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Efficacy of cognitive rehabilitation in cognition and brain networks: A randomised clinical trial in patients with multiple sclerosis
Get PDFCognitive rehabilitation; Multiple sclerosis; Structural networksRehabilitació cognitiva; Esclerosi múltiple; Xarxes estructuralsRehabilitación cognitiva; Esclerosis múltiple; Redes estructuralesThis study evaluated the efficacy of the computerised Guttmann, NeuroPersonalTrainer® (GNPT) cognitive rehabilitation (CR) and characterised the induced changes in cerebral networks in patients with multiple sclerosis (MS). This multicentre, double-blind, randomised clinical trial compared upward intensity training (active treatment) to low-intensity static training (static treatment). Cognition was assessed using the Brief Repeatable battery before and after 12 weeks of training and at 10-months follow-up, and patients were classified as having a mild or severe cognitive impairment (CI). Brain MRI pre- and post-CR were analysed using an advanced tractography algorithm, based on multishell diffusion MRI, to obtain node-based graph metrics (local efficiency and strength) from microscopic fractional anisotropy. Seventy MS patients completed the study (age 48.9 ± 8.8, disease duration 16.8 ± 9.0 years); active treatment: 36, static treatment: 34. Verbal memory improved significantly post-CR in both groups (55 % active; 34 % static treatment), accompanied by increases in local efficiency and strength in multimodal regions. At follow-up, verbal memory declined in both groups but remained above the pre-CR assessment (−25 % and −17 %, respectively). Patients with severe-CI (n = 36) showed improvement only with active treatment, while those with mild-CI (n = 34) improved regardless of intensity treatment. Network changes were more pronounced in patients in active treatment and in those with severe-CI. Quality of life did not change at post-CR, and cognitive improvement was influenced by cognitive reserve (p = 0.011). In MS, GNPT temporarily improves verbal memory and increases network connectivity, reinforcing the CR as a valuable tool for enhancing cognitive skills and promoting neuronal plasticity.This work was sponsored by the Instituto Carlos III (ISCIII) and co-funded by the European Union through the Plan Estatal de Investigación Científica y Técnica y de Innovación 2015–2024 (PI15/00587 to SL and AS; PI18/01030 to SL and AS; PI21/01189 to SL and AS), by AGAUR SGR-Cat 2021, by the Red Española de Esclerosis Múltiple (REEM − RD16/0015/0002, RD16/0015/0003), by Bristol-Myers Squibb, the Ayudas Merck de Investigación 2017 from the Fundación Merck Salud and the Proyecto Societat Catalana Neurologia 2017
Cognitive frailty: a useful concept or a source of confusion? Insights from a survey of European geriatricians
Get PDFCognitive frailty; Delirium; DementiaFragilitat cognitiva; Deliri; DemènciaFragilidad cognitiva; Delirio; DemenciaBackground
This report examines how European geriatricians understand the concept of ‘cognitive frailty’, which was first formally defined by the International Academy on Nutrition and Aging (IANA) and the International Association of Gerontology and Geriatrics (IAGG) in 2013.
Methods
An online survey about delirium, dementia and frailty relationships and pathways was distributed across Europe through appropriate professional groups. Eligible participants were geriatricians or trainees in their final two years of specialist geriatric training, in a European country. Snowball sampling was used. In total, 440 people replied to the survey, of which 324 responded to the section on cognitive frailty. Respondents were predominantly female and there was a marked under-representation of Eastern European participants.
Results
From a list of possible definitions, only one in four of the 324 respondents identified cognitive frailty as defined by the IANA and the IAGG, i.e., a combination of physical frailty and mild cognitive impairment. Almost two thirds of those who stated that they currently use the term in their work did not choose the IANA-IAGG definition. After the definition was shared with respondents, only 44% strongly agreed with it as an apt description of cognitive frailty, with some considering it too narrow (by omitting delirium and dementia) while others considered it too broad (by including physical frailty).
Conclusions
There is no clear consensus opinion among geriatricians in Europe on the definition of ‘cognitive frailty’. While there is some core support for the IANA-IAGG definition, it is not intuitive to those not already familiar with the term. The variance in the current understanding of cognitive frailty among geriatricians suggests the time is right for a meaningful debate on this issue. While there is ongoing, growing research on a shared pathophysiology between physical frailty and cognitive impairment, further studies are required to evaluate the added benefit of this particular conceptual theorization in older persons care rather than its single components, and if beneficial, how awareness, understanding and correct usage of the concept can be improved
Is Disease Stability an Attainable Chronic Obstructive Pulmonary Disease Treatment Goal?
Get PDFChronic obstructive pulmonary disease; Disease management; Treatment outcomeMalaltia pulmonar obstructiva crònica; Gestió de la malaltia; Resultat del tractamentEnfermedad pulmonar obstructiva crónica; Gestión de la enfermedad; Resultado del tratamientoChronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition characterized by progressive airflow obstruction. Despite advancements in diagnosis and treatment, the disease burden remains high; although clinical trials have shown improvements in outcomes such as exacerbations, quality of life, and lung function, improvement may not be attainable for many patients. For patients who do experience improvement, it is challenging to set management goals given the progressive nature of COPD. We therefore propose disease stability as an appropriate and attainable treatment goal. Other disease areas have developed definitions of no disease activity or remission, which provide relevant information for defining and achieving stability for patients with COPD. Disease stability builds on related concepts already defined in COPD, such as clinical control and clinically important deterioration. Current components that could form part of a disease stability definition include exacerbations, health status (including quality of life and symptoms), and lung function. Considerations should be given to intervals over which stability is defined and assessed, appropriate thresholds, and defining a composite. Ensuring a holistic approach, objective measurements, and harmonious, clear communication between patients and physicians can further support establishing disease stability. Here we propose a preliminary definition of disease stability, informed by existing research in COPD. Further research will be needed to validate the framework for use in clinical and research settings. Exploring disease stability as a goal, however, is an opportunity to develop and validate an attainable treatment target to advance the standard of care for patients with COPD.Supported by GSK
Scabie: prevenire și control. Ivermectina
No full textSarna; Prevenció i control; Invermectina oralSarna; Prevención y control; Ivermectina oralScabies; Prevention and control; Oral ivermectinAquest document explica què cal fer quan es diagnostica un cas de sarna, tant per a la persona afectada com per als seus contactes estrets. També detalla les mesures higièniques i el tractament mèdic que cal seguir, incloent-hi l’ús d’ivermectina oral.Este documento explica qué hacer cuando se diagnostica un caso de sarna, tanto para la persona afectada como para sus contactos estrechos. También detalla las medidas higiénicas y el tratamiento médico a seguir, incluyendo el uso de ivermectina oral.This document explains what to do when a case of scabies is diagnosed, both for the affected person and their close contacts. It also outlines the hygiene measures and medical treatment to follow, including the use of oral ivermectin
Summary of Research: Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02
Get PDFAdvanced solid tumors; HER2-expressing; Trastuzumab deruxtecanTumors sòlids avançats; Expressió HER2; Trastuzumab deruxtecanTumores sólidos avanzados; Expresión HER2; Trastuzumab deruxtecanSummary of the original article, ‘Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02’. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate, which is a chemotherapy with a linker (deruxtecan) joined to an antibody (trastuzumab). Trastuzumab binds to the human epidermal growth factor receptor 2 (HER2) protein on cancer cells, where it releases the chemotherapy to kill these cells. The DESTINY-PanTumor02 clinical study tested the effectiveness of T-DXd for people with various HER2-expressing cancers and the safety of treatment. Previous results from DESTINY-PanTumor02 showed that T-DXd had antitumor activity, and the greatest effects were seen in people with the highest tumor level of HER2 [defined as immunohistochemistry (IHC) 3+]. In this previous analysis, the HER2 expression was measured at a central laboratory. In clinical practice, HER2 expression will likely be measured at a local laboratory, so understanding whether T-DXd has similar effects regardless of how HER2 expression is measured is important. Here, we looked at the effects of T-DXd based on the HER2 test result used to determine a person’s eligibility for the study, which could be measured using a local or central laboratory. In people with IHC 3+ tumors (where HER2 was measured at a local or central laboratory), 51% had a decrease in the size or number of tumors, according to established criteria (referred to as an objective response), while, in people with IHC 2+ tumors, 26% had an objective response. Side effects with T-DXd were consistent with previous studies. These results confirm T-DXd has antitumor effects in HER2-expressing cancers where the HER2 expression is measured by a local or central laboratory.This study is sponsored by AstraZeneca. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201). AstraZeneca funded the Rapid Service and Open Access fees
Clinical decision impact of HER2DX, an algorithm-powered genomic diagnostic in early-stage HER2-positive breast cancer: results from a prospective real-world study
Get PDFEarly breast cancer; HER2 positive; Genomic testCàncer de mama precoç; HER2 positiu; Prova genòmicaCáncer de mama precoz; HER2 positivo; Prueba genómicaBackground
HER2DX is a clinically available genomic assay that provides prognostic (relapse risk score), predictive [pathological complete response (pCR) likelihood score], and ERBB2 expression data in stage I-III human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). This real-world study evaluated its clinical impact.
Patients and methods
This prospective study enrolled newly diagnosed patients with stage I-III HER2-positive BC across 12 hospitals in Spain (November 2021-September 2024). Thirty-four oncologists ordered HER2DX and completed questionnaires before and after receiving results to assess treatment changes (primary objective). Secondary objectives included evaluating the HER2DX pCR likelihood score association with pCR, test turnaround time, changes in physician confidence regarding treatment decisions, and cost-effectiveness.
Results
Among 297 recruited patients, 48.1% (95% confidence interval 42.5% to 53.7%) experienced treatment adjustments after HER2DX. Within these cases, 73.5% involved reduced treatment intensity, 24.5% involved increased treatment intensity, and the remaining cases (2.0%) involved mixed adjustments. Of the cases with reduced treatment intensity, 56.2% had a reduction in chemotherapy intensity, 26.7% had a reduction in anti-HER2 therapy, and 17.1% in both. Among the 182 patients with available pathological data at surgery, the pCR likelihood score was a significant predictor of pCR (P < 0.001). In 69 patients with pCR-high disease, less intensive treatment achieved similar pCR rates compared with multi-agent chemotherapy (81.5% versus 69.0%; odds ratio = 1.97, P = 0.256). Physician confidence improved (P < 0.001) and the estimated total cost savings, including direct drug costs, vein access devices, and HER2DX costs, amounted to €98 031.
Conclusions
HER2DX impacts clinical management in stage I-III HER2-positive BC by supporting treatment adjustments, enhancing physician confidence, maintaining pCR rates, and reducing health care costs.FS is supported by a Rio Hortega clinical scientist contract from the Instituto de Salud Carlos III (ISCIII) [grant number CM22/00073]. FBM received funding from Fundación científica AECC Ayudas Investigador AECC 2021 [grant number INVES21943BRAS]
Health-related quality of life associated with fruquintinib in patients with metastatic colorectal cancer: Results from the FRESCO-2 study
Get PDFFruquintinib; Health-related quality of life; Metastatic colorectal cancerFruquintinib; Calidad de vida relacionada con la salud; Cáncer colorrectal metastásicoFruquintinib; qualitat de vida relacionada amb la salut; Càncer colorectal metastàticIntroduction
Maintaining or improving health-related quality of life (HRQoL) is as important as extending survival in metastatic colorectal cancer. We report an HRQoL analysis from FRESCO-2 (NCT04322539).
Methods
Patients were randomized to fruquintinib +best supportive care (BSC; n = 461) or placebo +BSC (n = 230). Instruments of EORTC QLQ-C30 and 5-level EQ-5D, and ECOG performance status (PS) were assessed. Changes from baseline scores for QLQ-C30 and EQ-5D were evaluated and minimally important difference thresholds were used to define stable, improved, or deteriorated QoL. Time to deterioration (TTD) was assessed.
Results
With fruquintinib versus placebo, baseline QLQ-C30 global health status (GHS) and EQ-5D visual analog scale (VAS) scores were 65.2 versus 64.6 and 67.0 versus 66.6, respectively. Least-squares mean changes from baseline fluctuated throughout treatment. At end of treatment (EOT), mean scores with fruquintinib versus placebo were 53.8 versus 52.3 (QLQ-C30 GHS) and 58.9 versus 58.5 (EQ-5D VAS). For QLQ-C30 GHS, 38.3 % versus 36.5 % of patients receiving fruquintinib versus placebo had stable or improved scores at EOT; median TTD was 2.1 versus 1.8 months (HR, 0.9; 95 % CI, 0.7–1.0). For EQ-5D VAS, 47.9 % versus 42.7 % had stable or improved scores at EOT; median TTD was 2.6 versus 1.9 months (HR, 0.8; 95 % CI, 0.6–0.9). Median TTD to ECOG PS ≥ 2 or death within 30+ /7 days after EOT was 6.6 versus 2.9 months with fruquintinib versus placebo (HR, 0.6; 95 % CI, 0.4–0.7).
Conclusions
Fruquintinib delayed TTD of ECOG PS and did not negatively impact HRQoL versus placebo.This study was funded by HUTCHMED
Prediction of 90-day mortality among cancer patients with unplanned hospitalisation: a retrospective validation study of three prognostic scores
Get PDFCancer; Mortality; NutritionCàncer; Mortalitat; NutricióCáncer; Mortalidad; NutriciónBackground
Accurate prediction of 90-day mortality in hospitalised cancer patients is critical for guiding personalised treatment decisions and optimising oncologic care. However, existing prognostic models often lack sufficient precision, particularly in distinguishing between high- and low-risk patients. In this retrospective study, we independently evaluated the prognostic performance of three scoring systems—the Prognostic Score for Hospitalised Cancer Patients (PROMISE), the Gustave Roussy Immune (GRIm) score, and the C-reactive protein–Triglyceride–Glucose Index (CTI)—in patients admitted for unplanned hospitalisations.
Methods
This retrospective observational study was conducted at the Medical Oncology Clinic of Ankara Etlik City Hospital, Turkey, and included patients aged 18 years or older with a diagnosis of cancer who were hospitalised unexpectedly between February 2023 and February 2024. Laboratory data were retrieved from the institutional hospital information system. The PROMISE score was calculated using its original specification via the online tool (https://promise.vhio.net/). The GRIm score was calculated based on neutrophil-to-lymphocyte ratio (NLR), albumin, and lactate dehydrogenase (LDH). The CTI score was computed as: CTI = [0.412 × ln (C-reactive protein [CRP])] + ln [Triglyceride × Glucose/2], with a cut-off value of 4.78. A PROMISE–CTI Combined score was derived using regression-based weighting. Risk stratification was performed for all three scores using validated thresholds. Statistical analyses included Kaplan–Meier survival analysis, log-rank tests, univariable and multivariable logistic regression to assess predictors of 90-day mortality, and receiver operating characteristic (ROC) curve analysis to evaluate discriminatory performance.
Findings
Among 1657 hospitalised cancer patients screened during the study period, 1109 met the inclusion criteria and were included in the analysis. PROMISE and GRIm scores were calculated for all 1109 patients, while CTI score was assessed in 333 patients with complete laboratory data. The 90-day mortality rate was 63.7% (n = 707). High PROMISE score (OR: 3.32, 95% CI: 1.40–7.86; p = 0.006) and high CTI score (OR: 2.85, 95% CI: 1.32–6.18; p = 0.008) were associated with increased 90-day mortality. Low PROMISE score (OR: 0.22, 95% CI: 0.10–0.49; p = 0.001) and low CTI score (OR: 0.35, 95% CI: 0.17–0.73; p = 0.003) were associated with reduced 90-day mortality. High GRIm score (OR: 1.83, 95% CI: 0.83–2.91; p = 0.07) and low GRIm score (OR: 0.73, 95% CI: 0.47–1.20; p = 0.08) were not significantly associated with 90-day mortality. The area under the curve (AUC) of the PROMISE–CTI Combined score was 0.884 (95% CI: 0.849–0.919; p < 0.0001). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the PROMISE–CTI Combined score were 92.4%, 81.1%, 85.3%, 89.6%, and 86.7%, respectively.
Interpretation
The PROMISE score demonstrated strong discriminatory ability in predicting 90-day mortality among cancer patients admitted for unplanned hospitalisations. Integration of the CTI score further improved risk stratification by incorporating nutritional and inflammatory markers. The PROMISE–CTI Combined score may serve as a practical clinical tool for short-term prognostic assessment in this setting. Prospective, multicentre, randomised studies are needed to confirm the clinical utility and generalisability of the PROMISE–CTI Combined score
Improving pre-operative binary grading: relevance of p53 and PR expression in grade 2 endometrioid endometrial carcinoma
Get PDFEndometrial carcinoma; Grade 2; Progesterone receptorCarcinoma de endometrio; Grado 2; Receptor de progesteronaCarcinoma d'endometri; Grau 2; Receptor de progesteronaObjective
This study aimed to evaluate the association between pre-operative progesterone receptor (PR) and p53 expression and prognosis in pre-operative grade 2 endometrioid endometrial carcinoma compared with grade 1 and grade 3 carcinomas.
Methods
Three European endometrial carcinoma cohort studies were included. Patients with pre-operative grade 2 endometrioid carcinoma and known pre-operative PR and p53 status were included (n = 400), as were patients with pre-operative grade 1 (n = 602) or grade 3 (n = 148) endometrioid carcinomas. Kaplan-Meier and Cox regression analyses were performed to analyze disease-specific and disease-free survival.
Results
Patients with pre-operative grade 2 endometrial carcinoma and wild-type p53 plus PR-positive expression showed a similar 7-year disease-specific survival to grade 1 endometrial carcinoma patients (95.8% vs 97.5%, p = .13), while the 7-year disease-specific survival of patients with grade 2 endometrial carcinoma with p53 aberrant and/or negative PR expression (83.5%) was significantly lower (p < .001). The combination of these markers was an independent prognostic factor in multivariate Cox regression analyses.
Conclusions
The prognostic impact of pre-operative p53 and PR expression in patients with grade 2 endometrioid endometrial carcinoma supports a modified binary grading system in which grade 2 patients should be pre-operatively classified as low- or high-grade depending on p53 and PR expression
Mid-term outcomes of percutaneous pulmonary valve replacement with Edwards-Sapien bioprosthesis in native right ventricular outflow tract
Get PDFCongenital heart disease; Edwards sapien; Pulmonary valveCardiopatia congènita; Edwards Sapien; Vàlvula pulmonarCardiopatía congénita; Edwards Sapien; Válvula pulmonarInformation on mid-term outcomes of percutaneous pulmonary valve replacement (PPVR) with the Edwards Sapien (ES) valve in the native right ventricular outflow tract (RVOT) are limited. This study assesses mid-term outcomes in 76 patients who underwent PPVR between 2016 and 2022, comparing native (40.8%) and non-native (59.2%) RVOTs. The primary endpoint was a composite of endocarditis, reinterventions, and cardiovascular death and secondary outcomes included prosthetic valve dysfunction (PVD), tricuspid regurgitation (TR), right ventricular ejection fraction (RVEF), and indexed ventricular volumes. The median patient age was 23.9 years. Pulmonary regurgitation was predominant in the native RVOT group (67.7%), while pulmonary stenosis or combined lesions were more common in the non-native group (90.9%). Procedural success was 98.7%. After a median follow-up of 3.3 years, there was no significant difference in freedom from the primary outcome between groups (87.1% native vs. 93.1% non-native, p = 0.875). Endocarditis and reinterventions occurred at 1.2 per 100 patient-years, and PVD at 3.19 per 100 patient-years, with no differences between groups. A 1-year reduction in ventricular volumes and TR was seen only in the non-native group, with no improvement in RVEF. Overall, PPVR with the ES valve demonstrates satisfactory mid-term outcomes in both native and non-native RVOTs.Yassin Belahnech is supported by a research non-conditioned grant (Rio Hortega CM22/00242) unrelated to the content of this article