Switching Vedolizumab from IV to SC Injection in Inflammatory Bowel Disease Patients with Active Disease: Real-World Experience from a German IBD Cohort.

BACKGROUND: Vedolizumab (VDZ) for subcutaneous (SC) injection was approved for use in Europe in 2020 and the US in 2023. Promising efficacy and tolerability have been proven in pivotal trials. However, real-world data on the SC use of VDZ, especially in patients with active disease, are still lacking. We aimed to determine treatment persistence and the drug's efficacy in inflammatory bowel disease (IBD) patients with active disease in comparison to patients in clinical remission. METHODS: Patients treated for IBD in a tertiary care center from July 2020 to December 2021 were included in this study. Clinical and biochemical parameters and data on treatment adherence were collected. VDZ trough levels and disease activity before and after the switch from intravenous (IV) to SC injections were monitored during routine checkups and were retrospectively analyzed. The patients were followed up until week 20. RESULTS: Eighty-two patients were included in the study. Of them, 35 patients had active disease (35/82 = 43%) at the time of the switch and 47 patients (47/82 = 57%) were in remission. In total, 10 patients experienced switch failure, 5 were switched back to IV VDZ, and 5 were swapped to a different biologic agent. We observed an increase in VDZ trough levels from the switch to week 8 and from the switch to week 20 in the remission group. Vedolizumab trough levels of 7.4, 51.4, and 33.45 ug/mL at the switch, week 8, and week 20 were identified to discriminate between remission and disease activity in our cohort. There was no new safety signal detected during the study period. CONCLUSIONS: The switch from IV to SC VDZ proved to be efficient, safe, and even capable of reducing residual disease activity.

Impact of a shorter replacement interval of plastic stents on premature stent exchange rate in benign and malignant biliary strictures.

BACKGROUND AND AIM: The main disadvantage of plastic stents is the high rate of stent occlusion. The usual replacement interval of biliary plastic stents is 3 months. This study aimed to investigate if a shorter interval of 6-8 weeks impacts the median premature exchange rate (mPER) in benign and malignant biliary strictures. METHODS: All cases with endoscopic retrograde cholangiopancreatography (ERCP) and plastic stent placement were retrospectively analyzed since establishing an elective replacement interval of every 6-8 weeks at our institution and mPER was determined. RESULTS: A total of 3979 ERCPs (1199 patients) were analyzed, including 1262 (31.7%) malignant and 2717 (68.3%) benign cases, respectively. The median stent patency (mSP) was 41 days (range 14-120) for scheduled stent exchanges, whereas it was 17 days (1-75) for prematurely exchanged stents. The mPER was significantly higher for malignant (28.1%, 35-50%) compared with benign strictures (15.2%, 10-28%), P < 0.0001, respectively. mSP was significantly shorter in cases with only one stent (34 days [1-87] vs 41 days [1-120]) and in cases with only a 7-Fr stent (28 days [2-79]) compared with a larger stent (34 days [1-87], P = 0.001). Correspondingly, mPER was significantly higher in cases with only one stent (23% vs 16.2%, P < 0.0001) and only a 7-Fr stent (31.3% vs 22.4%, P = 0.03). CONCLUSION: A shorter replacement interval does not seem to lead to a clinically meaningful reduction of mPER in benign and malignant strictures. Large stents and multiple stenting should be favored as possible.

A Single-Center Case Series of Endoscopically Treated Aorto-Gastrointestinal Fistula after Endovascular Aortic Repair: Surgery Is Still the Only Valid Solution.

INTRODUCTION: Aortoesophageal fistula (AEF) is a life-threatening complication associated with endovascular aortic repair (EVAR) and occurs mostly in patients who undergo thoracic EVAR (TEVAR). To date, surgical treatment of AEF has been considered the most promising therapeutic approach. New endoscopic techniques could contribute to the therapy of AEF. The aim of this study was to analyze the outcome after endoscopic treatment of EVAR-associated AEF. METHODS: All patients who received endoscopic diagnostics and/or therapy for AEF after EVAR/TEVAR in our center between 2010 and 2019 were evaluated. RESULTS: Seven suitable patients were included. Six of them had undergone TEVAR and 1 had EVAR. Fistula occurred at an average of 307 days (range 21-2,774 days) post-EVAR. Endoscopic treatment was performed on 4 patients by using an over-the-scope clip (OTSC®). However, fistula recurred in all patients who were initially treated endoscopically. They were then treated either by sequential application of further OTSCs® or by implantation of a fully coated, self-expanding metal stent. One of these patients underwent a partial esophageal resection in a subsequent treatment approach. All patients died during the observational period, 5 as a direct consequence of the AEF/aortoduodenal fistula and 2 due to comorbidities. The median survival time after fistula occurrence was 120 days (range 5-823 days). CONCLUSION: Endoscopic treatment of AEF with OTSC® should be considered as a possible interim solution, especially in patients with severe comorbidities. However, surgical remediation still appears to be the only procedure with intermediate to long-term therapeutic success.

The presence of liver cirrhosis is a strong negative predictor of survival for patients admitted to the intensive care unit - Cirrhosis in intensive care patients.

BACKGROUND AND AIMS: Liver cirrhosis is a systemic disease that substantially impacts the body's physiology, especially in advanced stages. Accordingly, the outcome of patients with cirrhosis requiring intensive care treatment is poor. We aimed to analyze the impact of cirrhosis on mortality of intensive care unit (ICU) patients compared to other frequent chronic diseases and conditions. METHODS: In this retrospective study, patients admitted over three years to the ICU of the Department of Medicine of the University Hospital Frankfurt were included. Patients were matched for age, gender, pre-existing conditions, simplified acute physiology score (SAPS II), and therapeutic intervention scoring system (TISS). RESULTS: A total of 567 patients admitted to the ICU were included in the study; 99 (17.5 %) patients had liver cirrhosis. A total of 129 patients were included in the matched cohort for the sensitivity analysis. In-hospital mortality was higher in cirrhotic patients than non-cirrhotic patients (p < 0.0001) in the entire and matched cohort. Liver cirrhosis remained one of the strongest independent predictors of in-hospital mortality (entire cohort p = 0.001; matched cohort p = 0.03) along with dialysis and need for transfusion in the multivariate logistic regression analysis. Furthermore, in the cirrhotic group, the need for kidney replacement therapy (p < 0.001) and blood transfusion (p < 0.001) was significantly higher than in the non-cirrhotic group.  CONCLUSIONS: In the presented study, liver cirrhosis was one of the strongest predictors of in-hospital mortality in patients needing intensive care treatment along with dialysis and the need for ventilation. Therefore, concerted efforts are needed to improve cirrhotic patients' outcomes, prevent disease progression, and avoid complications with the need for ICU treatment in the early stages of the disease.

Not uncommon: HBV genotype G co-infections among healthy European HBV carriers with genotype A and E infection.

BACKGROUND & AIMS: HBV genotype G (HBV/G) is mainly found in co-infections with other HBV genotypes and was identified as an independent risk factor for liver fibrosis. This study aimed to analyse the prevalence of HBV/G co-infections in healthy European HBV carriers and to characterize the crosstalk of HBV/G with other genotypes. METHODS: A total of 560 European HBV carriers were tested via HBV/G-specific PCR for HBV/G co-infections. Quasispecies distribution was analysed via deep sequencing, and the clinical phenotype was characterized regarding qHBsAg-/HBV-DNA levels and frequent mutations. Replicative capacity and expression of HBsAg/core was studied in hepatoma cells co-expressing HBV/G with either HBV/A, HBV/D or HBV/E using bicistronic vectors. RESULTS: Although no HBV/G co-infection was found by routine genotyping PCR, HBV/G was detected by specific PCR in 4%-8% of patients infected with either HBV/A or HBV/E but only infrequently in other genotypes. In contrast to HBV/E, HBV/G was found as the quasispecies major variant in co-infections with HBV/A. No differences in the clinical phenotype were observed for HBV/G co-infections. In vitro RNA and DNA levels were comparable among all genotypes, but expression and release of HBsAg was reduced in co-expression of HBV/G with HBV/E. In co-expression with HBV/A and HBV/E expression of HBV/G-specific core was enhanced while core expression from the corresponding genotype was markedly diminished. CONCLUSIONS: HBV/G co-infections are common in European inactive carriers with HBV/A and HBV/E infection, but sufficient detection depends strongly on the assay. HBV/G regulated core expression might play a critical role for survival of HBV/G in co-infections.

Multinucleated giant cells within the in vivo implantation bed of a collagen-based biomaterial determine its degradation pattern.

OBJECTIVES: The aim of the present study was to characterize the cellular reaction to a xenogeneic resorbable collagen membrane of porcine origin using a subcutaneous implantation model in Wistar rats over 30 days. MATERIALS AND METHODS: Ex vivo, liquid platelet-rich fibrin (PRF), a leukocyte and platelet-rich cell suspension, was used to evaluate the blood cell membrane interaction. The material was implanted subcutaneously in rats. Sham-operated rats without biomaterial displayed physiological wound healing (control group). Histological, immunohistological, and histomorphometric analyses were focused on the inflammatory pattern, vascularization rate, and degradation pattern. RESULTS: The membrane induced a large number of mononuclear cells over the observation period, including lymphocytes, macrophages, and fibroblasts. After 15 days, multinucleated giant cells (MNGCs) were observed on the biomaterial surface. Their number increased significantly, and they proceeded to the center of the biomaterial on day 30. These cells highly expressed CD-68, calcitonin receptor, and MMP-9, but not TRAP or integrin-ß3. Thus, the membrane lost its integrity and underwent disintegration as a consequence of the induction of MNGCs. The significant increase in MNGC number correlated with a high rate of vascularization, which was significantly higher than the control group. Physiological wound healing in the control group did not induce any MNGCs at any time point. Ex vivo blood cells from liquid-PRF did not penetrate the membrane. CONCLUSION: The present study suggests a potential role for MNGCs in biomaterial degradation and questions whether it is beneficial to accept them in clinically approved biomaterials or focus on biomaterials that induce only mononuclear cells. Thus, further studies are necessary to identify the function of biomaterial-induced MNGCs. CLINICAL RELEVANCE: Understanding the cellular reaction to biomaterials is essential to assess their suitability for specific clinical indications and outline the potential benefit of specific group of biomaterials in the respective clinical indications.

Quadruple mutation GCAC1809-1812TTCT acts as a biomarker in healthy European HBV carriers.

Many mutation analyses of the HBV genome have been performed in the search for new prognostic markers. However, the Kozak sequence preceding precore was covered only infrequently in these analyses. In this study, the HBV core promoter/precore region was sequenced in serum samples from European inactive HBV carriers. Quadruple mutation GCAC1809-1812TTCT was found with a high prevalence of 42% in the Kozak sequence preceding precore among all HBV genotypes. GCAC1809-1812TTCT was strongly associated with coexistence of basal core promoter (BCP) double mutation A1762T/G1764A and lower HBV DNA levels. In vitro GCAC1809-1812TTCT lead to drastically diminished synthesis of pregenomic RNA (pgRNA), precore mRNA, core, HBsAg, and HBeAg. Calculation of the pgRNA secondary structure suggests a destabilization of the pgRNA structure by A1762T/G1764A that was compensated by GCAC1809-1812TTCT. In 125 patients with HBV-related cirrhosis, GCAC1809-1812TTCT was not detected. While a strong association of GCAC1809-1812TTCT with inactive carrier status was observed, BCP double mutation was strongly correlated with cirrhosis, but this was only observed in absence of GCAC1809-1812TTCT. In conclusion, our data reveal that GCAC1809-1812TTCT is highly prevalent in inactive carriers and acts as a compensatory mutation for BCP double mutation. GCAC1809-1812TTCT seems to be a biomarker of good prognosis in HBV infection.

The N-Terminus Makes the Difference: Impact of Genotype-Specific Disparities in the N-Terminal Part of The Hepatitis B Virus Large Surface Protein on Morphogenesis of Viral and Subviral Particles.

The N-terminus of the hepatitis B virus (HBV) large surface protein (LHB) differs with respect to genotypes. Compared to the amino terminus of genotype (Gt)D, in GtA, GtB and GtC, an additional identical 11 amino acids (aa) are found, while GtE and GtG share another similar 10 aa. Variants of GtB and GtC affecting this N-terminal part are associated with hepatoma formation. Deletion of these amino-terminal 11 aa in GtA reduces the amount of LHBs and changes subcellular accumulation (GtA-like pattern) to a dispersed distribution (GtD-like pattern). Vice versa, the fusion of the GtA-derived N-terminal 11 aa to GtD causes a GtA-like phenotype. However, insertion of the corresponding GtE-derived 10 aa to GtD has no effect. Deletion of these 11aa decreases filament size while neither the number of released viral genomes nor virion size and infectivity are affected. A negative regulatory element (aa 2-8) and a dominant positive regulatory element (aa 9-11) affecting the amount of LHBs were identified. The fusion of this motif to eGFP revealed that the effect on protein amount and subcellular distribution is not restricted to LHBs. These data identify a novel region in the N-terminus of LHBs affecting the amount and subcellular distribution of LHBs and identify release-promoting and -inhibiting aa residues within this motive.

Hepatitis C Clearance by Direct-Acting Antivirals Impacts Glucose and Lipid Homeostasis.

BACKGROUND: Chronic hepatitis C virus (HCV) infections are causally linked with metabolic comorbidities such as insulin resistance, hepatic steatosis, and dyslipidemia. However, the clinical impact of HCV eradication achieved by direct-acting antivirals (DAAs) on glucose and lipid homeostasis is still controversial. The study aimed to prospectively investigate whether antiviral therapy of HCV with DAAs alters glucose and lipid parameters. METHODS: 50 patients with chronic HCV who were treated with DAAs were screened, and 49 were enrolled in the study. Biochemical and virological data, as well as noninvasive liver fibrosis parameters, were prospectively collected at baseline, at the end of treatment (EOT) and 12 and 24 weeks post-treatment. RESULTS: 45 of 46 patients achieved sustained virologic response (SVR). The prevalence of insulin resistance (HOMA-IR) after HCV clearance was significantly lower, compared to baseline (5.3 ± 6.1 to 2.5 ± 1.9, p < 0.001), which is primarily attributable to a significant decrease of fasting insulin levels (18.9 ± 17.3 to 11.7 ± 8.7; p = 0.002). In contrast to that, HCV eradication resulted in a significant increase in cholesterol levels (total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein (HDL-C) levels) and Controlled Attenuated Score (CAP), although BMI did not significantly change over time (p = 0.95). Moreover, HOMA-IR correlated significantly with noninvasive liver fibrosis measurements at baseline und during follow-up (TE: r = 0.45; p = 0.003, pSWE: r = 0.35; p = 0.02, APRI: r = 0.44; p = 0.003, FIB-4: r = 0.41; p < 0.001). CONCLUSION: Viral eradication following DAA therapy may have beneficial effects on glucose homeostasis, whereas lipid profile seems to be worsened.

Anemia and Systemic Inflammation Rather than Arterial Circulatory Dysfunction Predict Decompensation of Liver Cirrhosis.

BACKGROUND: While systemic inflammation is recognized as playing a central role in the pathogenesis of organ failures in patients with liver cirrhosis, less is known about its relevance in the development of classical hepatic decompensation. AIM: To characterize the relationship between systemic inflammation, hemodynamics, and anemia with decompensation of liver cirrhosis. METHODS: This is a post-hoc analysis of a cohort study of outpatients with advanced liver fibrosis or cirrhosis. RESULTS: Analysis included 338 patients of whom 51 patients (15%) were hospitalized due to decompensation of liver cirrhosis during a median follow-up time of six months. In univariate analysis, active alcoholism (p = 0.002), model of end-stage liver disease (MELD) score (p = 0.00002), serum IL-6 concentration (p = 0.006), heart rate (p = 0.03), low arterial blood pressure (p < 0.05), maximal portal venous flow (p = 0.008), and low hemoglobin concentration (p < 0.00001) were associated with hospitalization during follow-up. Multivariate analysis revealed an independent association of low hemoglobin (OR = 0.62, 95% CI = 0.51-0.78, p = 0.001) and serum IL-6 concentration (OR = 1.02, 95% CI = 1.01-1.04, p = 0.03)-but not of hemodynamic parameters-with hepatic decompensation. An inverse correlation between hemoglobin concentration and portal venous flow (R = -0.362, p < 0.0001) was detected for the non-hospitalized patients. Accuracy of baseline hemoglobin levels for predicting hospitalization (AUC = 0.84, p < 0.000001) was high. CONCLUSION: Anemia and systemic inflammation, rather than arterial circulatory dysfunction, are strong and independent predictors of hepatic decompensation in outpatients with liver cirrhosis.

Real-world data about emotional stress, disability and need for social care in a German IBD patient cohort.

To date, there is insufficient insight into inflammatory bowel disease (IBD)-associated stress, recognized disability, and contact with the social care system. We aimed to assess these parameters in IBD patients and a non-IBD control group, who were invited to participate in an online survey developed specifically for this study (www.soscisurvey.de) with the help of IBD patients. 505 IBD patients and 166 volunteers (i.e., control group) participated in the survey. IBD patients reported significantly increased levels of stress within the last six months and five years (p<0.0001) and were more likely to have a recognized disability (p<0.0001). A low academic status was the strongest indicator of a disability (p = 0.006). Only 153 IBD patients (30.3%) reported contact with the social care system, and a disability was the strongest indicator for this (p<0.0001). Our study provides data on stress and disability in a large unselected German IBD cohort. We showed that patients with IBD suffer more often from emotional stress and more often have a recognized disability. As only about 1/3 of the patients had come into contact with the social care system and the corresponding support, this patient group is undersupplied in this area.

Efficacy of Direct-acting Antivirals for Chronic Hepatitis C Virus Infection in People Who Inject Drugs or Receive Opioid Substitution Therapy: A Systematic Review and Meta-analysis.

BACKGROUND: Treatment uptake for hepatitis C virus (HCV) infection in people who inject drugs (PWID) and patients on opioid substitution therapy (OST) is still low despite treatment guidelines that advocate the use of direct-acting antivirals (DAAs) in all patients. Our aim in this review was to investigate treatment outcomes among PWID and patients on OST in comparison to control cohorts. METHODS: A search of Embase, Medline, PubMed, and Web of Science (from October 2010 to March 2018) was conducted to assess sustained virologic response (SVR), discontinuation rates, adherence, and HCV reinfection in PWID and patients on OST. RESULTS: We identified 11 primary articles and 12 conference abstracts comprising 1702 patients on OST, 538 PWID, and 19 723 patients who served as controls. Among patients on OST, the pooled SVR was 90% (95% confidence interval [CI], 87% to 93%) and pooled treatment discontinuation rate was 7% (95% CI, 4% to 11%). Similarly, the pooled SVR was 88% (95% CI, 80% to 93%) in PWID and the pooled treatment discontinuation rate was 9% (95% CI, 5% to 15%). There was no significant difference regarding pooled rates of SVR, adherence, and discontinuation between patients on OST and controls as well as between PWID and controls. HCV reinfection rates among patients on OST ranged from 0.0 to 12.5 per 100 person-years. CONCLUSIONS: HCV treatment outcomes in PWID and patients on OST are similar to those in patients without a history of injecting drugs, supporting current guideline recommendations to treat HCV in these patient populations.

Quality of life of patients with head and neck cancer after prophylactic percutaneous-gastrostomy.

BACKGROUND: HNC patients often experience weight loss during treatment. To date, there is only limited data on patient quality of life (QLQ) and subjective benefit of the PEG insertion. OBJECTIVE: To investigate the nutritional status, QLQ, and overall benefit. METHODS: 181 patients fitting our inclusion criteria (01/2012-12/2012) were enrolled. Utilization rate, nutritional status, QLQ, and subjective PEG assessment were determined with electronic charts and the Quality of life-questionnaire (EORTC-QLQ-C30). RESULTS: The utilization rate of the entire cohort was 91.7%. The PEG was used full-time by 149 patients. No statistical differences in QLQ were observed between the groups. Of the patients that used the PEG entirely (99.7%), partially (85.3%) or not all (55.3%) would 99.7%, 85.3 and 55.8% undergo the procedure in the future if necessary. CONCLUSIONS: QLQ was not significantly reduced by insertion. Especially patients using the PEG full-time had an objective and subjective benefit from the inserted PEG tube.

Short and Long-Term Effectiveness of Ustekinumab in Patients with Crohn's Disease: Real-World Data from a German IBD Cohort.

: Background and Aims: The IL-12/23 inhibitor ustekinumab (UST) opened up new treatment options for patients with Crohn's disease (CD). Due to the recent approval, real-world German data on long-term efficacy and safety are lacking. This study aimed to assess the clinical course of CD patients under UST therapy and to identify potential predictive markers. Methods: Patients with CD receiving UST treatment in three hospitals and two outpatient centers were included and retrospectively analyzed. Rates for short- and long-term remission and response were analyzed with the help of clinical (Harvey-Bradshaw Index (HBI)) and biochemical (C-reactive protein (CRP), Fecal calprotectin (fCal)) parameters for disease activity. Results: Data from 180 patients were evaluated. One-hundred-and-six patients had a follow-up of at least eight weeks and were included. 96.2% of the patients were pre-exposed to anti- TNFα agents and 34.4% to both anti-TNFα and anti-integrin antibodies. The median follow-up was 49.1 weeks (95% CI 42.03-56.25). At week 8, 51 patients (54.8%) showed response to UST, and 24 (24.7%) were in remission. At week 48, 48 (51.6%) responded to UST, and 25 patients (26.9%) were in remission. Steroid-free response and remission at week eight was achieved by 30.1% and 19.3% of patients, respectively. At week 48, 37.6% showed steroid-free response to UST, and 20.4% of the initial patient population was in steroid-free remission. Conclusion: Our study confirms short- and long-term UST effectiveness and tolerability in a cohort of multi-treatment-exposed patients.

Time-saving polyp detection in colon capsule endoscopy: evaluation of a novel software algorithm.

BACKGROUND: Colon capsule endoscopy (CCE) is a reliable method to detect colonic polyps in the well-prepared colon. As CCE evaluation can be time consuming, a new software algorithm might aid in reducing evaluation time. OBJECTIVES: The aim of the study was to evaluate whether it is feasible to reliably detect colon polyps in CCE videos with a new software algorithm the "collage mode" (Rapid 8 Software, Covidien/Medtronic®). METHODS: Twenty-nine CCE videos were randomly presented to three experienced and to three inexperienced investigators. Videos were evaluated by applying the collage mode. Investigation time was documented and the results (≥one polyp vs. no polyp) were compared with the findings of two highly experienced central readers who read the CCE videos in the standard mode beforehand. RESULTS: It took a median time of 9.8, 3.5, and 7.5 vs. 4.3, 4.6 and 12.5 min for experienced vs. inexperienced investigators to review the CCE videos. For detecting ≥one polyp vs. no polyp, sensitivity of 93.3%, 73.3%, and 93.3% was observed for the experienced and sensitivity of 46.7%, 33.3%, and 93.3% for the inexperienced CCE readers. CONCLUSION: Collage mode might allow for a quick review of CCE videos with a high polyp detection rate for experienced CCE readers. Future prospective studies should include CCE collage mode for rapid polyp detection to further prove the feasibility of practical colon polyp detection by CCE and possibly support the role of CCE as a screening tool in CRC prevention.

Prophylactic percutaneous endoscopic gastrostomy in patients with head and neck cancer: Influence on nutritional status, utilisation rate and complications.

BACKGROUND: Patients with head and neck cancer (HNC) are at high risk for malnutrition because of tumour localisation and therapy. Prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement is common practice to prevent malnutrition. OBJECTIVE: To investigate the benefits of prophylactic PEG tube placement for HNC patients in terms of the influence on patients' nutritional status, utilisation rate, complications and to identify the predictors of PEG tube utilisation. METHODS: All consecutive HNC patients who underwent prophylactic PEG tube insertion between 1 January 2011 and 31 December 2012 prior to therapy were enrolled. The PEG tube utilisation rate, complications, the patients' nutritional status and tumour therapy were evaluated with the help of electronic patient charts and telephone interviews. RESULTS: A total of 181 patients (48 female, median 67.5 years) were included. The PEG utilisation rate in the entire cohort was 91.7%. One hundred and forty-nine patients (82.3%) used the PEG tube for total enteral nutrition, 17 patients (9.4%) for supplemental nutrition and 15 patients (8.3%) made no use of the PEG tube. Peristomal wound infections were the most common complications (40.3%) in this study. A high Nutritional Risk Screening (NRS) score prior to tube insertion was found to be independently associated with PEG utilisation. No significant weight changes were observed across the three patient subgroups. CONCLUSIONS: The overall PEG tube utilisation rate was high in this study. However, given the high rate of infections, diligent patient selection is crucial in order to determine which patients benefit most from prophylactic PEG tube insertion.

Vitamin D Deficiency is Associated with Increased Disease Activity in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Vitamin D has an inhibitory role in the inflammatory signaling pathways and supports the integrity of the intestinal barrier. Due to its immunomodulatory effect, vitamin D plays a role in chronic inflammatory bowel disease (IBD) and a deficiency is associated with an increased risk for a flare. We aimed to investigate to what extent the 25-hydroxyvitamin D (25(OH)D3) level correlates with disease activity and whether a cut-off value can be defined that discriminates between active disease and remission. METHODS: Patients with IBD, treated at the University Hospital Frankfurt were analyzed retrospectively. The 25(OH)D3 levels were correlated with clinical activity indices and laboratory chemical activity parameters. A deficiency was defined as 25(OH)D3 levels <30 ng/mL. RESULTS: A total of 470 (257 female) patients with IBD were included, 272 (57.9%) with Crohn's disease (CD), 198 (42.1%) with ulcerative colitis (UC). The median age of the patients was 41 (18-84). In 283 patients (60.2%), a vitamin D deficiency was detected. 245 (53.6%) patients received oral vitamin D supplementation, and supplemented patients had significantly higher vitamin D levels (p < 0.0001). Remission, vitamin D substitution, and male gender were independently associated with the 25(OH)D3 serum concentration in our cohort in regression analysis. A 25(OH)D3 serum concentration of 27.5 ng/mL was the optimal cut-off value. CONCLUSION: Vitamin D deficiency is common in IBD patients and appears to be associated with increased disease activity. In our study, vitamin D levels were inversely associated with disease activity. Thus, close monitoring should be established, and optimized supplementation should take place.

The Lipid Status in Patients with Ulcerative Colitis: Sphingolipids are Disease-Dependent Regulated.

The factors that contribute to the development of ulcerative colitis (UC), are still not fully identified. Disruption of the colon barrier is one of the first events leading to invasion of bacteria and activation of the immune system. The colon barrier is strongly influenced by sphingolipids. Sphingolipids impact cell-cell contacts and function as second messengers. We collected blood and colon tissue samples from UC patients and healthy controls and investigated the sphingolipids and other lipids by LC-MS/MS or LC-QTOFMS. The expression of enzymes of the sphingolipid pathway were determined by RT-PCR and immunohistochemistry. In inflamed colon tissue, the de novo-synthesis of sphingolipids is reduced, whereas lactosylceramides are increased. Reduction of dihydroceramides was due to posttranslational inhibition rather than altered serine palmitoyl transferase or ceramide synthase expression in inflamed colon tissue. Furthermore, in human plasma from UC-patients, several sphinglipids change significantly in comparison to healthy controls. Beside sphingolipids free fatty acids, lysophosphatidylcholines and triglycerides changed significantly in the blood of colitis patients dependent on the disease severity. Our data indicate that detraction of the sphingolipid de novo synthesis in colon tissue might be an important trigger for UC. Several lipids changed significantly in the blood, which might be used as biomarkers for disease control; however, diet-related variabilities need to be considered.

Multiwell three-dimensional systems enable in vivo screening of immune reactions to biomaterials: a new strategy toward translational biomaterial research.

In vivo experiments are accompanied by ethical issues, including sacrificing a large number of animals as well as large costs. A new in vivo 3D screening system was developed to reduce the number of required animals without compromising the results. The present pilot study examined a multiwell array system in combination with three different collagen-based biomaterials (A, B and C) using subcutaneous implantation for 10 days and histological and histomorphometrical evaluations. The tissue reaction towards the device itself was dominated by mononuclear cells. However, three independent biomaterial-specific tissue reactions were observed in three chambers. The results showed a mononuclear cell-based tissue reaction in one chamber (A) and foreign body reaction by multinucleated giant cells in the other two chambers (B and C). Statistical analysis showed a significantly higher number of multinucleated giant cells in cases B and C than in case A (A vs. B; ***P < 0.001), (A vs. C; P < 0.01). These outcomes were comparable to previously published observations with conventional biomaterial implantation. The present data lead to the conclusion that this 3D screening system could be an alternative tool to enhance the effectiveness of in vivo experiments, thus offering a more economic strategy to screen biomaterial-related cellular reactions, while saving animals, without influencing the final outcome.

A low-speed centrifugation concept leads to cell accumulation and vascularization of solid platelet-rich fibrin: an experimental study in vivo.

Platelet-rich fibrin (PRF) is generated from the patients' own venous blood by a single centrifugation step without the additional use of anticoagulants. Based on the previously described LSCC (low-speed centrifugation concept), our group showed that modification of the centrifugation setting, that is, reducing the relative centrifugal force (RCF) and mildly increasing the centrifugation time, resulted in modified solid and liquid PRF-matrices with increased number of platelets, leukocytes, and growth factors' concentrations. The aim of this study was to determine whether RCF reduction might also result in different tissue reactions toward the two PRF-based matrices, especially vascularization and cell distribution in vivo. Two centrifugation protocols (PRF-high [719 g] and PRF-medium [222 g]) were compared in a subcutaneous implantation model of SCID mice at 5 and 10 days. Histological and histomorphometrical analyses were performed to quantify lymphocyte, neutrophil, human macrophage, and monocyte populations. CD31 was used to detect newly formed vessels, while all human cells were detected by using human vimentin as a pan-cellular marker. The results demonstrated that PRF-high elicited a dense and stable fibrin structure and prevented cellular penetration of the host tissue. By contrast, PRF-medium was more porous, had a significantly higher in vivo vascularization rate, and included significantly more human cells, especially at day 10, compared to PRF-high. These findings highlight the possibility of modifying the structure and composition of PRF matrices and thus selectively altering their regenerative potential in vivo. Clinical studies now must evaluate the different PRF matrices for bone and soft-tissue regeneration to validate possible benefits using personalized preparation protocols.