Uterine cancer restaging according to the updated 2023 FIGO Guidelines does not uniformly affect prognosis: An institutional retrospective cohort study.

OBJECTIVE: Efforts have been made to better risk stratify patients given the rise in incidence of endometrial cancer (EC). The 2023 FIGO staging now incorporates histologic subtype and molecular classification into determination of EC stage. We sought to elucidate if the new staging system demonstrated prognostic differences compared to the 2009 staging system. METHODS: A retrospective chart review was performed on women treated for EC at our institution from September 2013 to May 2023 and combined with the publicly available TCGA Nature 2013 dataset. Detailed clinical information was captured. Patients were restaged according to the 2023 guidelines. Survival estimates were obtained using Kaplan-Meier method, and the log-rank test was used to compare survival curves for progression-free survival (PFS). RESULTS: 919 patients were included in our analysis. The datasets were comparable regarding histologic grade, stage, and age at diagnosis. 175 (31.5%) of patients in the institution dataset and 115 (31.6%) patients in the TCGA dataset experienced a stage change. Most patients whose stage changed were upstaged (275/290; 94.8%). 3-year PFS estimates for stage IA patients with no stage change versus those upstaged were 92.3% (95% CI: 87.2, 95.4) v. 72.0% (95% CI: 68.4, 84.9), p = 0.002. No significant differences in survival difference were seen in other stage subsets. CONCLUSION: Modest survival differences exist in patients with EC originally staged as IA who underwent upstaging. No significant survival difference is observed in patients who are restaged to stage II or III subsets. Improved risk stratification is needed in assessing prognosis and adjuvant therapy for patients with endometrial cancer.

Autonomous Motility of Polymer Films.

Adaptive soft materials exhibit a diverse set of behaviors including reconfiguration, actuation, and locomotion. These responses however, are typically optimized in isolation. Here, the interrelation between these behaviors is established through a state space framework, using Nylon 6 thin films in a humidity gradient as an experimental testbed. It is determined that the dynamic behaviors are a result of not only a response to but also an interaction with the applied stimulus, which can be tuned via control of the environment and film characteristics, including size, permeability, and coefficient of hygroscopic expansion to target a desired behavior such as multimodal locomotion. Using these insights, it is demonstrated that films simultaneously harvest energy and information from the environment to autonomously move down a stimulus gradient. Improved understanding of the coupling between an adaptive material and its environment aids the development of materials that integrate closed loop autonomous sensing, actuation, and locomotion.

A randomised phase II trial of selumetinib vs selumetinib plus temsirolimus for soft-tissue sarcomas.

BACKGROUND: The MEK inhibitor, selumetinib, suppresses soft-tissue sarcoma (STS) cell proliferation in vitro. Mammalian target of rapamycin inhibitors possess modest activity against STS; however, resistance develops via MAPK pathway feedback activation. The combination of selumetinib and temsirolimus synergistically inhibits STS cell line growth. Therefore, a randomized phase II trial of selumetinib vs selumetinib plus temsirolimus was conducted. METHODS: Seventy-one adults with advanced STS who received ⩽ 2 prior chemotherapeutics were randomized to selumetinib 75 mg p.o. bid and allowed to crossover upon progression, or to selumetinib 50 mg p.o. bid plus temsirolimus 20 mg i.v. weekly, with primary endpoint of progression-free survival (PFS). RESULTS: There was no difference in PFS between the two arms for the overall cohort (median 1.9 vs 2.1 months); an improved median PFS was observed in the combination arm (N = 11) over single agent (N = 10) in the prespecified leiomyosarcoma stratum (median 3.7 vs 1.8 months; P = 0.01). Four-month PFS rate was 50% (95% confidence interval 0.19-0.81) with the combination vs 0% with selumetinib alone in the leiomyosarcoma cohort. Most common grade 3/4 adverse events with the combination were mucositis (29%), lymphopenia (26%), neutropenia and anaemia (20% each). CONCLUSIONS: While single-agent selumetinib has no significant activity in STS, the combination may be active for leiomyosarcomas.

[Investigation of an outbreak of norovirus gastroenteritis in a geriatric hospital]. / Investigation d'une épidémie de gastro-entérite à norovirus dans un hôpital gériatrique.

In aged-care facilities, gastroenteritis outbreaks are responsible for big trouble in the management of cares to the elderly. In November 2002, a gastroenteritis outbreak was observed in 5 of the 6 wards of the geriatric hospital La Charité, University Hospital of Saint-Etienne, France, with an attack rate of 38.5% in the elderly (70 infected from 182 patients) and of 26.0% in the nursing staff (40 infected from 154 agents). The outbreak lasted 30 days with a peak corresponding to 79.8% of the cases between the 11(th) and the 20(th) of November. The first cases were observed in the two short-term-care wards; then, the outbreak spread rapidly to 3 of the 4 long-term care units. Health care workers were contaminated later than the elderly (P < 0.001 by Kruskal-Wallis test). A self-administered questionnaire was documented by most of the nursing staff; the most frequently observed clinical symptoms in this population were nausea (82.5%), abdominal pain (80.0%), diarrhoea (70.5%), asthenia (67.5%) and vomiting (62.5%). Thirty-five percent of the health care workers ceased their work. The causative agent of the gastroenteritis was identified by RT-PCR in the stools of 5 aged persons as a norovirus close to the Lordsdale strain (genogroup II). These findings illustrate the respective role of elderly and health care workers in the spread of the gastroenteritis outbreak inside the geriatric hospital.

[Outbreaks due to respiratory syncytial virus and influenzavirus A/H3N in institutionalized aged. Role of immunological status to influenza vaccine and possible implication of caregivers in the transmission]. / Infections groupées à virus respiratoire syncytial et à influenzavirus A/H3N2 chez des sujets âgés en institution. Influence du statut vaccinal anti-grippal et implication possible des soignants dans la transmission.

OBJECTIVES: Report of epidemiological, clinical and virological data collected from the prospective surveillance of febrile episodes observed in aged residents of a long-stay care unit of 33 beds, at the University Hospital of Saint-Etienne, during the 1997-1998 winter season. METHODS: Systematic collection of clinical and biological data from febrile patients (> or = 38 degrees C) on a form, including virological findings obtained from a nasal swab and paired serum specimens. RESULTS: From 38 patients (37 of them having been vaccinated against influenza in October 1997), 18 febrile episodes were recorded in 16 subjects, including 3 respiratory syncytial virus infections and a late-occurring outbreak (March 1998) of influenza due to a A/H3N2 strain (15 cases, 14 of them virologically confirmed). No death was noted after the influenza outbreak. In 8 of the 9 tested patients with influenza, "protective" titres of antibodies directed towards the hemagglutinin of the vaccinal strain were present by radial hemolysis test three months before the beginning of the outbreak. During the influenza outbreak, the attack rate of symptomatic infection was 45.5% in elderly and 47.5% in healthcare workers (mainly unvaccinated). The occurrence of the first cases in the latter suggests their possible role in the transmission of the virus to the aged. CONCLUSION: This study underlines the epidemic circulation of multiple respiratory viruses during the same winter season in long-stay care facilities, the occurrence of clinical influenza infections in vaccinated patients exhibiting protective antibody titres and the role of unvaccinated healthcare workers in the propagation of influenza in institutionalised aged.

Resistance to nevirapine of HIV-1 reverse transcriptase mutants: loss of stabilizing interactions and thermodynamic or steric barriers are induced by different single amino acid substitutions.

The kinetic parameters governing the inhibition by Nevirapine of the RNA-dependent DNA synthesis catalyzed by HIV-1 reverse transcriptase have been determined by steady-state kinetic analysis with the wild-type enzyme and with mutant reverse transcriptases containing the single amino acid substitutions L100I, K103N, V106A, V179D, Y181I and Y188L. While the mutant V179D was inhibited by Nevirapine as the wild-type enzyme, all the other mutations displayed a 17 to 90-fold reduced sensitivity to the drug in the order: Y181I<(i.e. less sensitive) Y188L < V106A < L100I < K103N < wild-type. Determination of the rate constants for Nevirapine binding (kon) and dissociation (koff) for the mutant and wild-type enzymes showed that mutations L100I and V106A increased the koff values by 12 and 8.5-fold, respectively, without significantly affecting the kon, whereas mutation K103N decreased the kon 5-fold without increasing the koff. Mutations Y181I and Y188L, on the other hand, conferred resistance to Nevirapine affecting both koff and kon values. In addition, mutations L100I and Y181I reduced the catalytic potential of HIV-1 RT. Thus, Nevirapine resistance could arise from a combination of loss of stabilizing interactions and emergence of steric and thermodynamic barriers for drug binding, depending on the particular amino acid substitution involved.