ImportanceFractures of the hip have devastating effects on function and quality of life. Intramedullary nails (IMN) are the dominant implant choice for the treatment of trochanteric fractures of... Show moreImportanceFractures of the hip have devastating effects on function and quality of life. Intramedullary nails (IMN) are the dominant implant choice for the treatment of trochanteric fractures of the hip. Higher costs of IMNs and inconclusive benefit in comparison with sliding hip screws (SHSs) convey the need for definitive evidence.ObjectiveTo compare 1-year outcomes of patients with trochanteric fractures treated with the IMN vs an SHS. Design, Setting, and ParticipantsThis randomized clinical trial was conducted at 25 international sites across 12 countries. Participants included ambulatory patients aged 18 years and older with low-energy trochanteric (AO Foundation and Orthopaedic Trauma Association [AO/OTA] type 31-A1 or 31-A2) fractures. Patient recruitment occurred between January 2012 and January 2016, and patients were followed up for 52 weeks (primary end point). Follow-up was completed in January 2017. The analysis was performed in July 2018 and confirmed in January 2022. InterventionsSurgical fixation with a Gamma3 IMN or an SHS.Main Outcomes and MeasuresThe primary outcome was health-related quality of life (HRQOL), measured by the EuroQol-5 Dimension (EQ5D) at 1-year postsurgery. Secondary outcomes included revision surgical procedure, fracture healing, adverse events, patient mobility (measured by the Parker mobility score), and hip function (measured by the Harris hip score).ResultsIn this randomized clinical trial, 850 patients were randomized (mean [range] age, 78.5 [18-102] years; 549 [64.6% female) with trochanteric fractures to undergo fixation with either the IMN (n=423) or an SHS (n=427). A total of 621 patients completed follow-up at 1 year postsurgery (304 treated with the IMN [71.9%], 317 treated with an SHS [74.2%]). There were no significant differences between groups in EQ5D scores (mean difference, 0.02 points; 95% CI, -0.03 to 0.07 points; P=.42). Furthermore, after adjusting for relevant covariables, there were no between-group differences in EQ5D scores (regression coefficient, 0.00; 95% CI, -0.04 to 0.05; P=.81). There were no between-group differences for any secondary outcomes. There were also no significant interactions for fracture stability (beta [SE] , 0.01 [0.05]; P=.82) or previous fracture (beta [SE], 0.01 [0.10]; P=.88) and treatment group.Conclusions and RelevanceThis randomized clinical trial found that IMNs for the treatment of trochanteric fractures had similar 1-year outcomes compared with SHSs. These results suggest that the SHS is an acceptable lower-cost alternative for trochanteric fractures of the hip.Trial RegistrationClinicalTrials.gov Identifier: NCT01380444 Show less
The 143 low- and middle-income countries (LMICs) of the world constitute 80% of the world's population or roughly 5.86 billion people with much variation in geography, culture, literacy, financial... Show moreThe 143 low- and middle-income countries (LMICs) of the world constitute 80% of the world's population or roughly 5.86 billion people with much variation in geography, culture, literacy, financial resources, access to health care, insurance penetration, and healthcare regulation. Unfortunately, their burden of cardiovascular disease in general and acute ST-segment-elevation myocardial infarction (STEMI) in particular is increasing at an unprecedented rate. Compounding the problem, outcomes remain suboptimal because of a lack of awareness and a severe paucity of resources. Guideline-based treatment has dramatically improved the outcomes of STEMI in high-income countries. However, no such focused recommendations exist for LMICs, and the unique challenges in LMICs make directly implementing Western guidelines unfeasible. Thus, structured solutions tailored to their individual, local needs, and resources are a vital need. With this in mind, a multicountry collaboration of investigators interested in LMIC STEMI care have tried to create a consensus document that extracts transferable elements from Western guidelines and couples them with local realities gathered from expert experience. It outlines general operating principles for LMICs focused best practices and is intended to create the broad outlines of implementable, resource-appropriate paradigms for management of STEMI in LMICs. Although this document is focused primarily on governments and organizations involved with improvement in STEMI care in LMICs, it also provides some specific targeted information for the frontline clinicians to allow standardized care pathways and improved outcomes. Show less
Vascular inflammation is present in many cardiovascular diseases, and exogenous glucocorticoids have traditionally been used as a therapy to suppress inflammation. However, recent data have shown... Show moreVascular inflammation is present in many cardiovascular diseases, and exogenous glucocorticoids have traditionally been used as a therapy to suppress inflammation. However, recent data have shown that endogenous glucocorticoids, acting through the endothelial glucocorticoid receptor, act as negative regulators of inflammation. Here, we performed ChIP for the glucocorticoid receptor, followed by next-generation sequencing in mouse endothelial cells to investigate how the endothelial glucocorticoid receptor regulates vascular inflammation. We identified a role of the Wnt signaling pathway in this setting and show that loss of the endothelial glucocorticoid receptor results in upregulation of Wnt signaling both in vitro and in vivo using our validated mouse model. Furthermore, we demonstrate glucocorticoid receptor regulation of a key gene in the Wnt pathway, Frzb, via a glucocorticoid response element gleaned from our genomic data. These results suggest a role for endothelial Wnt signaling modulation in states of vascular inflammation. Show less
Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far... Show morePurpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin-Siris patients (ARID1BCSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting.Methods: Clinicians entered clinical data in an extensive webbased survey.Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified.Conclusion: There are only minor differences between ARID1BID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features. Show less
