Clinical outcomes with utilization of high-potency topical steroids in patients with lichen sclerosus-associated vulvar cancer.

OBJECTIVES: To evaluate the impact of high-potency topical steroid use on risk of recurrence of lichen sclerosus-associated vulvar cancer. METHODS: This is a retrospective cohort study evaluating patients with lichen sclerosus (LS)- associated vulvar squamous cell cancer (VSCC). Demographic and clinical outcome data were compared between two comparison groups: patients who received steroids, mainly clobetasol, and patients who did not receive steroids following treatment of LS-related vulvar cancer. Categorical variables were compared using Fisher's exact test or chi-square test. Continuous variables were compared using a two-sided student's t-test. Time to recurrence (TTR) and overall survival (OS) were analyzed using Kaplan-Meier survival plot and compared using Mantel-Cox log rank test. Cox proportional hazard regression models were conducted to generate hazard ratios for both TTR and OS. A p value of <0.05 was considered statistically significant. RESULTS: A total of 49 patients were included, with 36 patients receiving steroid treatment and 13 patients in the expectant management group. The median age of diagnosis was 68. The average BMI was 31.7 +/- 7.0. The median length of follow up was 41 months. The majority of patients were diagnosed with stage I VSCC. There was no difference in demographics or oncologic management of vulvar cancer between the two cohorts. Overall recurrence was decreased among patients who received steroid treatment when compared to patients who did not, 12 patients (33.3%) versus 9 patients (69.2%) respectively (p = 0.048). CONCLUSIONS: High-potency topical steroid use following treatment of lichen sclerosus-associated vulvar squamous cell carcinoma is associated with decreased risk of recurrence and prolonged median time to recurrence.

Concurrent Validity of Four Activity Monitors in Older Adults.

Sedentary behaviour (SB) and physical activity (PA) have been shown to be independent modulators of healthy ageing. We thus investigated the impact of activity monitor placement on the accuracy of detecting SB and PA in older adults, as well as a novel random forest algorithm trained on data from older persons. Four monitor types (ActiGraph wGT3X-BT, ActivPAL3c VT, GENEActiv Original, and DynaPort MM+) were simultaneously worn on five anatomical sites during ten different activities by a sample of twenty older adults (70.0 (12.0) years; 10 women). The results indicated that collecting metabolic equivalent (MET) data for 60 s provided the most representative results, minimising variability. In addition, thigh-worn monitors, including ActivPAL, Random Forest, and Sedentary Sphere-Thigh, exhibited superior performance in classifying SB, with balanced accuracies ≥ 94.2%. Other monitors, such as ActiGraph, DynaPort MM+, and GENEActiv Sedentary Sphere-Wrist, demonstrated lower performance. ActivPAL and GENEActiv Random Forest outperformed other monitors in participant-specific balanced accuracies for SB classification. Only thigh-worn monitors achieved acceptable overall balanced accuracies (≥80.0%) for SB, standing, and medium-to-vigorous PA classifications. In conclusion, it is advisable to position accelerometers on the thigh, collect MET data for ≥60 s, and ideally utilise population-specific trained algorithms.

Diagnostic Accuracy of Endobronchial Optical Coherence Tomography for the Microscopic Diagnosis of Usual Interstitial Pneumonia.

Rationale: Early, accurate diagnosis of interstitial lung disease (ILD) informs prognosis and therapy, especially in idiopathic pulmonary fibrosis (IPF). Current diagnostic methods are imperfect. High-resolution computed tomography has limited resolution, and surgical lung biopsy (SLB) carries risks of morbidity and mortality. Endobronchial optical coherence tomography (EB-OCT) is a low-risk, bronchoscope-compatible modality that images large lung volumes in vivo with microscopic resolution, including subpleural lung, and has the potential to improve the diagnostic accuracy of bronchoscopy for ILD diagnosis. Objectives: We performed a prospective diagnostic accuracy study of EB-OCT in patients with ILD with a low-confidence diagnosis undergoing SLB. The primary endpoints were EB-OCT sensitivity/specificity for diagnosis of the histopathologic pattern of usual interstitial pneumonia (UIP) and clinical IPF. The secondary endpoint was agreement between EB-OCT and SLB for diagnosis of the ILD fibrosis pattern. Methods: EB-OCT was performed immediately before SLB. The resulting EB-OCT images and histopathology were interpreted by blinded, independent pathologists. Clinical diagnosis was obtained from the treating pulmonologists after SLB, blinded to EB-OCT. Measurements and Main Results: We enrolled 31 patients, and 4 were excluded because of inconclusive histopathology or lack of EB-OCT data. Twenty-seven patients were included in the analysis (16 men, average age: 65.0 yr): 12 were diagnosed with UIP and 15 with non-UIP ILD. Average FVC and DlCO were 75.3% (SD, 18.5) and 53.5% (SD, 16.4), respectively. Sensitivity and specificity of EB-OCT was 100% (95% confidence interval, 75.8-100.0%) and 100% (79.6-100%), respectively, for both histopathologic UIP and clinical diagnosis of IPF. There was high agreement between EB-OCT and histopathology for diagnosis of ILD fibrosis pattern (weighted κ: 0.87 [0.72-1.0]). Conclusions: EB-OCT is a safe, accurate method for microscopic ILD diagnosis, as a complement to high-resolution computed tomography and an alternative to SLB.

Contributing factors to lymph node recovery with esophagectomy by thoracic surgeons: an analysis of the Society of Thoracic Surgeons General Thoracic Surgery Database.

Given the association between lymphadenectomy and survival after esophagectomy, and the ongoing development of effective adjuvant protocols for identified residual disease, we determined factors contributing to lymph node yield and effects on postoperative morbidity following esophagectomy by thoracic surgeons. Using the Society of Thoracic Surgeons General Thoracic Surgery Database, all patients who underwent esophagectomy for primary esophageal cancer with gastric conduit reconstruction from 2012 to 2016 were identified. Patient demographics, technical factors, and tumor characteristics associated with lymph node yield were determined using a multivariable multilevel mixed-effects regression model. Associations between lymph node yield and perioperative morbidity and mortality were similarly assessed. A total of 8480 patients were included. The median number of nodes harvested was 16 [Interquartile Range 11-22]. Factors associated with fewer nodes included female gender (b=-0.53, P=0.032), body mass index <18.5 (b=-1.46, P=0.012), prior cardiothoracic surgery (b=-0.73, P=0.015), intraoperative blood transfusion (b=-1.43, P<0.001), squamous cell histology (b=-0.86, P=0.006), and neoadjuvant treatment (b=-1.41, P<0.001). Operative approach significantly affected lymph node yield, with minimally invasive approaches demonstrating higher lymph node counts, and open transhiatal esophagectomy recovering the fewest nodes. Findings were independent of clinical center. There was no association of higher lymph node yield with 30-day mortality, with only slightly increased risk for chyle leak (odds ratio [OR] 1.02, P=0.012). In conclusion, several patient and tumor factors affect lymph node recovery with esophagectomy, independent of hospital center. Technical aspects, specifically minimally invasive approach, play a significant role in quantified lymph node yield. Higher operative lymph node yield was associated with minimal increased morbidity.

Management and outcomes of esophageal perforation.

BACKGROUND: Esophageal perforation is a morbid condition and remains a therapeutic challenge. We report the outcomes of a large institutional experience with esophageal perforation and identify risk factors for morbidity and mortality. METHODS: A retrospective analysis was conducted on 142 patients who presented with a thoracic or gastroesophageal junction esophageal perforation from 1995 to 2020. Baseline characteristics, operative or interventional strategies, and outcomes were analyzed by etiology of the perforation and management approach. Multivariable cox and logistic regression models were constructed to identify predictors of mortality and morbidity. RESULTS: Overall, 109 (77%) patients underwent operative intervention, including 80 primary reinforced repairs and 21 esophagectomies and 33 (23%) underwent esophageal stenting. Stenting was more common in iatrogenic (27%) and malignant (64%) perforations. Patients who presented with a postemetic or iatrogenic perforation had similar 90-day mortality (16% and 16%) and composite morbidity (51% and 45%), whereas patients who presented with a malignant perforation had a 45% 90-day mortality and 45% composite morbidity. Risk factors for mortality included age >65 years (hazard ratio [HR] 1.89 [1.02-3.26], P = 0.044) and a malignant perforation (HR 4.80 [1.31-17.48], P = 0.017). Risk factors for composite morbidity included pleural contamination (odds ratio [OR] 2.06 [1.39-4.43], P = 0.046) and sepsis (OR 3.26 [1.44-7.36], P = 0.005). Of the 33 patients who underwent stent placement, 67% were successfully managed with stenting alone and 30% required stent repositioning. CONCLUSIONS: Risk factors for morbidity and mortality after esophageal perforation include advanced age, pleural contamination, septic physiology, and malignant perforation. Primary reinforced repair remains a reasonable strategy for patients with an esophageal perforation from a benign etiology.

Treatment of anastomotic leak after esophagectomy: insights of an international case vignette survey and expert discussions.

Anastomotic leak (AL) is a severe complication after esophagectomy. Clinical presentation of AL is diverse and there is large practice variation regarding treatment of AL. This study aimed to explore different AL treatment strategies and their underlying rationale. This mixed-methods study consisted of an international survey among upper gastro-intestinal (GI) surgeons and focus groups with expert upper GI surgeons. The survey included 10 case vignettes and data sources were integrated after separate analysis. The survey was completed by 188 respondents (completion rate 69%) and 6 focus groups were conducted with 20 international experts. Prevention of mortality was the most important goal of primary treatment. Goals of secondary treatment were to promote tissue healing, return to oral feeding and safe hospital discharge. There was substantial variation in the preferred treatment principles (e.g. drainage or defect closure) and modalities (e.g. stent or endoVAC) within different presentations of AL. Patients with local symptoms were treated by supportive means only or by non-surgical drainage and/or defect closure. Drainage was routinely performed in patients with intrathoracic collections and often combined with defect closure. Patients with conduit necrosis were predominantly treated by resection and reconstruction of the anastomosis or by esophageal diversion. This mixed-methods study shows that overall treatment strategies for AL are determined by vitality of the conduit and presence of intrathoracic collections. There is large variation in preferred treatment principles and modalities. Future research may investigate optimal treatment for specific AL presentations and aim to develop consensus-based treatment guidelines for AL after esophagectomy.

Development of a clinically relevant ovarian cancer model incorporating surgical cytoreduction to evaluate treatment of micro-metastatic disease.

OBJECTIVES: Mouse models of ovarian cancer commonly transfer large numbers of tumor cells into the peritoneal cavity to establish experimental metastatic disease, which may not adequately model early metastatic spread from a primary tumor site. We hypothesized we could develop an ovarian cancer model that predictably represents micro-metastatic disease. METHODS: Murine ID8VEGF ovarian cancer cells were transduced to express enhanced luciferase (eLuc) to enable intravital detection of microscopic disease burden and injected beneath the ovarian bursa of C57Bl/6 mice. At 6 or 10 weeks after orthotopic injection, when mice had detectable metastases, hysterectomy and bilateral salpingo-oophorectomy was performed to remove all macroscopic disease, and survival monitored. Immunohistochemistry and gene expression profiling were performed on primary and metastatic tumors. RESULTS: eLuc-transduced ID8VEGF cells were brighter than cells transduced with standard luciferase, enabling in vivo visualization of microscopic intra-abdominal metastases developing after orthotopic injection. Primary surgical cytoreduction removed the primary tumor mass but left minimal residual disease in all mice. Metastatic sites that developed following orthotopic injection were similar to metastatic human ovarian cancer sites. Gene expression and immune infiltration were similar between primary and metastatic mouse tumors. Surgical cytoreduction prolonged survival compared to no surgery, with earlier cytoreduction more beneficial than delayed, despite micro-metastatic disease in both settings. CONCLUSIONS: Mice with primary ovarian tumors established through orthotopic injection develop progressively fatal metastatic ovarian cancer, and benefit from surgical cytoreduction to remove bulky disease. This model enables the analysis of therapeutic regimens designed to target and potentially eradicate established minimal residual disease.

Static one-leg standing balance test as a screening tool for low muscle mass in healthy elderly women.

BACKGROUND: Identification of simple screening tools for detecting lower skeletal muscle mass may be beneficial for planning effective interventions in the elderly. AIMS: We aimed to (1) establish a threshold for one-leg standing balance test (OLST) time for low muscle mass, and (2) test the ability of that threshold to assess muscular impairments in a poor balance group. METHODS: Eyes-open OLST (maximum duration 30 s) was performed with right and left legs in 291 women (age 71 ± 6 years). OLST time was calculated as the sum of the OLST time of right and left legs. Fat-free mass (FFM), skeletal muscle mass (SMM), fat mass, biceps brachii and vastus lateralis sizes; handgrip strength (HGS), elbow flexion maximum torque (MVCEF) and knee extension maximum torque (MVCKE) were measured. Muscle quality was calculated as MVCKE/FFM and physical activity was assessed by questionnaire. Low muscle mass was defined as SMMrelative of 22.1%, a previously established threshold for pre-sarcopenia. RESULTS: The OLST threshold time to detect low muscle mass was 55 s (sensitivity: 0.63; specificity: 0.60). The poor balance group (OLST < 55 s) had higher fat mass (3.0%, p < 0.001), larger VL thickness (5.1%, p = 0.016), and lower HGS (- 10.2%, p < 0.001), MVCEF (- 8.2%, p = 0.003), MVCKE (- 9.5%, p = 0.012), MVCKE/FFM (- 11.0%, p = 0.004) and physical activity (- 8.0%, p = 0.024) compared to the normal balance group. While after adjusting age, the differences exist for HGS, fat mass and VL thickness only. DISCUSSION: An OLST threshold of 55 s calculated as the summed score from both legs discriminated pre-sarcopenic characteristics among active, community-dwelling older women with limited potential (sensitivity 0.63, specificity 0.60). CONCLUSION: OLST, which can be performed easily in community settings without the need for more complex muscle mass measurement, may help identify women at risk of developing sarcopenia.

Third-time ("redo-redo") anti-reflux surgery: patient-reported outcomes after a thoracoabdominal approach.

BACKGROUND: Approximately 3-6% of patients undergoing anti-reflux surgery require "redo" surgery for persistent gastroesophageal reflux disease (GERD). Further surgery for patients with two failed prior anti-reflux operations is controversial due to the morbidity of reoperation and poor outcomes. We examined our experience with surgical revision of patients with at least two failed anti-reflux operations. METHODS: Adults undergoing at least a second-time revision anti-reflux surgery between 1999 and 2017 were eligible. The primary outcomes were general and disease-specific quality-of-life (QoL) scores determined by Short-Form-36 (SF36) and GERD-Health-Related QoL (GERD-HRQL) instruments, respectively. Secondary outcomes included perioperative morbidity and mortality. RESULTS: Eighteen patients undergoing redo-redo surgery (13 with 2 prior operations, 5 with 3 prior operations) were followed for a median of 6 years [IQR 3, 12]. Sixteen patients (89%) underwent open revisions (14 thoracoabdominal, 2 laparotomy) and two patients had laparoscopic revisions. Indications for surgery included reflux (10 patients), regurgitation (5 patients), and dysphagia (3 patients). Intraoperative findings were mediastinal wrap herniation (9 patients), misplaced wrap (2 patients), mesh erosion (1 patient), or scarring/stricture (6 patients). Procedures performed included Collis gastroplasty + fundoplication (6 patients), redo fundoplication (5 patients), esophagogastrectomy (4 patients), and primary hiatal closure (3 patients). There were no deaths and 13/18 patients (72%) had no postoperative complications. Ten patients completed QoL surveys; 8 reported resolution of reflux, 6 reported resolution of regurgitation, while 4 remained on proton-pump inhibitors (PPI). Mean SF36 scores (± standard deviation) in the study cohort in the eight QoL domains were as follows: physical functioning (79.5 [± 19.9]), physical role limitations (52.5 [± 46.3]), emotional role limitations (83.3 [± 36.1]), vitality (60.0 [± 22.7]), emotional well-being (88.4 [± 8.7]), social functioning (75.2 [± 31.0]), pain (66.2 [± 30.9]), and general health (55.0 [± 39.0]). CONCLUSION: An open thoracoabdominal approach in appropriately selected patients needing third-time anti-reflux surgery carries low morbidity and provides excellent results as reflected in QoL scores.

Training for a new environment: Using military operational concepts in counseling veterans.

Since September 11, 2001, the United States has engaged in an extended period of military conflict, resulting in 4.1 million men and women serving in support of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn. Whereas not all servicemembers experience mental health issues, many have experienced difficulties with readjusting to the civilian world, often requiring mental health services both inside and outside of the Department of Veterans Affairs. Issues related to stigma and military culture contribute to barriers not only for veterans seeking treatment but for clinicians providing services who may lack experience with military culture. This article provides a framework to use military concepts in clinical sessions to further therapeutic engagement with the military/veteran client.

Benchmarking Complications Associated with Esophagectomy.

OBJECTIVE: Utilizing a standardized dataset with specific definitions to prospectively collect international data to provide a benchmark for complications and outcomes associated with esophagectomy. SUMMARY OF BACKGROUND DATA: Outcome reporting in oncologic surgery has suffered from the lack of a standardized system for reporting operative results particularly complications. This is particularly the case for esophagectomy affecting the accuracy and relevance of international outcome assessments, clinical trial results, and quality improvement projects. METHODS: The Esophageal Complications Consensus Group (ECCG) involving 24 high-volume esophageal surgical centers in 14 countries developed a standardized platform for recording complications and quality measures associated with esophagectomy. Using a secure online database (ESODATA.org), ECCG centers prospectively recorded data on all resections according to the ECCG platform from these centers over a 2-year period. RESULTS: Between January 2015 and December 2016, 2704 resections were entered into the database. All demographic and follow-up data fields were 100% complete. The majority of operations were for cancer (95.6%) and typically located in the distal esophagus (56.2%). Some 1192 patients received neoadjuvant chemoradiation (46.1%) and 763 neoadjuvant chemotherapy (29.5%). Surgical approach involved open procedures in 52.1% and minimally invasive operations in 47.9%. Chest anastomoses were done most commonly (60.7%) and R0 resections were accomplished in 93.4% of patients. The overall incidence of complications was 59% with the most common individual complications being pneumonia (14.6%) and atrial dysrhythmia (14.5%). Anastomotic leak, conduit necrosis, chyle leaks, recurrent nerve injury occurred in 11.4%, 1.3%, 4.7%, and 4.2% of cases, respectively. Clavien-Dindo complications ≥ IIIb occurred in 17.2% of patients. Readmissions occurred in 11.2% of cases and 30- and 90-day mortality was 2.4% and 4.5%, respectively. CONCLUSION: Standardized methods provide contemporary international benchmarks for reporting outcomes after esophagectomy.

Tumor infiltrating lymphocytes and homologous recombination deficiency are independently associated with improved survival in ovarian carcinoma.

OBJECTIVE: The presence of tumor infiltrating lymphocytes (TIL) and defects in homologous recombination (HR) are each important prognostic factors in ovarian carcinoma (OC). We characterized the association between HR deficiency (HRD) and the presence of TILs in a cohort of OC patients and the relative contribution to overall survival. METHODS: Patients with carcinoma of the ovary, fallopian tube, or peritoneum were prospectively enrolled. Malignant neoplasm and serum samples were collected. Immunohistochemistry for CD3+ T cells and CD68+ tumor associated macrophages (TAMs) was performed on specimens collected at primary surgery. Damaging germline and somatic mutations in genes in the HR-mediated repair (HRR) pathway were identified using BROCA sequencing. HRD was defined as a damaging mutation in one of 12 genes in the HRR pathway or promoter hypermethylation in BRCA1 or RAD51C. RESULTS: Ninety-eight of 250 patients included in the analysis had HRD OC (39.2%). HRD OC were enriched for CD3+ TILs and CD68+ TAMs. High CD3+ TIL was present in 65.3% of HRD OC compared to 43.4% of non-HRD OC (P = 0.001). High CD68+ TAM was present in 66.3% of HRD OC compared to 50.7% of non-HRD OC (P = 0.015). Patients with HRD OC and high CD3+ TILs had the longest median overall survival compared to non-HRD OC with low CD3+ TILs (70.9 vs. 35.8 months, adjusted HR 0.38, 95% CI (0.25-0.59)). CONCLUSIONS: Patients that have both CD3+ TILs and HRD OC are afforded the greatest improvement in overall survival. This finding may have therapeutic implications for OC patients treated with emerging immunotherapies.

Quality of life in adults with muscular dystrophy.

BACKGROUND: Muscle weakness is a defining characteristic of Muscular Dystrophy (MD); however, yet while speculated, objective measures of muscle weakness has not been reported in relation to quality of life in adults with MD. OBJECTIVES: 1) compare the self-reported QoL of adults with Duchenne MD (DMD), Beckers MD (BMD), Limb-Girdle MD (LGMD) and Fascioscapulohumeral MD (FSHD, and a non-MD (CTRL) group; 2) present and compare between groups measures of Impairment (Muscle Strength and Activities of Daily Living) and Perception (Fatigue, Pain and Self-Efficacy); and 3) identify associations between QoL domains and measures of Impairment and Perception (See above). METHODS: Seventy-Five males, including MD classifications DMD, BMD, LGMD, FSHD and CTRL, completed measures for QoL, Knee-Extension Maximal Voluntary Contraction (KEMVC), Fatigue, Pain, Self-Efficacy and Activities of Daily Living (ADL). RESULTS: QoL was lower across many domains in MD than CTRL. FSHD scored lower than DMD for mental wellbeing domains. KEMVC associated with Physical-Function domain for BMD. Pain, Self-Efficacy and ADLs associated with QoL domains, with Fatigue the most consistently associated. CONCLUSION: The present study identified differences between MD classifications within self-perceptions of mental-health. Muscle weakness is a defining feature of MD; however, it doesn't define QoL in adults with MD. A greater understanding of mental wellbeing, independence, and management of fatigue and pain, are required to improve QoL for adults with MD.

Nonglycemic Outcomes of Antidiabetic Medications.

IN BRIEF The number of medications used to treat diabetes has increased dramatically in the past 15 years. With so many options that have shown significant A1C improvement, it is important to consider side effects, precautions, and additional benefits these agents may offer. This article is a review of some of the most compelling literature available on the nonglycemic benefits of sulfonylureas, thiazolidinediones, biguanides, glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and sodium-glucose cotransporter 2 inhibitors. Other classes of antihyperglycemic agents, such as dopamine agonists, meglitinides, and amylin agonists, are not discussed in this article.

Surgical vs Endoscopic Management of T1 Esophageal Adenocarcinoma: A Modeling Decision Analysis.

BACKGROUND & AIMS: Although treatment of T1a esophageal adenocarcinoma (EAC) is shifting from esophagectomy to endoscopic therapy, T1b EACs are considered too high risk to be treated endoscopically. We investigated the effectiveness and cost effectiveness of esophagectomy vs endoscopic therapy for T1a and T1b EACs, and the effects of age and comorbidities, using a decision analytic Markov model. METHODS: We developed a model to simulate a hypothetical cohort of men 75 years old with Charlson comorbidity index scores of 0 and either T1aN0M0 or T1bN0M0 EAC, as a base case. We used the model to compare the effects of esophagectomy vs serial endoscopic therapy. We performed sensitivity analyses based on age at diagnosis of 60-85 years, comorbidity indices of 0-2, and utilities. Post-procedure cancer-specific mortality was derived from the Surveillance, Epidemiology, and End Results Medicare database. RESULTS: In the T1a base case, esophagectomy yielded more unadjusted life years than endoscopic therapy (6.97 vs 6.81), but fewer quality-adjusted life years (QALYs, 4.95 for esophagectomy vs 5.22 for endoscopic therapy). In the T1b base case, esophagectomy yielded more unadjusted life years than endoscopic therapy (5.73 vs 5.01) and QALYs (4.07 vs 3.85 for endoscopic therapy), but was not cost effective (incremental cost-effectiveness ratio $156,981). Sensitivity analyses showed endoscopic therapy optimized QALYs for patients more than 80 years old with a comorbidity index of 1 or 2, or if the ratio of post-esophagectomy to post-endoscopic therapy utilities was below 0.875. CONCLUSION: In a Markov model, we showed that endoscopic therapy of T1a EAC yields more QALYs and is more cost effective than esophagectomy for patients of all ages and comorbidity indices tested. In contrast, selection of therapy for T1b EAC depends on age and comorbidities, due to surgical mortality and the competing risk of non-cancer death.

Impact of Above-Average Proanabolic Nutrients Is Overridden by High Protein and Energy Intake in the Muscle-Tendon Unit Characteristics of Middle- to Older-Aged Adults.

Background: The impact, within a single cohort, of independent modulators of skeletal muscle quality, including age, adiposity and obesity, habitual nutritional intake, and physical activity (PA), is unclear. Objective: We examined the bivariate associations between age, adiposity, habitual nutritional intake, and PA against 11 key intrinsic muscle-tendon unit (MTU) characteristics to identify the strongest predictors. We also compared overall profile differences between MTU categories with the use of z scores shown in radar graphs. Methods: Fifty untrained independently living men (n = 15) and women (n = 35) aged 43-80 y (mean ± SD: 64 ±9 y) were categorized by adiposity [men: normal adiposity (NA) <28%, high adiposity (HA) ≥28%; women: NA <40%, HA ≥40%] and body mass index [BMI (in kg/m2); normal: 18 to <25; overweight: ≥25 to <30; and obese: ≥30]. Group differences were examined by body composition assessed with the use of dual-energy X-ray absorptiometry, habitual nutritional intake through a 3-d food diary, PA (work, leisure, sport) using the Baecke questionnaire, 14 serum cytokine concentrations using multiplex luminometry, and 11 MTU characteristics of the gastrocnemius medialis using a combination of isokinetic dynamometry, electromyography, and ultrasonography. Results: Interestingly, classification by BMI highlighted differences between normal and obese individuals in 6 of 11 MTU characteristics (P < 0.001 to P = 0.043). No significant differences were reported in serum cytokine concentrations between adiposity and BMI classifications. BMI predicted 8 of 11 (r = 0.62-0.31, P < 0.001 to P = 0.032), daily energy intake predicted 7 of 11 (r = 0.45-0.34, P = 0.002-0.036), age predicted 5 of 11 (r = -0.49-0.32, P < 0.001 to P = 0.032), work-based PA predicted 5 of 11 (r = 0.43-0.32, P = 0.003-0.048), and adiposity predicted 4 of 11 (r = 0.51-0.33, P < 0.001 to P = 0.022) MTU characteristics. Mathematical z scores and radar graphs showed how endocrine and dietary profiles, but not PA, differed between the top and bottom ∼20% of muscle unit size and specific force. Conclusions: Given the number of factors associated with MTU, education should be targeted to both adequate food quantity and quality (especially protein intake) and increasing habitual moderate to vigorous PA while decreasing sedentary behavior. Specific endocrine variables are also proposed as key pharmaceutical targets.

The cardiorespiratory response and physiological determinants of the assisted 6-minute handbike cycle test in adult males with muscular dystrophy.

INTRODUCTION: The assisted 6-minute cycle test (A6MCT) distance was assessed in adults with muscular dystrophy (MD). METHODS: Forty-eight males, including those with Duchenne MD (DMD), limb-girdle MD (LGMD), fascioscapulohumeral MD (FSHD), and Becker MD (BMD), as well as a group without MD (CTRL), completed handgrip strength (HGS), lung function [forced expiratory volume in 1 second (FEV1 ) and forced vital capacity (FVC)], body fat, and biceps thickness assessments. During the A6MCT, ventilation (VE), oxygen uptake (VO2 ), carbon dioxide (VCO2 ), and heart rate (HR) were recorded. RESULTS: A6MCT and HGS were lower in MD than CTRL subjects. FEV1 , FVC, and biceps thickness were lower in MD than CTRL; lower in DMD than BMD, LGMD, and FSHD; but were not different between BMD, LGMD, and FSHD. A6MCT correlated with HGS, FEV1 , FVC, body fat, VO2 , VCO2 , HR, and VE (r = 0.455-0.708) in pooled BMD, LGMD, and FSHD participants. DISCUSSION: A shorter A6MCT distance in adult males with MD was attributable to HGS and lung function. The A6MCT is appropriate for assessment of physical function in adults with MD. Muscle Nerve 58: 427-433, 2018.

Medial gastrocnemius specific force of adult men with spastic cerebral palsy.

INTRODUCTION: Muscle weakness determines functional impairment in spastic cerebral palsy (SCP). Measurement of specific force (SF) allows for strength comparison with unimpaired populations (controls) accounting for neural (activation and coactivation), architectural (fascicle length and pennation angle), and structural differences (moment arm length). METHODS: Medial gastrocnemius (MG) SF (and its determinants) was assessed in both paretic and non-paretic legs of 11 men with SCP and 11 age-matched controls during plantarflexion maximal voluntary isometric contraction (MVIC). RESULTS: SCP fascicles were 28% longer than control fascicles (P < 0.05). Pennation angle of SCP patients was 41% smaller than in controls. The physiological cross-sectional area of SCP MG patients was 47% smaller than in controls (P < 0.05). There was no difference in SF between controls and SCP patients. CONCLUSIONS: Weakness in SCP is primarily attributable to deficits in agonist activation and muscle size; consequently, SF measured in the MG is similar between SCP and controls. Muscle Nerve 56: 298-306, 2017.

Neoplastic cellularity is associated with clinical and molecular features of high-grade serous ovarian carcinoma.

OBJECTIVE: Most molecular analyses of high-grade serous ovarian, peritoneal and fallopian tube carcinomas (HGSC) require ≥70% tumor (neoplastic) cell nuclei. We characterized the distribution of the percentage of neoplastic nuclei (PNN) in a large cohort of HGSC and correlated PNN with clinical outcomes to determine the fraction of cases outside this range and whether this cut-off introduces selection bias. METHODS: Subjects were prospectively enrolled and normal and neoplastic tissues were snap-frozen. All subjects had grade 2 to 3 HGSC. Subjects that received neoadjuvant chemotherapy were excluded. PNN was determined by estimating the fraction of neoplastic nuclei relative to non-neoplastic nuclei on a representative hematoxylin and eosin stained frozen section from the primary neoplasm. Germline BRCA mutation status was determined with Sanger or BROCA sequencing. RESULTS: PNN was <70% in 101 (33%) of 306 cases. PNN was significantly higher among subjects without optimal cytoreduction (P=0.018). 55 subjects had germline BRCA1/BRCA2 mutations. HGSC associated with BRCA2 but not BRCA1 mutations had significantly lower PNN compared to HGSC in non-carriers (54% vs. 70%, P=0.018). Overall survival was not significantly different between subjects with <70% or ≥70% PNN (median survival 51.8 vs. 46.6months, P=0.858). CONCLUSIONS: One-third of HGSC has PNN <70%. Higher PNN is associated with suboptimal cytoreduction, while lower PNN is associated with inherited BRCA2 mutations. Our findings suggest a nonrandom distribution of PNN that may reflect cancer biology. Further studies exploring the stromal microenvironment are needed. Molecular analyses of HGSC selected for high PNN exclude a significant fraction of patients.