Precision Medicine in Inflammatory Bowel Disease: A Spotlight on Emerging Molecular Biomarkers.

Inflammatory bowel diseases (IBD) remain challenging in terms of understanding their causes and in terms of diagnosing, treating, and monitoring patients. Modern diagnosis combines biomarkers, imaging, and endoscopic methods. Common biomarkers like CRP and fecal calprotectin, while invaluable tools, have limitations and are not entirely specific to IBD. The limitations of existing markers and the invasiveness of endoscopic procedures highlight the need to discover and implement new markers. With an ideal biomarker, we could predict the risk of disease development, as well as the possibility of response to a particular therapy, which would be significant in elucidating the pathogenesis of the disease. Recent research in the fields of machine learning, proteomics, epigenetics, and gut microbiota provides further insight into the pathogenesis of the disease and is also revealing new biomarkers. New markers, such as BAFF, PGE-MUM, oncostatin M, microRNA panels, αvß6 antibody, and S100A12 from stool, are increasingly being identified, with αvß6 antibody and oncostatin M being potentially close to being presented into clinical practice. However, the specificity of certain markers still remains problematic. Furthermore, the use of expensive and less accessible technology for detecting new markers, such as microRNAs, represents a limitation for widespread use in clinical practice. Nevertheless, the need for non-invasive, comprehensive markers is becoming increasingly important regarding the complexity of treatment and overall management of IBD.

Mechanical and Fire Performance of Innovative Hollow Glue-Laminated Timber Beams.

Fire safety greatly contributes to feeling safe, and it is a key parameter for the selection of building materials. The combustibility of timber is one of the main reasons to have the strict restriction on timber for use as a building material, especially for multistory buildings. Therefore, the main prerequisite for the use of timber in buildings is to ensure adequate fire resistance, using passive and active fire protection measures. This article contains the results of mechanical and fire experimental tests of both normal and innovative hollow glued laminated timber beams. A total of 10 timber beams were tested at ambient temperature, and 3 timber beams in fire conditions, which differed in cross-section type but also in the applied fire protection. The first beam was a normal GL beam without fire protection, the second a hollow beam covered by intumescent paint, while the third was also hollow, additionally protected by mineral wool infill inside the holes. The load-carrying capacity of the hollow beam in ambient conditions was estimated at 65% of the load-carrying capacity of a normal GL beam. Fire tests indicated that hollow timber beams with both intumescent paint and mineral wool infill failed at a similar time as a normal GL beam without fire protection. One-dimensional ß0 and notional charring rates ßn were obtained. Time to the protective material failure was 17 min. The main cause of failure of hollow beams was the appearance of delamination due to the reduction of the lamella bonding surface.

Compressive Strength Properties Perpendicular to the Grain of Hollow Glue-Laminated Timber Elements.

Timber is one of the fundamental materials of human civilization, it is very useful and ecologically acceptable in its natural environment, and it fits very well with modern trends in green construction. The paper presents innovative hollow glued laminated (GL) timber elements intended for log-house construction. Due to the lack of data on the behavior of the hollow timber section in compression perpendicular to the grain, the paper presented involves testing the compression strength of elliptical hollow cross-section glue-laminated timber specimens made of softwood and hardwood, as well as full cross-section glue-laminated softwood timber specimens. The experimental research was carried out on a total of 120 specimens. With the maximal reduction of 26% compared to the full cross-section, regardless of the type of wood and direction of load, the compression strength perpendicular to the grain of hollow specimens decreases by about 55% compared to the full cross-section, with the coefficient kc,90 equal to 1.0. For load actions at the edge and the middle of the element, kc,90 factors were obtained with a value closer to those obtained for full cross-section, which indicates the same phenomenology, regardless of cross-sectional weakening. At the same time, the factors in the stronger axis are lower by about 10%, and in the weaker axis by about 30% compared to those prescribed by the Eurocode. Experimental research was confirmed by FEM analysis. Comparative finite element analysis was performed in order to provide recommendations for future research and, consequently, to determine the optimal cross-section form of the hollow GL timber element. By removing the holes in the central part of the cross-section, the stress is reduced. The distance of the holes from the edges defines the local cracking. Finally, if the holes are present only in the central part of the element, the behavior of the element is more favorable.

Personalized Approach in Eradication of Helicobacter pylori Infection.

The increase in antibiotic resistance to Helicobacter pylori (H. pylori) is associated with a decrease in the effectiveness of eradication therapy. Although some success has been achieved by adjusting therapeutic regimens according to local data on resistance to certain antibiotics, a new approach is needed to ensure a better therapeutic response. Tailored therapy, based on sensitivity tests to antibiotics, is increasingly proving to be a superior therapeutic option, even as a first-line therapy. Moreover, the recently published Maastricht VI guidelines emphasize utilizing a susceptibility-guided strategy in respect to antibiotic stewardship as the first choice for eradication therapy. In addition, polymerase chain reaction (PCR) technology is becoming a standard tool in the diagnosis of H. pylori infections through non-invasive testing, which further optimizes the eradication process. We provide a review regarding the current position of the individualized approach in eradication therapy and its future prospects. Based on novel understandings, the personalized approach is an effective strategy to increase the successful eradication of H. pylori infections.

Behavioral Assessment and Evaluation of Innovative Hollow Glue-Laminated Timber Elements.

Due to the growing need to preserve our planet and reduce carbon emissions during construction, the use of the only carbon-absorbing material, timber, is increasingly being imposed. In addition to the requirement of reducing emissions, there is a necessity for the shortest possible construction time and the minimum use of construction machinery, which has led to the development of prefabricated construction systems. This paper deals with the innovative, hollow, glue-laminated timber elements which are intended for modular construction. Comparing this new system with existing modular systems, the main features and behavior of the constitutive elements, i.e., the hollow, glue-laminated timber elements, are presented. Experimental and numerical analysis of the mechanical performance of the timber elements was carried out and a comparative analysis of the behavior of two different types of hollow timber elements was conducted. The finite element method was used to predict the behavior of this innovative structural system. The results are compared with the analytical procedure to provide a background for the development of standardized methods for the design of timber structures.

Randomized Clinical Trial Comparing Concomitant and Tailored Therapy for Eradication of Helicobacter pylori Infection.

As high clarithromycin resistance (>20%) in the Split-Dalmatia region of Croatia hinders the treatment of H. pylori infection, the primary objective of this study was to compare concomitant quadruple with the tailored, personalized therapy as first-line eradication treatment of H. pylori. In an open-label, randomized clinical trial, 80 patients with H. pylori infection were randomly assigned to either concomitant (esomeprazole 40 mg, amoxicillin 1 gr, metronidazole 500 mg, clarithromycin 500 mg, twice daily for 14 days) or tailored therapy in accordance with the results of the antimicrobial susceptibility testing. Eradication status was assessed 4 weeks after treatment. Eradication rates were significantly higher in tailored group than in concomitant group both in intention-to-treat (70 vs. 92.5%, p = 0.010) and per-protocol (87.5 vs. 100%, p = 0.030) analysis in the setting of increasing antibiotic resistance (clarithromycin 37.5%, metronidazole 17.5%, dual resistance 10%). Adverse effects were more frequent in the concomitant group (32.5 vs. 7.5%, p = 0.006). Tailored therapy achieves higher eradication with a lower adverse events rate. With the increasing resistance of H. pylori strains to antibiotic treatment, eradication regimes with such characteristics should be strongly considered as a reasonable choice for first-line treatment.

Blood markers of endothelial dysfunction and their correlation to cerebrovascular reactivity in patients with chronic hepatitis C infection.

Although liver cirrhosis and hepatocellular carcinoma are major consequences of hepatitis C (HCV), there has been an increasing number of studies examining extrahepatic manifestations, especially those caused by systemic chronic inflammation and metabolic complications that might predispose HCV patients to atherosclerosis and ischemic cerebrovascular disease (CVD). The aim of our study was to assess E-selectin, VCAM-1, ICAM-1 and VEGF-A serum levels in patients with chronic HCV infection and to correlate them with cerebrovascular reactivity. A blood sample was taken from eighteen patients with chronic hepatitis C infection and from the same number of healthy blood donors in the control group. The aim was to analyse markers of endothelial dysfunction and to correlate them with cerebrovascular reactivity expressed as breath-holding index (BHI) determined using transcranial color Doppler. The obtained results revealed significant differences between the groups in all endothelial markers except for the E selectin. While the ICAM-1 and sVCAM-1 were significantly increased in the hepatitis group, VEGF-A was significantly decreased. A significant reduction of 0.5 (95% CI 0.2, 0.8) in the mean BHI was found in the hepatitis group (mean BHI 0.64) compared to controls (mean BHI 1.10). No significant association between the BHI and any of the endothelial markers was found in the control group, while in the hepatitis group, the scatter plot of ICAM-1 vs BHI suggested that the association might be present. In conclusion, the results of this study confirm an association between a chronic HCV infection and altered cerebrovascular reactivity as well as higher levels of markers of endothelial activation (ICAM-1, VCAM-1) as possible indicators of an increased CVD risk.

Randomised clinical trial comparing concomitant and hybrid therapy for eradication of Helicobacter pylori infection.

BACKGROUND: The primary objective of this study was to compare concomitant and hybrid therapy in the first line eradication treatment of Helicobacter pylori infection in Split-Dalmatia County, Croatia, in which clarithromycin resistance is above 20%. The secondary objective of the study was to determine and compare compliance and adverse events rate between these therapeutic protocols. MATERIALS AND METHODS: In an open-label, randomised clinical trial 140 patients total with H. pylori infection were randomly assigned to either concomitant (esomeprazole 40 mg, amoxicillin 1 g, metronidazole 500 mg, clarithromycin 500 mg, twice daily for 14 days) or hybrid (esomeprazole 40 mg and amoxicillin 1 g twice daily during 14 days with adding metronidazole 500 mg and clarithromycin 500 mg twice daily, in the last 7 days,) treatment group. RESULTS: Eradication rates for concomitant group and hybrid therapy group were 84.1% (58/69) and 83.1% (59/71) respectively in the intention-to-treat analysis and 96.7% (58/60) and 95.2% (59/62) in per-protocol analysis. There was no significant difference between the groups (ITT analysis: P = 0.878; PP analysis: P = 0.675). Adverse events were more frequent in the concomitant group (33.3% vs 18.3%, P = 0.043). There was no difference among groups regarding compliance rate. CONCLUSION: Hybrid therapy has similar eradication rate as concomitant therapy, with lower adverse events rate. In the era of increasing antibiotic resistance, eradication regime with less antibiotic's usage, as hybrid therapy, should be reasonable first line treatment choice for H. pylori infection. Clinical Trials, gov: NCT03572777.

Evaluation of cerebrovascular reactivity in chronic hepatitis C patients using transcranial color Doppler.

Hepatitis C viral (HCV) infection is associated with systemic inflammation and metabolic complications that might predispose patients to atherosclerosis, including cerebrovascular atherosclerosis. The aim of this study was to assess cerebrovascular reactivity in patients with chronic hepatitis C. Seventeen patients with chronic hepatitis C infection, as well as 11 healthy blood donors in the control group, were assessed for cerebrovascular reactivity according to the well-established breath-holding test that uses the transcranial color Doppler for measurement of blood flow velocity. Results obtained during the breath-holding revealed significantly lower average peak systolic (AvPS start, P = 0.018), end-diastolic (AvED start, P = 0.031) and mean velocity values at the very beginning of the breath-holding procedure (AvmeanV start, P = 0.02), as well as a lower mean peak systolic velocity at the end of the breath-holding test (AvPS max, P = 0.02) in the hepatitis C group. Vascular reactivity values, calculated as the breath-holding index, were also significantly lower (P = 0.045) in the hepatitis C group. In conclusion, the results of this study suggest an association between chronic HCV infection and altered cerebrovascular reactivity which may ultimately have an unfavorable effect on cerebrovascular hemodynamics and lead to increased risk of cerebrovascular diseases.

A Foreign Body (Toothbrush) in the Esophagus of a Patient with Hiatal Hernia.

Toothbrush ingestion is rare and most commonly seen in patients with psychiatric comorbidities and in young women with a medical history of eating disorders who try to induce emesis. Long ingested objects, such as a toothbrush, cannot pass the gastrointestinal tract spontaneously and require endoscopic removal or even a surgical approach in cases of unsuccessful endoscopic removal or complication development. We present a case of a 71-year-old male with hiatal hernia without psychiatric or neurological comorbidity who accidentally ingested a toothbrush during oral hygiene routine. After X-ray confirmation, the toothbrush was removed endoscopically.

Colonoscopic Polypectomies and Recommendations on the Colonoscopy Follow-up Intervals Depending on Endoscopic and Histopathological Findings.

THE AIM: To show histopathological diagnoses after colonoscopic polypectomy in the University Hospital Center (KBC) Split with recommendations on further follow-up colonoscopy depending on the endoscopic and histological findings. PATIENTS AND METHODS: The study included 2842 patients who underwent colonoscopy in a two-year period (2008-2009), followed by a detailed analysis of 350 patients in which one or more polyps were simultaneously removed and 163 patients who were only sampled for histological analysis. Patients from the National Program for Colorectal Cancer Prevention and patients in which colonoscopy is indicated as part of daily outpatient or inpatient treatment were included as well. RESULTS: During 2008 and 2009 in KBC Split, out of a total of 2842 colonoscopies, 350 patients underwent colonoscopic polypectomy, whereby 618 polyps were removed (1-8 polyps in individual patients), while in 163 patients only biopsy specimens were sampled. Out of the total of 557 polyps sent for histological analysis, 236 were hyperplastic (42%), 193 were identified as tubular adenoma (35%), 84 were tubulovillous (15%), 18 villous (3%), 9 were adenocarcinoma (2%) and other 17 (3%). In 35 (15.4%) polyps high-grade dysplasia was found. The largest number of nonpolypectomized changes confirmed the presence of adenocarcinoma (76-47%), adenomas and hyperplastic polyps were 37 (22%) and regular findings 23 (14%). Mucosal high-grade dysplasia was demonstrated in 35 (23.1%) biopsied changes. CONCLUSION: Colonoscopies with polypectomy decreased the risk of the formation of colorectal cancer in these patients almost to the level of risk in patients who have not even had a polyp during colonoscopy. Arguably the best method of prevention and early detection of colorectal cancer are already widely established national programs. The next qualitative level is constantly improving the quality of colonoscopy with clear criteria and the establishment of a body to evaluate the performers and the equipment, and making recommendations on the colonoscopy follow-up intervals depending on endoscopic and histopathological findings of patients who for any reason underwent colonoscopy.

[Long-terme outcome of peritoneal dialysis treatment--27 years of single centre experience]. / Ishod dugogodisnjeg lijecenja peritonejskom dijalizom--27 godina iskustva u jednom centru.

By the end of 2007 we had 160 patients on CAPD treatment in our centre (44% male, 56% female) aged between 29-78 years. Till 1994 13% of our patients were diabetics. In the last 10 years (1997-2007) the percentage of diabetics increased to 36%. During the 27 years period 44% of our patients died, 35% switched to haemodialysis and 3% have undergone renal transplantation. The survival rate after three years of treatment was 75%, after five years 63% and after 10 years 44%. Technique survival was 77%, 65% and 48% respectively. There were 309 episodes of peritonitis as the main complication of treatment (one episode on every 9, 4 months of treatment till 1994 and one episode on every 25, 8 months in the last ten years), out of which 58% was caused by Gram positive bacteria, 18% by Gram negative, 4% were fungal infections while the remaining 20% were culture negative. Regarding other complications we had 42 exit-site infections and 8 episodes of sclerosing peritonitis with 4 deaths. We found peritonitis to be the main reason of switching to haemodialysis (71%) and the main reason of death (39%) among the patients on CAPD. In the last 10 years (1997-2007) we analyzed the diabetics group separately and we found that the rate of CAPD dropout was not significantly different between diabetics and non-diabetics group. However, when analysing the causes of CAPD dropout, we found significant difference in mortality ate (50% among diabetics versus 26% among non-diabetics) and the rate of switching to haemodialysis (37% versus 55% respectively). In addition we established that the rate of CAPD survival was better after 1994 and we speculate that the main reason is the diminished peritonitis rate.