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Systemic corticosteroids are commonly prescribed for palliation of dyspnoea in patients with cancer, despite scarce evidence to support their use. We aimed to assess the effect of high-dose dexamethasone versus placebo on cancer-related dyspnoea.The parallel-group, double-blind, randomised, controlled ABCD (Alleviating Breathlessness in Cancer Patients with Dexamethasone) trial was done at the at the University of Texas MD Anderson Cancer Center and the general oncology clinic at Lyndon B Johnson General Hospital (both in Houston, TX, USA). Ambulatory patients with cancer, aged 18 years or older, and with an average dyspnoea intensity score on an 11-point numerical rating scale (NRS; 0=none, 10=worst) over the past week of 4 or higher were randomly assigned (2:1) to receive dexamethasone 8 mg orally every 12 h for 7 days followed by 4 mg orally every 12 h for 7 days, or matching placebo capsules for 14 days. Pharmacists did permuted block randomisation with a block size of six, and patients were stratified by baseline dyspnoea score (4-6 vs 7-10) and study site. Patients, research staff, and clinicians were masked to group assignment. The primary outcome was change in dyspnoea NRS intensity over the past 24 h from baseline to day 7 (±2 days). Analyses were done by modified intention-to-treat (ie, including all patients who were randomly assigned and started the study treatment, regardless of whether they completed the study). Enrolment was stopped after the second preplanned interim analysis, when the futility criterion was met. This study is registered with ClinicalTrials.gov (NCT03367156) and is now completed.Between Jan 11, 2018, and April 23, 2021, we screened 2867 patients, enrolled 149 patients, and randomly assigned 128 to dexamethasone (n=85) or placebo (n=43). The mean change in dyspnoea NRS intensity from baseline to day 7 (±2 days) was -1·6 (95% CI -2·0 to -1·2) in the dexamethasone group and -1·6 (-2·3 to -0·9) in the placebo group, with no significant between-group difference (mean 0 [95% CI -0·8 to 0·7]; p=0·48). The most common all-cause grade 3-4 adverse events were infections (nine [11%] of 85 patients in the dexamethasone group vs three [7%] of 43 in the placebo group), insomnia (seven [8%] vs one [2%]), and neuropsychiatric symptoms (three [4%] vs none [0%]). Serious adverse events, all resulting in hospital admissions, were reported in 24 (28%) of 85 patients in the dexamethasone group and in three (7%) of 43 patients in the placebo group. No treatment-related deaths occurred in either group.High-dose dexamethasone did not improve dyspnoea in patients with cancer more effectively than placebo and was associated with a higher frequency of adverse events. These data suggest that dexamethasone should not be routinely given to unselected patients with cancer for palliation of dyspnoea.US National Cancer Institute.

Few studies have assessed interventions aimed at managing nonmedical opioid use (NMOU) behavior among patients with cancer. The authors developed the Compassionate High-Alert Team (CHAT) intervention to manage patients receiving opioids for cancer pain who demonstrate NMOU behavior. The objective of this study was to determine the change in frequency of NMOU behaviors, pain intensity, and opioid requirements among those who received the intervention.A total of 130 patients receiving opioids for cancer pain that had documented evidence of NMOU and received the CHAT intervention were reviewed. Demographic and clinical information such as NMOU behaviors, pain scores, and morphine equivalent daily dose at baseline, 3, and 6 months post-intervention was obtained.NMOU behaviors significantly decreased from a median (interquartile range) of 2 (1-3) at baseline to 0 (0-1) at both 3 and 6 months post-intervention (p .001). A total of 45 of 75 (60%) and 31 of 50 (62%) of CHAT recipients achieved complete response to the intervention at 3 and 6 months, respectively. Higher baseline number of NMOU behaviors was independently associated with patient response to the intervention (odds ratio [OR], 1.97; 95% confidence interval [CI],1.09-4.28, p = .049 at 3 months; OR, 2.5; 95% CI, 1.20-6.47, p = .03 at 6 months). The median pain score decreased from 7 at baseline to 6 at both 3 and 6 months (p = .01). Morphine equivalent daily dose did not significantly change during that same period (143 mg/day vs. 139 mg/day, p = .13).Most patients who received the CHAT intervention improved in their NMOU behaviors and pain intensity scores 3 and 6 months post-intervention. These preliminary findings support the efficacy of CHAT in managing patients receiving opioids for cancer pain who demonstrate NMOU behavior.

Introduction Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially. Methods We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for pneumonitis and mortality. Pneumonitis, pneumonia, and progression were modeled as time-dependent variables in mortality models. Results We evaluated 419 patients between 2013 and 2021. The cumulative incidence of pneumonitis was 9.5% (40/419). In a multivariate model, pneumonitis increased the risk for mortality (HR 1.6, 95% CI, 1.0-2.5), after adjustment for disease progression (HR 1.6, 95% CI, 1.4-1.8) and baseline shortness of breath (HR 1.5, 95% CI, 1.2-2.0). Incomplete resolution was more common with more severe pneumonitis. Interstitial lung disease was associated with higher risk for pneumonitis (HR 5.4, 95% CI, 1.1-26.6), particularly in never smokers (HR 26.9, 95% CI, 2.8-259.0). Conclusion Pneumonitis occurred at a high rate and significantly increased mortality. Interstitial lung disease, particularly in never smokers, increased the risk for pneumonitis.

Immune checkpoint inhibitors (ICI), combined with hypomethylating agents, can be used to treat acute myeloid leukemia (AML), but this strategy results in a high rate of pneumonitis. The authors sought to determine risk factors for pneumonitis development and whether pneumonitis increased mortality.The authors conducted a retrospective review of 258 AML patients who received ICI-containing regimens from 2016 to 2018. A multidisciplinary adjudication committee diagnosed pneumonia and pneumonitis by reviewing symptoms, imaging, microbiology, and response to therapies. To measure risk factors for pneumonitis and mortality, multivariate Cox proportional hazards models were constructed. Pneumonia, pneumonitis, and disease progression were modeled as a time-dependent variable and incorporated a standard risk set modifying variables into the models.Thirty patients developed pneumonitis (12%). Of these, 17 had partial or complete resolution, whereas 13 patients died from pneumonitis. Increasing age (hazard ratio [HR], 1.04 per year; 95% confidence interval [CI], 1.00-1.08), and baseline shortness of breath increased pneumonitis risk (HR, 2.51; 95% CI, 1.13-5.55). Female sex (HR, 0.33; 95% CI, 0.15-0.70) and increasing platelet count (HR, 0.52 per log-unit increase; 95% CI, 0.30-0.92) decreased pneumonitis risk. In adjusted models, ICI-related pneumonitis significantly increased mortality (HR, 2.84; 95% CI, 1.84-4.37).ICI-related pneumonitis occurs at a high rate in AML patients and increases mortality.Immune checkpoint inhibitors (ICIs) remove inhibitory signals that reduce T-cell function and allow T-cells to better attack cancer cells. In acute myeloid leukemia (AML), the effectiveness of ICIs is limited in part by inflammation of the lung, called pneumonitis. This study reviewed 258 patients with AML who received ICIs and identified 30 patients who developed pneumonitis, nearly half of whom died. Older age and baseline shortness of breath increased pneumonitis risk, whereas female sex and higher baseline platelet counts decreased pneumonitis risk. Pneumonitis increased mortality by nearly 3-fold. This work highlights the significant harm imposed by pneumonitis after ICI therapies.

Background Although intensity-modulated radiation therapy (IMRT) is considered the standard of care for the treatment of squamous cell carcinoma of the anus (SCCA), few large series have reported oncologic outcomes and toxicities. In this retrospective report, we aim to describe outcomes and toxicities after IMRT-based chemoradiation (CRT) for the treatment of SCCA, evaluate the impact of dose escalation (>54 Gy), and compare concurrent fluoropyrimidine in combination with either mitomycin or with cisplatin as chemosensitizers. Methods Patients treated at The University of Texas MD Anderson Cancer Center between January 1, 2003 and December 31, 2018 with IMRT-based CRT were included. Median time to locoregional recurrence, time to colostomy, and overall survival were estimated using the Kaplan–Meier method. Results A total of 428 patients were included; median follow-up was 4.4 years. Three hundred and thirty-four patients (78.0%) were treated with concurrent cisplatin and fluoropyrimidine, and 160 (37.4%) with >54 Gy. Two- and 5-year freedom from locoregional failure, freedom from colostomy failure, and overall survival were 86.5% and 81.2%, respectively, 90.0% and 88.3%, respectively, and 93.6% and 85.8%, respectively. Neither dose escalation nor mitomycin-based concurrent chemotherapy resulted in improved outcomes. Mitomycin-based concurrent chemotherapy was associated with in approximately 2.5 times increased grade 3 or greater acute toxicity. Radiation dose >54 Gy was associated with approximately 2.6 times increased Grade 3 or greater chronic toxicity. Conclusions Our results suggest IMRT-based CRT with concurrent fluoropyrimidine and cisplatin is a safe and feasible option for patient with SCCA and may cause less acute toxicity. The role for radiation dose escalation is unclear and requires further study.

The SARS‐CoV‐2 pandemic may negatively impact mood and emotion. Physical activity may protect against mood disturbance and promote positive affect. This study asked if physical activity before, during, or the change in physical activity with the pandemic, impacted affect and mood during the pandemic. US adult residents (18–74 years; N = 338) were surveyed from 29 April to 3 June 2020. Physical activity before and during the pandemic was assessed with the Physical Activity Rating survey. The Positive and Negative Affect Schedule measured affect and the Profile of Moods Questionnaire assessed mood. Comparisons between physically inactive and active participants by Analysis of Covariance found greater vigour in participants classed as physically active before the pandemic. Positive affect, vigour and esteem‐related affect were greater in participants physically active during the pandemic. Multiple linear regression revealed relationships between the change in physical activity and mood. Change in physical activity positively associated with positive affect (b = 1.06), esteem‐related affect (b = 0.33) and vigour (b = 0.53), and negatively associated with negative affect (b = −0.47), total mood disturbance (b = −2.60), tension (b = −0.31), anger (b = −0.24), fatigue (b = −0.54), depression (b = −0.50) and confusion (b = −0.23). These data demonstrate that physical activity during the pandemic, and increased physical activity relative to before the pandemic, related to better mood.

Background Previous work in HEK-293 cells demonstrated the importance of amino acid-induced mTORC1 translocation to the lysosomal surface for stimulating mTORC1 kinase activity and protein synthesis. This study tested the conservation of this amino acid sensing mechanism in human skeletal muscle by treating subjects with chloroquine—a lysosomotropic agent that induces in vitro and in vivo lysosome dysfunction. Methods mTORC1 signaling and muscle protein synthesis (MPS) were determined in vivo in a randomized controlled trial of 14 subjects (10 M, 4 F; 26 ± 4 year) that ingested 10 g of essential amino acids (EAA) after receiving 750 mg of chloroquine (CHQ, n = 7) or serving as controls (CON, n = 7; no chloroquine). Additionally, differentiated C2C12 cells were used to assess mTORC1 signaling and myotube protein synthesis (MyPS) in the presence and absence of leucine and the lysosomotropic agent chloroquine. Results mTORC1, S6K1, 4E-BP1 and rpS6 phosphorylation increased in both CON and CHQ 1 h post EAA ingestion (P P = 0.06; CHQ, P P Conclusions Chloroquine did not inhibit amino acid-induced activation of mTORC1 signaling and skeletal MPS in humans as it does in C2C12 muscle cells. Therefore, different in vivo experimental approaches are required for confirming the precise role of the lysosome and amino acid sensing in human skeletal muscle. Trial registration NCT00891696. Registered 29 April 2009.

Traumatic brain injury (TBI) induces cognitive deficits clinically and in animal models. Learning and memory testing is critical when evaluating potential therapeutic strategies and treatments to manage the effects of TBI. We evaluated three data analysis methods for the Morris water maze (MWM), a learning and memory assessment widely used in the neurotrauma field, to determine which statistical tool is optimal for MWM data. Hidden platform spatial MWM data aggregated from three separate experiments from the same laboratory were analyzed using 1) a logistic regression model, 2) an analysis of variance (ANOVA) model, and 3) an accelerated failure time (AFT) time-to-event model. The logistic regression model showed no significant evidence of differences between treatments among any swims over all days of the study, p > 0.11. Although the ANOVA model found significant evidence of differences between sham and TBI groups on three out of four swims on the third day, results are potentially biased due to the failure of this model to account for censoring. The time-to-event AFT model showed significant differences between sham and TBI over all swims on the third day, p

A bout of resistance exercise did not elicit the same T-cell responses as a bout of walking on a treadmill, and the response was also not the same for people who participate in regular exercise compared with those who do not. Although there were several similarities, these potential differences underscore the importance of careful selection of exercise protocol based on the population studied and the desired T-cell response to exercise outcome.

The paleo diet is popular among the general population due to promoted weight loss and disease prevention benefits. We examined the effectiveness of a self-administered paleo diet in improving cardiometabolic disease risk factors. Overweight, physically inactive but otherwise healthy adults (males = 4, females = 3, age 32.7 ± 4.9 years, body mass index [BMI] 29.4 ± 2.4 kg/m2) habitually eating a traditional Western diet (1853.4 ± 441.2 kcal; 34.0% carbohydrate; 41.4% fat; 19.2% protein) completed an ad libitum self-administered paleo diet for 8 weeks. Height, weight, blood pressure, and a fasting blood sample were collected pre– and post–paleo dietary intervention. Blood samples were analyzed for fasting cardiometabolic disease biomarkers—including brain-derived neurotropic factor (BDNF), fibroblast growth factor (FGF) 21, and leptin. After 8 weeks, body mass (−5.3 kg, P = .008), BMI (−1.7 kg/m2, P = .002), serum leptin (−56.2%, P = .012), serum FGF21 (−26.7%, P = .002), and serum BDNF (−25.8%, P = .045) significantly decreased. Systolic and diastolic blood pressure were unchanged following the paleo dietary intervention ( P > .05). Average energy intake (−412.6 kcal, P = .016) significantly decreased with the paleo dietary intervention mostly due to a reduction in carbohydrate consumption (−69.2 g; P = .003). An 8-week self-administered paleo dietary intervention was effective in improving cardiometabolic disease risk factors in a healthy, physically inactive overweight adult population.

12112 Background: Systemic corticosteroids are commonly prescribed for palliation of dyspnea in patients with cancer; however, evidence to support their use is limited. A small RCT suggested that dexamethasone may be efficacious. In this confirmatory RCT, we compared the effect of high dose dexamethasone and placebo on dyspnea in patients with cancer. Methods: This NCI-funded, multi-site, double-blind, parallel group RCT enrolled ambulatory patients with cancer, age ≥18, dyspnea ≥4/10 and randomly assigned them to receive dexamethasone 8 mg orally every 12 hours for 7 days followed by 4 mg orally every 12 hours for 7 days or matching placebo capsules. Permuted block randomization (block size = 6, 2:1) was conducted, stratified by baseline dyspnea and study site. Patients, research staff and clinicians were blinded. The primary outcome was change in average dyspnea intensity assessed with a 0-10 numeric rating scale (0 = none, 10 = worst) between baseline and day 7. Secondary outcomes included the Edmonton Symptom Assessment Scale (ESAS) and adverse effects (CTCAE v4.02). Intention-to-treat analysis was conducted with linear models to compare between groups. The planned sample size of 201 patients provided 80% power to detect a mean difference of 1.0 between treatment groups with a two-sided α of 5%, assuming a standard deviation of 2.0 and 15% attrition. (Clinicaltrials.gov NCT03367156). Results: Between 1/11/2017 and 4/23/2021, we enrolled 149 patients and 128 received the blinded study interventions (dexamethasone n = 85, placebo n = 43). Enrollment was terminated early by the Data Safety Monitoring Board when futility criterion was met in pre-planned interim analysis. The mean change in dyspnea NRS intensity between baseline and day 7 was -1.6 (95% CI -2, -1.2) in the dexamethasone group and -1.6 (95% CI -2.3, -0.9) in the placebo group, with no significant between-group difference (mean 0, 95% CI -0.8, 0.7; P = 0.91). Secondary analyses showed that the dexamethasone group had a significantly better ESAS appetite (mean difference -1.2, 95% CI -2.2, -0.1; P = 0.03) and well being (mean -1, 95% CI -1.8, -0.2; P = 0.02), and worse ESAS anxiety (mean 1.1, 95% CI 0.3, 1.9; P = 0.01) and depression (mean 0.9, 95% CI 0.1, 1.7; P = 0.02) compared to placebo. Similar magnitude of changes in dyspnea and ESAS symptoms were observed by day 14. Adverse effects were reported more frequently in the dexamethasone group (any grade): insomnia (38% v. 12%), neuropsychiatric symptoms (31% vs. 7%), infections (21% v. 12%), dyspepsia (26% v. 12%), edema (18% v. 9%), hiccups (12% v. 7%), flushing (9% v. 5%) and respiratory distress (6% v. 0%). More patients in the dexamethasone group required hospitalization within 30 d of last study medication (25% vs. 7%, P = 0.02). Conclusions: High dose dexamethasone did not improve dyspnea in patients with cancer more than placebo and was associated with more adverse events. Clinical trial information: NCT03367156.

Aging is associated with many chronic diseases that are maintained and perpetuated by immune dysregulation and chronic systemic inflammation. T-cells often undergo age-related changes, including an accumulation of memory cells, which places individuals at increased risk for novel infections and may predispose them to increased inflammation. Regular exercise training has been suggested to offset age-related changes in T-cells, but the majority of literature is derived from cardiorespiratory exercise (CRE) studies. Much less is understood about the T-cell response to resistance exercise (RE). The purpose of this study was to examine the effects of acute CRE and acute RE on the T-cell response among a cohort of physically active older adults (PA) compared to a cohort of physically inactive older adults (PI).METHODSTwenty-four healthy older adults (PA n=12; PI n=12; mean ± SD; age (yrs) PA 62 ± 5, PI 64 ± 5; height (cm) PA 170.9 ± 6.9, PI 162.9 ± 8.0; weight (kg) PA 69.3 ± 10.2, PI 68.2 ± 12.8; BMI (kg/m2) PA 23.9 ± 3.0, PI 25.6 ± 3.5) completed one bout of CRE and one bout of RE in a randomized order, both at a moderate intensity, and separated by at least 7 days. Blood samples drawn pre-exercise, post-exercise, and 1h post-exercise (recovery) were analyzed for CD4+ and CD8+ T-cells and their differentiation status using surface markers CD45RA, CD62L, and CD57, as well as for Th17 cells (CD4+ CD161+ CD196+) using flow cytometry.RESULTSPI had higher numbers of circulating CD57+ EMRA CD4+ T-cells (PA, mean ± SE, 1 ± 2 cells/uL; PI, 6 ± 2 cells/uL; p=0.01; z=2.32) than PA at pre-exercise. Both CRE and RE elicited a significant mobilization of highly-differentiated (CD45RA+ CD62L-; CD57+ CD45RA+ CD62L-) CD8+ T-cells into the circulation post-exercise in both PA and PI groups. Furthermore, CRE resulted in a decrease in the number of circulating Th17 cells post-exercise, while RE increased Th17 cell mobilization compared to the CRE response.CONCLUSIONTaken together, T-cells in PA and PI respond similarly to acute CRE and support previously reported data showing a significant mobilization of highly differentiated T-cells. The present study confirms that moderate intensity RE also elicits this response, but highlights potential differences between CRE and RE on the immune responses of T-cells, particularly in PI individuals.Clinical trial registrationThis research study was registered at clinicaltrials.gov NCT03794050

The Paleolithic diet, characterized by an emphasis on hunter-gatherer type foods accompanied by an exclusion of grains, dairy products, and highly processed food items, is often promoted for weight loss and a reduction in cardiometabolic disease risk factors. Specific adipokines, such as adiponectin, omentin, nesfatin, and vaspin are reported to be dysregulated with obesity and may respond favorably to diet-induced fat loss. We aimed to evaluate the effects of an eight-week Paleolithic dietary intervention on circulating adiponectin, omentin, nesfatin, and vaspin in a cohort of physically inactive, but otherwise healthy adults. Methods: Seven inactive adults participated in eight weeks of adherence to the Paleolithic Diet. Fasting blood samples, anthropometric, and body composition data were collected from each participant pre-and post-intervention. Serum adiponectin, omentin, nesfatin, and vaspin were measured. Results: After eight weeks of following the Paleolithic diet, there were reductions (p0.05), while serum vaspin levels for all participants were undetectable. Conclusions: It is possible that although eight weeks resulted in modest body composition changes, short-term fat loss will not induce changes in adiponectin, omentin, and nesfatin in apparently healthy adults. Larger, long-term intervention studies that examine Paleolithic diet-induced changes across sex, body composition, and in populations with metabolic dysregulation are warranted.

Background: Brief counseling and self-monitoring with a pedometer are common practice within primary care for physical activity promotion. It is unknown how high-tech electronic activity monitors compare to pedometers within this setting. This study aimed to investigate the outcomes, through effect size estimation, of an electronic activity monitor-based intervention to increase physical activity and decrease cardiovascular disease risk. Method: The pilot randomized controlled trial was pre-registered online at clinicaltrials.gov (NCT02554435). Forty overweight, sedentary participants 55&ndash, 74 years of age were randomized to wear a pedometer or an electronic activity monitor for 12 weeks. Physical activity was measured objectively for 7 days at baseline and follow-up by a SenseWear monitor and cardiovascular disease risk was estimated by the Framingham risk calculator. Results: Effect sizes for behavioral and health outcomes ranged from small to medium. While these effect sizes were favorable to the intervention group for physical activity (PA) (d = 0.78) and general health (d = 0.39), they were not favorable for measures. Conclusion: The results of this pilot trial show promise for this low-intensity intervention strategy, but large-scale trials are needed to test its efficacy.

Background: It is well accepted that exercise has numerous health benefits, including reducing the risk of developing cardiometabolic diseases and supporting a healthy immune system. Although these benefits are widely recognized, variations in the exercise response still exist. The aim of this study is to explore the variations that may be partially explained by participant age, physical activity status, and/or mode of exercise. Methods: The CAARE (Comparing Acute Aerobic vs. Resistance Exercise) study is a randomized cross-over design trial. Participants are young (18-30 years) or older (55-75 years), and within each age group are either physically active or inactive. All participants complete two acute exercise sessions of similar intensity and duration: a resistance training bout and a treadmill exercise bout. Blood is collected before exercise (PRE), immediately after exercise (POST), and after one hour of recovery (RECOV). Fresh blood is used for flow cytometry analyses to phenotype immune cells. Serum is stored for future analyses. The primary outcome variables are monocyte and T-cell phenotype. Discussion: CAARE is the first study to compare the immune cell response to acute exercise when including age, physical activity status, and mode of exercise. Clinical trial registration: This research study was registered at clinicaltrials.gov NCT03794050 in January 4, 2019. https://clinicaltrials.gov/ct2/show/NCT03794050

Introduction Mature T-cell lymphomas (TCLs) represent about 15% of the non-Hodgkin lymphomas in U.S. and are a heterogeneous group of neoplasms. TCLs usually have poor outcomes and are resistant to conventional chemotherapy regimens. Therefore, there is a need for identifying biomarkers that could translate into effective novel treatments. CD70 is the TNF superfamily ligand of CD27 and it is being explored as a potential target in CAR-T therapy against TCLs and other neoplasms. Although CD70 expression has been documented in TCL cell lines, thus providing a potential rationale for its use as a therapeutic target, the expression of CD70 among the most frequent TCL subtypes in patient samples has not been previously evaluated. Methods Patients with de novo and/or relapsed mature TCLs diagnosed between 01/2010 and 06/2020 and with available tissue sections were included in the study. The assessment of CD70 expression was performed by immunohistochemistry (IHC) using a novel proprietary antibody developed by CRISPR Therapeutics. CD70 expression was scored using % of expression, intensity (negative, +1, +2, and +3) and H-score {H-score = [(%positive cells intensity 1+) x 1] + [(%positive cells intensity 2+) x 2] + [(%positive cells intensity 3+) x 3]} in neoplastic cells (Figure 1). Clinicopathologic characteristics were collected retrospectively and included age, sex, staging, biopsy site, WHO pathologic classification, immunophenotype, presence of other malignancies, treatment status, disease progression/relapsed, and follow-up. These characteristics were compared with CD70 expression using ANOVA or non-parametric analysis. Overall-survival (OS) was estimated using Kaplan-Meier method and compared using log-rank. A p< 0.05 was considered statistically significant. Results One hundred thirty-six patient samples representing the major subtypes of the 4 categories of mature TCLs were included [nodal TCLs (n=64; including PTCL Th1, and Th2 subtypes and angioimmunoblastic T cell lymphoma - AITL), extranodal (n=35; including primary intestinal lymphomas), cutaneous (n=24; including mycosis fungoides (MF) with large cell transformation), and leukemic (n=13; including adult T cell leukemia/lymphoma)]. Most patients were male (58.8%), in the 6 th or 7 th decade (47.1%), with advanced stage IV (55.7%), no previous malignancies (69.9%) and previously treated (57.2%); 59 of which (88%) received two or more lines of treatment. The median expression of CD70 was 40% (ranged from 0 to 100%) and the median H-score was 110 (ranged from 0 to 300) and was significantly higher (p= 0.006) in peripheral T-cell lymphoma, NOS, primary cutaneous TCLs (non-mycosis fungoides), and AITL (180, 150, and 150, respectively) (Figure 1). The expression of CD70 was more frequent in nodal and extranodal subtypes (including skin), compared to leukemic TCLs (p= 0.005). The expression of CD70 was associated with advanced age at the diagnosis (p= 0.003), CD2 expression (p= 0.01), CD3 expression (p= 0.001), CD16 negativity (p= 0.03), and absence of ALK-1 expression (p= 0.005). After a median follow-up of 19 months (range: 1 - 300 months), 42% of the patients died of disease. The median OS was 76 months (CI95, 38.5 - 113.4 months) and it was not associated with CD70 expression. Conclusions CD70 was highly expressed in most mature TCLs and it was negative in most ALK-positive ALCL. Its expression was associated with nodal and extranodal subtypes, advanced age, expression of CD2, CD3, and negativity for CD16. Therefore, CD70 can be used as a potential biomarker and a target in clinical trials of patients with mature TCLs. Figure 1 Figure 1. Disclosures Iyer: CRISPRX: Research Funding; Seattle Genetics: Research Funding; Rhizen: Research Funding; Merck: Research Funding; Legend: Research Funding; Innate: Research Funding; Spectrum: Research Funding; Trillium: Research Funding; Astra Zeneca: Research Funding; Yingli: Research Funding; Cyclacel: Research Funding. Sagert: CRISPR Therapeutics: Current Employment. Pham: CRISPR Therapeutics: Current Employment. Tipton: CRISPR Therapeutics: Current Employment. Vega: i3Health, Elsevier, America Registry of Pathology, Congressionally Directed Medical Research Program, and the Society of Hematology Oncology: Research Funding; CRISPR Therapeutics and Geron: Research Funding.

Summary Background Sepsis, trauma, and burn injury acutely depress systolic and diastolic cardiac function; data for long-term cardiac sequelae of paediatric critical illness are sparse. We aimed to assess long-term systolic and diastolic function, myocardial fibrosis, and exercise tolerance in adolescent survivors of severe paediatric burn injury. Methods In this observational study, we prospectively studied consecutive participants (any age or sex) returning to our institution (Shriners Hospitals for Children, Galveston, TX, USA) for long-term follow-up or reconstructive procedures, who had a history of severe paediatric burn injury affecting at least 30% of their total body surface area, sustained the injury at least 5 years before enrolment, and were treated acutely at our institution. Age-matched healthy controls were individuals who underwent echocardiographic evaluation for systolic and diastolic function as well as exercise testing during the same time period at the institution. Participants underwent echocardiography to quantify systolic function (ejection fraction), diastolic function (E/e'), and myocardial fibrosis (calibrated integrated backscatter) of the left ventricle. Exercise tolerance was quantified by oxygen consumption (VO 2 ) and heart rate at rest and during peak exercise. Demographic information, clinical data, and biomarker expression were used to predict long-term cardiac dysfunction and fibrosis. Findings Between April 23, 2016, and April 5, 2017, 65 participants (40 post-burn and 25 healthy controls) were eligible for inclusion and were enrolled in the study. At study initiation, post-burn participants were an average age of 19 years (SD 5), were at 12 years (SD 4) post-burn, and had burns over 59% (SD 19) of total body surface area, sustained at 8 years (SD 5) of age. The post-burn group had a lower ejection fraction than healthy controls (ejection fraction 52% [SD 9] vs 61% [6], respectively; p=0·004), and more impaired diastolic function (E/e' 9·8 [SD 2·9] vs 5·4 [0·9]; p 2 peak 38 mL/min/kg [SD 12] vs 46 mL/min/kg [8], respectively; p=0·03) and a lower peak heart rate (161 beats per min [bpm; SD 26] vs 182 bpm [13], respectively; p=0·006). In the post-burn group, 11 (29%) individuals had moderate systolic dysfunction and six (15%) had severe systolic dysfunction; 19 (50%) had moderate diastolic dysfunction and eight (21%) had severe diastolic dysfunction; and seven (18%) individuals showed signs of myocardial fibrosis. Interpretation Severe paediatric burn injury might have lasting effect on cardiac function into late adolescence and is associated with myocardial fibrosis and reduced exercise tolerance. Given the strong predictive value of systolic and diastolic dysfunction, these patients might be at increased risk of early heart failure, associated morbidity, and mortality. Funding National Institutes of Health (NIH), National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR), Shriners Hospitals for Children, Foundation for Anesthesia Education and Research (FAER), and the US Department of Defense.

Objective To examine the effect of home- and community-based physical activity interventions on physical functioning among cancer survivors based on the most prevalent physical function measures, randomized trials were reviewed. Data Sources Five electronic databases—Medline Ovid, PubMed, CINAHL, Web of Science, and PsycINFO—were searched from inception to March 2016 for relevant articles. Study Selection Search terms included community-based interventions, physical functioning, and cancer survivors. A reference librarian trained in systematic reviews conducted the final search. Data Extraction Four reviewers evaluated eligibility and 2 reviewers evaluated methodological quality. Data were abstracted from studies that used the most prevalent physical function measurement tools—Medical Outcomes Study 36-Item Short-Form Health Survey, Late-Life Function and Disability Instrument, European Organisation for the Research and Treatment of Cancer Quality-of-Life Questionnaire, and 6-minute walk test. Random- or fixed-effects models were conducted to obtain overall effect size per physical function measure. Data Synthesis Fourteen studies met inclusion criteria and were used to compute standardized mean differences using the inverse variance statistical method. The median sample size was 83 participants. Most of the studies (n=7) were conducted among breast cancer survivors. The interventions produced short-term positive effects on physical functioning, with overall effect sizes ranging from small (.17; 95% confidence interval [CI], .07–.27) to medium (.45; 95% CI, .23–.67). Community-based interventions that met in groups and used behavioral change strategies produced the largest effect sizes. Conclusions Home and community-based physical activity interventions may be a potential tool to combat functional deterioration among aging cancer survivors. More studies are needed among other cancer types using clinically relevant objective functional measures (eg, gait speed) to accelerate translation into the community and clinical practice.

Acupuncture treatment has been used in China for2500 years, and at present it is used worldwide as a form of analgesia in patients with acute and chronic pain. Furthermore, acupuncture is regularly used not only as a single anesthetic technique but also as a supplement or in addition to general anesthesia (GA).The aim of this systematic review and meta-analysis was to assess the level of evidence for the clinical use of acupuncture in addition to GA in patients undergoing craniotomy.This is a systematic review of randomized controlled trials with meta-analyses.The literature search (PubMed, Cochrane Library, and Web of Science) yielded 56 citations, published between 1972 and March 01, 2015. No systematic review or meta-analyses on this topic matched our search criteria. Each article of any language was assessed and rated for the methodological quality of the studies, using the recommendation of the Oxford Centre for Evidence Based Medicine. Ten prospective randomized controlled clinical trials with a total of 700 patients were included.Included in the meta-analysis were studies that involved any craniotomy under GA compared with a combination of GA and acupuncture. Exclusion criteria were no acupuncture during surgery, no GA during surgery, only postoperative data available, animal studies, and low grade of evidence.The use of acupuncture significantly reduced the amount of volatile anesthetics during surgery (P0.001) and led to faster extubation time (P=0.001) and postoperative patient recovery (P=0.003). In addition, significantly reduced blood levels of the brain tissue injury marker S100β 48 hours after operation (P=0.001) and occurrence of postoperative nausea and vomiting (P=0.017) were observed. No patient studied suffered from awareness.The analysis suggests that the complementary use of acupuncture for craniotomy has additional analgesic effects, reduces the needed amount of volatile anesthetic, reduces the onset of postoperative nausea and vomiting, and might have protective effects on brain tissue. Our findings may stimulate future randomized controlled trials to provide definitive recommendations.

It has been proposed that protein supplementation during resistance exercise training enhances muscle hypertrophy. The degree of hypertrophy during training is controlled in part through the activation of satellite cells and myonuclear accretion.This study aimed to determine the efficacy of protein supplementation (and the type of protein) during traditional resistance training on myofiber cross-sectional area, satellite cell content, and myonuclear addition.Healthy young men participated in supervised whole-body progressive resistance training 3 d·wk for 12 wk. Participants were randomized to one of three groups ingesting a daily 22-g macronutrient dose of soy-dairy protein blend (PB, n = 22), whey protein isolate (WP, n = 15), or an isocaloric maltodextrin placebo (MDP, n = 17). Lean mass, vastus lateralis myofiber-type-specific cross-sectional area, satellite cell content, and myonuclear addition were assessed before and after resistance training.PB and the pooled protein treatments (PB + WP = PRO) exhibited a greater whole-body lean mass %change compared with MDP (P = 0.057 for PB) and (P = 0.050 for PRO), respectively. All treatments demonstrated similar leg muscle hypertrophy and vastus lateralis myofiber-type-specific cross-sectional area (P0.05). Increases in myosin heavy chain I and II myofiber satellite cell content and myonuclei content were also detected after exercise training (P0.05).Protein supplementation during resistance training has a modest effect on whole-body lean mass as compared with exercise training without protein supplementation, and there was no effect on any outcome between protein supplement types (blend vs whey). However, protein supplementation did not enhance resistance exercise-induced increases in myofiber hypertrophy, satellite cell content, or myonuclear addition in young healthy men. We propose that as long as protein intake is adequate during muscle overload, the adaptations in muscle growth and function will not be influenced by protein supplementation.

Objectives To demonstrate the feasibility and efficacy of the Google Glass as a tool to improve patient satisfaction and patient-physician communication for otolaryngology residents in the outpatient clinic setting. The primary outcome of the study was to improve patient satisfaction scores based on physician communication related questions from Consumer Assessment of Healthcare Providers and Systems (CAHPS) surveys. Study Design Prospective randomized trial. Setting Tertiary care hospital. Subject and Methods To evaluate the effect on patient satisfaction, five residents were recorded using the Google Glass in an outpatient clinic setting by 50 randomized patients. Modified surveys based on the CG-CAHPS survey were completed by patients at the conclusion of each clinic encounter. The recorded videos were evaluated by 2 independent faculty. Summarized data and video were distributed to each resident for review as the intervention. The residents were recorded again by 45 additional patients with evaluation by patients and faculty. Results After intervention, the scores from faculty-surveys regarding patient satisfaction including the subject of better explanations (p>0.001), listening carefully (p>0.001), addressing patient questions (p>0.001), displaying respect (p>0.001), and spending adequate time (p=0.0005) all significantly improved, as well as overall performance (p=0.014). The scores from patient-surveys did significantly improve. Conclusion This study demonstrates the improvements in patient satisfaction and patient-physician communication can be achieved with the use of Google Glass as a first person recording device in the outpatient otolaryngology clinic setting. This article is protected by copyright. All rights reserved.

BACKGROUND Previous work demonstrated that a soy-dairy protein blend (PB) prolongs hyperaminoacidemia and muscle protein synthesis in young adults after resistance exercise. OBJECTIVE We investigated the effect of PB in older adults. We hypothesized that PB would prolong hyperaminoacidemia, enhancing mechanistic target of rapamycin complex 1 (mTORC1) signaling and muscle protein anabolism compared with a whey protein isolate (WPI). METHODS This double-blind, randomized controlled trial studied men 55-75 y of age. Subjects consumed 30 g protein from WPI or PB (25% soy, 25% whey, and 50% casein) 1 h after leg extension exercise (8 sets of 10 repetitions at 70% one-repetition maximum). Blood and muscle amino acid concentrations and basal and postexercise muscle protein turnover were measured by using stable isotopic methods. Muscle mTORC1 signaling was assessed by immunoblotting. RESULTS Both groups increased amino acid concentrations (P < 0.05) and mTORC1 signaling after protein ingestion (P < 0.05). Postexercise fractional synthesis rate (FSR; P ≥ 0.05), fractional breakdown rate (FBR; P ≥ 0.05), and net balance (P = 0.08) did not differ between groups. WPI increased FSR by 67% (mean ± SEM: rest: 0.05% ± 0.01%; postexercise: 0.09% ± 0.01%; P < 0.05), decreased FBR by 46% (rest: 0.17% ± 0.01%; postexercise: 0.09% ± 0.03%; P < 0.05), and made net balance less negative (P < 0.05). PB ingestion did not increase FSR (rest: 0.07% ± 0.03%; postexercise: 0.09% ± 0.01%; P ≥ 0.05), tended to decrease FBR by 42% (rest: 0.25% ± 0.08%; postexercise: 0.15% ± 0.08%; P = 0.08), and made net balance less negative (P < 0.05). Within-group percentage of change differences were not different between groups for FSR, FBR, or net balance (P ≥ 0.05). CONCLUSIONS WPI and PB ingestion after exercise in older men induced similar responses in hyperaminoacidemia, mTORC1 signaling, muscle protein synthesis, and breakdown. These data add new evidence for the use of whey or soy-dairy PBs as targeted nutritional interventions to counteract sarcopenia. This trial was registered at clinicaltrials.gov as NCT01847261.

Background: To our knowledge the efficacy of soy-dairy protein blend (PB) supplementation with resistance exercise training (RET) has not been evaluated in a longitudinal study. Objective: Our aim was to determine the effect of PB supplementation during RET on muscle adaptation. Methods: In this double-blind randomized clinical trial, healthy young men [18–30 y; BMI (in kg/m2): 25 ± 0.5] participated in supervised whole-body RET at 60–80% 1-repetition maximum (1-RM) for 3 d/wk for 12 wk with random assignment to daily receive 22 g PB (n = 23), whey protein (WP) isolate (n = 22), or an isocaloric maltodextrin (carbohydrate) placebo [(MDP) n = 23]. Serum testosterone, muscle strength, thigh muscle thickness (MT), myofiber cross-sectional area (mCSA), and lean body mass (LBM) were assessed before and after 6 and 12 wk of RET. Results: All treatments increased LBM (P 0.10) between treatments. Testosterone was not altered. Conclusions: PB supplementation during 3 mo of RET tended to slightly enhance gains in whole-body and arm LBM, but not leg muscle mass, compared with RET without protein supplementation. Although protein supplementation minimally enhanced gains in LBM of healthy young men, there was no enhancement of gains in strength. This trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT01749189","term_id":"NCT01749189"}}NCT01749189.

To determine if there are any differences in the patient populations that choose subdermal implants versus intrauterine devices (IUDs) for contraceptive purposes.Retrospective chart review. Electronic medical records of women who presented to the University of Texas Medical Branch in Galveston's Regional Maternal Child Health Program Clinics in southeast Texas from March 2011 to March 2013 and received a subdermal implant or IUD were reviewed. Differences in characteristics of women who chose either form of contraception were determined.A total of 356 charts were reviewed. Of those, 188 (53%) women chose the subdermal implant and 168 (47%) chose an IUD. Patients who chose subdermal implants were more likely to have had a long-acting reversible contraceptive (LARC) method previously (p0.01), previous vaginal deliveries (p0.001), and an interval from delivery to LARC placement of1 year (p0.001). LARC choice was race-specific in that, when compared to Caucasian women, African-American women were significantly more likely to choose an IUD, while Hispanic women were significantly more likely to choose subdermal implants (p=0.002).Different populations choose subdermal implants versus IUDs for contraception. Further research is needed to determine etiologies for these differences.

BACKGROUND: Massive burns induce a hypermetabolic response that leads to total body wasting and impaired physical and psychosocial recovery. The administration of propranolol or oxandrolone positively affects postburn metabolism and growth. The combined administration of oxandrolone and propranolol (OxProp) for one year restores growth in children with large burns. Here we investigated whether the combined administration of oxandrolone and propranolol for one year would reduce scarring and improve quality of life compared to control. STUDY DESIGN: Children with large burns (n=480) were enrolled into this IRB-approved study; patients were randomized to control (n=226) or administration of OxProp (n=126) for 1 year postburn. Assessments were conducted at discharge and 6, 12, and 24 months postburn. Scar biopsies were obtained for histology. Physical scar assessments and patient reported outcome measures of physical and psychosocial function were obtained. RESULTS: Reductions in cellularity, vascular structures, inflammation, and abnormal collagen (p

BACKGROUND: The standard of burn treatment today reflects major advances. We sought to quantitate the impact of these advances on burn survival via age-stratified mortality ratios compared to other reported mortality analyses in burns. STUDY DESIGN: Age, percent of the total body surface area (TBSA) burned, presence of inhalation injury, length of stay, and survival status were recorded at admission and at discharge for all new burn admissions between 1989 and 2017. The expected mortality probability was calculated using historical multiple regression techniques and compared with observed data. We developed a prediction model for our observed data. RESULTS: Between 1989 and 2017, there were 10,384 consecutive new burn admissions with 355 mortalities (median age: 13 years; median percent TBSA burn: 11%). We observed a significant decrease in our observed mortality data compared to historical predictions (p

Background Essential amino acids (EAA) and aerobic exercise (AE) acutely and independently stimulate skeletal muscle protein anabolism in older adults. Objective In this Phase 1, double-blind, placebo-controlled, randomized clinical trial, we determined if chronic EAA supplementation, AE training, or a combination of the two interventions could improve muscle mass and function by stimulating muscle protein synthesis. Methods We phone-screened 971, enrolled 109, and randomized 50 independent, low-active, nonfrail, and nondiabetic older adults (age 72 ± 1 years). We used a 2 × 2 factorial design. The interventions were: daily nutritional supplementation (15 g EAA or placebo) and physical activity (supervised AE training 3 days/week or monitored habitual activity) for 24 weeks. Muscle strength, physical function, body composition, and muscle protein synthesis were measured before and after the 24-week intervention. Results Forty-five subjects completed the 24-week intervention. VO2peak and walking speed increased (p < .05) in both AE groups, irrespective of supplementation type, but muscle strength increased only in the EAA + AE group (p < .05). EAA supplementation acutely increased (p < .05) muscle protein synthesis from basal both before and after the intervention, with a larger increase in the EAA + AE group after the intervention. Total and regional lean body mass did not change significantly with any intervention. Conclusions In nonfrail, independent, healthy older adults AE training increased walking speed and aerobic fitness, and, when combined with EAA supplementation, it also increased muscle strength and EAA-stimulated muscle protein synthesis. These increases occurred without improvements in muscle mass.

Background:Staphylococcal aureus (SA) colonization in early infancy is common, but the pattern and factors affecting its acquisition and persistence in the first few months of life are not well studied. The aim is to study the rate of SA nasopharyngeal (NP) colonization at monthly intervals in the f

Background Conducting 5 A’s counseling in clinic and utilizing technology-based resources are recommended to promote physical activity but little is known about how to implement such an intervention. This investigation aimed to determine the feasibility and acceptability, using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework, of a pragmatic, primary care-based intervention that incorporated 5 A’s counseling and self-control through an activity monitor. Methods Primary care patients (n = 40) 55–74 years of age were recruited and randomized to receive a pedometer or an electronic activity monitor (EAM), Jawbone UP24, to monitor activity for 12 weeks. Participants were also invited to a focus group after completing the intervention. Stakeholders (n = 36) were recruited to provide feedback. Results The intervention recruitment rate was 24.7%. The attrition rate was 20% with a significantly higher rate for the pedometer group (p = 0.02). The EAM group increased their minutes of physical activity by 11.1 min/day while the pedometer maintained their activity (0.2 min/day), with no significant group difference. EAM participants liked using their monitor and would continue wearing it while the pedometer group was neutral to these statements (p

Background: Acupuncture treatment has been employed in China for over 2500 years and it is used worldwide as analgesia in acute and chronic pain. Acupuncture is also used in general anesthesia (GA). The aim of this systematic review and meta-analysis was to assess the efficacy of electroacupuncture (EA) in addition to GA in patients undergoing cardiac surgery. Methods: We searched 3 databases (Pubmed, Cochrane Library, and Web of Science—from 1965 until January 31, 2017) for randomized controlled trials (RCTs) including patients undergoing cardiac surgery and receiving GA alone or GA + EA. As primary outcomes, we investigated the association between GA + EA approach and the dosage of intraoperative anesthetic drugs administered, the duration of mechanical ventilation (MV), the postoperative dose of vasoactive drugs, the length of intensive care unit (ICU) and hospital stay, and the levels of troponin I and cytokines. Results: The initial search yielded 477 citations, but only 7 prospective RCTs enrolling a total of 321 patients were included. The use of GA + EA reduced the dosage of intraoperative anesthetic drugs ( P < .05), leading to shorter MV time ( P < .01) and ICU stay ( P < .05) as well as reduced postoperative dose of vasoactive drugs ( P < .001). In addition, significantly lower levels of troponin I ( P < .01) and tumor necrosis factor α ( P < .01) were observed. Conclusion: The complementary use of EA for open-heart surgery reduces the duration of MV and ICU stay, blunts the inflammatory response, and might have protective effects on the heart. Our findings stimulate future RCT to provide definitive recommendations.

Objective The purpose of this study is to find a correlation between closure technique in pharyngeal closure and outcomes of both pharyngocutaneous fistula and post-laryngectomy stricture after laryngectomy. Study Design Retrospective Chart Review. Methods We retrospectively reviewed a total of 151 patients over a 20 year period from January 1994 to December of 2013 who underwent primary pharyngeal reconstruction after total laryngectomy specifically looking at the closure technique in relation to pharyngo-cutaneous fistula (PCF) and post-laryngectomy stricture post-operatively. Patients were excluded based on secondary pharyngeal closure. Using logistic regression modeling, we performed univariate and multivariate analysis of our data. Results The overall PCF and post-laryngectomy stricture rates were 19.1% and 15.8%. When salvage laryngectomy was excluded, t-type closure had a significantly lower risk of fistula rate (p = 0.038) compared to vertical closure. In multivariate analysis, this statistical significance was lost (p = 0.23); however, non-salvage t-type closure remained significantly better than both salvage laryngectomy groups (t-type, p = 0.033, vertical, p = 0.037) while non-salvage vertical closure had no significant difference from other groups. There was no difference in stricture rate between the two closure techniques (p = 0.63) Conclusion Our study supports the role of t-type closure decreasing fistula rates in primary pharyngeal reconstruction. Orientation of the pharyngeal closure does not appear to change the risk of post-laryngectomy stricture formation after total laryngectomy. Salvage laryngectomy with primary pharyngeal reconstruction remains an independent risk factor for fistula formation. This article is protected by copyright. All rights reserved.

Background Interferences between pathogenic bacteria and specific commensals are known. We determined the interactions between nasopharyngeal microbial pathogens and commensals during viral upper respiratory tract infection (URI) and acute otitis media (AOM) in infants. Methods We analyzed 971 specimens collected monthly and during URI and AOM episodes from 139 infants. The 16S rRNA V4 gene regions were sequenced on the Illumina MiSeq platform. Results Among the high abundant genus-level nasopharyngeal microbiota were Moraxella, Haemophilus, and Streptococcus (3 otopathogen genera), Corynebacterium, Dolosigranulum, Staphylococcus, Acinetobacter, Pseudomonas, and Bifidobacterium. Bacterial diversity was lower in culture-positive samples for Streptococcus pneumoniae, and Haemophilus influenzae, compared to cultured-negative samples. URI frequencies were positively associated with increasing trend in otopathogen colonization. AOM frequencies were associated with decreasing trend in Micrococcus colonization. During URI and AOM, there were increases in abundance of otopathogen genera and decreases in Pseudomonas, Myroides, Yersinia, and Sphingomonas. Otopathogen abundance was increased during symptomatic viral infection, but not during asymptomatic infection. The risk for AOM complicating URI was reduced by increased abundance of Staphylococcus and Sphingobium. Conclusion Otopathogen genera played the key roles in URI and AOM occurrences. Staphylococcus counteracts otopathogens thus Staphylococcal colonization may be beneficial, rather than harmful. While Sphingobium may play a role in preventing AOM complicating URI, the commonly used probiotic Bifidobacterium did not play a significant role during URI or AOM. The role of less common commensals in counteracting the deleterious effects of otopathogens requires further studies.

Reductions in skeletal muscle function occur during the course of healthy aging as well as with bed rest or diverse diseases such as cancer, muscular dystrophy, and heart failure. However, there are no accepted pharmacologic therapies to improve impaired skeletal muscle function. Nitric oxide may influence skeletal muscle function through effects on excitation-contraction coupling, myofibrillar function, perfusion, and metabolism. Here we show that augmentation of nitric oxide-cyclic guanosine monophosphate signaling by short-term daily administration of the phosphodiesterase 5 inhibitor sildenafil increases protein synthesis, alters protein expression and nitrosylation, and reduces fatigue in human skeletal muscle. These findings suggest that phosphodiesterase 5 inhibitors represent viable pharmacologic interventions to improve muscle function.

Background Skeletal muscle loss accompanying aging or cancer is associated with reduced physical function and predicts morbidity and mortality. 3-Methylhistidine (3MH) has been proposed as a biomarker of myofibrillar proteolysis, which may contribute to skeletal muscle loss. Methods We hypothesized that the terminal portion of the isotope decay curve following an oral dose of isotopically labeled 3MH can be measured non-invasively from timed spot urine samples. We investigated the feasibility of this approach by determining isotope enrichment in spot urine samples and corresponding plasma samples and whether meat intake up to the time of dosing influences the isotope decay. Results Isotope decay constants (k) were similar in plasma and urine, regardless of diet. Post hoc comparison of hourly sampling over 10 h with three samples distributed over 10 or fewer hours suggests that three distributed samples over 5–6 h of plasma or urine sampling yield decay constants similar to those obtained over 10 h of hourly sampling. Conclusion The findings from this study suggest that an index of 3MH production can be obtained from an easily administered test involving oral administration of a stable isotope tracer of 3MH followed by three plasma or urine samples collected over 5–6 h the next day.