Synthesis, Anticancer Activity, and Docking Studies of Novel Hydroquinone-Chalcone-Pyrazoline Hybrid Derivatives.

A novel series of antitumor hybrids was synthesized using 1,4-benzohydroquinone and chalcone, furane, or pyrazoline scaffolds. This were achieved through isosteric substitution of the aryl group of the chalcone ß-carbon with the furanyl moiety and structural modification of the α,ß-unsaturated carbonyl system. The potential antitumor activity of these hybrids was evaluated in vivo on MCF-7 breast adenocarcinoma and HT-29 colorectal carcinoma cells, demonstrating cytotoxic activity with IC50 values ranging from 28.8 to 124.6 µM. The incorporation of furan and pyrazoline groups significantly enhanced antiproliferative properties compared to their analogues and precursors (VII-X), which were inactive against both neoplastic cell lines. Compounds 4, 5, and 6 exhibited enhanced cytotoxicity against both cell lines, whereas compound 8 showed higher cytotoxic activity against HT-29 cells. Molecular docking studies revealed superior free-energy values (ΔGbin) for carcinogenic pathway-involved kinase proteins, with our in silico data suggesting that these derivatives could be promising chemotherapeutic agents targeting kinase pathways. Among all the synthesized PIBHQ compounds, derivatives 7 and 8 exhibited the best drug-likeness properties, with values of 0.53 and 0.83, respectively. ADME results collectively suggest that most of these compounds hold promise as potential candidates for preclinical assays.

2-Acetyl-5,8-dihydro-6-(4-methyl-3-pentenyl)-1,4-naphthohydroquinone-Derived Chalcones as Potential Anticancer Agents.

Based on previous results with benzoindazolequinone (BIZQ) and 3-methylnaphtho [2,3-d]isoxazole-4,9-quinone (NIQ) derivatives, a novel series of chalcone-1,4-naphthoquinone/benzohydroquinone (CNQ and CBHQ) compounds were synthesized from 2-acetyl-5,8-dihydro-6-(4-methyl-3-pentenyl)-1,4-naphthohydroquinone. Their structures were elucidated via spectroscopy. These hybrids were assessed in vivo for their antiproliferative activity on MCF-7 breast adenocarcinoma and HT-29 colorectal carcinoma cells, revealing cytotoxicity with IC50 values between 6.0 and 110.5 µM. CBHQ hybrids 5e and 5f displayed enhanced cytotoxicity against both cell lines, whereas CNQ hybrids 6a-c and 6e exhibited higher cytotoxic activity against MCF-7 cells. Docking studies showed strong binding energies (ΔGbin) of CNQs to kinase proteins involved in carcinogenic pathways. Furthermore, our in silico analysis of drug absorption, distribution, metabolism, and excretion (ADME) properties suggests their potential as candidates for cancer pre-clinical assays.

[Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation GroupFactores impulsores y métodos de puntuación para mejorar el control de la hipertensión en la práctica clínica de la atención primaria: recomendaciones del grupo de innovación de HEARTS en las Américas]. / Fatores impulsionadores e scorecards para melhorar o controle da hipertensão arterial na atenção primária: recomendações do Grupo de Inovação da Iniciativa HEARTS nas Américas.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods: To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings: The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation: Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

Antecedentes: Las enfermedades cardiovasculares (ECV) son la principal causa de morbilidad y mortalidad en la Región de las Américas y la hipertensión es el factor de riesgo modificable asociado más importante. Sin embargo, las tasas de control de la hipertensión siguen siendo bajas y la mortalidad por ECV está estancada o en aumento después de décadas de reducción continua. En el 2016, la Organización Mundial de la Salud (OMS) presentó el paquete técnico HEARTS para mejorar el control de la hipertensión. La Organización Panamericana de la Salud (OPS) diseñó la iniciativa HEARTS en las Américas para mejorar el control del riesgo de ECV, que hace hincapié en el control de la hipertensión y que, hasta la fecha, se ha implementado en 21 países. Métodos: Para avanzar en la implementación, se creó un grupo interdisciplinario de profesionales de la salud con el objetivo de seleccionar los factores impulsores claves del control de la hipertensión basados en la evidencia y diseñar un método de puntuación integral para dar seguimiento a su implementación en los centros de atención de salud primaria (APS). El grupo estudió los sistemas de salud de alto desempeño que logran un control elevado de la hipertensión mediante programas de mejora de la calidad que se centran en medidas específicas con respecto a los procesos, con retroalimentación regular a los prestadores en los centros de salud. Resultados: Los ocho factores impulsores finales seleccionados se clasificaron en cinco dominios principales: 1) diagnóstico (exactitud de la medición de la presión arterial y evaluación del riesgo de ECV); 2) tratamiento (protocolo de tratamiento e intensificación del tratamiento estandarizados); 3) continuidad de la atención y seguimiento; 4) sistema de prestación del tratamiento (atención basada en un trabajo en equipo, reposición de la medicación) y 5) sistema para la evaluación del desempeño. Los factores impulsores y las recomendaciones se tradujeron en medidas con respecto a los procesos, lo que llevó a dos métodos de puntuación integrados e interconectados en el sistema de seguimiento y evaluación del programa HEARTS en las Américas. Conclusiones: El enfoque que se centra en estos factores impulsores clave de la hipertensión y los métodos de puntuación resultantes servirá de guía para el proceso de mejora de la calidad con objeto de alcanzar los objetivos de control a nivel poblacional en los centros de salud participantes de los países que implementan el programa HEARTS.

[Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation GroupFatores impulsionadores e scorecards para melhorar o controle da hipertensão arterial na atenção primária: recomendações do Grupo de Inovação da Iniciativa HEARTS nas Américas]. / Factores impulsores y métodos de puntuación para mejorar el control de la hipertensión en la práctica clínica de la atención primaria: recomendaciones del grupo de innovación de HEARTS en las Américas.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods: To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings: The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation: Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

Fundamentos: As doenças cardiovasculares (DCV) são as principais causas de morbimortalidade nas Américas, e a hipertensão arterial (HÁ) é o fator de risco modificável mais importante. Porém, as taxas de controle da HA continuam baixas, e a mortalidade por DCV está estagnada ou aumentando após décadas de redução contínua. Em 2016, a Organização Mundial da Saúde (OMS) lançou o pacote de medidas técnicas HEARTS para melhorar o controle da HA. A Organização Pan-Americana da Saúde (OPAS) criou a iniciativa HEARTS nas Américas para melhorar a gestão do risco cardiovascular (RCV), com ênfase no controle da HA. Até agora, essa iniciativa foi implementada em 21 países. Métodos: Para impulsionar a implementação, recrutou-se um grupo multidisciplinar de profissionais para selecionar impulsionadores-chave do controle da HA com base em evidências e elaborar um scorecard completo para monitorar sua implementação em unidades de atenção primária à saúde (APS). O grupo estudou sistemas de saúde com alto desempenho que haviam conseguido atingir um alto nível de controle da HA por meio de programas de melhoria da qualidade focados em medidas específicas de processo, com feedback regular para os profissionais das unidades de saúde. Resultados: Os oito fatores impulsionadores incluídos na seleção final foram categorizados em cinco domínios principais: (1) diagnóstico (exatidão da medição da pressão arterial e avaliação do RCV); (2) tratamento (protocolo padronizado de tratamento e intensificação do tratamento); (3) continuidade do cuidado e acompanhamento; (4) modelo de atenção (atendimento baseado em equipe, renovação da prescrição); e (5) sistema de avaliação do desempenho. Em seguida, os impulsionadores e as recomendações foram transformados em medidas de processo, gerando dois scorecards inter-relacionados integrados ao sistema de monitoramento e avaliação da Iniciativa HEARTS nas Américas. Interpretação: O foco nesses impulsionadores-chave da HA e nos scorecards resultantes orientará o processo de melhoria da qualidade para atingir as metas de controle, em nível populacional, dos centros de saúde participantes nos países que estão implementando a iniciativa HEARTS.

Perioperative fosfomycin disodium prophylaxis against urinary tract infection in renal transplant recipients: a randomized clinical trial.

BACKGROUND: Symptomatic urinary tract infection (UTI) is the most common infectious complication in renal transplant recipients (RTRs). Fosfomycin (FOS) is an attractive alternative for prophylaxis because it does not interact with immunosuppressants; although 90% is excreted unchanged in the urine, it does not require adjustment for renal function for single dose prophylaxis. METHODS: RTRs were recruited into this randomized, double-blind, placebo-controlled trial. Participants were randomized (1:1) to receive one 4 g dose of FOS disodium intravenously 3 h (FOS group) or placebo (placebo group) before placement and removal of a urinary catheter and before removal of a double-J ureteral stent. All participants received prophylaxis with trimethoprim/sulfamethoxazole. The main outcome was a comparison of the mean number of symptomatic UTI and asymptomatic bacteriuria (AB) episodes per patient during a 7-week follow-up period. The study was registered at ClinicalTrials.gov, NTC03235947. RESULTS: Eighty-two participants were included (41 in the FOS group and 41 in placebo group). The mean number of AB or symptomatic UTI episodes per patient was lower in the FOS group [intention-to-treat (ITT) 0.29 versus 0.60, P = 0.04]. The incidence of symptomatic UTI was lower in the FOS group (ITT, 7.3% versus 36.6%, P = 0.001), and there was no difference in the incidence of AB between both groups. The incidence of adverse events was similar in both groups. CONCLUSIONS: FOS addition is an effective and safe strategy to reduce the number of symptomatic UTIs during the first 7 weeks after renal transplant.

EVALUATION OF THE ROYAL FREE HOSPITAL CIRRHOSIS GLOMERULAR FILTRATION RATE FORMULA IN HISPANIC PATIENTS WITH CIRRHOSIS: AN EXTERNAL VALIDATION.

BACKGROUND AND AIMS: Glomerular filtration rate (GFR) measurement in patients with liver cirrhosis (LC) is the ideal method for adequate evaluation of kidney function. However, it is invasive, costly, and not widely accessible. Moreover, GFR estimation in patients with cirrhosis has been inaccurate. The aim of the present study was to evaluate and validate the recently described Royal Free Hospital (RFH) formula in a Hispanic cohort of patients with LC and compare it with other formulas, including the CKD-EPI cystatin C equation. METHODS: GFR was measured through the renal clearance of Tc-99m DTPA; it was cross-sectionally evaluated and compared with GFRs that were estimated utilizing the following formulas: RFH, Cockcroft-Gault, 6-variable Modification of Diet in Renal Disease-6, CKD-EPI cystatin C, CKD-EPI Creatinine, and CKD-EPI Cystatin C-Creatinine. RESULTS: We included 76 patients (53% women). The mean measured GFR in the entire cohort was 64 ml/min/1.73m2; 54% of the patients had a GFR < 60 ml/min/1.73 m2 at the time of evaluation. The RFH formula and the CKD-EPI cystatin C formula showed the best performance, with a p30 of 62% and 59%, respectively. All formulas performed poorly when GFR was < 60 ml/min/1.73 m2. CONCLUSIONS: The RFH formula showed a better performance than the other formulas based on serum creatinine in a Hispanic population with LC. There was no difference in performance between the RFH formula and the CKD-EPI cystatin C formula.

Carbonaceous fraction in PM2.5 of six Latin American cities: Seasonal variations, sources and secondary organic carbon contribution.

Latin American (LatAm) cities are grappling with elevated levels of gaseous and particulate pollutants, which are having detrimental effects on both the local ecosystem and human health. Of particular concern are aerosols with smaller diameters (lower or equal to 2.5 µm, PM2.5), known for their ability to penetrate deep into the respiratory system. While measurements in the region are increasing, they remain limited. This study addresses this gap by presenting the results of a comprehensive, year-long PM2.5 monitoring campaign conducted in six LatAm cities: Buenos Aires, São Paulo, Medellín, San José, Quito and Ciudad de México. Despite all six monitoring sites being urban, they exhibited significant variations in PM2.5 levels, as well as in the content and seasonal behavior of elemental carbon (EC) and organic carbon (OC). Estimations of secondary organic carbon (SOC) using the EC-tracer method revealed a notable SOC relevance across all cities: secondary organic aerosols (SOA) accounted in average for between 19 % to 48 % of the total carbonaceous matter. Source attribution, conducted through the Positive Matrix Factorization (PMF) model, highlights substantial contributions from gasoline and diesel traffic emissions (29 % to 49 % of total carbon, TC), regional biomass burning (21 % to 27 %), and SOA (20 % to 38 %) in all cities, with similar chemical signatures. Additionally, industrial emissions were significant in two cities (Medellín and San José), while two others experienced minor impacts from construction machinery at nearby sites (Buenos Aires and Quito). This comparative analysis underscores the importance of considering not only the thermal optical EC/OC fractions as tracers of sources but also the OC/EC ratio of the PMF factors. This dual approach not only adds depth to the research but also suggests varied methodologies for addressing this crucial environmental concern. This study lays the groundwork for future investigations into the factors influencing the content and seasonality of SOA in the region.

Image-Based Numerical Analysis for Isolated Type II SLAP Lesions in Shoulder Abduction and External Rotation.

The glenohumeral joint (GHJ) is one of the most critical structures in the shoulder complex. Lesions of the superior labral anterior to posterior (SLAP) cause instability at the joint. Isolated Type II of this lesion is the most common, and its treatment is still under debate. Therefore, this study aimed to determine the biomechanical behavior of soft tissues on the anterior bands of the glenohumeral joint with an Isolated Type II SLAP lesion. Segmentation tools were used to build a 3D model of the shoulder joint from CT-scan and MRI images. The healthy model was studied using finite element analysis. Validation was conducted with a numerical model using ANOVA, and no significant differences were shown (p = 0.47). Then, an Isolated Type II SLAP lesion was produced in the model, and the joint was subjected to 30 degrees of external rotation. A comparison was made for maximum principal strains in the healthy and the injured models. Results revealed that the strain distribution of the anterior bands of the synovial capsule is similar between a healthy and an injured shoulder (p = 0.17). These results demonstrated that GHJ does not significantly deform for an Isolated Type II SLAP lesion subjected to 30-degree external rotation in abduction.

Cardiac Operative Risk in Latin America: A Comparison of Machine Learning Models vs EuroSCORE-II.

BACKGROUND: Machine learning is a useful tool for predicting medical outcomes. This study aimed to develop a machine learning-based preoperative score to predict cardiac surgical operative mortality. METHODS: We developed various models to predict cardiac operative mortality using machine learning techniques and compared each model to European System for Cardiac Operative Risk Evaluation-II (EuroSCORE-II) using the area under the receiver operating characteristic (ROC) and precision-recall (PR) curves (ROC AUC and PR AUC) as performance metrics. The model calibration in our population was also reported with all models and in high-risk groups for gradient boosting and EuroSCORE-II. This study is a retrospective cohort based on a prospectively collected database from July 2008 to April 2018 from a single cardiac surgical center in Bogotá, Colombia. RESULTS: Model comparison consisted of hold-out validation: 80% of the data were used for model training, and the remaining 20% of the data were used to test each model and EuroSCORE-II. Operative mortality was 6.45% in the entire database and 6.59% in the test set. The performance metrics for the best machine learning model, gradient boosting (ROC: 0.755; PR: 0.292), were higher than those of EuroSCORE-II (ROC: 0.716, PR: 0.179), with a P value of .318 for the AUC of the ROC and .137 for the AUC of the PR. CONCLUSIONS: The gradient boosting model was more precise than EuroSCORE-II in predicting mortality in our population based on ROC and PR analyses, although the difference was not statistically significant.

Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation Group.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods: To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings: The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation: Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries. Funding: No funding to declare.

Sepsis in Trauma: A Deadly Complication.

Sepsis is a major cause of death following a traumatic injury. As a life-threatening medical emergency, it is defined as the body's extreme response to an infection. Without timely treatment, sepsis can rapidly lead to tissue damage, and organ failure The capacity to limit tissue damage through metabolic adaptation and repair processes is associated with an excessive immune response of the host. It is important to make an early prediction of sepsis, based on the quick Sepsis associated Organ Failure Assessment Score (qSOFA), so an accurate treatment can be initiated reducing the morbidity and mortality at the emergency and UCI services. Many factors increase the rate of complications and the development of sepsis in a trauma patient, representing a challenge to orthopedic surgeons. Several early biomarkers that help to identify and predict the inflammatory and immune responses of the host going through polytrauma and sepsis have been studied; procalcitonin (PCT), C-reactive protein (CRP), glycosylated hemoglobin (HbA1c), the Neutrophil/lymphocyte ratio (NLR), Interleukin-17 (IL-17), Caspase-1, Vanin-1, High-density lipoproteins (HDL), and the Thrombin-activable fibrinolysis inhibitor (TAFI). Once sepsis is diagnosed, treatment must be immediately initiated with an appropriate empiric antimicrobial, an all-purpose supporting treatment, and metabolic control, followed by the specific antibiotic therapy based on blood culture. Since the participation of sepsis in polytrauma has been recognized as a key event in the outcome of patients at the ICU, the ability of the specialist to early recognize a septic process has become a key feature to reduce mortality and improve clinical prognosis.

Mapping stages, barriers and facilitators to the implementation of HEARTS in the Americas initiative in 12 countries: A qualitative study.

The World Health Organization (WHO) Global Hearts Initiative offers technical packages to reduce the burden of cardiovascular diseases through population-wide and targeted health services interventions. The Pan American Health Organization (PAHO) has led implementation of the HEARTS in the Americas Initiative since 2016. The authors mapped the developmental stages, barriers, and facilitators to implementation among the 371 primary health care centers in the participating 12 countries. The authors used the qualitative method of document review to examine cumulative country reports, technical meeting notes, and reports to regional stakeholders. Common implementation barriers include segmentation of health systems, overcoming health care professionals' scope of practice legal restrictions, and lack of health information systems limiting operational evaluation and quality improvement mechanisms. Main implementation facilitators include political support from ministries of health and leading scientific societies, PAHO's role as a regional catalyst to implementation, stakeholder endorsement demonstrated by incorporating HEARTS into official documents, and having a health system oriented to primary health care. Key lessons include the need for political commitment and cultivating on-the-ground leadership to initiate a shift in hypertension care delivery, accompanied by specific progress in the development of standardized treatment protocols and a set of high-quality medicines. By systematizing an implementation strategy to ease integration of interventions into delivery processes, the program strengthened technical leadership and ensured sustainability. These study findings will aid the regional approach by providing a staged planning model that incorporates lessons learned. A systematic approach to implementation will enhance equity, efficiency, scale-up, and sustainability, and ultimately improve population hypertension control.

Bacteriuria is not associated with surgical site infection in patients undergoing cardiovascular surgery.

BACKGROUND: Despite absence of evidence, in practice, asymptomatic bacteriuria is perceived as a risk factor for surgical site infection (SSI) among patients with cardiac surgery. We aimed to identify whether an association exists between the preoperative presence of asymptomatic bacteriuria or urinary tract infection and SSI in patients undergoing cardiovascular surgery. METHODS: This is an analytical study with a retrospective cohort of patients undergoing coronary revascularization or valve replacement surgery. We identified cases of bacteriuria, urinary tract infection, and cardiovascular SSI and adjusted the results according to exposure to antibiotics and known risk factors for SSI using a multivariate logistic regression analysis. RESULTS: A total of 840 patients were included in the study, of whom 33 (3.9%) had asymptomatic bacteriuria and 13 (1.5%) had urinary tract infections. The incidence of SSI was 9.5% (80 patients), with 2.3% of cases having mediastinitis. In the multivariate analysis, asymptomatic bacteriuria (relative risk, 0.83; 95% confidence interval, 0.26-2.56; P = .74) and urinary tract infection (relative risk, 2.54; 95% confidence interval, 0.60-10.69; P = .20) were not risk factors for SSI. Traditional risk factors were found to increase the risk of SSI. CONCLUSIONS: The presence of bacteriuria is not a risk factor for presenting SSI in cardiovascular surgery. Screening with urinalysis or urine culture would not be recommended for patients undergoing cardiac surgery.

Cardiac surgery in systemic lupus erythematosus patients: Clinical characteristics and outcomes. / Cirugía cardiaca en pacientes con lupus eritematoso sistémico: características clínicas y desenlaces.

OBJECTIVES: To study the clinical characteristics and outcomes in systemic lupus erythematosus (SLE) patients who underwent cardiac surgery. METHODS: Retrospective analysis of 30 SLE patients who underwent cardiac surgery at a single center. Demographics, comorbidities, clinical and serologic characteristics, cardiovascular risk scores and treatment were recorded. Type of surgery, postoperative complications, mortality and histology were analyzed. RESULTS: Disease duration at surgery was 2 years. Valve replacement was the procedure most frequently performed (53%), followed by pericardial window (37%). At least one postoperative complication developed in 63% (mainly infections). An aortic cross-clamp time≥76minutes was associated with at least one postoperative complication (OR 6.4, 95% CI 1.1-35.4, p=.03). Early death occurred in 5 patients (17%) and late in 3 (10%); main causes were sepsis and heart failure. Disease activity was associated with pericardial window (OR 12.6, 95% CI 1.9-79, p=.007); lymphopenia≤1.200 (OR 10.1, 95% CI 1.05-97, p=.04); age≤30 years (OR 7.7, 95% CI 1.2-46.3, p=.02); and New York Heart Association class III (OR 7.0, 95% CI 1.1-42, p=.03). Postoperative infection was associated with length of hospital stay≥2 weeks (OR 54.9, 95% CI 5.0-602.1, p=.001); intensive care unit stay≥10 days (OR 20, 95% CI 1.6-171.7, p=.01); duration of mechanical ventilation≥5 days (OR 16.9, 95% CI 1.5-171.7, p=.01); and pulmonary artery systolic pressure≥50mmHg (OR 7.8, 95% CI 1.4-41.2, p=.01). CONCLUSIONS: Cardiac surgery in SLE confers high morbidity and mortality. SLE-specific preoperative risk scores should be designed to identify prognostic factors.

Biopsy-proven renal involvement and prognosis in 13 hispanic patients with primary Sjögren syndrome. / Afección renal confirmada mediante biopsia y pronóstico en 13 pacientes hispanos con síndrome de Sjögren primario.

BACKGROUND: The aim of this study was to describe a case series of 13 Hispanic patients with primary Sjögren syndrome (pSS) and biopsy-proven renal involvement. METHODS: We describe the clinical, serological and histological characteristics as well as the prognosis in a group of patients with pSS and biopsy-proven renal involvement, treated in 2 referral nephrology units in Mexico City. RESULTS: Thirteen patients with pSS underwent kidney biopsy (KB) over a period of 27 years. The median duration from pSS diagnosis to KB was 13.9 months. Seven patients (54%) had glomerulonephritis and 6 patients (46%) had tubulointerstitial nephritis. All patients were treated with corticosteroids and/or immunosuppressants. Eight patients (62%) remained stable or their renal function improved after a median follow-up of 12 months. CONCLUSIONS: This case series reflects the broad spectrum of renal involvement in pSS. We observed that in our Hispanic population, glomerular involvement was the most frequent abnormality, mainly membranous glomerulopathy, followed by tubulointerstitial disease. Tubular atrophy and interstitial fibrosis were also common biopsy findings. Treatment with corticosteroids or other immunosuppressive agents appear to slow renal disease progression.

Management of bladder neck stenosis and urethral stricture and stenosis following treatment for prostate cancer.

The aim of this review is to examine all urethral strictures and stenoses subsequent to treatment for prostate cancer, including radical prostatectomy (RP), radiotherapy, high intensity focused ultrasound (HIFU) and cryotherapy. The overall majority respond to endoscopic treatment, including dilatation, direct visual internal urethrotomy (DVIU) or bladder neck incision (BNI). There are adjunct treatments to endoscopic management, including injections of corticosteroids and mitomycin C (MMC) and urethral stents, which remain controversial and are not currently mainstay of treatment. Recalcitrant strictures are most commonly managed with urethroplasty, while recalcitrant stenosis is relatively rare yet almost always associated with bothersome urinary incontinence, requiring bladder neck reconstruction and subsequent artificial urinary sphincter (AUS) implantation, or urinary diversion for the devastated outlet.

Fatores impulsionadores e scorecards para melhorar o controle da hipertensão arterial na atenção primária: recomendações do Grupo de Inovação da Iniciativa HEARTS nas Américas / Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation Group / Factores impulsores y métodos de puntuación para mejorar el control de la hipertensión en la práctica clínica de la atención primaria: recomendaciones del grupo de innovación de HEARTS en las Américas

RESUMO Fundamentos. As doenças cardiovasculares (DCV) são as principais causas de morbimortalidade nas Américas, e a hipertensão arterial (HÁ) é o fator de risco modificável mais importante. Porém, as taxas de controle da HA continuam baixas, e a mortalidade por DCV está estagnada ou aumentando após décadas de redução contínua. Em 2016, a Organização Mundial da Saúde (OMS) lançou o pacote de medidas técnicas HEARTS para melhorar o controle da HA. A Organização Pan-Americana da Saúde (OPAS) criou a iniciativa HEARTS nas Américas para melhorar a gestão do risco cardiovascular (RCV), com ênfase no controle da HA. Até agora, essa iniciativa foi implementada em 21 países. Métodos. Para impulsionar a implementação, recrutou-se um grupo multidisciplinar de profissionais para selecionar impulsionadores-chave do controle da HA com base em evidências e elaborar um scorecard completo para monitorar sua implementação em unidades de atenção primária à saúde (APS). O grupo estudou sistemas de saúde com alto desempenho que haviam conseguido atingir um alto nível de controle da HA por meio de programas de melhoria da qualidade focados em medidas específicas de processo, com feedback regular para os profissionais das unidades de saúde. Resultados. Os oito fatores impulsionadores incluídos na seleção final foram categorizados em cinco domínios principais: (1) diagnóstico (exatidão da medição da pressão arterial e avaliação do RCV); (2) tratamento (protocolo padronizado de tratamento e intensificação do tratamento); (3) continuidade do cuidado e acompanhamento; (4) modelo de atenção (atendimento baseado em equipe, renovação da prescrição); e (5) sistema de avaliação do desempenho. Em seguida, os fatores impulsionadores e as recomendações foram transformados em medidas de processo, gerando dois scorecards inter-relacionados integrados ao sistema de monitoramento e avaliação da Iniciativa HEARTS nas Américas. Interpretação. O foco nesses impulsionadores-chave da HA e nos scorecards resultantes orientará o processo de melhoria da qualidade para atingir as metas de controle, a nível populacional, dos centros de saúde participantes nos países que estão implementando a iniciativa HEARTS.

ABSTRACT Background. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods. To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings. The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation. Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

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Factores impulsores y métodos de puntuación para mejorar el control de la hipertensión en la práctica clínica de la atención primaria: recomendaciones del grupo de innovación de HEARTS en las Américas / Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation Group / Fatores impulsionadores e scorecards para melhorar o controle da hipertensão arterial na atenção primária: recomendações do Grupo de Inovação da Iniciativa HEARTS nas Américas

resumen está disponible en el texto completo

ABSTRACT Background. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods. To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings. The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation. Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

RESUMO Fundamentos. As doenças cardiovasculares (DCV) são as principais causas de morbimortalidade nas Américas, e a hipertensão arterial (HÁ) é o fator de risco modificável mais importante. Porém, as taxas de controle da HA continuam baixas, e a mortalidade por DCV está estagnada ou aumentando após décadas de redução contínua. Em 2016, a Organização Mundial da Saúde (OMS) lançou o pacote de medidas técnicas HEARTS para melhorar o controle da HA. A Organização Pan-Americana da Saúde (OPAS) criou a iniciativa HEARTS nas Américas para melhorar a gestão do risco cardiovascular (RCV), com ênfase no controle da HA. Até agora, essa iniciativa foi implementada em 21 países. Métodos. Para impulsionar a implementação, recrutou-se um grupo multidisciplinar de profissionais para selecionar impulsionadores-chave do controle da HA com base em evidências e elaborar um scorecard completo para monitorar sua implementação em unidades de atenção primária à saúde (APS). O grupo estudou sistemas de saúde com alto desempenho que haviam conseguido atingir um alto nível de controle da HA por meio de programas de melhoria da qualidade focados em medidas específicas de processo, com feedback regular para os profissionais das unidades de saúde. Resultados. Os oito fatores impulsionadores incluídos na seleção final foram categorizados em cinco domínios principais: (1) diagnóstico (exatidão da medição da pressão arterial e avaliação do RCV); (2) tratamento (protocolo padronizado de tratamento e intensificação do tratamento); (3) continuidade do cuidado e acompanhamento; (4) modelo de atenção (atendimento baseado em equipe, renovação da prescrição); e (5) sistema de avaliação do desempenho. Em seguida, os impulsionadores e as recomendações foram transformados em medidas de processo, gerando dois scorecards inter-relacionados integrados ao sistema de monitoramento e avaliação da Iniciativa HEARTS nas Américas. Interpretação. O foco nesses impulsionadores-chave da HA e nos scorecards resultantes orientará o processo de melhoria da qualidade para atingir as metas de controle, em nível populacional, dos centros de saúde participantes nos países que estão implementando a iniciativa HEARTS.

Risk-adapted androgen deprivation and escalated three-dimensional conformal radiotherapy for prostate cancer: Does radiation dose influence outcome of patients treated with adjuvant androgen deprivation? A GICOR study.

PURPOSE: Multicenter study conducted to determine the impact on biochemical control and survival of risk-adapted androgen deprivation (AD) combined with high-dose three-dimensional conformal radiotherapy (3DCRT) for prostate cancer. Results of biochemical control are reported. PATIENTS AND METHODS: Between October 1999 and October 2001, 416 eligible patients with prostate cancer were assigned to one of three treatment groups according to their risk factors: 181 low-risk patients were treated with 3DCRT alone; 75 intermediate-risk patients were allocated to receive neoadjuvant AD (NAD) 4-6 months before and during 3DCRT; and 160 high-risk patients received NAD and adjuvant AD (AAD) 2 years after 3DCRT. Stratification was performed for treatment/risk group and total radiation dose. RESULTS: After a median follow-up of 36 months (range, 18 to 63 months), the actuarial biochemical disease-free survival (bDFS) at 5 years for all patients was 74%. The corresponding figures for low-risk, intermediate-risk, and high-risk disease were 80%, 73%, and 79%, respectively (P = .847). Univariate analysis showed that higher radiation dose was the only significant factor associated with bDFS for all patients (P = .0004). When stratified for treatment group, this benefit was evident for low-risk patients (P = .009) and, more interestingly, for high-risk patients treated with AAD. The 5-year bDFS for high-risk patients treated with AAD was 63% for radiation doses less than 72 Gy and 84% for those > or = 72 Gy (P = .003). CONCLUSION: The results of combined AAD plus high-dose 3DCRT are encouraging. To our knowledge, this is the first study showing an additional benefit of high-dose 3DCRT when combined with long-term AD for unfavorable disease.

The vasodilatory effects of levosimendan on the human internal mammary artery.

BACKGROUND: Levosimendan, an inotropic drug that enhances myocardial contractility through myofilment calcium sensitazion, induces peripheral vasodilation via opening ATP-dependent K(+) channels. It is unknown whether this drug can be used for the treatment of perioperative vasospasm of arterial conduits used for coronary artery bypass grafting. METHODS: We investigated the effects of levosimendan on human internal mammary artery (IMA) specimens taken from patients undergoing coronary artery bypass surgery. The rings were carefully prepared and placed between two wire hooks in organ bath chambers and then constricted submaximally with norepinephrine and thromboxane A(2) analog (U46619). Nitroglycerin, milrinone, and levosimendan were separately added in a cumulative fashion and concentration response curves for relaxation were constructed. In parallel experiments, the response to levosimendan was evaluated on rings with and without functional endothelium. Levosimendan prevention of norepinephrine-induced contraction was also estimated. RESULTS: Nitroglycerin, milrinone, and levosimendan completely reversed the contraction of the IMA segments induced by U46619 and norepinephrine. Levosimendan produced a potent, concentration-dependent preventive effect on the norepinephrine-induced contraction of IMA. The responses to levosimendan were similar in preparations with or without endothelium.