Molecular profile in endometrial carcinoma: can we predict the lymph node status? A systematic review and meta-analysis.

PURPOSE: Molecular classification of endometrial cancer (EC) has become a promising information to tailor preoperatively the surgical treatment. We aimed to evaluate the rate of lymph node metastases (LNM) in patients with EC according to molecular profile. METHODS: A systematic review and meta-analysis were performed according to PRISMA guidelines by searching in two major electronic databases (PubMed and Scopus), including original articles reporting lymph node metastases according to the molecular classification of EC as categorized in the ESGO-ESMO-ESP guidelines. RESULTS: Fifteen studies enrolling 3056 patients were included. Pooled prevalence LNM when considering only patients undergoing lymph node assessment was 4% for POLE-mutated (95%CI: 0-12%), 22% for no specific molecular profile (95% CI: 9-39%), 23% for Mismatch repair-deficiency (95%CI: 10-40%) and 31% for p53-abnormal (95%CI: 24-39%). CONCLUSIONS: The presence of LNM seems to be influenced by molecular classification. P53-abnormal group presents the highest rate of nodal involvement, and POLE-mutated the lowest.

[Community reorientation of primary care in a health area: ROCAP project]. / Reorientación comunitaria de la atención primaria en un área de salud: proyecto ROCAP.

AIM: Evaluate the effectiveness of an intervention to incorporate group and community activities on a sustained basis in all the Basic Health Zones (ZBS) of a health area. DESIGN: During January and February 2019, two members of the research team traveled to each ZBS to interview the medical and nursing coordinators who had previously received an ad hoc initial assessment questionnaire (QAI) by email. PLACE: The scope is the 11 ZBS of a health area. PARTICIPANTS: The study population is the ZBS and the respective teams represented by the medical and nursing coordinations. INTERVENTIONS: Promote a community health commission, carry out training actions, record activities in clinical history and incorporate management objectives. MAIN MEASUREMENTS: Quantitative and qualitative analysis was carried out pre and post after the first year of intervention. RESULTS: In the pre-evaluation: 6 primary care teams (EAP) reported having group activities, 4 were participating in local action projects, 4 had a professional referent for community activities, 3 participated in projects with populations in vulnerable situations and 4 stated have specific meetings on community health. After the intervention: 11 EAPs had group activities, 8 had a reference professional, 6 were participating in local action projects, 4 collaborated in projects with vulnerable populations and 5 held meetings on community health. CONCLUSIONS: The intervention proved effective after its first year of implementation, since all the EAPs carried out group activities and collaborated with the local councils in the area; the majority had leading professionals in community care and, to a lesser extent, participation in local action projects and in vulnerable populations increased.

Living Lab Data of Patient Needs and Expectations for eHealth-Based Cardiac Rehabilitation in Germany and Spain From the TIMELY Study: Cross-Sectional Analysis.

BACKGROUND: The use of eHealth technology in cardiac rehabilitation (CR) is a promising approach to enhance patient outcomes since adherence to healthy lifestyles and risk factor management during phase III CR maintenance is often poorly supported. However, patients' needs and expectations have not been extensively analyzed to inform the design of such eHealth solutions. OBJECTIVE: The goal of this study was to provide a detailed patient perspective on the most important functionalities to include in an eHealth solution to assist them in phase III CR maintenance. METHODS: A guided survey as part of a Living Lab approach was conducted in Germany (n=49) and Spain (n=30) involving women (16/79, 20%) and men (63/79, 80%) with coronary artery disease (mean age 57 years, SD 9 years) participating in a structured center-based CR program. The survey covered patients' perceived importance of different CR components in general, current usage of technology/technical devices, and helpfulness of the potential features of eHealth in CR. Questionnaires were used to identify personality traits (psychological flexibility, optimism/pessimism, positive/negative affect), potentially predisposing patients to acceptance of an app/monitoring devices. RESULTS: All the patients in this study owned a smartphone, while 30%-40% used smartwatches and fitness trackers. Patients expressed the need for an eHealth platform that is user-friendly, personalized, and easily accessible, and 71% (56/79) of the patients believed that technology could help them to maintain health goals after CR. Among the offered components, support for regular physical exercise, including updated schedules and progress documentation, was rated the highest. In addition, patients rated the availability of information on diagnosis, current medication, test results, and risk scores as (very) useful. Of note, for each item, except smoking cessation, 35%-50% of the patients indicated a high need for support to achieve their long-term health goals, suggesting the need for individualized care. No major differences were detected between Spanish and German patients (all P>.05) and only younger age (P=.03) but not sex, education level, or personality traits (all P>.05) were associated with the acceptance of eHealth components. CONCLUSIONS: The patient perspectives collected in this study indicate high acceptance of personalized user-friendly eHealth platforms with remote monitoring to improve adherence to healthy lifestyles among patients with coronary artery disease during phase III CR maintenance. The identified patient needs comprise support in physical exercise, including regular updates on personalized training recommendations. Availability of diagnoses, laboratory results, and medications, as part of a mobile electronic health record were also rated as very useful. TRIAL REGISTRATION: ClinicalTrials.gov NCT05461729; https://clinicaltrials.gov/study/NCT05461729.

Patient-reported preferences in eHealth-based cardiac rehabilitation: A qualitative investigation of behavior change techniques, barriers and facilitators.

Background: Cardiac rehabilitation (CR) reduces recurrent cardiac events and mortality in patients with cardiovascular diseases (CVD). Innovative eHealth methods can facilitate CR uptake and effectiveness by addressing barriers associated with clinic-based rehabilitation. Tailoring eHealth-based CR to patient preferences is needed to further enhance CR. Purpose: To identify preferred behavior change techniques (BCTs) as well as barriers and facilitators for the different health behaviors targeted in eHealth-based CR among patients who have been referred to CR. Methods: Thirty-nine patients were interviewed in nine focus groups in The Netherlands, Germany, and Spain. A thematic analysis, using a combined deductive and inductive approach to coding, was conducted to identify BCTs and barriers and facilitators to behavior change. Behaviors under investigation included physical activity, medication adherence, eating a cardiac healthy-diet, stress reduction and smoking cessation. Results: The perceived helpfulness of BCTs depended on the specific behavior targeted. Common barriers were negative emotional state and physical limitations. A desire to feel physically or mentally well and having experienced a cardiac life event were the most common facilitators across health behaviors. Specific BCTs, barriers and facilitators were found for each of the health behavior. Conclusions: Behavior change techniques that patients preferred for each health behavior targeted in eHealth-based CR were identified. A negative emotional state, experiencing a life event, and improving physical functioning are important barriers and facilitators in multiple behaviors targeted in eHealth-based CR programs. Additional tailoring of interventions to patient preferences for BCTs and patient-specific barriers and facilitators per health behavior could lead to further improvement of eHealth-based CR.

Molecular profile is a strong predictor of the pattern of recurrence in patients with endometrial cancer.

OBJECTIVES: To investigate the pattern of first recurrence of disease in patients with endometrial cancer according to molecular classification, and to assess the independent role of molecular profiling in each type of failure. METHODS: Retrospective single-center study including patients diagnosed with endometrial cancer stage I-IVB (International Federation of Gynecology and Obstetrics 2009) between December 1994 and May 2022, who underwent primary surgical treatment and had a complete molecular profile. First recurrence was classified as isolated or multiple, and as vaginal, pelvic, peritoneal, nodal, and distant according to its location. The log-rank test and univariate and multivariate adjusted Cox regression models were used for comparison between groups. RESULTS: A total of 658 patients were included. Recurrence was observed in 122 patients (18.5%) with a recurrence rate of 12.4% among mismatch-repair deficient tumors, 14.5% among non-specific molecular profile, 2.1% among POLE-mutated, and 53.7% among p53-abnormal tumors. Recurrences were found to be isolated in 80 (65.6%) and multiple in 42 (34.4%) patients, with no differences in molecular subtype (p=0.92). Patients with p53-abnormal tumors had a recurrence mainly as distant (28.4%) and peritoneal (21.1%) disease, while patients with non-specific molecular profile tumors presented predominantly with distant failures (10.3%), and mismatch-repair deficient tumors with locoregional recurrences (9.4%).On multivariate analysis, p53-abnormal molecular profile was the only independent risk factor for peritoneal failure (OR=8.54, 95% CI 2.0 to 36.3). Vaginal recurrence was independently associated with p53-abnormal molecular profile (OR=6.51, 95% CI 1.1 to 37.4) and lymphovascular space invasion. p53-abnormal and non-specific molecular profiles were independent predictors for distant recurrence (OR=3.13, 95% CI 1.1 to 8.7 and OR=2.35, 95% CI 1.1 to 5.0, respectively), along with lymphovascular space invasion and high-grade tumors. Molecular profile was not independently associated with pelvic and nodal recurrences. CONCLUSIONS: Endometrial cancer featured different patterns of recurrence depending on the molecular profile. p53-abnormal molecular profiling was the only independent risk factor for peritoneal relapse, while non-specific molecular profile showed a strong association with distant failures.

Exercise-based cardio-oncology rehabilitation for cardiotoxicity prevention during breast cancer chemotherapy: The ONCORE randomized controlled trial.

BACKGROUND: Breast cancer (BC) treatment with anthracyclines and/or anti-human epidermal growth factor receptor-2 (HER2) antibodies is associated with an increased risk of cardiovascular disease complications, including cancer therapy-related cardiac dysfunction (CTRCD). While Cardio-Oncology Rehabilitation (CORe) programs including exercise have emerged to minimize these risks, its role in preventing CTRCD is unclear. OBJECTIVES: We investigated the effectiveness of an exercise-based CORe program in preventing CTRCD [left ventricular ejection fraction (LVEF) drop ≥10% to a value <53% or a decrease >15% in global longitudinal strain (GLS)]. Secondary outcomes examined changes in cardiac biomarkers, physical performance including peak oxygen consumption, psychometric and lifestyle outcomes. Safety, adherence, and patient satisfaction were also assessed. METHODS: This is a randomized controlled trial including 122 early-stage BC women receiving anthracyclines and/or anti-HER2 antibodies, randomized to CORe (n = 60) or usual care with exercise recommendation (n = 62). Comprehensive assessments were performed at baseline and after cardiotoxic treatment completion. The average duration of the intervention was 5.8 months. RESULTS: No cases of CTRCD were identified during the study. LVEF decreased in both groups, but was significantly attenuated in the CORe group [-1.5% (-2.9, -0.1); p = 0.006], with no changes detected in GLS or cardiac biomarkers. The CORe intervention led to significant body mass index (BMI) reduction (p = 0.037), especially in obese patients [3.1 kg/m2 (1.3, 4.8)]. Physical performance and quality-of-life remained stable, while physical activity level increased in both groups. No adverse events were detected. CONCLUSIONS: This study suggests that CORe programs are safe and may help attenuate LVEF decline in BC women receiving cardiotoxic therapy and reduce BMI in obese patients.

Real life data: follow-up assessment on Spanish Gaucher disease patients treated with eliglustat. TRAZELGA project.

BACKGROUND: The availability of multiple treatments for type 1 Gaucher disease increases the need for real-life studies to evaluate treatment efficacy and safety and provide clinicians with more information to choose the best personalized therapy for their patients. AIMS: To determine whether treatment with eliglustat produces, in adult GD1 patients, ans optimal response in daily clinical practice. METHODS: We designed a real-life study with 2 years of follow-up (TRAZELGA [GEE-ELI-2017-01]) to uniformly evaluate the response and adverse events to eliglustat treatment. This study, conducted in 30 patients across Spain and previously treated with other therapies, included the evaluation of safety and efficacy by assessing visceral enlargement, bone disease (DEXA and T and Z scores), concomitant treatments and adverse events, as well as a quality of life evaluation (SF-36). In addition, the quantification of classical biomarkers (chitotriosidase activity, CCL18/PARC and glucosylsphingosine (GluSph)) and new candidates for GD biomarkers (YKL-40, cathepsin S, hepcidin and lipocalin-2 determined by immunoassay) were also assessed. Non-parametric statistical analysis was performed and p < 0.05 was considered statistically significant. MAIN RESULTS: Thirty patients were enrolled in the study. The median age was 41.5 years and the male-female ratio was 1.1:1. 84% of the patients had received ERT and 16% SRT as previous treatment. The most common symptoms at baseline were fatigue (42%) and bone pain (38%), no patient had a bone crisis during the study, and two years after switching, 37% had reduced their use of analgesics. Patient-reported outcomes showed a significant increase in physical function scores (p = 0.027) and physical pain scores (p = 0.010). None of the enrolled patients discontinued treatment due to adverse events, which were mild and transient in nature, mainly gastrointestinal and skin dryness. None of the biomarkers show a significant increase or decompensation after switching. CCL18/PARC (p = 0.0012), YKL-40 (p = 0.00004) and lipocalin-2 (p = 0.0155) improved after two years and GluSph after one year (p = 0.0008) and two years (p = 0.0245) of oral therapy. CONCLUSION: In summary, this real-life study, showed that eliglustat maintains stability and can improve quality of life with few side effects. Significant reductions in classic and other novel biomarkers were observed after two years of therapy.

Proposed methodology for designing and developing MOOCs for the deaf community.

Massive Open Online Courses (MOOCs) have become important resources in educational environments worldwide because they have a positive impact on teaching and learning processes. Nevertheless, the way they are designed is crucial to properly address the requirements of special needs people in educational processes. Thus, this paper proposes a methodology for designing and developing MOOCs for Deaf or hard-of-hearing individuals. This exploratory and descriptive study adopted an inclusive education approach based on a literature review and expert consultation. The results highlight the importance of four aspects in MOOC development for these special needs individuals: (i) designing and incorporating elements that meet the needs of Deaf or hard-of-hearing people so that they can use MOOCs effectively; (ii) combining different methodologies and resources; (iii) properly planning and sequencing the design stages; and (iv) using appropriate tools, contents, and times for the process. The findings show that MOOCs should be adequately designed to address the demands of the Deaf community by considering their characteristics and requirements and incorporating current tools, practices, and resources.

Breathing pattern and pulmonary gas exchange in elderly patients with and without left ventricular dysfunction-modification with exercise-based cardiac rehabilitation and prognostic value.

Background: Inefficient ventilation is an established prognostic marker in patients with heart failure. It is not known whether inefficient ventilation is also linked to poor prognosis in patients with left ventricular dysfunction (LVD) but without overt heart failure. Objectives: To investigate whether inefficient ventilation in elderly patients with LVD is more common than in patients without LVD, whether it improves with exercise-based cardiac rehabilitation (exCR), and whether it is associated with major adverse cardiovascular events (MACE). Methods: In this large multicentre observational longitudinal study, patients aged ≥65 years with acute or chronic coronary syndromes (ACS, CCS) without cardiac surgery who participated in a study on the effectiveness of exCR in seven European countries were included. Cardiopulmonary exercise testing (CPET) was performed before, at the termination of exCR, and at 12 months follow-up. Ventilation (VE), breathing frequency (BF), tidal volume (VT), and end-expiratory carbon dioxide pressure (PETCO2) were measured at rest, at the first ventilatory threshold, and at peak exercise. Ventilatory parameters were compared between patients with and without LVD (based on cardio-echography) and related to MACE at 12 month follow-up. Results: In 818 patients, age was 72.5 ± 5.4 years, 21.9% were women, 79.8% had ACS, and 151 (18%) had LVD. Compared to noLVD, in LVD resting VE was increased by 8%, resting BF by 6%, peak VE, peak VT, and peak PETCO2 reduced by 6%, 8%, and 5%, respectively, and VE/VCO2 slope increased by 11%. From before to after exCR, resting VE decreased and peak PETCO2 increased significantly more in patients with compared to without LVD. In LVD, higher resting BF, higher nadir VE/VCO2, and lower peak PETCO2 at baseline were associated with MACE. Conclusions: Similarly to patients with HF, in elderly patients with ischemic LVD, inefficient resting and exercise ventilation was associated with worse outcomes, and ExCR alleviated abnormal breathing patterns and gas exchange parameters.

Endometrial adenocarcinoma recurring in the lung: impact of molecular profile and role of local therapies on prognosis.

OBJECTIVES: The objective of our study was to describe the characteristics of patients with endometrial cancer diagnosed with a first recurrence involving the lung, and to describe the prognostic role of the molecular profile. We also aimed to describe the prognostic outcomes after local treatment of recurrence (resection of lung metastases or stereotactic body radiation therapy) in a group of patients with isolated lung recurrence. METHODS: This was a retrospective, single-center study between June 1995 and July 2021. The study included patients diagnosed with a first recurrence of endometrial cancer involving the lung. We defined two groups of patients: patients with isolated lung recurrence (confined to the lung) and patients with multisystemic recurrence (in the lung and other locations). RESULTS: Among 1413 patients diagnosed with endometrial cancer in stage IA to IVA of the International Federation of Gynecology and Obstetrics (FIGO) 2009, 64 (4.5%) patients had a first recurrence involving the lung. Of these, 15 (39.1%) were of a non-specific molecular profile, 16 (25%) were p53-abnormal, 15 (23.4%) were mismatch-repair deficient, and 0% POLE-mutated. P53-abnormal patients had the shortest 3 year progression-free survival after recurrence and those with mismatch-repair deficient had the longest 3 year progression-free survival (14.3% (range; 1.6-40.3) and 47.6% (range; 9.1-79.5) respectively, p=0.001). We found no differences on overall survival after recurrence by molecular profile. Thirty-one of 64 (48.4%) patients had an isolated recurrence in the lung, and 16 (25%) patients received local treatment. When comparing patients with isolated lung recurrence, locally treated patients had a longer median progression-free survival than patients treated systemically (41.9 (range, 15.4-NA) vs 7.8 (range, 7.2-10.6) months respectively, p=0.029), a complete response rate of 80% for stereotactic body radiation therapy and a complete resection of 90.9% for surgery. CONCLUSION: Although few patients will benefit from local treatment (stereotactic body radiation therapy or resection) after a recurrence involving the lung, local therapies might be considered as an option in oligometastatic lung recurrences as they achieve high local control rates and better oncological outcomes than systemic treatment alone.

Prevalence of Depression, Anxiety, Post-Traumatic Stress, and Insomnia Symptoms Among Frontline Healthcare Workers in a COVID-19 Hospital in Northeast Mexico.

OBJECTIVE: Frontline healthcare workers (FHCWs) exposed to COVID-19 patients are at an increased risk of developing psychological burden. This study aims to determine the prevalence of mental health symptoms and associated factors among Mexican FHCWs attending COVID-19 patients. METHODS: FHCWs, including attending physicians, residents/fellows, and nurses providing care to COVID-19 patients at a private hospital in Monterrey, Mexico, were invited to answer an online survey between August 28, and November 30, 2020. Symptoms of depression, anxiety, post-traumatic stress, and insomnia were evaluated with the Patient Health Questionnaire (PHQ)-9, Generalized Anxiety Disorder (GAD)-7, Impact of Event Scale-Revised (IES-R), and Insomnia Severity Index (ISI). Multivariate analysis was performed to identify variables associated with each outcome. RESULTS: 131 FHCWs, 43.5% attending physicians, 19.8% residents/fellows, and 36.6% nurses were included. The overall prevalence of depression, anxiety, post-traumatic stress, and insomnia was 36%, 21%, 23%, and 24% respectively. Multivariate analysis revealed that residents/fellows and nurses reported more depression and insomnia than attending physicians. Although not significant, residents/fellows were more likely to experience all symptoms than nurses. CONCLUSIONS: Mexican FHCWs, especially nurses and residents/fellows, experienced a significant psychological burden while attending to COVID-19 patients. Tailored interventions providing support to FHCWs during future outbreaks are required.

Resultados de un programa de ecocardioscopia realizada por neurólogos en el proceso integrado en red de atención al ictus en unidades de imagen cardiaca / Results of a focused cardiac ultrasound program conducted by neurologists within a stroke care network with cardiac imaging units

Introducción y objetivos Recientemente los neurólogos han comenzado a realizar ecocardioscopia para la detección de cardiopatías en pacientes con ictus isquémico, lo cual requiere un proceso previo de formación acreditada. Se diseñó un estudio prospectivo con el objetivo de analizar la incidencia de cardiopatías detectadas por ecocardioscopia en una unidad de ictus integrada en red con una Unidad de Imagen Cardiaca y el pronóstico de la detección de cardiopatía estructural a 1 año de seguimiento. Métodos Se incluyeron los casos que ingresaron por ictus isquémico o accidente isquémico transitorio en un hospital clínico universitario de 2017 a 2021 y fueron evaluados mediante ecocardioscopia. Se estudió la presencia de cardiopatía estructural y cardiopatía embolígena. Se analizaron los eventos cardiovasculares (ECV) durante el primer año de seguimiento. Resultados Se realizó ecocardioscopia a 706 pacientes. Se detectó cardiopatía estructural en el 52,1% de los casos y cardiopatía embolígena en el 31,9%. El 5,49% había sufrido ECV al año de seguimiento. La presencia de cardiopatía estructural de novo se asoció de manera independiente con una mayor probabilidad de ECV (HR=1,72; IC95%, 1,01-2,91; p=0,046). Conclusiones La ecocardioscopia dentro de un proceso integrado en red de atención al ictus con unidades de imagen cardiaca es una técnica accesible y de alta rentabilidad diagnóstica. Su uso permite actuaciones clínicas y terapéuticas directas en la prevención de nuevas embolias cerebrales y otros ECV en este grupo de pacientes. (AU)

Introduction and objectives Recently, neurologists have begun to perform focused cardiac ultrasound for the detection of a cardiac source of embolism in stroke patients, requiring them to undergo a prior accredited training process. We designed a prospective study to analyze the incidence of heart disease detected by a focused cardiac ultrasound program within a stroke care network with cardiac imaging units and to identify the outcomes of detected structural heart disease at 1 year of follow-up. Methods We included patients admitted to a university hospital for ischemic stroke or a transient ischemic attack between 2017 and 2021 who were evaluated by focused cardiac ultrasound. We studied the presence of structural heart disease and cardioembolic sources. We analyzed cardiovascular events (CVE) during the first year of follow-up. Results Focused cardiac ultrasound was performed in 706 patients. Structural heart disease was detected in 52.1% and a cardioembolic source in 31.9%. Adverse CVE occurred in 5.49% of the patients in the first year of follow-up. The presence of de novo structural heart disease was independently associated with a higher probability of adverse CVE (HR, 1.72; 95%CI, 1.01- 2.91; P=.046). Conclusions Focused cardiac ultrasound within a stroke care network with cardiac imaging units is an accessible technique with high diagnostic yield. Its use allows clinical and therapeutic actions in the prevention of stroke recurrences and other CVEs in this group of patients. (AU)

Results of a focused cardiac ultrasound program conducted by neurologists within a stroke care network with cardiac imaging units.

INTRODUCTION AND OBJECTIVES: Recently, neurologists have begun to perform focused cardiac ultrasound for the detection of a cardiac source of embolism in stroke patients, requiring them to undergo a prior accredited training process. We designed a prospective study to analyze the incidence of heart disease detected by a focused cardiac ultrasound program within a stroke care network with cardiac imaging units and to identify the outcomes of detected structural heart disease at 1 year of follow-up. METHODS: We included patients admitted to a university hospital for ischemic stroke or a transient ischemic attack between 2017 and 2021 who were evaluated by focused cardiac ultrasound. We studied the presence of structural heart disease and cardioembolic sources. We analyzed cardiovascular events (CVE) during the first year of follow-up. RESULTS: Focused cardiac ultrasound was performed in 706 patients. Structural heart disease was detected in 52.1% and a cardioembolic source in 31.9%. Adverse CVE occurred in 5.49% of the patients in the first year of follow-up. The presence of de novo structural heart disease was independently associated with a higher probability of adverse CVE (HR, 1.72; 95%CI, 1.01- 2.91; P=.046). CONCLUSIONS: Focused cardiac ultrasound within a stroke care network with cardiac imaging units is an accessible technique with high diagnostic yield. Its use allows clinical and therapeutic actions in the prevention of stroke recurrences and other CVEs in this group of patients.

Analisis del impacto de la pandemia por covid-19 en recursos de rehabilitacion psicosocial / Analysis of the impact of the covid-19 pandemic on psychosocial rehabilitation resources

Como se ha podido comprobar, la irrupción de una pandemia como la generada por el COVID-19, así como, las consiguientes restricciones, afectan en mayor medida a los grupos más vulnerables como, entre otros, son las personas con Trastorno Mental Grave (TMG). Los objetivos fundamentales de este estudio pasan por analizar y comparar con la población general a la que pertenecen, el porcentaje de infecciones, hospitalizaciones y fallecimientos relacionados con el COVID-19 en el caso de recursos destinados a la atención a personas con TMG, como son los gestionados por la Línea de Rehabilitación Psicosocial (LRHP) de la organización Hermanas Hospitalarias. A su vez, también se analizan y comparan con periodos previos otras variables que han podido verse afectadas en esta crisis sanitaria tales como ingresos psiquiátricos, abandono de los recursos, intentos autolíticos o suicidios consumados. A diferencia de lo encontrado en la literatura previa, los resultados indican que no existen diferencias estadísticamente significativas entre los porcentajes de infecciones, hospitalizaciones o fallecimientos por COVID-19 entre la LRHP y los registrados en la población general. En cuanto a variables relacionadas con la Salud Mental, se encuentran diferencias estadísticamente significativas entre el año 2020 y el anterior, en el porcentaje de ingresos psiquiátricos y abandono en los recursos ambulatorios, siendo estos menores en 2020. Sin embargo, en el caso de los recursos residenciales, se registra un porcentaje significativamente mayor en el porcentaje de abandonos en 2020. Dichos resultados han de ser tomados con cautela, puesto que existen múltiples limitaciones que pudieran estar afectando a los mismos y pueden ser interpretados teniendo en cuenta los cambios contextuales relacionados con la pandemia respecto al funcionamiento de los recursos hospitalarios o a las restricciones a nivel de movilidad (AU)

As has been seen, the outbreak of a pandemic such as that generated by COVID-19, as well as the consequent restrictions, affect to a greater extent the most vulnerable groups such as, among others, people with Severe Mental Disorder (SMD). The fundamental objectives of this study are to analyze and compare with the general population to which they belong, the percentage of infections, hospitalizations and deaths related to COVID-19 in the case of resources destined to the care of people with TMG, such as those managed by the Linea de Rehabilitacion Psicosocial (LRHP) of the Sisters Hospitallers organization. At the same time, other variables that have been affected in this health crisis such as psychiatric admissions, abandonment of resources, autolytic attempts or completed suicides are also analyzed and compared with previous periods. Unlike what was found in the previous literature, the results indicate that there are no statistically significant differences between the percentages of infections, hospitalizations or deaths from COVID-19 between the LRHP and those registered in the general population. As for variables related to Mental Health, there are statistically significant differences between 2020 and the previous year, in the percentage of psychiatric admissions and abandonment in outpatient resources, these being lower in 2020. However, in the case of residential resources, there is a significantly higher percentage of abandonments in 2020. These results must be taken with caution, since there are multiple limitations that could be affecting them and can be interpreted taking into account the contextual changes related to the pandemic regarding the functioning of hospital resources or restrictions at the level of mobility (AU)

ß-Xylosidase SRBX1 Activity from Sporisorium reilianum and Its Synergism with Xylanase SRXL1 in Xylose Release from Corn Hemicellulose.

Sposisorium reilianum is the causal agent of corn ear smut disease. Eleven genes have been identified in its genome that code for enzymes that could constitute its hemicellulosic system, three of which have been associated with two Endo-ß-1,4-xylanases and one with α-L-arabinofuranosidase activity. In this study, the native protein extracellular with ß-xylosidase activity, called SRBX1, produced by this basidiomycete was analyzed by performing production kinetics and its subsequent purification by gel filtration. The enzyme was characterized biochemically and sequenced. Finally, its synergism with Xylanase SRXL1 was determined. Its activity was higher in a medium with corn hemicellulose and glucose as carbon sources. The purified protein was a monomer associated with the sr16700 gene, with a molecular weight of 117 kDa and optimal activity at 60 °C in a pH range of 4-7, which had the ability to hydrolyze the ρ-nitrophenyl ß-D-xylanopyranoside and ρ-Nitrophenyl α-L-arabinofuranoside substrates. Its activity was strongly inhibited by silver ions and presented Km and Vmax values of 2.5 mM and 0.2 µmol/min/mg, respectively, using ρ-nitrophenyl ß-D-xylanopyranoside as a substrate. The enzyme degrades corn hemicellulose and birch xylan in combination and in sequential synergism with the xylanase SRXL1.

Translation and cultural adaptation of the pectus excavatum evaluation questionnaire to Spanish and Catalan.

PURPOSE: Pectus excavatum (PE) is the most common congenital chest wall deformity. It can have a negative effect in exercise tolerance. However, cosmetic features are the most frequent concerns in these patients. The PE evaluation questionnaire (PEEQ) is a patient reported outcome (PRO) tool to measure the physical and psychosocial quality-of-life changes after surgical repair of PE. No specific tool has been developed in our languages to evaluate PRO in PE patients. Our aim is to translate and culturally adapt the PEEQ to Spanish and Catalan. METHODS: Guidelines for translation of PRO were followed. The PEEQ, consisting of 34 items, was translated from English to Spanish and to Catalan. Three forward translations and one back translation were performed for each language. Cognitive debriefing interviews were developed. RESULTS: The reconciliation of the forward translations revealed a 14.7% of inconsistencies for each language. The Spanish back translation showed a 64.7% of disagreement with the source, the Catalan 58.8%. Changes in each reconciled version were made to amend the diverting items. Cognitive debriefing: Catalan version: 15 participants, 10 males, 5 patients had been operated. 12 patients showed difficulties for understanding 4 of the items. Spanish version: 17 participants, 11 males, 5 had been operated. 13 patients showed difficulties for understanding 4 of the items. We made modifications of the problematic items, in order to make them easier to understand for our patients. We tested the last version in a new group of patients. Catalan: 7 patients, 5 males. One patient showed difficulties for understanding item 11, so we added a further clarification of this item. Spanish: 7 patients, all males. There were any difficulties for understanding. CONCLUSION: After a thorough process of translation and cultural adaptation, we reached a Catalan and a Spanish version of PEEQ. This work constitutes the first step to reach a specific PE PRO tool in our languages. However, it needs to be validated, with a higher number of patients, before being widely used in a clinical setting.

Thirty-second sit-to-stand test as an alternative for estimating peak oxygen uptake and 6-min walking distance in women with breast cancer: a cross-sectional study.

PURPOSE: To determine whether the 30-s sit-to-stand (30STS) test can be a valid tool for estimating and stratifying peak oxygen uptake (VO2peak) and 6-min walking distance (6MWD) in women with breast cancer. METHODS: This cross-sectional study uses data from the ONCORE randomized controlled trial, including 120 women aged 18-70 years with early-stage breast cancer under treatment with anthracycline and/or anti-HER2 antibodies. Participant characteristics were collected at baseline and pooled data from functional assessment (30STS test, relative and absolute VO2peak, and 6MWD) were collected at baseline and post-intervention (comprehensive cardio-oncology rehabilitation program vs. usual care). Bivariate correlations and multivariate linear regression analyses were performed to study the relationship between functional test variables. RESULTS: The number of repetitions in the 30STS test showed (i) a moderate correlation with relative VO2peak (ml/kg/min) (r = 0.419; p < 0.001; n = 126), (ii) a weak correlation with absolute VO2peak (ml/min) (r = 0.241; p = 0.008; n = 120), and (iii) a moderate correlation with the 6MWD (r = 0.440; p < 0.001; n = 85). The ONCORE equations obtained from the multivariate regression models allowed the estimation of VO2peak and 6MWD (r2 = 0.390; r2 = 0.261, respectively) based on the 30STS test, and its stratification into tertiles (low, moderate, and high). CONCLUSION: The 30STS test was found to be a useful tool to estimate VO2peak and/or 6MWD in women with early-stage breast cancer. Its use may facilitate the assessment and stratification of functional capacity in this population for the implementation of therapeutic exercise programs if cardiopulmonary exercise testing (CPET) or 6MWT are not available. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03964142. Registered on 28 May 2019. Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03964142.

Genomic Validation of Endometrial Cancer Patient-Derived Xenograft Models as a Preclinical Tool.

Endometrial cancer (EC) is the second most frequent gynecological cancer worldwide. Although improvements in EC classification have enabled an accurate establishment of disease prognosis, women with a high-risk or recurrent EC face a dramatic situation due to limited further treatment options. Therefore, new strategies that closely mimic the disease are required to maximize drug development success. Patient-derived xenografts (PDXs) are widely recognized as a physiologically relevant preclinical model. Hence, we propose to molecularly and histologically validate EC PDX models. To reveal the molecular landscape of PDXs generated from 13 EC patients, we performed histological characterization and whole-exome sequencing analysis of tumor samples. We assessed the similarity between PDXs and their corresponding patient's tumor and, additionally, to an extended cohort of EC patients obtained from The Cancer Genome Atlas (TCGA). Finally, we performed functional enrichment analysis to reveal differences in molecular pathway activation in PDX models. We demonstrated that the PDX models had a well-defined and differentiated molecular profile that matched the genomic profile described by the TCGA for each EC subtype. Thus, we validated EC PDX's potential to reliably recapitulate the majority of histologic and molecular EC features. This work highlights the importance of a thorough characterization of preclinical models for the improvement of the success rate of drug-screening assays for personalized medicine.

Development of knowledge-based clinical decision support system for patients included in colorectal screening program / Desarrollo de un sistema de soporte a la decisión médica basado en el conocimiento para los pacientes incluidos en el programa de cribado del cáncer colorrectal

Background & aims: Colorectal (CRC) screening programs represent a large volume of procedures that need a follow-up endoscopy. A knowledge-based clinical decision support system (K-CDSS) is a technology which contains clinical rules and associations of compiled data that assist with clinical decision-making tasks. We develop a K-CDSS for management of patients included in CRC screening and surveillance of colorectal polyps. Methods: We collected information on 48 variables from hospital colonoscopy records. Using DILEMMA Solutions Platform © (https://www.dilemasolution.com) we designed a prototype K-CDSS (PoliCare CDSS), to provide tailored recommendations by combining patients data and current guidelines recommendations. The accuracy of rules was verified using four scenarios (normal colonoscopy, lesions different than polyps, non-advanced adenomas and advanced adenomas). We studied the degree of agreement between the clinical assessments made by expert doctors and nurses equipped with PoliCare CDSS. Two experts confirmed a correlation between guidelines and PoliCare recommendations. Results: 56 consecutive endoscopy cases from colorectal screening program were included (62.8 years; range 53-71). Colonoscopy results were: absence of colon lesions (n=7, 12.5%), lesions in the colon that are not polyps (n=3, 5.4%) and resected colonic polyps (n=46, 82.1%; 100% R0 resection). Patients with resected polyps presented non-advanced adenoma (n=21, 45.6%) or advanced lesions (n=25, 54.4%). There were no differences in erroneous orders with PoliCare CDSS (Kappa value 1.0). Conclusions: PoliCare CDSS can easily be integrated into the workflow for improving the overall efficiency and better adherence to evidence-based guidelines.(AU)

Antecedentes & objetivos: Los programas de cribado de cáncer colorrectal (CCR) generan un gran número de colonoscopias de seguimiento. Un sistema de soporte a la decisión clínica basado en el conocimiento (K-CDSS) es una tecnología que contiene reglas clínicas y asociaciones de datos que ayudan en la tarea de toma de decisiones clínicas. El objetivo fue desarrollar un K-CDSS para el manejo de los pacientes de cribado de CCR, y evaluar su eficacia. Métodos: Recolectamos información de 48 variables de registros de colonoscopia. Mediante el software DILEMMA (https://www.dilemasolution.com) diseñamos un prototipo de K-CDSS (PoliCare CDSS), para proporcionar recomendaciones personalizadas, combinando los datos de los pacientes y las recomendaciones de las guías actuales. La exactitud de las reglas se verificó mediante cuatro escenarios (colonoscopia normal, lesiones diferentes a pólipos, adenomas no avanzados y adenomas avanzados). Se estudió el grado de concordancia entre las valoraciones clínicas realizadas por médicos expertos y enfermeros equipados con PoliCare CDSS. Dos expertos confirmaron una correlación entre las pautas y las recomendaciones de PoliCare. Resultados: Se incluyeron 56 casos consecutivos del programa de cribado (62,8 años; rango 53-71). Los resultados de la colonoscopia fueron: ausencia de lesiones de colon (n = 7, 12,5%), lesiones en el colon que no son pólipos (n = 3, 5,4%) y pólipos de colon resecados (n = 46, 82,1%; resección R0 del 100%). Los pacientes con pólipos resecados presentaron adenoma no avanzado (n = 21, 45,6%) o lesiones avanzadas (n = 25, 54,4%). No hubo diferencias en recomendaciones erróneas con PoliCare CDSS (valor Kappa 1.0). Conclusiones: PoliCare CDSS se puede integrar fácilmente en el flujo de trabajo de una unidad de endoscopia digestiva.(AU)

Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression.

Analyzing different tumor regions by next generation sequencing allows the assessment of intratumor genetic heterogeneity (ITGH), a phenomenon that has been studied widely in some tumor types but has been less well explored in endometrial carcinoma (EC). In this study, we sought to characterize the spatial and temporal heterogeneity of 9 different ECs using whole-exome sequencing, and by performing targeted sequencing validation of the 42 primary tumor regions and 30 metastatic samples analyzed. In addition, copy number alterations of serous carcinomas were assessed by comparative genomic hybridization arrays. From the somatic mutations, identified by whole-exome sequencing, 532 were validated by targeted sequencing. Based on these data, the phylogenetic tree reconstructed for each case allowed us to establish the tumors' evolution and correlate this to tumor progression, prognosis, and the presence of recurrent disease. Moreover, we studied the genetic landscape of an ambiguous EC and the molecular profile obtained was used to guide the selection of a potential personalized therapy for this patient, which was subsequently validated by preclinical testing in patient-derived xenograft models. Overall, our study reveals the impact of analyzing different tumor regions to decipher the ITGH in ECs, which could help make the best treatment decision.