A lethal mitonuclear incompatibility in complex I of natural hybrids.

The evolution of reproductive barriers is the first step in the formation of new species and can help us understand the diversification of life on Earth. These reproductive barriers often take the form of hybrid incompatibilities, in which alleles derived from two different species no longer interact properly in hybrids1-3. Theory predicts that hybrid incompatibilities may be more likely to arise at rapidly evolving genes4-6 and that incompatibilities involving multiple genes should be common7,8, but there has been sparse empirical data to evaluate these predictions. Here we describe a mitonuclear incompatibility involving three genes whose protein products are in physical contact within respiratory complex I of naturally hybridizing swordtail fish species. Individuals homozygous for mismatched protein combinations do not complete embryonic development or die as juveniles, whereas those heterozygous for the incompatibility have reduced complex I function and unbalanced representation of parental alleles in the mitochondrial proteome. We find that the effects of different genetic interactions on survival are non-additive, highlighting subtle complexity in the genetic architecture of hybrid incompatibilities. Finally, we document the evolutionary history of the genes involved, showing signals of accelerated evolution and evidence that an incompatibility has been transferred between species via hybridization.

Sistema de Gestión Hospitalaria para la atención de la pareja infértil. Centro Territorial de Holguín, 2021

Introducción: La infertilidad es una enfermedad del sistema reproductivo que altera el equilibrio biológico, psicológico y social de las parejas. En Cuba existe un programa para el tratamiento de la pareja infértil y el Ministerio de Salud Pública incluye en sus directrices implementar las bases organizativas, sistema de trabajo, indicadores, funciones y control que garanticen el perfeccionamiento del Programa para la óptima atención de parejas infértiles, y dentro de esto se incluye confeccionar bases de datos donde se registren las parejas tratadas por este motivo. Objetivos: Implementar un Sistema de Gestión Hospitalaria para la atención de la pareja infértil, en el Centro Territorial de Holguín. Métodos: Se realizó un estudio de desarrollo tecnológico, se confeccionó sobre el sistema de base de datos relacional postgreSQL, se empleó la herramienta Odoo con el objetivo de englobar en un único software todas las prestaciones que necesita la consulta. Se utilizó el lenguaje de programación Python. Resultados: SCAPI, permite gestionar la información de los pacientes y sus historias clínicas, está compuesto por módulos relacionados: configuración general, permite crear los perfiles de usuarios y los permisos para interactuar con el sistema; SCAPI muestra y gestiona toda la información relacionada con la historia clínica digital, la agenda de turnos, medios diagnósticos (estudios de reserva ovárica, espermogramas, ecografías ováricas, estudios hormonales, técnicas de baja y alta tecnología entre otros). Conclusiones: El Sistema de Gestión Hospitalaria para la atención de la pareja infértil, contribuye al objetivo de una mayor calidad de la atención al paciente pues gestiona la información de estos y sus historias clínicas de manera rápida, oportuna y fiable.

Introduction: Biological infertility is a disease of the reproductive system that alters the psychological and social balance of couples. In Cuba there is a program for the treatment of infertile women and the Ministry of Public Health includes in its guidelines to implement the organizational bases, work system, indicators, functions and control that guarantee the improvement of the Program, including databases where couples treated for this reason are registered. Objective: To implement a Hospital Management System for the infertile couple care in the Holguín Territorial Center. Methods: A study of technological development was carried out using postgre SQL relational database system, Odoo tool, and Python programming language. Results: SCAPI allows to manage the information of patients and their medical records; it is made up of modules that are related to each other: the general configuration module which allows you to create user profiles and permissions to interact with the system; the SCAPI module which shows and manages all the information related to the digital medical history, appointment schedules, and diagnostic means (ovarian reserve studies, spermograms, ovarian ultrasound, hormonal studies, low and high technology techniques, among others). Conclusions: Hospital Management System for the care of infertile couples allows managing fast, timely and reliable information on patients and their medical records during care consultations for infertile couples with the aim of achieving a higher quality of patient care.

99mTc-Labeled Cyclic Peptide Targeting PD-L1 as a Novel Nuclear Imaging Probe.

Recent cancer therapies have focused on reducing immune suppression in the tumor microenvironment to prevent cancer progression and metastasis. PD-1 is a checkpoint protein that stops the immune response and is expressed on immune T cells. Cancer cells express a PD-1 ligand (PD-L1) to bind to the T-cell surface and activate immunosuppressive pathways. This study aimed to design, synthesize, and evaluate a 99mTc-labeled PD-L1-targeting cyclic peptide inhibitor (99mTc-iPD-L1) as a novel SPECT radiopharmaceutical for PD-L1 expression imaging. AutoDock software (version 1.5) was used to perform molecular docking for affinity calculations. The chemical synthesis was based on the coupling reaction of 6-hydrazinylpyridine-3-carboxylic acid with a 14-amino-acid cyclic peptide. iPD-L1 was prepared for 99mTc labeling. Radio-HPLC was used to verify radiochemical purity. The stability of the radiopeptide in human serum was evaluated by HPLC. iPD-L1 specificity was assessed by SDS-PAGE. [99mTc]Tc-iPD-L1 cellular uptake in PD-L1-positive cancer cells (HCC827 and HCT116) and biodistribution in mice with induced tumors were also performed. One patient with advanced plantar malignant melanoma received [99mTc]Tc-iPD-L1. The iPD-L1 ligand (AutoDock affinity: -6.7 kcal/mol), characterized by UPLC mass, FT-IR, and UV-Vis spectroscopy, was obtained with a chemical purity of 97%. The [99mTc]Tc-iPD-L1 was prepared with a radiochemical purity of >90%. In vitro and in vivo analyses demonstrated [99mTc]Tc-iPD-L1 stability (>90% at 24 h) in human serum, specific recognition for PD-L1, high uptake by the tumor (6.98 ± 0.89% ID/g at 1 h), and rapid hepatobiliary and kidney elimination. [99mTc]Tc-iPD-L1 successfully detected PD-L1-positive lesions in a patient with plantar malignant melanoma. The results obtained in this study warrant further dosimetric and clinical studies to determine the sensitivity and specificity of [99mTc]Tc-iPD-L1/SPECT for PD-L1 expression imaging.

Improving Overall Survival and Quality of Life in Patients with Prostate Cancer and Neuroendocrine Tumors Using 177Lu-iPSMA and 177Lu-DOTATOC: Experience after 905 Treatment Doses.

177Lu-iPSMA is a novel radioligand developed at ININ-Mexico with a high affinity for the PSMA protein heavily expressed in cancer cells of approximately 95% of patients with metastatic castration-resistant prostate cancer (mCRPC). 177Lu-DOTATOC is a patent-free radioligand, molecularly recognized by somatostatin receptors (SSTR-2) overexpressed in cancer cells of about 80% of patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET). This translational research aimed to determine the efficacy and safety of 177Lu-iPSMA and 177Lu-DOTATOC developed as GMP pharmaceutical formulations for treating progressive and advanced mCRPC and NET. One hundred and forty-five patients with mCRPC and one hundred and eighty-seven subjects with progressive NET (83% GEP-NET and 17% other NET), treated with 177Lu-iPSMA and 177Lu-DOTATOC, respectively, were evaluated. Patients received a mean dose of 7.4 GBq per administration of 177Lu-iPSMA (range 1-5 administrations; 394 treatment doses) or 177Lu-DOTATOC (range 2-8 administrations; 511 treatment doses) at intervals of 1.5-2.5 months. Efficacy was assessed by SPECT/CT or PET/CT. Results were stratified by primary tumor origin and number of doses administered. Patients with mCRPC showed overall survival (OS) of 21.7 months with decreased radiotracer tumor uptake (SUV) and PSA level in 80% and 73% of patients, respectively. In addition, a significant reduction in pain (numerical scale from 10-7 to 3-1) was observed in 88% of patients with bone metastases between one and two weeks after the second injection. In the GEP-NET population, the median progression-free survival was 34.7 months, with an OS of >44.2 months. The treatments were well tolerated. Only ten patients experienced grade ≥ 3 myelosuppression (3% of all patients). The observed safety profiles and favorable therapeutic responses demonstrated the potential of 177Lu-iPSMA and 177Lu-DOTATOC to improve overall survival and quality of life in patients with progressive and advanced mCRPC and NET.

Uso de aspirina en prevención primaria cardiovascular: es tiempo de cambiar el paradigma

La Aspirina es una droga ampliamente utilizada con un protagonismo indiscutido en el escenario de la prevención secundaria. Sin embargo, el rol de este medicamento en prevención primaria es aún motivo de discusión. Los primeros ensayos que evaluaron la Aspirina en prevención primaria sugerían reducciones en el infarto agudo al miocardio y el accidente cerebrovascular -aunque no en la mortalidad- con un riesgo no despreciable de hemorragia mayor. Esto llevó a diversas sociedades científicas a recomendar su prescripción sólo en aquellos individuos con alto riesgo de eventos cardiovasculares. Desde el año 2018 en adelante, surgen diversos ensayos aleatorizados que han cuestionado estas indicaciones, mostrando beneficios clínicos muy discretos o ausentes. El objetivo de esta revisión es realizar un análisis histórico de la evidencia sobre el rol de la Aspirina en prevención primaria y resumir las recomendaciones actuales en este escenario.

Aspirin is widely used with a clear role in secondary prevention of cardiovascular diseases. However, its benefit in primary prevention is still a matter of discussion. The first trials evaluating Aspirin for primary prevention suggested reductions in acute myocardial infarction and stroke (although not in mortality) but with a non-negligible risk of major bleeding. This led to aspirin being recommended by various scientific societies, albeit limited to individuals at high risk of cardiovascular events. Since 2018 various randomized trials in primary prevention showed minimal or no beneficial effects of aspirin thus questioning its indication for this purpose. The aim of this review is to make an historical analysis of the evidence for the role of Aspirin in primary prevention and suggest modified recommendations for these subjects.

Técnica minimalista para valvuloplastía aórtica percutánea / Minimally invasive balloon aortic valve valvuloplastyBackground

RESUMEN: ANTECEDENTES: La valvuloplastía aórtica es un procedimiento paliativo o como puente al reemplazo aórtico percutáneo o quirúrgico. Nuestro abordaje incluye una técnica minimalista y la utilización de balones de mayor tamaño que lo estándar. OBJETIVO: Evaluar los resultados clínicos inmediatos y alejados de pacientes tratados mediante esta técnica modificada. MÉTODOS: Se incluyó a todos los pacientes sometidos a balonplastía aórtica entre Julio del 2012 y Agosto del 2019 en nuestro centro. El procedimiento se realizó bajo sedación consciente mediante un único acceso femoral y sin instalación de un marcapasos transitorio. El éxito de la intervención se definió como caída de gradiente basal en 50% o más en ausencia de complicación mayor. RESULTADOS: Se realizaron un total de 52 procedimientos en 49 pacientes. La edad promedio fue 76 ± 9,9 años. Un tercio de los pacientes tenía una fracción de eyección del ventrículo izquierdo ≤35% y similar proporción tenía un perfil de riesgo STS score > 10 puntos. La duración total promedio fue de 31,1 + 10,0 min. Se utilizó un balón #28 en el 84.6% de los casos. El éxito del procedimiento se alcanzó en 94,2% de los casos. Ocurrieron 2 muertes intraoperatorias (3,9%), ambas en pacientes de muy alto riesgo y 2 (3,9%) complicaciones vasculares mayores. La sobreviva en el seguimiento alejado fue 32,7%. CONCLUSIÓN: La valvuloplastia aórtica percutánea con técnica modificada, utilizando balones de mayor tamaño que lo habitual, es una técnica segura que logra óptimos resultados hemodinámicos.

ABSTRACT: Aortic balloon valvuloplasty (ABV) is a palliative procedure or a bridge to percutaneous or surgical aortic valve replacement. Our group proposes a minimalist approach that reduces the use of resources and also stands out for using larger balloons. AIM: To assess the safety and the immediate results of patients undergoing aortic balloon valvuloplasty using a minimally invasive procedure. METHODS: All patients who underwent ballon aortic valvuloplasty (BAV) between July 2012 and Au- gust 2019 were included. The procedure was performed under conscious sedation using a single femoral access and without the installation of a temporary pacemaker. Success was defined as a 50% drop in the mean aortic gradient plus the absence of major complications. RESULTS: 52 procedures in 49 patients were performed; the average age was 76 ± 9,9 years. A third of patients included had a left ventricular ejection fraction ≤35% and a similar proportion had a high risk profile with an STS score> 10 points. A 28 mm balloon was used in 84.6% of cases. The procedure was successful in 94,2% of cases. There were 2 (3,85%) intraoperative deaths in very high-risk patients and 2 (3,85%) major vascular complications. The survival rate at late follow up was 32,7%. CONCLUSION: Aortic balloon valvuloplasty with a minimally invasive technique using larger than usual balloons is a safe technique that achieves optimal hemodynamic results.

Feasibility and safety of a transvenous lead extraction program implementation in South America: Challenges, early outcomes, and global collaboration-A single-center experience.

Background: Transvenous lead extraction is the standard of care for cardiac implantable electronic device (CIED) malfunction/infection-related removal. However, data on its performance and results in underdeveloped countries are limited. Objective: The purpose of this study was to report the feasibility and efficacy of a lead extraction program in a tertiary hospital in Chile, South America. Methods: Patients requiring CIED removal at the Electrophysiology Division of the Hospital las Higuera's were retrospectively analyzed. Outcomes including procedure-related mortality, procedural success and failure, and cardiac and vascular complications were reported. Results: A total of 15 patients were analyzed (median age 68 [interquartile range 52-75] years; 80% male). Patients with lead extraction difficulty index >10 represented 33% of patients. Infection was the indication for removal in all patients, with pocket infection (80%). Mechanical rotational tools were used in 66% of cases, and a total of 29 leads were removed. Procedural success was accomplished in 93% of cases. There was 1 (7%) intraprocedural complication and no procedure-related mortality. Conclusions: The development of a lead management program is feasible, safe, and effective in underdeveloped countries.

PRospective Observational Registry Evaluating the Safety and Effectivenessof Orsiro Stent in Chilean Patients - ROSES Registry.

BACKGROUND: There is little information on the performance of the new generation of stents with bioabsorbable polymers in the Latin American population. This registry aimed to further validate the safety and efficacy of the Orsiro bioresorbable-polymer sirolimus-eluting stent (BPSES) in unselected patients undergoing percutaneous coronary intervention (PCI) in Chilean centers. METHODS: We prospectively enrolled patients undergoing PCI with BPSES in 6 Chilean centers. The primary endpoint was defined as the composite of cardiac death, target vessel-related myocardial infarction (MI), and clinically driven target lesion revascularization at 1-year follow-up. RESULTS: From April 2017 to February 2019, 520 patients were enrolled in the registry, more frequently male (74.6%), with a mean age of 62.7 ± 10.8 years and a high prevalence of diabetes (40.2%). The clinical presentation was stable angina in 41.1% (n = 214), acute MI in 52.5% (n = 167 [32.1%] ST-elevation MI and n = 106 [20.4%] non-ST-elevation MI), and unstable angina in 6.3% (n = 33). Of 610 treated lesions, 425 (69.7%) were American College of Cardiology/American Heart Association type B or C lesions. Device and procedural success were achieved in 99.4% and 98.7% of the patients, respectively. The primary endpoint of the study occurred in 4%, primarily driven by cardiac death. CONCLUSIONS: The results of the ROSES multicenter registry indicated good clinical outcomes of BPSES Orsiro in all-comers Latin Americann patients undergoing PCI, despite the high-risk patients and treated lesions.

Enfermedad coronaria en el paciente portador del virus de la inmunodeficiencia humana / Coronary artery disease in patients infected with HIV

RESUMEN: Las enfermedades cardiovasculares, particularmente la enfermedad coronaria (EC), resultan de especial interés y preocupación en pacientes portadores del virus de la inmunodeficiencia humana (VIH). La ateromatosis acelerada como causa del aumento de prevalencia de enfermedad coronaria ha sido reconocida desde hace varios años en estos pacientes. No obstante, los mecanismos fisiopatológicos involucrados son múltiples y complejos e incluyen factores virales, la respuesta inflamatoria e inmunológica desencadenada por el virus, factores de riesgo cardiovascular tradicionales y efectos de la terapia antirretroviral combinada. Esta revisión de la literatura aborda dichos mecanismos y hace una actualización de los principales estudios clínicos que los sustentan. Se comenta además la evaluación de riesgo cardiovascular y los lineamientos para la revascularización de pacientes con EC portadores de VIH.

ABSTRACT: Cardiovascular diseases, particularly coronary artery disease are relevant in patients with the human immunodeficiency virus (HIV). For several years accelerated atheromatosis, a cause of increased prevalence in coronary disease, has been recognized in these patients. However, the pathophysiological mechanisms involved are multiple and complex, including viral factors, the inflammatory and immune response triggered by the virus, traditional cardiovascular risk factors, and the effects of combined antiretroviral therapy. This review of the literature addresses these mechanisms and updates the main clinical studies that support them. Cardiovascular risk assessment and guidelines for revascularization of HIV patients with CHD are also discussed.

Revascularización coronaria híbrida: un punto de encuentro entre cardiólogos intervencionistas y cirujanos cardíacos / Hybrid coronary revascularization: a meeting point between interventional cardiologists and cardiac surgeons

Resumen: La revascularización coronaria híbrida busca combinar el beneficio de las técnicas quirúrgicas y percutáneas para un manejo óptimo de pacientes seleccionados con enfermedad coronaria obstructiva multivaso. Esto permite asociar el beneficio del puente de arteria mamaria interna izquierda a la arteria descendente anterior (ADA) y combinarlo con el implante de stents en lesiones no-ADA. El objetivo de este trabajo es hacer una revisión de la literatura disponible con énfasis en sus resultados clínicos comparados con la estrategia convencional.

Abstract: Hybrid coronary revascularization seeks to combine the benefit of surgical and percutaneous techniques for optimal management of selected patients with multivessel coronary artery disease. This allows combining the benefit of the left internal mammary artery bypass to the anterior descending artery (LAD) and stent deployment in non-LAD lesions. The objective of this manuscript is to review the available literature with emphasis on its clinical results compared to the conventional strategy.

RNA-DNA strand exchange by the Drosophila Polycomb complex PRC2.

Polycomb Group (PcG) proteins form memory of transient transcriptional repression that is necessary for development. In Drosophila, DNA elements termed Polycomb Response Elements (PREs) recruit PcG proteins. How PcG activities are targeted to PREs to maintain repressed states only in appropriate developmental contexts has been difficult to elucidate. PcG complexes modify chromatin, but also interact with both RNA and DNA, and RNA is implicated in PcG targeting and function. Here we show that R-loops form at many PREs in Drosophila embryos, and correlate with repressive states. In vitro, both PRC1 and PRC2 can recognize R-loops and open DNA bubbles. Unexpectedly, we find that PRC2 drives formation of RNA-DNA hybrids, the key component of R-loops, from RNA and dsDNA. Our results identify R-loop formation as a feature of Drosophila PREs that can be recognized by PcG complexes, and RNA-DNA strand exchange as a PRC2 activity that could contribute to R-loop formation.

18F-FDG-PET/CT in Canine Mammary Gland Tumors.

Medical imaging techniques play a central role in clinical oncology, helping to obtain important information about the extent of disease, and plan treatment. Advanced imaging modalities such as Positron Emission Tomography-Computed Tomography (PET/CT), may help in the whole-body staging in a single procedure, although the lesions should be carefully interpreted. PET/CT is becoming commonly used in canine cancer patients, but there is still limited information available on specific tumors such as mammary cancer. We evaluated the utility of fluorine-18 fluorodeoxyglucose (18F-FDG)-PET/CT to detect malignant lesions in eight female dogs with naturally occurring mammary tumors. A whole-body scan was performed prior to surgery, and mammary and non-mammary lesions detected either on PET/CT or during pre-surgical physical exam were resected when possible and submitted for histopathological examination. Multiple mammary lesions involving different mammary glands were detected in 5/8 dogs, for a total of 23 lesions; there were 11 non-mammary-located lesions in 6/8 dogs, three of these were lung or lymph node metastasis. A total of 34 lesions were analyzed: 22 malignant (19 mammary tumors and three metastatic lesions), and 12 benign (four mammary lesions and eight of non-mammary tissues). Glucose uptake by maximum standardized uptake value (SUVmax) was analyzed and correlated with tumor size, and benign vs. malignant pathology. We found that the minimum tumor size needed to distinguish malignant lesions according to the SUVmax was 1.5 cm; benign and malignant lesions <1.5 cm did not differ in glucose uptake (mean SUVmax = 1.1). In addition, a SUVmax value >2 was 100% sensitive for malignancy. Combining these data, lesions >1.5 cm with a SUVmax >2 had a positive predictive value of 100%. Finally, we did not find an association between SUVmax and histologic subtype or grade, which may be present in a larger sample. Thus, 18F-FDG PET/CT is useful for distinguishing malignant from benign lesion but further imaging of dogs with diverse tumors, should establish characteristic SUV value cutoffs for detecting primary and metastatic disease, and distinguishing them from benign lesions.

Metabolic tumor volume changes assessed by interval 18fluorodeoxyglucose positron emission tomography-computed tomography for the prediction of complete response and survival in patients with diffuse large B-cell lymphoma.

An early discrimination of survival probability is required for patients with diffuse large B cell lymphoma (DLBCL), which may identify patients that require other treatment options, for example clinical trials. To the best of our knowledge, the impact of interim evaluation with 18fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has not yet been determined in this type of neoplasia. The aim of the present study was to determine the role of changes in metabolic tumor volume (MTV) between baseline and interim 18F-FDG PET/CT scans, following three courses of chemotherapy in order to predict complete response (CR) and overall survival (OS) in patients with DLBCL. Patients with previously untreated DLBCL who had received the standard 6-8 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone were included in the present study. A predictive model was constructed using changes in MTV and other clinical factors including age, gender, East Cooperative Oncology Group (ECOG) status, clinical stage, B symptoms, the presence of bulky disease and elevated lactate dehydrogenase levels, and data were analyzed using logistic regression analysis. In total, 50 patients with DLBCL were included in the present study. The majority of patients presented with stage III/IV disease (64%), B symptoms (72%) and bulky disease (58%). According to the International Prognostic Index score, 44% of patients were in the intermediate-high or high-risk categories for risk of relapse, and therefore considered to have poor prognosis. In total, ≥94% of patients achieving a decrease in total MTV had a 2-year OS rate of 95%, compared with the 58% OS rate of those with a suboptimal response. A multivariate model, including a change in MTV (a decrease of ≥94%), the ECOG performance status ≥2, a change in leukocyte counts and age, was used to predict CR. This model was used to define two groups according to the predicted probability of recurrence (cutoff, 0.69). The 2-year survival rates of the two groups were 95 and 59%, respectively. Analysis of changes in MTV in the interim 18F-FDG PET/CT revealed significant prognostic value for the prediction of CR and OS in patients with DLBCL.

Molecular imaging in musculoskeletal infections with 99mTc-UBI 29-41 SPECT/CT.

OBJECTIVE: To determine the added value of CT over planar and SPECT-only imaging in the diagnosis of musculoskeletal infection using 99mTc-UBI 29-4. MATERIALS AND METHODS: 184 patients with suspected musculoskeletal infection who underwent planar and SPECT/CT imaging with 99mTc-UBI 29-41 were included. Planar, SPECT-only and SPECT/CT images were reviewed by two independent analysts for presence of bone or soft tissue infection. Final diagnosis was confirmed with tissue cultures, surgery/histology or clinical follow-up. RESULTS: 99mTc-UBI 29-41 was true positive in 105/184 patients and true negative in 65/184 patients. When differentiating between soft tissue and bone infection, planar + SPECT-only imaging had a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 95.0, 74.3, 84.8, 91.3 and 86.9%, respectively, versus 99.0, 94.5, 92.5, 98.5 and 94.5% for SPECT/CT. SPECT/CT resulted in a change in reviewers' confidence in the final diagnosis in 91/184 patients. Inter-observer agreement was better with SPECT/CT compared with planar + SPECT imaging (kappa 0.87, 95% CI 0.71-0.85 versus kappa 0.81, 95% CI 0.58-0.75). CONCLUSION: Addition of CT to planar and SPECT-only imaging led to an increase in diagnostic performance and an improvement in reviewers' confidence and inter-observer agreement in differentiating bone from soft tissue infection.

Comparison of Three Chemotherapy Regimens in Elderly Patients with Diffuse Large B Cell Lymphoma: Experience at a Single National Reference Center in Mexico.

Background. Although chemotherapy added to rituximab is a standard of care for diffuse large B cell lymphoma (DLBCL), treatment of patients ≥65 years of age remains controversial due to comorbidities. Methods. This is a retrospective, comparative, nonrandomized study of patients ≥65 years of age, who were diagnosed with DLBCL but not previously treated. Demographic characteristics and comorbidities were analyzed. Three rituximab-containing treatment regimens (standard RCHOP, anthracycline dose-reduced RChOP, and RCOP) were compared. Descriptive analyses were conducted. Survival was calculated with the Kaplan-Meier method, and differences were compared with the log-rank test. Results. In total, 141 patients with a median age of 73.9 years were studied. The three treatment groups had comparable demographic characteristics. The overall response was 77%, 72.5%, and 59% in groups treated with RCHOP, RChOP, and RCOP, respectively. After multivariate analysis, the factors influencing the overall survival were the presence of B symptoms, poor performance status (ECOG ≥ 3), and febrile neutropenia. Factors influencing disease-free survival were febrile neutropenia, high-intermediate and high-risk IPI scores, and treatment without anthracycline. Conclusion. A higher ORR (overall response rate) was achieved with standard RCHOP, which influenced DFS and OS, although it was not statistically significant compared with the other groups. Interventional phase 3 trials testing new molecules in patients aged 70 to 80 years and older are required to improve the prognosis within this growing population.

Acceso radial derecho versus izquierdo para cateterismo coronario en pacientes mayores de 70 años / Right versus Left radial artery access for coronary angiography in elderly

Introducción: El acceso radial izquierdo (ARI) puede ser una alternativa para la realización de cateterismos coronarios, especialmente en pacientes añosos, donde modificaciones anatómicas pueden dificultar el procedimiento por acceso radial derecho (ARD). Objetivo: Determinar si el uso del ARI en pacientes mayores de 70 años disminuye el tiempo de fluoroscopía y la dosis de radiación durante una coronariografía realizada por operadores entrenados. Métodos: De forma prospectiva se evaluaron pacientes mayores de 70 años sometidos a cateterismo coronario por vía radial por operadores experimentados (>200 procedimiento por vía radial/año), utilizando la misma técnica. El acceso derecho o izquierdo fue asignado de forma aleatoria y se registraron los tiempos de procedimiento, la exposición a radiación, insumos utilizados y apreciación de dificultad del operador. Resultados: Se incluyeron 102 pacientes (ARD 52 / ARI 50). Ambos accesos fueron comparables en los tiempos utilizado para realizar el procedimiento (ARD 782 vs ARI 695 segundos, p= 0,06), aunque hubo un significativo menor tiempo utilizado para canular la arteria coronaria derecha en aquellos pacientes que se accedieron por ARI (206 vs 169 segundos; p= 0,01). No hubo diferencias en la radiación producida por el examen entre ambos grupos (PDA ARD 56,7 vs ARI 59,3 Gy/ cm2, p= 0,09), ni en la cantidad de medio de contraste utilizado (ARD 106,33 (31,04) vs ARI 108,13 (30,23), p=0,24). Se encontró una mayor frecuencia de tortuosidad (25% vs 6%, p <0,01) y de dificultad del procedimiento (58% vs 28%, p <0,01) en el grupo de ARD, principalmente debido al uso de una guía adicional (33% vs 4%, p< 0,01). Conclusión: Tanto el acceso radial derecho como el izquierdo son alternativas factibles para la realización de una coronariografía en pacientes de edad avanzada, no existiendo diferencias entre éstos en el tiempo total del procedimiento. Sin embargo, el ARD en pacientes añosos se asocia más frecuentemente con dificultades a nivel braquiocefálico y mayor uso de guías adicionales para sortear estos desafíos.

Background: Left radial access (LRA) for coronary angiography is an alternative to right radial access (RRA), especially in elderly patients in whom anatomic features may complicate the latter approach. Aim: To determine whether LRA in patients 70 years or older involves a decreased fluoroscopy time and radiation doses in coronary angiography performed by experienced operators. Method: Patients 70 years or older were randomly assigned to undergo coronary angiography through de RRA (n=52) or LRA (n=50). The procedure was performed by experienced operators (>200 radial access coronary angiographies, yearly). Duration of the procedure, exposure to radiation, materials used and subjective evaluation of the difficulty in performing the angiography were assessed. Results: Mean procedure duration was similar between accesses (RRA = 782 vs LRA = 695 seconds (p=0.06). The time to access the right coronary artery was significantly greater for de RRA compared to the LRA (206 vs 169 seconds, respectively, p=0.01). There was no difference in radiation dose (PDA) between groups (RRA = 106.3 ± 31.4 vs LRA = 108.1 ± 30.2 Gy/cm2, p=0.24), nor in the amount of contrast (ARD 106,33 (31,04) vs ARI 108,13 (30,23), p=0,24). Tortuosity (25% vs 6%, p <0,01) and subjective evaluation of procedure difficulties (58% vs 28%, p <0,01) were higher in RRA compared to LRA. An additional guide was needed with RRA compared to LRA (33% were higher in RRA compared to LRA, an additional guide was used in RRA 33% than in LRA (33% vs 4%, p< 0,01). Conclusion: RRA may be used in elderly patients within the same procedure duration compared to LRA. However, RRA is more frequently associated to the presence of tortuosity at the brachio-cephalic site, leading to greater use of additional wire.

Factores de riesgo para la formación de trombos sobre el dispositivo ULTRASEPT®, en pacientes con fibrilación auricular sometidos a cierre percutáneo de orejuela izquierda / Risk factors for thrombus formation on the ULTRASEPT® device in patiens with atrial fibrillation being submitted to left atrial appendage closure

Introducción: El cierre percutáneo de orejuela izquierda con dispositivos percutáneos (CPOI) ha demostrado ser útil en la prevención de embolia arterial como alternativa al tratamiento anticoagulante (TACO) en pacientes con fibrilación auricular no valvular (FANV). Sin embargo, en las primeras semanas post implante, existe el riesgo de formación de trombos sobre el dispositivo. Objetivos: Describir e Identificar los factores de riesgo para la formación de trombos sobre el dispositivo posterior al cierre de orejuela izquierda. Métodos: Se incluyeron 15 pacientes con FANV y alto riesgo hemorrágico, sometidos a CPOI con dispositivo Ultrasept (Cardia Inc., Eagan, MN), en el Hospital Clínico de la Universidad Católica, entre Abril 2013 y Junio 2014. A todos se les realizó eco-cardiograma transesofágico (ETE) al primer, tercer y sexto mes post implante. Todos los pacientes recibieron aspirina en forma permanente y TACO por 45 días el que se reemplazó por clopidogrel hasta el sexto mes post implante. Se analizaron parámetros clínicos y ecocardiográficos en forma retrospectiva para identificar los factores de riesgo asociados a la formación de trombos sobre el dispositivo. Resultados: La edad promedio de los pacientes fue 77± 8 años, 73% de sexo masculino. El 80% tenía FA permanente y 20% FA paroxística. EL Score de CHA2DS2VASc promedio fue de 5 (mínimo 3, máximo 8 puntos). En 4 pacientes (26.6%), encontramos trombos en el dispositivo en el seguimiento con ETE (1 paciente al primer mes y 3 al tercer mes), sin consecuencias clínicas. Al comparar los pacientes que formaron trombos con el resto, no hubo diferencias en las variables clínicas (edad, sexo, Hipertensión arterial (HTA), Diabetes Mellitus (DM), Dislipidemia, Tabaquismo, Insuficiencia Renal, AVE previos), ni en las variables ecocardiográficas estudiadas, como el área de la aurícula izquierda (AI), contraste espontáneo en la AI, insuficiencia mitral ni cierre incompleto de orejuela (medida por la existencia de flujo peridispositivo). Sin embargo, los pacientes con trombos presentaron CHA2DS2VASc score más alto (7.1 vs 4.7; p= 0.001) y fracción de eyección (FE) más baja (43% vs 55%; p= 0.001). En la curva ROC de CHA2DS2VASc para predecir una mayor probabilidad de formación de trombos, un valor > 6 obtiene una sensibilidad de un 100% y una especificidad de un 80%. En nuestro seguimiento clínico de 2 años ± 5.7 meses posterior al implante, 1 paciente tuvo un AVE isquémico identificando como fuente enfermedad carotidea (no tenía trombos en el dispositivo). El resto de los pacientes se mantienen asintomáticos. Conclusiones: En nuestra experiencia, el CHA2DS-2VASc score (> 6) y la fracción de eyección baja, fueron factores de riesgo para la formación de trombos sobre el dispositivo de cierre de orejuela. Este hallazgo debería confirmarse en series más grandes dado que podría cambiar la estrategia de anticoagulación post implante.

Background: Percutaneous closure of the left atrial appendage (LAA) has been shown to be useful in the prevention of arterial embolism as an alternative to oral anticoagulants in patients with non valvular atrial fibrillation. However, thrombus formation may develop in the first weeks following device implantation/ Aim: to identify risk factors for thrombus development on devices used for LAA closure. Methods: 15 patients with non valvular AF and high risk for anticoagulant treatment were included. Patients received an Ultrasept (Cardia Inc., Eagan, MN) between April 2013 and June 2014. Transesophageal echocardiography was performed in all patients 1, 3 and 6 months post implant. All patients received aspirin permanently and acenocumarol for 45 days, followed by clopidogrel until 6 months post implant. Results: Mean age was 77 years old (SD 8). 73% were males. AF was permanent in 80% and paroxysmal in 20%. Mean CHA2DS2VASC was 8 (range 3 to 8). Thrombus were revealed by TEE in 4 patients (26.6%), at 1 month (1 patient) and at 3 months post implant (3 patients). No complications occurred in these patients. Clinical variables (age, sex, hyper-tension, diabetes, dyslipidemia, smoking habit, renal failure and prior strokes) were no different in patients with or without thrombus. The same was true for left atrial size, mitral insufficiency or incomplete closure of LAA. In contrast, patients with thrombus formation had a higher CHA2DS2VASc score (7.1 vs 4.7, p=0.001 and a lower LV ejection fraction (43% vs 55%, p=0.001). A CHA2DS2VASc score > 6 was 100% sensible and 80% specific for thrombus formation (ROC curve). After a follow-up of 24 ± 5 months only 1 patients had and ischemic cerebro-vascular event which was attributed to carotid artery disease (the patient had no evidence of device thrombus). All other patients remain asymptomatic. Conclusion: A CHA2DS2VASc score > 6 and a low ejection fraction were risk factors for thrombus formation on LAA closing device. Confirmation of these findings in a larger series of patients could lead to a change in anticoagulant strategy following the implantation of devices to close the LAA.

La coronarioectasia difiere en los factores de riesgo clásicos de enfermedad coronaria / Compared to usual coronary artery disease risk factors are different in those with coronary ectasia

Introducción: La coronarioectasia (CE), es una infrecuente forma de enfermedad coronaria, en que dilataciones coronarias coexisten con placas ateroes-cleróticas. Puede presentarse como cuadros agudos o crónicos, aún sin estenosis significativa. Distintas series lo han asociado a perfiles variados de factores de riesgo cardiovascular. Métodos: Se efectuó un estudio analítico de cohorte retrospectivo, evaluando las coronariografías realizadas en nuestro centro entre Junio de 2009 a Julio de 2015. Se definió CE como dilatación >1,5 veces comparado con el diámetro de la arteria de referencia. Se estudiaron factores de riesgo cardiovascular clásicos y se compararon con un grupo control elegido de forma aleatoria. Resultados: De 9648 coronariografías, 64 presentaban CE. La mayor parte eran hombres, de menor edad, con menos hipertensión arterial, diabetes e hiperlipidemia, comparados con los controles. En la mayoría de los casos la CE afectaba a 3 vasos (83,3%) y en solo 5 casos (28%) coexistía con estenosis. El análisis multivariado señaló como factores de riesgo significativos a la edad < 55 años (OR: 2,63, IC: 1,4 -4,9, p<0,05), Obesidad (OR: 3,2; IC:1,7-5,8, p<0,05) e Hiperlipidemia (OR: 0,09; IC: 0,016-0,54). Considerando los pacientes que se presentaron como SCA se observó que los pacientes con CE fueron más jóvenes (45,9 años; DE: 5,9 v/s 48,8 años; DE: 5,3; p=0,02), y con menos hiperlipidemia (OR:0,2; IC:0,06-0,7, p=0,01). Respecto a la obesidad, esta fue más preva-lente en pacientes con CE (OR: 2,49; IC: 0,956-6,4. p=ns). Conclusión: La CE es una entidad poco frecuente, que puede producir SCA aun en ausencia de estenosis significativa. Son pacientes más jóvenes y con menos antecedente de dislipidemia, por lo que en su patogenia aparentemente participan factores diferentes a los de la enfermedad ateroesclerótica obstructiva.

Background: Coronary ectasia (CE) is an uncommon condition where coronary artery dilatation coexists with atherosclerotic plaques. It may present as either acute or chronic syndromes even in the absence of coronary artery stenosis. Differences in risk factors associated to CE compared to those associated to usual CAD have been described. Methods: We retrospectively analyzed coronary arteriograms performed between June 2009 and July 2015. CE was defined as the presence of dilatation >1.5 times the diameter of the unaffected vessel. Cardiovascular risk factors were compared in CE vs a random sample of non-CE patients. Results: Out of 9648 coronary arteriograms 64 showed CE (9.5%). Compared to controls, CE patients were males, younger and hat lower prevalence or hypertension, diabetes and hyperlipidemia. CE was present in all 3 main vessels in 83.3% of CE patients and co-existed with significant stenosis in only 28%. Multivariate analysis showed that significant differences in risk factors were age <55 years (OR: 2.63; CI: 1.4 to 4.9, p <0.05), obesity (OR: 3 2; CI: 1.7 to 5.8, p <0.05) and hyperlipidemia (OR: 0.09; CI: 0.016 to 0.54). In patients presenting with an acute coronary syndrome, those with CE were younger (45,9 years; SD: 5,9 v/s 48,8 years; SD: 5,3; p=0,02), y and a lower prevalence or hyperlipidemia (OR:0,2; IC:0,06-0,7, p=0,01). Conclusion: CE is an infrequent condition in CAD. It may me associated to either acute or chronic syndromes. They are younger, have a lower prevalence of dyslipidemia suggesting that risk factors other than traditionally recognized in obstructive CAD influence de development of CE.

Phospholipid makeup of the breast adipose tissue is impacted by obesity and mammary cancer in the mouse: Results of a pilot study.

Obesity, an established risk factor for breast cancer (BC), is associated with systemic inflammation. The breast contains adipose tissue (bAT), yet whether it plays a role in BC progression in obese females is being intensively studied. There is scarce knowledge on the lipid composition of bAT in health and disease. The purpose of this pilot study was: 1) to determine whether obesity and BC are associated with inflammatory changes in bAT 2) to analyze for the first time the lipid profile of bAT in obese and lean mammary tumor-bearing and normal mice. Syngeneic E0771 mammary tumor cells were implanted into the mammary fat pad of lean and diet-induced obese C57BL/6 mice. BATs were analyzed four weeks after tumor cell inoculation by immunohistochemistry and mass spectrometry. Phospholipids were identified and subjected to ratiometric quantification using a TSQ Quantum Access Max triple quadrupole mass spectrometer utilizing precursor ion scan or neutral ion loss scan employing appropriate class specific lipid standards in a two step quantification process. Four main classes of phospholipids were analyzed: phosphatidylcholines phosphatidylserines, phosphatidylethanolamines and phosphatidylinositols. Our results showed that bAT in obese (normal and tumor-bearing) mice contained hypertrophic adipocytes compared with their corresponding samples in lean mice; higher numbers of macrophages and crown-like structures were observed in obese tumor bearers compared to obese normal mice. BAT from normal obese mice revealed higher concentrations of phosphatidylethanolamines. Furthermore, bAT from tumor-bearing mice expressed higher phosphatidylcholines than that from non-tumor bearing mice, suggesting the presence of the tumor is associated with phosphatidylcholines. Conversion of phosphatidylethanolamines to phosphatidylcholines will be investigated in E0771 cells. Additional studies are projected to investigate macrophage activation by these specific classes of phospholipids. Occurrence of triglycerides and free fatty acids will be examined in bAT and similar lipidomic analyses will be carried out visceral adipose tissue, highly inflamed in obesity.