External validation of biomarkers for immune-related adverse events after immune checkpoint inhibition

Immune checkpoint inhibitors have revolutionized treatment of advanced melanoma, but commonly cause serious immune-mediated complications. The clinical ambition of reserving more aggressive therapies for patients least likely to experience immune-related adverse events (irAE) has driven an extensive search for predictive biomarkers. Here, we externally validate the performance of 59 previously reported markers of irAE risk in a new cohort of 110 patients receiving Nivolumab (anti-PD1) and Ipilimumab (anti-CTLA-4) therapy. Alone or combined, the discriminatory value of these routine clinical parameters and flow cytometry biomarkers was poor. Unsupervised clustering of flow cytometry data returned four T cell subsets with higher discriminatory capacity for colitis than previously reported populations, but they cannot be considered as reliable classifiers. Although mechanisms predisposing some patients to particular irAEs have been described, we are presently unable to capture adequate information from pre-therapy flow cytometry and clinical data to reliably predict risk of irAE in most cases

Physician awareness of knee and hip pain in the context of coronary heart disease treatment

Contains fulltext : 136527.pdf (publisher's version ) (Open Access

Total joint arthroplasty versus resection-interposition arthroplasty for thumb carpometacarpal arthritis: a randomized controlled trial

Background and purpose: Thumb carpometacarpal (TCMC) osteoarthritis is a common condition that causes pain and functional limitations. We compared the outcomes of 2 surgical procedures for TCMC osteoarthritis, the Epping resection-suspension arthroplasty and the double-mobility TCMC prosthesis, and focused on pain relief, functional outcomes, and patient quality of life. Patients and methods: Over a 7-year period a randomized controlled trial including 183 cases of TCMC osteoarthritis was conducted comparing a double mobility TCMC prosthesis (Moovis, Stryker, Kalamazoo, MI, USA) with the Epping resection-suspension arthroplasty. Pre- and postoperative examinations included the range of motion (ROM), SFMcGill score, visual analogue scale (VAS), the disabilities of the arm, shoulder and hand questionnaire (DASH), and the hospital anxiety and depression scale (HADS). Results: At the 6-week postoperative follow-up, significant differences were found in VAS: Epping median 4.0 (interquartile range [IQR] 2.0–5.0) vs. TCMC prosthesis 2.0 (IQR 0.25–4.0), p = 0.03, effect size (area under the curve [AUC]) 0.64 (95% confidence interval [CI] 0.55–0.73), in DASH score: Epping 61 (IQR 43–75) vs. TCMC prosthesis 45 (IQR 29–57), p < 0.001, AUC 0.69 (CI 0.61– 0.78), and in radial abduction: Epping 55 (IQR 50–60) vs. TCMC prosthesis 62 (IQR 60–70), p = 0.001, AUC 0.70 (CI 0.61–0.79). No significant group differences were found at the 6- and 12-months follow-up. During the follow-up period, 3 of 82 prostheses had to be revised but there was no revision in the Epping group. Conclusion: The double mobility TCMC prosthesis had superior outcomes compared with the Epping procedure at 6 weeks; however, there were no significant differences in outcomes at 6 months and 1 year postoperatively. The implant survival rate of 96% after 12 months was acceptabl