Citations

Abstract Harty, PS, Zabriskie, HA, Stecker, RA, Currier, BS, Moon, JM, Richmond, SR, Jagim, AR, and Kerksick, CM. Position-specific body composition values in female collegiate rugby union athletes. J Strength Cond Res 35(11): 3158–3163, 2021—Rugby union is a full-contact, intermittent team sport. Anthropometric characteristics of rugby union athletes have been shown to influence suitability for a given position and affect performance. However, little anthropometric data exist in female rugby union athletes. Thus, the purpose of this study was to report position-specific anthropometric, body composition, and bone density values in female collegiate rugby union athletes and to identify between-position differences in these variables. This investigation was a cross-sectional study involving 101 female collegiate rugby union athletes, categorized as forwards and backs as well as by position (props, hookers, locks, flankers, number 8 forwards, halfback, fly-half, centers, wings, and fullbacks). Anthropometric characteristics of all athletes were measured, and body composition was assessed via dual-energy x-ray absorptiometry. Outcome variables included age, height, body mass, BMI, body fat percentage, fat mass (FM), FM index, fat-free mass (FFM), FFM index, lean soft tissue, bone mineral content, bone mineral area, and bone mineral density. Anthropometric and body composition differences between forwards and backs were identified via independent t -tests and Mann-Whitney U tests, depending on normality of the variable. Between-position differences were assessed using one-way analysis of variances (ANOVAs) with Tukey post-hoc comparisons or Welch's ANOVA with Dunnett's T3 post-hoc test. Significant differences ( p < 0.014) were identified between forwards and backs for every anthropometric variable, with forwards displaying greater height (167.7 ± 7.2 cm), body mass (81.5 ± 15.1 kg), and body fat percentage (28.2 ± 6.1%) relative to backs (164.5 ± 5.1 cm; 64.5 ± 7.7 kg; 21.9 ± 3.7%). Likewise, significant differences were identified for every anthropometric variable between several positions ( p < 0.01). Significant ( p < 0.05) interposition differences were identified within the subgroup of forwards, but not within the subgroup of backs. The present investigation is the first to report position-specific anthropometric and body composition data in female collegiate rugby union athletes. The results of this study can be used by rugby union coaches for recruiting and personnel decisions, to determine a player's suitability for a given position, and to further inform training and nutritional interventions in this population.

Background: Little research has focused on the rates and patterns of elbow injuries in National Collegiate Athletic Association (NCAA) student-athletes. Purpose: To describe the epidemiological patterns of elbow injuries in NCAA athletes during 5 seasons over the academic years 2009 through 2014 using the NCAA Injury Surveillance Program (NCAA-ISP) database. Study Design: Descriptive epidemiology study. Methods: A voluntary convenience sample of NCAA varsity teams from 11 sports was examined to determine the rates and patterns of elbow injuries. Rates and distributions of elbow injuries were identified within the context of sport, event type, time in season, mechanism, time lost from sport, surgical treatment, and injury type. Rates of injury were calculated as the number of injuries divided by the total number of athlete-exposures (AEs). An AE was defined as any student participation in 1 NCAA-sanctioned practice or competition with an inherent risk of exposure to potential injury. Injury rate ratios (IRRs) and injury proportion ratios (IPRs) were then calculated to compare the rates within and between sports by event type, season, sex, mechanism, surgical treatment, and time lost from sport. Comparisons between sexes were made using only sports data that had both male and female samples. Results: Overall, 373 elbow injuries were reported in the NCAA-ISP data set during the 2009-2010 through 2013-2014 academic years among 11 varsity sports. The overall rate of injury was 1.76 per 10,000 AEs. The rate of elbow injuries in men was 0.74 per 10,000 AEs, while women experienced injuries at a rate of 0.63 per 10,000 AEs. In sex-comparable sports, men were 1.17 times more likely to experience an elbow injury compared with women. Men’s wrestling (6.00/10,000 AEs) and women’s tennis (1.86/10,000 AEs) were the sports with the highest rates of elbow injuries by sex, respectively. The top 3 highest injury rates overall occurred in men’s wrestling, baseball, and tennis. Elbow injuries were 3.5 times more likely to occur during competition compared with practice. Athletes were 0.76 times less likely to sustain an elbow injury during the preseason compared with in-season. Contact events were the most common mechanism of injury (67%). For sex-comparable sports, men were 2.41 times more likely than women to have contact as their injury mechanism (95% CI, 0.78-7.38). The majority of athletes missed less than 24 hours of participation time (67%), and only a minority (3%) of patients with elbow injuries went on to have surgical intervention. Elbow ulnar collateral ligament injuries were most common (26% of total injuries). Conclusion: Analysis of the study data demonstrated a significant rate of elbow injuries, 1.76 injuries per 10,000 AEs in NCAA collegiate athletes. Higher injury rates can be expected in males within sex-comparable sports. Elbow injuries are most common in the setting of competitions and most commonly occur secondary to contact-type mechanisms. Injuries were more likely to occur during in-season play. The majority of injuries required less than 24 hours of time away from sport and did not require surgical intervention.

Abstract Purpose: The majority of patients with high-grade serous ovarian cancer (HGSC) develop progressive disease following primary treatment, with a five-year survival rate of ~30%. However, a subset of patients have an extraordinary response to treatment and ~15% survive more than ten years (long-term survivors). The Multidisciplinary Ovarian Cancer Outcomes Group (MOCOG) aims to uncover factors that influence long-term survival of HGSC patients. Here, we investigated the genomic and immunologic determinants of exceptional survival of this deadly disease. Experimental Design: Patient characteristics and clinical histories were evaluated to identify patients diagnosed with advanced stage (Stage IIIC/IV) and histopathologically confirmed HGSC with greater than 10-year overall survival. Whole-genome sequencing (WGS) was performed on primary tumors (median 78x coverage) and germline samples (median 39x coverage) of 55 long-term survivors. Primary tumor samples were also characterised by RNA sequencing, DNA methylation profiling and immunohistochemistry. Results: A total 38 (69%) of long-term surviving patients had residual disease following surgery, suggestive of highly chemo-sensitive disease. Most patients (41, 75%) were alive at last follow-up and 26 (47%) were progression-free. Somatic mutation burden was higher in primary tumors of long-term survivors relative to controls (316 unselected HGSC patients in The Cancer Genome Atlas). Genome-wide mutational signatures were predominantly Signature 3 (associated with homologous recombination deficiency), Signature 1 (age related) and Signatures 5, 8 and 16 (unknown etiology). Inactivation of the tumor suppressor RB1 by structural rearrangements or homozygous deletion was frequent in long-term survivors, with 33% of tumors showing associated loss of RB1 protein expression by immunohistochemistry compared to 13% of unselected HGSC controls (n=207; P = 0.001). Staining of adjacent tumor tissue revealed that RB1 loss was associated with increased numbers of PD-1+ tumor-infiltrating lymphocytes (P = 0.015) and MHC class I on tumor cells (P = 0.002). In an independent HGSC cohort (n=847), RB1 protein loss was associated with prolonged survival (HR: 0.75, P &lt; 0.001) compared to patients with RB1 positive tumors. Furthermore, co-occurrence of germline mutations in BRCA1 or BRCA2 and RB1 loss was associated with a significantly longer overall survival compared to patients with retained RB1 protein expression and no germline BRCA mutation (HR: 0.44, P &lt; 0.001). Conclusions: This study delineates the full landscape of genomic alterations in HGSC of long-term survivors. Our findings indicate that specific mutations might be associated with enhanced host immune responses and long-term survival. Citation Format: Dale W. Garsed, Ahwan Pandey, Sian Fereday, Kathryn Alsop, Maartje C. Wouters, Flurina Saner, Jessica A. Beach, Katy Milne, Catherine J. Kennedy, Joy Hendley, Nadia Traficante, Celeste L. Pearce, Malcolm C. Pike, Multidisciplinary Ovarian Cancer Outcomes Group, Susan J. Ramus, Martin Köbel, Brad H. Nelson, Ellen L. Goode, Anna deFazio, David D. Bowtell. The genomic landscape of high-grade serous ovarian cancer in long-term survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2722.

Excess fat within bone marrow is associated with lower bone density. Metabolic stressors such as chronic caloric restriction (CR) can exacerbate marrow adiposity, and increased glucocorticoid signaling and adrenergic signaling are implicated in this phenotype. The current study tested the role of glucocorticoid signaling in CR-induced stress by conditionally deleting the glucocorticoid receptor ( Nr3c1 ; hereafter abbreviated as GR) in bone marrow osteoprogenitors (Osx1-Cre) of mice subjected to CR and ad libitum diets. Conditional knockout of the GR (GR-CKO) reduced cortical and trabecular bone mass as compared to WT mice under both ad libitum feeding and CR conditions. No interaction was detected between genotype and diet, suggesting that the GR is not required for CR-induced skeletal changes. The lower bone mass in GR-CKO mice, and the further decrease in bone by CR, resulted from suppressed bone formation. Interestingly, treatment with the β-adrenergic receptor antagonist propranolol mildly but selectively improved metrics of cortical bone mass in GR-CKO mice during CR, suggesting interaction between adrenergic and glucocorticoid signaling pathways that affects cortical bone. GR-CKO mice dramatically increased marrow fat under both ad libitum and CR-fed conditions, and surprisingly propranolol treatment was unable to rescue CR-induced marrow fat in either WT or GR-CKO mice. Additionally, serum corticosterone levels were selectively elevated in GR-CKO mice with CR, suggesting the possibility of bone–hypothalamus–pituitary–adrenal crosstalk during metabolic stress. This work highlights the complexities of glucocorticoid and β-adrenergic signaling in stress-induced changes in bone mass, and the importance of GR function in suppressing marrow adipogenesis while maintaining healthy bone mass.

Abstract Objective To assess the negative predictive value (NPV) of breast MRI in detecting residual disease after neoadjuvant chemotherapy (NAC) in women with invasive breast cancer, overall and by tumor subtype. Methods An institutional review board approved retrospective study from January 2010 through December 2016 identified patients with invasive breast cancer who achieved complete MRI response to NAC, defined as the absence of residual enhancement in the tumor bed above background parenchymal enhancement. During the study period, it was our routine practice to assign a BI-RADS 1 or 2 assessment to these cases. The NPV was defined as the ability of a complete MRI response to predict pathologic complete response (pCR) at final surgical pathology. Statistical analyses were performed using a Fisher exact test. Results Among 244 patients who underwent MRI to assess NAC response, 38 (16%) were determined to have complete MRI response by the interpreting radiologist. Of these, 20/38 (53%) had pCR. Complete MRI response did not significantly predict pCR for the total group (P &lt; 0.9). However, NPVs significantly varied by molecular subtype (P &lt; 0.004). True negative MRIs by tumor subtype were 2/10 (20%) for hormone receptor (HR)+/HER2–, 3/10 (30%) for HR+/HER2+, 6/8 (75%) for HR–/HER+, and 9/10 (90%) for triple negative (TN) subtypes. Complete MRI response significantly predicted pCR for only the TN subtype (NPV 90%; P &lt; 0.02). Conclusions In patients with complete MRI response, 53% had pCR. While MRI lacks sufficient NPV to obviate the need for surgical excision, it may add prognostic value for certain molecular subtypes. The TN subtype demonstrated the highest NPV.

ABSTRACTWe describe how our institution responded when an interpreter who participated in the consent process involving an individual with limited English proficiency refused to cosign consent documents attesting that the individual enrolling in the study understood the consent information and that her consent to enroll was voluntary. In developing our approach, our institution took into account ethical tensions between the Belmont principles of respect for persons, beneficence, and justice that apply to the protection of research participants and the professional principles of beneficence, fidelity, and respect for the importance of culture that are outlined in ethical guidelines for medical interpreters.

Biospecimens acquired during routine medical practice are the primary sources of molecular information about patients and their diseases that underlies precision medicine and translational research. In cancer care, molecular analysis of biospecimens is especially common because it often determines treatment choices and may be used to monitor therapy in real time. However, patient specimens are collected, handled, and processed according to routine clinical procedures during which they are subjected to factors that may alter their molecular quality and composition. Such artefactual alteration may skew data from molecular analyses, render analysis data uninterpretable, or even preclude analysis altogether if the integrity of a specimen is severely compromised. As a result, patient care and safety may be affected, and medical research dependent on patient samples may be compromised. Despite these issues, there is currently no requirement to control or record preanalytical variables in clinical practice with the single exception of breast cancer tissue handled according to the guideline jointly developed by the American Society of Clinical Oncology and College of American Pathologists (CAP) and enforced through the CAP Laboratory Accreditation Program. Recognizing the importance of molecular data derived from patient specimens, the CAP Personalized Healthcare Committee established the Preanalytics for Precision Medicine Project Team to develop a basic set of evidence-based recommendations for key preanalytics for tissue and blood specimens. If used for biospecimens from patients, these preanalytical recommendations would ensure the fitness of those specimens for molecular analysis and help to assure the quality and reliability of the analysis data.

Headache disorders are among the most common and disabling medical conditions worldwide. Pharmacologic acute and preventive treatments are often insufficient and poorly tolerated, and the majority of patients are unable to adhere to their migraine treatments due to these issues. With improvements in our understanding of migraine and cluster headache pathophysiology, neuromodulation devices have been developed as safe and effective acute and preventive treatment options. In this review, we focus on neuromodulation devices that have been studied for migraine and cluster headache, with special attention to those that have gained food and drug administration (FDA) clearance. We will also explore how these devices can be used in patients who might have limited pharmacologic options, including the elderly, children, and pregnant women.

Abstract Context Dipeptidyl peptidase 4 (DPP4) inhibitors may increase the risk of heart failure. Decreased degradation of vasoactive peptides like substance P [also degraded by angiotensin-converting enzyme (ACE)] and Y1 agonists peptide YY (PYY 1-36) and neuropeptide Y (NPY 1-36) could contribute. Objective This study tested the hypothesis that there is an interactive effect of DPP4 inhibition and ACE inhibition (vs antihypertensive control subjects) on vasoactive peptides after a mixed meal. Participants and Design Fifty-three patients with type 2 diabetes and hypertension were randomized to double-blind treatment with ramipril, valsartan, or amlodipine for 15 weeks in parallel groups. During the 5th, 10th, and 15th weeks, participants also received placebo + placebo, sitagliptin 100 mg/d + placebo, and sitagliptin + aprepitant 80 mg/d in random order. On the last day of each crossover treatment, participants underwent a mixed-meal study. Results Sitagliptin increased postprandial glucagon-like peptide-1 and decreased glucose in all antihypertensive groups. Sitagliptin increased NPY 1-36 and decreased Y2 agonists NPY 3-36 and PYY 3-36 in all groups. During ramipril or valsartan, but not amlodipine, sitagliptin increased postprandial norepinephrine; substance P receptor blockade with aprepitant prevented this effect. Despite increased norepinephrine, sitagliptin decreased postprandial blood pressure during ACE inhibition. Conclusion DPP4 inhibition increases postprandial concentrations of the Y1 agonist NPY 1-36. During treatment with an ACE inhibitor or angiotensin receptor blocker, DPP4 inhibition increased postprandial norepinephrine through a substance P receptor–dependent mechanism. Increased NPY 1-36 and norepinephrine could increase risk of heart failure but did not result in higher postprandial blood pressure.