Antithrombotic regimens for the prevention of major adverse cardiac events in chronic coronary syndrome: A systematic review and network meta-analysis.

Backgroud: Antithrombotic therapy is the cornerstone of chronic coronary syndrome (CCS) management. However, the best treatment option that optimally balances bleeding risk and efficacy remains undefined. Our objective was to evaluate the effectiveness and safety of antithrombotic options and identify the optimal treatment option for patients with CCS. Methods: We used the MEDLINE, CENTRAL and Embase databases to search for randomized controlled trials with follow-up periods longer than 12 months that compared aspirin (ASA) monotherapy with other antithrombotic therapies in patients with CCS. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Extracted data [hazard ratios (HR)] were pooled using Bayesian fixed-effect models, allowing the estimation of credible intervals (CrI) and posterior probabilities of benefit, harm, and practical equivalence. Confidence in the results was assessed with the Confidence In Network Meta-Analysis (CINeMA) tool. The primary efficacy and safety outcomes were major adverse cardiovascular events (MACE) and primary bleeding, respectively. Secondary outcomes were acute myocardial infarction, ischemic stroke, all-cause, and cardiovascular-specific mortality. Results: Five trials with a total of 80,605 patients were included. Mean patient age ranged from 61 to 69 years, while 20.3% to 31.4% were women. The reference treatment was ASA monotherapy. ASA + prasugrel 10 mg and clopidogrel 75 mg monotherapy presented the greatest benefit for MACE [HR 0.52 (95% CrI, 0.39-0.71); and 0.68 (95% CrI, 0.54-0.88)]. There was a probability of 98.8% that ASA + ticagrelor was practically equivalent to ASA monotherapy. Regarding the primary bleeding outcome, clopidogrel 75 mg monotherapy performed best [HR 0.64 (0.42, 0.99)]. There was a probability of 97.4% that ASA + Prasugrel 10 mg increases bleeding (HR > 1.0). Secondary outcome results followed a similar treatment ranking pattern as in primary outcomes. Overall, CINeMA confidence ratings were judged as either low or very low. Conclusions: These results revealed that clopidogrel monotherapy might provide the best risk-benefit balance in treating CCS. However, low CINeMA confidence ratings may preclude more forceful conclusions. Our analysis suggests that current guidelines recommending ASA as first-line therapy for CCS management need to be revised to include additional pharmacological options.

Transcriptomic profiling of cardiac tissues from SARS-CoV-2 patients identifies DNA damage.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS-CoV-2 infection is likely to lead to more severe disease, with multi-organ effects, including cardiovascular disease. SARS-CoV-2 has been associated with acute and long-term cardiovascular disease, but the molecular changes that govern this remain unknown. In this study, we investigated the host transcriptome landscape of cardiac tissues collected at rapid autopsy from seven SARS-CoV-2, two pH1N1, and six control patients using targeted spatial transcriptomics approaches. Although SARS-CoV-2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1-like macrophage infiltration in the cardiac tissues of COVID-19 patients. The DNA damage present in the SARS-CoV-2 patient samples, were further confirmed by γ-H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of interferon-stimulated genes, in particular interferon and complement pathways, when compared with COVID-19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS-CoV-2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra-pulmonary organs, including the cardiovascular system of COVID-19 patients, to delineate the immunopathobiology of SARS-CoV-2 infection, and long term impact on health.

Bone density and quality in patients treated with direct-acting oral anticoagulants versus warfarin.

INTRODUCTION: Direct-acting oral anticoagulants (DOACs) are therapeutic alternatives to warfarin that act independently of vitamin K, thus not affecting bone matrix formation. The aim of this study was to compare bone mineral density (BMD) and microarchitecture in patients treated with DOACs versus warfarin. METHODS: Cross-sectional, observational study in patients using oral anticoagulants for >1 year and a paired control group (CG). Based on the type of anticoagulant used, the patients were grouped into a DOAC (DOACG) or warfarin (WG) group. All patients filled out a questionnaire and underwent BMD evaluation and trabecular bone score (TBS) measurement. RESULTS: In all, 150 patients were included (50 patients in each group). The mean age was 60.49 ± 7.48 years, and most participants were men (64%). The most frequent comorbidities were hypertension, dyslipidemia, and hyperglycemia (comparison between groups p > 0.05). Low bone mass was diagnosed in 42%, 50%, and 66% of the patients in the CG, DOACG, and WG, respectively (p = 0.012). On logistic regression analysis, BMD was associated with body mass index (BMI; odds ratio [OR] 0.846, 95% confidence interval [CI] 0.763-0.926, p = 0.001), creatinine level (OR 0.024, 95%CI 0.001-0.434, p = 0.017), and TBS value (OR 17.777, 95%CI 4.526-96.903, p = 0.000). The mean TBS decreased progressively from the CG to the DOACG and WG (1.328 ± 0.112, 1.264 ± 0.138, and 1.203 ± 0.112, respectively, p < 0.001). On multivariate linear regression, negative predictors of TBS included warfarin use (-0.06, 95%CI -0.11 to -0.02, p = 0.006), BMI (-0.01, 95%CI -0.01 to -0.00, p < 0.001), and hyperglycemia (-0.07, 95%CI -0.11 to -0.03, p = 0.003), while positive predictors were an active IPAQ classification (0.06, 95%CI 0.01-0.11, p = 0.029) and family history of hip fracture (0.07, 95%CI 0.01-0.14, p = 0.029). CONCLUSION: Patients using anticoagulants have lower BMD and TBS values compared with controls. This negative effect on bone was more pronounced with warfarin, but was also seen with DOACs.

Osteoprotegerin is a marker of cardiovascular mortality in patients with chronic kidney disease stages 3-5.

Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Osteoprotegerin (OPG), known to regulate bone mass by inhibiting osteoclast differentiation and activation, might also play a role in vascular calcification. Increased circulating OPG levels in patients with CKD are associated with aortic calcification and increased mortality. We assessed the predictive role of OPG for all-cause and cardiovascular mortality in patients with CKD stages 3-5 over a 5-year follow-up period. We evaluated the relationship between OPG and all-cause and cardiovascular mortality in 145 CKD patients (stages 3-5) in a prospective observational follow-up study. Inflammation markers, including high-sensitivity C-reactive protein, standard echocardiography, and estimation of intima-media thickness in the common carotid artery, were assessed at baseline, and correlations with OPG levels were determined. The cutoff values for OPG were defined using ROC curves for cardiovascular mortality. Survival was assessed during follow up lasting for up to 5.5 years using Fine and Gray model. A total of 145 (89 men; age 58.9 ± 15.0 years) were followed up. The cutoff value for OPG determined using ROC was 10 pmol/L for general causes mortality and 10.08 pmol/L for CV causes mortality. Patients with higher serum OPG levels presented with higher mortality rates compared to patients with lower levels. Aalen-Johansen cumulative incidence curve analysis demonstrated significantly worse survival rates in individuals with higher baseline OPG levels for all-cause and cardiovascular mortality (p < 0.001). In multivariate analysis, OPG was a marker of general and cardiovascular mortality independent of sex, age, CVD, diabetes, and CRP levels. When CKD stages were included in the multivariate analysis, OPG was an independent marker of all-cause mortality but not cardiovascular mortality. Elevated serum OPG levels were associated with higher all-cause and cardiovascular mortality risk, independent of age, CVD, diabetes, and inflammatory markers, in patients with CKD.

Age-dependent histomorphometric evolution of the corpus spongiosum.

PURPOSE: To quantify the age-dependent changes in the relative volume of elastic fibers, collagen fibers and the proportion of collagen types I/III in the corpus spongiosum of rats. METHODS: Forty-eight rats, raised under similar conditions, were divided into four groups (G1 to G4) and underwent penectomy at the ages of 6, 9, 12 and 24 months, respectively. Histological sections from the middle segment of the penis were stained with Weigert's resorcin-fuchsin, Masson's trichrome and Picrosirius red, the volumetric density of elastic fibers, collagen fibers and the proportion of collagen types I and III in the corpus spongiosum were determined by stereological analysis. RESULTS: A reduction in the proportion of collagen I/III between the groups G3 and G4 (p < 0.048) was observed. In the volumetric analysis of elastic fiber, we observed a significant rise between the groups G2 and G3 (p < 0.03) and a reduction of the volume between the groups G3 and G4 (p < 0.01). However, there was no difference in the quantity of total collagen between the groups (p > 0.54). CONCLUSIONS: Aging in rats did not change the quantity of total collagen but reduced the proportion of collagen types I/III and the volume of elastic fibers.

Nebivolol for the Treatment of Essential Systemic Arterial Hypertension: A Systematic Review and Meta-Analysis.

INTRODUCTION: Cardiovascular diseases are the main cause of mortality worldwide, and systemic arterial hypertension is associated with a large number of these cases. The objective of health professionals and health policies should be searching for the best therapeutics to control this disease. A recent consensus indicated that ß-blockers have recently lost their place in initial indications for the treatment of systemic arterial hypertension and are now more indicated for the treatment of hypertension in association with other clinical situations such as angina, heart failure and arrhythmia; however, it is known that this approach was based on studies that evaluated older ß-blockers such as atenolol. OBJECTIVE: The main objective of this study was to perform a systematic review with subsequent meta-analysis on the use of nebivolol for hypertensive disease treatment, comparing it with drugs of the main antihypertensive classes. METHODS: This systematic review was based on a search of the MEDLINE (via Pubmed), Scopus, Cochrane, International Pharmaceuticals Abstracts (IPA), and Lilacs databases for randomized and double-blind clinical trials. In addition, we also searched for gray literature studies, to 31 July 2015. Next, a cumulative meta-analysis was performed, with studies being added in a sequential manner, evaluating their impact on the combined effect. For this project, we only meta-analyzed direct comparisons of random effect. RESULTS: Overall, 981 clinical trials were included in this systematic review. After careful analysis, 34 randomized and double-blind clinical trials were included to investigate the efficacy of nebivolol on systolic (SBP) and diastolic blood pressure (DBP) control and adverse effects. The study population comprised 12,465 patients with systemic arterial hypertension (SAH) aged between 18 and 85 years; 17% of subjects were of Black ethnicity, approximately 55% were men, and almost 10% had diabetes. In SBP management, nebivolol was superior to other ß-blockers and diuretics and showed no difference in efficacy when compared with angiotensin receptor blockers or calcium channel blockers. There were insufficient studies on angiotensin-converting enzyme inhibitors for adequate comparison of both SBP and DBP control. For DBP control, nebivolol was more efficient than other ß-blockers, angiotensin receptor blockers, diuretics, and calcium channel blockers. DISCUSSION: Nebivolol is a third-generation ß-blocker with additional capabilities to improve blood pressure levels in patients with arterial hypertension, because it acts by additional mechanisms such as endothelium-dependent vasodilation associated with L-arginine and oxide nitric acid, nitric oxide activity on smooth muscle cells, decreasing platelet aggregation, and leukocyte adhesion in the endothelium, decreasing oxidative stress. Although nebivolol has shown good results in controlling hypertension in this study (with few adverse events when compared with placebo treatment) and has an unquestionable benefit in individuals with heart failure (mainly with reduced ejection fraction), there is a lack of studies proving the benefit of this drug for controlling hypertension and reducing clinical outcomes such as cardiovascular (or general) mortality, acute myocardial infarction, or stroke. CONCLUSIONS: Nebivolol demonstrated at least similar control of blood pressure levels in hypertensive individuals when compared with drugs of the most used classes. In addition, in relation to the control of arterial hypertension, studies with clinical outcomes should be performed to ensure the use of this drug in detriment to others with these well-established results.

Early medical school graduation during the COVID-19 pandemic: preliminary assessment / Graduação antecipada do curso de medicina durante a pandemia de COVID-19: avaliação preliminar

Abstract: Introduction: The current outbreak of the new coronavirus or SARS-CoV-2, which causes COVID-19, was first reported to the World Health Organization on December 31, 2019, being declared a pandemic on March 11, 2020. As for the clinical spectrum of SARS-CoV-2 infection, it is a broad one, ranging from asymptomatic, mild upper respiratory tract disease to severe viral pneumonia with respiratory failure and death. With a chance of severe clinical presentation close to 25%, SARS-CoV-2 infection can lead to health service overload and increase the demand for material and human resources. Aiming to increase the availability of health professionals directly involved in care during the pandemic, the Ministry of Education authorized the early graduation for students pursuing careers in health, including medicine. Objective: The aim of this article is to obtain preliminary results of the impact of early graduation for medical students during the COVID-19 pandemic. Method: Observational and cross-sectional study, carried out by applying a questionnaire with 13 questions, five of which used a Likert scale of assessment, six in multiple choice format and two descriptive, via Google Forms, applied to medical students from the universities of Curitiba-PR that graduated earlier in mid-year 2020, due to the COVID-19 pandemic. Results: 113 recently graduated students answered the questionnaire.101 participants reported that they are working as physicians and, among them, 63.36% stated that they are working directly in the treatment of COVID-19 cases. Regarding the importance of an early graduation, most participants fully agree or agree, while only three participants totally disagree. More than half of the interviewees do not feel harmed by the early graduation. However, 43.3% believe they have failed to acquire important information for their training. Finally, regarding their performance in the pandemic, 79.6% consider important their role in the fight against COVID-19 pandemic. Conclusion: The study shows that, at first, the efforts to give the Class of 2020 an early graduation were successful, since these new physicians are contributing to alleviate workforce shortages and provide better care for patients during the pandemic.

Resumo: Introdução: O atual surto do novo coronavírus ou Sars-CoV-2, causador da Covid-19, foi relatado pela primeira vez à Organização Mundial da Saúde, pela China, em 31 de dezembro de 2019, sendo declarada pandemia em 11 de março de 2020. Quanto ao espectro clínico da infecção pelo Sars-CoV-2, ele é amplo, variando de quadro assintomático, doença leve do trato respiratório superior, a pneumonia viral grave com insuficiência respiratória e morte. Com uma chance de apresentação clínica grave próxima a 25%, a infecção pelo Sars-CoV-2 pode levar à sobrecarga dos serviços de saúde e aumentar a demanda tanto por recursos materiais como humanos. Para aumentar a disponibilidade de profissionais da área da saúde envolvidos diretamente no atendimento durante a pandemia, o Ministério da Educação autorizou a antecipação da formatura para estudantes de várias áreas da saúde, incluindo Medicina. Objetivo: O objetivo do presente artigo é realizar uma avaliação preliminar do impacto da antecipação da graduação para os formandos de Medicina durante a pandemia de Covid-19. Método: Trata-se de estudo observacional e transversal realizado por meio da aplicação de questionário com 13 perguntas: em cinco, utilizou-se escala Likert de avaliação; em seis, adotou-se o formato de múltipla escolha; e duas foram descritivas. O questionário foi enviado, via Formulário Google, a alunos de Medicina das universidades de Curitiba, no Paraná, formados no primeiro semestre de 2020, que anteciparam a outorga de grau em razão da pandemia de Covid-19. Resultados: Responderam ao questionário 113 formandos, dos quais 101 relataram que já atuam como médicos. Destes, 63,36% afirmaram que estão trabalhando diretamente no atendimento de casos de Covid-19. Sobre a importância da antecipação da outorga de grau, a maioria dos participantes concorda totalmente ou concorda, e apenas três participantes discordam totalmente. Mais da metade dos entrevistados não se sentem prejudicados com a antecipação da outorga de grau. Contudo, 43,3% acreditam que deixaram de adquirir informações importantes em sua formação. Por fim, quanto ao fato de trabalharem na pandemia, 79,6% consideram importante a atuação de médicos recém-formados no combate à Covid-19. Conclusão: Este estudo mostra que, a princípio, os esforços para a antecipação de formatura foram bem-sucedidos, já que os novos médicos estão contribuindo para aliviar a pressão imposta pela falta de profissionais e promover um melhor cuidado aos pacientes durante a pandemia.

Trabecular bone score (TBS) and bone mineral density in patients with long-term therapy with warfarin.

In this study, we compared patients using the anticoagulant warfarin for more than a year with a control group with similar characteristics but without using the drug. We demonstrated worse BMD and bone quality by trabecular bone score (TBS) in patients using warfarin for more than 1 year. PURPOSE: Evaluate the bone mineral density (BMD) and the trabecular bone score (TBS) of patients taking warfarin for more than 1 year compared with a control group. METHODS: Male patients aged 25-65 years in warfarin use for more than 1 year were included. Patients answered a questionnaire regarding lifestyle habits and realized a dual X-ray densitometry (DXA) (lumbar spine and hip), and TBS was evaluated. RESULTS: From the 96 patients invited, 33 patients accepted to participate and comprised the warfarin group (WG), and 3 were excluded. The control group (CG) was composed of 21 individuals matched by age and race. The mean age of WG was 57.0 ± 7.6 and in the CG 54.0 ± 10.6 years (p = 0.095). The BMD in WG was lower than that in the CG in all sites (spine p < 0.001, total hip p = 0.001, and femoral neck p = 0.005). A longer time of warfarin use increased the likelihood of having low BMD (OR = 1.239, CI 1.064-1.674, p = 0.01), whereas high BMI decreased it (OR = 0.732, CI 0.533-0.918, p = 0.03). The TBS was lower in WG than the CG (p = 0.04). Lower TBS was associated with hypertension in both groups and to the hip BMD (neck and total) (p < 0.005) in the WG. In the multivariate analysis, only hypertension (- 0.10, CI - 0.17 to - 0.03, p = 0.008) and total hip BMD ( 0.26, CI 0.07-0.46, p = 0.009) influenced TBS. CONCLUSION: We demonstrated an association between worsening of BMD and bone quality in patients taking warfarin for more than 1 year.

C-reactive Protein is a predictor of mortality in ST-segment elevation acute myocardial infarction / Proteína C-reativa é um preditor de mortalidade no infarto agudo do miocárdio com elevação do segmento ST

Background: Inflammation is a major component of the response to tissue injury caused by myocardial infarction. High-sensitivity C-reactive protein (hs-CRP) levels might be a simple marker of the severity of this inflammatory response, providing prognostic information. Objective: To associate hs-CRP level on admission and other clinical characteristics with in-hospital mortality of patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: A retrospective cohort study of patients admitted with STEMI was carried out. Patients were analyzed regarding clinical characteristics, reperfusion therapy, hs-CRP on admission and outcomes. Continuous variables were analyzed by non-parametric Mann-Whitney U test and categorical variables by chi-square test. A p value of < 0.05 was considered statistically significant. Results: Of the 118 patients analyzed, 20 died during hospitalization. Higher levels of hs-CRP (p = 0.001) and older ages (p = 0.003) were observed among those patients who died. Logistic regression showed that a one unit increase in hs-CRP increased the risk of death by 15% (p = 0.0017), after adjustment for established risk factors. Similarly, each one-year increase in age increases the risk of death by 6.6% (p = 0.003). Conclusion: Our results demonstrate a strong association between hs-CRP obtained on admission and in-hospital mortality after STEMI. It suggests that hs-CRP can be a marker of inflammatory response to myocardial ischemia, providing prognostic information regarding the risk of death

Avaliação de um curso para a capacitação dos profissionais da enfermagem na urgência e emergência / Evaluation of a course for the training of nursing professionals in urgency and emergency

OBJETIVO: Esse trabalho visa avaliar um modelo de curso para a capacitação da equipe de enfermagem no atendimento de urgências e emergências, estabelecendo o período pelo qual o conhecimento adquirido no curso é memorizado e o prazo em que deveria ser reaplicado para garantir a proficiência. MÉTODOS: Foram selecionados 45 profissionais da enfermagem que atuavam nas unidades de cardiologia e aplicado um pré-teste de 20 questões de múltipla escolha, avaliando o conhecimento prévio da equipe. Após o pré-teste, ministrou-se um curso teórico-prático presencial acerca do reconhecimento de pacientes críticos e manejo inicial de uma parada cardiorrespiratória, praticando as manobras de reanimação em um manequim. Após o curso era reaplicado o mesmo teste para identificar se houve melhora no número de acertos. Dentro de três e seis meses o teste foi novamente aplicado, a fim de estabelecer a taxa de memorização do conhecimento no período. RESULTADOS: Observamos que a média de acertos no pré-teste foi de 9,4±3,3 questões. No pós-teste imediato houve um aumento da média de acertos para 15,3±2 questões. Após três meses, o número médio de acertos caiu para 12±3,1 questões e transcorridos seis meses foi de 10±3,3 questões. Foi possível identificar ainda que os profissionais que atuavam na Unidade de Cuidados Intensivos e Hemodinâmica apresentaram um maior número de acertos (12,6±3,42) quando comparados com os profissionais que atuavam na Enfermaria (9,4±4,4). Realizando uma análise regressiva, observamos uma melhora estatisticamente significativa nos resultados dos testes logo após o treinamento e em três meses (p<0.05) ­ o que não ocorreu em seis meses. CONCLUSÃO: Podemos inferir a partir da melhora no número de acertos que o modelo de curso teórico-prático presencial foi efetivo em promover a capacitação dos profissionais da enfermagem. No entanto, a fixação do conhecimento decai ao longo dos meses, retornando a valores próximos do inicial em seis meses.

AIMS: This work aims to evaluate a course model for the training of the nursing team in emergency care, as well as establishing the period which the knowledge acquired in the course is still memorized and when the course should be reministered to guarantee the professional's proficiency. METHODS: We selected 45 nursing professionals who worked at the Cardiology Units of the Hospital de Clínicas of the Federal University of Paraná. In this group, a pre-test of 20 multiple choice questions was applied, mentioning the previous knowledge of the team. After the pre-test, a two-hour theoretical-practical course was given on the recognition of severe patients and initial management of a cardiorespiratory arrest, practicing ventilation maneuvers and chest compression on a manikin. After the course, the same test was reapplied to identify if there was improvement in the number of correct answers. Within three and six months the test was again applied in order to establish the knowledge storage rate over that period. RESULTS: We observed that the average accuracy in the pre-test was 9.4±3.3 questions. In the immediate post-test, there was an increase in the mean of correct answers to 15.3±2 questions. After three months, the average number of correct answers fell to 12±3.1 questions and after six months was 10±3.3 questions. It was also possible to identify that the professionals who worked in the Intensive Care Unit and Hemodynamics presented a greater number of correct answers (12.6±3.4) when compared to the professionals who worked in the Infirmary (9.4±4.4). Performing a regressive analysis, we observed a statistically significant improvement in the test results shortly after the training and in three months (p<0.05) ­ which did not occur in the time of six months. CONCLUSION: We can infer from the improvement in the number of correct answers to the questionnaire that the theoretical-practical course model was effective in promoting the training of nursing professionals. However, the fixation of knowledge decays over the months, returning to values close to the initial within six months.

Seborrheic Keratoses as the First Sign of Bladder Carcinoma: Case Report of Leser-Trélat Sign in a Rare Association with Urinary Tract Cancer.

Introduction. Skin disorders can be the first manifestation of occult diseases. The recognition of typical paraneoplastic dermatoses may anticipate the cancer diagnosis and improve its prognosis. Although rarely observed, the sudden appearance and/or rapid increase in number and size of seborrheic keratoses can be associated with malignant neoplasms, known as the sign of Leser-Trélat. The aim of this report is to unveil a case of a patient whose recently erupted seborrheic keratoses led to investigation and consequent diagnosis of bladder cancer. Case Presentation. A 67-year-old man was admitted to the intensive care unit due to an exacerbation of chronic obstructive pulmonary disease (COPD). On physical examination, multiple seborrheic keratoses on the back of the hands, elbows, and trunk were observed; the patient had a 4-month history of these lesions yet was asymptomatic. The possibility of Leser-Trélat syndrome justified the investigation for neoplasia, and a bladder carcinoma was detected by CT-scan. The patient denied previous hematuria or any other related symptoms. Many of the lesions regressed during oncologic treatment. Conclusion. Despite the critics on the validity of the sign of Leser-Trélat, our patient fulfills the description of the disease, though urinary malignancy is a rare association. That corroborates the need of further investigation when there is a possibility of paraneoplastic manifestation.

Oxidative Damage in the Aging Heart: an Experimental Rat Model.

INTRODUCTION: Several theories have been proposed to explain the cause of 'aging'; however, the factors that affect this complex process are still poorly understood. Of these theories, the accumulation of oxidative damage over time is among the most accepted. Particularly, the heart is one of the most affected organs by oxidative stress. The current study, therefore, aimed to investigate oxidative stress markers in myocardial tissue of rats at different ages. METHODS: Seventy-two rats were distributed into 6 groups of 12 animals each and maintained for 3, 6, 9, 12, 18 and 24 months. After euthanasia, the heart was removed and the levels of non-protein thiols, lipid peroxidation, and protein carbonylation, as well as superoxide dismutase and catalase activities were determined. RESULTS: Superoxide dismutase, catalase activity and lipid peroxidation were reduced in the older groups of animals, when compared with the younger group. However, protein carbonylation showed an increase in the 12-month group followed by a decrease in the older groups. In addition, the levels of non-protein thiols were increased in the 12-month group and not detected in the older groups. CONCLUSION: Our data showed that oxidative stress is not associated with aging in the heart. However, an increase in non-protein thiols may be an important factor that compensates for the decrease of superoxide dismutase and catalase activity in the oldest rats, to maintain appropriate antioxidant defenses against oxidative insults.

Acute kidney injury in patients infected by H1N1: clinical histological correlation in a series of cases.

INTRODUCTION: Influenza A (H1N1) virus was first reported on April 2009 and, since then, several studies have reported the characteristics concerning the clinical presentation and pulmonary involvement. However, accurate information about the acute kidney injury (AKI) and kidney histopathological findings in these patients remain scarce. OBJECTIVE: To describe the kidney histopathological findings of 6 patients with H1N1 who developed AKI and underwent kidney biopsy, correlating them with clinical features. METHODS: We studied six patients admitted to Hospital de Clínicas UFPR with a PCR-confirmed diagnosis of H1N1who developed ARF and underwent kidney biopsy. We reviewed their medical file and the microscopy findings of the biopsy. RESULTS: Clinical and/or laboratory evidence of AKI was present in all cases, and only one did not present oliguria. Kidney tissues revealed glomerular lesions in two patients: one patient, with systemic lupus erythematosus, showed changes consistent with lupus nephritis class III A-C according to the ISN/RPS 2003 and focal thrombotic microangiopathy; the other one had intercapillary nodular glomerulosclerosis, but without clinical or laboratory evidence of diabetes. Vacuolar degenerative tubular changes were present in all cases, with focus of oxalosis in two cases. Mild to moderate atherosclerosis was found in two patients. CONCLUSION: In this study, varying degrees of vacuolar degenerative tubular changes were present in all patients, but there were no signs of acute tubular necrosis. It seems that in the present study a prerenal cause of acute renal failure was the main involved mechanim to explain the cause of renal failure in these patients.

Insuficiência renal aguda em pacientes infectados pelo H1N1: correlação clínico-histológica em uma série de casos / Acute kidney injury in patients infected by H1N1: clinical histological correlation in a series of cases

INTRODUÇÃO: O vírus Influenza A (H1N1) foi primeiramente descrito em abril de 2009 e, desde então, diversos estudos relataram as características pertinentes à apresentação clínica e ao acometimento pulmonar da doença. Contudo, informações precisas referentes à insuficiência renal aguda (IRA) e às alterações histopatológicas renais nesses pacientes ainda são escassas. OBJETIVO: O objetivo deste estudo é descrever os achados histopatológicos renais de seis pacientes comprovadamente infectados pelo H1N1, que desenvolveram IRA e realizaram biópsia renal, correlacionando-os com os aspectos clínicos. MÉTODOS: Avaliamos seis pacientes do Hospital de Clínicas da UFPR com diagnóstico de H1N1 por PCR viral em 2009 que evoluíram com IRA e que foram submetidos à biópsia renal. Foram revisados os seus prontuários e das lâminas da biópsia renal. RESULTADOS: Todos os casos estudados apresentaram dados clínicos e/ou laboratoriais de IRA, sendo que somente um não apresentou oligúria. À biópsia renal, dois pacientes apresentaram alterações glomerulares: um deles, portador de lupus eritematoso sistêmico, apresentou lesões compatíveis com nefrite lúpica classe III A-C da ISN/RPS 2003 e microangiopatia trombótica focal; outro paciente apresentou glomerulosclerose nodular intercapilar, porém, sem comemorativos clínicos ou laboratoriais de diabetes. Todos os pacientes mostraram graus variáveis de alterações degenerativas vacuolares dos túbulos, com focos de oxalose em dois casos. Dois pacientes possuíam arteriosclerose em grau discreto a moderado. CONCLUSÃO: Em nosso estudo, todos os pacientes apresentarem graus variáveis de alteração degenerativa vacuolar, contudo, não foram encontrados sinais evidentes de necrose tubular aguda, parecendo existir um componente pré-renal como a causa principal de IRA nestes pacientes.

INTRODUCTION: Influenza A (H1N1) virus was first reported on April 2009 and, since then, several studies have reported the characteristics concerning the clinical presentation and pulmonary involvement. However, accurate information about the acute kidney injury (AKI) and kidney histopathological findings in these patients remain scarce. OBJECTIVE: To describe the kidney histopathological findings of 6 patients with H1N1 who developed AKI and underwent kidney biopsy, correlating them with clinical features. METHODS: We studied six patients admitted to Hospital de Clínicas UFPR with a PCR-confirmed diagnosis of H1N1who developed ARF and underwent kidney biopsy. We reviewed their medical file and the microscopy findings of the biopsy. RESULTS: Clinical and/or laboratory evidence of AKI was present in all cases, and only one did not present oliguria. Kidney tissues revealed glomerular lesions in two patients: one patient, with systemic lupus erythematosus, showed changes consistent with lupus nephritis class III A-C according to the ISN/RPS 2003 and focal thrombotic microangiopathy; the other one had intercapillary nodular glomerulosclerosis, but without clinical or laboratory evidence of diabetes. Vacuolar degenerative tubular changes were present in all cases, with focus of oxalosis in two cases. Mild to moderate atherosclerosis was found in two patients. CONCLUSION: In this study, varying degrees of vacuolar degenerative tubular changes were present in all patients, but there were no signs of acute tubular necrosis. It seems that in the present study a prerenal cause of acute renal failure was the main involved mechanim to explain the cause of renal failure in these patients.

[Nutcraker syndrome as a cause of recurrent hematuria in a young woman: a case report]. / Síndrome de quebra-nozes (nutcracker) em uma mulher jovem em investigação por quadro de hematúria recorrente: um relato de caso.

INTRODUCTION: The nutcracker syndrome is defined by the compression of the left renal vein between the aorta and superior mesenteric arteries, accompanied by a classic, but less specific, symptomatology. CASE REPORT: We reported a case of a 37-year-old woman who had been investigated because of intermittent gross hematuria of unknown origin. Computed tomographic angiography revealed compression of the left renal vein as it ran between the superior mesenteric artery and the abdominal aorta, associated with significant dilation of the left ovarian vein. DISCUSSION: The nutcracker syndrome, caused by compression of the left renal vein by the aorta and superior mesenteric arteries, is probably more prevalent in women, and it is caused by specific situations, such as renal ptosis and paucity of retroperitoneal fat. Hematuria, a typical symptom, is due to rupture of the thin-walled septum separating the veins of the urinary collecting system. Imaging tests may help with the diagnosis. The best treatment is still elusive, but there are several surgical approaches, such as intravascular stenting, and also a conservative management. Diagnosis is usually delayed, and the syndrome should be included in the differential of hematuria of unknown origin.

Síndrome de quebra-nozes (nutcracker) em uma mulher jovem em investigação por quadro de hematúria recorrente: um relato de caso / Nutcraker syndrome as a cause of recurrent hematuria in a young woman: a case report

INTRODUÇÃO: A síndrome de quebra-nozes (SQN) é uma condição na qual há compressão da veia renal esquerda pela aorta e a artéria mesentérica superior, associada a uma sintomatologia característica, porém pouco específica. RELATO DO CASO: Trata-se de uma paciente de 37 anos, apresentando hematúria macroscópica intermitente sem etiologia estabelecida até então. Durante a investigação, uma angiotomografia evidenciou compressão da veia renal esquerda no seu trajeto entre a artéria mesentérica superior e aorta abdominal, associada a importante dilatação de veia ovariana esquerda. DISCUSSÃO: A síndrome desencadeada pela compressão da veia renal esquerda pela aorta e artéria mesentérica superior apresenta prevalência provavelmente aumentada no sexo feminino e postula-se que seja associada a situações particulares, como a nefroptose e a escassez de gordura retroperitoneal. Hematúria, sinal típico, teria como causa a ruptura do fino septo que separa as veias do sistema coletor urinário. Vários exames de imagem podem auxiliar no diagnóstico. O tipo de tratamento que deve ser adotado ainda é controverso, existindo diversas opções cirúrgicas, como o uso de stent intravascular e a conduta conservadora. De diagnóstico costumeiramente tardio, essa síndrome deve ser incluída na investigação de pacientes com quadro de hematúria a esclarecer.

INTRODUCTION: The nutcracker syndrome is defined by the compression of the left renal vein between the aorta and superior mesenteric arteries, accompanied by a classic, but less specific, symptomatology. CASE REPORT: We reported a case of a 37-year-old woman who had been investigated because of intermittent gross hematuria of unknown origin. Computed tomographic angiography revealed compression of the left renal vein as it ran between the superior mesenteric artery and the abdominal aorta, associated with significant dilation of the left ovarian vein. DISCUSSION: The nutcracker syndrome, caused by compression of the left renal vein by the aorta and superior mesenteric arteries, is probably more prevalent in women, and it is caused by specific situations, such as renal ptosis and paucity of retroperitoneal fat. Hematuria, a typical symptom, is due to rupture of the thin-walled septum separating the veins of the urinary collecting system. Imaging tests may help with the diagnosis. The best treatment is still elusive, but there are several surgical approaches, such as intravascular stenting, and also a conservative management. Diagnosis is usually delayed, and the syndrome should be included in the differential of hematuria of unknown origin.