Submucosal Injection of the RNA Oligonucleotide GUT-1 in Active Ulcerative Colitis Patients: A Randomized, Double-Blind, Placebo-Controlled Phase 2a Induction Trial.

BACKGROUND AND AIMS: Carbohydrate sulfotransferase 15 [CHST15] biosynthesizes sulphated matrix glycosaminoglycans and is implicated in intestinal inflammation and fibrosis. Here, we evaluate the efficacy and safety of the double-stranded RNA oligonucleotide GUT-1, a specific blocker of CHST15, as induction therapy in patients with ulcerative colitis [UC]. METHODS: In this randomized, double-blind, placebo-controlled, phase 2a study, we enrolled endoscopically active UC patients, refractory to conventional therapy, in five hospital centres across Germany. Patients were randomized 1:1:1 using a block randomized technique to receive a single dosing of 25 nM GUT-1, 250 nM GUT-1, or placebo by endoscopic submucosal injections. The primary outcome measure was improvement of endoscopic lesions at weeks 2 or 4. The secondary outcome measures included clinical and histological responses. Safety was assessed in all patients who received treatment. RESULTS: Twenty-eight patients were screened, 24 were randomized, and 21 were evaluated. Endoscopic improvement at weeks 2 or 4 was achieved by 71.4% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 28.6% in the placebo group. Clinical remission was shown by 57.1% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 14.3% in the placebo groups. Histological improvement was shown by 42.9% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 0% in the placebo groups. GUT-1 250 nM reduced CHST15 expression significantly and suppressed mucosal inflammation and fibrosis. GUT-1 application was well tolerated. CONCLUSION: Single dosing by submucosal injection of GUT-1 repressed CHST15 mucosal expression and may represent a novel induction therapy by modulating tissue remodelling in UC.

The Role of Sphere Size in the Context of Pancreatin Therapy for Exocrine Pancreatic Insufficiency: A Systematic Review.

While lipase content and appropriate acid protection of pancreatin preparations (PP) are well defined determinants of an effective therapy of exocrine pancreatic insufficiency, the optimal sphere size of PP has remained a matter of discussion. We performed a systematic review to assess the optimal sphere size of enteric coated pancreatin products that may best guarantee coordinated delivery of PP and food to the duodenum. PubMed was searched for studies on gastric emptying of indigestible spheres in the digestive phase, using overlapping search algorithms; identified sources were searched for further leads, extending the investigation to Google Scholar. Of 739 screened publications, 26 were included in the final assessment. Contrary to current guideline recommendations, no scientific evidence was found to support a 2 mm diameter threshold for gastric emptying of indigestible particles. There is no documented advantage of ≤2 mm spheres regarding duodenal delivery and restoring maldigestion. The evolving picture is that of a gradation of sizes, over which gastric emptying becomes slower and more variable as particle size increases. Even 7 mm particles may be emptied from the stomach in conjunction with nutrient uptake. In conclusion sphere size of PP is not the essential parameter for selecting an effective PP fitting all patients. A variety of brands offer different lipase contents and sphere sizes that allow the physician to tailor treatment to the individual patient`s needs.

Successful endoscopic recanalization of complete pharyngoesophageal obstruction after therapy of head and neck cancer.

BACKGROUND: Neopharyngeal obstruction after therapy of head and neck cancer is a frequent and clinically challenging problem without evidence-based guideline recommendations. CASE: We present two cases of complete esophageal obstruction after treatment for head and neck cancer. Due to complete obstruction of long distance stricture standard dilatation procedures were impossible to perform. In both cases, recanalization was achieved by combining an antegrade with a retrograde maneuver. In one patient endoscopic cutting with a papillotome was needed. CONCLUSION: Even in complex cases of post-therapeutic stenosis an endoscopic approach may offer a feasible alternative to surgical therapy, especially in the subset of frail patients.

Endoscopic findings and outcome in caustic ingestion of acidic and alkaline agents in adults: A retrospective analysis.

Caustic ingestion in adults is a rare but potentially life-threatening problem. It remains controversial whether endoscopic findings and mortality differ between acid and alkali ingestion. We compared ingestion of these agents and evaluated prediction parameters for survival and complications.Adult patients who presented with caustic ingestion were analyzed from 2005 to 2016. Mucosal injury was graded endoscopically by Zargar's score. Age, gender, intent of ingestion, caustic agents, comorbidities, management, complications, and mortality were examined.Thirty-one patients met inclusion criteria and were divided into acid (n = 10) and alkali group (n = 21). Ingestion of alkali resulted in higher grades (≥III) of esophageal (56% vs 24%, P = .01) and stomach injuries (43% vs 13%, P = .05) and was mostly done with suicidal intent (76% vs 30%, P = .003). Patients in the alkali group received more often surgical interventions, mechanical ventilation and tracheotomy. Overall complications including Zargar's-score ≥ grade III, mediastinitis, and aspiration pneumonia were higher in alkali group but all showed no statistical significance (P = .73). Mortality (acid: 1 (10%), alkali: 4 (19%), P = .52), age, gender, comorbidities, and intensive care management did not differ significantly between the groups. Chronic renal failure and mediastinitis were promising prediction parameters for mortality but did not reach statistical significance. No independent risk factors for the development of esophageal stenosis were identified.Alkaline agents caused a higher mucosal injury severity and were more often used in suicidal intent. Mediastinitis and chronic renal failure might be potential prediction parameters for survival but need to be evaluated in larger studies.

The Diagnosis and Treatment of Pinworm Infection.

BACKGROUND: Symptomatic infection with pinworm (Enterobius vermicularis), a human pathogen, is clinically relevant in Germany, with an estimated prevalence in childhood of 2-20%. Enterobiasis can cause major mental distress. There is little systematically verified knowledge on the treatment of this condition, and there is no corresponding German guideline. This review is, therefore, intended as a summary of the current state of knowledge. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed for literature appearing from 1 January 1990 to 5 February 2019 and containing the search terms "enterobiasis," "oxyuriasis," "Enterobius vermicula- ris," "pinworm," and "threadworm." RESULTS: More than one billion people worldwide are thought to be infected with pinworm. Estimates of its prevalence among kindergarten and primary-school pupils in Europe are generally near 20%. Infants (<2 years of age), adolescents (>14 years of age), and adults are only sporadically affected. The main risk factors are age 4-11 years, uncontrolled anus-finger-mouth contact, nail-biting (onychophagia/peri- onychophagia), unsupervised body hygiene, and poor compliance with basic hand hygiene. No large-scale, randomized, controlled trials of treatment are available. The approved antihelminthic agents are mebendazole, pyrantel embonate, and pyrvinium embonate (success rates up to >90%). For recurrent infections, prolonged treatment for up to 16 weeks (a "pulse scheme") is recommended. CONCLUSION: In nearly all cases, antihelminthic treatment along with attention to hygienic measures can successfully eradicate pinworm infection and prevent recurrence and autoinfection. The involvement of all persons living in the patient's house- hold, including sexual partners, is a prerequisite to the lasting success of treatment.

Azithromycin does not improve disease severity in acute experimental pancreatitis.

Acute pancreatitis is a severe systemic disease triggered by a sterile inflammation and initial local tissue damage of the pancreas. Immune cells infiltrating into the pancreas are main mediators of acute pancreatitis pathogenesis. In addition to their antimicrobial potency, macrolides possess anti-inflammatory and immunomodulatory properties which are routinely used in patients with chronic airway infections and might also beneficial in the treatment of acute lung injury. We here tested the hypothesis that the macrolide antibiotic azithromycin can improve the course of acute experimental pancreatitis via ameliorating the damage imposed by sterile inflammation, and could be used as a disease specific therapy. However, our data show that azithromycin does not have influence on caerulein induced acute pancreatitis in terms of reduction of organ damage, and disease severity. Furthermore Infiltration of immune cells into the pancreas or the lungs was not attenuated by azithromycin as compared to controls or ampicillin treated animals with acute experimental pancreatitis. We conclude that in the chosen model, azithromycin does not have any beneficial effects and that its immunomodulatory properties cannot be used to decrease disease severity in the model of caerulein-induced pancreatitis in mice.

Endoscopic full-thickness transoral outlet reduction with semicircumferential endoscopic submucosal dissection.

BACKGROUND: Endoscopic full-thickness transoral outlet reduction (efTOR) is a therapeutic option to reduce a dilated gastrojejunal anastomosis (GJA) after Roux-en-Y gastric bypass (RYGB). Mucosal ablation with argon plasma coagulation (APC) is usually performed to achieve tissue adaptation. However, rupture of sutures before scarring can lead to recurrent dilatation of the GJA. Here, we describe efTOR with a semicircumferential endoscopic submucosal dissection (ESD-efTOR) as an alternative to APC-efTOR. METHODS: We enrolled 41 patients with comparable baseline characteristics (APC-efTOR 26; ESD-efTOR 15). The main objectives were reduction in the GJA diameter and in ruptured sutures. Technical success, complications, total weight loss (TWL), and percentage of total and excess weight loss (%TWL and %EWL) at 3 and 12 months, were assessed. RESULTS: ESD-efTOR resulted in significantly fewer ruptured sutures (20 % vs. 69 %; P = 0.004) and a greater reduction in the GJA (major 20 % vs. 0 %; minor 54 % vs. 37 %; no reduction 13 % vs. 58 %; P = 0.02) after 3 months. Technical efficacy, examination time, and rate of complications were comparable. CONCLUSIONS: ESD-efTOR resulted in a significantly greater reduction in the GJA diameter and a lower risk of ruptured sutures compared with APC-efTOR.

Author Correction: Predicting hepatic complications of allogeneic hematopoietic stem cell transplantation using liver stiffness measurement.

In the original article, the affiliations were presented incorrectly. David Petroff is in fact the only author at affiliation 2. All other authors listed as being at affiliation 2 (Tina Weiße, Sebastian Beer, Franziska Gnatzy, Joachim Mössner, Michael Tröltzsch, Johannes Wiegand and Volker Keim) are in fact just at affiliation 1. These have now been corrected in the original article.

Severe ileocecal inflammatory syndrome in adult patients with cystic fibrosis.

The relevance of gastrointestinal manifestations of cystic fibrosis (CF) is increasing due to an improved life expectancy. We report on 2 adult patients with prior lung transplantation who presented with a severe inflammatory disorder of the ileocecal region. One patient underwent ileocecal resection; the second patient died after emergency surgery for intestinal perforation. Both cases did not show typical signs of CF-related distal intestinal obstruction syndrome or extensive fibrosing colonopathy. However, the clinical and histopathological findings revealed CF-induced inflammatory alterations of the intestinal mucosa. Thus, these cases illustrate a further CF-related bowel disorder, which can be especially relevant in long-term CF survivors.

Predicting hepatic complications of allogeneic hematopoietic stem cell transplantation using liver stiffness measurement.

Allogeneic hematopoietic stem cell transplantation is the only curative option for a variety of diseases. Despite advances, it is associated with considerable morbidity and mortality, often involving liver complications. Liver disease can be characterized using ultrasound-based liver stiffness measurement. To assess its prognostic value, consecutive patients undergoing allogeneic hematopoietic stem cell transplantation were prospectively evaluated in a single-center study. Endpoints included liver event-free survival and all-cause mortality at 1 year. Competing risk and Cox-regression were used for analysis. We evaluated 106 patients (42 female, age 57) and observed 33 life-threatening events (14 died) including 16 liver complications at 100 days. At 1 year, 36 patients had died, 20 with disease relapse. The hazard ratios for liver-related complications at 100 days were 3.2 (95% CI: 1.8-14.6, p = 0.0022) and 4.4 (95% CI: 1.6-11.9, p = 0.0042) for elevated transient elastography (n = 11) and shear-wave velocity (n = 31), respectively. Results were analogous for all-cause mortality at 1 year. Prior stem cell therapy and elevated gamma glutamyltransferase were also associated with outcome. This demonstrates that elastography is a promising and viable tool for risk prediction and should be included in upcoming multi-center trials to establish new means of guiding treatment and prophylaxis.

Endoscopic suturing as a less invasive approach for the treatment of anastomotic leakage after esophagogastrostomy - a case report.

Anastomotic leakage is a frequent complication after gastrointestinal (GI) surgery and is associated with high morbidity and mortality. Endoluminal therapy offers numerous advantages compared to surgical revision. We present the case of a 74-year-old female patient with anastomotic leakage after esophagogastrostomy. The defect was closed using the OverStitch endoscopic suturing system with immediate technical and clinical success. Hereby, an example of the feasibility of this novel technique in a case of anastomotic leakage is presented and provides an outlook for the rising importance of endoscopic therapy.

Is CO2 insufflation an amelioration of routine colonoscopy?

BACKGROUND: The insufflation of gas during colonoscopy leads to distention of the colon with abdominal discomfort and pain for the patients. Use of CO2 during endoscopy is reported to minimize abdominal discomfort during and after endoscopy. Aim of this study was to find out whether this improvement leads to decreased dosage of sedation drugs in order to improve patient's safety and satisfaction. METHODS: In this double-blind, randomized and controlled study 150 Patients referred to colonoscopy were assigned to either CO2 or air insufflation. We recorded basic characteristics of colonoscopy and the amount of drugs used for sedation. Patients and investigators filled out questionnaires to record pain, abdominal bloating and flatulence. RESULTS: Seventy-two patients were randomized for examination with room air, 78 patients for use of CO2. We found no difference in basic characteristics of colonoscopy (cecal intubation time and procedure time). Both groups were administered the same amount of drugs for sedation. We found only slight improvement of pain, abdominal bloating and flatulence. CONCLUSIONS: The study revealed only moderate positive effects for use of CO2 during colonoscopy. We found only modest improvement of patient's comfort during and after colonoscopy. No reduced doses of drugs for sedation could be recorded.

p8 deficiency leads to elevated pancreatic beta cell mass but does not contribute to insulin resistance in mice fed with high-fat diet.

BACKGROUND: p8 was initially described as being overexpressed in acute pancreatitis and encoding a ubiquitous stress protein. Analysis of insulin sensitivity and glucose tolerance in p8-knockout and haplodeficient mice revealed counterintuitive results. Thus, we determined glycemic control of p8 in mice fed with standard (SD) and high-fat diet (HFD). METHODS: p8-/- and wild type (p8+/+) mice were used for analysis of glucagon (immunohistochemistry), insulin levels (ELISA) and beta cell mass. Hyperinsulinemic- euglycemic glucose clamp technique, i.p. glucose tolerance test (ipGTT), i.p. insulin tolerance test (ipITT) and metabolic chamber analysis were performed in SD (4% fat) and HFD (55% fat) groups. RESULTS: p8-/- mice showed no differences in glucagon or insulin content but higher insulin secretion from pancreatic islets upon glucose stimulation. p8 deficiency resulted in elevated beta cell mass but was not associated with increased insulin resistance in ipGTT or ipITT. Glucose clamp tests also revealed no evidence of association of p8 deficiency with insulin resistance. Metabolic chamber analysis showed equal energy expenditure in p8-/- mice and wild type animals. CONCLUSION: p8 depletion may contribute to glucose metabolism via stress-induced insulin production and elevated beta cell mass. Nevertheless, p8 knockout showed no impact on insulin resistance in SD and HFD-fed mice.