A phase I trial of LXS196, a protein kinase C (PKC) inhibitor, for metastatic uveal melanoma.

BACKGROUND: Up to 50% of patients with uveal melanoma develop metastases (MUM) with a poor prognosis and median overall survival of approximately 1 year. METHODS: This phase I study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the oral protein kinase C inhibitor LXS196 in 68 patients with MUM (NCT02601378). Patients received LXS196 doses ranging from 100-1000 mg once daily (QD; n = 38) and 200-400 mg twice daily (BID; n = 30). RESULTS: First cycle dose-limiting toxicities (DLTs) were observed in 7/38 (18.4%) QD and 2/17 (11.8%) BID patients. Hypotension was the most common DLT, occurring at doses ≥500 mg/day, and manageable with LXS196 interruption and dose reduction. Median duration of exposure to LXS196 was 3.71 months (range: 1.81-15.28) for QD and 4.6 months (range: 0.33-58.32) for BID dosing. Clinical activity was observed in 6/66 (9.1%) evaluable patients achieving response (CR/PR), with a median duration of response of 10.15 months (range: 2.99-41.95); 45/66 had stable disease (SD) per RECIST v1.1. At 300 mg BID, the recommended dose for expansion, 2/18 (11.1%) evaluable patients achieved PR and 12/18 (66.7%) had SD. CONCLUSION: These results suggest manageable toxicity and encouraging clinical activity of single-agent LXS196 in patients with MUM.

Single-agent anti-PD-1 or combined with ipilimumab in patients with mucosal melanoma: an international, retrospective, cohort study.

BACKGROUND: Mucosal melanoma (MM) is a rare melanoma subtype with distinct biology and poor prognosis. Data on the efficacy of immune checkpoint inhibitors (ICIs) are limited. We determined the efficacy of ICIs in MM, analyzed by primary site and ethnicity/race. PATIENTS AND METHODS: A retrospective cohort study from 25 cancer centers in Australia, Europe, USA and Asia was carried out. Patients with histologically confirmed MM were treated with anti-programmed cell death protein 1 (PD-1) ± ipilimumab. Primary endpoints were response rate (RR), progression-free survival (PFS), overall survival (OS) by primary site (naso-oral, urogenital, anorectal, other), ethnicity/race (Caucasian, Asian, Other) and treatment. Univariate and multivariate Cox proportional hazards model analyses were conducted. RESULTS: In total, 545 patients were included: 331 (63%) Caucasian, 176 (33%) Asian and 20 (4%) Other. Primary sites included 113 (21%) anorectal, 178 (32%) urogenital, 206 (38%) naso-oral and 45 (8%) other. Three hundred and forty-eight (64%) patients received anti-PD-1 and 197 (36%) anti-PD-1/ipilimumab. RR, PFS and OS did not differ by primary site, ethnicity/race or treatment. RR for naso-oral was numerically higher for anti-PD-1/ipilimumab [40%, 95% confidence interval (CI) 29% to 54%] compared with anti-PD-1 (29%, 95% CI 21% to 37%). Thirty-five percent of patients who initially responded progressed. The median duration of response (mDoR) was 26 months (95% CI 18 months-not reached). Factors associated with short PFS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3 (P < 0.01), lactate dehydrogenase (LDH) more than the upper limit of normal (ULN) (P = 0.01), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). Factors associated with short OS were ECOG PS ≥1 (P < 0.01), LDH >ULN (P = 0.03), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). CONCLUSIONS: MM has poor prognosis. Treatment efficacy of anti-PD-1 ± ipilimumab was similar and did not differ by ethnicity/race. Naso-oral primaries had numerically higher response to anti-PD-1/ipilimumab, without difference in survival. The addition of ipilimumab did not show greater benefit over anti-PD-1 for other primary sites. In responders, mDoR was short and acquired resistance was common. Other factors, including site and number of metastases, were associated with survival.

Factores de riesgo y protección del estrés traumático secundario en los cuidados intensivos: un estudio exploratorio en un hospital terciario de Madrid / Risk and protective factors of secondary traumatic stress in Intensive Care Units: An exploratory study in a hospital in Madrid (Spain)

OBJETIVO: Proponer un modelo de predictores del estrés traumático secundario. DISEÑO: Se trata de un diseño transversal descriptivo. Ámbito: El estudio se llevó a cabo en las unidades de cuidados intensivos de un hospital terciario de Madrid. PARTICIPANTES: La muestra estuvo formada por 103 profesionales sanitarios. INTERVENCIONES: Se creó una batería de cuestionarios que fue rellenada por los profesionales. Respecto al análisis de datos, se utilizó una metodología de redes y análisis de regresión jerárquica. Variables de interés: Se evaluaron variables sociodemográficas tales como género, años de experiencia y puesto, el estrés traumático secundario, la pasión por el trabajo, los estresores laborales, el esfuerzo emocional, la empatía, la autocompasión. RESULTADOS: Se establece: a) para la fatiga por compasión, los años de experiencia como factor de riesgo (β = 0,224 y p = 0,029) y la pasión armoniosa como protector (β = −0,363 y p = 0,001); b) para la sacudida de creencias, el esfuerzo emocional y la empatía como factores de riesgo (β = 0,304 y p = 0,004; β = 0,394 y p = 0,000, respectivamente) y c) para la sintomatología, los estresores laborales y la empatía como factores de riesgo (β = 0,189 y p = 0,039; β = 0,395 y p = 0,000, respectivamente) y los años de experiencia como protector (β = −0,266 y p = 0,002). CONCLUSIONES: Este modelo predictivo del estrés traumático secundario asienta factores protectores que podrían aumentarse, como la pasión armoniosa, y factores de riesgo que sería conveniente reducir, como la empatía y el esfuerzo emocional, con el fin de mejorar la calidad asistencial y de vida de los profesionales

AIM: To propose a predictive model of secondary traumatic stress. DESIGN: A descriptive cross-sectional study was carried out. Context: The study was conducted in the Intensive Care Units of a hospital in Madrid (Spain). PARTICIPANTS: The sample comprised 103 health professionals. INTERVENTIONS: A series of questionnaires were created and completed by the participants. Network analysis and multiple regression were used for data analysis. Variables of interest: Sociodemographic variables such as gender, years of experience and position, secondary traumatic stress, passion for work, work stressors, emotional effort, empathy and self-compassion were evaluated. RESULTS: The result identified the following: a) years of experience as a risk factor for compassion fatigue (β=0.224 and P=0.029), and harmonious passion as a protector (β=−0.363 and P=0.001); b) emotional effort and empathy as risk factors for shattered assumptions (β=0.304 and P=0.004; β=0.394 and P=0.000, respectively); and c), work stressors and empathy as risk factors for symptomatology (β=0.189 and P=0.039; β=0.395 and P=0.000, respectively), and years of experience as a protector (β=−0.266 and P=0.002). CONCLUSIONS: This predictive model of secondary traumatic stress identifies protective factors which could be reinforced, such as harmonious passion, and risk factors which should be reduced, such as empathy and emotional effort, with a view to promoting quality of care and quality of life among these professionals

Risk and protective factors of secondary traumatic stress in Intensive Care Units: An exploratory study in a hospital in Madrid (Spain). / Factores de riesgo y protección del estrés traumático secundario en los cuidados intensivos: un estudio exploratorio en un hospital terciario de Madrid.

AIM: To propose a predictive model of secondary traumatic stress. DESIGN: A descriptive cross-sectional study was carried out. CONTEXT: The study was conducted in the Intensive Care Units of a hospital in Madrid (Spain). PARTICIPANTS: The sample comprised 103 health professionals. INTERVENTIONS: A series of questionnaires were created and completed by the participants. Network analysis and multiple regression were used for data analysis. VARIABLES OF INTEREST: Sociodemographic variables such as gender, years of experience and position, secondary traumatic stress, passion for work, work stressors, emotional effort, empathy and self-compassion were evaluated. RESULTS: The result identified the following: a) years of experience as a risk factor for compassion fatigue (ß=0.224 and P=0.029), and harmonious passion as a protector (ß=-0.363 and P=0.001); b) emotional effort and empathy as risk factors for shattered assumptions (ß=0.304 and P=0.004; ß=0.394 and P=0.000, respectively); and c), work stressors and empathy as risk factors for symptomatology (ß=0.189 and P=0.039; ß=0.395 and P=0.000, respectively), and years of experience as a protector (ß=-0.266 and P=0.002). CONCLUSIONS: This predictive model of secondary traumatic stress identifies protective factors which could be reinforced, such as harmonious passion, and risk factors which should be reduced, such as empathy and emotional effort, with a view to promoting quality of care and quality of life among these professionals.

Dual checkpoint inhibitor-associated eosinophilic enteritis.

BACKGROUND: Eosinophilia has been reported as a rare, new biological effect of immune checkpoint inhibition that may be associated with improved treatment response and the development of immune-related adverse events. CASE PRESENTATION: We report a case of dual checkpoint inhibitor-associated hypereosinophilia and eosinophilic enteritis in a patient with advanced cutaneous melanoma. Rapid resolution of peripheral eosinophilia and associated symptoms was achieved with steroids alone. CONCLUSIONS: Immune checkpoint inhibition can trigger inflammation in virtually any organ in the body, leading to diverse clinical manifestations. To our knowledge, this is the first case report of eosinophilic enteritis due to ipilimumab plus nivolumab.

Meta-analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an international rare cancers initiative (IRCI) ocular melanoma study.

BACKGROUND: Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) and overall survival (OS), we carried out a meta-analysis using individual patient level trial data. METHODS: Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated. RESULTS: OS data were available for 912 patients. The median PFS was 3.3 months (95% CI 2.9-3.6) and 6-month PFS rate was 27% (95% CI 24-30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3 cm versus <3 cm) to be substantially associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH and elevated ALP were substantially associated with shorter PFS. The most substantial factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2 months (95% CI 9.5-11.0) and 1 year OS was 43% (95% CI 40-47). The most substantial prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS. CONCLUSION: Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.

Situación de la ventilación mecánica domiciliaria en la Comunidad de Madrid, visión desde Castilla La Mancha / Situation of home mechanical ventilation in Madrid area, view from Castilla La Mancha

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Mental health, positive affectivity and wellbeing in prison: a comparative study between young and older prisoners.

OBJECTIVES: To explore sociodemographic, psychological and psychopathological characteristics, as well as to evaluate the behaviour in an inmate sample. MATERIALS AND METHODS: There is a total sample of 182 young and elderly inmates of the Madrid III Prison. The investigation has been carried out with a battery of self-report psychological questionnaires and objective measurements obtained through the prison files. Comparisons of means were made to see if there are significant differences between the two groups (young and elderly inmates) in the variables analysed. RESULTS: The analysis shows that there are no significant differences in wellbeing between young and elderly inmates. However, young people have higher levels of psychological distress, more presence of negative emotions and have a more maladjusted behaviour in prison (they consume more cannabis and have more disciplinary records). Older people better regulate their emotions, adopt better the perspectives of others, showing themselves to be friendlier. CONCLUSIONS: The elderly inmates in prison, compared with the youngest, have a better psychological adjustment, more internal resources and a better adaptation to the prison environment despite of no differences in related variables such as time in prison.

Trombectomía reolítica: una herramienta efectiva, versátil y segura / Rheolytic thrombectomy: An effective, versatile, and safe treatment

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Efficacy and safety of nilotinib in patients with KIT-mutated metastatic or inoperable melanoma: final results from the global, single-arm, phase II TEAM trial.

BACKGROUND: The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT-mutated advanced melanoma without prior KIT inhibitor treatment. PATIENTS AND METHODS: Forty-two patients with KIT-mutated advanced melanoma were enrolled and treated with nilotinib 400 mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients; the design was amended to a single-arm trial due to an observed low number of KIT-mutated melanomas. Thirteen patients were randomized to DTIC before the protocol amendment removing this study arm. The primary endpoint was objective response rate (ORR), determined according to Response Evaluation Criteria In Solid Tumors. RESULTS: ORR was 26.2% (n = 11/42; 95% CI, 13.9%-42.0%), sufficient to reject the null hypothesis (ORR ≤10%). All observed responses were partial responses (PRs; median response duration, 7.1 months). Twenty patients (47.6%) had stable disease and 10 (23.8%) had progressive disease; 1 (2.4%) response was unknown. Ten of the 11 responding patients had exon 11 mutations, four with an L576P mutation. The median progression-free survival and overall survival were 4.2 and 18.0 months, respectively. Three of the 13 patients on DTIC achieved a PR, and another patient had a PR following switch to nilotinib. CONCLUSION: Nilotinib activity in patients with advanced KIT-mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential activity, although the low patient number limits interpretation. Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01028222.

Protocolo SANTIAGO. Planificación reparación endovascular de aorta (EVAR) en situaciones de urgencia / SANTIAGO protocol. Endovascular aortic repair planning in emergency situations

INTRODUCCIÓN: La reparación endovascular de los aneurismas de la aorta abdominal (EVAR) con éxito precisa la previa realización de una medición anatómica precisa basada en el estudio angio-TC aórtica. En situaciones de urgencia el tiempo para medición y planificación del caso es limitado y la disponibilidad del estudio en formato DICOM no siempre es posible. OBJETIVO: Presentar un protocolo de planificación desarrollado en nuestro centro que permite reducir el tiempo necesario para realizar las medidas en terapia EVAR de aneurismas de aorta abdominal (AAA) rotos en situaciones de urgencia y describir los resultados de nuestro centro antes y después de la aplicación de este protocolo. MÉTODO: Presentamos un análisis descriptivo de morbimortalidad a 30 días y a un año basado en un registro prospectivo de todos los casos de rotura de AAA admitidos de modo consecutivo (n = 32) en el servicio de urgencias de un hospital nacional de referencia durante el periodo enero del 2013 a mayo del 2015 (28 meses). El protocolo SANTIAGO es un acrónimo que describe (en lengua inglesa) 8 pasos que deben ser siempre tenidos en cuenta para una planificación EVAR: S (Size the aneurysms), A (Access), N (Neck), T (bifurcaTion), I (Iliacs), A (Angulations), G (LenGth-LonGitud) y O (OK for material). En nuestro centro, la terapia EVAR en rotura aórtica se realiza bajo anestesia local y de modo percutáneo si la situación clínica del paciente lo permite. RESULTADOS: Tras la aplicación del protocolo SANTIAGO en nuestro centro, desde junio del 2014, se consiguió reducir la mortalidad en el tratamiento urgente de aneurismas aórticos infrarrenales rotos. Fueron desestimados para ningún tipo de intervención por su elevada morbimortalidad 3 pacientes de los 32 (9,3%) admitidos en urgencias. La mortalidad total a 30 días en pacientes tratados disminuyó del 46,6% (7/15) preprotocolo frente al 35,7%(5/14) posprotocolo y en pacientes intervenidos mediante técnica endovascular pasó del 25% (1/4) preprotocolo frente a un 0%(0/6) de mortalidad posprotocolo. El 66,6% (4/6) de los pacientes tratados mediante EVAR tras el implante del protocolo fueron intervenidos de modo percutáneo y bajo anestesia local. La mortalidad al año, registrada en mayo del 2016, fue en el grupo EVAR del 10% (1/10), tasa de reintervención al año del 7,1% (1/9) por endofuga tipo ib, resuelta con éxito. En el grupo de cirugía abierta la morbimortalidad a 12 meses fue del 63,15% (12/19) de los pacientes intervenidos, con registro de un fallecimiento por IAM 7 meses postintervención y sin datos de reintervenciones mayores al año. CONCLUSIONES: Basados en la mejora de resultados observada en nuestro centro, consideramos que la existencia de un protocolo de planificación EVAR permite una planificación esquemática y reproducible que optimiza el tiempo necesario para afrontar una situación de urgencia crítica y propicia el éxito de la reparación. Asimismo, existe la tendencia progresiva en nuestro centro a considerar el tratamiento EVAR como primera opción terapéutica para pacientes con AAA-r. La posibilidad de realizar esta técnica con anestesia local y abordaje percutáneo podría ser considerada como un factor independiente que condiciona la menor morbimortalidad global del procedimiento

INTRODUCTION: Successful endovascular treatment of ruptured abdominal aortic aneurysms (R-EVAR) requires a detailed planning of the procedure, as planning is the key step. Nevertheless, in cases of emergency the limited time for planning and the non-availability of good quality scan images (DICOM format) are common issues that determine the final result. OBJECTIVE: The aim of this paper is to present the results of r-AAA survival before and after a fast protocol was implemented in our centre for measuring and sizing r-EVAR in emergency situations. METHOD: Morbidity and mortality at 30 days and 1 year was prospectively recorded in all consecutive cases of r-AAA admitted to the emergency department of our hospital (n = 32) from January 2013 to May 2015 (28 months). The «SANTIAGO planning & sizing protocol» was implemented in June 2014. It is a fast method to remember key steps in planning EVAR. With the word SANTIAGO being a mnemonic device in which 8 basic and mandatory steps in planning can be summarised: S: Size, A: Access N: Neck, T: Bifurcation I: Iliacs, A: Angulations, G: Length, O: Ok for material. R-EVAR is performed in this centre under local anaesthesia and using a percutaneous approach, if the patient tolerates it, since June 2014. RESULTS: After implementation of the SANTIAGO protocol in June 2014, the 30 day mortality was reduced from 46.6% (7/15) to 35.7% (5/14) in all patients treated in our centre for a ruptured AAA. The mortality recorded in the endovascular group was 25% (1/4) pre-protocol and 0% (0/6) after in the period analysed. A percutaneous approach and local anaesthesia was used in 66% (4/6) patients in the EVAR Group after the protocol was implemented. The 1 year mortality was 10% for all patients treated in the R-EVAR group, with a secondary intervention rate of 7.1% (1/9) due to a type Ib endoleak. In the open repair group, the 1 year morbidity/mortality was 63.15% (12/19), with a patient death at 7 months due to a myocardial infarction. CONCLUSIONS: Our first results suggest that a fast protocol for planning and sizing in emergency situations seems to be associated with a lower 30 day mortality. A higher trend for considering the patient candidate for r-EVAR has been observed in our centre. Local anaesthesia and percutaneous approach have a probable influence on the lower morbidity and mortality of the endovascular cases

Proinflammatory environment and role of TNF-α in endometrial function of obese women having polycystic ovarian syndrome.

BACKGROUND/OBJECTIVES: A high percentage of women having polycystic ovarian syndrome (PCOS) exhibit hyperinsulinemia and obesity. Transforming necrosis factor-α (TNF-α) is an adipokine that increases in obesity and negatively affects insulin action in several tissues, including the endometrium. In fact, it has been reported that insulin signaling is altered in the endometrium of PCOS women, affecting its reproductive function. The aim of this study was to determine the proinflammatory environment and TNF-α signaling in endometrium from obese women with PCOS, and also to evaluate the effect of TNF-α on endometrial cell energy homeostasis. METHODS: Serum and endometrial tissues were obtained from four study groups: normal-weight, normal-weight-PCOS, obese and obese-PCOS (hyperandrogenemia/hyperinsulinemia) (n=7 per group). Serum TNF-α level was assayed by enzyme-linked immunosorbent assay (ELISA); endometrial TNF-α level and its receptors (TNFR1/TNFR2) as well as nuclear factor (NF)-κB content were determined by immunohistochemistry. Finally, we evaluated TNF-α effect on glucose uptake in cultured human endometrial stromal cells (T-HESC) treated or not with testosterone/insulin resembling partially the PCOS condition. RESULTS: TNF-α plasma levels were similar between groups, whereas cytokine levels and macrophage number increased in endometrium from obese-PCOS women (P<0.001). Both receptor types were higher in obese vs normal-weight women, particularly TNFR2 content in the obese-PCOS group (P<0.001). Furthermore, an increased NF-κB nuclear content in endometrium from obese-PCOS was observed (P<0.001). Finally, TNF-α treatment of T-HESC cultures exhibited a decrease of glucose uptake (P<0.05), although similar to cells treated with testosterone or testosterone/insulin/TNF-α. CONCLUSIONS: These results suggest that the PCOS condition induces an inflammatory state exacerbated when obesity is present, where a higher TNF-α signaling is observed, all of which could affect glucose uptake in the tissue and may cause fertility failures in these women.

Corrigendum to "Sarcoma Immunotherapy: Past Approaches and Future Directions".

[This corrects the article DOI: 10.1155/2014/391967.].

Association between Abnormal Electrocardiogram and Less Complex Heart Rate Variability Estimated by the Correlation Dimension / Asociación entre Electrocardiograma Anormal y Menor Complejidad de la Variabilidad de la Frecuencia Cardiaca Estimada Mediante la Dimensión de Correlación

Objective: To compare the correlation dimension (CD) of heart rate variability (HRV) in adults with and without abnormal electrocardiogram (ECG). Methods: A 24-hr Holter and a standard ECG were recorded from 100 university workers. After exclusion of 10 recordings with more than 5% of false RR intervals, a total of 90 subjects (age 46.2±8.7 years old, 45 were women) were included in the study. Two cardiologists classified 29 standard ECG as abnormal. CD was calculated from HRV time-series of 10,000 beats in the morning (from 11am), afternoon (from 5pm) and night (from 2am). Demographical characteristics were compared by ANOVA (considering ECG diagnosis and sex as independent factors) or by Fisher's exact test. Mean CD values were compared by analysis of variance considering as independent factors the ECG diagnosis, sex and time of day. Results: All demographical characteristics were similar except for a higher proportion of males with abnormal ECG (69%) than with normal ECG (41%). CD was not different with respect to the time of day, but it was higher in subjects with normal ECG (10.86 ± 2.41) than those with abnormal ECG (10.20 ± 2.48), and it was also higher in females than males: 11.04 ± 2.14 versus 10.63 ± 2.71 (normal ECG group), 10.84 ± 2.41 versus 9.92 ± 2.44 (abnormal ECG group). Conclusion: The finding of abnormal ECG is associated with HRV decreased complexity in adults.

Objetivo: Comparar la dimensión de correlación (DC) de la variabilidad de la frecuencia cardiaca (VFC) entre adultos con electrocardiograma (ECG) normal y anormal. Métodos: Se registró un Holter de 24 horas y un electrocardiograma (ECG) estándar de 100 trabajadores universitarios. Después de la exclusión de 10 registros con más de 5% de intervalos RR falsos, se incluyeron en el estudio a 90 sujetos (edad 46.2±8.7 años, 45 mujeres). Dos cardiólogos clasificaron 29 ECG estándar como anormales. La DC se calculó en series de tiempo de VFC de 10,000 latidos en la mañana (desde las 11:00), tarde (desde las 17:00) y noche (desde las 2:00). Las características demográficas fueron comparadas mediante análisis de varianza (considerando diagnóstico de ECG y sexo como factores independientes) o con prueba exacta de Fisher. Los valores promedio de DC fueron comparados con análisis de varianza considerando como factores independientes el diagnóstico de ECG, sexo y hora del día. Resultados: Las características demográficas fueron similares excepto por mayor proporción de hombres con ECG anormal (69%) que normal (41%). La DC no fue diferente con respecto a la hora del día, pero fue mayor en sujetos con ECG normal (10.86 ± 2.41) que con ECG anormal (10.20 ± 2.48), y también fue mayor en mujeres que en hombres: 11.04 ± 2.14 vs 10.63 ± 2.71 (grupo de ECG normal), 10.84 ± 2.41 vs 9.92 ± 2.44 (grupo de ECG anormal). Conclusión: El hallazgo de ECG anormal en adultos está asociado con menor complejidad de la VFC.

Sarcoma immunotherapy: past approaches and future directions.

Sarcomas are heterogeneous malignant tumors of mesenchymal origin characterized by more than 100 distinct subtypes. Unfortunately, 25-50% of patients treated with initial curative intent will develop metastatic disease. In the metastatic setting, chemotherapy rarely leads to complete and durable responses; therefore, there is a dire need for more effective therapies. Exploring immunotherapeutic strategies may be warranted. In the past, agents that stimulate the immune system such as interferon and interleukin-2 have been explored and there has been evidence of some clinical activity in selected patients. In addition, many cancer vaccines have been explored with suggestion of benefit in some patients. Building on the advancements made in other solid tumors as well as a better understanding of cancer immunology provides hope for the development of new and exciting therapies in the treatment of sarcoma. There remains promise with immunologic checkpoint blockade antibodies. Further, building on the success of autologous cell transfer in hematologic malignancies, designing chimeric antigen receptors that target antigens that are over-expressed in sarcoma provides a great deal of optimism. Exploring these avenues has the potential to make immunotherapy a real therapeutic option in this orphan disease.

High-risk features in radiation-associated breast angiosarcomas.

BACKGROUND: Radiation-associated breast angiosarcoma (RT-AS) is an uncommon malignancy with an incidence of less than 1 % of all soft tissue sarcomas. The overall prognosis is quite dismal with high rates of recurrences and poor overall survival. There is an obvious paucity of data regarding clinical outcomes of patients with breast RT-AS. METHODS: We identified all patients with RT-AS treated at the Memorial Sloan-Kettering Cancer Center between 1982-2011 and collected their correlative clinical information. RESULTS: We identified 79 women with RT-AS with a median age of 68 (range 36-87). The median interval between radiation and development of RT-AS was 7 years (range 3-19). The median time to local and distant recurrence was 1.29 years (95 % CI 0.72-NA) and 2.48 years (95 % CI 1.29-NA), respectively. The median disease-specific survival was 2.97 years (95 % CI 2.21-NA). Independent predictors of worse disease-specific survival included age 68 years (HR 3.11, 95 % CI 1.20-8.08, P=0.020) and deep tumors (HR 3.23, 95 % CI 1.02-10.21, P=0.046.) CONCLUSION: RT-AS has high local/distant recurrence rates, limited duration on standard chemotherapy and poor disease-specific survival.

Managing obesity in primary care practice: an overview with perspective from the POWER-UP study.

Primary care practitioners (PCPs) have been encouraged to screen all adults for obesity and to offer behavioral weight loss counseling to the affected individuals. However, there is limited research and guidance on how to provide such intervention in primary care settings. This led the National Heart, Lung and Blood Institute in 2005 to issue a request for applications to investigate the management of obesity in routine clinical care. Three institutions were funded under a cooperative agreement to undertake the practice-based opportunities for weight reduction (POWER) trials. The present article reviews selected randomized controlled trials, published before the initiation of POWER, and then provides a detailed overview of the rationale, methods and results of the POWER trial conducted at the University of Pennsylvania (POWER-UP). POWER-UP's findings are briefly compared with those from the two other POWER trials, conducted at Johns Hopkins University and Harvard University/Washington University. The methods of delivering behavioral weight loss counseling differed markedly across the three trials, as captured by an algorithm presented in the article. Delivery methods ranged from having medical assistants and PCPs from the practices provide counseling to using a commercially available call center, coordinated with an interactive website. Evaluation of the efficacy of primary care-based weight loss interventions must be considered in light of costs, as discussed in relation to the recent treatment model proposed by the Centers for Medicare and Medicaid Services.

Síndrome de apneas centrales del sueño, apneas complejas y tratamiento con servoventilación adaptativa, luces y sombras / No disponible

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Ipilimumab for metastatic melanoma.

Malignant melanoma is currently the fifth most common cancer in American men and the seventh most common in American women. Despite the advances made for early disease, the prognosis for metastatic melanoma is dismal, with an overall 5-year mortality rate of 90%. It is estimated that 8,000 Americans will die of melanoma in 2012. Recent advances in the understanding of the complex cellular interactions regulating cancer immunity have led to new strategies in the development of cancer immunotherapy. The discovery of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a negative regulator of immune activity, has led to the development of a monoclonal antibody, ipilimumab, that can abrogate immune suppression. Ipilimumab is the first immunotherapy approved by the FDA for patients with advanced melanoma based on the overall survival benefit in a phase III setting. It represents a paradigm shift in melanoma management with its success promoting the evaluation of monoclonal antibodies targeted against a number of other regulatory checkpoints in patients with advanced melanoma.