Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors.

BACKGROUND: Treatment options for penile squamous cell carcinoma are limited. We sought to investigate clinical outcomes and safety profiles of patients with penile squamous cell carcinoma receiving immune checkpoint inhibitors. METHODS: This retrospective study included patients with locally advanced or metastatic penile squamous cell carcinoma receiving immune checkpoint inhibitors between 2015 and 2022 across 24 centers in the United States, Europe, and Asia. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Objective response rates were determined per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events, version 5.0. Two-sided statistical tests were used for comparisons. RESULTS: Among 92 patients, 8 (8.7%) were Asian, 6 (6.5%) were Black, and 24 (29%) were Hispanic and/or Latinx. Median (interquartile range) age was 62 (53-70) years. In all, 83 (90%) had metastatic penile squamous cell carcinoma, and 74 (80%) had received at least second-line treatment. Most patients received pembrolizumab monotherapy (n = 26 [28%]), combination nivolumab-ipilimumab with or without multitargeted tyrosine kinase inhibitors (n = 23 [25%]), or nivolumab (n = 16 [17%]) or cemiplimab (n = 15 [16%]) monotherapies. Median overall and progression-free survival were 9.8 months (95% confidence interval = 7.7 to 12.8 months) and 3.2 months (95% confidence interval = 2.5 to 4.2 months), respectively. The objective response rate was 13% (n = 11/85) in the overall cohort and 35% (n = 7/20) in patients with lymph node-only metastases. Visceral metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 1 or higher, and a higher neutrophil/lymphocyte ratio were associated with worse overall survival. Treatment-related adverse events occurred in 27 (29%) patients, and 9.8% (n = 9) of the events were grade 3 or higher. CONCLUSIONS: Immune checkpoint inhibitors are active in a subset of patients with penile squamous cell carcinoma. Future translational studies are warranted to identify patients more likely to derive clinical benefit from immune checkpoint inhibitors.

Identification of a Papain-Like Protease Inhibitor with Potential for Repurposing in Combination with an Mpro Protease Inhibitor for Treatment of SARS-CoV-2

SARS-CoV-2 requires two cysteine proteases for viral polypeptide processing to allow maturation and replication: the 3C-like protease also known as the Main protease (Mpro) and the papain-like protease (PLpro). In addition to its critical role in viral replication, PLpro removes post-translational modifications like ubiquitin and interferon-stimulated gene product 15 (ISG15) from host proteins through its deubiquitinase domain, leading to host immunosuppression and increased ability of the virus to evade the host antiviral immune response. Through screening of a custom clinical compound library, we identified eltrombopag (DDL-701), a thrombopoietin receptor agonist, as having PLpro inhibitory activity that is sustained in the presence of the Mpro inhibitor nirmatrelvir. DDL-701 also suppressed both the deubiquitinase and ISG15 cleavage activities of PLpro. In addition, DDL-701 partially restored interferon-{beta} induction - an element of the host immune response - in an in vitro model system. Further, modeling and docking studies suggest DDL-701 interacts with the active site region of the PLpro enzyme and pilot pharmacokinetic studies indicate it is brain permeable. DDL-701 is already approved for treatment of thrombocytopenia and has previously been shown to achieve human plasma levels after oral dosing that is above the IC50 needed for it to exert its PLpro inhibitory activity in vivo. In addition, it has also been reported to have antiviral efficacy against SARS-CoV-2. DDL-701 thus represents a drug that can immediately be repurposed and undergo clinical evaluation as a PLpro inhibitor that may be most effectively used in a protease inhibitor cocktail with an Mpro inhibitor such as nirmatrelvir (Paxlovid) for the treatment of COVID-19.

Blood Biomarkers of Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of non-small cell lung cancer (NSCLC), either used in monotherapy or in combination with chemotherapy. While some patients achieve durable responses, some will not get benefit from this treatment. Early identification of non- responder patients could avoid unnecessary treatment, potentially serious immune-related adverse events and reduce treatment costs. PD-L1 expression using immunohistochemistry is the only approved biomarker for the selection of patients that can benefit from immunotherapy. However, application of PD-L1 as a biomarker of treatment efficacy shows many deficiencies probably due to the complexity of the tumor microenvironment and the technical limitations of the samples. Thus, there is an urgent need to find other biomarkers, ideally blood biomarkers to help us to identify different subgroups of patients in a minimal invasive way. In this review, we summarize the emerging blood-based markers that could help to predict the response to ICIs in NSCLC.

Croton urucurana Baill. Ameliorates Metabolic Associated Fatty Liver Disease in Rats.

Background: Metabolic associated fatty liver disease (MAFLD) affects a quarter of the worldwide population, but no drug therapies have yet been developed. Croton urucurana Baill. (Euphorbiaceae) is a medicinal species, that is, widely distributed in Brazil. It is used in popular medicine to treat gastrointestinal, cardiovascular, and endocrine system diseases. However, its hepatoprotective and lipid-lowering effects have not yet been scientifically investigated. Aim of the study: The present study investigated the effects of an extract of C. urucurana in a rat model of MAFLD that was associated with multiple risk factors, including hypertension, smoking, and dyslipidemia. Material and Methods: The phytochemical composition of C. urucurana was evaluated by liquid chromatography-mass spectrometry. Spontaneously hypertensive rats received a 0.5% cholesterol-enriched diet and were exposed to cigarette smoke (9 cigarettes/day for 10 weeks). During the last 5 weeks, the animals were orally treated with vehicle (negative control [C-] group), C. urucurana extract (30, 100, and 300 mg/kg), or simvastatin + enalapril (two standard reference drugs that are commonly used to treat dyslipidemia and hypertension, respectively). One group of rats that were not exposed to these risk factors was also evaluated (basal group). Blood was collected for the analysis of cholesterol, triglyceride, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. The liver and feces were collected for lipid quantification. The liver was also processed for antioxidant and histopathological analysis. Results: The main constituents of the C. urucurana extract were flavonoids, glycosides, and alkaloids. The model successfully induced MAFLD, reflected by increases in AST and ALT levels, and induced oxidative stress in the C- group. Treatment with the C. urucurana extract (300 mg/kg) and simvastatin + enalapril decreased plasma and hepatic lipid levels. In contrast to simvastatin + enalapril treatment, C. urucurana reduced AST and ALT levels. Massive lesions were observed in the liver in the C- group, which were reversed by treatment with the C. urucurana extract (300 mg/kg). Conclusion: C. urucurana extract exerted promising hepatoprotective and lipid-lowering effects in a preclinical rat model of MAFLD.

Bacopa monnieri: historical aspects to promising pharmacological actions for the treatment on central nervous system diseases / Bacopa monnieri: aspectos históricos de las acciones farmacológicas prometedoras para el tratamiento de enfermedades del sistema nervioso central

Bacopa monnieri(L.) Wettst. (Plantaginaceae), also known as Brahmi, has been used to improve cognitive processes and intellectual functions that are related to the preservation of memory. The objective of this research is to review the ethnobotanical applications, phytochemical composition, toxicity and activity of B. monnieri in the central nervous system. It reviewed articles on B. monnieri using Google Scholar, SciELO, Science Direct, Lilacs, Medline, and PubMed. Saponins are the main compounds in extracts of B. monnieri. Pharmacological studies showed that B. monnieri improves learning and memory and presents biological effects against Alzheimer's disease, Parkinson's disease, epilepsy, and schizophrenia. No preclinical acute toxicity was reported. However, gastrointestinal side effects were reported in some healthy elderly individuals. Most studies with B. monnieri have been preclinical evaluations of cellular mechanisms in the central nervous system and further translational clinical research needs to be performed to evaluate the safety and efficacy of the plant.

Bacopa monnieri (L.) Wettst. (Plantaginaceae), también conocida como Brahmi, se ha utilizado para mejorar los procesos cognitivos y las funciones intelectuales que están relacionadas con la preservación de la memoria. El objetivo de esta investigación es revisar las aplicaciones etnobotánicas, composición fitoquímica, toxicidad y actividad de B. monnieri en el sistema nervioso central. Se revisaron artículos sobre B. monnieri utilizando Google Scholar, SciELO, Science Direct, Lilacs, Medline y PubMed. Las saponinas son los principales compuestos de los extractos de B. monnieri. Los estudios farmacológicos mostraron que B. monnieri mejora el aprendizaje y la memoria y presenta efectos biológicos contra la enfermedad de Alzheimer, la enfermedad de Parkinson, la epilepsia y la esquizofrenia. No se informó toxicidad aguda preclínica. Sin embargo, se informaron efectos secundarios gastrointestinales en algunos ancianos sanos. La mayoría de los estudios con B. monnieri han sido evaluaciones preclínicas de los mecanismos celulares en el sistema nervioso central y es necesario realizar más investigaciones clínicas traslacionales para evaluar la seguridad y eficacia de la planta.

Molecular Mechanisms of Resistance to Immunotherapy and Antiangiogenic Treatments in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype arising from renal cell carcinomas. This tumor is characterized by a predominant angiogenic and immunogenic microenvironment that interplay with stromal, immune cells, and tumoral cells. Despite the obscure prognosis traditionally related to this entity, strategies including angiogenesis inhibition with tyrosine kinase inhibitors (TKIs), as well as the enhancement of the immune system with the inhibition of immune checkpoint proteins, such as PD-1/PDL-1 and CTLA-4, have revolutionized the treatment landscape. This approach has achieved a substantial improvement in life expectancy and quality of life from patients with advanced ccRCC. Unfortunately, not all patients benefit from this success as most patients will finally progress to these therapies and, even worse, approximately 5 to 30% of patients will primarily progress. In the last few years, preclinical and clinical research have been conducted to decode the biological basis underlying the resistance mechanisms regarding angiogenic and immune-based therapy. In this review, we summarize the insights of these molecular alterations to understand the resistance pathways related to the treatment with TKI and immune checkpoint inhibitors (ICIs). Moreover, we include additional information on novel approaches that are currently under research to overcome these resistance alterations in preclinical studies and early phase clinical trials.

In Vitro Development of a New Sponge-Based Delivery System for Intracanal Antimicrobial Administration in Endodontic Treatment.

This study aimed to evaluate the in vitro performance of collagen-based sponges as a drug delivery system for intracanal antimicrobial administration. Four groups of loaded collagen-based sponges (A, 0.3% w/v amoxicillin trihydrate: potassium clavulanate (4:1); B, 0.03% w/v chlorhexidine gluconate [CHX]; C, 0.3% w/v amoxicillin trihydrate: potassium clavulanate (4:1) and 0.03% w/v CHX; D, 1% w/v amoxicillin trihydrate: potassium clavulanate (4:1) and 0.03% w/v CHX) were designed. Release kinetics were tested in vitro on cultures in Petri dishes, and the effect on bacterial biofilms was studied ex vivo on 114 extracted human single-rooted teeth. Biofilm formation was tested by scanning electron microscopy (SEM). Collagen sponges containing amoxicillin and chlorhexidine showed a time-sustained antimicrobial effect in vitro and were also able to destroy mature biofilms ex vivo. This datum was validated by means of SEM-based study of E. faecalis and S. aureus biofilms.

Motor Evoked Potential Warning Criteria in Supratentorial Surgery: A Scoping Review.

During intraoperative monitoring of motor evoked potentials (MEP), heterogeneity across studies in terms of study populations, intraoperative settings, applied warning criteria, and outcome reporting exists. A scoping review of MEP warning criteria in supratentorial surgery was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Sixty-eight studies fulfilled the eligibility criteria. The most commonly used alarm criteria were MEP signal loss, which was always a major warning sign, followed by amplitude reduction and threshold elevation. Irreversible MEP alterations were associated with a higher number of transient and persisting motor deficits compared with the reversible changes. In almost all studies, specificity and Negative Predictive Value (NPV) were high, while in most of them, sensitivity and Positive Predictive Value (PPV) were rather low or modest. Thus, the absence of an irreversible alteration may reassure the neurosurgeon that the patient will not suffer a motor deficit in the short-term and long-term follow-up. Further, MEPs perform well as surrogate markers, and reversible MEP deteriorations after successful intervention indicate motor function preservation postoperatively. However, in future studies, a consensus regarding the definitions of MEP alteration, critical duration of alterations, and outcome reporting should be determined.

Repurposing Drugs for the Management of Patients with Confirmed Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19) by the World Health Organization, is a newly emerging zoonotic agent that emerged in China in December 2019. No specific treatment for COVID-19 is currently available. Usual palliative treatment includes maintaining hydration and nutrition and controlling fever and cough. The clinical severity and extent of transmission need to be determined, and therapeutic options need to be developed and optimized. METHODS: The present review discusses the recent repurposing of drugs for COVID-19 treatment. RESULTS: Several compounds, including remdesivir, lopinavir, ritonavir, interferon-ß, ribavirin, chloroquine/ hydroxychloroquine, azithromycin, tocilizumab, and ivermectin, have emerged as promising alternatives. They block the virus from entering host cells, prevent viral replication, and attenuate exacerbation of the host's immune response. CONCLUSION: Although some evidence indicates the positive actions of different classes of compounds for the treatment of COVID-19, few clinical assays have been established to definitively demonstrate their therapeutic value in humans. Multicenter clinical studies are urgently needed to validate and standardize therapeutic regimens that involve these agents. Although science has not yet presented us with a specific drug against COVID-19, the repurposing of drugs appears to be promising in our fight against this devastating disease.

Effect of motivational interviewing on self-care of people with heart failure: a randomized clinical trial. / Efeito da entrevista motivacional no autocuidado de pessoas com insuficiência cardíaca: ensaio clínico randomizado.

OBJECTIVE: To analyze the effect of motivational interviewing on self-care for people with chronic heart failure. METHOD: A multicenter randomized clinical trial, which divided people into an intervention group (n=59) and a control group (n=59), followed for 60 days in centers of Brazil and Uruguay. The intervention group received three consultations per motivational interviewing, with an interval of 30 days, and the control group maintained conventional follow-up in specialized clinics. The data were assessed using the Self-Care of Heart Failure Index 6.2, before and after intervention in each of the centers. They were analyzed using the mean, median, t-test, correlation analysis using the Spearman coefficient and effect of the intervention by Cohen's d. RESULTS: One hundred and eighteen people completed the study. In view of the assessment of the effect of the motivational interviewing on self-care, compared to conventional follow-up, a medium effect on maintenance and management (Cohen's d=0.6723; 0.5086) and high on self-care confidence (Cohen's d=0.9877). CONCLUSION: Motivational interviewing was effective in improving self-care in patients with heart failure, being a feasible strategy to be implemented in specialized clinics. Brazilian Registry of Clinical Trials (Registro Brasileiro de Ensaios Clínicos): RBR-6fp5qt.

Baccharis trimera (Less.) DC: An Innovative Cardioprotective Herbal Medicine Against Multiple Risk Factors for Cardiovascular Disease.

Cardiovascular disease (CVD) is the leading cause of death worldwide and among its modifiable risk factors are dyslipidemia, diabetes, and smoking. Experimental models evaluated this risk factors singly, however, there is a lack of models that agglomerate these risk factors, resembling real patients and elucidating the pathophysiology of CVD. Moreover, few studies have investigated the cardioprotective effects of Baccharis trimera, a species with lipid-lowering effects. In this study, ethanol-soluble fraction of B. trimera was characterized by liquid chromatography-mass spectrometry. Diabetes was induced by streptozotocin in Wistar rats that also received 0.5% cholesterol-enriched chow and were exposed to the smoke of nine cigarettes, 5 days/week, for 4 weeks. During the last 2 weeks, the animals were treated with vehicle (C-), B. trimera, or simvastatin plus insulin. At the end, cholesterol, triglyceride, urea, and creatinine levels; blood pressure (BP); heart rate (HR); abdominal aortic morphometry; vascular reactivity; renal and cardiac oxidative status; and histopathological changes were evaluated. The agglomerate of risk factors promoted alterations contrary to those described in the literature for the isolated risk factors. The C- group exhibited oxidative stress, increase in biochemical parameters, and thickening of the wall of the abdominal aorta. HR, systolic, diastolic, and mean BP decreased, and vascular reactivity was altered. Cardiac and renal histopathological changes were observed. Treatment with B. trimera reversed these changes and this effect may be partially attributable to lipid-lowering action and to the inhibition of free radical generation. B. trimera has cardioprotective effects in this model, with no toxicity.

Efeito da entrevista motivacional no autocuidado de pessoas com insuficiência cardíaca: ensaio clínico randomizado / Efecto de la entrevista motivacional sobre el autocuidado de personas con insuficiencia cardíaca: ensayo clínico aleatorizado / Effect of motivational interviewing on self-care of people with heart failure: a randomized clinical trial

RESUMO Objetivo: Analisar o efeito da entrevista motivacional no autocuidado de pessoas com insuficiência cardíaca crônica. Método: Ensaio clínico randomizado, multicêntrico, dividindo as pessoas em grupo intervenção (n=59) e grupo controle (n=59), acompanhadas por 60 dias nos centros do Brasil e Uruguai. O grupo intervenção recebeu três consultas por entrevista motivacional, com intervalo de 30 dias, e o grupo controle manteve o acompanhamento convencional nas clínicas especializadas. Os dados foram avaliados através do Self-Care of Heart Failure Index 6.2, antes e após a intervenção, em cada um dos centros e analisados através de média, mediana, teste-t, análise de correlação pelo coeficiente de Spearman e efeito da intervenção pelo d de Cohen. Resultados: 118 pessoas concluíram o estudo. Diante da avaliação do efeito da entrevista motivacional no autocuidado, comparando-se ao acompanhamento convencional, foi identificado efeito médio na manutenção e manejo (Cohen-d=0,6723; 0,5086) e alto na confiança do autocuidado (Cohen-d=0,9877). Conclusão: A entrevista motivacional foi efetiva na melhora do autocuidado dos pacientes com insuficiência cardíaca, sendo uma estratégia factível a ser implementada em clínicas especializadas. Registro Brasileiro de Ensaios Clínicos: RBR-6fp5qt.

RESUMEN Objetivo: Analizar el efecto de las entrevistas motivacionales en el autocuidado de personas con insuficiencia cardíaca crónica. Método: Ensayo clínico aleatorizado, multicéntrico, que divide a las personas en un grupo de intervención (n=59) y un grupo de control (n=59), seguidos durante 60 días en centros de Brasil y Uruguay. El grupo de intervención recibió tres consultas por entrevista motivacional, con un intervalo de 30 días, y el grupo de control mantuvo el monitoreo convencional en clínicas especializadas. Los datos se evaluaron utilizando el Self-Care of Heart Failure Index 6.2, antes y después de la intervención, en cada uno de los centros y se analizaron utilizando la media, la mediana, la prueba t, el análisis de correlación utilizando el coeficiente de Spearman y el efecto de la intervención por el d de Cohen. Resultados: 118 personas completaron el estudio. En vista de la evaluación del efecto de la entrevista motivacional sobre el autocuidado, en comparación con el seguimiento convencional, un efecto medio en el mantenimiento y el manejo (Cohen-d=0.6723; 0.5086) y alto en la confianza en el autocuidado (Cohen-d=0,9877). Conclusión: La entrevista motivacional fue efectiva para mejorar el autocuidado de pacientes con insuficiencia cardíaca, siendo una estrategia factible para ser implementada en clínicas especializadas. Registro brasileño de ensayos clínicos: RBR-6fp5qt.

ABSTRACT Objective: To analyze the effect of motivational interviewing on self-care for people with chronic heart failure. Method: A multicenter randomized clinical trial, which divided people into an intervention group (n=59) and a control group (n=59), followed for 60 days in centers of Brazil and Uruguay. The intervention group received three consultations per motivational interviewing, with an interval of 30 days, and the control group maintained conventional follow-up in specialized clinics. The data were assessed using the Self-Care of Heart Failure Index 6.2, before and after intervention in each of the centers. They were analyzed using the mean, median, t-test, correlation analysis using the Spearman coefficient and effect of the intervention by Cohen's d. Results: One hundred and eighteen people completed the study. In view of the assessment of the effect of the motivational interviewing on self-care, compared to conventional follow-up, a medium effect on maintenance and management (Cohen's d=0.6723; 0.5086) and high on self-care confidence (Cohen's d=0.9877). Conclusion: Motivational interviewing was effective in improving self-care in patients with heart failure, being a feasible strategy to be implemented in specialized clinics. Brazilian Registry of Clinical Trials (Registro Brasileiro de Ensaios Clínicos): RBR-6fp5qt.

Tradução e adaptação transcultural do instrumento self care of heart failure index 6. 2 para uso no Uruguai / Traducción y adaptación transcultural del instrumento self care of heart failure index 6. 2 para su uso en Uruguay / Translation and transcultural adaptation of the self-care instrument of heart failure index 6. 2 for use in Uruguay

RESUMO Objetivo: traduzir e adaptar transculturalmente o instrumento Self-Care of Heart Failure Index 6.2 para uso no Uruguai. Método: estudo metodológico, realizado em clínica de cuidados multidisciplinares em insuficiência cardíaca no Uruguai entre novembro de 2016 e setembro de 2017. Foram desenvolvidas as etapas: tradução, síntese das versões traduzidas, retrotradução, avaliação pelo comitê de experts e pré-teste. Para análise, utilizou-se o índice de validade de conteúdo (adequado > 0,9), percentual de concordância (adequado ≥ 80%) e o alfa de Cronbach no pré-teste (adequado ≥ 0,70). Resultado: na primeira avaliação, seis itens apresentaram IVC < 0,9 e/ou concordância total menor que 70% e por este motivo foram alterados e posteriormente reavaliados, atingindo IVC > 0,9 e/ou percentual de concordâncias maior que 70%. A consistência interna da escala foi de0 ,78. Conclusão: a tradução e adaptação deste instrumento proporciona o desenvolvimento de estudos multicêntricos por proporcionar as mesmas medidas de avaliação de desfechos.

RESUMEN Objetivo: traducir y adaptar transculturalmente el instrumento Self-Care of Heart Failure Index 6.2 para su uso en Uruguay. Método: estudio metodológico, realizado en una clínica de cuidados multidisciplinares para insuficiencias cardíacas de Uruguay entre noviembre de 2016 y septiembre de 2017. Se desarrollaron las siguientes etapas: síntesis de las versiones traducidas, retrotraducción, evaluación a cargo de un comité de expertos y prueba previa. Para el análisis, se utilizó el índice de validez del contenido (adecuado > 0,9), el porcentaje de concordancia (adecuado ≥ 80%) y el coeficiente alfa de Cronbach en la prueba previa (adecuado ≥ 0,70). Resultado: en la primera evaluación, seis puntos presentaron un valor de IVC < 0,9 y/o una concordancia inferior al 70% y, por este motivo, se los modificó y reevaluó posteriormente, con lo que se alcanzó un valor de IVC > 0,9 y/o un porcentaje de concordancias superior al 70%. La consistencia interna de la escala fue de 0,78. Conclusión: la traducción y adaptación de este instrumento proporciona la capacidad para desarrollar estudios multicéntricos por ofrecer las mismas medidas de evaluación de resultados.

ABSTRACT Objective: To translate and cross-culturally adapt the Self-Care of Heart Failure Index 6.2 instrument for use in Uruguay. Method: A methodological study, performed at a multidisciplinary heart failure care clinic in Uruguay between November 2016 and September 2017. The following stages were developed: translation, synthesis of translated versions, back-translation, expert committee evaluation and pre-test. For the analysis, the content validity index (adequate > 0.9), agreement percentage (adequate ≥ 80%) and Cronbach's alpha in the pre-test (adequate ≥ 0.70) were used. Result: In the first evaluation, six items displayed CVI < 0.9 and/or a total agreement lower than 70% and for this reason were changed and subsequently reevaluated, reaching CVI > 0.9 and/or an agreement percentage greater than 70%. The internal consistency of the scale was 0.78. Conclusion: The translation and adaptation of this instrument enables the development of multicenter studies by providing the same outcome assessment measures.

Remarkable Diagnostic Magnetic Resonance Imaging Findings in Sellar Xanthogranuloma: Report of Three First Cases in Latin America.

The sellar xanthogranuloma is a rare lesion of the sellar-parasellar region difficult to differentiate from other tumors such as craniopharyngiomas or Rathke's cleft cyst in the preoperative evaluation. As they are recently recognized as a separate entity and the few number of reports in the literature, its etiology is unknown and its impact remains uncertain. This article will describe the first three cases reported in Latin America, identified in one of them an imaging feature that may be helpful to elucidate an imaging growth pattern. Current evidence will be described regarding to the clinicopathological features, imaging diagnosis, and etiology origin theories.

A novel double-enhanced suicide gene therapy in a colon cancer cell line mediated by gef and apoptin.

BACKGROUND: Double-suicide gene therapy is a promising strategy for the treatment of advanced cancer. It has become an important research line in the development of gene therapy to overcome the drawbacks of single-gene therapy. OBJECTIVE: The aim of this study was to investigate the usefulness of double-suicide gene therapy with the two suicide genes, gef and apoptin, in colon carcinoma. METHODS: gef and apoptin genes were cloned into a doxycycline-regulated retrovirus-mediated gene expression system. Expression of both genes in the DLD-1 cell line was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). Cell viability was determined with the sulforhodamine B colorimetric assay, and the cell cycle was studied by propidium iodide (PI) staining. Annexin V-FITC and PI assays were used to evaluate apoptosis, and the results were confirmed by electron microscopy. The mitochondrial membrane potential was measured by JC-1 assay. RESULTS: Our results showed that the combined expression of gef and apoptin genes was strikingly more effective than the expression of either gene alone. Co-expression of gef and apoptin synergistically enhanced the decrease in cell viability, increasing necrosis and inducing apoptosis in colon cancer cells via the mitochondrial pathway, which can be deficient in advanced or metastatic colon cancer. CONCLUSIONS: Double-suicide gene therapy based on gef and apoptin genes may be a candidate for the development of new colon cancer strategies, and further studies are warranted to establish the usefulness of double-suicide gene therapy in vivo.

NT-ProBNP: marcador biológico útil para monitorización del estado clínico y como factor pronóstico en pacientes ambulatorios portadores de insuficiencia cardíaca sistólica / NT-Pro BNP: biomarker for monitoring of clinical status and as a prognostic marker in ambulatory patients with systolic heart failure / NT-proBNP: biomarcador útil para monitorizaþÒo do estado clínico e como um fator de prognóstico em pacientes ambulatoriais com insuficiÛncia cardíaca sistólica

Resumen Introducción. Los péptidos natriuréticos (BNP y NT-proBNP) representan una herramienta de notable valor en el contexto de la insuficiencia cardíaca. El objetivo de este estudio fue evaluar la utilidad del NT-proBNP para la monitorización del estado clínico y como marcador pronóstico en pacientes ambulatorios con insuficiencia cardíaca sistólica (ICS), estableciendo un valor de corte de dicho marcador que permitiese predecir el riesgo de presentar eventos adversos. Material y métodos. Se realizó un estudio longitudinal prospectivo y analítico, de una cohorte de 74 pacientes con ICS (fracción de eyección del ventrículo izquierdo, FEVI < 40%) pertenecientes a la Unidad Multidisciplinaria de Insuficiencia Cardíaca (UMIC). El estudio constó de dos etapas analíticas separadas por un período de seguimiento de 18 meses. En cada consulta un médico del área asistencial consignó el estado clínico del paciente, la determinación de los valores de NT-proBNP y el cálculo de la FEVI por ecocardiografía en la primera consulta (t0) y en la evolución (t1). Se analizaron las variables: clase funcional (CF), FEVI y concentración de NT-proBNP al inicio del estudio (t0) y en la evolución (t1), así como la relación entre las mismas, y el desarrollo de eventos adversos durante el seguimiento. Para la determinación del punto de corte se calcularon medidas de sensibilidad y especificidad mediante la utilización de curvas ROC. Resultados. Se objetivó una relación entre los valores de NT-proBNP y la CF con valores progresivamente mayores de NT-proBNP en pacientes con peor CF. La media de NT-proBNP (pg/ml) para los pacientes con FEVI 35% fue de 492,6 ± 105,7 (t0) y 607,4± 107,9 (t1), con valores de p=0,000 y 0,001, respectivamente. El 50% de los pacientes presentó un evento adverso durante la evolución. Para la ausencia de eventos adversos la media de NT-proBNP fue de 411,6 ± 89,6 (t0) y 368,6± 59,2 (t1), mientras que para la presencia de eventos adversos fue de 1716,6 ± 62,0 (t0) y 1382,1 ± 152,3 (t1), con valores de p=0,000. Respecto al punto de corte de NT-proBNP, se evidenció que el valor de 1000 pg/ml es estadísticamente significativo como predictor de eventos adversos en pacientes con similar CF y FEVI, con una sensibilidad del 91,9%y una especificidad del 78,4%, un coeficiente falso negativo del 8,1% y un coeficiente falso positivo del 21,6%. Conclusión. Este análisis confirma la evidencia de la eficacia del NT-proBNP como parámetro para la monitorización del estado clínico en pacientes con ICS, destacando el hallazgo de un valor de corte (1000 pg/ml) como predictor de eventos adversos con sensibilidad y especificidad aceptables.(AU)

Introduction. The natriuretic peptides (BNP and NT-proBNP) represent a tool of considerable value in the context of heart failure (HF). The aim of this study was to evaluate the utility of NT-proBNP for monitoring of clinical status and as a prognostic biomarker in ambulatory patients with systolic heart failure (SHF) setting a cutoff value that enable us to predict the risk of adverse events. Methods. An analytic and prospective longitudinal study of a cohort of 74 patients with SHF (left ventricular ejection fraction, LVEF < 40%) from the Multidisciplinary Heart Failure Unit was performed. The study was carried out in two different analytic stages separated by a 18 month-follow-up period. At each visit a doctors care area appropriated the patients clinical status, the determination of NT-proBNP blood values and the calculation of LVEF by echocardiography at the first visit (t0) and evolution (t1). Variables were analyzed: functional class (FC), LVEF and concentration of NT-proBNP at baseline (t0) and evolution (t1), and the relationship between them, and the development of adverse events during the follow-up. To determine the cutoff point were calculated measures of sensitivity and specificity by using ROC curves. Results. A relationship between progressively higher NT-proBNP values and the degree CF was observed. The mean value of NT-proBNP (pg/ml) for patients with LVEF 35% was 492.6 ± 105.7 pg/ml (t0) and 607.4 ± 107.9 pg/ml (t1), with value of p=0.000 and 0.001, respectively. The 50% of patients presented an adverse event during the followup. To the absence of adverse events mean NT-proBNP was 411.6 ± 89.6 pg/ml (t0) and 368.6 ± 59.2 pg/ml (t1), whereas the presence of adverse events was 1716.6 ± 62.0 (t0) and 1382.1 ± 152.3 (t1), with values of p = 0.000. Regarding the cutoff of NT-proBNP, it was shown that the value of 1000 pg/ml is statistically significant as a predictor of adverse events in patients with similar degree of HF and LVEF, with a sensibility of 91.9%, specificity of 78.4%, and false negative rate of 8.1% and false positive rate of 21.6%. Conclusion. This study confirms the evidence of the efficacy of NT-proBNP as a parameter for monitoring of clinical status in patients with SHF, highlighting the finding of a cut-off value of 1000 pg/ml as a predictor of adverse events with an acceptable sensibility and specificity.(AU)

IntroduþÒo. Os peptídeos natriuréticos (BNP e NT-proBNP) representam uma ferramenta de valor considerável no quadro de insuficiÛncia cardíaca. O objetivo deste estudo foi avaliar a utilidade de NT-proBNP para monitorizaþÒo do estado clínico e como um biomarcador de prognóstico em pacientes ambulatoriais com insuficiÛncia cardíaca sistólica (ICS), estabelecendo um valor de corte deste marcador, que permitiria predizer o risco de eventos efeitos. Material e métodos. Foi realizado um estudo longitudinal prospectivo e analítico de uma coorte de 74 pacientes com ICS (fraþÒo de ejeþÒo do ventrículo esquerdo, FEVE < 40%), pertencentes O Unidade Multidisciplinar de InsuficiÛncia Cardíaca (UMIC). O estudo consistiu em duas etapas analíticas separadas por um período de seguimento de 18 meses. Em cada visita, um médico da área de assistÛncia corroborou o estado clínico do paciente, a determinaþÒo dos valores de NT-proBNP e o cálculo da FEVE pela ecocardiografia na primeira visita (t0) e evoluþÒo (t1). Foram analisadas as va

NT-ProBNP: marcador biológico útil para monitorización del estado clínico y como factor pronóstico en pacientes ambulatorios portadores de insuficiencia cardíaca sistólica / NT-Pro BNP: biomarker for monitoring of clinical status and as a prognostic marker in ambulatory patients with systolic heart failure / NT-proBNP: biomarcador útil para monitorização do estado clínico e como um fator de prognóstico em pacientes ambulatoriais com insuficiência cardíaca sistólica

Resumen Introducción. Los péptidos natriuréticos (BNP y NT-proBNP) representan una herramienta de notable valor en el contexto de la insuficiencia cardíaca. El objetivo de este estudio fue evaluar la utilidad del NT-proBNP para la monitorización del estado clínico y como marcador pronóstico en pacientes ambulatorios con insuficiencia cardíaca sistólica (ICS), estableciendo un valor de corte de dicho marcador que permitiese predecir el riesgo de presentar eventos adversos. Material y métodos. Se realizó un estudio longitudinal prospectivo y analítico, de una cohorte de 74 pacientes con ICS (fracción de eyección del ventrículo izquierdo, FEVI < 40%) pertenecientes a la Unidad Multidisciplinaria de Insuficiencia Cardíaca (UMIC). El estudio constó de dos etapas analíticas separadas por un período de seguimiento de 18 meses. En cada consulta un médico del área asistencial consignó el estado clínico del paciente, la determinación de los valores de NT-proBNP y el cálculo de la FEVI por ecocardiografía en la primera consulta (t0) y en la evolución (t1). Se analizaron las variables: clase funcional (CF), FEVI y concentración de NT-proBNP al inicio del estudio (t0) y en la evolución (t1), así como la relación entre las mismas, y el desarrollo de eventos adversos durante el seguimiento. Para la determinación del punto de corte se calcularon medidas de sensibilidad y especificidad mediante la utilización de curvas ROC. Resultados. Se objetivó una relación entre los valores de NT-proBNP y la CF con valores progresivamente mayores de NT-proBNP en pacientes con peor CF. La media de NT-proBNP (pg/ml) para los pacientes con FEVI 35% fue de 492,6 ± 105,7 (t0) y 607,4± 107,9 (t1), con valores de p=0,000 y 0,001, respectivamente. El 50% de los pacientes presentó un evento adverso durante la evolución. Para la ausencia de eventos adversos la media de NT-proBNP fue de 411,6 ± 89,6 (t0) y 368,6± 59,2 (t1), mientras que para la presencia de eventos adversos fue de 1716,6 ± 62,0 (t0) y 1382,1 ± 152,3 (t1), con valores de p=0,000. Respecto al punto de corte de NT-proBNP, se evidenció que el valor de 1000 pg/ml es estadísticamente significativo como predictor de eventos adversos en pacientes con similar CF y FEVI, con una sensibilidad del 91,9%y una especificidad del 78,4%, un coeficiente falso negativo del 8,1% y un coeficiente falso positivo del 21,6%. Conclusión. Este análisis confirma la evidencia de la eficacia del NT-proBNP como parámetro para la monitorización del estado clínico en pacientes con ICS, destacando el hallazgo de un valor de corte (1000 pg/ml) como predictor de eventos adversos con sensibilidad y especificidad aceptables.

Introduction. The natriuretic peptides (BNP and NT-proBNP) represent a tool of considerable value in the context of heart failure (HF). The aim of this study was to evaluate the utility of NT-proBNP for monitoring of clinical status and as a prognostic biomarker in ambulatory patients with systolic heart failure (SHF) setting a cutoff value that enable us to predict the risk of adverse events. Methods. An analytic and prospective longitudinal study of a cohort of 74 patients with SHF (left ventricular ejection fraction, LVEF < 40%) from the Multidisciplinary Heart Failure Unit was performed. The study was carried out in two different analytic stages separated by a 18 month-follow-up period. At each visit a doctor's care area appropriated the patient's clinical status, the determination of NT-proBNP blood values and the calculation of LVEF by echocardiography at the first visit (t0) and evolution (t1). Variables were analyzed: functional class (FC), LVEF and concentration of NT-proBNP at baseline (t0) and evolution (t1), and the relationship between them, and the development of adverse events during the follow-up. To determine the cutoff point were calculated measures of sensitivity and specificity by using ROC curves. Results. A relationship between progressively higher NT-proBNP values and the degree CF was observed. The mean value of NT-proBNP (pg/ml) for patients with LVEF 35% was 492.6 ± 105.7 pg/ml (t0) and 607.4 ± 107.9 pg/ml (t1), with value of p=0.000 and 0.001, respectively. The 50% of patients presented an adverse event during the followup. To the absence of adverse events mean NT-proBNP was 411.6 ± 89.6 pg/ml (t0) and 368.6 ± 59.2 pg/ml (t1), whereas the presence of adverse events was 1716.6 ± 62.0 (t0) and 1382.1 ± 152.3 (t1), with values of p = 0.000. Regarding the cutoff of NT-proBNP, it was shown that the value of 1000 pg/ml is statistically significant as a predictor of adverse events in patients with similar degree of HF and LVEF, with a sensibility of 91.9%, specificity of 78.4%, and false negative rate of 8.1% and false positive rate of 21.6%. Conclusion. This study confirms the evidence of the efficacy of NT-proBNP as a parameter for monitoring of clinical status in patients with SHF, highlighting the finding of a cut-off value of 1000 pg/ml as a predictor of adverse events with an acceptable sensibility and specificity.

Introdução. Os peptídeos natriuréticos (BNP e NT-proBNP) representam uma ferramenta de valor considerável no quadro de insuficiência cardíaca. O objetivo deste estudo foi avaliar a utilidade de NT-proBNP para monitorização do estado clínico e como um biomarcador de prognóstico em pacientes ambulatoriais com insuficiência cardíaca sistólica (ICS), estabelecendo um valor de corte deste marcador, que permitiria predizer o risco de eventos efeitos. Material e métodos. Foi realizado um estudo longitudinal prospectivo e analítico de uma coorte de 74 pacientes com ICS (fração de ejeção do ventrículo esquerdo, FEVE < 40%), pertencentes à Unidade Multidisciplinar de Insuficiência Cardíaca (UMIC). O estudo consistiu em duas etapas analíticas separadas por um período de seguimento de 18 meses. Em cada visita, um médico da área de assistência corroborou o estado clínico do paciente, a determinação dos valores de NT-proBNP e o cálculo da FEVE pela ecocardiografia na primeira visita (t0) e evolução (t1). Foram analisadas as variáveis: classe funcional (CF), FEVE e concentração de NT-proBNP no início do estudo (t0) e evolução (t1), e a relação entre eles, e no desenvolvimento de eventos adversos durante o seguimento. Para determinar o ponto de corte foram calculadas as medidas de sensibilidade e especificidade, utilizando curvas ROC. Resultados. Observou-se uma relação entre os valores de NT-proBNP e CF com valores progressivamente mais elevados de NT-proBNP em pacientes com uma pior CF. O valor médio de NT-proBNP (pg/ml) para os pacientes com FEVE 35% foi 492,6 ± 105,7 pg/ml (t0) e 607,4 ± 107,9 pg/ml (t1), com valores de p=0,000 e 0,001, respectivamente.O 50% dos pacientes apresentou um evento adverso durante a evolução. O valor médio de NT-proBNP (pg/ml) para a ausência de eventos adversos foi de 411,6 ± 89,6 pg/ml (t0) e 368,6 ± 59,2 pg/ml (t1), enquanto a presença de eventos adversos foi de 1716,6 ± 62,0 (t0) e 1382,1 ± 152,3 (t1), com valores de p=0,000. Em relação ao ponto de corte de NT-proBNP, demonstrou-se que o valor de 1000 pg/ml é estatisticamente significativa como um preditor de eventos adversos em pacientes com grau semelhante de CF e FEVE, com uma sensibilidade do 91,9% e especificidade do 78,4% , taxa de falso negativo do 8,1% e taxa de falso positivo do 21,6%. Conclusão. Este estudo confirma a evidência da eficácia de NT-proBNP como parâmetro para a monitorização do estado clínico em pacientes com ICS, destacando um valor de corte de 1000 pg/ml como preditor de eventos adversos com uma sensibilidade e especificidade aceitável.

Melhoria da Atenção à Saúde dos Usuários Hipertensos e/ou Diabéticos na UBS Deus Me Deu, José de Freitas/PI

SUAREZ, Alvarez, Pablo. Melhoria da atenção à saúde dos usuários hipertensos e/ou diabéticos na UBS Deus me Deu, José de Freitas / PI. Ano. 2015. 65f. Trabalho de Conclusão de Curso (Curso de Especialização em Saúde da Família) - Departamento de Medicina Social, Faculdade de Medicina, Universidade Federal de Pelotas, Pelotas, Ano 2015. A hipertensão arterial sistêmica representa grave problema de saúde no país e que apresenta elevada prevalência. As complicações crônicas do diabetes são as principais responsáveis pela morbidade e mortalidade dos pacientes diabéticos. Devido ao crescimento destas doenças crônicas não transmissíveis e à baixa cobertura encontrada na UBS Deus me Deu a equipe acordou em realizar a intervenção como foco hipertensão arterial e diabetes mellitus. O projeto de intervenção teve como objetivo melhorar a atenção à saúde dos usuários com hipertensão e/ou diabetes na UBS Deus Me Deu no município de José de Freitas, Piauí. A intervenção exigiu capacitação de toda a equipe de acordo com o protocolo do Ministério da Saúde. Como metodologia empregada foram seguidos quatro eixos pedagógicos: organização e gestão dos serviços, qualificação da prática clínica, engajamento público e monitoramento e avaliação. Utilizamos as fichas espelho fornecidas pelo curso e planilha de coleta de dados. A intervenção teve duração de 12 semanas de março a junho de 2015. Os indicadores mostraram que houve melhoria na atenção a saúde dos usuários e a maioria das metas foram alcançadas. Antes da intervenção tinha-se como meta atingir 75% de cobertura para os hipertensos e 80% para os diabéticos. Ao final da intervenção 237 (86,5%) usuários com hipertensão e 67 (98,5%) com diabetes foram cadastrados. Em relação aos indicadores de qualidade todos os usuários cadastrados estavam com os exames clínicos e complementares em dia, todos possuem prescrição de medicamentos da farmácia popular e estão com a avaliação da necessidade de atendimento odontológico em dia. As ações relativas à promoção da saúde como orientações sobre atividade física, risco do tabagismo e sobre higiene bucal foram repassadas para todos os usuários cadastrados. A intervenção permitiu organizar o trabalho de forma sistemática, fazendo com que cada membro da equipe saiba sua função. O sucesso da melhoria da cobertura desta intervenção foi fruto de trabalho de toda a equipe, comunidade e gestão. Com experiência já obtida pretende-se incrementar futuramente a ação programática relativa à prevenção do câncer de mama e colo do útero, contribuindo assim para a saúde geral da população.