Quantitative chemometric phenotyping of three-dimensional liver organoids by Raman spectral imaging.

Confocal Raman spectral imaging (RSI) enables high-content, label-free visualization of a wide range of molecules in biological specimens without sample preparation. However, reliable quantification of the deconvoluted spectra is needed. Here we develop an integrated bioanalytical methodology, qRamanomics, to qualify RSI as a tissue phantom calibrated tool for quantitative spatial chemotyping of major classes of biomolecules. Next, we apply qRamanomics to fixed 3D liver organoids generated from stem-cell-derived or primary hepatocytes to assess specimen variation and maturity. We then demonstrate the utility of qRamanomics for identifying biomolecular response signatures from a panel of liver-altering drugs, probing drug-induced compositional changes in 3D organoids followed by in situ monitoring of drug metabolism and accumulation. Quantitative chemometric phenotyping constitutes an important step in developing quantitative label-free interrogation of 3D biological specimens.

Denervação simpática renal no tratamento da hipertensão arterial resistente: relato de caso / Renal sympathetic denervation in the treatment of resistant arterial hypertension: case report

Introdução: A hipertensão arterial sistêmica (HAS) pode levar a consequências cardiovasculares graves quando não tratadas adequadamente. No entanto, alguns indivíduos, mesmo realizando tratamento recomendado, a pressão arterial (PA) se mantém elevada, passando a ser chamada de hipertensão arterial refratária (HAR). A denervação simpática renal (DSR) é uma terapia amplamente estuda e com resultados promissores que surgiu como alternativa para controlar a PA em pacientes resistentes ao tratamento convencional. Relato de caso: Participante da pesquisa, sexo masculino, 67 anos, com queixa de cefaleia e elevação dos níveis pressóricos. Avaliação cardíaca com alteração apenas da PA (182x113 mmHg), demais sistemas sem variações. Diagnosticado com HAS estágio 3, realizou todas as etapas do tratamento medicamentoso, porém resistente as terapias propostas. Diante do caso, foi diagnosticado com HAR. Sendo realizado DSR que mostrou resultados satisfatórios de redução progressiva da pressão arterial central e periférica. Conclusão: A DSR mostrou-se eficaz no controle gradual e sustentado da PA do participante da pesquisa. Contudo, somente através de estudos clínicos mais amplos e rigorosos será capaz de comprovar a eficácia da DSR no tratamento da PA alta persistente (AU).

Introduction: Systemic arterial hypertension (SHT) can lead to severe cardiovascular outcomes when not properly treated. However, in some individuals, even with recommended treatment, blood pressure (BP) remains high, and is now referred to as Resistant hypertension (RHTN). Renal sympathetic denervation (RDn) is a widely studied and promising therapy that has emerged as an alternative to control BP in patients resistant to conventional treatment. Case report: Research participant, male, 67 years old, complaining of headache and elevated blood pressure. Cardiac assessment with only BP alteration (182x113 mmHg), other systems without variations. Diagnosed with stage 3 hypertension, performed all stages of drug treatment, but resistant to the proposed therapies. Given the case, was diagnosed with RHTN. Being performed RDn that showed satisfactory results of progressive reduction of central and peripheral blood pressure. Discussion: Sympathetic hyperactivity of the renal nervous system releases catecholamines that raise BP. Based on this, the RDn uses a catheter connected to the radiofrequency device that through the femoral artery goes to the two renal arteries and emits energy in the sympathetic fibers attached to the walls of these arteries, destroying them. RDn has been the target of several clinical studies, the best-known being Simplicity HTN-1, 2 and 3 which brought significant and questionable results regarding the efficacy of the procedure. Conclusion: RDn proved to be effective in gradually and sustained BP control of the research participant. However, only through broader and more rigorous clinical studies will it be able to prove the efficacy of RDn in combating persistent high BP (AU).

Spontaneous expulsion of a submucosal uterine fibroid without embolization in a pre-menopausal woman.

Uterine leiomyomas are benign tumors that develop from smooth muscle tissue and are present in up to 77% of women in menacme. They are often asymptomatic but can cause pelvic pain, compression, abnormal uterine bleeding, and degeneration. We present the first case report of a perimenopausal woman who exhibited complete and spontaneous expulsion of uterine fibroids without embolization or use of medication. She complained of a mass extruding from the vaginal orifice associated with bleeding and pain for a couple of hours. The anatomopathological findings showed a myomatous lesion. Complete expulsion of a uterine fibroid is a rare condition that may be associated with profuse hemorrhage and can pose a risk to the patient. When it occurs during perimenopause, it can mimic several clinical conditions. Therefore, gynecologists must remain alert to make the correct diagnosis and treatment.

The accuracy of the Montenegro skin test for leishmaniasis in PCR-negative patients.

INTRODUCTION: As highly specific molecular biology-based techniques may not be sensitive enough for the diagnosis of American tegumentary leishmaniasis (ATL), clinicians frequently rely on immunological tests before treatment initiation. Hence, the correct combination of diagnostic tests is imperative for ATL diagnosis. We aimed to evaluate the accuracy of the Montenegro (Leishmanin) skin test (MST) in polymerase chain reaction (PCR)-negative patients to accurately detect ATL. METHODS: Patients with a clinical picture compatible with ATL were divided into ATL (confirmed by lesion smear, culture indirect immunofluorescence, and/or histopathology) and no-ATL (diseases that can mimic leishmaniasis) groups. Conventional PCR for the minicircle kDNA of Leishmania was performed, and the MST was carried out for PCR-negative patients. RESULTS: Ninety-nine patients were included in this study, including 79 diagnosed with ATL (6 with mucocutaneous leishmaniasis) and 20 without ATL (no-ATL group). The MST showed a high sensitivity of 90.0% (95% confidence interval [CI] = 69.90-97.21) in PCR-negative patients that was 10% higher than the sensitivity reported in PCR-positive population (79.66%; 95% CI = 67.73-87.96). CONCLUSIONS: One of the most important reasons for PCR negativity among patients with active ATL is the presence of a strong cellular immunological response, especially in chronic and mucocutaneous leishmaniasis. This reinforces the considerable utility of the tests that detect cellular responses against Leishmania antigens such as the MST in PCR-negative patients when the performance in screening situations is questionable.

The accuracy of the Montenegro skin test for leishmaniasis in PCR-negative patients

Abstract INTRODUCTION: As highly specific molecular biology-based techniques may not be sensitive enough for the diagnosis of American tegumentary leishmaniasis (ATL), clinicians frequently rely on immunological tests before treatment initiation. Hence, the correct combination of diagnostic tests is imperative for ATL diagnosis. We aimed to evaluate the accuracy of the Montenegro (Leishmanin) skin test (MST) in polymerase chain reaction (PCR)-negative patients to accurately detect ATL. METHODS: Patients with a clinical picture compatible with ATL were divided into ATL (confirmed by lesion smear, culture indirect immunofluorescence, and/or histopathology) and no-ATL (diseases that can mimic leishmaniasis) groups. Conventional PCR for the minicircle kDNA of Leishmania was performed, and the MST was carried out for PCR-negative patients. RESULTS: Ninety-nine patients were included in this study, including 79 diagnosed with ATL (6 with mucocutaneous leishmaniasis) and 20 without ATL (no-ATL group). The MST showed a high sensitivity of 90.0% (95% confidence interval [CI] = 69.90-97.21) in PCR-negative patients that was 10% higher than the sensitivity reported in PCR-positive population (79.66%; 95% CI = 67.73-87.96). CONCLUSIONS: One of the most important reasons for PCR negativity among patients with active ATL is the presence of a strong cellular immunological response, especially in chronic and mucocutaneous leishmaniasis. This reinforces the considerable utility of the tests that detect cellular responses against Leishmania antigens such as the MST in PCR-negative patients when the performance in screening situations is questionable.

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial.

BACKGROUND: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage. METHODS: This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution. DISCUSSION: The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil. TRIAL REGISTRATION: Clinical Trials NCT00970931.

A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double-blind controlled trial.

BACKGROUND: Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted. METHODS/DESIGN: This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution. DISCUSSION: The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov: NCT00971165.

Do Brazilian physicians follow the Brazilian guidelines on hypertension?

OBJECTIVE: To evaluate whether procedures adopted by Brazilian physicians in the diagnosis and treatment of hypertension are in compliance with those advocated by the IV Brazilian Hypertension Guidelines. METHOD: Survey carried out by means of telephone interviews with Brazilian physicians. The survey featured application of a questionnaire aimed to assess receipt of and compliance with the guidelines, and to evaluate various aspects regarding the treatment of hypertensive patients. RESULTS: 68.3% of the respondents had received the guidelines and answered the questionnaire in full. The total sample consisted of 483 physicians--47% cardiologists, 31.7% internists, and 21.3% nephrologists. The survey showed high compliance with certain guideline topics such as more than one measurement at different times for the diagnosis of hypertension (94%), and providing guidance regarding lifestyle changes as a therapeutic strategy. As to arterial pressure levels used for diagnosis and therapeutic target, compliance with guideline recommendations lacks uniformity. The survey showed a clear preference for pressure levels lower than those recommended, especially in patients with comorbidities. Attempts to assess cardiovascular risk also proved to be low. Only 64.7% of the respondents reported that they seek to determine the presence of diabetes mellitus, and 56.4% check for dyslipidemia. The majority (59.3%) mentioned diuretics as the preferred drug class for initial drug treatment of hypertension. CONCLUSION: We concluded that there is only partial compliance with Brazilian Hypertension Guidelines and that certain factors should be taken into consideration when drawing up future guidelines, such as: improved distribution; standardization of values for diagnosis and therapeutic target; more extensive coverage of ways for physicians to approach hypertensive patients to better evaluate their overall cardiovascular risk.

Os médicos brasileiros seguem as diretrizes brasileiras de hipertensão? / Do Brazilian physicians follow the Brazilian guidelines on hypertension?

OBJETIVO: Avaliar os procedimentos adotados pelos médicos brasileiros para o diagnóstico e tratamento da hipertensão em relação aos preconizados pelas IV Diretrizes Brasileiras de Hipertensão. MÉTODOS: Questionário aplicado por entrevista telefônica a médicos brasileiros, buscando levantar recebimento e adesão às diretrizes, bem como avaliar vários aspectos relacionados ao manejo do paciente hipertenso. RESULTADOS: 68,3 por cento dos médicos receberam às diretrizes e responderam completamente o questionário, perfazendo uma amostra de 483 médicos, sendo 47 por cento cardiologistas, 31,7 por cento clínicos e 21,3 por cento nefrologistas. A adesão a certos pontos das diretrizes é alta, tais como à utilização de mais de uma medida em ocasiões diferentes para o diagnóstico de hipertensão (94,0 por cento) e orientação quanto a mudanças no estilo de vida como estratégia terapêutica. Quanto aos valores utilizados para diagnóstico e alvo-terapêutico, o seguimento as recomendações não é uniforme, com uma nítida preferência por valores inferiores aos preconizados, particularmente para pacientes com co-morbidades. A procura por fatores de risco cardiovascular também se mostrou baixa, com apenas 64,7 por cento e 56,4 por cento dos médicos referindo pesquisar, respectivamente, a presença de diabetes e dislipidemia. Os diuréticos são a classe de droga preferencialmente citada (59,3 por cento) como tratamento medicamentoso inicial da hipertensão. CONCLUSÃO: O seguimento as diretrizes é apenas parcial. Questões como uma melhor distribuição do documento, normatização de valores para diagnóstico e alvo-terapêutico e formas de abordar o paciente hipertenso dentro de seu risco cardiovascular global deverão ser mais bem abordadas quando da confecção de futuras diretrizes.

OBJECTIVE: To evaluate whether procedures adopted by Brazilian physicians in the diagnosis and treatment of hypertension are in compliance with those advocated by the IV Brazilian Hypertension Guidelines. METHOD: Survey carried out by means of telephone interviews with Brazilian physicians. The survey featured application of a questionnaire aimed to assess receipt of and compliance with the guidelines, and to evaluate various aspects regarding the treatment of hypertensive patients. RESULTS: 68.3 percent of the respondents had received the guidelines and answered the questionnaire in full. The total sample consisted of 483 physicians - 47 percent cardiologists, 31.7 percent internists, and 21.3 percent nephrologists. The survey showed high compliance with certain guideline topics such as more than one measurement at different times for the diagnosis of hypertension (94 percent), and providing guidance regarding lifestyle changes as a therapeutic strategy. As to arterial pressure levels used for diagnosis and therapeutic target, compliance with guideline recommendations lacks uniformity. The survey showed a clear preference for pressure levels lower than those recommended, especially in patients with comorbidities. Attempts to assess cardiovascular risk also proved to be low. Only 64.7 percent of the respondents reported that they seek to determine the presence of diabetes mellitus, and 56.4 percent check for dyslipidemia. The majority (59.3 percent) mentioned diuretics as the preferred drug class for initial drug treatment of hypertension. CONCLUSION: We concluded that there is only partial compliance with Brazilian Hypertension Guidelines and that certain factors should be taken into consideration when drawing up future guidelines, such as: improved distribution; standardization of values for diagnosis and therapeutic target; more extensive coverage of ways for physicians to approach hypertensive patients to better evaluate their overall...

Tratamento cirúrgico da origem anômala da coronária esquerda da artéria pulmonar: nova técnica e relato de caso / Surgical treatment of anomalous origin of the left coronary artery from pulmonary artery: new technic and report of a case

Uma nova técnica para correçäo de origem anômala da artéria coronária esquerda da pulmonar é descrita. Consiste na confecçäo de un túnel transpulmonar, entre a aorta e o orifício coronário anômalo, utilizando um retalho da parede anterior da artéria pulmonar e parede posterior da artéria pulmonar. É apresentado o estudo hemodinâmico, pré e pós-operatório, de um caso operado por esta técnica

Fio radiopaco para localização de pontes de safena / Radiopaque thread for localization of saphenous grafts

E apresentada uma tecnica simples e efetiva para marcacao do orificio de anastomose de pontes de safena na aorta. Consiste no aproveitamento do fio radiopaco que acompanha as gases cirurgicas comuns, que a fixado em torno da anastomose aortica

Avaliação hemodinâmica pós-operatória da via de saída do ventrículo direito / Postoperative hemodynamic evaluation of the right ventricular outflow tract

Foram estudados hemodinamicamente, apos um ano de pos-operatorio, dez pacientes portadores de tetralogia de Fallot e estenose pulmonar valvar e infundibular. A via de saida do ventriculo direito foi analisada traves de manometria e angiocardiografia.Sao comentados aspectos da correcao cirurgica os quais foram relacionados aos achados hemodinamicos pos-operatorios