Cutaneous Application of Capsaicin Cream Reduces Clinical Signs of Experimental Colitis and Repairs Intestinal Barrier Integrity by Modulating the Gut Microbiota and Tight Junction Proteins.

Capsaicin, a pungent compound in chili peppers, is described as having potent anti-inflammatory, antioxidant, and antimicrobial properties. It is also described as a potential modulator of the immune system and intestinal microbiota. Oral or rectal administration of capsaicin has been studied to treat or prevent colitis. However, those vias are often not well accepted due to the burning sensation that capsaicin can cause. Our objective was to evaluate whether the application of capsaicin skin creams (0.075%) would be effective in improving inflammation and epithelial barrier function as well as the composition of the gut microbiota in a model of mild colitis induced by dextran sulfate sodium (1.5%). The results showed that the cutaneous application of capsaicin reversed weight loss and decreased colon shortening and diarrhea, all typical signs of colitis. There was also an improvement in the intestinal epithelial barrier, preserving proteins from tight junctions. We also evaluated the biodistribution of 99mtechnetium-radiolabeled capsaicin (99mTc-CAPS) applied to the back skin of the animals. We found significant concentrations of 99 mTc-Cap in the colon and small intestine after 2 and 4 h of administration. In addition, there was an increased expression of capsaicin receptor TRPV1 in the colon. Moreover, animals with colitis receiving cutaneous capsaicin presented a better short-chain fatty acid profile and increased levels of SIgA, suggesting increased microbiota diversity. In conclusion, our work opens avenues for further studies to better understand capsaicin's potential benefits and mechanisms in addressing colitis through cutaneous application.

Biomarkers in the early prediction of rescue therapy in acute severe colitis-a single-centre retrospective study.

Nil.

Cystic and alveolar echinococcosis of the hepatobiliary tract - the role of new imaging techniques for improved diagnosis.

Cystic echinococcosis (CE) or hydatidosis (hydatid cysts) is an infection with a wide spectrum of manifestations, from symptomatic infection to fatal disease. Ultrasound (US) allows screening, diagnosis, differential diagnosis, treatment guidance and follow-up of CE under many circumstances. Hydatid cysts are predominantly observed in the liver. Herewith we present a review to demonstrate established and innovative imaging features of CE of the hepatobiliary tract.

Narrow-Band Imaging for Detection of Neoplasia at Colonoscopy: A Meta-analysis of Data From Individual Patients in Randomized Controlled Trials.

BACKGROUND & AIMS: Adenoma detection rate (ADR) is an important quality assurance measure for colonoscopy. Some studies suggest that narrow-band imaging (NBI) may be more effective at detecting adenomas than white-light endoscopy (WLE) when bowel preparation is optimal. We conducted a meta-analysis of data from individual patients in randomized controlled trials that compared the efficacy of NBI to WLE in detection of adenomas. METHODS: We searched MEDLINE, EMBASE, and Cochrane Library databases through April 2017 for randomized controlled trials that assessed detection of colon polyps by high-definition WLE vs NBI and from which data on individual patients were available. The primary outcome measure was ADR adjusted for bowel preparation quality. Multilevel regression models were used with patients nested within trials, and trial included as a random effect. RESULTS: We collected data from 11 trials, comprising 4491 patients and 6636 polyps detected. Adenomas were detected in 952 of 2251 (42.3%) participants examined by WLE vs 1011 of 2239 (45.2%) participants examined by NBI (unadjusted odds ratio [OR] for detection of adenoma by WLE vs NBI, 1.14; 95% CI, 1.01-1.29; P = .04). NBI outperformed WLE only when bowel preparation was best: adequate preparation OR, 1.07 (95% CI, 0.92-1.24; P = .38) vs best preparation OR, 1.30 (95% CI, 1.04-1.62; P = .02). Second-generation bright NBI had a better ADR than WLE (second-generation NBI OR, 1.28; 95% CI, 1.05-1.56; P = .02), whereas first-generation NBI did not. NBI detected more non-adenomatous polyps than WLE (OR, 1.24; 95% CI, 1.06-1.44; P = .008) and flat polyps than WLE (OR, 1.24; 95% CI, 1.02-1.51; P = .03). CONCLUSIONS: In a meta-analysis of data from individual patients in randomized controlled trials, we found NBI to have a higher ADR than WLE, and that this effect is greater when bowel preparation is optimal.

Imaging of toxocariasis.

Parasitäre Erkrankungen werden in Europa relativ selten diagnostiziert und behandelt. Somit sind auch klinische Besonderheiten und bildgebende Merkmale weniger bekannt. In den heutigen Zeiten von Migration und weltweiter Flüchtlingsströme ist die Kenntnis parasitärer Infektionen zunehmend von Bedeutung. Anhand von klinischen Beschreibungen der Echinokokkose, Schistosomiasis, Fasciolosis und Ascariasis wurden entsprechende Berichte in der Zeitschrift für Gastroenterologie publiziert. In der hier präsentierten Veröffentlichung werden klinische Besonderheiten und Bildgebungsmerkmale der Toxocariasis diskutiert.

Never seen before? Opisthorchiasis and Clonorchiasis.

Parasitic diseases are relatively rarely diagnosed and treated in Europe. Therefore, European clinicians are not familiar with their clinical and imaging features. In an era of increased human migration, it is fundamental for clinicians to be able to identify such diseases. We have recently described the features of cystic echinococcosis, schistosomiasis, fascioliasis and ascariasis. Here, we report on the clinical and imaging features as well as on the current therapy options of infections by the small liver flukes: Clonorchis sinensis, Opisthorchis viverrini (Southeast Asian liver fluke) and Opisthorchis felineus (cat liver fluke) and other Opisthorchis species prevalent in South Asia.

Gastrointestinal ultrasound in inflammatory bowel disease: an underused resource with potential paradigm-changing application.

Evolution of treatment targets in IBD has increased the need for objective monitoring of disease activity to guide therapeutic strategy. Although mucosal healing is the current target of therapy in IBD, endoscopy is invasive, expensive and unappealing to patients. GI ultrasound (GIUS) represents a non-invasive modality to assess disease activity in IBD. It is accurate, cost-effective and reproducible. GIUS can be performed at the point of care without specific patient preparation so as to facilitate clinical decision-making. As compared with ileocolonoscopy and other imaging modalities (CT and MRI), GIUS is accurate in diagnosing IBD, detecting complications of disease including fistulae, strictures and abscesses, monitoring disease activity and detecting postoperative disease recurrence. International groups increasingly recognise GIUS as a valuable tool with paradigm-changing application in the management of IBD; however, uptake outside parts of continental Europe has been slow and GIUS is underused in many countries. The aim of this review is to present a pragmatic guide to the positioning of GIUS in IBD clinical practice, providing evidence for use, algorithms for integration into practice, training pathways and a strategic implementation framework.

How to perform gastrointestinal ultrasound: Anatomy and normal findings.

Gastrointestinal ultrasound is a practical, safe, cheap and reproducible diagnostic tool in inflammatory bowel disease gaining global prominence amongst clinicians. Understanding the embryological processes of the intestinal tract assists in the interpretation of abnormal sonographic findings. In general terms, the examination principally comprises interrogation of the colon, mesentery and small intestine using both low-frequency and high-frequency probes. Interpretation of findings on GIUS includes assessment of bowel wall thickness, symmetry of this thickness, evidence of transmural changes, assessment of vascularity using Doppler imaging and assessment of other specific features including lymph nodes, mesentery and luminal motility. In addition to B-mode imaging, transperineal ultrasonography, elastography and contrast-enhanced ultrasonography are useful adjuncts. This supplement expands upon these features in more depth.

Ultrasound contrast agents.

Endoscopic ultrasound (EUS) plays an important role in imaging of the mediastinum and abdominal organs. Since the introduction of US contrast agents (UCA) for transabdominal US, attempts have been made to apply contrast-enhanced US techniques also to EUS. Since 2003, specific contrast-enhanced imaging was possible using EUS. Important studies have been published regarding contrast-enhanced EUS and the characterization of focal pancreatic lesions, lymph nodes, and subepithelial tumors. In this manuscript, we describe the relevant UCA, their application, and specific image acquisition as well as the principles of image tissue characterization using contrast-enhanced EUS. Safety issues, potential future developments, and EUS-specific issues are reviewed.

Ultrasound-guided central vascular interventions, comments on the European Federation of Societies for Ultrasound in Medicine and Biology guidelines on interventional ultrasound.

Central venous access has traditionally been performed on the basis of designated anatomical landmarks. However, due to patients' individual anatomy and vessel pathology and depending on individual operators' skill, this landmark approach is associated with a significant failure rate and complication risk. There is substantial evidence demonstrating significant improvement in effectiveness and safety of vascular access by realtime ultrasound (US)-guidance, as compared to the anatomical landmark-guided approach. This review comments on the evidence-based recommendations on US-guided vascular access which have been published recently within the framework of Guidelines on Interventional Ultrasound (InVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) from a clinical practice point of view.

WFUMB Position Paper. Learning Gastrointestinal Ultrasound: Theory and Practice.

Gastrointestinal ultrasound (GIUS) is an ultrasound application that has been practiced for more than 30 years. Recently, GIUS has enjoyed a resurgence of interest, and there is now strong evidence of its utility and accuracy as a diagnostic tool for multiple indications. The method of learning GIUS is not standardised and may incorporate mentorship, didactic teaching and e-learning. Simulation, using either low- or high-fidelity models, can also play a key role in practicing and honing novice GIUS skills. A course for training as well as establishing and evaluating competency in GIUS is proposed in the manuscript, based on established learning theory practice. We describe the broad utility of GIUS in clinical medicine, including a review of the literature and existing meta-analyses. Further, the manuscript calls for agreement on international standards regarding education, training and indications.

Lung B-line artefacts and their use.

BACKGROUND: The analysis of lung artefacts has gained increasing importance as markers of lung pathology. B-line artefact (BLA), caused by a reverberation phenomenon, is the most important lung artefact. In this review, we discuss the current role of BLA in pneumology and explore open questions of the published consensus. METHODS: We summarized current literature about BLA. Also, we presented observations on healthy subjects and patients with interstitial syndrome (pulmonary fibrosis and edema), to investigate technical factors influencing BLA visualization. RESULTS: BLA imaging is influenced by more factors than recently assumed. When multiple BLA is visualized in the lung, they represent a sign of increased density due to the loss of aeration in the lung periphery. This condition may indicate different diseases including cardiogenic pulmonary edema, diffuse or focal interstitial lung diseases (ILD), infections and acute respiratory distress syndrome (ARDS). Correct interpretation of BLA in lung ultrasound is strongly influenced by associated sonographic signs and careful integration of all relevant clinical information. CONCLUSIONS: BLA is useful to monitor clinical response, and may become crucial in directing the diagnostic process. Further research is warranted to clarify technical adjustments, different probe and machine factors that influence the visualization of BLA.

Systematic Review and Meta-analysis: Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis.

BACKGROUND AND AIMS: Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and remission rates in UC RCTs and identify trial design factors influencing them. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched from inception through April 2014 for placebo-controlled trials in adult patients with UC of a biological agent, corticosteroid, immunosuppressant, or aminosalicylate. Data were independently doubly extracted. Quality was assessed using the Cochrane risk of bias tool. RESULTS: In all, 51 trials [48 induction and 10 maintenance phases] were identified. Placebo response and remission rates were pooled according to random-effects models, and mixed-effects meta-regression models were used to evaluate effects of study-level characteristics on these rates. Pooled estimates of placebo remission and response rates for induction trials were 10% (95% confidence interval [CI] 7-13%) and 33% [95% CI 29-37%], respectively. Corresponding values for maintenance trials were 19% [95% CI 11-30%] and 22% [95% CI 17-28%]. Trials enrolling patients with more active disease confirmed by endoscopy [endoscopy subscore ≥ 2] were associated with lower placebo rates. Conversely, placebo rates increased with increasing trial duration and number of study visits. CONCLUSIONS: Objective assessment of greater disease activity at trial entry by endoscopy lowered placebo rates, whereas increasing trial duration and more interactions with healthcare providers increased placebo rates. These findings have important implications for design and conduct of clinical trials.

Helicobacter Pylori Infection: Diagnostic Strategies in Primary Diagnosis and After Therapy.

Accurate diagnosis of Helicobacter pylori infection pre- and post-treatment is mandatory in the current era of decreasing prevalence and increasing antibiotic resistance. The diagnostic performance of most tests is poorer in clinical situations with low bacterial density which is seen in conditions such as atrophic gastritis or intake of antisecretory and antibiotic medications. Noninvasive tests require less cost and resource but provide excellent accuracy; however, endoscopy with testing of gastric biopsy specimens is indicated where alarming symptoms are present or antibiotic susceptibility testing by culture is desired. Newer modalities such as polymerase chain reaction testing provide additional virulence and antibiotic sensitivity profiling. This article outlines new developments and the key parameters of each test, as careful selection of test modality within the clinical context is required for adequate management of infected symptomatic patients.

'Lemonade Legs': Why do Some Patients Get Profound Hypomagnesaemia on Proton-Pump Inhibitors?

Proton pump inhibitors (PPIs) are widely used though an association with hypomagnesaemia and hypocalcaemia has only been described since 2006. Patients typically present after years of stable dosing with musculoskeletal, neurological or cardiac arrhythmic symptoms, but it is likely that many cases are under-recognised. Magnesium levels resolve rapidly on discontinuation of PPI therapy and hypomagnesaemia recurs rapidly on rechallenge with any agent in the class. The cellular mechanisms of magnesium homeostasis are increasingly being understood, including both passive paracellular absorption through claudins and active transcellular transporters, including the transient receptor potential channels (TRPM6) identified in the intestine and nephron. PPIs may alter luminal pH by modulating pancreatic secretions, affecting non-gastric H+K+ATPase secretion, altering transporter transcription or channel function. A small reduction in intestinal absorption appears pivotal in causing cumulative deficiency. Risk factors have been associated to help identify patients at risk of this effect but clinical vigilance remains necessary for diagnosis.

'Lemonade Legs': Why do Some Patients Get Profound Hypomagnesaemia on Proton-Pump Inhibitors?

Proton pump inhibitors (PPIs) are widely used though an association with hypomagnesaemia and hypocalcaemia has only been described since 2006. Patients typically present after years of stable dosing with musculoskeletal, neurological or cardiac arrhythmic symptoms, but it is likely that many cases are under-recognised. Magnesium levels resolve rapidly on discontinuation of PPI therapy and hypomagnesaemia recurs rapidly on rechallenge with any agent in the class. The cellular mechanisms of magnesium homeostasis are increasingly being understood, including both passive paracellular absorption through claudins and active transcellular transporters, including the transient receptor potential channels (TRPM6) identified in the intestine and nephron. PPIs may alter luminal pH by modulating pancreatic secretions, affecting non-gastric H+K+ATPase secretion, altering transporter transcription or channel function. A small reduction in intestinal absorption appears pivotal in causing cumulative deficiency. Risk factors have been associated to help identify patients at risk of this effect but clinical vigilance remains necessary for diagnosis.

The orthopaedic research scene and strategies to improve it.

Trauma and orthopaedics is the largest of the surgical specialties and yet attracts a disproportionately small fraction of available national and international funding for health research. With the burden of musculoskeletal disease increasing, high-quality research is required to improve the evidence base for orthopaedic practice. Using the current research landscape in the United Kingdom as an example, but also addressing the international perspective, we highlight the issues surrounding poor levels of research funding in trauma and orthopaedics and indicate avenues for improving the impact and success of surgical musculoskeletal research.

Restoring the anatomical tibial slope and limb axis may maximise post-operative flexion in posterior-stabilised total knee replacements.

The optimal management of the tibial slope in achieving a high flexion angle in posterior-stabilised (PS) total knee replacement (TKR) is not well understood, and most studies evaluating the posterior tibial slope have been conducted on cruciate-retaining TKRs. We analysed pre- and post-operative tibial slope differences, pre- and post-operative coronal knee alignment and post-operative maximum flexion angle in 167 patients undergoing 209 TKRs. The mean pre-operative posterior tibial slope was 8.6° (1.3° to 17°) and post-operatively it was 8.0° (0.1° to 16.7°). Multiple linear regression analysis showed that the absolute difference between pre- and post-operative tibial slope (p < 0.001), post-operative coronal alignment (p = 0.02) and pre-operative range of movement (p < 0.001) predicted post-operative flexion. The variance of change in tibial slope became larger as the post-operative maximum flexion angle decreased. The odds ratio of having a post-operative flexion angle < 100° was 17.6 if the slope change was > 2°. Our data suggest that recreation of the anatomical tibial slope appears to improve maximum flexion after posterior-stabilised TKR, provided coronal alignment has been restored.

Affinity-selected heparan sulfate for bone repair.

Bone morphogenetic protein (BMP)-2 is a potent bone healing compound produced at sites of bone trauma. Here we present a therapeutic strategy to harness the activity of endogenously produced BMP-2 by delivery of an affinity-matched heparan sulfate (HS) glycos aminoglycan biomaterial that increases the bioavailability, bioactivity and half-life of this growth factor. We have developed a robust, cost effective, peptide-based affinity platform to isolate a unique BMP-2 binding HS variant from commercially available preparations of HS, so removing the manufacturing bottleneck for their translation into the clinic. This affinity-matched HS enhanced BMP-2-induced osteogenesis through improved BMP-2 kinetics and receptor modulation, prolonged pSMAD signaling and reduced interactions with its antagonist noggin. When co-delivered with a collagen implant, the HS was as potent as exogenous BMP-2 for the healing of critical-sized bone defects in rabbits. This affinity platform can be readily tuned to isolate HS variants targeted ata range of clinically-relevant growth and adhesive factors.

Three-dimensional porous silk tumor constructs in the approximation of in vivo osteosarcoma physiology.

The lack of good preclinical models has hampered anticancer drug discovery. Standard preclinical protocols require the growth of cells in high throughput two-dimensional (2D) culture systems. However, such in vitro drug testing methods yield drug efficacy results that differ greatly from animal models. Conversely, it is much more difficult and expensive to use animal models for large-scale molecular biology research. It is conceivable that three-dimensional (3D) growth may be responsible for some of these changes. Porous silk sponges were fabricated through freeze drying and seeded with 143.98.2 osteosarcoma cells. Molecular profiles were obtained by carrying out real-time polymerase chain reaction for angiogenic growth factors and proliferation markers for osteosarcoma cells grown under 2D, 3D, and SCID mouse xenograft conditions. The angiogenic factor expression profiles for cells grown in 2D differed greatly from the 3D silk scaffold model (P < 0.05 for bFGF, HIF-1α, IL-8, and VEGF-A), whereas 3D tumor model profiles were found to be able to approximate that for the in vivo tumor better with no statistically different expression of HIF-1α and VEGF-A between the two. Immunohistochemistry staining for HIF-1α, VEGF-A, and VEGF receptor on osteosarcoma cells grown on the scaffolds validated the results obtained with the gene expression profiles. The results suggest that 3D tumor models could be used to bridge the gap between in vitro and in vivo tumor studies, and aid in the study of mechanisms activated during tumorigenesis for the development of novel targeted chemotherapy.