Background: β-Defensins are a newly identified family of antimicrobial peptides that are expressed by epithelia on mucosal surfaces where their production is augmented by infection or inflammation. Helicobacter pylori colonises the gastric epithelium causing persistent gastric inflammation leading to antral and corpus gastritis, and peptic ulcer disease. Aims: To evaluate the role of β-defensins in the innate immune response of the gastric epithelium to infection and inflammation, we have assessed mRNA expression and regulation of human β-defensins 1 and 2 (hBD1, hBD2) by H pylori and proinflammatory stimuli. We have also compared gene and peptide expression of these bactericidal agents in H pylori induced gastritis with that in normal gastric mucosa. Methods: Modulation of expression of hBD1 and hBD2 by various stimuli was studied in three (AGS, MKN7, MKN45) gastric epithelial cell lines by quantitative competitive reverse transcriptionpolymerase chain reaction (RT-PCR). Defensin mRNA expression was measured by semiquantitative RT-PCR in gastritis tissue and compared with controls. Peptide localisation was assessed by immunohistochemistry. Results: Cytotoxic H pylori and interleukin 1β (IL-1β) markedly upregulated expression of hBD2 in a dose and time dependent manner in both AGS and MKN7 cell lines. A modest increase in hBD1 expression was also noted during infection. Interestingly, induction of hBD1 gene expression by IL-1β was only observed in MKN7 cells. The magnitude of this response was delayed and reduced compared with hBD2 expression. In gastric biopsies, hBD2 was undetectable in normal gastric antrum but a marked increase was observed in H pylori positive gastritis compared with control tissue (p<0.001). Constitutive expression of hBD1 was observed in normal gastric mucosa and there was a significant increase in gastritis (p<0.05). Immunohistochemistry revealed a parallel increase in hBD1 and hBD2 peptide expression in gastritis tissue with positive staining confined to the surface epithelium of the gastric glands. Conclusions: Modulation of β-defensin expression by pathogenic and/or inflammatory stimuli and their cellular localisation places these antimicrobial peptides in the front line of innate host defence in the human stomach.

IMPORTANCEThe burden of injury and costs of wrist fractures are substantial. Surgical treatment became popular without strong supporting evidence.OBJECTIVE To assess whether current surgical treatment for displaced distal radius fractures provided better patient-reported wrist pain and function than nonsurgical treatment in patients 60 years and older. DESIGN, SETTING, AND PARTICIPANTSIn this multicenter randomized clinical trial and parallel observational study, 300 eligible patients were screened from 19 centers in Australia and New Zealand from December 1, 2016, until December 31, 2018. A total of 166 participants were randomized to surgical or nonsurgical treatment and followed up at 3 and 12 months by blinded assessors. Those 134 individuals who declined randomization were included in a parallel observational cohort with the same treatment options and follow-up. The primary analysis was intention to treat; sensitivity analyses included as-treated and per-protocol analyses. INTERVENTION Surgical treatment was open reduction and internal fixation using a volar-locking plate (VLP). Nonsurgical treatment was closed reduction and cast immobilization (CR).MAIN OUTCOMES AND MEASURES The primary outcome was the Patient-Rated Wrist Evaluation score at 12 months. Secondary outcomes were Disabilities of Arm, Shoulder, and Hand questionnaire score, health-related quality of life, pain, major complications, patient-reported treatment success, bother with appearance, and therapy use. RESULTS In the 300 study participants (mean [SD] age, 71.2 [7.5] years; 269 [90%] female; 166 [81 VLP and 85 CR] in the randomized clinical trial sample and 134 [32 VLP and 102 CR] in the observational sample), no clinically important between-group difference in 12-month Patient-Rated Wrist Evaluation scores (mean [SD] score of 19.8 [21.1] for VLP and 21.5 [24.3] for CR; mean difference, 1.7 points; 95% CI −5.4 to 8.8) was observed. No clinically important differences were found in quality of life, wrist pain, or bother at 3 and 12 months. No significant difference was found in total complications between groups (12 of 84 [14%] for the CR group vs 6 of 80 [8%] for the VLP group; risk ratio [RR], 0.53; 95% CI, 0.21-1.33). Patient-reported treatment success favored the VLP group at 12 months (very successful or successful: 70 [89%] vs 57 [70%]; RR, 1.26; 95% CI, 1.07-1.48; P = .005). There was greater use of postoperative physical therapy in the VLP group (56 [72%] vs 44 [54%]; RR, 1.32; 95% CI, 1.04-1.69; P = 0.02).CONCLUSIONS AND RELEVANCE This randomized clinical trial found no between-group differences in improvement in wrist pain or function at 12 months from VLP fixation over CR for displaced distal radius fractures in older people.

Small bowel diaphragm disease presenting as a surgical emergency is likely to become more common due to the increased use of NSAIDs. A history of NSAID use in patients with iron deficiency anaemia or obstructive symptoms should lead to a high index of suspicion for this condition and should be preoperatively investigated.

In the UK, more than 2.5 million endoscopic procedures are carried out each year. Most are performed under conscious sedation with benzodiazepines and opioids administered by the endoscopist. However, in prolonged and complex procedures, this form of sedation may provide inadequate patient comfort or result in oversedation. As a result, this may have a negative impact on procedural success and patient outcome. In addition, there have been safety concerns on the high doses of benzodiazepines and opioids used particularly in prolonged and complex procedures such as endoscopic retrograde cholangiopancreatography. Diagnostic and therapeutic endoscopy has evolved rapidly over the past 5 years with advances in technical skills and equipment allowing interventions and procedural capabilities that are moving closer to minimally invasive endoscopic surgery. It is vital that safe and appropriate sedation practices follow the inevitable expansion of this portfolio to accommodate safe and high-quality clinical outcomes. This position statement outlines the current use of sedation in the UK and highlights the role for anaesthetist-led deep sedation practice with a focus on propofol sedation although the choice of sedative or anaesthetic agent is ultimately the choice of the anaesthetist. It outlines the indication for deep sedation and anaesthesia, patient selection and assessment and procedural details. It considers the setup for a deep sedation and anaesthesia list, including the equipment required, the environment, staffing and monitoring requirements. Considerations for different endoscopic procedures in both emergency and elective setting are also detailed. The role for training, audit, compliance and future developments are discussed.

Peripheral nerve grafts were implanted bilaterally into the diencephalon of adult hamsters. One graft segment contained both viable Schwann cells and their basal lamina tubes. The Schwann cell population in the second graft segment was killed by freezing prior to implantation. Seven weeks after graft implantations, the extracranial end of each graft segment was exposed, transected and labelled with a fluorescent tracer substance. One week after the labelling procedure each animal was perfused and the diencephalon and midbrain were examined. Ultrastructural analyses of both types of graft demonstrated the persistence of the Schwann cell-derived basal lamina tubes. Retrogradely labelled neurons were found in all cases in which an intact graft remained in place for two months, but were seen in only one case with a frozen graft. Large numbers of myelinated and unmyelinated axons were seen within the intact grafts, but no axons were found in the previously frozen grafts. These results indicate that lesioned CNS axons are able to regenerate vigorously when provided with an environment which includes viable Schwann cells. But, CNS axons regenerate less well, if at all, when Schwann cells are absent. Further, it appears that Schwann cell-derived basal lamina tubes, when isolated from their parent cells, are insufficient to initiate or sustain CNS axonal regeneration.