Profile of Daughters and Sisters of Women With Polycystic Ovary Syndrome: The Role of Proband's Glucose Tolerance.

CONTEXT: First-degree relatives of women with polycystic ovary syndrome (PCOS) present hormonal and metabolic alterations compared to girls unrelated to PCOS. It is unknown whether glucose intolerance in the PCOS proband confers a more severe metabolic predisposition on their first-degree relatives. OBJECTIVE: To determine whether glucose tolerance status in women with PCOS is associated with worsened glucose metabolism and sex hormone levels in their peripubertal daughters or sisters. DESIGN: Cross-sectional study. SETTING: Seven academic centers in North America, South America, and Europe. PATIENTS: Sixty-four pairs of women with PCOS and their daughters or younger sisters aged between 8 and 14 years were recruited. Twenty-five mothers or older sisters with PCOS were glucose intolerant (GI) and 39 were normal glucose tolerant (NGT). MAIN OUTCOME MEASURES: Beta-cell function estimated by the insulin secretion-sensitivity index-2 (ISSI-2) during an oral glucose tolerance test and by the disposition index during a frequently sampled IV glucose tolerance test. Free testosterone and 17-hydroxyprogesterone (17-OHP) levels. RESULTS: Being related to a GI PCOS proband was associated with a lower ISSI-2 (P-value = 0.032) after adjusting for ethnicity, body mass index z-score, and pubertal stage. They also had higher free testosterone (P-value = 0.011) and 17-OHP levels compared to girls with an NGT proband, the latter becoming significant after adjusting for confounders (P-value = 0.040). CONCLUSIONS: Compared to first-degree female relatives of women with PCOS and NGT, first-degree relatives of women with PCOS and GI display lower beta-cell function and hyperandrogenemia, putting them at higher risk of GI and PCOS development.

Effect of Periodized Resistance Training on Skeletal Muscle During Androgen Deprivation Therapy for Prostate Cancer: A Pilot Randomized Trial.

PURPOSE: Prostate cancer survivors (PCS) receive androgen deprivation therapy (ADT) as treatment for recurrent cancer, yet ADT is associated with loss of skeletal muscle and physical function. Resistance training can counter both muscle and physical function loss; however, an understanding of the molecular responses of skeletal muscle to resistance training during ADT is still undefined. This sub-analysis of the original randomized, controlled pilot trial investigated effects of 12 weeks of periodized resistance training on mRNA expression of the anabolic genes IGF-1, myogenin, PGC-1α4 and the catabolic genes myostatin and MuRF-1 in skeletal muscle of PCS on ADT. Secondary aims investigated if changes in lean mass and physical function correlated with changes in mRNA expression. METHODS: PCS on ADT (n = 17) were randomized to 12 weeks of supervised resistance training (EXE, n = 9) or home-based stretching (STRETCH, n = 8) 3 days per week. Outcomes were assessed at baseline and post-intervention. Muscle biopsies were analyzed by RT-PCR for mRNA expression. Body composition was assessed through dual-energy X-ray absorptiometry, and physical function through muscular strength, timed up and go, stair climb, and 400 m walk. RESULTS: MuRF-1 mRNA expression was significantly greater in EXE compared to STRETCH post-intervention (P = .005). Change in MuRF-1 mRNA expression significantly correlated with improvements in strength and physical function (P < .05), while change in IGF-1 expression correlated with change in lean mass (P = .015). CONCLUSION: Twelve weeks of resistance training increased mRNA expression of MuRF-1 in skeletal muscle of PCS on ADT. Elevations in resting mRNA expression of IGF-1, myogenin and PGC-1α4, and reduction in mRNA expression of myostatin that are typically expected following resistance training were not observed.

Imagine HEALTH: Randomized Controlled Trial of a Guided Imagery Lifestyle Intervention to Improve Obesity-Related Lifestyle Behaviors in Predominantly Latinx Adolescents.

Introduction: To determine the effects of a novel lifestyle intervention combining lifestyle behavioral education with the complementary-integrative health modality of guided imagery (GI) on dietary and physical activity behaviors in adolescents. The primary aim of this study was to determine the incremental effects of the lifestyle education, stress reduction GI (SRGI), and lifestyle behavior GI (LBGI) components of the intervention on the primary outcome of physical activity lifestyle behaviors (sedentary behavior, light, moderate, and vigorous physical activity), as well as dietary intake behaviors, at the completion of the 12-week intervention. The authors hypothesized that the intervention would improve obesity-related lifestyle behaviors. Materials and Methods: Two hundred and thirty-two adolescent participants (aged 14-17 years, sophomore or junior year of high school) were cluster randomized by school into one of four intervention arms: nonintervention Control (C), Lifestyle education (LS), SRGI, and LBGI. After-school intervention sessions were held two (LS) or three (SRGI, LBGI) times weekly for 12 weeks. Physical activity (accelerometry) and dietary intake (multiple diet recalls) outcomes were assessed pre- and postintervention. Primary analysis: intention-to-treat (ITT) mixed-effects modeling with diagonal covariance matrices; secondary analysis: ad hoc subgroup sensitivity analysis using only those participants adherent to protocol. Results: ITT analysis showed that the Healthy Eating Index (HEI) increased in the LS group compared with C (p = 0.02), but there was no additional effect of GI. Among adherent participants, sedentary behavior was decreased stepwise relative to C in SRGI (d = -0.73, p = 0.004) > LBGI (d = -0.59, p = 0.04) > LS (d = -0.41, p = 0.07), and moderate + vigorous physical activity was increased in SRGI (d = 0.58, p = 0.001). Among adherent participants, the HEI was increased in LS and SRGI, and glycemic index reduced in LBGI. Conclusions: While ITT analysis was negative, among adherent participants, the Imagine HEALTH lifestyle intervention improved eating habits, reduced sedentary activity, and increased physical activity, suggesting that GI may amplify the role of lifestyle education alone for some key outcomes. Clinical Trials.gov ID: NCT02088294.

Parenteral nutrition prolongs hospital stay in children with nonoperative blunt pancreatic injury: A propensity score weighted analysis.

BACKGROUND: Blunt pancreatic injury is frequently managed nonoperatively in children. Nutritional support practices - either enteral or parenteral - are heterogeneous and lack evidence-based guidelines. We hypothesized that use of parenteral nutrition (PN) in children with nonoperatively managed blunt pancreatic injury would 1) be associated with longer hospital stay and more frequent complications, and 2) differ in frequency by trauma center type. METHODS: We conducted a retrospective cohort study using the National Trauma Data Bank (2007-2016). Children (≤18 years) with blunt pancreatic injury were included. Patients were excluded for duodenal injury, mortality <4 days from admission, or laparotomy. We compared children that received versus those that did not receive PN. Logistic regression was used to model patient characteristics, injury severity, and trauma center type as predictors for propensity to receive PN. Treatment groups were balanced using the inverse probability of treatment weights. Outcomes included hospital length of stay, intensive care unit days, incidence of complications and mortality. RESULTS: 554 children with blunt pancreatic injury were analyzed. PN use declined in adult centers from 2012 to 2016, but remained relatively stable in pediatric centers. Propensity-weighted analysis demonstrated longer median length of stay in patients receiving PN (14 versus 4 days, rate ratio 2.19 [95% CI: 1.97, 2.43]). Children receiving PN also had longer ICU stay (rate ratio 1.73 [95% CI: 1.30, 2.30]). There was no significant difference in incidence of complications or mortality. CONCLUSIONS: Use of PN in children with blunt pancreatic injury that are managed nonoperatively differs between adult and pediatric trauma centers, and is associated with longer hospital stay. Early enteral feeding should be attempted first, with PN reserved for children with prolonged intolerance to enteral feeds. LEVEL OF EVIDENCE: III, Retrospective cohort.

Timing of tracheostomy placement among children with severe traumatic brain injury: A propensity-matched analysis.

BACKGROUND: Early tracheostomy has been associated with shorter hospital stay and fewer complications in adult trauma patients. Guidelines for tracheostomy have not been established for children with severe traumatic brain injury (TBI). The purpose of this study was to (1) define nationwide trends in time to extubation and time to tracheostomy and (2) determine if early tracheostomy is associated with decreased length of stay and fewer complications in children with severe TBI. METHODS: Records of children (<15 years) with severe TBI (head Abbreviated Injury Severity [AIS] score ≥3) who were mechanically ventilated (>48 hours) were obtained from the National Trauma Data Bank (2007-2015). Outcomes after early (≤14 days) and late (≥15 days) tracheostomy placement were compared using 1:1 propensity score matching to control for potential confounding by indication. Propensity scores were calculated based on age, race, pulse, blood pressure, Glasgow Coma Scale motor score, injury mechanism, associated injury Abbreviated Injury Severity scores, TBI subtype, craniotomy, and intracranial pressure monitor placement. RESULTS: Among 6,101 children with severe TBI, 5,740 (94%) were extubated or died without tracheostomy, 95% of the time within 18 days. Tracheostomy was performed in 361 children (6%) at a median [interquartile range] of 15 [10, 22] days. Using propensity score matching, we compared 121 matched pairs with early or late tracheostomy. Early tracheostomy was associated with fewer ventilator days (14 [9, 19] vs. 25 [19, 35]), intensive care unit days (19 [14, 25] vs. 31 [24, 43]), and hospital days (26 [19, 41] vs. 39 [31, 54], all p < 0.05). Pneumonia (24% vs. 41%), venous thromboembolism (3% vs. 13%), and decubitus ulcer (4% vs. 13%) occurred less frequently with early tracheostomy (p < 0.05). CONCLUSIONS: Early tracheostomy is associated with shorter hospital stay and fewer complications among children with severe TBI. Extubation without tracheostomy is rare beyond 18 days after injury. LEVEL OF EVIDENCE: Prognostic and epidemiological, retrospective comparative study, level III.

Monitoring Twitter Conversations for Targeted Recruitment in Cancer Trials in Los Angeles County: Protocol for a Mixed-Methods Pilot Study.

BACKGROUND: Insufficient recruitment of participants remains a critical roadblock to successful clinical research, particularly clinical trials. Social media provide new ways for connecting potential participants with research opportunities. Researchers suggest that the social network Twitter may serve as a rich avenue for exploring how patients communicate about their health issues and increasing enrollment in cancer clinical trials. However, there is a lack of evidence that Twitter offers practical utility and impact. OBJECTIVE: This pilot study aimed to examine the feasibility and impact of using Twitter monitoring data (ie, user activity and their conversations about cancer-related conditions and concerns expressed by Twitter users in Los Angeles County) as a tool for enhancing clinical trial recruitment at a comprehensive cancer center. METHODS: We will conduct a mixed-methods interrupted time series study design with a before-and-after social media recruitment intervention. On the basis of a preliminary analysis of eligible trials, we plan to onboard at least 84 clinical trials across 6 disease categories: breast cancer, colon cancer, kidney cancer, lymphoma, non-small cell lung cancer, and prostate cancer that are open to accrual at the University of Southern California (USC) Norris Comprehensive Cancer Center. We will monitor messages about these 6 cancer conditions posted by Twitter users in Los Angeles County. Recruitment for the trials will occur through the Twitter account (@USCTrials). Primary study outcomes-feasibility and acceptance of the social media intervention among targeted Twitter users and the study teams of the onboarded trials-will be assessed using qualitative interviews and the 4-point Likert scale and by calculating the proportion of targeted Twitter users who engaged with outreach messages. Second, impact of the social media intervention will be measured by calculating the proportion of enrollees in trials. The enrollment rate will be compared between the active intervention period and the prior 10 months as historical control for each disease trial group. This study has been funded by the National Center for Advancing Translational Science through a Clinical and Translational Science Award. Study approval was obtained from the clinical investigations committee at USC Norris and the institutional review board at USC. RESULTS: Recruitment on Twitter started in February 2018. Data collection will be completed in November 2018. CONCLUSIONS: This pilot project will provide preliminary data and practical insight into the application of publicly available Twitter data to identify and recruit clinical trial participants across 6 cancer disease types. We will shed light on the acceptance of the social media intervention among Twitter users and study team members of the onboarded trials. If successful, the findings will inform a multisite randomized controlled trial to determine the efficacy of the social media intervention across different locations and populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03408561; https://clinicaltrials.gov/ct2/show/NCT03408561 (Archived by WebCite at http://www.webcitation.org/72LihauzW). REGISTERED REPORT IDENTIFIER: RR1-10.2196/9762.

Impact of resistance training on body composition and metabolic syndrome variables during androgen deprivation therapy for prostate cancer: a pilot randomized controlled trial.

BACKGROUND: Prostate cancer patients on androgen deprivation therapy (ADT) experience adverse effects such as lean mass loss, known as sarcopenia, fat gain, and changes in cardiometabolic factors that increase risk of metabolic syndrome (MetS). Resistance training can increase lean mass, reduce body fat, and improve physical function and quality of life, but no exercise interventions in prostate cancer patients on ADT have concomitantly improved body composition and MetS. This pilot trial investigated 12 weeks of resistance training on body composition and MetS changes in prostate cancer patients on ADT. An exploratory aim examined if a combined approach of training and protein supplementation would elicit greater changes in body composition. METHODS: Prostate cancer patients on ADT were randomized to resistance training and protein supplementation (TRAINPRO), resistance training (TRAIN), protein supplementation (PRO), or control stretching (STRETCH). Exercise groups (EXE = TRAINPRO, TRAIN) performed supervised exercise 3 days per week for 12 weeks, while non-exercise groups (NoEXE = PRO, STRETCH) performed a home-based stretching program. TRAINPRO and PRO received 50 g⋅day- 1 of whey protein. The primary outcome was change in lean mass assessed through dual energy x-ray absorptiometry. Secondary outcomes examined changes in sarcopenia, assessed through appendicular skeletal mass (ASM) index (kg/m2), body fat %, strength, physical function, quality of life, MetS score and the MetS components of waist circumference, blood pressure, glucose, high-density lipoprotein-cholesterol, and triglyceride levels. RESULTS: A total of 37 participants were randomized; 32 participated in the intervention (EXE n = 13; NoEXE n = 19). At baseline, 43.8% of participants were sarcopenic and 40.6% met the criteria for MetS. Post-intervention, EXE significantly improved lean mass (d = 0.9), sarcopenia prevalence (d = 0.8), body fat % (d = 1.1), strength (d = 0.8-3.0), and prostate cancer-specific quality of life (d = 0.9) compared to NoEXE (p < 0.05). No significant differences were observed between groups for physical function or MetS-related variables except waist circumference (d = 0.8). CONCLUSIONS: A 12-week resistance training intervention effectively improved sarcopenia, body fat %, strength and quality of life in hypogonadal prostate cancer patients, but did not change MetS or physical function. PRO did not offer additional benefit in improving body composition. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01909440 . Registered 24 July 2013.

Timing of mortality in pediatric trauma patients: A National Trauma Data Bank analysis.

BACKGROUND/PURPOSE: The classic "trimodal" distribution of death has been described in adult patients, but the timing of mortality in injured children is not well understood. The purpose of this study was to define the temporal distribution of mortality in pediatric trauma patients. METHODS: A retrospective cohort of patients with mortality from the National Trauma Data Bank (2007-2014) was analyzed. Categorical comparison of 'dead on arrival', 'death in the emergency department', and early (≤24h) or late (>24h) inpatient death was performed. Secondary analyses included mortality by pediatric age, predictors of early mortality, and late complication rates. RESULTS: Children (N=5463 deaths) had earlier temporal distribution of death compared to adults (n=104,225 deaths), with 51% of children dead on arrival or in ED compared to 44% of adults (p<0.001). For patients surviving ED resuscitation, children and adolescents had a shorter median time to death than adults (1.2 d and 0.8 days versus 1.6 days, p<0.001). Older age, penetrating mechanism, bradycardia, hypotension, tube thoracostomy, and thoracotomy were associated with early mortality in children. CONCLUSIONS: Injured children have higher incidence of early mortality compared to adults. This suggests that injury prevention efforts and strategies for improving early resuscitation have potential to improve mortality after pediatric injury. LEVEL OF EVIDENCE: Level III: Retrospective cohort study.

A pilot randomised controlled trial of a periodised resistance training and protein supplementation intervention in prostate cancer survivors on androgen deprivation therapy.

INTRODUCTION: Prostate cancer survivors (PCS) receiving androgen deprivation therapy (ADT) experience deleterious side effects such as unfavourable changes in cardiometabolic factors that lead to sarcopenic obesity and metabolic syndrome (MetS). While loss of lean body mass (LBM) compromises muscular strength and quality of life, MetS increases the risk of cardiovascular disease and may influence cancer recurrence. Exercise can improve LBM and strength, and may serve as an alternative to the pharmacological management of MetS in PCS on ADT. Prior exercise interventions in PCS on ADT have been effective at enhancing strength, but only marginally effective at enhancing body composition and ameliorating cardiometabolic risk factors. This pilot trial aims to improve on existing interventions by employing periodised resistance training (RT) to counter sarcopenic obesity in PCS on ADT. Secondary aims compare intervention effects on cardiometabolic, physical function, quality of life and molecular skeletal muscle changes. An exploratory aim examines if protein supplementation (PS) in combination with RT elicits greater changes in these outcomes. METHODS AND ANALYSIS: A 2×2 experimental design is used in 32 PCS on ADT across a 12-week intervention period. Participants are randomised to resistance training and protein supplementation (RTPS), RT, PS or control. RT and RTPS groups perform supervised RT three times per week for 12 weeks, while PS and RTPS groups receive 50 g whey protein per day. This pilot intervention applies a multilayered approach to ameliorate detrimental cardiometabolic effects of ADT while investigating molecular mechanisms underlying skeletal muscle changes in PCS. ETHICS AND DISSEMINATION: This trial was approved by the University of Southern California Institutional Review Board (HS-13-00315). Results from this trial will be communicated in peer-reviewed publications and scientific presentations. TRIAL REGISTRATION NUMBER: NCT01909440; Pre-results.

Distinct intracellular signaling mediates C-MET regulation of dendritic growth and synaptogenesis.

Hepatocyte growth factor (HGF) activation of the MET receptor tyrosine kinase influences multiple neurodevelopmental processes. Evidence from human imaging and mouse models shows that, in the forebrain, disruptions in MET signaling alter circuit formation and function. One likely means of modulation is by controlling neuron maturation. Here, we examined the signaling mechanisms through which MET exerts developmental effects in the neocortex. In situ hybridization revealed that hgf is located near MET-expressing neurons, including deep neocortical layers and periventricular zones. Western blot analyses of neocortical crude membranes demonstrated that HGF-induced MET autophosphorylation peaks during synaptogenesis, with a striking reduction in activation between P14 and P17 just before pruning. In vitro analysis of postnatal neocortical neurons assessed the roles of intracellular signaling following MET activation. There is rapid, HGF-induced phosphorylation of MET, ERK1/2, and Akt that is accompanied by two major morphological changes: increases in total dendritic growth and synapse density. Selective inhibition of each signaling pathway altered only one of the two distinct events. MAPK/ERK pathway inhibition significantly reduced the HGF-induced increase in dendritic length, but had no effect on synapse density. In contrast, inhibition of the PI3K/Akt pathway reduced HGF-induced increases in synapse density, with no effect on dendritic length. The data reveal a key role for MET activation during the period of neocortical neuron growth and synaptogenesis, with distinct biological outcomes mediated via discrete MET-linked intracellular signaling pathways in the same neurons. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1160-1181, 2016.

Imagine HEALTH: results from a randomized pilot lifestyle intervention for obese Latino adolescents using Interactive Guided ImagerySM.

BACKGROUND: There is an urgent need for innovative and developmentally appropriate lifestyle interventions to promote healthy lifestyle behaviors and to prevent the early onset of type 2 diabetes and cardiovascular disease risk in obese Latino adolescents. Guided imagery offers promise to reduce stress and promote lifestyle behavior change to reduce disease risk in obese adolescents. Our objectives were: 1) To pilot test a new 12-wk lifestyle intervention using a randomized trial design in obese Latino adolescents, in order to determine the effects of the mind-body modality of Interactive Guided ImagerySM (IGI), over and above those of a didactic lifestyle education, on insulin resistance, eating and physical activity behaviors, stress and stress biomarkers; and 2) To explore the role of intervention-related changes in stress and stress biomarkers on changes in metabolic outcomes, particularly insulin resistance. METHODS: Obese (BMI > 95th percentile), Latino adolescents (n = 35, age 14-17) were randomized to receive either 12 weekly sessions of a lifestyle education plus guided imagery program (GI), or lifestyle education plus a digital storytelling computer program (DS). Between-group differences in behavioral, biological, and psychological outcomes were assessed using unpaired T-tests and ANCOVA in the 29 subjects who completed the intervention. RESULTS: The GI group demonstrated significant reductions in leisure sedentary behavior (p < .05) and increases in moderate physical activity (p < .05) compared to DS group, and a trend toward reduced caloric intake in GI vs DS (p = .09). Salivary cortisol was acutely reduced by stress-reduction guided imagery (p < .01). There were no group differences in adiposity, insulin resistance, perceived stress, or stress biomarkers across the 12-week intervention, though decrease in serum cortisol over the course of the intervention was associated with improved insulin sensitivity (p = .03) independent of intervention group and other relevant co-variates. CONCLUSIONS: The improvements in physical activity and stress biomarkers following this pilot intervention support the role of guided imagery in promoting healthy lifestyle behavior change and reducing metabolic disease risk in obese Latino adolescent populations. Future investigations will be needed to determine the full effects of the Imagine HEALTH intervention on insulin resistance, stress, and stress biomarkers. TRIAL REGISTRATION: Clinicaltrials.gov Registry #: NCT01895595.

The modified fasanella-servat procedure: description and quantified analysis.

PURPOSE: To describe a modified Fasanella-Servat procedure and nomogram for the correction of minimal amounts of ptosis. METHODS: Retrospective review of this modified Fasanella-Servat procedure was performed on 118 eyelids in 86 consecutive patients over 2, 4-year periods by 1 surgeon (S.C.D.). The amount of tarsectomy was based on the amount of ptosis. RESULTS: Mean pre- and postoperative margin-to-reflex distance 1 were +0.7 mm and +2.4mm, respectively. One hundred and twelve eyelids (95%) had satisfactory results with postoperative margin-to-reflex distance 1 ≥ 1.5 mm. Eyelid symmetry was achieved in 92% of eyelids to within 0.5 mm. There was no incidence of overcorrection, tarsal buckling, or corneal abrasion. One eyelid had a contour deficit. Tarsectomy amount ranged from 2 mm to 5 mm. Average amount of tarsectomy to eyelid elevation was 2.4:1. CONCLUSIONS: The modified Fasanella-Servat procedure is technically easy, time-efficient, and has a low complication rate for the treatment of minimal blepharoptosis (< 2.5 mm) with good levator function and negative phenylephrine test. In the authors' hands, the ratio of tarsectomy to eyelid elevation is approximately 2:1. In addition to other techniques such as levator advancement and Müller's muscle conjunctival resection, the modified Fasanella-Servat technique is a useful adjunct to the modern ptosis surgeon's armamentarium.

Dynamic telecytology compares favorably to rapid onsite evaluation of endoscopic ultrasound fine needle aspirates.

BACKGROUND AND AIMS: Rapid onsite evaluation (ROSE) has been demonstrated to correlate with final cytologic interpretations and improves the diagnostic yield of endoscopic ultrasound (EUS)-fine needle aspiration (FNA); however, its availability is variable across centers. The aim of this prospective study was to evaluate whether remote telecytology can substitute for ROSE. METHODS: Consecutive patients who underwent EUS-FNA for diverse indications at a high volume referral center were enrolled and all samples were prospectively evaluated by three methods. ROSE was performed by a cytopathologist in the procedure room; simultaneously dynamic telecytology was done by a different cytopathologist in a remote location at our institution. The third method, final cytologic interpretation in the laboratory, was the gold standard. Telecytology was performed using an Olympus microscope system (BX) which broadcasts live images over the Internet. Accuracy of telecytology and agreement with other methods were the principle outcome measurements. RESULTS: Twenty-five consecutive samples were obtained from participants 40-87 years old (median age 63, 48 % male). There was 88 % agreement between telecytology and final cytology (p < 0.001) and 92 % agreement between ROSE and final cytology (p < 0.001). There was consistency between telecytology and ROSE (p value for McNemar's χ(2) = 1.0). Cohen's kappa for agreement for telecytology and ROSE was 0.80 (SE = 0.11), confirming favorable correlation. CONCLUSION: Dynamic telecytology compares favorably to ROSE in the assessment of EUS acquired fine needle aspirates. If confirmed by larger trials, this system might obviate the need for onsite interpretation of EUS-FNA specimens.