Association Between Preoperative Patient Resilience and Patient-Reported Outcomes After Rotator Cuff Repair.

Background: Mental and emotional health can affect outcomes after orthopaedic surgery, and patient resilience has been found to be significantly related to postoperative functional outcomes. Purpose: To evaluate the relationship between preoperative patient resilience and 2-year postoperative patient-reported outcomes after rotator cuff repair (RCR). It was hypothesized that patients with low preoperative resilience will have worse patient-reported outcomes at 2 years after RCR versus those with high resilience. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent primary arthroscopic RCR in 2020 at a single institution and completed the Brief Resilience Scale (BRS) preoperatively were identified. Other inclusion criteria were American Shoulder and Elbow Surgeons (ASES) and Single Assessment Numeric Evaluation (SANE) scores at the 2-year follow-up. Outcomes were compared in patients as divided into low resilience (BRS score >1 SD below the mean), normal resilience (BRS score ≤1 SD of the mean), and high resilience (BRS score >1 SD above the mean) groups. Results: Overall, 100 patients (52 male, 48 female; mean age, 60 ± 9 years) were included in this study. Mean BRS scores did not change significantly from preoperative to 2-year follow-up (3.8 ± 0.7 vs 3.9 ± 0.8, P = .404). All patients had preoperative ASES scores. Low-resilience patients (n = 17) had significantly lower preoperative ASES scores compared with normal (n = 64) and high resilience (n = 19) patients (35 vs 42 vs 54, respectively; P = .022). There were no significant group differences in postoperative outcomes (revision rate, ASES score, ASES score improvement from preoperative to 2-year follow-up, or SANE score). Multivariate analysis indicated that preoperative resilience was not significantly associated with ASES score improvement (ß estimate = -5.64, P = .150), while resilience at 2-year follow-up was significantly related to ASES score improvement (ß estimate = 6.41, P = .031). Conclusion: Patient-reported outcomes at 2-year follow-up did not differ based on preoperative patient resilience for arthroscopic RCR patients. Multivariate analysis also showed that preoperative resilience was not associated with improvement in ASES scores; however, resilience at 2-year follow-up was associated with ASES score improvement.

Tumor microenvironmental determinants of high-risk DCIS progression.

Ductal carcinoma in situ (DCIS) constitutes an array of morphologically recognized intraductal neoplasms in the mammary ductal tree defined by an increased risk for subsequent invasive carcinomas at or near the site of biopsy detection. However, only 15-45% of untreated DCIS cases progress to invasive cancer, so understanding mechanisms that prevent progression is key to avoid overtreatment and provides a basis for alternative therapies and prevention. This study was designed to characterize the tumor microenvironment and molecular profile of high-risk DCIS that grew to a large size but remained as DCIS. All patients had DCIS lesions >5cm in size with at least one additional high-risk feature: young age (<45 years), high nuclear grade, hormone receptor negativity, HER2 positivity, the presence of comedonecrosis, or a palpable mass. The tumor immune microenvironment was characterized using multiplex immunofluorescence to identify immune cells and their spatial relationships within the ducts and stroma. Gene copy number analysis and whole exome DNA sequencing identified the mutational burden and driver mutations, and quantitative whole-transcriptome/gene expression analyses were performed. There was no association between the percent of the DCIS genome characterized by copy number variants (CNAs) and recurrence events (DCIS or invasive). Mutations, especially missense mutations, in the breast cancer driver genes PIK3CA and TP53 were common in this high-risk DCIS cohort (47% of evaluated lesions). Tumor infiltrating lymphocyte (TIL) density was higher in DCIS lesions with TP53 mutations (p=0.0079) compared to wildtype lesions, but not in lesions with PIK3CA mutations (p=0.44). Immune infiltrates were negatively associated with hormone receptor status and positively associated with HER2 expression. High levels of CD3+CD8- T cells were associated with good outcomes with respect to any subsequent recurrence (DCIS or invasive cancer), whereas high levels of CD3+Foxp3+ Treg cells were associated with poor outcomes. Spatial proximity analyses of immune cells and tumor cells demonstrated that close proximity of T cells with tumor cells was associated with good outcomes with respect to any recurrence as well as invasive recurrences. Interestingly, we found that myoepithelial continuity (distance between myoepithelial cells surrounding the involved ducts) was significantly lower in DCIS lesions compared to normal tissue (p=0.0002) or to atypical ductal hyperplasia (p=0.011). Gene set enrichment analysis identified several immune pathways associated with low myoepithelial continuity and a low myoepithelial continuity score was associated with better outcomes, suggesting that gaps in the myoepithelial layer may allow access/interactions between immune infiltrates and tumor cells. Our study demonstrates the immune microenvironment of DCIS, in particular the spatial proximity of tumor cells and T cells, and myoepithelial continuity are important determinants for progression of disease.

Comparing the Performance of ChatGPT-4 and Medical Students on MCQs at Varied Levels of Bloom's Taxonomy.

Introduction: This research investigated the capabilities of ChatGPT-4 compared to medical students in answering MCQs using the revised Bloom's Taxonomy as a benchmark. Methods: A cross-sectional study was conducted at The University of the West Indies, Barbados. ChatGPT-4 and medical students were assessed on MCQs from various medical courses using computer-based testing. Results: The study included 304 MCQs. Students demonstrated good knowledge, with 78% correctly answering at least 90% of the questions. However, ChatGPT-4 achieved a higher overall score (73.7%) compared to students (66.7%). Course type significantly affected ChatGPT-4's performance, but revised Bloom's Taxonomy levels did not. A detailed association check between program levels and Bloom's taxonomy levels for correct answers by ChatGPT-4 showed a highly significant correlation (p<0.001), reflecting a concentration of "remember-level" questions in preclinical and "evaluate-level" questions in clinical courses. Discussion: The study highlights ChatGPT-4's proficiency in standardized tests but indicates limitations in clinical reasoning and practical skills. This performance discrepancy suggests that the effectiveness of artificial intelligence (AI) varies based on course content. Conclusion: While ChatGPT-4 shows promise as an educational tool, its role should be supplementary, with strategic integration into medical education to leverage its strengths and address limitations. Further research is needed to explore AI's impact on medical education and student performance across educational levels and courses.

Pharmaceutical and biotech industry perspectives on optimizing patient experience and treatment adherence through subcutaneous drug delivery design.

Subcutaneous (SC) drug delivery can be a safe, effective alternative to the traditional intravenous route of administration, potentially offering notable advantages for both patients and healthcare providers. The SC Drug Development & Delivery Consortium convened in 2018 to raise awareness of industry challenges to advance the development of patient-centric SC drug delivery strategies. The SC Consortium identified better understanding of patient preferences and perspectives as necessary to optimize SC product design attributes and help guide design decisions during SC product development. This manuscript provides a comprehensive overview of patient-centric factors for consideration in the SC drug delivery design and development process with the aim of establishing a foundation of existing knowledge for patient experiences related to SC drug delivery. This overview is informed by the outcomes of a multi-step survey of Consortium members and key pharmaceutical stakeholders. Framed in the context of the patient's treatment journey, the survey findings offer future perspectives to fill data gaps to advance patient-centric SC drug delivery.

Performance evaluation of the FastIC readout ASIC with emphasis on Cherenkov emission in TOF-PET.

Objective.The efficient usage of prompt photons like Cherenkov emission is of great interest for the design of the next generation, cost-effective, and ultra-high-sensitivity time-of-flight positron emission tomography (TOF-PET) scanners. With custom, high power consuming, readout electronics and fast digitization the prospect of sub-300 ps FWHM with PET-sized BGO crystals have been shown. However, these results are not scalable to a full system consisting of thousands of detector elements.Approach.To pave the way toward a full TOF-PET scanner, we examine the performance of the FastIC ASIC with Cherenkov-emitting scintillators (BGO), together with one of the most recent SiPM detector developments based on metal trenching from FBK. The FastIC is a highly configurable ASIC with 8 input channels, a power consumption of 12 mW ch-1and excellent linearity on the energy measurement. To put the timing performance of the FastIC into perspective, comparison measurements with high-power consuming readout electronics are performed.Main results.We achieve a best CTR FWHM of 330 ps for 2 × 2 × 3 mm3and 490 ps for 2 × 2 × 20 mm3BGO crystals with the FastIC. In addition, using 20 mm long LSO:Ce:Ca crystals, CTR values of 129 ps FWHM have been measured with the FastIC, only slightly worse to the state-of-the-art of 95 ps obtained with discrete HF electronics.Significance.For the first time, the timing capability of BGO with a scalable ASIC has been evaluated. The findings underscore the potential of the FastIC ASIC in the development of cost-effective TOF-PET scanners with excellent timing characteristics.

Physiological and Molecular Mechanisms Associated with Potato Tuber Dormancy.

Tuber dormancy is an important physiological trait that impacts postharvest storage and end use qualities of potatoes. Overall, dormancy regulation of potato tuber is a complex process driven by genetic as well as environmental factors. Elucidation of the molecular and physiological mechanisms that influence different dormancy stages of tuber has wider potato breeding and industry relevant implications. Therefore, the primary objective of this review is to present the current knowledge on the diversity in tuber dormancy traits among wild relatives of potatoes and discuss how genetic and epigenetic factors contribute to the tuber dormancy. Advancements in understanding of key physiological mechanisms involved in tuber dormancy regulations, such as apical dominance, phytohormone metabolism, and oxidative stress responses were also discussed. This review highlights the impacts of common sprout suppressors on the molecular and physiological mechanisms associated with tuber dormancy and other storage qualities. Collectively, the literature suggests that significant changes in expressions of genes associated with cell cycle, phytohormone metabolism, and oxidative stress response influence initiation, maintenance, and termination of dormancy in potato tubers. Commercial sprout suppressors mainly alter the expressions of genes associated with cell cycle and stress responses and suppress sprout growth rather than prolonging the tuber dormancy.

Lysophosphatidic Acid Receptor 1 (LPA1) Antagonists as Potential Migrastatics for Triple Negative Breast Cancer.

Metastasis is responsible for about 90 % of cancer deaths. Anti-metastatic drugs, termed as migrastatics, offer a distinctive therapeutic approach to address cancer migration and invasion. However, therapeutic exploitation of metastasis-specific targets remains limited, and the effective prevention and suppression of metastatic cancer continue to be elusive. Lysophosphatidic acid receptor 1 (LPA1) is activated by an endogenous lipid molecule LPA, leading to a diverse array of cellular activities. Previous studies have shown that the LPA/LPA1 axis supports the progression of metastasis for many types of cancer. In this study, we report the synthesis and biological evaluation of fluorine-containing triazole derivatives as potent LPA1 antagonists, offering potential as migrastatic drugs for triple negative breast cancer (TNBC). In particular, compound 12 f, the most potent and highly selective in this series with an IC50 value of 16.0 nM in the cAMP assay and 18.4 nM in the calcium mobilization assay, inhibited cell survival, migration, and invasion in the TNBC cell line. Interestingly, the compound did not induce apoptosis in TNBC cells and demonstrated no cytotoxic effects. These results highlight the potential of LPA1 as a migrastatic target. Consequently, the LPA1 antagonists developed in this study hold promise as potential migrastatic candidates for TNBC.

Evaluation of Failed ACL Reconstruction: An Updated Review.

Failure rates among primary Anterior Cruciate Ligament Reconstruction (ACLR) range from 3.2% to 11.1%. Recently, there has been increased focus on surgical and anatomic considerations which predispose patients to failure, including excessive posterior tibial slope (PTS), unaddressed high-grade pivot shift, and improper tunnel placement. The purpose of this review was to provide a current summary and analysis of the literature regarding patient-related and technical factors surrounding revision ACLR, rehabilitation considerations, overall outcomes and return to sport (RTS) for patients who undergo revision ACLR. There is a convincingly higher re-tear and revision rate in patients who undergo ACLR with allograft than autograft, especially amongst the young, athletic population. Unrecognized Posterior Cruciate Ligament (PLC) injury is a common cause of ACLR failure and current literature suggests concurrent operative management of high-grade PLC injuries. Given the high rates of revision surgery in young active patients who return to pivoting sports, the authors recommend strong consideration of a combined ACLR + Anterolateral Ligament (ALL) or Lateral extra-articular tenodesis (LET) procedure in this population. Excessive PTS has been identified as an independent risk factor for ACL graft failure. Careful consideration of patient-specific factors such as age and activity level may influence the success of ACL reconstruction. Additional technical considerations including graft choice and fixation method, tunnel position, evaluation of concomitant posterolateral corner and high-grade pivot shift injuries, and the role of excessive posterior tibial slope may play a significant role in preventing failure.

Self-reported side effects of COVID-19 vaccines among health professions students in India.

Studies focusing on the safety and common side effects of vaccines play a crucial role in enhancing public acceptance of vaccination. Research is scarce regarding the usage of COVID-19 vaccines and the side effects experienced by health professions students in India and other countries. This study aimed to document self-reported side effects associated with COVID-19 vaccination among medical and dental students of six medical and dental colleges and teaching hospitals in four states (Tamil Nadu, Madhya Pradesh, Gujarat, and West Bengal) of India. A cross-sectional survey using purposive sampling of medical and dental students was conducted from 26 April to 26 May 2021. Data was collected using a Google Forms questionnaire capturing information regarding receiving COVID-19 vaccines, side effects and symptoms, onset and duration of symptoms, use of treatment to alleviate symptoms, awareness of haematologic risks associated with vaccination, and side effects from previous (non-COVID-19) vaccinations. The majority (94.5%) of participants received both doses of the Covishield/AstraZeneca COVID-19 vaccine. Among participants (n = 492), 45.3% (n = 223) reported one or more side effects. The most frequently reported side effects were soreness of the injected arm (80.3%), tiredness (78.5%), fever (71.3%), headache (64.1%), and hypersomnia (58.7%). The two most common severe symptoms were fever (14.8%) and headache (13%). Most side effects appeared on the day of vaccination: soreness of the injection site (57%), fever (43.1%), and tiredness (42.6%). Most reported symptoms persisted for one to three days-soreness of the injection site (53%), fever (47.1%), and headache (42.6%). Logistic regression showed that women were almost 85% less likely to report side effects. The study's findings corroborate the safety of the Covishield/AstraZeneca vaccine's first dose, evidenced by the relatively minor and transient nature of the side effects. However, the study underscores the necessity for ongoing research to assess the long-term impacts of COVID-19 vaccines, especially in the context of booster doses, thereby contributing to the global understanding of vaccine safety and efficacy.

Knowledge, Attitudes, and Practices of Hand Hygiene, Mask Use, and Social Distancing among Public Hospital and Polyclinic Nurses in Barbados during the Coronavirus 2019 Pandemic.

BACKGROUND: Nurses are essential members of the healthcare workforce and were among the first-line carers for patients in community and hospital settings during the COVID-19 pandemic. As a result, they were at a heightened risk of infection, resulting in several reported deaths among nursing staff. Several preventive measures were adopted to contain the spread of the COVID-19 virus. This study aims to explore the knowledge, attitudes, and practices (KAP) of nurses regarding hand hygiene, mask wearing, and social distancing measures in healthcare settings in Barbados during the COVID-19 pandemic. METHOD: An online survey of nurses working in public hospitals and polyclinics (public primary care clinics) in Barbados from March 2021 to December 2021 was conducted. A nonsystematic convenience sampling method was employed to recruit nurses who were readily available and willing to participate. A questionnaire captured the sociodemographic information and knowledge and practices related to hand hygiene, the use of face masks, and social distancing. Each correct response received one mark. Overall knowledge scores were categorized as poor (<60%), average (60-80%), or good (>80-100%). RESULTS: Of the 192 participants, the majority were female (82.8%) and had >5 years of experience (82%). The findings revealed that 45.8% had poor knowledge of hand hygiene, and that the knowledge of 43.8% of respondents was average. Multivariable logistic regression showed that, after adjustment for age and gender, registered nurses had 2.1 times increased odds (95% confidence interval 1.0, 4.2) of having good knowledge compared to other nursing categories. Regarding mask wearing, 53.6% of nurses had average knowledge, and 27.1% had good knowledge. Multivariable logistic regression showed that, after adjustment for age and gender, registered nurses had 3.3 times increased odds (95% confidence interval 1.5, 7.4) of having good knowledge compared to nursing assistants. A total of 68.6% of respondents followed the correct steps of handwashing every time, and 98.3% wore a mask in public places. More than half of the nurses (51.2%) kept a safe distance from others to avoid spreading SARS-CoV-2; one-third were in a crowded place(s) in the past three months, and 55.8% usually followed guidelines for social isolation as recommended by the WHO. CONCLUSIONS: The study identified knowledge deficiencies related to hand hygiene and wearing masks among nurses. It is imperative to provide additional training on infection control measures.

Cardiac Involvement in Patients With Multisystem Inflammatory Syndrome in Adults.

Multisystemic inflammatory syndrome in adults is a hyperinflammatory condition following (within 4-12 weeks) SARS-CoV-2 infection. Here, the dysregulation of the immune system leads to a multiorgan involvement often affecting the heart. Cardiac involvement in multisystemic inflammatory syndrome in adults has been described mainly in young men without other comorbidities and may present with different clinical scenarios, including acute heart failure, life-threatening arrhythmias, pericarditis, and myocarditis, with a nonnegligible risk of mortality (up to 7% of all cases). The heterogeneity of its clinical features and the absence of a clear case definition make the differential diagnosis with other postinfectious (eg, infective myocarditis) and hyperinflammatory diseases (eg, adult Still disease and macrophage activation syndrome) challenging. Moreover, the evidence on the efficacy of specific treatments targeting the hyperinflammatory response underlying this clinical condition (eg, glucocorticoids, immunoglobulins, and other immunomodulatory agents) is sparse and not supported by randomized clinical trials. In this review article, we aim to provide an overview of the clinical features and the diagnostic workup of multisystemic inflammatory syndrome in adults with cardiac involvement, highlighting the possible pathogenetic mechanisms and the therapeutic management, along with remaining knowledge gaps in this field.

A scoping review of endoscopic and robotic techniques for lateral neck dissection in thyroid cancer.

Introduction: Lateral neck dissection (LND) in thyroid cancer has traditionally been performed by a transcervical technique with a large collar incision. With the rise of endoscopic, video-assisted, and robotic techniques for thyroidectomy, minimally invasive LND is now being performed more frequently, with better cosmetic outcomes. Methods: The purpose of this paper is to review the different minimally invasive and remote access techniques for LND in thyroid cancer. A comprehensive literature review was performed using PubMed and Google Scholar search terms "thyroid cancer" and "lateral neck dissection" and "endoscopy OR robot OR endoscopic OR video-assisted". Results: There are multiple surgical options now available within each subset of endoscopic, video-assisted, and robotic LND. The approach dictates the extent of the LND but almost all techniques access levels II-IV, with variability on levels I and V. This review provides an overview of the indications, contraindications, surgical and oncologic outcomes for each technique. Discussion: Though data remains limited, endoscopic and robotic techniques for LND are safe, with improved cosmetic results and comparable oncologic and surgical outcomes. Similar to patient selection in minimally invasive thyroidectomy, it is important to consider the extent of the LND and select appropriate surgical candidates.

Incidence, Presentation, and Natural History of Adrenal Hemorrhage: An Institutional Analysis.

INTRODUCTION: Adrenal hemorrhage (AH) can occur due to multiple etiologies with variable radiographic appearance, often indistinguishable from underlying adrenal neoplasms. There is a lack of AH literature and evidence-based guidelines. Our study aimed to understand the prevalence and etiology of AH, follow-up, and incidence of underlying neoplasm. METHODS: An institutional database was queried from January 2006 to October 2021 for patients with AH on imaging, excluding patients with known malignancies, adrenal masses, or prior adrenal surgery. Demographics, medical history, hematoma size, laterality, biochemical evaluation, intervention, and additional imaging were reviewed. RESULTS: Of 490,301 imaging reports queried, 530 (0.11%) with AH met inclusion criteria. Most imaging (n = 485, 91.5%) was performed during trauma evaluation. Two patients underwent dedicated intervention at presentation. Interval imaging was performed in 114 (21.5%) patients at a median of 2.6 (interquartile range 0.99-13.4) mo, with resolution (n = 84, 73.7%) or decreased size of AH (n = 21, 18.4%) in most patients. Only 10 patients (1.9%) saw an outpatient provider in our system to address AH or evaluate for underlying mass, and 9 (1.7%) underwent biochemical screening. Thirteen patients (11% of 118 patients with any follow-up) had evidence of an adrenal mass, confirmed on serial imaging (n = 10) or adrenalectomy (n = 3). Scans performed for nontrauma indications were significantly more likely to have an underlying mass (n = 6/26 [23.1%]) than those performed for trauma evaluation (n = 7/92 [7.6%], P = 0.04). CONCLUSIONS: AH is a rare finding associated with an increased rate of underlying adrenal mass, particularly when unrelated to trauma. Most AH resolves spontaneously without intervention. Follow-up imaging at 6 mo can help distinguish mass-associated AH from simple hemorrhage.

Who Serves Where: A Geospatial Analysis of Access to Endocrine Surgeons in the United States and Puerto Rico.

BACKGROUND: The association between surgical volume and patient outcome is well established, with higher case volume associated with a lower risk of complications. We hypothesized that the geographic distribution of endocrine/head and neck surgeons with an endocrine focus in the United States and Puerto Rico may limit access to many potential patients, particularly in rural areas. METHODS: We used web-based directories from the American Association of Endocrine Surgeons, American Head and Neck Society, and the American Academy of Otolaryngology-Head and Neck Surgery to identify endocrine surgery specialists in the United States and Puerto Rico. Using geographic coordinates and OpenStreetMap and Valhalla software, we calculated the areas within a 60-, 90-, or 120-minute driving distance from specialist offices. We used 2020 U.S. Census Data to calculate census tract populations inside or outside the accessible areas. RESULTS: Excluding duplicate providers across organizations, we geocoded 603 specialist addresses in the United States and Puerto. We found that 23.76% (78.3 million) of Americans do not have access to a society-affiliated endocrine/head and neck surgeon with an endocrine focus within a 60-minute drive, 14.37% (47.4 million) within a 90-minute drive, and 8.38% (27.6 million) within a 120-minute drive. We observed that the areas of coverage are primarily focused on metropolitan areas. CONCLUSION: Nearly one-third of Americans do not have access to a society-affiliated endocrine/head and neck surgeon with an endocrine focus within a 1-hour drive, highlighting a concerning geographic barrier to care. Further work is needed to facilitate patient access and mitigate disparities in quality care.

Protein signaling and drug target activation signatures to guide therapy prioritization: Therapeutic resistance and sensitivity in the I-SPY 2 Trial.

Molecular subtyping of breast cancer is based mostly on HR/HER2 and gene expression-based immune, DNA repair deficiency, and luminal signatures. We extend this description via functional protein pathway activation mapping using pre-treatment, quantitative expression data from 139 proteins/phosphoproteins from 736 patients across 8 treatment arms of the I-SPY 2 Trial (ClinicalTrials.gov: NCT01042379). We identify predictive fit-for-purpose, mechanism-of-action-based signatures and individual predictive protein biomarker candidates by evaluating associations with pathologic complete response. Elevated levels of cyclin D1, estrogen receptor alpha, and androgen receptor S650 associate with non-response and are biomarkers for global resistance. We uncover protein/phosphoprotein-based signatures that can be utilized both for molecularly rationalized therapeutic selection and for response prediction. We introduce a dichotomous HER2 activation response predictive signature for stratifying triple-negative breast cancer patients to either HER2 or immune checkpoint therapy response as a model for how protein activation signatures provide a different lens to view the molecular landscape of breast cancer and synergize with transcriptomic-defined signatures.

Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer.

Importance: There has been little consideration of genomic risk of recurrence by breast cancer subtype despite evidence of racial disparities in breast cancer outcomes. Objective: To evaluate associations between clinical trial end points, namely pathologic complete response (pCR) and distant recurrence-free survival (DRFS), and race and examine whether gene expression signatures are associated with outcomes by race. Design, Setting, and Participants: This retrospective cohort study used data from the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2 (I-SPY 2) multicenter clinical trial of neoadjuvant chemotherapy with novel agents and combinations for patients with previously untreated stage II/III breast cancer. Analyses were conducted of associations between race and short- and long-term outcomes, overall and by receptor subtypes, and their association with 28 expression biomarkers. The trial enrolled 990 female patients between March 30, 2010, and November 5, 2016, with a primary tumor size of 2.5 cm or greater and clinical or molecular high risk based on MammaPrint or hormone receptor (HR)-negative/ERBB2 (formerly HER2 or HER2/neu)-positive subtyping across 9 arms. This data analysis was performed between June 10, 2021, and October 20, 2022. Exposure: Race, tumor receptor subtypes, and genomic biomarker expression of early breast cancer. Main Outcomes and Measures: The primary outcomes were pCR and DRFS assessed by race, overall, and by tumor subtype using logistic regression and Cox proportional hazards regression models. The interaction between 28 expression biomarkers and race, considering pCR and DRFS overall and within subtypes, was also evaluated. Results: The analytic sample included 974 participants (excluding 16 self-reporting as American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, or multiple races due to small sample sizes), including 68 Asian (7%), 120 Black (12%), and 786 White (81%) patients. Median (range) age at diagnosis was 47 (25-71) years for Asian, 49 (25-77) for Black, and 49 (23-73) years for White patients. The pCR rates were 32% (n = 22) for Asian, 30% for Black (n = 36), and 32% for White (n = 255) patients (P = .87). Black patients with HR-positive/ERBB2-negative tumors not achieving pCR had significantly worse DRFS than their White counterparts (hazard ratio, 2.28; 95% CI, 1.24-4.21; P = .01), with 5-year DRFS rates of 55% (n = 32) and 77% (n = 247), respectively. Black patients with HR-positive/ERBB2-negative tumors, compared with White patients, had higher expression of an interferon signature (mean [SD], 0.39 [0.87] and -0.10 [0.99]; P = .007) and, compared with Asian patients, had a higher mitotic score (mean [SD], 0.07 [1.08] and -0.69 [1.06]; P = .01) and lower estrogen receptor/progesterone receptor signature (mean [SD], 0.31 [0.90] and 1.08 [0.95]; P = .008). A transforming growth factor ß signature had a significant association with race relative to pCR and DRFS, with a higher signature associated with lower pCR and worse DRFS outcomes among Black patients only. Conclusions and Relevance: The findings show that women with early high-risk breast cancer who achieve pCR have similarly good outcomes regardless of race, but Black women with HR-positive/ERBB2-negative tumors without pCR may have worse DRFS than White women, highlighting the need to develop and test novel biomarker-informed therapies in diverse populations.

Medical Educators' Perceptions and Experiences of Transgender Curriculum in Barbados.

Purpose: This study explored medical educators' understanding of the term transgender and their attitudes and perspectives regarding (1) health system responsiveness to transgender needs and (2) transgender curriculum in medical education. Methods: The study employed purposive sampling of medical educators responsible for design and delivery of curriculum. Fifteen of 18 eligible educators participated in Zoom focus groups (FG1 n=7, FG2 n=8). FGs averaged 93 min and were recorded, transcribed verbatim, and analyzed using a qualitative interpretivist methodology with deductive and inductive coding assisted by NVivo 12 Pro software. Results: Educators were knowledgeable about the term transgender and the physical and psychosocial needs of transgender people. Participants viewed transgender care as a significant emerging health area. However, infrequent personal or clinical contact, coupled with constraints in human and other resources, resulted in the perception that transgender content as a stand-alone component of curriculum is difficult to justify. Participants articulated a need for broad-based diversity content, including disabilities, primarily at the undergraduate level. Educators saw transgender health as relevant for undergraduate-level psychiatry and postgraduate medical specializations. Analysis and discussion framed participant perspectives in the context of stigma, discrimination, and medicolegal and health systems that impede access to health care for transgender people. Conclusion: Participants demonstrated knowledge of transgender and transgender health care needs. Areas for improvements in health care responsiveness were identified, particularly related to structural stigma and discrimination. Although participants expressed interest in including transgender health in the curriculum, this would require pragmatic optimization of teaching resources.

Outcomes of Osteochondral Allograft Transplantation: A Comparative Study of BioUni and Snowman Techniques for Ovoid Lesions.

BACKGROUND: Treatment of large articular cartilage lesions of the knee includes surgical options one of which includes cartilage replacement therapies. Among these therapies include osteochondral allograft (OCA) transplantation, which can be performed utilizing a BioUni® (Arthrex BioUni® Instrumentation System; Arthrex, Naples, FL) replacement and a 'snowman' technique of repair. HYPOTHESIS/PURPOSE: To compare clinical and radiographic outcomes in patients who have undergone multiplug OCA transplantations utilizing a BioUni® replacement and a 'snowman' technique of repair. METHODS: Patients who underwent OCA transplantation utilizing a snowman technique or BioUni® replacement between January 1st, 2012 and December 31st, 2018, and who had a minimum 1-year follow-up at the same institution were identified for inclusion in this study via current procedural terminology (CPT) codes. Charts of included patients were reviewed for injury and treatment details as well as demographic information. Imaging studies and operative reports were reviewed and pre and postoperative subjective and objective outcome measures were recorded. RESULTS: Twenty-eight patients underwent OCA transplantation with either BioUni® replacement (n=5) or with snowman technique repair (n=23). Defects in both groups had similar characteristics including size, area, location, and classifications. Patient-reported outcomes using the Knee Injury and Osteoarthritis Outcome Score-Joint Replacement (KOOS-JR), International Knee Documentation Committee (IKDC), and Physical Health Composite Score (PCS-12) were similar at baseline and increased post-operatively for both groups with no significant differences between techniques after a mean follow-up of 2.77 ± 0.83. Although it did not reach significance, the snowman group had higher rates of knee-related complications (13%) and need for revision surgery (22%) when compared to BioUni® (0% and 0%, respectively). CONCLUSION: The use of both BioUni® and snowman techniques for large, unicondylar articular cartilage lesions of the femoral condyle demonstrate improved patient-reported outcomes at short-term follow-up. The use of the snowman technique presents relatively higher rates of revision similar to previous studies with no statistical difference in patient-reported outcomes when compared to those of a single plug OCA using a BioUni® system.

B-cells and regulatory T-cells in the microenvironment of HER2+ breast cancer are associated with decreased survival: a real-world analysis of women with HER2+ metastatic breast cancer.

BACKGROUND: Despite major improvements in treatment of HER2-positive metastatic breast cancer (MBC), only few patients achieve complete remission and remain progression free for a prolonged time. The tumor immune microenvironment plays an important role in the response to treatment in HER2-positive breast cancer and could contain valuable prognostic information. Detailed information on the cancer-immune cell interactions in HER2-positive MBC is however still lacking. By characterizing the tumor immune microenvironment in patients with HER2-positive MBC, we aimed to get a better understanding why overall survival (OS) differs so widely and which alternative treatment approaches may improve outcome. METHODS: We included all patients with HER2-positive MBC who were treated with trastuzumab-based palliative therapy in the Netherlands Cancer Institute between 2000 and 2014 and for whom pre-treatment tissue from the primary tumor or from metastases was available. Infiltrating immune cells and their spatial relationships to one another and to tumor cells were characterized by immunohistochemistry and multiplex immunofluorescence. We also evaluated immune signatures and other key pathways using next-generation RNA-sequencing data. With nine years median follow-up from initial diagnosis of MBC, we investigated the association between tumor and immune characteristics and outcome. RESULTS: A total of 124 patients with 147 samples were included and evaluated. The different technologies showed high correlations between each other. T-cells were less prevalent in metastases compared to primary tumors, whereas B-cells and regulatory T-cells (Tregs) were comparable between primary tumors and metastases. Stromal tumor-infiltrating lymphocytes in general were not associated with OS. The infiltration of B-cells and Tregs in the primary tumor was associated with unfavorable OS. Four signatures classifying the extracellular matrix of primary tumors showed differential survival in the population as a whole. CONCLUSIONS: In a real-world cohort of 124 patients with HER2-positive MBC, B-cells, and Tregs in primary tumors are associated with unfavorable survival. With this paper, we provide a comprehensive insight in the tumor immune microenvironment that could guide further research into development of novel immunomodulatory strategies.