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Summary Background Regulatory requirements for claims of mucosal healing in ulcerative colitis ( UC ) will require demonstration of both endoscopic and histologic healing. Quantifying these rates is essential for future drug development. Aims To meta‐analyse endoscopic and histologic placebo response and remission rates in UC randomised controlled trials ( RCT s) and identify factors influencing these rates. Methods MEDLINE , EMBASE and the Cochrane Library were searched from inception to March 2017 for placebo‐controlled trials of pharmacological interventions for UC . Endoscopic and histologic placebo rates were pooled by random effects. Mixed effects univariable and multivariable meta‐regression was used to evaluate the influence of patient, intervention and trial‐related study‐level covariates on these rates. Results Fifty‐six induction (placebo n = 4171) and 8 maintenance trials (placebo n = 1011) were included. Pooled placebo endoscopic remission and response rates for induction trials were 23% [95 confidence interval ( CI ) 19‐28%] and 35% [95% CI 27‐42%] respectively, and 20% [95% CI 16‐24%] for maintenance of remission. The pooled histologic placebo remission rate was 14% [95% CI 8‐22%] for induction trials. High heterogeneity was observed for all outcomes ( I 2 56.2%‐88.3%). On multivariable meta‐regression, central endoscopy reading was associated with significantly lower endoscopic placebo remission rates (16% vs 25%; OR = 0.52, [95% CI 0.29‐0.92], P = 0.03). On univariable meta‐regression, higher histologic placebo remission was associated with concomitant corticosteroids ( OR = 1.17 [95% CI 1.08‐1.26], P < 0.0001, per 10% increase in corticosteroid use). Conclusions Placebo endoscopic and histologic rates range from 14% to 35% in UC RCT s but are highly heterogeneous. Outcome standardisation may reduce heterogeneity and is needed in this field.

Key Points PRS, based on the known CLL loci, predicts CLL risk with high discrimination. This PRS predicts risk of monoclonal B-cell lymphocytosis, a precursor to CLL and a condition that has clinical impact beyond risk for CLL.

AbstractOrthopaedic surgeons commonly have the misconception that patients with tibial plateau fractures will likely go on to posttraumatic knee arthritis requiring total knee arthroplasty (TKA). In younger patients, osteochondral allograft (OCA) transplantation is an alternative method to address posttraumatic knee arthritis. The purpose of this study was (1) to identify our institutional failure rate following tibial plateau open reduction and internal fixation (ORIF) (failure was defined as conversion to TKA or OCA); (2) to determine if there are patient- or injury-related risk factors predictive of failure; and (3) to characterize differences between patients treated with TKA versus those treated with OCA transplantation. A 10-year retrospective review was conducted to identify patients treated at our institution with a tibial plateau fracture. Patients included in the final analysis were at least 18 years of age with an articular fracture (AO/OTA 41 B/C). The primary outcome was subsequent ipsilateral OCA or TKA. There were 350 patients (359 tibial plateau fractures) with a mean follow-up of 22.3 months (range, 6–133 months) who met inclusion criteria. Twenty-seven fractures (7.5%) were subsequently converted to a TKA or OCA at an average of 3.75 ± 3.1 years following their initial surgery. Patients who consumed tobacco were 2.3 times more likely to require a joint replacement (confidence interval [CI], 1.0–5.2; p = 0.04). Those patients who received an OCAs were significantly younger as compared with their TKA peers, both at time of initial injury (37 vs. 51 years, p = 0.02) and at time of surgery (41 vs. 55 years, p = 0.009). The joint replacement rate in this study is similar to those studies in the published literature that focused solely on the prevalence of conventional TKA. Tobacco is a risk factor for failure following tibial plateau ORIF. Patients who were treated with an OCA were younger at time of injury and failure.

Background— Women have higher rates of all-cause mortality after percutaneous coronary intervention. Whether this is because of greater age and comorbidity burden or a sex-specific factor remains unclear. Methods and Results— We retrospectively assessed cause-specific long-term mortality after index percutaneous coronary intervention over 3 time periods (1991–1997, 1998–2005, and 2006–2012). Cause of death was determined using telephone interviews, medical records, and death certificates. We performed competing risks analyses of cause-specific mortality. A total of 6847 women and 16 280 men survived index percutaneous coronary intervention hospitalization 1991 to 2012. Women were older (mean±SD: 69.4±12 versus 64.8±11.7 years; P <0.001) with more comorbidities (mean±SD: Charlson index 2.1±2.1 versus 1.9±2.1; P <0.001). Across the 3 time periods, both sexes exhibited a decline in cardiac deaths at 5 years (26% relative decrease in women, 17% in men, trend P <0.001 for each). Although women had higher all-cause mortality compared with men in all eras, the excess mortality was because of noncardiac deaths. In the contemporary era, only a minority of deaths were cardiac (33.8% in women, 38.0% in men). After adjustment, there was no evidence for a sex-specific excess of risk for cardiac or noncardiac mortality. The commonest causes of death were chronic diseases and heart failure in women (5-year cumulative mortality, 5.4% and 3.9%) but cancer and myocardial infarction/sudden death in men (5.4% and 4.3%). Conclusions— The higher mortality after percutaneous coronary intervention in women is because of death from noncardiac causes. This is accounted for by baseline age and comorbidities rather than an additional sex-specific factor. These findings have implications for sex-specific clinical care and trial design.

BackgroundEndotypic and prognosticating features of chronic rhinosinusitis without nasal polyposis (CRSsNP) are poorly understood. Our objectives were to use an unbiased symptom‐based approach to: (1) study symptoms, clinical and endotypic features; and (2) identify features predicating outcomes from endoscopic sinus surgery (ESS).MethodsClinical, computed tomography (CT), histopathology, and 22‐item Sino‐Nasal Outcome Test (SNOT‐22) data was collected on 146 adult CRSsNP patients who underwent ESS. Unsupervised network modeling of presurgical SNOT‐22 scores was performed to classify symptom‐based clusters. Subject characteristics and post‐ESS SNOT‐22 scores were compared between clusters.ResultsBaseline characteristics of the subject population were as follows: females, 56.2%; revision ESS status in 35%; asthma prevalence, 32.6%; median Lund‐Mackay CT score, 8; and median SNOT‐22 total score, 43. Network mapping and unsupervised clustering of preoperative SNOT‐22 scores revealed 4 clusters: (A) severely burdened with high scores in all 4 subdomains; (B) moderately burdened with high scores in the rhinologic subdomain; (C) moderately burdened with high scores in psychological‐sleep subdomains; and (D) mildly burdened. The number of previous ESS and asthma prevalence differed significantly between clusters; CT scores were similar. Asthma burden and tissue eosinophilia were greatest in cluster A (p = 0.03). All groups showed significant improvement at 3 months post‐ESS (p < 0.0001). At 6 months, patients in cluster C tended to worsen.ConclusionSNOT‐22–based network modeling of CRSsNP patients yielded 4 clusters with distinct features. Asthma prevalence and tissue eosinophilia were highest in the cluster with highest SNOT‐22 scores. All patients showed significant improvement from ESS at 3 months; those with high sleep‐psychosocial symptoms tended to show worsening at 6 months.