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PURPOSE This study aimed to assess the efficacy of the combination of nivolumab (nivo) plus ipilimumab (ipi) as a first-line therapy with respect to the 12-month overall survival (OS) in patients with metastatic uveal melanoma (MUM) who are not eligible for liver resection. METHODS This was a single-arm, phase II trial led by the Spanish Multidisciplinary Melanoma Group (GEM) on nivo plus ipi for systemic treatment-naïve patients of age > 18 years, with histologically confirmed MUM, Eastern Cooperative Oncology Group-PS 0/1, and confirmed progressive metastatic disease (M1). Nivo (1 mg/kg once every 3 weeks) and ipi (3 mg/kg once every 3 weeks) were administered during four inductions, followed by nivo (3 mg/kg once every 2 weeks) until progressive disease, toxicity, or withdrawal. The primary end point was 12-month OS. OS, progression-free survival (PFS), and overall response rate were evaluated every 6 weeks using RECIST (v1.1). Safety was also evaluated. Logistic regression and Cox proportional hazard models comprising relevant clinical factors were used to evaluate the potential association with response to treatment and survival. Cytokines were quantified in serum samples for their putative role in immune modulation/angiogenesis and/or earlier evidence of involvement in immunotherapy. RESULTS A total of 52 patients with a median age of 59 years (range, 26-84 years) were enrolled. Overall, 78.8%, 56%, and 32% of patients had liver M1, extra-liver M1, and elevated lactate dehydrogenase. Stable disease was the most common outcome (51.9%). The primary end point was 12-month OS, which was 51.9% (95% CI, 38.3 to 65.5). The median OS and PFS were 12.7 months and 3.0 months, respectively. PFS was influenced by higher LDH values. CONCLUSIONS Nivo plus ipi in the first-line setting for MUM showed a modest improvement in OS over historical benchmarks of chemotherapy, with a manageable toxicity profile.

Ultrasound is an essential tool in the management of the nephrological patient allowing the diagnosis, monitoring and performance of kidney intervention. However, the usefulness of ultrasound in the hands of the nephrologist is not limited exclusively to the ultrasound study of the kidney. By ultrasound, the nephrologist can also optimize the management of arteriovenous fistula for hemodialysis, measure cardiovascular risk (mean intimate thickness), implant central catheters for ultrasound-guided HD, as well as the patient's volemia using basic cardiac ultrasound, ultrasound of the Cava Inferior vein and lungs.From the Working Group on Interventional Nephrology of the Spanish Society of Nephrology (G.N.D.I. of the S.E.N.) we have prepared this Consensus Document that summarizes the main applications of ultrasound to Nephrology, including the necessary basic technical requirements, the framework normative and the level of training of nephrologists in this area. The objective of this work is to promote the inclusion of ultrasound, both diagnostic and interventional, in the usual clinical practice of the nephrologist and in the Nephrology Services portfolio with the final objective of offering diligent, efficient and comprehensive management to the nephrological patient. Resumen: La ecografía es una herramienta esencial en el manejo del paciente nefrológico permitiendo el diagnóstico, seguimiento y realización de intervencionismo sobre el riñón. La utilidad de los ultrasonidos en Nefrología no se circunscribe exclusivamente al estudio ecográfico del riñón. Mediante ecografía el nefrólogo puede, además, optimizar el manejo de la fístula arteriovenosa para hemodiálisis, medir el riesgo cardiovascular (grosor íntima media), implantar catéteres centrales para hemodiálisis ecoguiados y ayudar en la colocación de los peritoneales, así como calcular la volemia del paciente medianteecografía cardiaca básica, ecografía de la vena cava inferior y pulmonar.Desde el G.N.D.I. de la S.E.N hemos elaborado este documento de consenso en el que se resumen las principales aplicaciones de la ecografía en Nefrología, incluyendo los requisitos técnicos básicos necesarios, el marco normativo y el nivel de capacitación de los nefrólogos en esta materia. El objetivo de este trabajo es promover la inclusión de la ecografía, tanto diagnóstica como intervencionista, en la práctica clínica habitual del nefrólogo y en la cartera de servicios de Nefrología con el objetivo final de ofrecer un manejo diligente, eficiente e integral al paciente nefrológico.

Introduction and objectives: This report presents the findings of the 2018 Spanish Catheter Ablation Registry. Methods: Data collection was retrospective. A standardized questionnaire was completed by each of the participating centers. Results: Data sent by 100 centers were analyzed, with a total number of 16,566 ablation procedures performed (the highest historically reported in this registry) for a mean of 165.5 ± 127.9 and a median of 119 procedures per center. The ablation targets most frequently treated were atrial fibrillation (n = 4234; 25.6%), atrioventricular nodal re-entrant tachycardia (n = 3525; 21.3%) and cavotricuspid isthmus (n = 3425; 20.7%). A new peak was observed in the ablation of atrial fibrillation, increasing the distance from the other substrates. The overall success rate was 91%. The rate of major complications was 2.2%, and the mortality rate was 0.04%. A total of 2.1% of the ablations were performed in pediatric patients. Conclusions: The Spanish Catheter Ablation Registry systematically and continuously enrolls the ablation procedures performed in Spain, showing a progressive increase in the number of ablations over the years, with a high success rate and low percentage of complications.

BackgroundIntratumoral immunotherapies are being tested in different solid tumors. They trigger local and systemic responses.1 2 BO-112 is a double stranded RNA nanoplexed with polyethyleneimine (PEI), which mimics a viral infection and mobilizes the immune system.In preclinical models and in a first in human clinical trial BO-112 activated dendritic cells, induced CD-8 infiltration, apoptosis and enhancement of immunogenic cell death and achieved an objective response in 2 out of 10 patients with melanoma with primary resistance to antiPD-1.3 4MethodsIn this phase 2 study, BO-112 plus pembrolizumab is evaluated in patients with advanced melanoma, who have developed progressive disease while on or within 12 weeks after anti-PD1/PD-L1 based therapy (either as first line or as adjuvant treatment). BO-112 is administered intratumorally once weekly in 1 to 8 tumor lesions, total dose 1 to 2 mg, for the first 7 weeks and thereafter every three weeks; pembrolizumab 200 mg is administered intravenously every three weeks. Overall response rate (ORR) is analyzed as primary endpoint by independent reviewer. Secondary objectives include disease control rate (DCR), duration of response and progression free survival (PFS); response assessment is done by RECIST 1.1 and iRECIST; in addition, CD-8 and PD-L1 IHC, NGS, itRECIST and radiomics signatures are prospectively assessed. Key eligibility criteria include cutaneous or mucosal melanoma with known BRAF status; at least one lesion RECIST 1.1 measurable and amenable for IT injection. Enrollment has been completed on 26th August.ResultsWith 26 evaluable patients with a first response assessment, seven have progressive disease (PD), five have partial response (PR) and fourteen patients show stable disease (SD). Preliminary ORR is 19.2% and DCR is 73.1% at week 8. Three patients with PR at week 8 have undergone a second assessment at week 16, with further decrease in sum of diameters (SOD) in both injected and non-injected lesions. Three out of five patients with SD and a second assessment maintain SD, showing a decrease in SOD in two cases (figure 1). In addition, two patients with only skin lesions have a pathological complete response. CD8 and PD-L1 have increased in 8 and 7 out of 13 patients with paired biopsies, being related with clinical benefit (figure 2).Abstract 961 Figure 1Swimmer plot, efficacy data for evaluable patients undergoing at least one response assessmentAbstract 961 Figure 2Immunohistochemistry data for CPS and CD8 data from paired biopsiesConclusionsDespite these data being preliminary, there is a trend for benefit in terms of ORR and also in long lasting stable diseases. BO-112 is able to increase PD-L1 expression in tumor cells and increase CD8-T cell infiltrates.AcknowledgementsMerck, Pivotal SLU, Quibim radiomics, Pangaea laboratories, all participating sites and patientsTrial RegistrationNCT04570332ReferencesAznar MA, Planelles L, Perez-Olivares M, et al. Immunotherapeutic effects of intratumoral nanoplexed poly I:C. J Immunother Cancer. 2019 May 2;7(1):116.5. Hamid O, Ismail R, Puzanov I. Intratumoral immunotherapy-update 2019. The Oncologist 2020;25:e423–438.Márquez-Rodas I, Longo F, Rodríguez-Ruiz M, et al. Intratumoral nanoplexed poly I:C BO-112 in combination with systemic anti-PD-1 for patients with anti-PD-1-refractory tumors. Sci Transl Med 2020 Oct 14;12(565):eabb0391.Kalbasi A, Tariveranmoshabad M, Hakimi K, Kremer S, et al. A. Uncoupling interferon signaling and antigen presentation to overcome immunotherapy resistance due to JAK1 loss in melanoma. Sci Transl Med 2020 Oct 14;12(565):eabb0152.Ethics ApprovalThe study obtained ethics approval by Spanish Health Agency (AEMPS), on 11th December 2020, and French Health Agency (ANSM) on 27th January 2021; study obtained approval from two Ethics Committee: Vall D’Hebron, Barcelona, Spain on 7th December 2020 (number 467), and Centre Léon Bérard, Lyon, France, CPP 20.11.10.38825 on 11th February 2021.For each study patient, written informed consent is obtained prior to any protocol-related activities. As part of this procedure, the principal investigator or one of his/her associates must explain orally and in writing the nature, duration, and purpose of the study, and the action of the study drug in such a manner that the patient is aware of the potential risks, inconveniences, or adverse effects that may occur. They should be informed that the patient may withdraw from the study at any time. They will receive all information that is required by the regulatory authorities and ICH guidelines. The ICF has been signed by the patient and a copy provided to them.ConsentN/A

Bendamustine is a drug widely used in the treatment of follicular lymphoma. Although it was initially approved as monotherapy in patients refractory to rituximab [1], better results were obtained w...

Rationale: Airway colonization by Potentially Pathogenic Microorganisms ( PPM) in bronchiectasis is associated with worse clinical outcomes. The electronic nose is a non-invasive technology capable of distinguishing volatile organic compounds ( VOC) in exhaled breath. We aim to explore if an electronic nose can reliably discriminate airway bacterial colonization in patients with bronchiectasis. Methods: Seventy-three clinically stable bronchiectasis patients were included. PPM presence was determined using sputum culture. Exhaled breath was collected in Tedlar bags and VOC breath-prints were detected by the electronic nose Cyranose 320(R). Raw data was reduced to three factors with principal component analysis. Univariate ANOVA followed by post-hoc least significant difference test was performed with these factors. Patients were then classified using linear canonical discriminant analysis. Cross-validation accuracy values were defined by the percentage of correctly classified patients. Results: Forty-one (56%) patients were colonized with PPM. Pseudomonas aeruginosa ( n=27, 66%) and Haemophilus influenzae ( n=7, 17%) were the most common PPM. VOC breath-prints from colonized and non-colonized patients were significantly different ( accuracy of 72%, AUROC 0.75, p < 0.001). VOC breath-prints from Pseudomonas aeruginosa colonized patients were significantly different from those of patients colonized with other PPM ( accuracy of 89%, AUROC 0.97, p < 0.001) and non-colonized patients ( accuracy 73%, AUROC 0.83, p=0.007). Conclusions: An electronic nose can accurately identify VOC breath-prints of clinically stable bronchiectasis patients with airway bacterial colonization, especially in those with Pseudomonas aeruginosa.

Background: BO-112 is a double stranded synthetic RNA formulated with polyethyleneimine (PEI), that acts as an agonist to toll-like receptor 3 and targets the cytosolic helicase melanoma differentiation-associated gene 5 and retinoic acid-inducible gene I. By mimicking the effect of a viral infection, it mobilizes the immune system, including activation of dendritic cells, CD8 T-cell infiltration, induction of interferons (IFNs), induction of apoptosis and enhancement of immunogenic cell death. Clinical data are available from the first-in-human study (NCT02828098) which evaluated single intratumoral (IT) BO-112 (Part 1; N = 16) and the combination of IT BO-112 with pembrolizumab or nivolumab (Part 2; N = 28). Part 2 showed an ORR of 11% and DCR of 46% in patients with multiple tumor types. Of them, 2 out of 10 (20%) patients with melanoma resistant to anti PD-1 achieved a partial response. Safety profile of BO-112, both as single agent and in combination with anti-PD-1, is manageable and currently characterized by Grade 1 fever and other flu-like symptoms. A phase 2 clinical study of IT BO-112 in combination with pembrolizumab in patients with liver metastases from colorectal or gastric/gastro-esophageal junction cancer patients is currently ongoing. Methods: Phase 2, single arm, open label study of IT BO-112 in combination with pembrolizumab in patients with advanced and/or metastatic melanoma that have progressed on anti-PD-1-containing treatment (NCT04570332). BO-112 will be administered once weekly (QW) in 1 to 8 tumor lesions, total dose 1-2 mg (depending on the number of injected lesions), for the first 7 weeks and then once every three weeks (Q3W); pembrolizumab 200 mg will be administered Q3W. Key eligibility criteria include histologically confirmed, unresectable cutaneous or mucosal melanoma with known BRAF status. Patients must have progressed on or after treatment with an anti-PD-1/L1 mAb. At least one lesion RECIST 1.1 measurable and amenable for weekly IT injection is needed. Primary efficacy variable is ORR by RECIST 1.1, assessed by independent central radiologist (by QUIBIM Precision platform). Secondary efficacy variables include clinical activity in terms of DCR, DOR, PFS, OS, iRECIST, safety and PKs. Exploratory objectives include itRECIST and evaluation of tumor microenvironment (by Pangaea laboratory). A 1-sided alpha of 4.19% and power of 81.8% are used. A total of 40 patients will be enrolled. If less than 8 patients out of 40 have ORR, the study will not meet the statistical bar. Study was approved on 14 December in Spain; enrollment is open; two sites are active as of 18 December 2020. Nineteen sites (12 in Spain and 7 in France) are planned to be activated. Citation Format: Iván Márquez-Rodas, Miguel Fernández de Sanmamed Gutiérrez, María González Cao, Ana M. Arance, Alfonso Berrocal, Eduardo Castañon, Sofía España, Pablo Cerezuela-Fuentes, Juan F. Rodríguez-Moreno, Pilar López Criado, Juana Oramas, Luis de la Cruz Merino, Stéphane Dalle, Caroline Dutriaux, Julie Charles, Caroline Robert, Brigitte Dréno, Henri Montaudié, Philippe Saiag, Javier Sánchez-López, María Rojas, Helena Escuin-Ordinas, Vanesa Pons Sanz, Sonia Maciá, Marisol Quintero. Phase 2 clinical study to evaluate the efficacy and safety of intratumoral BO-112 in combination with pembrolizumab in patients with advanced melanoma that have progressive disease on anti-PD-1-based therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT233.

espanolLas infecciones respiratorias representan la primera causa de morbilidad infecciosa tanto en adultos y ninos en atencion primaria en Espana. Se tratan generalmente de infecciones autolimitadas, causadas principalmente por virus. Sin embargo, esta documentado un alto porcentaje de prescripcion antibiotica innecesaria. Las tecnicas de diagnostico rapido son pruebas biomedicas que puede ser utilizadas en la misma consulta con el paciente sin la necesidad de disponer de un laboratorio. El uso de estas pruebas, muchas de las cuales se han desarrollado recientemente, esta aumentando rapidamente en atencion primaria. No obstante, debemos reflexionar sobre si su uso contribuye siempre a que se realice un diagnostico apropiado y de alta calidad por parte de los medicos de atencion primaria. Presentamos un conjunto de criterios que pueden ser utilizados por los clinicos y se discuten las ventajas e inconvenientes de los instrumentos disponibles para el abordaje de las infecciones respiratorias y como utilizarlos adecuadamente. EnglishRespiratory tract infections rank first as causes of adult and paediatric infectious morbidity in primary care in Spain. These infections are usually self-limiting and are mainly caused by viruses. However, a high percentage of unnecessary antibiotic prescription is reported. Point-of-care tests are biomedical tests, which can be used near the patient, without interference of a laboratory. The use of these tests, many of which have been recently developed, is rapidly increasing in general practice. Notwithstanding, we must mull over whether they always contribute to an effective and high-quality diagnostic process by primary care clinicians. We present a set of criteria that can be used by clinicians and discuss the pros and cons of the instruments available for the management of respiratory tract infections and how to use them appropriately.

Introduction: Interstitial lung diseases (ILD) constitute a heterogeneous group of entities with significant impact on survival. Early diagnosis is fundamental, however it is difficult in clinical practice. The electronic nose is a non-invasive technology capable to distinguishing volatile organic compound (VOC) breath-prints in exhaled breath. Objective: To determine if electronic nose was able to discriminate ILD patients from healthy controls and other prevalent lung diseases like chronic obstructive pulmonary disease (COPD). Methods: Prospective observational study. Fifty-nine ILD patients, 31 healthy controls and 40 COPD patients were included. In each case, exhaled air was collected in Tedlar bags and VOCs breath-prints were detected by the commercially available electronic nose Cyranose320®. Cross-validatin accuracy was assessed using principal component reduction analysis, as our group previously described and validated. Results: Median age of ILD patients, healthy controls and COPD patients were (65±13 years; 37±22 years; 68±5 years) and median FEV1 of these groups were (82±20% ref; 102±9%; 41±10% ref). Patients under study of ILD showed a different VOCs breath-print from healthy controls (accuracy 90%, AUROC 0.92, p Conclusions: The electronic nose is able to identify ILD patients from healthy controls as well as COPD patients. More studies are needed to determine if an electronic nose could play a role as a non-invasive diagnostic method in the screening of ILD.

BackgroundThe efficacy of intravenous (IV) ferric carboxymaltose (FCM) has been demonstrated in haemodialysis and non-dialysis studies, but evidence is lacking in patients undergoing peritoneal dialysis (PD).MethodsThis multicentre, retrospective study evaluated the effectiveness and safety of FCM in patients on PD over 12 months. We retrospectively reviewed the electronic medical records of PD patients who initiated FCM treatment between 2014 and 2017 across seven Spanish centres.ResultsNinety-one patients were included in the safety population (mean ± SD age 57.7 ± 15.0 years) and 70 in the efficacy population (mean age 50.9 ± 14.5 years). No hypersensitivity reaction, FCM discontinuation or dose adjustment due to a serious adverse event (SAE) was registered in the safety population. The most common non-SAEs reported were headache (four events), mild hypotension (three events) and hypertension (two events), among others. In the efficacy population (n = 70), 68.6% of patients achieved ferritin levels of 200–800 ng/mL, 78.4% achieved transferrin saturation (TSAT) >20%, and 62.8% achieved TSAT >20% and ferritin >200 ng/mL after 12 months of FCM initiation (P 11 g/dL with a lower dose of darbepoetin throughout the follow-up. The sub-analysis of patients naïve to IV iron and with absolute or relative iron deficiency (n = 51) showed that 76.5% reached ferritin >200 ng/mL, 80.4% TSAT >20% and Hb increased (1.2 g/dL) after 4 months of FCM treatment (P ConclusionIn this multicentre, retrospective, real-world study conducted in the PD population, FCM was effective, safe and easy to administer during routine clinical visits.

WPW ablation is one of the most rewarding procedures performed in electrophysiology. Fluoroscopy has been used to guide catheters into the heart chambers, but even in EP labs using fluoroscopy, 3D mapping systems are utilized more and more for accessory pathway (AP) ablation to tag AP location, a feature not possible to achieve using X-ray-only approach. We describe in detail how to approach AP ablation with little or no fluoroscopy in the right and left chambers of the heart.

8019 Background: Lenalidomide is an immunomodulatory drug that could reverse rituximab refractoriness in lymphoma patients (pts). We conducted an open label multicenter phase 2 trial testing the efficacy and toxicity of a combination of lenalidomide and rituximab (R2) plus GDP schedule (R2-GDP) in Relapsed/Refractory Diffuse Large B Cell Lymphoma (R/R DLBCL) pts, not suitable for autologous stem cell transplant (ASCT). Methods: Patients with R/R DLBCL previously treated with at least 1 prior line of immunochemotherapy including rituximab, and not candidates for ASCT, were eligible. After a run-in phase period, treatment consisted of an induction phase with lenalidomide (LEN) 10 mg po d1-14, rituximab 375 mg/m2 iv d1, cisplatin 60 mg/m2 iv d1, gemcitabine 750 mg/m2 iv d1 and d8 and dexamethasone 20 mg d1-3, up to a maximum of 6 cycles. Pts without disease progression (DP) entered into a maintenance phase with LEN 10 mg, or last LEN dose received in the induction phase, d1-21 in cycles every 28 days. Primary endpoint was overall response rate (ORR) by investigator assessment. Secondary endpoints included disease free survival (DFS), event free survival (EFS), overall survival (OS), safety and response by cell of origin (COO), type of DLBCL (double-triple hit) and other microenvironment and genomic biomarkers. Results: 79 pts were enrolled between April 2015 and September 2018. Median age was 70 years (range 23-86), 48,7% women. 78 pts were considered for efficacy and safety in the intention to treat (ITT) analysis. With a median follow-up of 13 months at the time of cut-off (November 2019), ORRwas 59.0%, with 32.1% complete responses (CR) and 26.9% partial responses (PR). In the primary refractory population (n = 33), ORR was 45.5%, with 21.2% CR and 24.3% PR. There were no statistically significant differences in ORR with respect to COO. In Double-Hit R/R DLBCL (n = 16), ORR was 37.5% with 25% CR. Median OS was 12.0 months (6.9-17.0). Most common grade 3/4 (G3/4) adverse events were thrombocytopenia (60.2%), neutropenia (60.2%) and anemia (26.9%). Febrile neutropenia occurred in 14.1% pts. Most frequent non-hematologic G3/4 events were asthenia (19.2%), infection (15.3%) and renal insufficiency (6.4%). There were 4 toxic deaths related to the R2-GDP schedule. Conclusions: LEN with Rituximab and GDP (R2-GDP) is feasible and active in R/R DLBCL. Results in the primary refractory DLBCL population are particularly promising. Analysis of COO did not revealed differences in response rates. Immune biomarkers results will be showed at the meeting. Clinical trial information: EudraCT 2014-001620-29 .

TPS10081 Background: CNS mets, a common complication of melanoma, are associated with poor survival prognosis (median of 4-5 months). The rationale for combining PD-L1 pathway blockade using atezolizumab (A) with the small molecule BRAF pathway–targeted inhibitors cobimetinib (C) and vemurafenib (V) for the treatment of BRAFV600 mutation–positive melanoma is based on preclinical and translational evidence supporting the synergistic antitumoral effects of these approaches. Recently, the phase 3 IMspire150 study (NCT02908672) demonstrated improved progression-free survival outcomes with A + C + V vs C + V. Methods: This phase 2 study (NCT03625141) is currently evaluating A + C + V in pts with BRAFV600 mutation–positive advanced melanoma and CNS mets. The study originally included a parallel cohort evaluating A + C in pts with BRAFV600wild-type advanced melanoma and CNS mets. This cohort was closed at an enrollment of 15 pts after the primary analysis of the phase 3 IMspire170 study (NCT03273153), which showed no added benefit with A + C vs pembrolizumab in pts with BRAFV600 wild-type disease. Eligible pts are aged ≥18 years with histologically confirmed melanoma and magnetic resonance imaging–confirmed brain mets ≥5 mm in at least 1 dimension. In addition, pts should not have received prior systemic treatment for metastatic disease; they were required to have ECOG performance status ≤2 and adequate hematologic and end organ function. Prior stereotactic or surgical therapy of ≤10 brain mets is allowed. The primary endpoint is intracranial objective response rate (ORR) with A + C + V in BRAFV600mutation–positive melanoma as assessed by an independent review committee. Key secondary endpoints include investigator-assessed intracranial ORR, extracranial ORR, overall ORR, safety, and quality of life. Exploratory biomarker analyses are planned. The sample size for the cohort will be approximately 60 pts. No formal statistical hypothesis is being tested in this study. The primary study analysis and the analyses of all efficacy endpoints and safety summaries will be based on data collected ≤6 months after the last pt is enrolled. Clinical trial information: NCT03625141.

Introduction: Hospital readmissions are critical in the natural history of severe COPD patients. However, its prediction is complicated in clinical practice. The electronic nose is a non-invasive technology capable of distinguish volatile organic compounds (VOC) breath-prints in exhaled breath. Objective: We aim to explore if an electronic nose can reliably predict the presence of future hospital readmissions in admitted patients with Chronic Obstructive Pulmonary Disease (COPD) and frequent severe exacerbations. Methods: Eighty-eight hospitalized COPD patients with two ore more severe exacerbations in the previous year were included. On admission, clinical, functional, microbiological and laboratory data were recorded. During the first 24 hours of admission, exhaled breath was collected in Tedlar bags and VOCs breath-prints were detected by the commercially available electronic nose Cyranose 320®. Cross-validation accuracy was assessed using principal component reduction analysis (PCA). Patients were followed during 90 days after discharge. Results: Seventeen patients (19%) were readmitted at 30-days, and 33 patients (37%) were readmitted at 90-days. No clinical differences on admission were observed among patients who were readmitted or not. However, VOC breath-prints were different among both groups. In predicting 30-day readmission, the accuracy was of 87.5%, sensitivity of 90% and specificity of 76.5% (AUROC 0.85, p Conclusions: An electronic nose may identify admitted severe COPD patients at risk of 30-day and 90-day readmission. Suported by SEPAR, FUCAP.

espanolLa faringoamigdalitis aguda (FAA) en el adulto es una de las enfermedades infecciosas mas comunes en la consulta del medico de familia. La etiologia mas frecuente es viral. Dentro de la etiologia bacteriana, el principal agente responsable es Streptococcus pyogenes o estreptococo β-hemolitico del grupo A (EBHGA), causante del 5-30% de los casos. En el manejo diagnostico las escalas de valoracion clinica, para predecir la posible etiologia bacteriana, son una buena ayuda para seleccionar a que pacientes se deben practicar las tecnicas de deteccion rapida de antigeno estreptococico. Es conocido que, en general, sin estas tecnicas, se tiende al sobrediagnostico de FAA estreptococica, con la consiguiente prescripcion innecesaria de antibioticos, muchas veces de amplio espectro. Asi, con el manejo de las escalas y la tecnica de diagnostico rapido, elaboramos los algoritmos de manejo de la FAA. Los objetivos del tratamiento son acelerar la resolucion de los sintomas, reducir el tiempo de contagio y prevenir las complicaciones supurativas locales y no supurativas. Los antibioticos de eleccion para el tratamiento de la FAA estreptococica son penicilina y amoxicilina. La asociacion de amoxicilina y clavulanico no esta indicada en el tratamiento inicial en la infeccion aguda. Los macrolidos tampoco son un tratamiento de primera eleccion; su uso debe reservarse para pacientes con alergia a la penicilina. Es importante en nuestro pais adecuar tanto el diagnostico de la FAA bacteriana y la prescripcion de antibioticos a la evidencia cientifica disponible. La implantacion de protocolos de actuacion en las farmacias comunitarias puede ser de utilidad para identificar y cribar los casos que no requieran tratamiento antibiotico. EnglishThe acute pharyngotonsillitis (APT) in adults is one the most common infectious diseases in the family physician’s surgery. The most frequent etiology is viral. Within the bacterial etiology, the main agent responsible is Streptococcus pyogenes or streptococcus β-GROUP A hemolytic (EBHGA), causing 5-30% of cases. In the diagnostic management, to predict the possible bacterial etiology, clinical evaluation scales are a good help for selecting which patients should undergo quick detection techniques for the streptococcic antigen. It is known that, in general, without these techniques streptococcic APT tends to be overdiagnosed, with the ensuing unnecessary prescription for antibiotics, often broad-spectrum. Thus, with the management of the steps and the quick diagnosis technique, we can draw up algorithms for managing APT. The objectives of the treatment are to accelerate the resolution of symptoms, reduce contagion time and prevent local suppurative and non-suppurative complications. The antibiotics of choice for treating streptococcic APT are penicillin and amoxicillin. The combination of amoxicillin and clavulanic acid is not indicated for the initial treatment of acute infection. Macrolides are not a first-choice treatment either; their use must be reserved for patients with allergy to penicillin. In our country it is important to adapt both the diagnosis of bacterial APT and the prescription of antibiotics to the scientific evidence available. The implementation of protocols of action in community pharmacies may be of use in identifying and screening cases that do not require antibiotic treatment.

Anaplastic Thyroid Carcinoma (ATC) is one of the most lethal tumours in humans, extremely rare in occurrence and very aggressive in nature. We hereby present a rare case of ATC with airway compromise. A 66-year-old male, presented complaining of a non-tender anterior neck mass rapidly increasing in size associated with dry cough, hoarseness and voice changes. Imaging studies revealed a large heterogeneous centrally necrotic lobulated left thyroid mass with metastatic lymph nodes and rightward tracheal deviation. Core biopsy and immunohistochemistry stains revealed a profile consistent with ATC. Patient's airway was compromised. Options for treatment and prognosis were discussed. Patient was discharged home with home hospice. A high index of suspicion for ATC is necessary in patients presenting with a rapidly enlarging neck mass. A prompt cytologic evaluation with metastatic work up is important to establish diagnosis. Due to its poor prognosis, an honest discussion regarding end-of-life issues must be initiated at diagnosis. Novel therapies toward genetic and epigenetic pathways have been developed, which is the basis of current clinical trials that are intended to improve clinical outcomes in the coming years.

Background The aim of this study was to explore whether interactions between FTO rs9939609 and ABCA1 rs9282541 affect BMI and waist circumference (WC), and could explain previously reported population differences in FTO-obesity and FTO-BMI associations in the Mexican and European populations. Methods A total of 3938 adults and 636 school-aged children from Central Mexico were genotyped for both polymorphisms. Subcutaneous and visceral adipose tissue biopsies from 22 class III obesity patients were analyzed for FTO and ABCA1 mRNA expression. Generalized linear models were used to test for associations and gene-gene interactions affecting BMI, WC and FTO expression. Results FTO and ABCA1 risk alleles were not individually associated with higher BMI or WC. However, in the absence of the ABCA1 risk allele, the FTO risk variant was significantly associated with higher BMI (P = 0.043) and marginally associated with higher WC (P = 0.067), as reported in Europeans. The gene-gene interaction affecting BMI and WC was statistically significant only in adults. FTO mRNA expression in subcutaneous abdominal adipose tissue according to ABCA1 genotype was consistent with these findings. Conclusions This is the first report showing evidence of FTO and ABCA1 gene variant interactions affecting BMI, which may explain previously reported population differences. Further studies are needed to confirm this interaction. Electronic supplementary material The online version of this article (doi:10.1186/s12881-017-0410-y) contains supplementary material, which is available to authorized users.

Vegetation cover plays a major role in the restoration and stabilization of disturbed systems. The analysis of relationships between restored vegetation and soil hydrology has special relevance for the evaluation and operation of mining reclamation, particularly in Mediterranean-Continental environments, where climatic conditions restrict the development of continuous vegetation cover. The effect of herbaceous vegetation cover on soil hydrology was analysed by means of rainfall simulation (63 mm h − 1 ; 0.24 m 2 ) in reclaimed soils derived from opencast coal mining (a non-saline and clay-loam textured spoil) in central-eastern Spain. A total of 75 simulation experiments were conducted at three different times throughout the year (late winter, summer and autumn) to control the influence of seasonal climatic fluctuations. Sediment concentrations in runoff and the runoff coefficient decreased exponentially with vegetation cover, while increases in steady infiltration rates were obtained with vegetation cover. Additional delays in runoff responses (longer time to runoff start and stabilization) and increases in the wetting front depth were observed with vegetation cover. Seasonal variations in soil surface state and moisture strongly influenced hydrological responses; although the influence of season on the analysed hydrological responses was attenuated by vegetation cover, especially in the case of infiltration rates. We also determined a practical ground cover threshold for site restoration and evaluation of over 50% vegetation cover, which could help achieve an optimum biological control of hydrological soil responses in the studied environment.

This article contains a review of the most important developments in clinical arrhythmology and interventional cardiac electrophysiology that have been reported during the past year. Special emphasis has been placed on clinical conditions that are most prevalent in the general population as well as on progress that has been achieved using the main therapeutic approaches, whether pharmacologic or interventional.

Los pacientes con desfibrilador automatico implantable (DAI) constituyen una poblacion en riesgo de presentar alteraciones psicologicas y una peor calidad de vida. Sin embargo, datos derivados de la mayoria de los grandes ensayos clinicos aleatorios con DAI ponen de manifiesto que el efecto del dispositivo sobre la calidad de vida es beneficioso o neutro. El principal predictor de empeoramiento de la calidad de vida y ajuste psicologico al DAI, tras el implante, es el numero de descargas del dispositivo. Otros predictores son la juventud, los antecedentes de trastornos de ansiedad o depresion, y el escaso apoyo social o familiar. En la mayor parte de los estudios se han realizado evaluaciones de la calidad de vida a corto plazo y se desconoce si esta puede cambiar a mas largo plazo. Ademas, hay menos informacion sobre la calidad de vida en pacientes con indicacion de DAI como prevencion primaria. Disponemos de diversos recursos para ayudar al paciente en el proceso de adaptacion a la vida con DAI. Una adecuada programacion de los criterios de deteccion y las terapias de estimulacion antitaquicardia reducira significativamente el numero de descargas y hara menos probable el deterioro de la calidad de vida. En pacientes que han experimentado una reduccion en esta tras el implante de DAI, diversas terapias psicologicas, tanto farmacologicas como de intervencion psicoterapeutica, han demostrado ser eficaces en la mejoria de la calidad de vida.

Background The electronic nose (e-nose) detects volatile organic compounds (VOCs) in exhaled air. We hypothesized that the exhaled VOCs print is different in stable vs. exacerbated patients with chronic obstructive pulmonary disease (COPD), particularly if the latter is associated with airway bacterial infection, and that the e-nose can distinguish them. Methods Smell-prints of the bacteria most commonly involved in exacerbations of COPD (ECOPD) were identified in vitro. Subsequently, we tested our hypothesis in 93 patients with ECOPD, 19 of them with pneumonia, 50 with stable COPD and 30 healthy controls in a cross-sectional case-controlled study. Secondly, ECOPD patients were re-studied after 2 months if clinically stable. Exhaled air was collected within a Tedlar bag and processed by a Cynarose 320 e-nose. Breath-prints were analyzed by Linear Discriminant Analysis (LDA) with One Out technique and Sensor logic Relations (SLR). Sputum samples were collected for culture. Results ECOPD with evidence of infection were significantly distinguishable from non-infected ECOPD (p = 0.018), with better accuracy when ECOPD was associated to pneumonia. The same patients with ECOPD were significantly distinguishable from stable COPD during follow-up (p = 0.018), unless the patient was colonized. Additionally, breath-prints from COPD patients were significantly distinguished from healthy controls. Various bacteria species were identified in culture but the e-nose was unable to identify accurately the bacteria smell-print in infected patients. Conclusion E-nose can identify ECOPD, especially if associated with airway bacterial infection or pneumonia., This project was supported by the Instituto de Salud Carlos III (FIS PI12/02628) and the Spanish Respiratory Society. The funding sources were used to cover fungible expenses and had no influence on the results.

Cardiac electrophysiology laboratories deal with a wide range of pathological conditions, diagnostic techniques, and treatments. Since a huge quantity of material has been published in recent months, this article will be limited to discussion of the most significant developments in the prognostic evaluation of arrhythmias, hereditary disease, syncope, atrial fibrillation, implantable cardioverter-defibrillators, cardiac resynchronization therapy, and catheter ablation. Even within these areas, discussion will be restricted to specific concrete topics and to a limited number of publications that were judged to have important implications for clinical practice. Our principal aim was to provide clinical cardiologists with an overview of the latest developments in cardiac electrophysiology.

7537 Background: Follicular lymphoma (FL) is an incurable malignancy with patients (pts) ultimately relapsing following standard therapies. Active immunotherapy has the potential to induce life-long host anti-tumor immunity and disease control. G100 consists of glucopyranosyl lipid-A (GLA), a TLR-4 agonist in a specific formulation. Preclinically, G100 activates dendritic cells, T cells and NK cells, and triggers systemic anti-tumor immunity. In Merkel Cell carcinoma pts, G100 administered intratumorally (IT) induced tumor inflammation and responses including a CR after G100 alone. This is the first study of G100 IT in pts with NHL. Methods: Previously treated or naïve pts with FL with an injectable tumor site and distal sites of disease were eligible. In Part 1, G100 cohorts of 5 or 10µg were enrolled in a 3+3 design, followed by a large tumor ( > 4cm) cohort at 20µg. Pts received 6-9 doses of G100 IT ~qwk after radiation (RT, 2 Gy x2 doses) to the lesion. A 2nd course of G100 could be given without RT to an additional site. Results: As of 31Dec16, all 9 pts in Part 1 dose escalation (3 pts each at 5, 10, or 20 µg/dose) were evaluable for safety and efficacy. An additional 13 pts at 10µg/dose were included in the safety analysis only. No G100-related DLTs or SAEs were observed at any dose level. Of 22 safety pts, all G100 related AEs were grade 1/2 and none occurred in > 2 pts. Tumor biopsies following G100 demonstrated diffuse infiltration of CD8+ T cells in 5/5 pts and T cell repertoire analyses indicated an increased frequency of clonal tumor infiltrating lymphocytes (TILs). Best responses include: 4 PRs (45%), 3 SDs (33%) and 2 pending (22%). Of the 4 PR pts, tumor regression ranged 58-89% including up to 56% shrinkage of abscopal (distal) sites. Conclusions: G100 IT was safe, well-tolerated, induced CD8+ T cell infiltration and expansion of TIL clones. G100/RT treated and abscopal lesion regressions were observed signifying the induction or boosting of systemic anti-tumor immunity. The induction of immune responses, favorable safety profile and clinical activity indicate that G100 IT is an active agent that warrants further investigation. Part 2 enrollment continues with randomization to G100/RT ± pembrolizumab. Clinical trial information: NCT02501473.

TPS1118 Background: Antiestrogen therapy, including AI, is standard for ER+ tumors in the adjuvant and metastatic setting; however, resistance is common. These tumors may respond to alternative second-line anti-estrogen therapies such as fulvestrant but response durations are often short. Preclinical and clinical studies suggest that simultaneous inhibition of ER and PI3K/mTOR could prevent/delay the emergence of hormone-independent cancer cells, thereby improving patient (pt) outcomes. This study will test whether fulvestrant plus TAK-228, a dual TORC1/2 inhibitor, can overcome endocrine therapy resistance in ER+ mBC. This is an open-label, randomized, phase 2 study of continuous once-daily TAK-228 (4 mg) or once-weekly TAK-228 (30 mg) plus fulvestrant (per label), vs fulvestrant alone, in pts with ER+/HER2– advanced or mBC that has progressed during/after AI therapy (EudraCT 2015-003612-20). Methods: 153 pts will be randomized 1:1:1 and stratified (presence or absence of visceral metastasis, prior hormonal therapy sensitivity, and prior exposure to CDK 4/6 inhibitors). Pts will receive study drug(s) until progressive disease (PD), unacceptable toxicity, or consent withdrawal. Pts with histological confirmation of ER+/HER2– advanced or mBC with measureable disease, ECOG 0–1, PD during/after prior AI therapy (progression ≤12 mos after discontinuation of adjuvant therapy or ≤1 mo after discontinuation in the metastatic setting) and adequate organ function, but not prior therapy with mTOR, PI3K, dual PI3K-mTOR or AKT inhibitors, or fulvestrant, > 1 prior line of chemotherapy for mBC or recurrent or progressive disease on > 2 endocrine therapies for mBC are eligible. This study aims to determine the efficacy (primary endpoint: PFS; secondary endpoints: OS, TTP, ORR), safety and tolerability of TAK-228 plus fulvestrant vs fulvestrant alone. The primary hypothesis (TAK-228 plus fulvestrant can improve median PFS to 8 mos [hazard ratio, HR 0.5] vs fulvestrant-alone median PFS of 4 mos) is to be tested at the 0.10 significance level (2-sided; dropout rate 10%). To date, 24 pts have been enrolled. Clinical trial information: EudraCT 2015-003612-20.

Background: Airway bacterial colonization by potentially pathogenic microorganisms occurs in a proportion of patients with Chronic Obstructive Pulmonary Disease (COPD). It increases airway inflammation and influences outcomes negatively. Yet, its diagnosis in clinical practice is not straightforward. The electronic nose is a new non-invasive technology capable of distinguishing volatile organic compound (VOC) breath-prints in exhaled breath. We aim to explore if an electronic nose can reliably discriminate COPD patients with and without airway bacterial colonization. Methods: We studied 37 clinically stable COPD patients (67.8 +/- 5.2 yrs, FEV1 41 +/- 10% ref.) and 13 healthy controls (62.8 +/- 5.2 yrs, FEV1 99 +/- 10% ref.). The presence of potentially pathogenic microorganisms in the airways of COPD patients (n = 10, 27%) was determined using quantitative bacterial cultures of protected specimen brush. VOCs breath-prints were analyzed by discriminant analysis on principal component reduction, resulting in cross-validated accuracy values. Area Under Receiver Operating Characteristics (AUROC) was calculated using multiple logistic regression. Results: Demographic, functional and clinical characteristics were similar in colonized and non-colonized COPD patients but their VOC breath-prints were different (accuracy 89%, AUROC 0.92, p > 0.0001). Likewise, VOCs breath-prints from colonized (accuracy 88%, AUROC 0.98, p < 0.0001) and non-colonized COPD patients (accuracy 83%, AUROC 0.93, p < 0.0001) were also different from controls. Conclusions: An electronic nose can identify the presence of airway bacterial colonization in clinically stable patients with COPD. (C) 2014 Elsevier Ltd. All rights reserved.

Radiofrequency catheter ablation has become a first line therapy for several types of tachycardias because of its high efficacy and low complication rate. The development of proarrhythmic complications due to a direct effect of radiofrequency is very unusual. We describe a patient with previous myocardial infarction and well tolerated sustained monomorphic ventricular tachycardia who underwent catheter ablation of the tachycardia substrate. During two of the radiofrequency applications, ventricular fibrillation developed and external defibrillation was required.

Radiofrequency catheter ablation is a first line therapy for many supraventricular and some ventricular tachycardias due to a high success rate and a low probability of complications. Although the majority of them are related to the catheterization technique, some are due to a direct effect of radiofrequency application. We report a patient with a nonsustained, repetitive, monomorphic ventricular arrhythmia that presented, after a successful radiofrequency ablation, an incessant sustained monomorphic ventricular tachycardia requiring a new ablation procedure.

A patient with a complex congenital abnormality required the implantation of an interatrial septum patch through a right lateral atriotomy. Nine years later he developed two different morphologies of an incessant uncommon atrial flutter refractory to antiarrhythmic drug treatment. The electrophysiological study localized a site on the right atrium lateral wall where local activation time was 75 ms earlier than the onset of the P wave, transient entrainment with concealed fusion was obtained, the first postpacing interval after transient entrainment was 5 ms longer than tachycardia cycle length and the stimulus to P wave interval was 50 ms. At this site, radiofrequency delivery terminated the atrial flutter in less than 1 second. No further induction or recurrences of any morphology of the atrial flutter were observed after a four month follow up. These findings suggest the existence of a narrow conduction isthmus amenable to interruption by focal delivery of radiofrequency. The isthmus was most probably located between the atriotomy and the crista terminalis, posterior to the former and anterior to the latter.

Although atrial fibrillation is usually caused by multiple circulating reentrant wavelets, a focal origin has recently been reported. This focal source could be successfully treated by discrete radiofrequency catheter ablation. We report a patient without structural heart disease, but with multiple episodes of palpitations related to atrial premature beats, irregular atrial tachycardia and atrial fibrillation. The electrophysiological study demonstrated that all the atrial arrhythmias were due to the same focus firing irregularly and exhibiting a unique and centrifugal pattern of activation. Successful radiofrequency catheter ablation of the focus was performed, without complications. After three months follow-up the patient is asymptomatic and she has not presented arrhythmia recurrences.

Radiofrequency catheter ablation has recently emerged as a therapeutic option for ventricular tachycardia in postinfarction patients. However, the indications for its use and the mapping procedure remain controversial. The most common arrhythmogenic circuit found fits an "8" shape model. This model incorporates a slow conducting central area, separated from the surrounding myocardium by conduction blocking areas and with entrance and exit sites. This circuit has classically been confined in the left ventricle. However, recently successful radiofrequency catheter ablation of ventricular tachycardia has been reported from the right ventricle. Several markers for adequate positioning of the ablation catheter have been reported: local presystolic activity, isolated mid diastolic potential, transient entrainment with concealed fusion, match between electrogram-QRS and stimulus-QRS intervals, match between first postpacing interval and tachycardia cycle length and tachycardia electrocardiographic reproduction by pace-mapping. Procedure related complications are rare and the success rate is around 70%. Nevertheless, currently this technique should be limited to postinfarction patients with ventricular tachycardia meeting certain requisites.

Introduccion En los ultimos anos se ha descritola ablacion con cateter mediante radiofrecuenciade taquicardias auriculares guiada mediante cartografiade activacion bipolar. Este trabajo describelos resultados de nuestro centro con esta tecnicautilizando simultaneamente cartografia de activacionbipolar y unipolar. Metodos Se seleccionaron para ablacion con catetermediante radiofrecuencia 9 pacientes (7 varonesy 2 mujeres, edad media 37,2 ± 24,1 anos)con taquicardia auricular. El procedimiento se guiomediante cartografia de activacion bipolar y unipolar,analizandose el tiempo de activacion electricalocal y la morfologia de los electrogramas unipolares. Resultados La ablacion se realizo con exitoen 7 pacientes (78%) con una media de 6,8 ± 3,1aplicaciones de radiofrecuencia. Ningun pacientepresento complicaciones ni recurrencias en el seguimiento.La actividad electrica bipolar fue significativamentemas precoz en las posiciones de liberacionde radiofrecuencia eficaz que en las deliberacion ineficaz (–30 ± 21,1 ms frente a –18,3 ±20,6 ms; p = 0,01), no observandose sin embargo diferenciasen el tiempo de activacion local unipolar(–22,5 ± 26,2 ms frente a –19,8 ± 21,5 ms; p = 0,56).El analisis de la morfologia del electrograma unipolarno permitio la discriminacion precisa delpunto de ablacion definitiva, dado que se encontroun patron «QS» en 21 posiciones de fracaso y en 2de eficacia definitiva. Por ultimo, se encontro unapendiente rapida de caida de la deflexion negativadel electrograma unipolar en 2 de las 45 posicionesde fracaso y en 3 de las 6 de eficacia definitiva. Conclusiones La ablacion con cateter medianteradiofrecuencia de taquicardias auriculares se puederealizar en un alto porcentaje de pacientes sincomplicaciones. La cartografia de activacion bipolarlocaliza adecuadamente la posicion de liberacionde radiofrecuencia eficaz. El registro de unelectrograma unipolar de morfologia tipo «QS» noparece ser predictivo de exito.

The R230C variant of the ATP-binding cassette transporter A1 (ABCA1) gene has been consistently associated with decreased HDL-cholesterol (HDL-C) concentrations in several studies in the Mexican mestizo population. However, information on how diet composition modifies the effect of the ABCA1-R230C variant on HDL-C concentrations is very scarce. The aim of the present study was to analyze whether the effect of ABCA1-R230C on HDL-C concentrations is modulated by dietary factors in a nationwide population sample of 3591 adults from the National Health and Nutrition Survey conducted by the State’s Employees’ Social Security and Social Services Institute. All participants answered a validated questionnaire to assess health status and weekly food consumption. Fasting blood samples were drawn for biochemical analysis and DNA extraction, and the ABCA1-R230C variant was genotyped using TaqMan assays. Statistical analyses consisted of simple linear and multiple regression modeling adjusting for age, BMI, smoking, and alcohol consumption. The overall C risk allele frequency was 9.3% and the variant was significantly associated with low HDL-C concentrations in both sexes. A significant negative correlation between carbohydrate consumption and HDL-C concentrations was observed in women bearing the R230C variant (P = 0.021) and a significant gene-diet interaction was found only in premenopausal women (P = 0.037). In conclusion, the effect of the ABCA1-R230C gene variant on HDL-C concentrations is modulated by carbohydrate intake in premenopausal women. This finding may help design optimized dietary interventions according to sex and ABCA1-R230C genotype. J. Nutr. doi: 10.3945/jn.111.152421.

We report a case of a 58-year-old woman with rheumatic mitral stenosis scheduled for percutaneous valvuloplasty. Prior left and right ventricular angiograms showed multiple diverticula at left ventricular apical and diaphragmatic walls and right ventricular diaphragmatic wall. Chest x-ray and echocardiogram were normal. Magnetic resonance imaging was concordant with catheterization findings and ruled out other cardiac malformations. The risk of ventricular perforation changed our indication of percutaneous valvuloplasty in favor of open heart commissurotomy.

e11583 Background: The CONFIRM study showed greater efficacy of F500 as compared to F250.Based on these results a dosage change was authorized in Spain.The aim of this study is to describe the efficacy of F500 (progression free survival(PFS) and clinical benefit rate(CBR) in Spanish patients (P) with estrogen receptor (ER+) Metastatic Breast Cancer (MBC) through a retrospective data collection. Methods: After written informed consent, data collection was recorded from clinical records of P who previously had progressed on hormonal treatment and who received at any time F 500 from 1st January 2010 to 31st October 2011. Results: 102 P in 14 centers were included in the study, 93 P were evaluable.Median age was 65 (39-88). Histology: 80.6% ductal ;15% lobulillar. Hormonal receptors: ER+/ PgR+ 77.4%; ER+/PgR- 21.6 %. HER2 status was documented in 80P, 15% of them were HER2+. 45.4% were Ki67 +. Mean from diagnosis to metastatic disease:3.7 years, 19.3% of P had de novo metastatic disease. 21.5% of P had visceral metastases.82.8% of P had good PS (0-1) when F started.F received as 1st line in 7.5%, as 2nd line in 52.7% and 3rdor more in 39.8% of the P. Average cycles administered: 10(3-48). With a median follow up of 16 months (m) since F treatment (1.4-34.4), median PFS was 10.6 m[8.3-13.0]. CBR was 59.1% (12.9%CR, 12.9 PR and 33.3% SD≥ 24 weeks). Median PFS in P with or without CB was 23.3 m and 5.6 m respectively. Median PFS in P with F in 1 st line was 10.3 m, 11.6 m in 2nd line and 9 m in 3rd line or more. No significant differences in CBR were observed between P with or without visceral metastases (58.9 vs 60%). There was a trend in the CBR between HER –ve and +ve groups (64.7% vs 33.3% p = 0.0565). 1-year survival rate was 86% (77.3-92.3). Median Overall Survival was not calculated because only 20 P had died when data were analyzed. More frequent toxicities were: local injection site pain (11.8%), hot flushes (11.8%) and gastrointestinal disorders (8.6%). Conclusions: F500 in real life setting showed a PFS of 10.6 m and got CB in 2/3 of P with a good toxicity profile, in line with phase III trials. In P who achieve a CB the median PFS was almost two years. P with visceral metastases may benefit from F same as those with non visceral involvement.

Desde el primer implante en humanos en el ano 1980, la tecnologia de los desfibriladores automaticos implantables ha mejorado considerablemente y el numero de implantes sigue creciendo cada ano. Los desfibriladores automaticos implantables que utilizan cable endocardico y choques bifasicos son actualmente los dispositivos de eleccion y son suficientes en casi el 100% de los pacientes. Este documento revisa las recomendaciones para la cualificacion del personal y de los centros que implantan y realizan seguimientos de los desfibriladores automaticos implantables. Tambien se actualizan las indicaciones para la utilizacion del desfibrilador automatico implantable.

Two steroidal ene lactams, N-methyl-4-aza-5-androsten-3,17-dione and N-methyl-6-methoxy-4-aza-5-androsten-3,17-dione, and an enamine, N-methyl-4-aza-5-androsten-17β-ol, have been synthetized and their sensitized photooxygenations were investigated. The two ene lactams yield fragmentation compounds via the corresponding dioxetanes. Comparison with the previously reported behavior of an analogous N-unsubstituted ene lactam, seems to indicate that N-substitution is essential for the fragmentation to take place. On the other hand, the enamine yields a ketol. All results are briefly discussed from the mechanistic point of view.