Patella and Trochlea Osteochondritis Dissecans: Demographics and Treatment Paradigms.

OBJECTIVE: Previous research on patellar and trochlear groove osteochondritis dissecans (OCD) is limited by small sample sizes. This study aims to describe the presentation of patients with OCD lesions of the patella and trochlea and characterize the outcomes of operative and nonoperative treatments. METHODS: This retrospective cohort study identified all patients from a single institution from 2008 to 2021 with patellar and/or trochlear OCD lesions. Patients were excluded from the study if surgical records were unavailable or if the patient had knee surgery for a different injury at index surgery or in the 12 months postoperative. Minimum follow-up was 12 months. Outcomes included a return to sports (RTS), pain resolution, radiographic healing, and treatment "success" (defined as full RTS, complete pain resolution, and full healing on imaging). RESULTS: A total of 68 patients (75 knees) were included-45 (60%) with patellar OCD and 30 (40%) with trochlear. Of the patients, 69% were males. The median age at knee OCD diagnosis was 14 years. At the final follow-up, 62% of knees (n = 44) recovered sufficiently to allow a full RTS and 54% of knees (n = 39) had full pain resolution. Of the 46 knees with radiographic imaging at least 1 year apart, 63% had full healing of the lesion. There was no significant difference in RTS, pain resolution, radiographic healing, or overall success when comparing treatments. CONCLUSIONS: This study provides valuable epidemiologic demographic and outcome data regarding the scarcely reported patellar and trochlear OCD. While over half of patients fully returned to sports and reported full pain resolution, a large proportion continued to experience symptoms over a year after presentation. Future research should aim to better define the treatment algorithms for these OCD subtypes. LEVEL OF EVIDENCE: Level III.

Removing or Only Moving a Barrier? Screening Applications with US Medical Licensing Examination Step 2CK Instead of Step 1 May Benefit Women but Not Underrepresented Minorities in Orthopaedics.

Most orthopaedic surgery program directors report using a minimum score cutoff for the US Medical Licensing Examination Step 1 examination when evaluating residency applicants. The transition to a Pass/Fail grading system beginning in the 2022-2023 application cycle will alter applicant evaluation in the interview selection process. The impact of this change, particularly on women and underrepresented minority (URM) applicants, remains unclear. This study was designed to evaluate how a shift to screening applications using Step 2 Clinical Knowledge (CK) instead of Step 1 scores could impact selection for residency interviews. Methods: We reviewed all 855 Electronic Residency Application Service applications submitted to the University of Pennsylvania's orthopaedic surgery residency program in the 2020-2021 cycle. Applicant age, sex, medical school of graduation, self-identified race, and permanent zip code were evaluated for association with Step 1 and Step 2CK scores using a 2-sample t test. A multivariable linear regression analysis was conducted to understand the predictive value of demographic features and medical school features on Step 1 and 2CK scores. Results: Multivariable linear regression revealed both Step 1 and 2CK scores were lower for applicants of URM status (Step 1: p < 0.001; Step 2CK: p < 0.001) and from international medical schools (p = 0.043; p = 0.006). Step 1 scores but not Step 2CK scores were lower for applicants who were women (p < 0.001; p = 0.730), ≥30 years of age (p < 0.001; p = 0.079), and from medical schools outside the top 25 in National Institutes of Health (NIH) funding or US News and World Report (USNWR) ranking (p = 0.001; p = 0.193). Conclusions: Conversion of Step 1 grading to Pass/Fail may reduce barriers for groups with lower average Step 1 scores (URM, female, ≥30 years of age, and from institutions with lower NIH funding or USNWR rankings). However, if Step 2CK scores replace Step 1 as a screening tool, groups with lower Step 2CK scores, notably URM applicants, may not experience this benefit. Level of Evidence: Level IV. See Instructions for Authors for a complete description of levels of evidence.

Association of Thoracic MRI Findings With Specialty and Training.

STUDY DESIGN: Retrospective. OBJECTIVE: To compare the rate of positive pathology on thoracic MRI ordered by surgical spine specialists to those ordered by nonsurgical spine specialists. METHODS: Outpatient thoracic MRIs from January-March 2019 were evaluated from a single academic health care system. Studies without a known ordering provider, imaging report, or patients with known presence of malignancy, multiple sclerosis, recent trauma, or surgery were excluded (n = 320). Imaging studies were categorized by type of provider placing the order (resident, attending, or advanced practice practitioner) and department. MRIs were deemed positive if they showed relevant pathology that correlated with indication for exam as determined by a radiologist. One-sided chi-squared analysis was performed to determine statistical significance. RESULTS: Overall, our data demonstrated 17.2% of studies with positive pathology. Compared to nonspecialty clinicians, subspecialists showed 35/184 (19.0%) positivity rate versus the non-specialist with 20/136 (14.7%) positivity rate (P = .156). Posthoc analysis demonstrated that surgical specialists who order thoracic MRIs yield significantly higher positivity rates at 19/79 (24.0%) compared to nonsurgical specialists at 36/241 (14.9%) (P < .05). Overall, neurosurgery demonstrated the highest rate of positive thoracic MRIs at 14/40 (35.0%). Comparison between the rate of positivity between physicians and advanced practitioners was insignificant (P > .05). CONCLUSIONS: Clinical diagnosis of symptomatic thoracic spine degenerative disease requires an expert physical exam combined with careful attention to radiology findings. Although the percent of relevant pathology on thoracic MRI is low, our data suggests evaluation by a surgical specialist should precede ordering a thoracic spine MRI.

Orthopaedic Surgery Residency Program Social Media Presence During the COVID-19 Pandemic.

In light of away rotation and in-person interview cancellations for the 2020 to 2021 application cycle, social media has become a popular tool for orthopaedic surgery residency programs to highlight their strengths, curricula, and social life to prospective applicants. The authors sought to explore the proliferation and utilization of 3 popular social media platforms by both orthopaedic surgery departments and residencies. METHODS: Orthopaedic surgery departmental and residency program social media accounts and their creation dates across Facebook, Twitter, and Instagram were identified using a standardized search methodology. Residency Instagram accounts were further evaluated for the number of posts, followers, likes, and comments. Both departments and residency programs were cohorted by affiliation with a US News &World Report (USNWR) top 50 American hospital for orthopaedics or by status as a Doximity top 20 program based on reputation. RESULTS: Across a total of 192 residency programs included for analysis, Instagram was the most popular social media platform (61.5%), followed by Twitter (19.8%) and Facebook (10.4%). Conversely, orthopaedic departments more frequently used Facebook (33.9%) and Twitter (28.1%) over Instagram (17.2%). Of the 118 residency Instagram accounts, 102 (86.4%) were created after the onset of the COVID-19 pandemic. Larger residency programs (≥6 spots/year) and those programs in the Doximity top 20 or affiliated with USNWR top 50 orthopaedic hospitals had a greater number of followers as well as likes and comments per post (p < 0.05 for all). CONCLUSIONS: Given the recruitment challenges faced by residency programs because of the COVID-19 pandemic, Instagram has rapidly become a prominent platform for attracting orthopaedic surgery applicants. These accounts have a large number of followers, particularly for residency programs with higher Doximity reputation rankings.

The current state of animal models in research: A review.

Animal models have provided invaluable information in the pursuit of medical knowledge and alleviation of human suffering. The foundations of our basic understanding of disease pathophysiology and human anatomy can largely be attributed to preclinical investigations using various animal models. Recently, however, the scientific community, citing concerns about animal welfare as well as the validity and applicability of outcomes, has called the use of animals in research into question. In this review, we seek to summarize the current state of the use of animal models in research.

Modulation of neuroinflammation and memory dysfunction using percutaneous vagus nerve stimulation in mice.

BACKGROUND: The vagus nerve is involved in regulating immunity and resolving inflammation. Current strategies aimed at modulating neuroinflammation and cognitive decline, in many cases, are limited and ineffective. OBJECTIVE: We sought to develop a minimally invasive, targeted, vagus nerve stimulation approach (pVNS), and we tested its efficacy with respect to microglial activation and amelioration of cognitive dysfunction following lipopolysaccharide (LPS) endotoxemia in mice. METHODS: We stimulated the cervical vagus nerve in mice using an ultrasound-guided needle electrode under sevoflurane anesthesia. The concentric bipolar needle electrode was percutaneously placed adjacent to the carotid sheath and stimulation was verified in real-time using bradycardia as a biomarker. Activation of vagal fibers was confirmed with immunostaining in relevant brainstem structures, including the dorsal motor nucleus and nucleus tractus solitarius. Efficacy of pVNS was evaluated following administration of LPS and analyses of changes in inflammation and behavior. RESULTS: pVNS enabled stimulation of the vagus nerve as demonstrated by changes in bradycardia and histological evaluation of c-Fos and choline acetyltransferase expression in brainstem nuclei. Following LPS administration, pVNS significantly reduced plasma levels of tumor necrosis factor-α at 3 h post-injection. pVNS prevented LPS-induced hippocampal microglial activation as analyzed by changes in Iba-1 immunoreactivity, including cell body enlargement and shortened ramifications. Cognitive dysfunction following endotoxemia was also restored by pVNS. CONCLUSION: Targeted cervical VNS using this novel percutaneous approach reduced LPS-induced systemic and brain inflammation and significantly improved cognitive responses. These results provide a novel therapeutic approach using bioelectronic medicine to modulate neuro-immune interactions that affect cognition.

Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase.

The Aurora kinases play critical roles in the regulation of mitosis and are frequently overexpressed or amplified in human tumors. Selective inhibitors may provide a new therapy for the treatment of tumors with Aurora kinase amplification. Herein we describe our lead optimization efforts within a 7-azaindole-based series culminating in the identification of GSK1070916 (17k). Key to the advancement of the series was the introduction of a 2-aryl group containing a basic amine onto the azaindole leading to significantly improved cellular activity. Compound 17k is a potent and selective ATP-competitive inhibitor of Aurora B and C with K(i)* values of 0.38 +/- 0.29 and 1.5 +/- 0.4 nM, respectively, and is >250-fold selective over Aurora A. Biochemical characterization revealed that compound 17k has an extremely slow dissociation half-life from Aurora B (>480 min), distinguishing it from clinical compounds 1 and 2. In vitro treatment of A549 human lung cancer cells with compound 17k results in a potent antiproliferative effect (EC(50) = 7 nM). Intraperitoneal administration of 17k in mice bearing human tumor xenografts leads to inhibition of histone H3 phosphorylation at serine 10 in human colon cancer (Colo205) and tumor regression in human leukemia (HL-60). Compound 17k is being progressed to human clinical trials.

Novel ATP-competitive kinesin spindle protein inhibitors.

Kinesin spindle protein (KSP), an ATPase responsible for spindle pole separation during mitosis that is present only in proliferating cells, has become a novel and attractive anticancer target with potential for reduced side effects compared to currently available therapies. We report herein the discovery of the first known ATP-competitive inhibitors of KSP, which display a unique activity profile as compared to the known loop 5 (L5) allosteric KSP inhibitors that are currently under clinical evaluation. Optimization of this series led to the identification of biphenyl sulfamide 20, a potent KSP inhibitor with in vitro antiproliferative activity against human cells with either wild-type KSP (HCT116) or mutant KSP (HCT116 D130V). In a murine xenograft model with HCT116 D130V tumors, 20 showed significant antitumor activity following intraperitoneal dosing, providing in vivo proof-of-principle of the efficacy of an ATP-competitive KSP inhibitor versus tumors that are resistant to the other known KSP inhibitors.