Robersonforsyth6428

Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity.

To assess whether a dose reduction of preoperative radiotherapy for myxoid liposarcoma would result in comparable oncological outcome with less morbidity.

The Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas (DOREMY) trial is a prospective, single-group, phase 2 nonrandomized controlled trial being conducted in 9 tertiary sarcoma centers in Europe and the US. Participants include adults with nonmetastatic, biopsy-proven and translocation-confirmed myxoid liposarcoma of the extremity or trunk who were enrolled between November 24, 2010, and August 1, 2019. Data analyses, using both per-protocol and intention-to-treat approaches, were conducted from November 24, 2010, to January 31, 2020.

The tion requiring intervention was 17%, and the rate of grade 2 or higher toxic effects was 14%.

The findings of the DOREMY nonrandomized clinical trial suggest that deintensification of preoperative radiotherapy dose is effective and oncologically safe and is associated with less morbidity than historical controls, although differences in radiotherapy techniques and follow-up should be considered. A 36-Gy dose delivered in once-daily 2-Gy fractions is proposed as a dose-fractionation approach for myxoid liposarcoma, given that phase 3 trials are logistically impossible to execute in rare cancers.

ClinicalTrials.gov Identifier NCT02106312.

ClinicalTrials.gov Identifier NCT02106312.

One-third of singers and vocal professionals report experiencing a benefit from empirical vitamin B12 injections for improvement of mild singing-related symptoms (eg, reduced stamina, vocal fatigue, and effort). However, there is no objective evidence to support or refute these claims.

To assess the presence and magnitude of the effect of empirical vitamin B12 injection on the vocal performance of singers.

A randomized, double-blind, placebo-controlled, crossover trial was conducted from November 7, 2017, to November 30, 2018, at an academic voice center among 20 active adult singers without dysphonia but with mild vocal symptoms. Individuals with known or suspected vitamin B12 deficiency or active or recent vitamin B12 treatment were excluded. Analysis was on a per-protocol basis.

Participants were randomized to receive an intramuscular (deltoid) injection of either vitamin B12 (1000 μg of cyanocobalmin) or placebo (0.9% sodium chloride). After a washout period of at least 4 weeks, participants were he VFI, and -1 (95% CI, -3 to 2) for the EASE. The improvements after both injections failed to reach the estimated minimal clinically important difference. Of the 20 participants, 4 (20%) reached the estimated minimal clinically important difference in their SVHI-10 score after 72 hours for both vitamin B12 and placebo injections.

This randomized, double-blind, placebo-controlled, crossover trial found that after empirical vitamin B12 injection to improve mild voice-related symptoms, the improvement in self-reported voice measures in singers shows no meaningful difference compared with placebo.

ClinicalTrials.gov Identifier NCT03437824.

ClinicalTrials.gov Identifier NCT03437824.

Coronavirus disease 2019 (COVID-19) may lead to serious illness as a result of an excessive immune response. Fluvoxamine may prevent clinical deterioration by stimulating the σ-1 receptor, which regulates cytokine production.

To determine whether fluvoxamine, given during mild COVID-19 illness, prevents clinical deterioration and decreases the severity of disease.

Double-blind, randomized, fully remote (contactless) clinical trial of fluvoxamine vs placebo. Participants were community-living, nonhospitalized adults with confirmed severe acute respiratory syndrome coronavirus 2 infection, with COVID-19 symptom onset within 7 days and oxygen saturation of 92% or greater. One hundred fifty-two participants were enrolled from the St Louis metropolitan area (Missouri and Illinois) from April 10, 2020, to August 5, 2020. The final date of follow-up was September 19, 2020.

Participants were randomly assigned to receive 100 mg of fluvoxamine (n = 80) or placebo (n = 72) 3 times daily for 15 days.

The primarudy is limited by a small sample size and short follow-up duration, and determination of clinical efficacy would require larger randomized trials with more definitive outcome measures.

ClinicalTrials.gov Identifier NCT04342663.

ClinicalTrials.gov Identifier NCT04342663.

More than 1 million people in the US identify as transgender; however, few studies have examined the experiences and outcomes of transgender patients with cancer.

To examine clinical characteristics, experiences, and outcomes of transgender patients with cancer.

This retrospective case series assessed transgender patients with at least 1 cancer diagnosis who were evaluated at Dana-Farber Cancer Institute or Brigham and Women's Hospital in Boston, Massachusetts, between January 1, 2005, and December 31, 2019.

Demographic, clinical, and treatment characteristics for all patients and documentation by oncologic practitioners of important aspects of providing gender-affirming care, including pronouns used by the patient, were recorded.

A total of 37 transgender patients with cancer were assessed (mean [SD] age, 38.9 [21.8] years at first cancer diagnosis). Fifteen patients (40.5%) had hematologic malignant cancers, and 25 patients (67.6%) had solid malignant tumors. Sixteen patients (43.2%) initiated gennder-affirming hormone therapy or surgery after their diagnosis. Documentation by oncologic practitioners infrequently included pronouns used by the patient or discussion surrounding the interactions between cancer treatment and gender-affirming care, signifying that urgent improvements are needed in cancer care for transgender patients.

This case series study found that transgender patients were diagnosed with diverse cancers, and many initiated gender-affirming hormone therapy or surgery after their diagnosis. Documentation by oncologic practitioners infrequently included pronouns used by the patient or discussion surrounding the interactions between cancer treatment and gender-affirming care, signifying that urgent improvements are needed in cancer care for transgender patients.Uncertain diagnostic performance has limited clinical adoption of salivary pepsin, a noninvasive diagnostic tool for gastroesophageal reflux disease (GERD). This study aimed to assess diagnostic performance of salivary pepsin, and test validity of thresholds in an external cohort of patients with or without GERD. This two-phase prospective study conducted at two centers enrolled adult asymptomatic volunteers, patients with symptoms of GERD undergoing reflux monitoring, and patients with Barrett's esophagus (BE). Fasting saliva samples were processed for pepsin concentration using Peptest. Fenretinide solubility dmso Phase 1 compared pepsin concentration between No GERD (volunteers/functional heartburn) and GERD (erosive reflux disease/nonerosive reflux disease (NERD)/BE). Phase 2 tested validity of the diagnostic thresholds identified from Phase 1 among external functional heartburn and NERD cohorts. Of 243 enrolled subjects, 156 met inclusion criteria. Phase 1 (n = 114) Pepsin concentrations were significantly higher in GERD (n = 84) versus No GERD (n = 30) (73.8 ng/mL vs. 21.1 ng/mL; P  less then  0.001). Area under the curve for pepsin concentration was 0.74 (95% CI 0.65, 0.83). A salivary pepsin threshold of 24.9 ng/mL optimized the true negative rate and 100.0 ng/mL optimized the true positive rate. Phase 2 (n = 42) Pepsin concentrations were significantly higher in NERD (n = 22) versus Functional Heartburn (n = 20) (176.0 ng/mL vs. 53.3 ng/mL, P  less then  0.001). Applying Phase 1 thresholds in this external cohort, salivary pepsin 24.9 ng/mL was 86% sensitive (64%, 97%) and 100.0 ng/mL was 72% specific for distinguishing NERD from functional heartburn. Given modest sensitivity and specificity for GERD, salivary pepsin may have clinical utility as a noninvasive office based diagnostic screening tool for GERD.CD8+ T reg cells play an important role in the maintenance of self-tolerance and can inhibit the development of autoimmune disease. In this issue of JEM, Mishra et al. (https//doi.org/10.1084/jem.20200030) reveal that TGF-β signaling and an Eomes-dependent genetic program contribute to CD8 T reg cell differentiation and function.The delivery of glucose and antioxidants is vital to maintain homeostasis and lens transparency. Here, we report a new mechanism whereby mechanically activated connexin (Cx) hemichannels serve as a transport portal for delivering glucose and glutathione (GSH). Integrin α6β1 in outer cortical lens fiber activated by fluid flow shear stress (FFSS) induced opening of hemichannels. Inhibition of α6 activation prevented hemichannel opening as well as glucose and GSH uptake. The activation of integrin β1, a heterodimeric partner of α6 in the absence of FFSS, increased Cx50 hemichannel opening. Hemichannel activation by FFSS depended on the interaction of integrin α6 and Cx50 C-terminal domain. Moreover, hemichannels in nuclear fiber were unresponsive owing to Cx50 truncation. Taken together, these results show that mechanically activated α6β1 integrin in outer cortical lens fibers leads to opening of hemichannels, which transport glucose and GSH into cortical lens fibers. This study unveils a new transport mechanism that maintains metabolic and antioxidative function of the lens.

We explored the association of N-terminal probrain natriuretic peptide (NT-proBNP) with metabolic traits in a bi-ethnic African-Caucasian cohort.

Baseline examinations of the Sympathetic activity and Ambulatory Blood Pressure in African (SABPA) prospective cohort study were performed between 2008 and 2009, and re-examination after a three-year follow up in South African teachers (black African,

= 194; Caucasian,

= 203).

Each one standard deviation increment of NT-proBNP was significantly inversely associated with body mass index ( β -1.01), glycated haemoglobin ( β -0.14 %), waist circumference (β -1.82), HOMA-IR (β -0.47), insulin (β -1.66) and triglyceride levels (β -0.04). Each one standard deviation increment of NT-proBNP was also associated with reduced odds of incident diabetes, and subjects within the highest quartile of NT-proBNP were at lowest risk (OR 0.24; 95% CI 0.06-0.96;

= 0.041).

In the SABPA cohort, Africans and Caucasians had similar NT-proBNP levels; however, the associations for Africans were stronger. Those findings suggest that BNP may affect the propensity for metabolic disturbances differently in Africans and Caucasians.

In the SABPA cohort, Africans and Caucasians had similar NT-proBNP levels; however, the associations for Africans were stronger. Those findings suggest that BNP may affect the propensity for metabolic disturbances differently in Africans and Caucasians.