Exploring the interplay of frailty, physical function, physical activity, nutritional status, and their association with quality of life and depressive symptoms in older adults with the frailty phenotype.

OBJECTIVE: This study aimed to explore the interplay between frailty, physical function, physical activity, nutritional status, and their impact on the quality of life and depressive status in older adults with frailty. METHODS: A cross-sectional study involving 235 pre-frail/frail older adults residing in Spanish communities was conducted. Frailty was assessed using Fried's criteria, physical function was evaluated using the Short Physical Performance Battery, and physical activity levels were measured via wrist-worn accelerometers. Nutritional status was determined using the Mini-Nutritional Assessment alongside anthropometric measurements. Quality of life was gauged using the EuroQoL 5-Dimension 5-Level, while depressive status was assessed using the Yesavage 15-item Geriatric Depression Scale. Multivariate linear regression and logistic regression analyses were employed to elucidate the associations of these factors with quality of life and depression. RESULTS: Our findings revealed significant correlations between various factors and quality of life. Notably, reported fatigue (ß = -0.276, p = 0.002), performance in the 4-m gait test (ß = -0.242, p = 0.001), the score on the short version of the Mini-Nutritional Assessment (ß = 0.312, p = 0.002), and engagement in light physical activity (ß = 0.180, p = 0.023) were all found to be associated with quality of life. In terms of depressive symptoms, the Mini-Nutritional Assessment score emerged as a protective factor (Odds ratio, OR: 0.812, p < 0.001), as did participation in moderate physical activity (OR: 0.988, p = 0.028). Conversely, fatigue (OR: 3.277, p = 0.003) and a slow gait speed (OR: 1.136, p = 0.045) were identified as risk factors for depressive symptoms. CONCLUSIONS: This study underscores the detrimental association of fatigue and slow gait speed on both quality of life and depressive status among older adults with frailty. In contrast, engaging in physical activity and addressing malnutrition risk emerge as critical protective factors for enhancing quality of life and ameliorating depressive symptoms in this population. CLINICAL TRIAL REGISTRATION: This is a study that uses cross-sectional data from a trial registered at ClinicalTrials.gov (Identifier: NCT05610605).

Predictors of Urinary and Fecal Incontinence in Prefrail and Frail Older Adults: A Cross-Sectional Study of the FRAGSALUD Project.

BACKGROUND: Frailty is associated with urinary and fecal incontinence, which are common geriatric syndromes. This study aims to identify health factors associated with incontinence in prefrail or frail older adults living in the community. METHODS: This multicenter cross-sectional study included 225 older adults (75.0 ±â€…6.4 years) with prefrailty or frailty based on the 5-component Fried phenotype. Physical function was assessed using the Short Physical Performance Battery (SPPB). Physical activity, inactivity, and sleep were estimated using a wrist-worn accelerometer. Urinary or fecal incontinence was registered using the Barthel scale (urine and bowel items). Multivariable logistic regression analyses, with age as a covariate, were conducted to identify associations of incontinence. RESULTS: In our participants, 27% presented urinary or fecal incontinence with no sex differences (p = .266). Our results showed that age, daily medication count, and number of falls in the previous year independently predicted incontinence in frail and prefrail older adults (p < .05). Some Fried's criteria, including self-reported exhaustion, gait speed, and handgrip strength, were associated with the presence of incontinence (p < .05), but not Fried's classification. The SPPB total score and its isolated variables were significantly associated with the urinary and fecal incontinence (p < .05). However, none of the accelerometer outcomes showed significant associations with incontinence status. CONCLUSIONS: According to this study, age, number of medications, and falls (but not sex) are linked to urinary and fecal incontinence in frail or prefrail older adults living in the community, recommending the assessment of physical function using the SPPB rather than estimating daily physical activity, inactivity, or sleep.

Latin American Consensus for the Evaluation and Treatment of Patients With Metastatic/Locally Advanced Urothelial Carcinoma.

PURPOSE: Urothelial cancer accounts for approximately 3% of new cancer cases worldwide, with a high burden of disease in countries with medium and low human development indexes where its incidence and mortality are increasing. The purpose of this consensus is to develop statements on the evaluation and treatment of locally advanced and metastatic urothelial carcinoma that would further guide the clinical practice in Latin America. METHODS: A systematic review of the literature was conducted by an independent team of methodologists. Then, a modified Delphi method was developed with clinical specialists from different Latin American countries. RESULTS: Forty-two consensus statements, based on evidence, were developed to address the staging, the evaluation (suitability for chemotherapy, risk assessment, and biomarkers), and systemic treatment (first-line and subsequent therapies) of locally advanced or metastatic urothelial carcinoma. The statements made in this consensus are suggested practice recommendations in the Latin American context; however, the importance of a complete and individualized patient evaluation as a guide for therapeutic selection is highlighted. The availability and affordability of support tools for the evaluation of the disease, as well as specific therapies, may limit the application of the best practices suggested. RECOMMENDATIONS: Therapeutic decisions need to be tailored to the context-specific clinical setting and availability of resources. Local research is promoted to improve outcomes for patients with this challenging cancer in Latin America.

Associations Between Physical Activity and Inactivity Levels on Physical Function and Sleep Parameters of Older Adults With Frailty Phenotype.

This study investigated the relationship between physical activity, inactivity, physical function, and sleep in older adults with a frailty phenotype. A total of 184 pre-frail/frail older adults were included. Physical activity, inactive behavior, and sleep parameters were assessed using a wrist-worn accelerometer. Participants were categorized into four groups based on their levels of inactivity and physical activity. The results showed that individuals with lower levels of inactivity had better lower body mean velocity and sleep regularity than those with higher levels of inactivity. Physically active older adults exhibited faster gait speed and performed better in lower body strength tests than physically inactive participants. Further analysis revealed that specific combinations of inactivity and physical activity were associated with varying levels of physical function. The findings highlight the importance of physical activity and the negative impact of inactivity on physical function and sleep in older adults with a frailty phenotype.

Effects of an educational intervention on frailty status, physical function, physical activity, sleep patterns, and nutritional status of older adults with frailty or pre-frailty: the FRAGSALUD study.

Introduction: The prevalence of frailty is increasing worldwide, emphasizing the importance of prioritizing healthy ageing. To address this, cost-effective and minimally supervised interventions are being sought. This study aimed to assess the impact of an educational program on frailty status, physical function, physical activity, sleep patterns, and nutritional status in community-dwelling older adults with at least 1 Fried's frailty criteria. Methods: A 6-month multicentre randomized controlled trial was conducted from March 2022 to February 2023 in 14 health centres located in Cadiz and Malaga, Spain. The educational intervention consisted of 4 group sessions and 6 follow-up phone calls spread over 6 months. The program focused on educating participants about frailty and its impact on health, providing guidelines for physical activity, healthy dietary habits, cognitive training, psychological well-being and social activities. A total of 163 participants, divided into control (n = 80) and educational groups (n = 83) were assessed before and after the intervention. Results: The results showed a significant group-time interaction in the physical function evaluated with a large effect on Short Physical Performance Battery score (η2p = 0.179, -0.1 [-1.2-1.0] points for control group vs. 1.0 [0.0-3.0] points for educational group, p < 0.001), and an effect on the 4-meter gait test ((η2p = 0.122, 0.5 [0.1-0.0] s for control group vs. -0.4 [-0.5- -0.3] s for educational group, p < 0.001), and the 5-repetition sit-to-stand test (η2p = 0.136, 1.0 [0.0-1.2] s for control group vs. -4.3 [-7.0- -2.3] for educational group, p < 0.001). Additionally, the use of accelerometers to assess physical activity, inactivity, and sleep patterns revealed a significant small effect in the number of awakenings at night ((η2p = 0.040, 1.1 [-0.5-3.4] awakenings for control group vs. 0.0 [-2.2-0.0] awakenings for educational group, p = 0.009). The findings also highlighted a significant medium effect regarding malnutrition risk, which was assessed using the Mini-Nutritional Assessment score (η2p = 0.088, -0.7 [-2.3-1.5] points for control group vs. 1.5 [-0.5-3.0] points for educational group, p < 0.001). Discussion: Thus, the 6-month educational program effectively improved physical function, sleep patterns, and nutritional status compared to usual healthcare attendance in community-dwelling older adults with frailty or pre-frailty. These findings underscore the potential of minimally supervised interventions in promoting a healthy lifestyle in this vulnerable population.

Health factors associated with cognitive frailty in older adults living in the community.

Introduction: This study aims to investigate the health factors associated with cognitive frailty in frail and pre-frail older adults living in the community. Methods: A total of 233 older adults meeting Fried's criteria for pre-frailty or frailty were included. Cognitive status was evaluated using the Short Portable Mental Status Questionnaire. Health factors encompassed nutritional status (evaluated using the Mini Nutritional Assessment tool, body mass index, and waist, arm, and leg circumferences), physical function (assessed with the Short Physical Performance Battery), quality of life (measured with the total index of the EuroQoL 5-Dimension 5-Level questionnaire - EQoL-Index -, and the Visual-Analogue Scale - QoL-VAS - for today's health state), as well as sleep, physical activity, and inactivity estimated through wrist-worn accelerometers. Multivariable logistic regression analyses were conducted to identify potential predictors of cognitive frailty, considering age as a confounding factor. Results: Cognitive frail participants exhibited advanced age, heightened self-reported exhaustion, diminished overall physical performance, reduced leg perimeter, decreased engagement in moderate-to-vigorous physical activity, and higher levels of inactivity (all p<0.05). However, after adjusting for age, only QoL-VAS emerged as a cognitive frailty risk factor (Odds ratio: 1.024), while the EQoL-Index, calf perimeter, and levels of moderate-to-vigorous physical activity were identified as protective factors (Odds ratios: 0.025, 0.929, and 0.973, respectively). Discussion: This study highlights the complex relationship between non-modifiable factors such as age, and modifiable factors including quality of life, nutritional status, and physical activity in the development of cognitive frailty among older adults with a frailty phenotype living in the community.

Risk and Protective Factors for Frailty in Pre-Frail and Frail Older Adults.

This study aims to evaluate the differences in body composition, physical function, and physical activity between pre-frail/frail older adults and to detect risk and protective factors against frailty and physical frailty. Fried's criteria for frailty and physical frailty using the short-performance physical battery (SPPB) were measured in 179 older participants (75.3 ± 6.4 years old). Body weight, height, and waist, arm, and leg circumferences were obtained as body composition variables. Daily accelerometer outcomes (physical activity and inactivity) were obtained. Pre-frail participants showed overall better physical function and spent more time in physical activity and less time in long inactivity periods than frail participants (p < 0.05). Risk frailty factors were higher waist perimeter (Odds Ratio [OR]: 1.032, 95%CI: 1.003-1.062), low leg performance (OR: 1.025, 95%CI: 1.008-1.043), and inactivity periods longer than 30 min (OR:1.002, 95%CI: 1.000-1.005). Protective factors were standing balance (OR:0.908, 95%CI: 0.831-0.992) and SPPB score (OR: 0.908, 95%CI: 0.831-0.992) for frailty, handgrip strength (OR: 0.902, 95%CI: 0.844-0.964) for physical frailty, and light (OR: 0.986, 95%CI: 0.976-0.996) and moderate-to-vigorous (OR: 0.983, 95%CI: 0.972-0.996) physical activity for both. Our findings suggest that handgrip strength, balance, and physical activity are protective frailty factors and can be monitored in pre-frail older adults. Moreover, poor lower body performance and long inactivity periods are frailty risk factors, which highlights their importance in frailty assessment.

Diagnóstico y tratamiento multidisciplinario de melanoma temprano y localmente avanzado. Consenso de expertos. Asociación Colombiana de Hematología y Oncología (ACHO) / Diagnosis and multidisciplinary treatment of early-stage and locally advanced melanoma: Expert consensus, Colombian Association of Hemato-Oncology (ACHO)

Resumen Introducción: El melanoma ocasiona el 75% de las muertes por cáncer de piel. Según GLOBOCAN, en 2018 se presentaron 287.723 casos nuevos de melanoma, con una mortalidad de 60.712 casos, que equivale al 20% del total de los casos incidentes. Las alternativas para el tratamiento del melanoma se fundamentan en la estatificación de la enfermedad, y en las características moleculares de la enfermedad. Objetivo: Consensuar, por común acuerdo de expertos, sugerencias para el diagnóstico y manejo de melanoma temprano basadas en la evidencia y ajustadas al contexto colombiano. Métodos: Se llevó a cabo un consenso de expertos multidisciplinario, constituido por 19 oncólogos clínicos, 2 cirujanos de mama y tejidos blandos, 2 dermatólogos, 2 patólogos y 2 radioterapeutas, miembros activos de la Asociación Colombiana de Hemato Oncología (ACHO). Este consenso se realizó en 4 etapas: 1. Estructuración de 29 preguntas, que se calificaron de 1 a 9. 2. Reenvío de las preguntas no consensuadas. 3. Análisis y discusión de las respuestas. 4. Las respuestas no consensuadas se llevaron a un consenso nominal. Resultados: Se discutieron 29 preguntas relacionadas con el diagnóstico y tratamiento de melanoma temprano, se construyeron sugerencias basadas en evidencia utilizada por los expertos y en guías de manejo de oncología reconocidas internacionalmente, adaptadas al contexto y realidad colombianos. Conclusiones: Se presentan sugerencias multidisciplinarias para el diagnóstico y tratamiento de melanoma temprano, las cuales debe considerarse para orientar la toma de decisiones y homogenizar la práctica clínica de acuerdo al contexto colombiano y a las características propias del sistema de salud del país. Este es un documento académico y no regulatorio.

Abstract Introduction: Melanoma causes 75% of deaths from skin cancer. In 2018, according to GLOBOCAN, 287,723 new melanoma cases were registered, with a mortality of 60,712 cases, which is equivalent to 20% of all incident cases. Alternatives for the treatment of melanoma are based on disease staging and the molecular characteristics of the disease. Objective: To establish a consensus by common agreement of experts and construct suggestions for the diagnosis and management of early-stage melanoma based on evidence and adjusted to the Colombian context. Methods: A multidisciplinary expert consensus was established, wth the participation of 19 clinical oncologists, 2 soft tissue surgeons, 2 dermatologists, 2 pathologists, and 2 radiotherapists, active members of the Colombian Association of Hemato-Oncology (ACHO). This consensus was carried out in four stages: 1) Structuring of 29 questions, which were scored from 1 to 9; 2) Resubmission of non-consensual questions; 3) Analysis and discussion of responses; and 4) Validation of non-consensual responses by nominal consensus. Results: Twenty-nine questions related to the diagnosis and treatment of early-stage melanoma were discussed in order to construct suggestions based on evidence proven by experts, as well as on internationally recognized oncology management guidelines adapted to the Colombian context and reality. Conclusions: Multidisciplinary suggestions are offered for the diagnosis and treatment of early-stage melanoma, which should be considered in order to guide decision-making and homogenize clinical practice according to the Colombian context and the characteristics of the Colombian health care system. This is an academic and non-regulatory document.

Optimization of Insecticidal Triterpene Derivatives by Biomimetic Oxidations with Hydrogen Peroxide and Iodosobenzene Catalyzed by MnIII and FeIII Porphyrin Complexes.

Semisynthetic functionalized triterpenes (4α,14-dimethyl-5α,8α-8,9-epoxycholestan-3ß-yl acetate; 4α,14-dimethyl-5α-cholest-8-ene-3,7,11-trione; 4α,14-dimethyl-5α-cholesta-7,9(11)-dien-3-one and 4α,14-dimethyl-5α-cholest-8-en-3ß-yl acetate), previously prepared from 31-norlanostenol, a natural insecticide isolated from the latex of Euphorbia officinarum, have been subjected to oxidation with hydrogen peroxide (H2 O2 ) and iodosobenzene (PhIO) catalyzed by porphyrin complexes (cytochrome P-450 models) in order to obtain optimized derivatives with high regioselectivity. The main transformations were epoxidation of the double bonds and hydroxylations of non-activated C-H groups and the reaction products were 25-hydroxy-4α,14-dimethyl-5α-cholesta-7,9(11)-dien-3ß-yl acetate (59 %), 25-hydroxy-4α,14-dimethyl-5α-cholest-8-ene-3,7,11-trione (60 %), 4α,14-dimethyl-5α,7ß-7,8-epoxycholest-9(11)-en-3-one (22 %), 8-hydroxy-4α,14-dimethyl-5α-cholest-9(11)-ene-3,7-dione (16 %), 12α-hydroxy-4α,14-dimethyl-5α,7ß-7,8-epoxycholest-9(11)-en-3-one (16 %), and 4α,14-dimethyl-5α,8α-8,9-epoxycholestan-3ß-yl acetate (26 %), respectively. We also investigated the insect (Myzus persicae, Rhopalosiphum padi and Spodoptera littoralis) antifeedant and postingestive effects of these terpenoid derivatives. None of the compounds tested had significant antifeedant effects, however, all were more effective postingestive toxicants on S. littoralis larvae than the natural compound 31-norlanostenol, with 4α,14-dimethyl-5α,8α-8,9-epoxycholestan-3ß-yl acetate being the most active. The study of their structure-activity relationships points out at the importance of C3 and C7 substituents.

Hyperprogression in Pediatric Melanoma Metastatic to the Breast Treated with a Checkpoint Inhibitor.

Metastatic melanomas in the pediatric population are rare, but they have been appearing more frequently. Unfortunately, little is known about the differences in the biology and therapeutic implications of pediatric metastatic melanomas when compared to those found in adults. Herein, we have presented the case of a 13-year-old girl with a stage IIID malignant melanoma arising from a congenital nevus. This patient underwent surgical management, and she received adjuvant interferon therapy; however, this treatment was incomplete due to a grade 3 transaminase elevation and the early recurrence of the disease. An isolated metastasis to the breast was documented, and a mastectomy was performed. Soon afterward, low-volume lung metastases developed, and she was treated with nivolumab. After two treatment cycles, the disease continued to develop in a hyperprogressive manner. Advances in the characterization and understanding of pediatric melanomas are needed, as well as experience in the management of new therapies in these cases, which would help clarify the extent to which we can extrapolate the data obtained from the adult population. Therapeutic interventions in melanoma cases are evolving rapidly, and the role of metastasectomies in the era of immunotherapy and BRAF and MEK-targeted therapies is largely unknown. Moreover, the identification of risk factors for the development of hyperprogression and its underlying mechanisms are also warranted.