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

BACKGROUND: Current dressing materials cannot secure a cell survival-promoting wound environment for stem cell delivery due to insufficient assimilation to skin motion. The authors developed a novel motion-accommodating dual-layer hydrogel dressing for stem cell delivery into such wounds. METHODS: Dorsal hand skin movement was evaluated to determine the potential range of deformation for a dressing.The outer hydrogel (OH) was fabricated with an alginate–acrylamide double-network hydrogel with a covalently crosslinked elastomer coat. The tough adhesive consisted of a chitosan-based bridging polymer and coupling reagents. OH material properties and adhesiveness on porcine skin were measured. An oxidized alginate-based inner hydrogel (IH) containing human adipose-derived stem cells (ASCs) was evaluated for cell-supporting and cell-releasing properties. The OH’s function as a secondary dressing, and dual-layer hydrogel cell delivery potential in wounds were assessed in a rodent model. RESULTS: The dual-layer hydrogel consisted of OH and IH. The OH target range of deformation was up to 25% strain. The OH adhered to porcine skin, and showed significantly higher adhesion energy than common secondary dressings and endured 900 flexion–extension cycles without detachment. OH showed a similar moisture vapor transmission rate as moisture-retentive dressings. IH maintained embedded cell survival for three days with significant cell release on the contacting surface. OH showed less fibrotic wound healing than other secondary dressings in vivo. The dual-layer hydrogel successfully delivered ASCs into open wounds of nude mice (13 ± 3 cells/HPF). CONCLUSIONS The novel dual-layer hydrogel can accommodate patient movement and deliver ASCs into the wound bed by securing the wound microenvironment.

The coronavirus disease 2019 (COVID-19) pandemic has affected all Canadian families, with some impacted differently than others. Our study aims to: (1) determine the prevalence and transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among Canadian families, (2) identify predictors of infection susceptibility and severity of SARS-CoV-2, and (3) identify health and psychosocial impacts of the COVID-19 pandemic. This study builds upon the CHILD Cohort Study, an ongoing multi-ethnic general population prospective cohort consisting of 3,454 Canadian families with children born in Vancouver, Edmonton, Manitoba, and Toronto between 2009 and 2012. During the pandemic, CHILD households were invited to participate in the CHILD COVID-19 Add-On Study involving: (1) brief biweekly surveys about COVID-19 symptoms and testing; (2) quarterly questionnaires assessing COVID-19 exposure and testing, vaccination status, physical and mental health, and pandemic-driven life changes; and (3) in-home biological sampling kits to collect blood and stool. In total, 1,462 households (5,378 participants) consented to the CHILD COVID-19 Add-On Study: 2,803 children (mean±standard deviation [SD], 9.0±2.7 years; range, 0-17 years) and 2,576 adults (mean±SD, 43.0±6.5 years; range, 18-85 years). We will leverage the wealth of pre-pandemic CHILD data to identify risk and resilience factors for susceptibility and severity to the direct and indirect pandemic effects. Our short-term findings will inform key stakeholders and knowledge users to shape current and future pandemic responses. Additionally, this study provides a unique resource to study the long-term impacts of the pandemic as the CHILD Cohort Study continues.

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.

OBJECTIVE: A growing interest in extracorporeal cardiopulmonary resuscitation (ECPR) as a rescue strategy for refractory adult out-of-hospital cardiac arrest (OHCA) currently exists. This study aims to determine current standards of care and practice variation for ECPR patients in the USA and Korea. METHODS: In December 2015, we surveyed centers from the Korean Hypothermia Network (KORHN) Investigators and the US National Post-Arrest Research Consortium (NPARC) on current targeted temperature management and ECPR practices. This project analyzes the subsection of questions addressing ECPR practices. We summarized survey results using descriptive statistics. RESULTS: Overall, 9 KORHN and 4 NPARC centers reported having ECPR programs and had complete survey data available. Two KORHN centers utilized extracorporeal membrane oxygenation only for postarrest circulatory support in patients with refractory shock and were excluded from further analysis. Centers with available ECPR generally saw a high volume of OHCA patients (10/11 centers care for >75 OHCA a year). Location of, and providers trained for cannulation varied across centers. All centers in both countries (KORHN 7/7, NPARC 4/4) treated comatose ECPR patients with targeted temperature management. All NPARC centers and four of seven KORHN centers reported having a standardized hospital protocol for ECPR. Upper age cutoff for eligibility ranged from 60 to 75 years. No absolute contraindications were unanimous among centers. CONCLUSION: A wide variability in practice patterns exist between centers performing ECPR for refractory OHCA in the US and Korea. Standardized protocols and shared research databases might inform best practices, improve outcomes, and provide a foundation for prospective studies.
Adult* ; Cardiopulmonary Resuscitation* ; Catheterization ; Coma ; Extracorporeal Membrane Oxygenation ; Heart Arrest ; Humans ; Hypothermia ; Korea ; Out-of-Hospital Cardiac Arrest* ; Practice Guidelines as Topic ; Prospective Studies ; Research Personnel ; Shock ; Standard of Care

No abstract available.
Anesthesia* ; Dexmedetomidine* ; Lidocaine* ; Spine*

BACKGROUND: Acne vulgaris is a disease of the pilosebaceous unit characterized by increased sebum production, hyperkeratinization, and immune responses to Propionibacterium acnes (PA). Here, we explore a possible mechanism by which a lipid receptor, G2A, regulates immune responses to a commensal bacterium. OBJECTIVE: To elucidate the inflammatory properties of G2A in monocytes in response to PA stimulation. Furthermore, our study sought to investigate pathways by which lipids modulate immune responses in response to PA. METHODS: Our studies focused on monocytes collected from human peripheral blood mononuclear cells, the monocytic cell line THP-1, and a lab strain of PA. Our studies involved the use of enzyme-linked immunosorbent, Western blot, reverse transcription polymerase chain reaction, small interfering RNA (siRNA), and microarray analysis of human acne lesions in the measurements of inflammatory markers. RESULTS: G2A gene expression is higher in acne lesions compared to normal skin and is inducible by the acne therapeutic, 13-cis-retinoic acid. In vitro, PA induces both the Toll-like receptor 2-dependent expression of G2A as well as the production of the G2A ligand, 9-hydroxyoctadecadienoic acid, from human monocytes. G2A gene knockdown through siRNA enhances PA stimulation of interleukin (IL)-6, IL-8, and IL-1β possibly through increased activation of the ERK1/2 MAP kinase and nuclear factor kappa B p65 pathways. CONCLUSION: G2A may play a role in quelling inflammatory cytokine response to PA, revealing G2A as a potential attenuator of inflammatory response in a disease associated with a commensal bacterium.
Acne Vulgaris ; Blotting, Western ; Cell Line ; Cytokines* ; Gene Expression ; Gene Knockdown Techniques ; Humans* ; In Vitro Techniques ; Interleukin-8 ; Interleukins ; Isotretinoin ; Microarray Analysis ; Monocytes* ; NF-kappa B ; Phosphotransferases ; Polymerase Chain Reaction ; Propionibacterium acnes* ; Propionibacterium* ; Reverse Transcription ; RNA, Small Interfering ; Sebum ; Skin ; Toll-Like Receptors

Central neurocytoma (CN) is a rare, benign brain tumor often located in the lateral ventricles. CN may cause obstructive hydrocephalus and manifest as signs of increased intracranial pressure. The goal of treatment for CN is a gross total resection (GTR), which often yields excellent prognosis with a very high rate of tumor control and survival. Adjuvant radiosurgery and radiotherapy may be considered to improve tumor control when GTR cannot be achieved. Chemotherapy is also not considered a primary treatment, but has been used as a salvage therapy. The radiological features of CN are indistinguishable from those of other brain tumors; therefore, many histological markers, such as synaptophysin, can be very useful for diagnosing CNs. Furthermore, the MIB-1 Labeling Index seems to be correlated with the prognosis of CN. We also discuss oncogenes associated with these elusive tumors. Further studies may improve our ability to accurately diagnose CNs and to design the optimal treatment regimens for patients with CNs.
Brain Neoplasms ; Drug Therapy ; Humans ; Hydrocephalus ; Intracranial Pressure ; Lateral Ventricles ; Neurocytoma* ; Oncogenes ; Prognosis ; Radiosurgery ; Radiotherapy ; Salvage Therapy ; Synaptophysin