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Objective To assess the frequency of adverse events associated with periendoscopic management of direct oral anticoagulants (DOACs) in patients undergoing elective GI endoscopy and the efficacy and safety of the British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) recommendations (NCT 02734316). Design Consecutive patients on DOACs scheduled for elective GI endoscopy were prospectively included. The timing of DOAC interruption and resumption before and after the procedures were recorded, along with clinical and procedural data. Procedures were stratified into low-risk and high-risk for GI-related bleeding, and patients into low-risk and high-risk for thromboembolic events. Patients were followed-up for 30 days for major and clinically relevant non-major bleeding events (CRNMB), arterial and venous thromboembolism and death. Results Of 529 patients, 38% and 62% underwent high-risk and low-risk procedures, respectively. There were 45 (8.5%; 95% CI 6.3% to 11.2%) major or CRNMB events and 2 (0.4%; 95% CI 0% to 1.4%) thromboembolic events (transient ischaemic attacks). Overall, the incidence of bleeding events was 1.8% (95% CI 0.7% to 4%) and 19.3% (95% CI 14.1% to 25.4%) in low-risk and high-risk procedures, respectively. For high-risk procedures, the incidence of intraprocedural bleeding was similar in patients who interrupted anticoagulation according to BSG/ESGE guidelines or earlier (10.3%vs10.8%, p=0.99), with a trend for a lower risk as compared with those who stopped anticoagulation later (10.3%vs25%, p=0.07). The incidence of delayed bleeding appeared similar in patients who resumed anticoagulation according to BSG/ESGE guidelines or later (6.6%vs7.7%, p=0.76), but it tended to increase when DOAC was resumed earlier (14.4%vs6.6%, p=0.27). The risk of delayed major bleeding was significantly higher in patients receiving heparin bridging than in non-bridged ones (26.6%vs5.9%, p=0.017). Conclusion High-risk procedures in patients on DOACs are associated with a substantial risk of bleeding, further increased by heparin bridging. Adoption of the BSG/ESGE guidelines in periendoscopic management of DOACs seems to result in a favourable benefit/risk ratio. Trial registration number NCT 02734316; Pre-results.

Introduction: Talc is currently the most common agent used for pleurodesis. Despite its role acknowledged as an effective bed side strategy primarily in neoplastic pleural effusion, recently it has been introduced in the treatment of benign diseases such as spontaneous pneumothorax. Aim of this study is to investigate side effects and results of different concentrations of talc pleurod- esis (TP) in rabbits. Materials and Methods: Twenty-six New Zealand rabbits were randomly injected intrapleurally with saline (n=6) or talc slurry at usual dosage 40mg/kg (T40, n=10) and 200mg/kg (T200, n=10). Chest tube was opened at day1 post-operative and removed in day4. Clinical signs and symptoms, fluid lactate dehydrogenase and protein levels were measured daily after the injection until drainage removal, then on day7 and before sacrifice. All groups were equally divided in two endpoints: day14 and day28. At post- mortem examination, pleurodesis was graded, according to Light criteria, from 1(none) to 8(>50% symphysis), by two observers blinded to treatment groups. Results: Adverse reactions were discovered with fever and weight loss in T200 group at 14 and 28 days. Pleurodesis score in the control Saline was negative while it did not differ significantly between T200 (4.0±1.4 at 14 days, 4.2±1.6 at 28 days) and T40 (2.8±2.0 at 14 days, 3.6±1.9 at 28 days) at days 14 and 28 (p=0.25 and p=0.56 respectively). Microscopically several granulomas, moderate localized pleural thickness, few areas of neoangiogen- esis and mediastinal lymphathic tissue infiltration were present in both study groups. Conclusions: TP at usual clinical dosage is well tolerated with acceptable clinical results. By increasing the concentration we observed severe side-effects with only mild improvement of pleurodesis.

The following paper on functional testing of the pharynx includes commentaries on the use of 24-h pH-impedance testing to identify patients with nonacid reflux and the caveats associated with automatic and visual analysis; the potential diagnostic yield of ambulatory high-resolution manomentry (HRM), particularly in identifying non-cardiac chest pain and transient lower esophageal sphincter relaxations; the differential manometric identification of conditions facilitated by using solid swallows, and the advantages of the newly developed ResTech oropharyngeal pH probe in the detection of proximal reflux events.

Background We investigated whether tigecycline (TIGE) is more effective than talc in inducing pleurodesis in rabbits. Methods Fifty-six New Zealand rabbits were utilized in a two-phase study: Effects at 14 d (phase I) and at 28 d (phase II) were assessed. Saline solution (SAL n = 3), talc slurry (TALC 200 mg/kg, n = 5), and TIGE at different concentrations (mg/kg): TIGE0.5 (n = 5); TIGE1 (n = 5); TIGE3 (n = 5); TIGE25 (n = 5); TIGE50 (n = 5) were randomly injected, for each phase, through a right chest drainage. TIGE0.5 and TIGE1 were ineffective during phase I and were thus excluded from further investigation. At post mortem examination, pleurodesis was graded grossly and microscopically by three observers blinded to treatment groups. Results Phase I: pleurodesis was more effective in TIGE25 and TIGE50 (P < 0.001); TALC was better than TIGE0.5 (P < 0.001), and TIGE1 (P = 0.49), macroscopically. Pleural thickness was significantly higher in TIGE25 compared with SAL, TALC, TIGE0.5, TIGE1, and TIGE3 (P < 0.01). No significant differences were evident between TALC and TIGE3, both macroscopically (P = 0.90) and microscopically (inflammation P = 0.99, fibrosis P = 0.96, pleural thickness P = 0.99). Phase II: better effectiveness of TIGE50 compared with all other groups (P < 0.001) except TIGE 25 (P = 0.29); results similar to phase I for TALC and TIGE3 (P = 0.99), macroscopically. Microscopically greater inflammation in TALC compared with TIGE3 (P < 0.05) and in TIGE50 to TIGE3 (P = 0.05). Significant complications occurred in all TIGE50 group. One of TIGE25 and one of TIGE50 died of respiratory distress and of right hemothorax+ascites, respectively. Conclusions Intrapleural TIGE3 mg/kg is as effective as talc in inducing pleurodesis in rabbits. The intrapleural TIGE toxicity threshold was reached at TIGE25 mg/kg concentration.