Endometrial carcinoma: 10 years of TCGA (the cancer genome atlas): A critical reappraisal with comments on FIGO 2023 staging.

The Cancer Genome Atlas (TCGA) Research Network described 4 molecular subgroups of endometrial carcinomas with different outcome: 1) POLE ultramutated endometrioid carcinomas which have an indolent behavior; 2) microsatellite instability hypermutated endometrioid carcinomas associated with intermediate prognosis; 3) copy-number low endometrioid carcinomas also with intermediate prognosis; and 4) copy-number high predominantly serous (non-endometrioid) but also serous-like endometrioid carcinomas, almost always carrying TP53 mutations, with poor clinical outcome. After 10 years of comprehensive analysis, it appears that the only real contribution of TCGA to the clinical management of these patients would be limited to the infrequent high-grade, early-stage endometrioid carcinomas with POLE exonuclease domain mutations, as these patients could benefit from a de-escalating treatment; knowledge about the other three subgroups has not changed significantly. The copy-number low (or non-specific genetic profile) which is the most frequent subgroup, is a mixture subgroup where investigators are currently trying to establish prognostic markers; for example, unexpected variations in a relatively small percentage of cases (i.e., CTNNB1 mutated or p53 aberrant low-grade and low-stage endometrioid carcinomas associated with unfavorable prognosis). On the other hand, TCGA has underlined that a small number of grade 3 endometrioid carcinomas, all TP53 mutated, overlap with copy-number high serous carcinomas. Recently, TCGA molecular subgroups have been integrated into the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging classification which incorporates other non-anatomic parameters like histotype, tumor grade, and lymphovascular space invasion. The result is a complicated and non-intuitive classification that makes its clinical application difficult and does not facilitate correspondence with the 2009 FIGO staging.

Biological and Physical Performance Markers for Early Detection of Cognitive Impairment in Older Adults.

Dementia is a major cause of poor quality of life, disability, and mortality in old age. According to the geroscience paradigm, the mechanisms that drive the aging process are also involved in the pathogenesis of chronic degenerative diseases, including dementia. The dissection of such mechanisms is therefore instrumental in providing biological targets for interventions and new sources for biomarkers. Within the geroscience paradigm, several biomarkers have been discovered that can be measured in blood and that allow early identification of individuals at risk of cognitive impairment. Examples of such markers include inflammatory biomolecules, markers of neuroaxonal damage, extracellular vesicles, and DNA methylation. Furthermore, gait speed, measured at a usual and fast pace and as part of a dual task, has been shown to detect individuals at risk of future dementia. Here, we provide an overview of available biomarkers that may be used to gauge the risk of cognitive impairment in apparently healthy older adults. Further research should establish which combination of biomarkers possesses the highest predictive accuracy toward incident dementia. The implementation of currently available markers may allow the identification of a large share of at-risk individuals in whom preventive interventions should be implemented to maintain or increase cognitive reserves, thereby reducing the risk of progression to dementia.

Prevention, Assessment, and Management of Malnutrition in Older Adults with Early Stages of Cognitive Disorders.

Malnutrition is common in older adults, and its risk is greater in those living with dementia. Relative to cognitively healthy peers, the prevalence of malnutrition is also increased in individuals with early stages of cognitive disorders owing to pathophysiological, cognitive, and psychosocial changes related to cognitive impairment. Malnutrition is associated with adverse health outcomes, including faster cognitive and functional decline. Here, we provide an overview of the prevention, assessment, and management of malnutrition in older adults, with a special focus on the aspects that are important to consider in individuals with early stages of cognitive disorders. Strategies to prevent malnutrition include systematic screening for malnourishment using validated tools to detect those at risk. If the screening reveals an increased risk of malnutrition, a detailed assessment including the individual's nutritional, medical, and functional status as well as dietary intake should be performed. The management of malnutrition in the early stages of cognitive disorders should be based on the findings of a comprehensive assessment and be personalized according to the individual's specific characteristics. In the article, we also provide an overview of the evidence on vitamin supplements and specific dietary patterns to prevent cognitive decline or attenuate its progression.

Performance and Failure of Right Ventricle to Pulmonary Artery Conduit in Congenital Heart Disease.

Surgical implantation of a right ventricle to pulmonary artery (RV-PA) conduit is an important component of congenital heart disease (CHD) surgery, but with limited durability, leading to re-intervention. The present single-center, retrospective, cohort study reports the results of surgically implanted RV-PA conduits in a consecutive series of children and adults with CHD. Patients with CHD referred for RV-PA conduit surgical implantation (from October 1997 to January 2022) were included. The primary outcome was conduit failure, defined as a peak gradient above 64 mm Hg, severe regurgitation, or the need for conduit-related interventions. Longitudinal echocardiographic studies were available for mixed-effects linear regression analysis. A total of 252 patients were initially included; 149 patients were eligible for follow-up data collection. After a median follow-up time of 49 months, the primary study end point occurred in 44 (29%) patients. A multivariable Cox regression model identified adult age (>18 years) at implantation and pulmonary homograft implantation as protective factors (hazard ratio 0.11, 95% confidence interval [CI] 0.02 to 0.47 and hazard ratio 0.34, 95% CI 0.16 to 0.74, respectively). Fever within 7 days of surgical conduit implantation was a risk factor for early (within 24 months) failure (odds ratio 4.29, 95% CI 1.41 to 13.01). Long-term use of oral anticoagulants was independently associated with slower progression of peak echocardiographic gradient across the conduits (mixed-effects linear regression p = 0.027). In patients with CHD, the rate of failure of surgically implanted RV-PA conduits is higher in children and after nonhomograft conduit implantation. Early fever after surgery is a strong risk factor for early failure. Long-term anticoagulation seems to exert a protective effect.