide explicit description for each graded component. Compared with a hyperquadric, it may contain additional components consisting of nonlinear vector fields defined in terms of complex tangential variables. As a consequence, we obtain exact results on jet determination for hypersurfaces with such models. The results generalize directly the fundamental result of Chern and Moser from quadratic models to polynomials of higher degree. (C) 2014 Elsevier Inc. All rights reserved.

In this paper we will study the Hessian matrices of composite functions F which are in the form F (x) = f(g(x)) with f : R ! R and g : R n ! R. We present an explicit formulas for the Hessian of F and for the inverse of the Hessian matrix. Mathematics Subject Classication: 26B05

We consider the effects of salt (sodium iodide) on pristine carbon nanotube (CNT) dispersions in an organic solvent, N-methyl-2-pyrrolidone (NMP). We investigate the molecular-scale mechanisms of ion interactions with the nanotube surface and we show how the microscopic ion-surface interactions affect the stability of CNT dispersions in NMP. In our study we use a combination of fully atomistic Molecular Dynamics simulations of sodium and iodide ions at the CNT-NMP interface with direct experiments on the CNT dispersions. In the experiments we analyze the effects of salt on the stability of the dispersions by photoluminescence (PL) and optical absorption spectroscopy of the samples as well as by visual inspection. By fully atomistic Molecular Dynamics simulations we investigate the molecular-scale mechanisms of sodium and iodide ion interactions with the nanotube surface. Our simulations reveal that both ions are depleted from the CNT surface in the CNT-NMP dispersions mainly due to the two reasons: (1) there is a high energy penalty for the ion partial desolvation at the CNT surface; (2) NMP molecules form a dense solvation layer at the CNT surface that prevents ions to come close to the CNT surface. As a result, an increase of the salt concentration increases the "osmotic" stress in the CNT-NMP system and, thus, decreases the stability of the CNT dispersions in NMP. Direct experiments confirm the simulation results: addition of NaI salt into the NMP dispersions of pristine CNTs leads to precipitation of CNTs (bundle formation) even at very small salt concentration (∼10 -3 mol L -1). In line with the simulation predictions, the effect increases with the increase of the salt concentration. Overall, our results show that dissolved salt ions have strong effects on the stability of CNT dispersions. Therefore, it is possible to stimulate the bundle formation in the CNT-NMP dispersions and regulate the overall concentration of nanotubes in the dispersions by changing the NaI concentration in the solvent.

This article follows recent work of Miyajima on the complex-analytic approach to deformations of the regular part (i.e. the punctured smooth neighbourhood) of isolated singularities. Attention has previously focused on stably-embeddable infinitesimal deformations as those which correspond to standard algebraic deformations of the germ of a variety, and which also lead to convergent series solutions of the Kodaira-Spencer integrability equation. The emphasis of the present paper, however, is on the subspaces Z(0) of first cohomology classes containing infinitesimal deformations with vanishing Kodaira- Spencer bracket, and W(0), consisting more broadly of deformations for which the bracket represents the trivial second cohomology class. Deformations representing classes in Z(0) are automatically integrable, regardless of their analytic behaviour near the singular point. Classes in W(0) are those for which only the first formal obstruction to integrability is overcome. After some preliminary results on cohomology, the main theorem of this paper gives a partial description of the analytic geometry of Z(0) and W(0) for affine cones of arbitrary

The first part of this paper considers higher order CR invariants of three dimensional hypersurfaces of finite type. Using a full normal form we give a complete characterization of hypersurfaces with trivial local automorphism group, and analogous results for finite groups. The second part considers hypersurfaces of finite Catlin multitype and the Kohn-Nirenberg phenomenon in higher dimensions. We give a necessary condition for local convexifiability of a class of pseudoconvex hypersurfaces in $\mathbb C^{n+1}$.

In this study we investigate salt effects on bundle formation of carbon nanotubes (CNTs) dispersed in an organic solvent, N-methyl-2-pyrrolidone (NMP). Addition of NaI salt leads to self-assembly of CNTs into well-recognizable bundles. It is possible to control the size of the CNT bundles by varying the salt concentration.

Internal and external anti-infective coating of central venous catheters (CVCs) may reduce the rate of catheter colonization (CC) and bloodstream infection (BSI) [1]. Our objective was to evaluate the efficacy of a protective nonleaching polyhexanide coating on the rate of CC and BSI in ICU settings.

Secondary brain injury contributes to poor outcome for patients sustaining brain trauma. Matrix metalloproteinase-9 (MMP-9) is a potential marker, as well as effector of secondary brain injury. This enzyme degrades components of extracellular matrix, and thus it can contribute to blood-brain barrier disruption.We studied dynamics of MMP-9 in jugular venous blood of 15 patients sustaining either an isolated head injury or a head injury as a part of major trauma, and requiring intensive care (Glasgow Coma Scale8 at the time of admission). Blood samples were taken at the 1st, 3rd and 5th day, levels of MMP-9 in plasma were assessed using ELISA. Outcome quality was assessed at the time of discharge from our hospital.Our results show an increase of MMP-9 levels on the 1st day after the brain trauma, followed by a drop on the 3rd day and a rise on day 5. This biphasic time-course was observed in all patients, but no statistically significant differences between each group (major trauma vs. isolated brain trauma, good outcome vs. poor outcome) were found.Initially increased MMP-9 levels in the 1st posttraumatic day is probably related to transient blood-brain barrier dysruption. The decrease of MMP-9 levels observed on the 3rd day can be explained by restoration of blood-brain barrier integrity and its reduced permeability. The second rise of MMP-9 levels observed in the 5th day probably indicates a developing secondary brain injury during which MMP-9 is produced in the brain as a part of an inflammatory response.of our study suggest that MMP-9 could play an important role in pathogenesis of secondary brain injury.

BACKGROUND: Secondary brain injury contributes to poor outcome for patients sustaining brain trauma. Matrix metalloproteinase-9 (MMP-9) is a potential marker, as well as effector of secondary brain injury. This enzyme degrades components of extracellular matrix, and thus it can contribute to blood-brain barrier disruption. METHODS: We studied dynamics of MMP-9 in jugular venous blood of 15 patients sustaining either an isolated head injury or a head injury as a part of major trauma, and requiring intensive care (Glasgow Coma Scale

We construct normal forms for Levi degenerate hypersurfaces of finite type in $\mathbb{C}^2$. As one consequence, an explicit solution to the problem of local biholomorphic equivalence is obtained. Another consequence determines the dimension of the stability group of the hypersurface.