No abstract available.
Anesthesia, Conduction* ; Muscular Dystrophies*

BACKGROUND:The purpose of this study was to use point-of-care ultrasound (POCUS) to investigate the relationship between tobacco smoke exposure and the characteristics of the common carotid artery (CCA). The effect of both primary and secondary smoking on CCA properties was evaluated. METHODS:We performed a prospective cross-sectional study across 20 primary care clinics in Bandung, West Java, Indonesia in July 2016. Point of care ultrasound was performed on a convenience sample of Indonesian patients presenting to clinic. The CCA wall stiffness and carotid intima-media thickness (CIMT) were measured during diastole and systole. These measurements were correlated with smoke exposure and cardiovascular disease. RESULTS: We enrolled 663 patients in the study, with 426 patients enrolled in the smoking category and 237 patients enrolled in the second-hand smoke category. There was an overall positive correlation with the measured lifestyle factors and the ultrasound-measured variables in the group of individuals who smoked. For all variables, age seemed to contribute the most out of all of the lifestyle factors for the positive changes in CIMT and CCA wall stiffness. CONCLUSION:Our data yielded correlations between CCA properties and cardiovascular risk, as well as between CIMT and arterial stiffness. We were also able to demonstrate an increase in thickness of the CIMT in patients who have been exposed by tobacco through the use of ultrasound. Further large scale studies comparing patients with multiple cardiac risk factors need to be performed to confirm the utility of ultrasound findings of cardiovascular disease and stroke.

The world is facing the new challenges of an aging population, and understanding the process of aging has therefore become one of the most important global concerns. Sarcopenia is a condition which is defined by the gradual loss of skeletal muscle mass and function with age. In research and clinical practice, sarcopenia is recognized as a component of geriatric disease and is a current target for drug development. In this review we define this condition and provide an overview of current therapeutic approaches. We further highlight recent findings that describe key pathophysiological phenotypes of this condition, including alterations in muscle fiber types, mitochondrial function, nicotinamide adenine dinucleotide (NAD+) metabolism, myokines, and gut microbiota, in aged muscle compared to young muscle or healthy aged muscle. The last part of this review examines new therapeutic avenues for promising treatment targets. There is still no accepted therapy for sarcopenia in humans. Here we provide a brief review of the current state of research derived from various mouse models or human samples that provide novel routes for the development of effective therapeutics to maintain muscle health during aging.

Methods: Patients undergoing primary, elective 1–3 level ACDF for radiculopathy at a single academic center between 2015 and 2021 were identified retrospectively. Cervical FS was evaluated using axial T2-weighted MRI images via a validated grading scale. The maximum degree of stenosis was used for multilevel disease. Motor symptoms were classified using encounters at their final preoperative and first postoperative visits, with examinations ≤3/5 indicating weakness. PROMs were obtained preoperatively and at 1-year follow-up. Bivariate analysis was used to compare outcomes based on stenosis severity, followed by multivariable analysis. Results: This study included 354 patients, 157 with moderate stenosis and 197 with severe stenosis. Overall, 58 patients (16.4%) presented with upper extremity weakness ≤3/5. A similar number of patients in both groups presented with baseline motor weakness (13.5% vs. 16.55, p =0.431). Postoperatively, 97.1% and 87.0% of patients with severe and moderate FS, respectively, experienced full motor recovery (p =0.134). At 1-year, patients with severe neuroforaminal stenosis presented with significantly worse 12-item Short Form Survey Physical Component Score (PCS-12) (33.3 vs. 37.3, p =0.049) but demonstrated a greater magnitude of improvement (Δ PCS-12: 5.43 vs. 0.87, p =0.048). Worse stenosis was independently associated with greater ΔPCS-12 at 1-year (β =5.59, p =0.022). Conclusions Patients with severe FS presented with worse preoperative physical health. While ACDF improved outcomes and conferred similar motor recovery in all patients, those with severe FS reported much better improvement in physical function.

Background: Ovarian cancer has the highest mortality among gynecologic cancers, primarily because it typically is diagnosed at a late stage and because of the development of chemoresistance in recurrent disease. Improving outcomes in women with platinumresistant ovarian cancer is a substantial unmet need. Activation of the glucocorticoidreceptor (GR) by cortisol has been shown to suppress the apoptotic pathways used by cytotoxic agents, limiting their efficacy. Selective GR modulation may be able to counteract cortisol’s antiapoptotic effects, enhancing chemotherapy’s efficacy. A previous phase 2 study has shown that adding intermittently dosed relacorilant, a selective GR modulator, to nab-paclitaxel improved outcomes, including progression-free survival (PFS) and overall survival (OS), with minimal added toxicity, in women with recurrent platinum-resistant ovarian cancer. The ROSELLA study aims to confirm and expand on these findings in a larger population. Methods ROSELLA is a phase 3, randomized, 2-arm, open-label, global multicenter study in women with recurrent, platinum-resistant, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. Eligible participants have received 1 to 3 lines of prior systemic anticancer therapy, including ≥1 prior line of platinum therapy and prior treatment with bevacizumab, with documented progressive disease or intolerance to the most recent therapy. There is no biomarker-based requirement for participant selection. Participants are randomized 1:1 to receive intermittently dosed relacorilant in combination with nabpaclitaxel or nab-paclitaxel monotherapy. The study’s primary efficacy endpoint is PFS as assessed by blinded independent central review. Secondary efficacy endpoints include OS, investigator-assessed PFS, objective response rate, best overall response, duration of response, clinical benefit rate at 24 weeks, and cancer antigen 125 response. The study is also evaluating safety and patient-reported outcomes.Trial Registration: ClinicalTrials.gov Identifier: NCT05257408; European Union Drug Regulating Authorities Clinical Trials Database Identifier: 2022-000662-18

Background: Ovarian cancer has the highest mortality among gynecologic cancers, primarily because it typically is diagnosed at a late stage and because of the development of chemoresistance in recurrent disease. Improving outcomes in women with platinumresistant ovarian cancer is a substantial unmet need. Activation of the glucocorticoidreceptor (GR) by cortisol has been shown to suppress the apoptotic pathways used by cytotoxic agents, limiting their efficacy. Selective GR modulation may be able to counteract cortisol’s antiapoptotic effects, enhancing chemotherapy’s efficacy. A previous phase 2 study has shown that adding intermittently dosed relacorilant, a selective GR modulator, to nab-paclitaxel improved outcomes, including progression-free survival (PFS) and overall survival (OS), with minimal added toxicity, in women with recurrent platinum-resistant ovarian cancer. The ROSELLA study aims to confirm and expand on these findings in a larger population. Methods ROSELLA is a phase 3, randomized, 2-arm, open-label, global multicenter study in women with recurrent, platinum-resistant, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. Eligible participants have received 1 to 3 lines of prior systemic anticancer therapy, including ≥1 prior line of platinum therapy and prior treatment with bevacizumab, with documented progressive disease or intolerance to the most recent therapy. There is no biomarker-based requirement for participant selection. Participants are randomized 1:1 to receive intermittently dosed relacorilant in combination with nabpaclitaxel or nab-paclitaxel monotherapy. The study’s primary efficacy endpoint is PFS as assessed by blinded independent central review. Secondary efficacy endpoints include OS, investigator-assessed PFS, objective response rate, best overall response, duration of response, clinical benefit rate at 24 weeks, and cancer antigen 125 response. The study is also evaluating safety and patient-reported outcomes.Trial Registration: ClinicalTrials.gov Identifier: NCT05257408; European Union Drug Regulating Authorities Clinical Trials Database Identifier: 2022-000662-18

Background: Ovarian cancer has the highest mortality among gynecologic cancers, primarily because it typically is diagnosed at a late stage and because of the development of chemoresistance in recurrent disease. Improving outcomes in women with platinumresistant ovarian cancer is a substantial unmet need. Activation of the glucocorticoidreceptor (GR) by cortisol has been shown to suppress the apoptotic pathways used by cytotoxic agents, limiting their efficacy. Selective GR modulation may be able to counteract cortisol’s antiapoptotic effects, enhancing chemotherapy’s efficacy. A previous phase 2 study has shown that adding intermittently dosed relacorilant, a selective GR modulator, to nab-paclitaxel improved outcomes, including progression-free survival (PFS) and overall survival (OS), with minimal added toxicity, in women with recurrent platinum-resistant ovarian cancer. The ROSELLA study aims to confirm and expand on these findings in a larger population. Methods ROSELLA is a phase 3, randomized, 2-arm, open-label, global multicenter study in women with recurrent, platinum-resistant, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. Eligible participants have received 1 to 3 lines of prior systemic anticancer therapy, including ≥1 prior line of platinum therapy and prior treatment with bevacizumab, with documented progressive disease or intolerance to the most recent therapy. There is no biomarker-based requirement for participant selection. Participants are randomized 1:1 to receive intermittently dosed relacorilant in combination with nabpaclitaxel or nab-paclitaxel monotherapy. The study’s primary efficacy endpoint is PFS as assessed by blinded independent central review. Secondary efficacy endpoints include OS, investigator-assessed PFS, objective response rate, best overall response, duration of response, clinical benefit rate at 24 weeks, and cancer antigen 125 response. The study is also evaluating safety and patient-reported outcomes.Trial Registration: ClinicalTrials.gov Identifier: NCT05257408; European Union Drug Regulating Authorities Clinical Trials Database Identifier: 2022-000662-18