Impact of telenurse-led intervention in clinical trials on health literacy, empowerment, and health outcomes in patients with solid tumours: a pilot quasi-experimental study.

BACKGROUND: During the COVID-19 pandemic, decentralised clinical trials incorporated self-monitoring, self-reporting, and telenursing tools to address health literacy and health empowerment of patients enrolled in clinical trials. We aimed to determine the impact of an educational intervention using telenursing consultations on health literacy, health empowerment, and health-related quality of life in cancer patients enrolled in clinical trials by measuring the level of satisfaction with the care received and assessing the views of healthcare professionals concerning the advanced practice nurse (APN) role in oncology clinical trials. METHODS: In this pilot analytical, descriptive, longitudinal, quasi-experimental, and pre-post test study, an educational intervention was conducted by 5 visits with an APN using synchronous teleconsultation in patients starting cancer treatment for the first time in a clinical trial (n = 60), and health professionals working with the APN (n = 31). A descriptive analysis of the samples and questionnaires were utilised along with statistical comparisons. RESULTS: After the intervention, patients' health literacy (31.7%), health empowerment (18.3%), and health-related quality of life (33.3%) increased (p < 0.05), with a decrease and trend towards resolution of care needs (p < 0.05). Satisfaction with the quality and care received in terms of perceived convenience, transition, and continuity of care showed positive results in 64.9 ± 20.7, 77.6 ± 19.5, and 72.1 ± 20.4 of respondents, respectively. On the overall assessment of the APN role, healthcare professionals expressed a high level of agreement with the statements related to their work performance. CONCLUSIONS: The data indicates that a clinical trial APN-led telenursing educational intervention results in an overall increase in health literacy, an improvement in health empowerment and health-related quality of life, and a decrease in care needs of oncology clinical trials patients. Patients stated that they received a high quality of care and health professionals indicated high levels of acceptance with APNs. Based on these results, we suggest that the APN role should gain more recognition in the Spanish healthcare system and their professional competencies should be aligned with those of other countries.

Portal vein thrombosis in a patient with severe hemophilia B: A challenging balanced management.

Key Clinical Message: The increased life expectancy in patients with hemophilia (PwH) over the last years has raised the incidence of comorbidities, including thromboembolic events. Thromboembolic events are rare in PwH and most of them occur in the presence of exogenous risk factors. There is still scarce scientific evidence on the optimal antithrombotic treatment and management approach in this population. Abstract: In the hemophilic population thromboembolic events are rare. Most of them are often multifactorial and occur in the presence of both exogenous (orthopedic surgery, intensive replacement therapy, use of central venous catheters…) and endogenous (cardiovascular diseases) risk factors. We describe the case of a 43-year-old patient with severe hemophilia B (sHB) receiving prophylaxis with eftrenonacog alfa (rFIXFc) and antithrombotic treatment due to portal vein thrombosis. The patient was treated with extended half- life factor IX (EHL-FIX) prophylaxis maintaining higher trough levels to avoid new bleeding episodes associated to the underlying disease and the use of antithrombotic therapy with low molecular weight heparin. EHL-FIX concentrates allow prolonged intervals between intravenous infusions and higher hemostatic protection thanks to increased factor trough levels. This current case report provides clinical evidence in antithrombotic management in a patient with severe hemophilia B.

Validity of a video-analysis-based app to detect prefrailty or frailty plus sarcopenia syndromes in community-dwelling older adults: Diagnostic accuracy study.

Objectives: Sarcopenia and frailty have been associated with an increased risk of suffering health-related adverse events but the combination of both conditions results in worse health-related outcomes than either condition alone. Since both syndromes are reversible states, their early detection is fundamental. This study aims to validate a video analysis-based App to detect the presence of frailty or prefrailty plus sarcopenia syndromes and to analyze its construct validity with health-related risk factors. Methods: A total of 686 community-dwelling older adults (median-age: 72, 59% female) were enrolled. Muscle power generated during a sit-to-stand test using the App and calf circumference were considered the index test. The reference standards were the EWGSOP2 criteria (five-chair stand test plus appendicular skeletal mass or skeletal muscle index) and Fried's frailty phenotype. Area under the curve (AUC), sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated. Results: The prevalence of both syndromes varied from 2.9% to 7.2% depending on the diagnostic criteria used for sarcopenia assessment. Excellent-to-outstanding AUC values were observed (range 0.80-0.92). Sensitivity and specificity ranged from 75% to 100% and 81.7% to 87.2%, respectively. PPV and NPV ranged from 12.1% to 37.5% and 97.9% to 100%, respectively. Individuals diagnosed by the App showed an increased risk of polypharmacy, depression, comorbidities, falls, hospitalization, low socioeconomical and educational levels, and smoking and poor self-perceived health compared to their healthy counterparts. Conclusions: This App seems to be reliable to detect the simultaneous presence of both syndromes in community-dwelling older adults. Individuals diagnosed by the App showed more odds to have health-related risk factors.

Spanish version of the short European Health Literacy Survey Questionnaire HLS-Q12: Transcultural adaptation and psychometric properties.

BACKGROUND: Health literacy has a direct impact on the health of populations. It is related to education, capacity for self-care, and management of health resources. The Health Literacy Survey Questionnaire HLS-Q12 is one of the reference instruments but has not yet been adapted to Spanish. The aims of the study were to cross-culturally adapt and evaluate the psychometric properties of the Spanish version of the HLS-Q12. METHODS: Data was collected from June 2020 to March 2022. The sample consisted of 60 patients who initiated cancer treatment for the first time within a clinical trial. Double direct translation, back-translation, cognitive debriefing with a 10-patient sample, and an expert committee were used for cross-cultural adaptation. For validation of the HLS-Q12, a psychometric analysis was performed to assess feasibility, reliability, sensitivity to change and construct validity with other measures such as health-related quality of life, empowerment, and health needs. RESULTS: The HLS-Q12 is equivalent at the semantic, conceptual, and content level to the original version and its psychometric properties demonstrated good internal consistency with a Cronbach's alpha of 0.88 and a McDonald´s omega of 0.91, a high degree of fit for the confirmatory factor analysis, and a statistically significant sensitivity to change (p = 0.025). CONCLUSIONS: Based on robust psychometric values, the Spanish version of HLS-Q12 was found to be a good cross-culturally adapted tool for collecting correct information on health literacy in cancer patients regardless of tumour type or stage. Although more studies are needed, this version of HLS-Q12 could be used in research for collecting data on the health literacy needs of Spanish-speaking patients.

Sit-to-Stand Video Analysis-Based App for Diagnosing Sarcopenia and Its Relationship With Health-Related Risk Factors and Frailty in Community-Dwelling Older Adults: Diagnostic Accuracy Study.

BACKGROUND: Probable sarcopenia is determined by a reduction in muscle strength assessed with the handgrip strength test or 5 times sit-to-stand test, and it is confirmed with a reduction in muscle quantity determined by dual-energy X-ray absorptiometry or bioelectrical impedance analysis. However, these parameters are not implemented in clinical practice mainly due to a lack of equipment and time constraints. Nowadays, the technical innovations incorporated in most smartphone devices, such as high-speed video cameras, provide the opportunity to develop specific smartphone apps for measuring kinematic parameters related with sarcopenia during a simple sit-to-stand transition. OBJECTIVE: We aimed to create and validate a sit-to-stand video analysis-based app for diagnosing sarcopenia in community-dwelling older adults and to analyze its construct validity with health-related risk factors and frailty. METHODS: A total of 686 community-dwelling older adults (median age: 72 years; 59.2% [406/686] female) were recruited from elderly social centers. The index test was a sit-to-stand video analysis-based app using muscle power and calf circumference as proxies of muscle strength and muscle quantity, respectively. The reference standard was obtained by different combinations of muscle strength (handgrip strength or 5 times sit-to-stand test result) and muscle quantity (appendicular skeletal mass or skeletal muscle index) as recommended by the European Working Group on Sarcopenia in Older People-2 (EWGSOP2). Sensitivity, specificity, positive and negative predictive values, and area under the curve (AUC) of the receiver operating characteristic curve were calculated to determine the diagnostic accuracy of the app. Construct validity was evaluated using logistic regression to identify the risks associated with health-related outcomes and frailty (Fried phenotype) among those individuals who were classified as having sarcopenia by the index test. RESULTS: Sarcopenia prevalence varied from 2% to 11% according to the different combinations proposed by the EWGSOP2 guideline. Sensitivity, specificity, and AUC were 70%-83.3%, 77%-94.9%, and 80.5%-87.1%, respectively, depending on the diagnostic criteria used. Likewise, positive and negative predictive values were 10.6%-43.6% and 92.2%-99.4%, respectively. These results proved that the app was reliable to rule out the disease. Moreover, those individuals who were diagnosed with sarcopenia according to the index test showed more odds of having health-related adverse outcomes and frailty compared to their respective counterparts, regardless of the definition proposed by the EWGSOP2. CONCLUSIONS: The app showed good diagnostic performance for detecting sarcopenia in well-functioning Spanish community-dwelling older adults. Individuals with sarcopenia diagnosed by the app showed more odds of having health-related risk factors and frailty compared to their respective counterparts. These results highlight the potential use of this app in clinical settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05148351; https://clinicaltrials.gov/study/NCT05148351. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3390/s22166010.

Drastic Microbial Count Reduction in Soy Milk Using Continuous Short-Wave Ultraviolet Treatments in a Tubular Annular Thin Film UV-C Reactor.

Vegetative cells of Listeria monocytogenes and Escherichia coli and spores of Bacillus subtilis and Aspergillus niger were inoculated in soy milk at an initial concentration of ≈5 log CFU/mL. Inoculated and control (non-inoculated) soy milk samples were submitted to three types of treatments using a tubular annular thin film short-wave ultraviolet (UV-C) reactor with 1 mm of layer thickness. Treatments applied depended on the flow rate and the number of entries to the reactor, with UV-C doses ranging from 20 to 160 J/mL. The number of entries into the reactor tube (NET) was established as the most determining parameter for the efficiency of the UV-C treatments. Conidiospores of A. niger were reported as the most resistant, followed by B. subtilis spores, while vegetative cells were the most sensible to UV-C, with Listeria monocytogenes being more sensible than Escherichia coli. Treatments of just 80 J/mL were needed to achieve a 5 log CFU/mL reduction of L. monocytogenes while 160 J/mL was necessary to achieve a similar reduction for A. niger spores.

Competencias profesionales de las enfermeras oncológicas: reconociendo la Práctica Avanzada en Enfermería / Professional competencies of oncology nurses: Recognizing advanced practice in nursing

Objetivo: Identificar el perfil competencial de las enfermeras de práctica avanzada que intervienen en el proceso asistencial del paciente oncológico. Método: Estudio descriptivo transversal. El estudio incluyó a todas las enfermeras que intervienen en el proceso asistencial del paciente oncológico en un hospital terciario de Barcelona. Se recogieron los datos del perfil competencial a través del instrumento de definición del rol de la enfermera de práctica avanzada (IDREPA), así como las variables sociodemográficas y laborales. Se compararon datos sociodemográficos y laborales con el desempeño de actividades de práctica avanzada. Resultados: Participaron un total de 29 (82,9%) enfermeras con una media de edad de 42,6± 12,54 años. Se han identificado 9 (31%) enfermeras que alcanzan el estándar en los 6 dominios en la escala IDREPA para considerarse enfermeras de práctica avanzada (EPA). De estas 9 (31%), cumplían los estándares de formación requeridos por el CIE, 7 (24,1%) con máster oficial y 2 (6,9%) con doctorado. Conclusiones: Existen enfermeras que desarrollan su actividad en el ámbito oncológico del Hospital del Mar con perfil de EPA. La identificación de EPA en nuestro sistema de salud es esencial para poder reconocer las competencias de dichas profesionales y crear puestos específicos que ayuden a abordar la cronicidad, la calidad de vida de los pacientes, su supervivencia y la optimización de los recursos sanitarios. Este estudio pone en relieve la importancia de la cronicidad y el cáncer como ámbitos para el desarrollo de la EPA.(AU)

Objective: To identify the competency profile of advanced practice nurses involved in the care process of cancer patients. Methods: Cross-sectional and descriptive study. The study included all nurses involved in the cancer patient care process in a tertiary hospital in Barcelona. Competence profile data were collected using the instrument for defining the role of the advanced practice nurse (APRD), as well as sociodemographic and occupational variables. Sociodemographic and occupational data were compared against the performance of advanced practice activities. Results: A total of 29 (82.9%) nurses participated with a mean age of 42.6±12.54 years. Nine (31%) nurses were identified as meeting the standard in all 6 domains on the APRD scale to be considered advanced practice nurses. Of these 9 (31%) nurses, 7 (24.1%) met the training standards required by the International Council of Nurses (ICN) with an official master's degree and 2 (6.9%) with a PhD. Conclusions: There are nurses who carry out their activity in the oncology field of the Hospital del Mar with the EPA profile. The identification of advanced practice nurses (APNs) in our health system is essential to be able to recognize the competencies of these professionals and create specific positions that help to address chronicity, patients’ quality of life, their survival, and the optimization of health resources. Our study highlights the importance of chronicity and cancer as areas for the development of the APNs.(AU)

Serum metabolomics profiling by proton nuclear magnetic resonance spectrometry of the response to single oral macronutrient challenges in women with polycystic ovary syndrome (PCOS) compared with male and female controls.

BACKGROUND: The polycystic ovary syndrome (PCOS) is associated with insulin resistance, obesity and cardiometabolic comorbidities. We here challenged the hypothesis, using state-of-the-art proton nuclear magnetic resonance spectrometry (1H-NMRS) metabolomics profiling, that androgen excess in women induces a certain masculinization of postprandial metabolism that is modulated by obesity. MATERIALS AND METHODS: Participants were 53 Caucasian young adults, including 17 women with classic PCOS consisting of hyperandrogenism and ovulatory dysfunction, 17 non-hyperandrogenic women presenting with regular menses, and 19 healthy men, selected to be similar in terms of age and body mass index (BMI). Half of the subjects had obesity. Patients were submitted to isocaloric separate glucose, lipid and protein oral challenges in alternate days and fasting and postprandial serum samples were submitted to 1H-NMRS metabolomics profiling for quantification of 36 low-molecular-weight polar metabolites. RESULTS: The largest postprandial changes were observed after glucose and protein intake, with lipid ingestion inducing smaller differences. Changes after glucose intake consisted of a marked increase in carbohydrates and byproducts of glycolysis, and an overall decrease in byproducts of proteolysis, lipolysis and ketogenesis. After the protein load, most amino acids and derivatives increased markedly, in parallel to an increase in pyruvate and a decrease in 3-hydroxybutyric acid and glycerol. Obesity increased ß- and D-glucose and pyruvate levels, with this effect being observed mostly after glucose ingestion in women with PCOS. Regardless of the type of macronutrient, men presented increased lysine and decreased 3-hydroxybutyric acid. In addition, non-obese men showed increased postprandial ß-glucose and decreased pyroglutamic acid, compared with non-obese control women. We observed a common pattern of postprandial changes in branched-chain and aromatic amino acids, where men showed greater amino acids increases after protein intake than control women and patients with PCOS but only within the non-obese participants. Conversely, this increase was blunted in obese men but not in obese women, who even presented a larger increase in some amino acids compared with their non-obese counterparts. Interestingly, regardless of the type of macronutrient, only obese women with PCOS showed increased leucine, lysine, phenylalanine and tryptophan levels compared with non-obese patients. CONCLUSIONS: Serum 1H-NMRS metabolomics profiling indicated sexual dimorphism in the responses to oral macronutrient challenges, which were apparently driven by the central role of postprandial insulin effects with obesity, and to a lesser extent PCOS, exerting modifying roles derived from insulin resistance. Hence, obesity impaired metabolic flexibility in young adults, yet sex and sex hormones also influenced the regulation of postprandial metabolism.

The polycystic ovary syndrome (PCOS) is a common endocrine disorder in women. PCOS is associated with diabetes, obesity and cardiometabolic disease. Mild excess of androgens (male hormones) characterize PCOS, and facilitate that body fat accumulates in the visceral abdominal area. Visceral fat promotes insulin resistance increasing the risk for diabetes and cardiometabolic disease, and further androgen excess. We here explored intermediate metabolism after the separate administration of either carbohydrates, fats or proteins, in young adult women with or without PCOS and in men, using state-of-the-art proton nuclear magnetic resonance metabolomics profiling. Results suggest that postprandial metabolomics profiles reflect mostly insulin actions, with changes derived from insulin resistance being more important with obesity but also being influenced by male sex and PCOS in women.

SEOM-GEINO clinical guidelines for high-grade gliomas of adulthood (2022)

High-grade gliomas (HGG) are the most common primary brain malignancies and account for more than half of all malignant primary brain tumors. The new 2021 WHO classification divides adult HGG into four subtypes: grade 3 oligodendroglioma (1p/19 codeleted, IDH-mutant); grade 3 IDH-mutant astrocytoma; grade 4 IDH-mutant astrocytoma, and grade 4 IDH wild-type glioblastoma (GB). Radiotherapy (RT) and chemotherapy (CTX) are the current standard of care for patients with newly diagnosed HGG. Several clinically relevant molecular markers that assist in diagnosis and prognosis have recently been identified. The treatment for recurrent high-grade gliomas is not well defined and decision-making is usually based on prior strategies, as well as several clinical and radiological factors. Whereas the prognosis for GB is grim (5-year survival rate of 5–10%) outcomes for the other high-grade gliomas are typically better, depending on the molecular features of the tumor. The presence of neurological deficits and seizures can significantly impact quality of life (AU)

Professional competencies of oncology nurses: Recognizing advanced practice in nursing.

OBJECTIVE: To identify the competency profile of advanced practice nurses involved in the care process of cancer patients. METHODS: Cross-sectional and descriptive study. The study included all nurses involved in the cancer patient care process in a tertiary hospital in Barcelona. Competence profile data were collected using the instrument for defining the role of the advanced practice nurse (APRD), as well as sociodemographic and occupational variables. Sociodemographic and occupational data were compared against the performance of advanced practice activities. RESULTS: A total of 29 (82.9%) nurses participated with a mean age of 42.6±12.54 years. 9 (31%) nurses were identified as meeting the standard in all 6 domains on the APRD scale to be considered advanced practice nurses. Of these 9 (31%) nurses, 7 (24.1%) met the training standards required by the International Council of Nurses (ICN) with an official master's degree and 2 (6.9%) with a PhD. CONCLUSIONS: There are nurses who carry out their activity in the oncology field of the hospital analyzed with the EPA profile. The identification of advanced practice nurses (APNs) in our health system is essential to be able to recognize the competencies of these professionals and create specific positions that help to address chronicity, patients' quality of life, their survival, and the optimization of health resources. Our study highlights the importance of chronicity and cancer as areas for the development of the APNs.

Concurrent and discriminant validity and reliability of an Android App to assess time, velocity and power during sit-to-stand test in community-dwelling older adults.

INTRODUCTION: Nowadays, smartphones are equipped with the most sophisticated hardware which provides the opportunity to develop specific smartphone apps to analyze kinetic and kinematic parameters during sit-to-stand test in a clinical setting. The aims were to ascertain whether a new Android video-analysis based-App is comparable to the previously validated Apple-App for measuring time, velocity and power during sit-to-stand test, to determine its reliability and discriminant validity. METHODS: One-hundred sixty-one older adults (61-86 years) were recruited from an elderly social center. Sit-to-stand variables were simultaneously recorded through the Android and Apple-App. Their validity and inter-rater, intra-rater, and test-retest reliability was tested using an intraclass correlation coefficient (ICC2-1). Low gait speed (< 1.0 m/s), low physical performance (Short Physical Performance Battery < 10 points), and sarcopenia (EWGSOP2 guideline) were used to determine discriminant validity which was reported as the area under the curves (AUC) and their effect sizes (Hedges' g) for independent sample t-test. RESULTS: Excellent reproducibility (ICC2-1 > 0.85) and strong agreement (ICC2-1 > 0.90) between operating systems for sit-to-stand variables derived from the App was found. Older adults classified as sarcopenic (11.2%), low physical performance (15.5%), or reduced gait speed (14.3%) showed worse sit-to-stand time, velocity and power with large effect sizes (Hedges' g: > 0.8) compared to their respective counterpart. These variables showed the acceptable-to-excellent ability to identify low gait speed, low physical performance, and sarcopenic older adults (AUC-range: 0.73-0.82). CONCLUSION: The new Sit-to-Stand App running on the Android operating system is comparable to the previously validated Apple App. Excellent reproducibility and acceptable-to-excellent discriminant validity were found.

Evaluation of the efficacy of an antioxidant combination for the modulation of metabolic, endocrine, and clinical parameters in patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate the efficacy of dietary supplementation with a combination of antioxidants (lipoic acid, N-acetylcysteine, vitamin B6, and S-adenosyl-L-methionine) for the modulation of metabolic, endocrine, and clinical parameters in comparison with oral contraception in non-diabetic women newly diagnosed with polycystic ovary syndrome (PCOS). METHODS: This was a prospective, partially randomized, multicenter study in which non-diabetic women with PCOS were recruited under routine clinical practice conditions and distributed in three groups to receive the following regimen for 6 months: 1) antioxidant combination (MN group); 2) oral contraception (OC group); or 3) oral contraception and the antioxidant combination (MN + OC group). General recommendation of healthy diet and regular exercise was given to all patients. Metabolic, endocrine, clinical, and quality of life parameters were recorded at baseline and after 6 months of therapy. RESULTS: A total of 96 women with PCOS were included in the study. After 6 months of treatment, the homeostasis model assessment-estimated insulin resistance (HOMA-IR) level was reduced only in the MN group, with a significant mean reduction of -0.92 points. Androstenedione was significantly reduced in all groups. Clinical parameters that significantly improved in all groups were hirsutism, acne, irregular menstruation, and quality of life, with no statistical differences between the groups. CONCLUSIONS: This study showed that the antioxidant combination might be a suitable therapy for patients with PCOS when oral contraceptive is not indicated, because in all groups clinical parameters, irregular menstruation as well as androstenedione and quality of life were significantly improved with no statistical difference between groups.

Musculoskeletal pain and muscular weakness as the main symptoms of adult hypophosphatasia in a Spanish cohort: clinical characterization and identification of a new ALPL gene variant.

INTRODUCTION: Hypophosphatasia (HPP) is a rare inherited disorder, caused by mutations in the alkaline phosphatase (ALPL) gene, which encodes for the tissue non-specific alkaline phosphatase (TNSALP) isoform of alkaline phosphatase (ALP). Adult HPP is one of the mild forms that presents with unspecific signs such as osteopenia, osteomalacia and muscle involvement. Our purpose was to identify and characterize possibly misdiagnosed adult HPP patients at a clinical and biochemical level. MATERIAL AND METHODS: At the laboratory of Miguel Servet University Hospital we retrospectively reviewed serum ALP levels in adults over a 48-month period. The clinical records of individuals with consistently low ALP levels were reviewed to exclude secondary causes. Those with persistent hypophosphatasemia were screened for symptoms of HPP. The study participants were evaluated at biochemical and genetic levels. RESULTS: We identified 705 ALP determinations (out of 384,000 processed) in 589 patients below the reference range (30 U/l). Only 21 patients with clinical signs and symptoms of HPP were selected for genetic testing. Finally, only 12 patients participated in the study, 83.3% of whom (10/12) harbored a pathogenic or likely pathogenic variant in a heterozygous state. The major symptoms of our cohort were the presence of musculoskeletal pain (100% of patients) and muscular weakness (83.3% patients). CONCLUSION: Mild HPP patients presenting with diffuse symptoms such as musculoskeletal pain may be undiagnosed or misdiagnosed as osteoporosis patients by routine diagnosis. It is important to identify these individuals, to avoid inappropriate treatment with antiresorptive drugs.

Narrative Review of Multidisciplinary Management of Central Nervous Involvement in Patients with HER2-Positive Metastatic Breast Cancer: Focus on Elderly Patients.

The tumor biology of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) promotes the development of central nervous system (CNS) metastases, with 25% of patients with HER2-positive BC developing CNS metastases. Furthermore, the incidence of HER2-positive BC brain metastases has increased in the last decades, likely because of the improved survival with targeted therapies and better detection methods. Brain metastases are detrimental to quality of life and survival and represent a challenging clinical problem, particularly in elderly women, who comprise a substantial proportion of patients diagnosed with BC and often have comorbidities or an age-related decline in organ function. Treatment options for patients with BC brain metastases include surgical resection, whole-brain radiation therapy, stereotactic radiosurgery, chemotherapy, and targeted agents. Ideally, local and systemic treatment decisions should be made by a multidisciplinary team, with input from several specialties, based on an individualized prognostic classification. In elderly patients with BC, additional age-associated conditions, such as geriatric syndromes or comorbidities, and the physiologic changes associated with aging, may impact their ability to tolerate cancer therapy and should be considered in the treatment decision-making process. This review describes the treatment options for elderly patients with HER2-positive BC and brain metastases, focusing on the importance of multidisciplinary management, the different points of view from the distinct disciplines, and the role of oncogeriatric and palliative care in this vulnerable patient group.

A first-in-human study of the fibroblast activation protein-targeted, 4-1BB agonist RO7122290 in patients with advanced solid tumors.

This first-in-human study evaluated RO7122290, a bispecific fusion protein carrying a split trimeric 4-1BB (CD137) ligand and a fibroblast activation protein α (FAP) binding site that costimulates T cells for improved tumor cell killing in FAP-expressing tumors. Patients with advanced or metastatic solid tumors received escalating weekly intravenous doses of RO7122290 as a single agent (n = 65) or in combination with a 1200-milligram fixed dose of the anti-programmed death-ligand 1 (anti-PD-L1) antibody atezolizumab given every 3 weeks (n = 50), across a tested RO7122290 dose range of 5 to 2000 milligrams and 45 to 2000 milligrams, respectively. Three dose-limiting toxicities were reported, two at different RO7122290 single-agent doses (grade 3 febrile neutropenia and grade 3 cytokine release syndrome) and one for the combination (grade 3 pneumonitis). No maximum tolerated dose was identified. The pharmacokinetic profile of RO7122290 suggested nonlinearity in elimination. The observed changes in peripheral and tissue pharmacodynamic (PD) biomarkers were consistent with the postulated mechanism of action. Treatment-induced PD changes included an increase in proliferating and activated T cells in peripheral blood both in the single-agent and combination arms. Increased infiltration of intratumoral CD8+ and Ki67+CD8+ T cells was observed for both treatment regimens, accompanied by the up-regulation of T cell activation genes and gene signatures. Eleven patients experienced a complete or partial response, six of whom were confirmed to be immune checkpoint inhibitor naive. These results support further evaluation of RO7122290 in combination with atezolizumab or other immune-oncology agents for the treatment of solid tumors.

VHrare study: Prevalence, clinical features and management of severe rare bleeding disorders in a large cohort.

INTRODUCTION: Rare bleeding disorders (RBD) constitute 5% of total hereditary bleeding disorders, although the number could be higher, due to the presence of undiagnosed asymptomatic patients. The objective of this study was to analyze the prevalence and characteristics of patients with severe RBDs in our area. MATERIAL AND METHODS: We analyzed the patients with RBD followed at a tertiary-level hospital between January 2014 and December 2021. RESULTS: A total of 101 patients were analyzed, with a median age at diagnosis of 27.67 years (range 0-89), of which 52.47% were male. The most frequent RBD in our population was FVII deficiency. Regarding the diagnostic reason, the most frequent cause was a preoperative test and only 14.8% reported bleeding symptoms at the time of diagnosis. A genetic study was carried out in 63.36% of patients and the most frequent mutation type found was finding a missense mutation. CONCLUSIONS: The distribution of RBDs in our centre is similar to the one reported in the literature. The majority of RBDs were diagnosed from a preoperative test and this allowed preventive treatment prior to invasive procedures to avoid bleeding complications. 83% of patients did not have a pathological bleeding phenotype according to ISTH-BAT.

Handling Ill-Conditioned Omics Data With Deep Probabilistic Models.

The advent of high-throughput technologies has produced an increase in the dimensionality of omics datasets, which limits the application of machine learning methods due to the great unbalance between the number of observations and features. In this scenario, dimensionality reduction is essential to extract the relevant information within these datasets and project it in a low-dimensional space, and probabilistic latent space models are becoming popular given their capability to capture the underlying structure of the data as well as the uncertainty in the information. This article aims to provide a general classification and dimensionality reduction method based on deep latent space models that tackles two of the main problems that arise in omics datasets: the presence of missing data and the limited number of observations against the number of features. We propose a semi-supervised Bayesian latent space model that infers a low-dimensional embedding driven by the target label: the Deep Bayesian Logistic Regression (DBLR) model. During inference, the model also learns a global vector of weights that allows it to make predictions given the low-dimensional embedding of the observations. Since this kind of dataset is prone to overfitting, we introduce an additional probabilistic regularization method based on the semi-supervised nature of the model. We compared the performance of the DBLR against several state-of-the-art methods for dimensionality reduction, both in synthetic and real datasets with different data types. The proposed model provides more informative low-dimensional representations, outperforms the baseline methods in classification, and can naturally handle missing entries.

Gal-1 Expression Analysis in the GLIOCAT Multicenter Study: Role as a Prognostic Factor and an Immune-Suppressive Biomarker.

Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population. The ß-galactoside binding protein Galectin-1 (Gal-1) is a protein with a wide range of pro-tumor functions such as proliferation, invasion, angiogenesis, and immune suppression. Here, we evaluated Gal-1 expression by immunohistochemistry in a homogenously treated cohort of GBM (the GLIOCAT project) and correlated its expression with clinical and molecular data. We observed that Gal-1 is a negative prognostic factor in GBM. Interestingly, we observed higher levels of Gal-1 expression in the mesenchymal/classical subtypes compared to the less aggressive proneural subtype. We also observed a Gal-1 expression correlation with immune suppressive signatures of CD4 T-cells and macrophages, as well as with several GBM established biomarkers, including SHC1, PD-L1, PAX2, MEOX2, YKL-40, TCIRG1, YWHAG, OLIG2, SOX2, Ki-67, and SOX11. Moreover, Gal-1 levels were significantly lower in grade 4 IDH-1 mutant astrocytomas, which have a better prognosis. Our results confirm the role of Gal-1 as a prognostic factor and also suggest its value as an immune-suppressive biomarker in GBM.

Consequences of applying the different criteria of the EWGSOP2 guideline for sarcopenia case-finding in Spanish community-dwelling older adults.

INTRODUCTION: Sarcopenia prevalence varies according to differences in diagnostic criteria used. In order to overcome this issue, the European Working Group on Sarcopenia in Older People-2 (EWGSOP2) published a consensus to increase harmonization for sarcopenia diagnosis. This study aimed to determine the prevalence and risk factors across the different sarcopenia diagnosis criteria recommended by EWGSOP2 and to analyze its agreement. METHODS: A total of 699 community-dwelling older adults (median-age: 72, 60% female) were recruited in this cross-sectional study. Sarcopenia prevalence was obtained by different combinations of muscle strength (handgrip strength or 5-times sit-to-stand) and muscle quantity (appendicular skeletal mass or skeletal muscle index) as recommended by the EWGSOP2. Cohen's Kappa coefficient was calculated to analyze agreement among the four sarcopenia diagnostic criteria and logistic regressions were performed to identify risks associated to health-related outcomes for each diagnostic criterion. RESULTS: Sarcopenia prevalence varied from 2.1% to 11.6%, depending on the diagnostic criteria used. Weak-to-moderate agreements (κ-range: 0.13-0.66) were observed among the four sarcopenia diagnosis criteria. There was scarce overlap in sarcopenic people when different diagnostic criteria were used leading to up to 10.4% of underdiagnosis. Sarcopenia defined by 5-times sit-to-stand was more associated with health-related outcomes compared to handgrip strength. CONCLUSIONS: Sarcopenia prevalence rates vary considerably depending on the diagnostic criteria used. These criteria should not be used in an interchangeable way due to their weak agreement. Sarcopenia diagnosis criteria defined by 5-times sit-to-stand could be more suitable in Spanish community-dwelling older adults due their associations with health-related outcomes.

Association between Clinical Frailty Scale (CFS) and clinical presentation and outcomes in older inpatients with COVID-19.

BACKGROUND: Frailty is a physiological condition characterized by a decreased reserve to stressors. In patients with COVID-19, frailty is a risk factor for in-hospital mortality. The aim of this study was to assess the relationship between clinical presentation, analytical and radiological parameters at admission, and clinical outcomes according to frailty, as defined by the Clinical Frailty Scale (CFS), in old people hospitalized with COVID-19. MATERIALS AND METHODS: This retrospective cohort study included people aged 65 years and older and admitted with community-acquired COVID-19 from 3 March 2020 to 31 April 2021. Patients were categorized using the CFS. Primary outcomes were symptoms of COVID-19 prior to admission, mortality, readmission, admission in intensive care unit (ICU), and need for invasive mechanical ventilation. Analysis of clinical symptoms, clinical outcomes, and CFS was performed using multivariable logistic regression, and results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the 785 included patients, 326 (41.5%, 95% CI 38.1%-45.0%) were defined as frail (CFS ≥ 5 points): 208 (26.5%, 95% CI 23.5%-29.7%) presented mild-moderate frailty (CFS 5-6 points) and 118 (15.0%, 95% CI 12.7%-17.7%), severe frailty (7-9 points). After adjusting for epidemiological variables (age, gender, residence in a nursing home, and Charlson comorbidity index), frail patients were significantly less likely to present dry cough (OR 0.58, 95% CI 0.40-0.83), myalgia-arthralgia (OR 0.46, 95% CI 0.29-0.75), and anosmia-dysgeusia (OR 0.46, 95% CI 0.23-0.94). Confusion was more common in severely frail patients (OR 3.14; 95% CI 1.64-5.97). After adjusting for epidemiological variables, the risk of in-hospital mortality was higher in frail patients (OR 2.79, 95% CI 1.79-4.25), including both those with mild-moderate frailty (OR 1.98, 95% CI 1.23-3.19) and severe frailty (OR 5.44, 95% CI 3.14-9.42). Readmission was higher in frail patients (OR 2.11, 95% CI 1.07-4.16), but only in mild-moderate frailty (OR 2.35, 95% CI 1.17-4.75).. CONCLUSION: Frail patients presented atypical symptoms (less dry cough, myalgia-arthralgia, and anosmia-dysgeusia, and more confusion). Frailty was an independent predictor for death, regardless of severity, and mild-moderate frailty was associated with readmission.