[Modern anticoagulation with factor Xa inhibitors in oncology: is the gastrointestinal bleeding rate (also) decisive?] / Moderne Antikoagulation mit FXa-Inhibitoren in der Onkologie: Ist die gastrointestinale Blutungsrate (mit)-entscheidend?

The increased risk of thrombosis and bleeding with an active tumor disease is known as the so-called "thrombo-hemorrhagic syndrome", which places high demands on anticoagulation. There are currently 4 randomized, prospective studies on the use of new, non-vitamin K dependent oral anticoagulants (NOAC) for the treatment of venous thromboembolism (VTE) that have occurred in oncology. The FXa inhibitors rivaroxaban, edoxaban and twice apixaban were each used in individual studies versus the standard therapeutic agent dalteparin. Since there is no direct head-to-head comparison of the FXa inhibitors mentioned within a study, the largest study - always compared to dalteparin - was evaluated for each NOAC. The studies were analyzed with regard to their effectiveness, safety, fatal bleeding rates, the risk of gastrointestinal bleeding (GIB) and other differences using descriptive statistics. With dalteparin, the mean VTE recurrence rate was approximately 9% over a 6-month treatment period. All three FXa inhibitors were not inferior to dalteparin in terms of potency. The VTE recurrence rate was - 2.3% lower in edoxaban and apixaban-treated patients and - 5.0% in rivaroxaban-treated patients. In terms of safety, there was an increased rate of severe bleeding (both + 2.4%) for rivaroxaban and edoxaban compared to dalteparin; in particular, the number of GIBs was significantly increased. In contrast, the number of severe bleeding was not increased for apixaban, as was the case for various bleeding types including GIB. In the Apixaban study, the overall rate of severe GIB, which accounted for about 50% of all severe bleeding, and that of clinically relevant non-severe bleeding, were the lowest. The FXa inhibitors are not inferior to the standard therapy with dalteparin in the VTE recurrence rate in oncological patients. The GIB rate appears to be an important predictive factor for the safety of this group of substances, so that tumor location, gastrointestinal risk factors and other individual criteria should be given greater consideration in future therapy decisions for or against an FXa inhibitor.

Mucosal Mast Cell Distribution in the Gastrointestinal Tract of Children: A Preliminary Study for Establishing Reference Values.

OBJECTIVES: The physiological number and distribution of mast cells (MCs) in the pediatric gastrointestinal (GI) tract is not well defined and reference values of normality are missing. To define a physiological and disease defining cut-off, a systematic histological exploration of MC distribution from the esophagus to the rectum in healthy as well as in patients with gastrointestinal food allergies (GFA) was performed. METHODS: Nine pediatric subjects that exhibited unremarkable histopathological evaluations or underwent endoscopy for surveillance reasons after a previous polypectomy of single colonic juvenile polyps served as reference cohort. In all of these subjects, a chronic inflammatory disease (eg, inflammatory bowel disease, celiac disease) or allergy was excluded. In addition, a group of 15 patients with gastrointestinal complaints suspected to be caused by a GFA were investigated. Immunohistochemistry was performed from all biopsies using CD117 (c-Kit) as a reliable marker to identify MCs in the lamina propria. RESULTS: There were distinct differences of MC counts in all parts of the pediatric GI tract. The highest counts of MCs in both symptomatic patients and control cohort, were found in the duodenum, terminal ileum, cecum and ascending colon. The lowest counts were found in the esophagus. Significant disparities between GFA and healthy subjects were found in the gastric corpus (22.1 ±â€Š4.0/ high power field [HPF] vs 32.0 ±â€Š10.1/HPF; P = 0.034) and ascending colon (44.8 ±â€Š10.4/HPF vs 60.4 ±â€Š24.3/HPF; P = 0.047). CONCLUSIONS: Mucosal MC counts in the pediatric GI tract are higher than previously reported, with a considerable overlap between healthy and GFA patients. These results provide detailed information on distribution and numbers of MCs in pediatric allergic patients while allowing estimates of physiological values in childhood for the first time. With regard to diagnostic procedures in GFA further laboratory parameters have to be integrated.

The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.

Application of Acoustic Radiation Force Impulse Elastography in Imaging of Delayed Onset Muscle Soreness: A Comparative Analysis With 3T MRI.

CONTEXT: Delayed onset muscle soreness is one of the most common reasons for impaired muscle performance in sports and is associated with reduced muscle strength and frequently observed both in professional and recreational athletes. OBJECTIVE: To emphasize the diagnostic value of acoustic radiation force impulse (ARFI) in imaging of delayed onset muscle soreness by comparing findings with high-resolution 3T magnetic resonance imaging T2-weighted sequences. DESIGN: Case series. SETTING: Laboratory environment. PARTICIPANTS: Fifteen healthy students (7 females and 8 males; mean [SD]: age 24 [4] y, height 178 [10] cm, body weight 67 [12] kg). MAIN OUTCOME MEASURES: ARFI values, represented as shear wave velocities of the gastrocnemius muscle and soleus muscle, as well as conventional ultrasound, high-resolution 3T magnetic resonance imaging, creatine kinase activity, extension range of the ankle joint, calf circumference, and muscle soreness were assessed before (baseline) and 60 hours after (postintervention) a standardized eccentric exercise. RESULTS: ARFI shear wave velocity values of the gastrocnemius muscle revealed a statistically significant decrease of 19.1% between baseline (2.2 [0.26] m/s) and postintervention (1.78 [0.24] m/s); P = .01. At follow-up, the magnetic resonance imaging investigations showed intramuscular edema for the gastrocnemius muscle in all participants corresponding to a significant raise in T2 signal intensity (P = .001) and in T2-time values (P = .004). CONCLUSIONS: ARFI elastography seems to be an additional sensitive diagnostic modality in the diagnostic workup of delayed onset muscle soreness. Intramuscular shear wave velocities could represent an additional imaging marker for the assessment and monitoring of ultrastructural muscle injuries and therefore be helpful for individual training composition in elite sports.

[Non-allergic gluten sensitivity. A controversial disease - or not yet sufficiently explored?]. / Nichtallergische Glutensensitivität. Ein umstrittenes Krankheitsbild - oder noch nicht ausreichend erforscht?

The avoidance of wheat, gluten and other cereal products is a growing phenomenon in industrialized countries. The diagnostic criteria of celiac disease and of food allergy to wheat flour and/or other cereals are clearly defined. Only about 0.5-25 % of the population are affected from both of these immunological diseases.Nevertheless, there exists a significantly greater proportion of people reporting at least subjectively significant complaints and quality of life improvements after switching to a wheat- or gluten-free diet. Celiac disease or wheat allergy cannot be detected in these individuals on the basis of established criteria. The absence of clear diagnostic autoimmune or allergic criteria in these wheat sensitive patients has resulted in the description of non-celiac gluten sensitivity.It is clinically detectable in only very few individuals and may manifest with either intestinal, extra-intestinal or neurovegetative and psychosomatic symptoms, respectively. However, non-celiac disease gluten sensitivity has to be differentiated critically from irritable bowel syndrome, carbohydrate malassimilation, postinfectious conditions and psychosomatic diseases.Pathophysiologically, non-celiac disease gluten sensitivity is still poorly characterized; several non-immunological mechanisms are discussed to contribute to non-celiac gluten sensitivity. These include the effects of fructo- and galacto-oligosaccharides, of trypsin inhibitors of amylase, and wheat lectin agglutinins, which may influence or modulate intestinal permeability and/or a non-specific immune or effector cell degranulation within the gastrointestinal tract. In addition, further metabolic effects with direct or indirect influence on the intestinal flora are currently discussed.In addition to subjectively reported changes in symptoms that may affect variably intestinal, as well as extra-intestinal and/or neuropsychiatric symptoms, some studies suggest that there is little reproducibility of complaints from gluten exposure. For a definitive diagnosis of non-celiac gluten sensitivity, structured (blinded) challenge tests with wheat or gluten are mandatory as well as re-challenge after a defined time of gluten avoidance to establish non-celiac disease gluten sensitivity as a persistent disease entity.

Mast cell activation disease: An underappreciated cause of neurologic and psychiatric symptoms and diseases.

Neurologists and psychiatrists frequently encounter patients whose central and/or peripheral neurologic and/or psychiatric symptoms (NPS) are accompanied by other symptoms for which investigation finds no unifying cause and for which empiric therapy often provides little to no benefit. Systemic mast cell activation disease (MCAD) has rarely been considered in the differential diagnosis in such situations. Traditionally, MCAD has been considered as just one rare (neoplastic) disease, mastocytosis, generally focusing on the mast cell (MC) mediators tryptase and histamine and the suggestive, blatant symptoms of flushing and anaphylaxis. Recently another form of MCAD, MC activation syndrome (MC), has been recognized, featuring inappropriate MC activation with little to no neoplasia and likely much more heterogeneously clonal and far more prevalent than mastocytosis. There also has developed greater appreciation for the truly very large menagerie of MC mediators and their complex patterns of release, engendering complex, nebulous presentations of chronic and acute illness best characterized as multisystem polymorbidity of generally inflammatory ± allergic themes--including very wide arrays of central and peripheral NPS. Significantly helpful treatment--including for neuropsychiatric issues--usually can be identified once MCAD is accurately diagnosed. We describe MCAD's pathogenesis, presentation (focusing on NPS), and therapy, especially vis-à-vis neuropsychotropes. Since MCAD patients often present NPS, neurologists and psychiatrists have the opportunity, in recognizing the diagnostic possibility of MCAD, to short-circuit the often decades-long delay in establishing the correct diagnosis required to identify optimal therapy.

Excretion of urinary histamine and N-tele methylhistamine in patients with gastrointestinal food allergy compared to non-allergic controls during an unrestricted diet and a hypoallergenic diet.

BACKGROUND: Patients with gastrointestinal food allergy are characterised by increased production of mast cell derived mediators upon allergen contact and present often with unspecific symptoms. The aim of this study was to evaluate urinary histamine and methylhistamine excretion in patients with food allergy and to compare their values with food-tolerant controls. METHODS: In a retrospective case control study the urinary excretion parameters were analysed from 56 patients (40.9, 19 - 58 years) in whom later food challenge tests confirmed food allergy. During their diagnostic work-up urine was collected during a 12-h period under an unrestricted diet with staple foods and a hypoallergenic potato-rice-diet (each 2 days). Healthy controls underwent the same diet types to define normal excretion parameters. Urinary histamine and n-methylhistamine were determined by ELISA or tandem mass spectrometry, respectively, and were expressed as median (25 - 75% range, µg/mmol creatinine x m(2)BSA). RESULTS: During unrestricted diet urinary histamine was significantly higher in gastrointestinal food allergy than healthy controls (1.42, 0.9 - 2.7 vs 0.87, 0.4 - 1.3; p < 0.0001), while the difference between both groups became marginal during potato-rice diet (1.30, 0.7 - 2.1 vs 1.05, 0.5 - 1.5; p = 0.02). N-methylhistamine was found to be significantly elevated in gastrointestinal food allergy both during unrestricted diet (7.1, 5.0 - 11.2) and potato-rice diet (5.7, 3.7 - 8.7) compared to controls (p < 0.0001). Interestingly, urinary methylhistamine excretion (p < 0.004) and clinical symptom score (p < 0.02) fell significantly when the diet was switched from unrestricted to hypoallergenic food, but was not correlated with symptom scores. CONCLUSIONS: In gastrointestinal food allergy significantly higher levels of urine histamine and methylhistamine excretion were found under unrestricted diet, reflecting an increased secretion of histamine due to offending foods. Measurement of urinary n-methylhistamine levels may help to find out patients with increased histamine production and/or food-allergen induced clinical symptoms, respectively.

QuickView video preview software of colon capsule endoscopy: reliability in presenting colorectal polyps as compared to normal mode reading.

OBJECTIVE. Colon capsule endoscopy (CCE) proved to be highly sensitive in detection of colorectal polyps (CP). Major limitation is the time-consuming video reading. The aim of this prospective, double-center study was to assess the theoretical time-saving potential and its possible impact on the reliability of "QuickView" (QV), in the presentation of CP as compared to normal mode (NM). METHODS. During NM reading of 65 CCE videos (mean patient´s age 56 years), all frames showing CPs were collected and compared to the number of frames presented by QV at increasing QV settings (10, 20, ... 80%). Reliability of QV in presenting polyps <6 mm and ≥6 mm (significant polyp), and identifying patients for subsequent therapeutic colonoscopy, capsule egestion rate, cleansing level, and estimated time-saving potential were assessed. RESULTS. At a 30% QV setting, the QV video presented 89% of the significant polyps and 86% of any polyps with ≥1 frame (per-polyp analysis) identified in NM before. At a 10% QV setting, 98% of the 52 patients with significant polyps could be identified (per-patient analysis) by QV video analysis. Capsule excretion rate was 74% and colon cleanliness was adequate in 85%. QV´s presentation rate correlates to the QV setting, the polyp size, and the number of frames per finding. CONCLUSIONS. Depending on its setting, the reliability of QV in presenting CP as compared to NM reading is notable. However, if no significant polyp is presented by QV, NM reading must be performed afterwards. The reduction of frames to be analyzed in QV might speed up identification of candidates for therapeutic colonoscopy.

Osteonecrosis of the jaw in a Crohn's disease patient following a course of Bisphosphonate and Adalimumab therapy: a case report.

BACKGROUND: Bisphosphonates have a widespread indication for osteoporosis and are also applied in cancer patients with skeletal-related conditions. Bisphosphonate-associated osteonecrosis of the jaw (BRONJ) is a feared side effect which is hard to treat and often affects patient's quality of life in an extensive manner. Adalimumab (Humira®), a fully human recombinant antibody specific for tumor necrosis factor- α, is approved for treatment in patients with Inflammatory Bowel Disease like ulcerative colitis or Crohn's disease. CASE PRESENTATION: In March 2013, a 36-year-old female presented with right-sided perimandibular swelling, recurrent facial pain and exposed necrotic bone after previous extraction of tooth 47. She had the medical history of Crohn's disease for more than one decade with chronic active enterocolitis, fistula disease as well as previous oral manifestation and was currently treated with Adalimumab since September 2008. Due to steroid-induced osteoporosis, diagnosed in 2004, she received oral Bisphosphonates (Risedronate) from 2004 until 2007 followed by two infusions of Zoledronic acid in 2008 and 2009. CONCLUSION: This patient with a medical history of Crohn's disease and gastrointestinal remission under Adalimumab therapy presented with osteonecrosis of the jaw after suspended oral and intravenous Bisphosphonate therapy implicating that the biologic therapy with an anti-TNF-α antibody might promote the manifestation of osteonecrosis and compromise oral healing capacity.

Brown bowel syndrome: a rare complication in diseases associated with long-standing malabsorption.

BACKGROUND/AIMS: Longtime chronic malabsorption may among other things cause a lack of liposoluble vitamins. Vitamin E deficiency can lead to formation of lipofuscin aggregates. Its deficiency is also associated with an increased lipofuscinosis of the bowel, i.e. brown bowel syndrome. METHODS: Systematic research via Medline on brown bowel syndrome, lipofuscinosis, and vitamin E deficiency was performed. We combined our own clinical experience and a review of the literature for this paper. Its goal is to inform about the possible consequences of severe malabsorption and brown bowel syndrome. RESULTS: Systematic data about the occurrence of severe malabsorption and brown bowel syndrome are rare. Only about 27 scientific reports can be found on this subject. Brown bowel syndrome is found mostly in conjunction with vitamin E deficiency and lipofuscinosis of the bowel. The clinical findings are caused by both malabsorption and lipofuscinosis. Case reports show a therapeutic effect of vitamin E. CONCLUSION: Vitamin deficiency caused by longtime chronic malabsorption can lead to the development of brown bowel syndrome, which is seen as the expression of lipofuscinosis of the bowel, and can cause further clinical disorders. Patients with malabsorption should therefore be monitored regarding their vitamin E levels.

Outcome and complications of endoscopic balloon dilatations in various types of ileocaecal and colonic stenosis in patients with Crohn's disease.

AIM: We examined the outcome and the complications of endoscopic balloon dilatation (EBD) of ileocaecal and colonic strictures due to Crohn's disease. METHODS: We examined 237 dilatation procedures in 77 patients with symptomatic ileocaecal and colonic stenosis regarding outcome, individual perforation risk, the need for further interventions, and other complications within a 10 years observation period. RESULTS: In 50 of 77 patients (64.9%), endoscopic dilatation procedures were successful within a median follow-up period of 24 months (25th and 75th percentile 10-38.5 months). Thirty five patients (45.5%) were successfully dilated with only one endoscopic procedure, while the remaining patients required two or more EBDs. Albeit the EBD, 27 patients of the whole cohort (35.1%) underwent surgical repair of the stenosis in due course. Overall complication rate was 7.6%, with postdilatation bleeding in 1.7% and abdominal pain longer than 24 h in 4.2%. Perforation occurred in 4 of 77 patients (5.2%), resulting in a perforation rate of 1.7% per intervention, or, more importantly, for the individual patient in a long-term perforation rate of 5.2% per patient, respectively. DISCUSSION: Endoscopic balloon dilatation (EBD) is a safe and effective approach to ileocaecal and colonic stenosis in approximately 65% of Crohn's disease patients. Even in case of recurrence, further endoscopic treatments can be undertaken. The perforation rate depending on the number of interventions is low, but for the individual patient a cumulative per patient perforation risk of 5.2% in the long-term should be considered during patient information and decisions for or against surgical interventions.

Eosinophilic gastroenteritis with refractory ulcer disease and gastrointestinal bleeding as a rare manifestation of seronegative gastrointestinal food allergy.

Gastrointestinal bleeding and iron deficiency anaemia may cause severe symptoms and may require extensive diagnostics and substantial amounts of health resources.This case report focuses on the clinical presentation of a 22 year old patient with recurrent gastrointestinal bleeding from multilocular non-healing ulcers of the stomach, duodenum and jejunum over a period of four years. Extensive gastroenterological and allergological standard diagnostic procedures showed benign ulcerative lesions with tissue eosinophilia, but no conclusive diagnosis. Multiple diagnostic procedures were performed, until finally, endoscopically guided segmental gut lavage identified locally produced, intestinal IgE antibodies by fluoro-enzyme-immunoassay.IgE antibody concentrations at the intestinal level were found to be more-fold increased for total IgE and food-specific IgE against nuts, rye flour, wheat flour, pork, beef and egg yolk compared with healthy controls.Thus, a diet eliminating these allergens was introduced along with antihistamines and administration of a hypoallergenic formula, which resulted in complete healing of the multilocular ulcers with resolution of gastrointestinal bleeding. All gastrointestinal lesions disappeared and total serum IgE levels dropped to normal within 9 months. The patient has been in remission now for more than two years.Eosinophilic gastroenteritis (EG) is well known to induce refractory ulcer disease. In this case, the mechanisms for intestinal damage and gastrointestinal bleeding were identified as local gastrointestinal type I allergy. Therefore, future diagnostics in EG should also be focused on the intestinal level as identification of causative food-specific IgE antibodies proved to be effective to induce remission in this patient.

Activation of the transcription factor Nrf2 in macrophages, Caco-2 cells and intact human gut tissue by Maillard reaction products and coffee.

In addition to direct antioxidative effects, Maillard reaction products (MRPs) could increase the antioxidative capacity of cells through the induction of cytoprotective enzymes. Since many of those enzymes are regulated by the transcription factor Nrf2, the effect of MRPs on nuclear translocation of Nrf2 in macrophages and Caco-2 cells was investigated. Stimulation of both cell types by MRPs showed a concentration-dependent significant increase in nuclear translocation of Nrf2 up to fivefold after short-term (2 h) and up to 50-fold after long-term treatment (24 h). In intact human gut tissue, nuclear translocation of Nrf2 was significantly twofold increased after short-term incubation. To study the activation mechanisms, macrophages and Caco-2 cells were stimulated with MRPs in the presence of catalase, which significantly suppressed Nrf2 activation. Thus, activation was related to extracellular H2O2 continuously formed from MRPs. Short-term incubation with coffee, a MRP-rich beverage, led to a trend towards Nrf2 activation in macrophages, but not in Caco-2 cells or intact human gut tissue. Long-term incubation with coffee (1-4 mg/mL) significantly increased nuclear Nrf2 up to 17-fold. Since raw coffee was inactive under the tested conditions, the effect was related to roasting products. Coffee-induced Nrf2 translocation was, however, only slightly reversed by catalase. Therefore, the Nrf2 activity of coffee can only partially be explained by MRP-induced, H2O2-dependent mechanisms. Thus, it can be concluded that MRPs may increase the antioxidative capacity inside the cell by inducing Nrf2-regulated signalling pathways not only in different cell types, but also in intact gut tissue.

Chronic calcium pyrophosphate crystal inflammatory arthritis induced by extreme hypomagnesemia in short bowel syndrome.

BACKGROUND: Short bowel syndrome (SBS) may induce a plethora of clinical symptoms ranging from underweight to nutrient-, vitamin- and electrolyte deficiencies. The objective of this case report is to illustrate how demanding the management of a 60 year old patient with SBS and recurrent joint attacks was for different medical disciplines. CASE PRESENTATION: The patient with SBS presented with a body mass index of 16.5 kg/m2 after partial jejunoileal resection of the small intestine with a six year long history of recurrent pain attacks in multiple peripheral joints, chronic diarrhoea and food intolerances. Pain attacks occurred 4-5 times a week with a median consumption of 15 mg prednisone per day. The interdisciplinary workup after several gastroenterologic, rheumatologic, radiologic, psychiatric and orthopedic consultations is shown including successful treatment steps.Clinical diagnosis revealed no systemic inflammatory disease, but confirmed extreme hypomagnesemia (0.2 mmol/l) after reproducible pathological magnesium resorption tests as causative for chronic calcium pyrophosphate crystal inflammatory arthritis (pseudogout, chondrocalcinosis).Multidisciplinary treatment included application of colchicines, parenteral nutrition and magnesium substitution, antiperistaltic agents and avoidance of intolerant foods. Normalization of magnesium levels and a marked remission of joint attacks were achieved after six months with significant reduction of prednisone to 1.5 mg/day. CONCLUSION: Despite the rarity of this condition, it is important to know that hypomagnesaemia may be associated with calcium pyrophosphate crystal inflammatory arthritis (chondrocalcinosis) and that SBS patients may be prone to develop extreme hypomagnesaemia causing recurrent joint attacks without systemic inflammation.

Paradoxical Reactions to Biologicals in Chronic Inflammatory Systemic Diseases.

BACKGROUND: Biological agents that contain substances affecting the immune system are increasingly being used to treat chronic inflammatory systemic diseases. Aside from the expected adverse effects, they can also induce unexpected paradoxical reactions (PR). A reaction is called paradoxical when a substance that is generally therapeutically effective induces the opposite of what is intended, with the new appearance or exacerbation of inflammatory changes in the skin and other organs. METHODS: The paradoxical reactions that have been described since 1997 are presented here on the basis of the available literature on the main types of chronic inflammatory systemic disease, which was retrieved by a selective search in the PubMed and Google Scholar databases. RESULTS: Many studies and registers to date contain no mention of paradoxical reactions. Anti-TNF-alpha treatment for patients with ankylosing spondylitis leads to paradoxical reactions in 19 per 1000 patient years, compared to 11 per 1000 patient years with conventional treatment; the corresponding frequency for paradoxical psoriasis in patients with other chronic inflammatory systemic diseases are 1.04-3.68 versus 1.45 per 1000 patient years. Paradoxical reactions tend to be more common with anti-TNF-alpha treatment than, for example, with the administration of ustekinumab, vedolizumab, and other agents. It is unclear whether some drugs have been noted to cause PR more commonly than others because of varying times since their approval, differences in immunogenicity, and differences between their target structures. CONCLUSION: Paradoxical reactions induced by biological agents are a problem confronting physicians in multiple specialties. They need to be distinguished from infectious and neoplastic diseases and from autoimmune conditions of other types. The treatment options for paradoxical reactions include local treatment, symptomatic therapy, prednisolone administration, and the discontinuation or switching of the biological agent, although some patients will react with a further paradoxical reaction to a different biological agent that is used instead.

The serotonin receptor 3E variant is a risk factor for female IBS-D.

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D.

Cleaning of occluded pancreatic duct endoprostheses: a new indication for extracorporeal shock wave lithotripsy?

BACKGROUND: Pancreatic duct stenting is widely performed for bridging main pancreatic duct obstruction in patients with chronic pancreatitis. The major limitation is early stent occlusion, making regular stent exchange necessary. OBJECTIVE: To date, no measures are available to prevent stent occlusion. The aim of this study was to evaluate the cleansing effect of shock wave application (SWA) on occluded pancreatic duct stents in vitro. DESIGN: In vitro study. PATIENTS: We analyzed occlusion rates of 25 plastic endoprostheses removed from 21 patients with chronic pancreatitis. INTERVENTION: We administered 350 shock wave pulses every 10 mm along the prosthesis, which was stored in a latex balloon filled with gas-free physiologic saline solution, by using a pressure of 42 megapascals. MAIN OUTCOME MEASUREMENTS: After SWA, the occlusion rate was measured again, and the cleansing rate was calculated in comparison with the native prosthesis. RESULTS: The mean (± SD) occlusion rate was significantly reduced (64.7 ± 28.7 [15%-100%]) before SWA vs 9.8 ± 25.3 [0-100%]) after SWA; P = .038). In 16 of 25 prostheses (64%), cleaning was complete. Four of the remaining 9 prostheses (16%) showed satisfactory cleaning of 95%, on average. Residual clogging material was found mainly at the duodenal tip and the middle of the stent. No significant association was found between patient-related or stent-related parameters and the cleansing effect of SWA. LIMITATIONS: In vitro study design. CONCLUSION: SWA is effective in cleaning occluded pancreatic endoprostheses in vitro. Prolongation of stent placement seems possible if regular SWA is performed. Extracorporeal shock wave lithotripsy therefore might become a new indication for patients under treatment with pancreatic endoprostheses.

Successful interventional treatment of postoperative bile duct leakage after Billroth II resection by unusual procedure using double balloon enteroscopy.

BACKGROUND: Endoscopic treatment of advanced biliary disorders and their complications following surgical procedures is often difficult especially after Billroth II gastric resection. In such cases, endoscopic access to the papilla and neopapilla is often low, and access to the choledocho- or hepaticojejunostomy is often difficult. Thus, percutaneous cholangiodrainage or re-operation is therefore indicated when endoscopic access to the papilla failed. But both of those methods are much more invasive and more likely to be followed by complications than use of a purely endoscopic approach. CASE REPORT: The present case report describes endoscopic access to the papilla with both push enteroscopy and double-balloon enteroscopy (DBE, push-and-pull enteroscopy) in a female patient after Billroth II resection with bile leakage following cholecystectomy. Successful closure of the bile duct fistula could be achieved via an unusual abdominal-biliary-jejunal cannulation way after several attempts of modern enteroscopy and in this way re-operation was avoided. CONCLUSIONS: Modern enteroscopy by experienced investigators using push-and-pull enteroscopes can provide access to the papilla even in complex postoperative anatomic rearrangements. Push-and-pull enteroscopes offer a further option for successful cannulation of the papilla and therapeutic interventions via additional stabilization with balloons and the modern enteroscopic approach by push-and-pull enteroscopy appears to provide more patient comfort, requires less analgo-sedation and examination time and in cases with intra-abdominal drainage this external access may be used as an additional aid for exploration and intervention in complex individual cases with extremely difficult treatable bile duct injuries.

Update of the S2k guideline on the management of IgE-mediated food allergies.

Not available.