ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer.

BACKGROUND: Pembrolizumab plus chemotherapy provides clinically meaningful benefit as first-line therapy for advanced (locoregional extension and residual disease after surgery)/metastatic/recurrent mismatch repair-proficient (pMMR) and mismatch repair-deficient (dMMR) endometrial cancer, with greater magnitude of benefit in the dMMR phenotype. We evaluated the addition of pembrolizumab to adjuvant chemotherapy (with/without radiation therapy) among patients with newly diagnosed, high-risk endometrial cancer without any residual macroscopic disease following curative-intent surgery. METHODS: We included patients with histologically confirmed high-risk [International Federation of Gynecology and Obstetrics (FIGO) stage I/II of non-endometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA of any histology] endometrial cancer following surgery with curative intent and no evidence of disease postoperatively, with no prior radiotherapy or systemic therapy. Patients were randomised to pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for six cycles added to carboplatin-paclitaxel followed by pembrolizumab 400 mg or placebo every 6 weeks (Q6W) for six cycles per treatment assignment. Radiotherapy was at the investigator's discretion. The primary endpoints were investigator-assessed disease-free survival (DFS) and overall survival in the intention-to-treat population. RESULTS: A total of 1095 patients were randomised (pembrolizumab, n = 545; placebo, n = 550). At this interim analysis (data cut-off, 4 March 2024), 119 (22%) DFS events occurred in the pembrolizumab group and 121 (22%) occurred in the placebo group [hazard ratio 1.02, 95% confidence interval (CI) 0.79-1.32; P = 0.570]. Kaplan-Meier estimates of 2-year DFS rates were 75% and 76% in the pembrolizumab and placebo groups, respectively. The hazard ratio for DFS was 0.31 (95% CI 0.14-0.69) in the dMMR population (n = 281) and 1.20 (95% CI 0.91-1.57) in the pMMR population (n = 814). Grade ≥3 adverse events (AEs) occurred in 386 of 543 (71%) and 348 of 549 (63%) patients in the pembrolizumab and placebo groups, respectively. No treatment-related grade 5 AEs occurred. CONCLUSIONS: Adjuvant pembrolizumab plus chemotherapy did not improve DFS in patients with newly diagnosed, high-risk, all-comer endometrial cancer. Preplanned subgroup analyses for stratification factors suggest that pembrolizumab plus chemotherapy improved DFS in patients with dMMR tumours. Safety was manageable. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04634877; EudraCT, 2020-003424-17. RESEARCH SUPPORT: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Interrater Reliability of the Pediatric Neuromuscular Recovery Scale in Children with Spina Bifida.

Purpose: The purpose of this study was to examine the interrater reliability of the Pediatric Neuromuscular Recovery Scale (Peds NRS) to classify motor capacity in children with myelomeningocele (MMC) form of spina bifida.Methods: Twenty-one children with MMC (1.5-10 years of age) were each scored on the Peds NRS three times: two live testing sessions and one video recorded session. Every child was scored by two physical therapists and one occupational therapist. Interrater reliability was analyzed using intraclass correlation coefficients (ICC) for individual items and the summary score.Results: Strong interrater reliability was determined for the overall Peds NRS score (ICC = 0.89; 95% CI, .80-.95). Eleven of 16 individual items exhibited good to excellent reliability (ICC ≥ 0.80). Pediatric clinicians were able to reliably administer and score the Peds NRS on children with MMC, representing a wide range of ages and functional levels.

[Effect of chlorhexidine on Staphylococcus aureus hospital isolates under different environmental conditions]. / Efecto de clorhexidina sobre aislamientos hospitalarios de Staphylococcus aureus en diferentes condiciones ambientales.

Antiseptic agents are widely used in hospitals, being essential when prevention and control of nosocomial infections are required. It is necessary to consider several aspects that affect the biocide activity, since they have direct incidence in hospital hygiene, health and also in the nosocomial infection rate. Organisms belonging to Staphylococcus genus are involved in such infections and, digluconate of chlorhexidine is one of the most used antiseptic agents for human and animal health. The current study involved the evaluation of this biocide agent against 19 nosocomial isolates of Staphylococcus with and without organic substances and applying distilled water and water of 300 ppm hardness as dilution means. Results show that hard water was one of the factors that most highly affected the bactericidal activity of chlorhexidine. Moreover we found that it affected bactericidal activity more than the interference generated by organic substances. Our study proves that chlorhexidine is an effective antiseptic for these gram-positive microorganisms.

Efecto de clorhexidina sobre aislamientos hospitalarios de Staphylococcus aureus en diferentes condiciones ambientales / [Effect of chlorhexidine on Staphylococcus aureus hospital isolates under different environmental conditions]

Antiseptic agents are widely used in hospitals, being essential when prevention and control of nosocomial infections are required. It is necessary to consider several aspects that affect the biocide activity, since they have direct incidence in hospital hygiene, health and also in the nosocomial infection rate. Organisms belonging to Staphylococcus genus are involved in such infections and, digluconate of chlorhexidine is one of the most used antiseptic agents for human and animal health. The current study involved the evaluation of this biocide agent against 19 nosocomial isolates of Staphylococcus with and without organic substances and applying distilled water and water of 300 ppm hardness as dilution means. Results show that hard water was one of the factors that most highly affected the bactericidal activity of chlorhexidine. Moreover we found that it affected bactericidal activity more than the interference generated by organic substances. Our study proves that chlorhexidine is an effective antiseptic for these gram-positive microorganisms.

SOME DIFFERENCES IN COGNITIVE ABILITIES BETWEEN SELECTED CANADIAN AND FILIPINO STUDENTS.

This study was designed to compare both profiles of mean performance and relationships between performances on cognitive tasks in groups of children and adolescents in Canada and The Philippines with similar educational experience. A battery of eighteen tests, including the Raven's Progressive Matrices (1968), the SRA Primary Mental Abilities Tests, and selected tests from the ETS kit, was used. The samples included 219 students from an urban centre in Ontario, boys, and girls in grades 6 and 8 from private, public, and Catholic schools, and 203 students in Manila from similar sources. The results demonstrate the existence of two general factors of intellectual funotioning, one concerned with conceptual or relational thinking and the other with forming associations. There was a marked difference between the profiles of mean factor scores for the Canadian and Filipino groups, but an equally marked similarity within groups.