Management of Grade 1 Open Distal Radius Fractures: A Survey of Practicing Surgeons.

Introduction Standard of care management for open fractures historically mandates emergent systemic antibiotic administration, followed by urgent irrigation and debridement in the operating room, regardless of injury severity. However, significant controversy exists regarding the specific implementation and importance of these commonly accepted guidelines. We aimed to define differences in the management of grade 1 open distal radius fractures. Methods An anonymous online survey was distributed to attending surgeon members of either the Orthopaedic Trauma Association (OTA) between January 2019 and April 2019 or the New York Society for Surgery of the Hand (NYSSH) in January 2019. Results A total of 68 attending surgeons responded to the survey. A total of 24 OTA members and 40 NYSSH members replied and were included in the study. Several factors influenced management in addition to the level of contamination. Of the surgeons, 68% stated that litigation was not a major factor of concern. When compared to surgeons who trained in trauma fellowships, more surgeons who trained in hand/upper extremity fellowships considered closed reduction alone as reasonable definitive treatment (when excluding antibiotic administration and debridement considerations, p = 0.024) and oral antibiotics as a supplement to IV antibiotics (p < 0.001). Of the surgeons, 90% would nonoperatively treat a patient who presented with a grade 1 open distal radius fracture greater than 72 hours after injury with stable and acceptable alignment on X-rays. Conclusion Some surgeons are willing to deviate from standard-of-care management protocols.

Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome.

CTNND1 encodes the p120-catenin (p120) protein, which has a wide range of functions, including the maintenance of cell-cell junctions, regulation of the epithelial-mesenchymal transition and transcriptional signalling. Due to advances in next-generation sequencing, CTNND1 has been implicated in human diseases including cleft palate and blepharocheilodontic (BCD) syndrome albeit only recently. In this study, we identify eight novel protein-truncating variants, six de novo, in 13 participants from nine families presenting with craniofacial dysmorphisms including cleft palate and hypodontia, as well as congenital cardiac anomalies, limb dysmorphologies and neurodevelopmental disorders. Using conditional deletions in mice as well as CRISPR/Cas9 approaches to target CTNND1 in Xenopus, we identified a subset of phenotypes that can be linked to p120-catenin in epithelial integrity and turnover, and additional phenotypes that suggest mesenchymal roles of CTNND1. We propose that CTNND1 variants have a wider developmental role than previously described and that variations in this gene underlie not only cleft palate and BCD but may be expanded to a broader velocardiofacial-like syndrome.

PTEN Loss Mediates Clinical Cross-Resistance to CDK4/6 and PI3Kα Inhibitors in Breast Cancer.

The combination of CDK4/6 inhibitors with antiestrogen therapies significantly improves clinical outcomes in ER-positive advanced breast cancer. To identify mechanisms of acquired resistance, we analyzed serial biopsies and rapid autopsies from patients treated with the combination of the CDK4/6 inhibitor ribociclib with letrozole. This study revealed that some resistant tumors acquired RB loss, whereas other tumors lost PTEN expression at the time of progression. In breast cancer cells, ablation of PTEN, through increased AKT activation, was sufficient to promote resistance to CDK4/6 inhibition in vitro and in vivo. Mechanistically, PTEN loss resulted in exclusion of p27 from the nucleus, leading to increased activation of both CDK4 and CDK2. Because PTEN loss also causes resistance to PI3Kα inhibitors, currently approved in the post-CDK4/6 setting, these findings provide critical insight into how this single genetic event may cause clinical cross-resistance to multiple targeted therapies in the same patient, with implications for optimal treatment-sequencing strategies. SIGNIFICANCE: Our analysis of serial biopsies uncovered RB and PTEN loss as mechanisms of acquired resistance to CDK4/6 inhibitors, utilized as first-line treatment for ER-positive advanced breast cancer. Importantly, these findings have near-term clinical relevance because PTEN loss also limits the efficacy of PI3Kα inhibitors currently approved in the post-CDK4/6 setting.This article is highlighted in the In This Issue feature, p. 1.

Impact of a Resident-Guided Rounding Initiative on the Hospital Consumer Assessment of Healthcare Providers and Systems Survey Scores in Orthopaedic Surgery Inpatients.

Patient-centered medicine is becoming the main focus of many healthcare systems, and the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey is a tool used to track patient satisfaction. In this study, we evaluate the HCAHPS scores in orthopaedic surgery inpatients before and after implementation of a resident-guided rounding protocol. Analyses of the HCAHPS surveys for 154 orthopaedic surgical inpatients at one community hospital were compared 6 months before and after implementation of a resident-guided rounding initiative. Specific questions of the HCAHPS survey were analyzed using the top box, mean, and positive scores. Implementation of the rounding initiative resulted in an increase in the top box, mean, and positive scores for all questions evaluated; however, no significance was noted in the results, with the exception of the positive score for a staff cohesiveness question (P = 0.046). Physician and hospital recommendation questions showed a 5-point increase (91st to 96th percentile) compared with 42-point increase (21st to 63rd percentile) by publicly reported national data. Implementation of the rounding initiative resulted in increases in HCAHPS scores across multiple questions and domains; however, these were not significant. These results suggest that simple interventions can help increase the overall patient satisfaction and promote future investigations.

Subcutaneous extraskeletal osteosarcoma of the forearm: a case report and review of the literature.

Extraskeletal osteosarcoma (ESOS) originating in the subcutaneous tissue is a rare occurrence, accounting for less than 10 % of ESOS cases. Osteosarcoma of extraskeletal origin accounts for approximately 2-4 % of all osteosarcomas, and 1 % of soft tissue sarcomas. We report a case of an 80-year-old female with an isolated primary subcutaneous tumor of the forearm. After imaging, surgical excision, and pathological analysis, the diagnosis of a subcutaneous osteosarcoma was made. This report documents the clinical and pathological findings of subcutaneous ESOS in this case, along with a review of previous cases of subcutaneous ESOS.

Fuz mutant mice reveal shared mechanisms between ciliopathies and FGF-related syndromes.

Ciliopathies are a broad class of human disorders with craniofacial dysmorphology as a common feature. Among these is high arched palate, a condition that affects speech and quality of life. Using the ciliopathic Fuz mutant mouse, we find that high arched palate does not, as commonly suggested, arise from midface hypoplasia. Rather, increased neural crest expands the maxillary primordia. In Fuz mutants, this phenotype stems from dysregulated Gli processing, which in turn results in excessive craniofacial Fgf8 gene expression. Accordingly, genetic reduction of Fgf8 ameliorates the maxillary phenotypes. Similar phenotypes result from mutation of oral-facial-digital syndrome 1 (Ofd1), suggesting that aberrant transcription of Fgf8 is a common feature of ciliopathies. High arched palate is also a prevalent feature of fibroblast growth factor (FGF) hyperactivation syndromes. Thus, our findings elucidate the etiology for a common craniofacial anomaly and identify links between two classes of human disease: FGF-hyperactivation syndromes and ciliopathies.