Multicenter observational study on the reliability of the HEART score

Objective To rapidly and safely identify the risk of developing acute coronary syndrome in patients with chest pain who present to the emergency department, the clinical use of the History, Electrocardiogram, Age, Risk Factors, and Troponin (HEART) scoring has recently been proposed. This study aimed to assess the inter-rater reliability of the HEART score calculated by a large number of Italian emergency physicians. Methods The study was conducted in three academic emergency departments using clinical scenarios obtained from medical records of patients with chest pain. Twenty physicians, who took the HEART score course, independently assigned a score to different clinical scenarios, which were randomly administered to the participants, and data were collected and recorded in a spreadsheet by an independent investigator who was blinded to the study\u2019s aim. Results After applying the exclusion criteria, 53 scenarios were finally included in the analysis. The general inter-rater reliability was good (kappa statistics [\u3ba], 0.63; 95% confidence interval, 0.57 to 0.70), and a good inter-rater agreement for the high- and low-risk classes (HEART score, 7 to 10 and 0 to 3, respectively; \u3ba, 0.60 to 0.73) was observed, whereas a moderate agreement was found for the intermediate-risk class (HEART score, 4 to 6; \u3ba, 0.51). Among the different items of the HEART score, history and electrocardiogram had the worse agreement (\u3ba, 0.37 and 0.42, respectively). Conclusion The HEART score had good inter-rater reliability, particularly among the high- and low-risk classes. The modest agreement for history suggests that major improvements are needed for objectively assessing this component. Keywords HEART score; HEART pathway; Chest pain; Acute coronary syndrome; Emergency service, hospita

Club y centro de día como dispositivos de atención progresiva de la dependencia en adultos mayores

Se trata de describir y reflexionar críticamente sobre la construcción de dispositivos prestacionales diurnos de atención a la dependencia: Club de Día y Centro de Día. Los mismos están dirigidos específicamente a aquellos adultos mayores en riesgo de fragilización por aislamiento y soledad o porque hayan iniciado un proceso franco de deterioro que comienzan a necesitar de instancias de intervención y estimulación, tendientes a recuperar o a evitar la pérdida de funciones instrumentales. Ambas opciones se presentan por los autores como alternativas al proceso de institucionalización y medicalización de la población envejecida. Además se plantean estas alternativas como aporte al entorno de los adultos mayores y un alivio al cuidador de los mismos. Club y Centro de Día forman parte de una estrategia reciente del INSSJP de acciones desarrolladas en la Comunidad como derecho del sujeto adulto mayor a no perder los lazos y redes, como así también a generar un nuevo marco de relaciones vinculares. Se incluyen como acciones desarrolladas en ambas propuestas, la multiestimulación, la intervención profesional interdisciplinaria y una alimentación nutricional y culturalmente adecuada. La atención en la comunidad se coloca en el centro de las intervenciones además, por la gestión asociada con diferentes actores sociales de la comunidad apuntando a incluir la problematización sobre el pensamiento gerontológico actual en la agenda del/los Estado/s y la generación de respuestas prestacionales adecuadas.Facultad de Trabajo Socia

Club y centro de día como dispositivos de atención progresiva de la dependencia en adultos mayores

Se trata de describir y reflexionar críticamente sobre la construcción de dispositivos prestacionales diurnos de atención a la dependencia: Club de Día y Centro de Día. Los mismos están dirigidos específicamente a aquellos adultos mayores en riesgo de fragilización por aislamiento y soledad o porque hayan iniciado un proceso franco de deterioro que comienzan a necesitar de instancias de intervención y estimulación, tendientes a recuperar o a evitar la pérdida de funciones instrumentales. Ambas opciones se presentan por los autores como alternativas al proceso de institucionalización y medicalización de la población envejecida. Además se plantean estas alternativas como aporte al entorno de los adultos mayores y un alivio al cuidador de los mismos. Club y Centro de Día forman parte de una estrategia reciente del INSSJP de acciones desarrolladas en la Comunidad como derecho del sujeto adulto mayor a no perder los lazos y redes, como así también a generar un nuevo marco de relaciones vinculares. Se incluyen como acciones desarrolladas en ambas propuestas, la multiestimulación, la intervención profesional interdisciplinaria y una alimentación nutricional y culturalmente adecuada. La atención en la comunidad se coloca en el centro de las intervenciones además, por la gestión asociada con diferentes actores sociales de la comunidad apuntando a incluir la problematización sobre el pensamiento gerontológico actual en la agenda del/los Estado/s y la generación de respuestas prestacionales adecuadas.Facultad de Trabajo Socia

Club y centro de día como dispositivos de atención progresiva de la dependencia en adultos mayores

Se trata de describir y reflexionar críticamente sobre la construcción de dispositivos prestacionales diurnos de atención a la dependencia: Club de Día y Centro de Día. Los mismos están dirigidos específicamente a aquellos adultos mayores en riesgo de fragilización por aislamiento y soledad o porque hayan iniciado un proceso franco de deterioro que comienzan a necesitar de instancias de intervención y estimulación, tendientes a recuperar o a evitar la pérdida de funciones instrumentales. Ambas opciones se presentan por los autores como alternativas al proceso de institucionalización y medicalización de la población envejecida. Además se plantean estas alternativas como aporte al entorno de los adultos mayores y un alivio al cuidador de los mismos. Club y Centro de Día forman parte de una estrategia reciente del INSSJP de acciones desarrolladas en la Comunidad como derecho del sujeto adulto mayor a no perder los lazos y redes, como así también a generar un nuevo marco de relaciones vinculares. Se incluyen como acciones desarrolladas en ambas propuestas, la multiestimulación, la intervención profesional interdisciplinaria y una alimentación nutricional y culturalmente adecuada. La atención en la comunidad se coloca en el centro de las intervenciones además, por la gestión asociada con diferentes actores sociales de la comunidad apuntando a incluir la problematización sobre el pensamiento gerontológico actual en la agenda del/los Estado/s y la generación de respuestas prestacionales adecuadas.Facultad de Trabajo Socia

po 053 the phospholipase ddhd1 as a new target in colorectal cancer therapy

Introduction We have recently demonstrated that Citrus-limon derived nanovesicles are able to decrease colon cancer cell viability and that this effect is associated with the down-regulation of the intracellular phospholipase DDHD domain-containing protein 1 (DDHD1). While few studies are currently available on DDHD1 contribution in neurological disorders, information on its involvement in cancer is missing. Here we investigate the role of DDHD1 in colon cancer. Material and methods DDHD1 siRNAs and overexpression vector were transfected into colorectal cancer and normal cells to down-regulate or up-regulate DDHD1 expression. In vitro and in vivo assays were performed to investigate the functional role of DDHD1 in colorectal cancer cell growth. Quantitative proteomics by SWATH-MS was performed to determinate the molecular effects induced by DDHD1 silencing in colorectal cancer cells. Results and discussions Our evidences indicate that DDHD1 supports colon cancer cell proliferation and survival, since its down-regulation reduces in vitro colon cancer cell viability and increases apoptosis rate, without affecting normal cells. On the contrary, in vivo studies demonstrate that the xenograft tumours, derived from DDHD1-overexpressing cells, have a higher proliferation rate compared to control animals. Finally, a proteomic analysis of silenced cells opens up to the opportunity to define the molecular effects of DDHD1 silencing: we found that functional categories, significantly affected by DDHD1 silencing, was specifically related to cancer phenotype and for the first time associated to DDHD1 activity. Conclusion In summary, here we provide the first evidence of DDHD1 role in cancer, pointing out the possibility to define a new target to design more effective therapies for colon cancer patients. In addition, the proteomic analysis allows us to add new knowledge of DDHD1 cytoplasmic activity, highlighting its involvement in both known and previously unrecognised intracellular pathways and identifying multiple mechanisms that may explain the suppressed cancer cell growth induced by DDHD1 silencing

STRATEGIES TO PREDICT TREATMENT RESPONSE AND SELECT THERAPIES IN METASTATIC BREAST CANCER PATIENTS USING A NEXT GENERATION SEQUENCING MULTI-GENE PANEL

The standard of care for many patients with advanced breast cancer (BC )is gradually evolving from empirical treatment based on clinicalpathological characteristics to the use of targeted approaches based on the molecular profile of the tumor. In the last decade, an increasing number of molecularly targeted drugs have been developed for the treatment of metastatic BC. These drugs target specific molecular abnormalities that confer to cancer cells a survival advantage. Interestingly, the ability to perform multigene testing for a range of molecular alterations may provide an opportunity to clarify the mechanisms of treatment response, to find the strategies to overcome treatment resistance and thus, to identify patients who are more likely to develop relapse and who may be candidates for matched targeted therapies. The main aim of this study is to find prognostic and predictive molecular biomarkers for the management of metastatic BC patients in clinical practice

STRATEGIES TO PREDICT TREATMENT RESPONSE AND SELECT THERAPIES IN METASTATIC BREAST CANCER PATIENTS USING A NEXT GENERATION SEQUENCING (NGS) MULTI-GENE PANEL

The standard of care for many patients with advanced breast cancer (BC )is gradually evolving from empirical treatment based on clinicalpathological characteristics to the use of targeted approaches based on the molecular profile of the tumor. In the last decade, an increasing number of molecularly targeted drugs have been developed for the treatment of metastatic BC. These drugs target specific molecular abnormalities that confer to cancer cells a survival advantage [1]. Interestingly, the ability to perform multigene testing for a range of molecular alterations may provide an opportunity to clarify the mechanisms of treatment response, to find the strategies to overcome treatment resistance and thus, to identify patients who are more likely to develop relapse and who may be candidates for matched targeted therapies [2-3]. The main aim of this study is to find prognostic and predictive molecular biomarkers for the management of metastatic BC patients in clinical practice. MATERIALS AND METHODS The amplicon-sequencing analyses took advantage of the Ion AmpliSeq™ technology (Thermo Fisher, Waltham, MA, USA). A custom panel was designed with the help of the Designer online tool (www.ampliseq.com), which was employed to generate optimized primers encompassing the coding DNA sequences (with 100bp of exon padding and the UTRs regions) of 25 genes in the Human Reference Genome (hg19); these genes were selected searching and screening scientific literature for treatments resistance in BC and are reported in Table 1. Primer pairs were divided into two pools to optimize multiplex PCR conditions and the coverage, that assessed to 89.02%. The customized Ion AmpliSeq panel was employed on samples from 7 primary BC samples and matched metastatic sites (3 skin, 3 lymph node and 1 lung metastases). They were all processed using the Ion AmpliSeq Library Kit 2.0, starting from 15 nanograms of FFPE extracted DNA/pool. Samples were barcoded with the Ion Express Kit to optimize matched patients pooling on the same 318 Chip v2 sequencing chip. The template-positive Ion Sphere Particles were sequenced on a Personal Genome Machine (Thermo Fisher, Waltham, MA, USA). RESULTS The mutation profiles of paired primary and secondary tumors of the seven patients enrolled in this study are presented in Table 2. Ten different genes (PTEN, PIK3CA, mTOR, ERBB2, ERBB3, MET, INPP4B, MAP2K1, CDK6, KRAS) in 6 different patients showed possible damaging variants as shown in Table 2. • Four patients (number 1, 3, 5 and 6) showed no additional or different mutations in secondary tumors if compared to primary samples. • In patient number 2, the metastatic site presented new mutations if compared to the primary tumor. • Finally in patient number 4 and 7 we did not detect in metastases some of the mutations found in the primary tumor. DISCUSSION In 5 patients (71,4%) the mutational status of primary tumor could explain treatment resistance and thus predict relapse, in one patient the mutational status of the new subclones could be relevant for guiding differently the subsequent treatment choices. In 2 patients (28,5%) we were not able to detect in metastases some of the mutations found in the primary tumor. This could be explained by considering the clonal evolution of metastases. These preliminary data suggest that the multi-gene panel analysis of primary and secondary tumors may help clinicians: • in discriminating BC patients HR+ and/or HER2+ with mutations predicting an increased risk of adjuvant treatment resistance and thus relapse • in guiding treatment selection strategies in the metastatic setting. The study is still open and we are currently recruiting other patients.The main aim of this study is to find prognostic and predictive molecular biomarkers for the management of metastatic BC patients in clinical practice. The preliminary data suggest that the multi-gene panel analysis of primary and secondary tumors may help clinicians: • in discriminating BC patients HR+ and/or HER2+ with mutations predicting an increased risk of adjuvant treatment resistance and thus relapse • in guiding treatment selection strategies in the metastatic setting. The study is still open and we are currently recruiting other patients

Evaluating Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes

Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is associated with a recognisable facial pattern. However, the heterogeneity in causal genes and the presence of overlapping syndromes have made it increasingly difficult to diagnose only by clinical features. DeepGestalt technology, and its app Face2Gene, is having a growing impact on the diagnosis and management of genetic diseases by analysing the features of affected individuals. Here, we performed a phenotypic study on a cohort of 49 individuals harbouring causative variants in known CdLS genes in order to evaluate Face2Gene utility and sensitivity in the clinical diagnosis of CdLS. Based on the profile images of patients, a diagnosis of CdLS was within the top five predicted syndromes for 97.9% of our cases and even listed as first prediction for 83.7%. The age of patients did not seem to affect the prediction accuracy, whereas our results indicate a correlation between the clinical score and affected genes. Furthermore, each gene presents a different pattern recognition that may be used to develop new neural networks with the goal of separating different genetic subtypes in CdLS. Overall, we conclude that computer-assisted image analysis based on deep learning could support the clinical diagnosis of CdL

Multicenter observational study on the reliability of the HEART score

Objective To rapidly and safely identify the risk of developing acute coronary syndrome in patients with chest pain who present to the emergency department, the clinical use of the History, Electrocardiogram, Age, Risk Factors, and Troponin (HEART) scoring has recently been proposed. This study aimed to assess the inter-rater reliability of the HEART score calculated by a large number of Italian emergency physicians. Methods The study was conducted in three academic emergency departments using clinical scenarios obtained from medical records of patients with chest pain. Twenty physicians, who took the HEART score course, independently assigned a score to different clinical scenarios, which were randomly administered to the participants, and data were collected and recorded in a spreadsheet by an independent investigator who was blinded to the study’s aim. Results After applying the exclusion criteria, 53 scenarios were finally included in the analysis. The general inter-rater reliability was good (kappa statistics [κ], 0.63; 95% confidence interval, 0.57 to 0.70), and a good inter-rater agreement for the high- and low-risk classes (HEART score, 7 to 10 and 0 to 3, respectively; κ, 0.60 to 0.73) was observed, whereas a moderate agreement was found for the intermediate-risk class (HEART score, 4 to 6; κ, 0.51). Among the different items of the HEART score, history and electrocardiogram had the worse agreement (κ, 0.37 and 0.42, respectively). Conclusion The HEART score had good inter-rater reliability, particularly among the high- and low-risk classes. The modest agreement for history suggests that major improvements are needed for objectively assessing this component