Bone-marrow mononuclear cells and acellular human amniotic membrane improve global cardiac function without inhibition of the NLRP3 Inflammasome in a rat model of heart failure.

Recent studies have suggested that therapies with stem cells and amniotic membrane can modulate the inflammation following an ischemic injury in the heart. This study evaluated the effects of bone-marrow mononuclear cells (BMMC) and acellular human amniotic membrane (AHAM) on cardiac function and NLRP3 complex in a rat model of heart failure.On the 30th day,the echocardiographic showed improvements on ejection fraction and decreased pathological ventricular remodeling on BMMC and AHAM groups.Oxidative stress analysis was similar between the three groups,and the NLRP3 inflammasome activity were not decreased with the therapeutic use of both BMMC and AHAM,in comparison to the control group.

Biological therapy, surgery, and hospitalization rates for inflammatory bowel disease: An observational Latin American comparative study between adults and pediatric patients.

OBJECTIVE: Compare the proportions of use of biological therapy, surgeries, and hospitalizations between adults and pediatric inflammatory bowel disease (IBD)-Crohn's disease (CD) and ulcerative colitis (UC)-patients. PATIENTS AND METHODS: Observational, retrospective, and multicenter study. Data were collected from all consecutive IBD patients seen as outpatients or admitted to hospital, during 2015-2021, in two IBD tertiary centers in a South Brazilian capital. Patients with unclassified colitis diagnosis were excluded from this study. Patients were classified as having CD or UC and sub-categorized as adult or pediatric according to age. Data were analyzed using frequency, proportion, Fisher's exact test, and Chi-square test. RESULTS: A total of 829 patients were included: 509 with CD (378 adults/131 pediatric) and 320 with UC (225/95). Among patients with CD, no differences were observed for proportions of use of biological therapy (80.2% in pediatric vs. 73.3% in adults; P=0.129), surgery (46.6% vs. 50.8%; P=0.419), or hospitalization (64.9% vs. 56.9%; P=0.122). In UC, significant differences were observed for biological therapy (40.0% vs. 28.0%; P=0.048) and hospitalization (47.4% vs. 24.0%; P<0.001). No significant difference was observed in surgery rates (17.9% vs. 12.4%; P=0.219). CONCLUSIONS: Biological therapy and incidence of hospitalization were greater among pediatric patients with UC, compared with adults; no difference was observed in the need for abdominal surgery. In CD, no significant difference was observed in the three main outcomes between the age groups.

Immunohistochemical Profiling of PD-1, PD-L1, CD8, MSI, and p53 and Prognostic Implications in Advanced Serous Ovarian Carcinoma: A Retrospective Study.

Advanced high-grade serous ovarian carcinoma is a serious malignant neoplasm with a late diagnosis and high mortality rate. Even when treated with standard therapy, such as surgery followed by carboplatin and paclitaxel chemotherapy, the prognosis remains unfavorable. Immunotherapy is a treatment alternative that requires further study. Therefore, we aimed to evaluate the expression of PD-1, PD-L1, CD8, MSI (MLH1, MSH2, MSH6, and PMS2), and p53 in the paraffin samples of high-grade serous ovarian carcinoma. A retrospective study of 28 southern Brazilian patients with advanced serous ovarian carcinoma (EC III or IV) was conducted between 2009 and 2020. The expression of these proteins was evaluated using immunohistochemistry, and the results were correlated with the patients' clinicopathological data. At diagnosis, the mean age was 61 years, and the most common clinical stage (60%) was EC III. Among the cases, 84.6% exhibited p53 overexpression, 14.8% had MSI, 92.0% were sensitive to platinum, and more than 50.0% relapsed after treatment. Patients with MSI had a lower CD8/PD-1 ratio and more relapses (p = 0.03). In conclusion, analysis of immunotherapeutic markers in paraffin-embedded advanced serous ovarian carcinoma samples is feasible and may assist in prognosis.

Human Adipose-Derived Stem Cells Reduce Cellular Damage after Experimental Spinal Cord Injury in Rats.

Traumatic spinal cord injury (SCI) is a devastating condition without an effective therapy. Cellular therapies are among the promising treatment strategies. Adult stem cells, such as mesenchymal stem cells, are often used clinical research for their immunomodulatory and regenerative potential. This study aimed to evaluate the effect of human adipose tissue-derived stem cells (ADSC) infusion through the cauda equina in rats with SCI. The human ADSC from bariatric surgery was isolated, expanded, and characterized. Wistar rats were subjected to blunt SCI and were divided into four groups. Two experimental groups (EG): EG1 received one ADSC infusion after SCI, and EG2 received two infusions, the first one after SCI and the second infusion seven days after the injury. Control groups (CG1 and CG2) received infusion with a culture medium. In vivo, cell tracking was performed 48 h and seven days after ADSC infusion. The animals were followed up for 40 days after SCI, and immunohistochemical quantification of myelin, neurons, and astrocytes was performed. Cellular tracking showed cell migration towards the injury site. ADSC infusion significantly reduced neuronal loss, although it did not prevent the myelin loss or enhance the area occupied by astrocytes compared to the control group. The results were similar when comparing one or two cell infusions. The injection of ADSC distal to the injured area was shown to be a safe and effective method for cellular administration in spinal cord injury.

A three-sequence dynamic contrast enhanced abbreviated MRI protocol to evaluate response to breast cancer neoadjuvant chemotherapy.

PURPOSE: To develop an ABP-MRI to evaluate response to NAC for invasive breast carcinoma. STUDY TYPE: A single-center, cross-sectional study. SUBJECTS: A consecutive series of 210 women with invasive breast carcinoma who underwent breast MRI after NAC between 2016 and 2020. FIELD STRENGTH/SEQUENCE: 1.5 T / Dynamic contrast-enhanced. ASSESSMENT: MRI scans were independently reevaluated, with access to dynamic contrast-enhanced without contrast and to the first, second, and third post-contrast time (ABP-MRI 1-3). STATISTICAL TESTS: The diagnostic performance of the ABP-MRIs and the Full protocol (FP-MRI) were analyzed. The Wilcoxon non-parametric test (p-value <0.050) was used to compare the capability in measuring the most extensive residual lesion. RESULTS: The median age was 47 (24-80) years. ABP-MRI 1 showed higher specificity (84.6%; 77/91) but a higher probability of false-negatives (16.8%) and lower sensitivity (83.2%; 99/119) than ABP-MRI 2,3 and the FP-MRI, which were identical in specificity (81.3%; 74/91), probability of false-negatives (8.4%), and sensitivity (91.6%; 109/119). ABP-MRI 2 showed a mean underestimation of only 0.03 cm in the measurement of the longest axis of the residual lesion (p = 0.008) with an average reduction in the acquisition time of 75%, compared with the FP-MRI. CONCLUSION: ABP-MRI 2 showed diagnostic performance equivalent to the FP-MRI with a 75% reduction in the acquisition time.

Insuficiência Tricúspide e Mortalidade em Pacientes Submetidos à Troca da Valva Aórtica Transcateter: Uma Revisão Sistemática e Metanálise / Tricuspid Regurgitation and Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis

Resumo Fundamento A extensão do dano cardíaco associada à estenose aórtica tem importantes implicações prognósticas após a substituição da valva aórtica transcateter (TAVR). Contudo, ainda não está claro qual é o papel da insuficiência tricúspide (IT) nesse cenário clínico. Objetivos Explorar a associação entre IT e mortalidade em pacientes submetidos a TAVR e avaliar as alterações na gravidade da IT após a TAVR e sua relação com mortalidade de curto e médio prazo. Métodos Foram feitas pesquisas em bases de dados relevantes de artigos publicados do início até agosto de 2020. Dos 414 estudos triados, selecionamos 24 que relataram o grau de IT pré- ou pós-TAVR. O desfecho primário foi mortalidade por todas as causas, e foram conduzidos modelos de metanálise de efeitos aleatórios (a um nível de significância de 5%). Resultados Dezessete estudos relataram associações entre IT pré-TAVR e mortalidade por todas as causas (> 45.000 participantes), e 13 avaliaram a gravidade da IT pós-TAVR (709 participantes). A IT basal moderada/grave foi associada a maior mortalidade por todas as causas em 30 dias [razão de risco (RR) 1,65; intervalo de confiança (IC) 95% 1,20-2,29] e 1,2 ano (RR 1,56; IC95% 1,31-1,84). Após a TAVR, 43% dos pacientes apresentaram redução de pelo menos um grau na IT (30 dias, IC95% 30-56%), que se sustentou em 12,5 meses em 44% dos participantes (IC95% 35-52%).A persistência de IT significativa foi associada a um aumento de duas vezes na mortalidade por todas as causas (RR 2,12; IC95% 1,53-2,92). Conclusões A IT significativa pré-TAVR está associada a maior mortalidade. Ainda que a gravidade da IT possa melhorar, a persistência de IT significativa após a TAVR está fortemente associada ao aumento da mortalidade. Nossos achados destacam a importância de uma avaliação detalhada da IT pré- e pós-TAVR e podem ajudar a identificar pacientes que possam se beneficiar de uma vigilância mais cuidadosa nesse cenário.

Abstract Background The extent of cardiac damage associated with aortic stenosis has important prognostic implications after transcatheter aortic valve replacement (TAVR). However, the role of tricuspid regurgitation (TR) in this clinical setting is still unclear. Objectives To explore the association between TR and mortality in patients undergoing TAVR and assess changes in TR severity post TAVR and its relationship with short and mid-term mortality. Methods Relevant databases were searched for articles published from inception until August 2020. Out of 414 screened studies, we selected 24 that reported the degree of TR pre or post TAVR. The primary outcome was all-cause mortality, and random effects meta-analysis models were conducted (at a significance level of 5%). Results Seventeen studies reported associations between pre-TAVR TR and all-cause mortality (> 45,000 participants) and thirteen accessed TR severity post TAVR (709 participants). Moderate/severe baseline TR was associated to higher all-cause mortality both at 30 days (HR 1.65; 95% CI, 1.20-2.29) and 1.2 years (HR 1.56; 95% CI, 1.31-1.84). After TAVR, 43% of patients presented a decrease of at least one grade in TR (30 days, 95% CI, 30-56%), sustained at 12.5 months in 44% of participants (95% CI, 35-52%). Persistence of significant TR was associated with a two-fold increase in all-cause mortality (HR 2.12; 95% CI, 1.53-2.92). Conclusions Significant TR pre TAVR is associated with higher mortality. Although TR severity may improve, the persistence of significant TR post TAVR is strongly associated with increased mortality. Our findings highlight the importance of a detailed assessment of TR pre and post TAVR and might help identify patients who may benefit from more careful surveillance in this scenario.

Alcance das Metas de Colesterol LDL após Infarto Agudo do Miocárdio: Dados Reais do Sistema Público de Saúde da Cidade de Curitiba / Achievement of LDL-Cholesterol Goals after Acute Myocardial Infarction: Real-World Data from the City of Curitiba Public Health System

Resumo Fundamento A redução dos níveis de colesterol LDL é a pedra angular na redução de risco, mas muitos pacientes de alto risco não estão atingindo as metas lipídicas recomendadas, mesmo em países de alta renda. Objetivo Avaliar se os pacientes atendidos na rede pública de saúde da cidade de Curitiba estão atingindo as metas de colesterol LDL após infarto agudo do miocárdio (IAM). Métodos Esta coorte retrospectiva explorou os dados de pacientes internados com IAM entre 2008 e 2015 em hospitais públicos da cidade de Curitiba. Para avaliar o atingimento da meta de colesterol LDL, utilizamos o último valor registrado no banco de dados para cada paciente até o ano de 2016. Para aqueles que tinham pelo menos um valor de colesterol LDL registrado no ano anterior ao IAM, calculou-se o percentual de redução. O nível de significância adotado para a análise estatística foi p<0,05. Resultados Dos 7.066 pacientes internados por IAM, 1.451 foram acompanhados em ambiente ambulatorial e tiveram pelo menos uma avaliação de colesterol LDL. A média de idade foi 60,8±11,4 anos e 35,8%, 35,2%, 21,5% e 7,4% dos pacientes apresentavam níveis de colesterol LDL≥100, 70-99, 50-69 e <50 mg/dL, respectivamente. Destes, 377 pacientes também tiveram pelo menos uma avaliação de colesterol LDL antes do IAM. As concentrações médias de colesterol LDL foram 128,0 e 92,2 mg/dL antes e após o IAM, com redução média de 24,3% (35,7 mg/dL). Os níveis de colesterol LDL foram reduzidos em mais de 50% em apenas 18,3% dos casos. Conclusão Na cidade de Curitiba, pacientes do sistema público de saúde, após infarto do miocárdio, não estão atingindo níveis adequados de colesterol LDL após IAM.

Abstract Background Reduction of LDL-cholesterol (LDL-c) levels is the cornerstone in risk reduction, but many high-risk patients are not achieving the recommended lipid goals, even in high-income countries. Objective To evaluate whether patients seen in the city of Curitiba public health system are reaching LDL-c goals after an acute myocardial infarction (AMI). Methods This retrospective cohort explored the data of patients admitted with AMI between 2008 and 2015 in public hospitals from the city of Curitiba. In order to evaluate the attainment of the LDL-c target, we have used the last value registered in the database for each patient up to 2016. For those who had at least one LDL-c registered in the year before AMI, percentage of reduction was calculated. The level of significance adopted for statistical analysis was p<0.05. Results Of 7,066 patients admitted for AMI, 1,451 were followed up in an out-patient setting and had at least one evaluation of LDL-c. Mean age was 60.8±11.4 years and 35.8%, 35.2%, 21.5%, and 7.4% of patients had LDL-c levels ≥100, 70-99, 50-69 and <50 mg/dL, respectively. Of these, 377 patients also had at least one LDL-c evaluation before the AMI. Mean LDL-c concentrations were 128.0 and 92.2 mg/dL before and after AMI, with a mean reduction of 24.3% (35.7 mg/dL). LDL-c levels were reduced by more than 50% in only 18.3% of the cases. Conclusion In the city of Curitiba public health system patients, after myocardial infarction, are not achieving adequate LDL-c levels after AMI.

Estudo Comparativo Entre Diário Vesical e Estudo Urodinâmico para Identificação de Sintomas do Trato Urinário Inferior / Comparative Study Between Bladder Diary and Urodynamic Study to Identify Lower Urinary Tract Symptoms / Estudio Comparativo Entre el Diario Vesical y el Estudio Urodinámico para Identificar los Síntomas del Tracto Urinario Inferior

Objetivo:Avaliar a efetividade do diário vesical para identificar sintomas do trato urinário inferior, em comparação ao estudo urodinâmico. Método: Trata-se de estudo observacional de corte transversal realizado em uma clínica de urodinâmica do sul catarinense com 44 pacientes submetidos ao exame. A coleta de dados deu-se por aplicação de questionário de dados epidemiológicos e de sintomas e diário vesical de 72 horas e comparação deste com os achados do estudo urodinâmico por meio do programa Stata/SE v.14.1. Resultados: O diário vesical apresentou alta especificidade, sensibilidade e acurácia para identificação de hiperatividade detrusora e incontinência urinária de esforço. Não apresentou diferença para capacidade vesical (p* 0,198) e apontou sensibilidade vesical com volume menor do que o apresentado pelo estudo urodinâmico (p*<0,001). Foi capaz de identificar sintomas de trato urinário inferior que não haviam se revelado no estudo urodinâmico. Conclusão: O diário vesical mostrou-se tão efetivo quanto o estudo urodinâmico para identificação de sintomas de trato urinário inferior, podendo ser utilizado para definição de tratamento de primeira linha com maior abrangência de diagnóstico populacional, menor tempo entre queixa e tratamento, redução de custo para o sistema e menor desconforto para o paciente.

Objective:To identify the similarity of lower urinary tract symptoms presented in the urodynamic study compared to the urinary diary. Method: This is a comparative study carried out in an urodynamics clinic in southern Santa Catarina, Brazil, with 44 patients who underwent the examination. Data collection was carried out by applying a questionnaire and a 72-hour bladder diary and comparing it with the findings of the urodynamic study using the SPSS for Windows and Stata/SE v.14.1 programs. Results: The bladder diary showed high specificity, sensitivity, and accuracy for identifying detrusor hyperactivity and stress urinary incontinence. There was no difference for bladder capacity (p* 0.198). It pointed to bladder sensitivity with a volume smaller than that presented by the urodynamic study (p*<0.001). It was able to identify lower urinary tract symptoms that were not present in the urodynamic study. Conclusion: The bladder diary was effective for identifying lower urinary tract symptoms and can be used to define first-line treatment with a broader range of population diagnosis, shorter time between complaints and treatment, cost reduction for the system, and less discomfort for the patient.

Objetivo:Evaluar la efectividad del diario vesical para identificar síntomas del tracto urinario inferior, en comparación con el estudio urodinámico. Método: estudio observacional de corte transversal realizado en una clínica de urodinamia en la región sur del estado de Santa Catarina (Brasil) con 44 pacientes sometidos al examen. La recolección de datos fue realizada por medio de la aplicación de cuestionario de datos epidemiológicos, caracterización de síntomas y diário vesical de 72 horas. La comparación entre los mismos y los hallazgos del estudio urodinámico fue realizada por medio del programa Stata/SE v.14.1. Resultados: el diario vesical presentó alta especificidad, sensibilidad y validez para la identificación de la hiperactividad detrusora y de la incontinencia urinaria de esfuerzo. No hubo diferencia en la capacidad vesical (p* 0,198), el diario vesical indentificó sensibilidad vesical con un volumen menor que el presentado por el estudio urodinámico (p*<0,001). El diário fue capaz de identificar síntomas del tracto urinario inferior que no fueron revelados en el estudio urodinámico. Conclusión: el diario vesical se mostró tan efectivo como el estudio urodinámico para la identificación de síntomas del tracto urinario inferior, con gran potencial de ser utilizado para definición de tratamiento de primera linea con mayor cobertura de diagnóstico poblacional, menor tiempo entre la queja y el tratamiento, reducción de costo para el sistema de salud y menor incomodidad para el paciente.

Relationship between ventricular repolarization parameters and the inducibility of ventricular arrhythmias during electrophysiological study in patients with coronary artery disease.

OBJECTIVE: Risk stratification of sudden cardiac death in patients with coronary artery disease is of great importance. We evaluated the association between ventricular repolarization and induction of malignant ventricular arrhythmias on electrophysiological study of patients with coronary artery disease. METHODS AND RESULTS: A total of 177 patients (65±10.1 years, 83.6% male, mean left ventricular ejection fraction [LVEF] 37.5±13.6%) were analyzed. For each 10 ms increment in the QT interval, there was a 7% increase in malignant ventricular arrhythmias inducibility; QT cutoff point of 452 ms had an accuracy of 0.611 for predicting malignant ventricular arrhythmias (p=0.011). Male gender (odds ratio [OR]=4.18, p=0.012), LVEF <35% (OR=2.32, p=0.013), amiodarone use (OR=2.01, p=0.038), and prolonged QT (OR=1.07, p=0.023) were associated with malignant ventricular arrhythmias. In patients with ventricular dysfunction, QT >452 ms was associated with significantly increased risk of malignant ventricular arrhythmias (OR=5.44, p=0.0004). In those with LVEF ³35%, QT dispersion (QTd) was significantly higher in patients with inducible malignant ventricular arrhythmias. QTd >20 ms had 0.638 accuracy and 81.3% negative predictive value in predicting malignant ventricular arrhythmias. CONCLUSION: QT interval is an independent factor associated with malignant ventricular arrhythmias in patients with coronary artery disease. The combination of ventricular dysfunction and prolonged QT interval is associated with a 5.44-fold increase of malignant ventricular arrhythmias induction. Male gender, amiodarone use, and decreased left ventricular ejection fraction are also associated with increased risk of inducibility of malignant ventricular arrhythmias on the electrophysiological study.

Impact of the COVID-19 pandemic on the epidemiology of traffic accidents: a cross-sectional study / Impacto da pandemia da COVID-19 na epidemiologia dos acidentes de trânsito: um estudo transversal

ABSTRACT Objective: to assess the epidemiological profile of traffic accident victims in the setting of the Coronavirus Disease 2019 (COVID-19) pandemic and analyze the admissions throughout the different levels of restriction (flags), as well as compare the results with the pre-pandemic period. Methods: a cross-sectional study was performed, with probability sampling, in a trauma center in Brazil. Medical records of patients involved in traffic accidents from June 2020 to May 2021 were evaluated. Aside from epidemiological characteristics, variables such as the current flag, the trauma mechanism, the resulting injuries, and the Revised Trauma Score (RTS) were also considered. Data were compared between three different flag periods and the proportion of consultations during the pandemic was compared with that from pre-pandemic time (December 2016 to February 2018). Results: it was observed that 62.2% of the patients were victims of motorcycle accidents, 77.5% were male, and the mean age was 33 ± 12.4 years. The mean and median RTS were 7.5 and 7.8, respectively. Statistical difference was stated when comparing the number of visits per day between the yellow and red flags (p=0.001) and orange and red flags (p=0.016). A significantly lower number of consultations for traffic accidents was observed in the pandemic when compared to the pre-pandemic period. Conclusions: the epidemiological profile of the study consisted mostly of young men who were victims of motorcycle accidents. There was a lower incidence of admissions during red flag periods and a lower proportion of consultations throughout the survey when compared to the pre-pandemic period.

RESUMO Introdução: avaliar o perfil epidemiológico das vítimas de acidentes de trânsito no contexto da pandemia da doença do coronavírus 2019 (COVID-19), analisar os atendimentos entre os níveis de restrição implementados (bandeiras) e comparar os dados com o período pré-pandêmico. Métodos: trata-se de um estudo transversal, com amostragem probabilística, realizado em um hospital de trauma no sul do Brasil utilizando prontuários de pacientes vítimas de acidente de trânsito entre junho de 2020 a maio de 2021. Além das variáveis epidemiológicas, coletou-se a bandeira vigente, o mecanismo de trauma, as lesões resultantes e o Revised Trauma Score (RTS). Os dados foram comparados entre as três bandeiras e a proporção de atendimentos do período pandêmico foi comparada com a do período pré-pandêmico (dezembro de 2016 a fevereiro de 2018). Resultados: observou-se que 62,2% dos pacientes foram vítimas de acidentes com motocicletas, 77,5% da amostra era do sexo masculino e que a média etária foi de 33 ± 12,4 anos. A média e mediana do RTS foram 7,5 e 7,8, respectivamente. Houve diferença significativa ao comparar o número de atendimentos ao dia entre as bandeiras amarela e vermelha (p=0,001) e laranja e vermelha (p=0,016). Constatou-se um número significativamente menor de atendimentos por acidentes de trânsito no período pandêmico quando comparado com o período pré-pandêmico. Conclusões: o perfil epidemiológico do estudo foi composto em sua maioria por homens jovens vítimas de acidentes com motocicleta. Houve menor incidência de admissões na bandeira vermelha e menor proporção de atendimentos no período da pesquisa quando comparado ao pré-pandêmico.

Management of Airway Remodeling in a Mouse Model of Allergic Airways Inflammation Using Extracellular Vesicles from Human Bone Marrow-Derived Mesenchymal Stromal Cells

Abstract: Asthma is a chronic respiratory disease affecting 300 million people worldwide. It results in several structural changes in the airways, which are minimally accessible in clinical practice. Cell therapy using mesenchymal stromal cells (MSCs) is a promising strategy for treating asthma due to the paracrine activity of MSCs, which influences tissue regeneration and modulates the immune response. Studies using extracellular vesicles (EV) released by MSCs have demonstrated their regenerative properties in animal models. The aim of this study was to evaluate the potential of EVs isolated from human bone marrow MSCs (hBM-MSCs) to control lung tissue remodeling in ovalbumin-induced allergic asthma in Balb/c mice. We isolated hBM-MSCs from a single donor, expanded and characterized them, and then isolated EVs. Asthma was induced in 43 male Balb/c mice, divided into four groups: control, asthmatic (AS), asthmatic plus systemic EVs (EV-S), and asthmatic plus intratracheal EVs (EV-IT). Upon completion of asthma induction, animals were treated with EVs either locally (EV-IT) or intravenously (EV-S). Seven days after, we performed bronchoalveolar lavage (BAL) and the total nuclear cells were counted. The animals were euthanized, and the lungs were collected for histopathological analysis of the airways. The EV-S group showed improvement in only the total BAL cell count compared with the AS group, while the EV-IT group showed significant improvement in almost all evaluated criteria. Therefore, we demonstrate that the local application of EVs derived from hBM-MSCs may be a potential treatment in controlling asthma.

Bone-Marrow Stem Cells and Acellular Human Amniotic Membrane in a Rat Model of Heart Failure.

Myocardial infarction (MI) remains the leading cause of cardiovascular death worldwide and a major cause of heart failure. Recent studies have suggested that cell-based therapies with bone marrow stem cells (BMSC) and human amniotic membrane (hAM) would recover the ventricular function after MI; however, the mechanisms underlying these effects are still controversial. Herein, we aimed to compare the effects of BMSC and hAM in a rat model of heart failure. MI was induced through coronary occlusion, and animals with an ejection fraction (EF) < 50% were included and randomized into three groups: control, BMSC, and hAM. The BMSC and hAM groups were implanted on the anterior ventricular wall seven days after MI, and a new echocardiographic analysis was performed on the 30th day, followed by euthanasia. The echocardiographic results after 30 days showed significant improvements on EF and left-ventricular end-sistolic and end-diastolic volumes in both BMSC and hAM groups, without significant benefits in the control group. New blood vessels, desmine-positive cells and connexin-43 expression were also elevated in both BMSC and hAM groups. These results suggest a recovery of global cardiac function with the therapeutic use of both BMSC and hAM, associated with angiogenesis and cardiomyocyte regeneration after 30 days.

Prevalência de automedicação para sintomas dispépticos na atenção primária / Prevalence of self-medication for dyspeptic symptoms in primary care: a brazilian survey

ABSTRACT BACKGROUND: Dyspeptic symptoms are among the eight symptoms that most lead to the use of self-medication globally. OBJECTIVE: The aim of the present study was to evaluate the frequency of use and profile of the population doing self-medication to control dyspeptic symptoms in a capital from South Brazil. METHODS: Application of a survey consisting of topics regarding individual's socio-cultural data, self-reported comorbidities, use of self-medication in the 15 days prior to the interview and information on the use of this medication. Statistical analysis was performed on the data collected to determine the prevalence of self-medication for dyspeptic symptoms (SMDS) and to establish correlations with independent factors, such as gender, age, body mass index (BMI), education, family income and self-reported comorbidities. RESULTS: A total of 719 individuals from the public health system were interviewed. Overall, 67.7% were female, 65.3% had a BMI greater than 25; 28.4% presented with self-reported hypertension, 21.4% with depression and 13.8% with diabetes. The prevalence of self-medication to control digestive symptoms in this population was 28.7% (95%CI: 25.3-32), 91.8% (n=189) due to complaints of dyspeptic origin. Proton pump inhibitors were the most used class of medication (67%), followed by antacids (15%). There was a relationship between SMDS and age >38 years (OR=1.734, 95%CI: 1.177-2.580, P=0.001), BMI >26 (OR=1.660, 95%CI: 1.166-2.362, P<0.001) and self-reported depression (OR=1.471, 95%CI: 0.983-2.201, P=0.04). CONCLUSION: There was a higher prevalence of the use of self-medication to control dyspeptic symptoms in relation to previous data from the literature. Age >38 years, BMI >26 and self-reported depression were associated with SMDS.

RESUMO CONTEXTO: Os sintomas dispépticos estão entre os oito sintomas que mais levam uso de automedicação. OBJETIVO: O presente estudo teve como objetivo avaliar a prevalência e o perfil da população que utiliza automedicação para controle dos sintomas dispépticos em uma capital do Sul do Brasil. MÉTODOS: Aplicação de inquérito composto por tópicos relativos aos dados socioculturais do indivíduo, comorbidades autorreferidas, uso de automedicação nos 15 dias anteriores à entrevista e informações sobre o uso deste medicamento. Foi realizada a análise estatística dos dados coletados para determinar a prevalência de automedicação para controle dos sintomas dispépticos e estabelecer correlações com fatores independentes, como sexo, idade, índice de massa corporal (IMC), escolaridade, renda familiar e comorbidades autorrelatadas. RESULTADOS: Foram entrevistados 719 indivíduos atendidos pela atenção primária. Destes, 67,7% de indivíduos do sexo feminino, 65,3% apresentavam IMC maior que 25 kg/m², 28,4% autorrelataram apresentar hipertensão arterial sistêmica, 21,4% depressão e 13,8% diabetes. A prevalência de uso de automedicação para controle de sintomas digestivos nesta população foi de 28,7% (n=206, IC95% 25,3-32), 91,8% (n=189) por queixas de origem dispéptica. A classe de medicação mais utilizada foi a dos inibidores de bomba de prótons (67%), seguidos dos antiácidos (15%). Houve relação entre o uso deste tipo de automedicação e idade maior de 38 anos (OR=1,734, IC95% 1,177-2,580, P=0,001), IMC acima de 26 kg/m² (OR=1,660, IC95% 1,166-2,362, P<0,001) e presença de autorrelato de depressão (OR= 1,471, IC95% 0,983-2,201, P=0,04). CONCLUSÃO: O presente estudo revelou uma alta prevalência do uso de automedicação para controle dos sintomas dispépticos em comparação com dados da literatura, sendo os inibidores de bomba de prótons a classe de droga mais utilizada. Idade maior que 38 anos, índice de massa corporal maior 26 kg/m² e autorrelato de depressão foram associados ao uso de automedicação para sintomas dispépticos.

High prevalence of biochemical disturbances of chronic kidney disease - mineral and bone disorders (CKD-MBD) in a nation-wide peritoneal dialysis cohort: are guideline goals too hard to achieve? / Alta Prevalência de Distúrbios Bioquímicos Minerais e Ósseos na Doença Renal Crônica em uma coorte de diálise peritoneal nacional: as metas das diretrizes são muito difíceis de alcançar?

Abstract Introduction: Chronic kidney disease - mineral and bone disorders (CKD-MBD) are common in dialysis patients. Definition of targets for calcium (Ca), phosphorus (P), parathormone (iPTH), and alkaline phosphatase (ALP) and their treatment recommendations, are provided by international guidelines. There are few studies analyzing CKD-MBD in peritoneal dialysis (PD) patients and the impact of guidelines on mineral metabolism control. The aim of our study was to describe the prevalence of biomarkers for CKD-MBD in a large cohort of PD patients in Brazil. Methods: Data from the nation-wide prospective observational cohort BRAZPD II was used. Incident patients were followed between December 2004 and January 2011. According to KDOQI recommendations, reference ranges for total Ca were 8.4 to 9.5 mg/dL, for P, 3.5 to 5.5 mg/dL, for iPTH, 150-300 pg/mL, and for ALP, 120 U/L. Results: Mean age was 59.8 ± 16 years, 48% were male, and 43% had diabetes. In the beginning, Ca was 8.9 ± 0.9 mg/dL, and 48.3% were on the KODQI target. After 1 year, Ca increased to 9.1 ± 0.9 mg/dL and 50.4% were in the KDOQI preferred range. P at baseline was 5.2 ± 1.6 mg/dL, with 52.8% on target, declining to 4.9 ± 1.5 mg/dL after one year, when 54.7% were on target. Median iPTH at baseline was 238 (P25% 110 - P75% 426 pg/mL) and it remained stable throughout the first year; patients within target ranged from 26 to 28.5%. At the end of the study, 80% was in 3.5 meq/L Ca dialysate concentration, 66.9% of patients was taking any phosphate binder, and 25% was taking activated vitamin D. Conclusions: We observed a significant prevalence of biochemical disorders related to CKD-MBD in this dialysis population.

Resumo Introdução: Os distúrbios minerais e ósseos da doença renal crônica (DMO-DRC) são comuns em pacientes em diálise. A definição de metas para cálcio (Ca), fósforo (P), paratormônio (PTHi) e fosfatase alcalina (FA) e suas recomendações de tratamento são fornecidas por diretrizes internacionais. Há poucos estudos analisando o DMO-DRC em pacientes em diálise peritoneal (DP) e o impacto das diretrizes no controle do metabolismo mineral. O objetivo do nosso estudo foi descrever a prevalência de alterações nos marcadores para DMO-DRC em uma grande coorte de pacientes em DP no Brasil. Métodos: Foram utilizados dados da coorte observacional prospectiva nacional BRAZPD II. Pacientes incidentes foram acompanhados entre Dezembro de 2004 e Janeiro de 2011. De acordo com as recomendações do KDOQI, os intervalos de referência para Ca total foram de 8,4 a 9,5 mg/dL, para P, 3,5 a 5,5 mg/dL, para PTHi, 150-300 pg/mL, e para FA, 120 U/L. Resultados: A idade média foi de 59,8 ± 16 anos, 48% eram homens e 43% tinham diabetes. No início, o Ca era de 8,9 ± 0,9 mg/dL, e 48,3% estavam na meta do KODQI. Após 1 ano, o Ca aumentou para 9,1 ± 0,9 mg/dL e 50,4% estavam na faixa preferida do KDOQI. P basal era 5,2 ± 1,6 mg/dL, com 52,8% na meta, diminuindo para 4,9 ± 1,5 mg/dL após um ano, quando 54,7% estavam na meta. O PTHi basal mediano foi de 238 (P25% 110 - P75% 426 pg/mL) e permaneceu estável durante o primeiro ano; os pacientes dentro da meta variaram de 26 a 28,5%. No final do estudo, 80% estavam na concentração de 3,5 meq/L de Ca dialisato, 66,9% dos pacientes estavam tomando qualquer quelante de fosfato, e 25% estavam tomando vitamina D ativada. Conclusões: Observamos uma prevalência significativa de distúrbios bioquímicos relacionados ao DMO-DRC nesta população em diálise.

Association of estrogen receptor alpha 1 and TMJ dysfunction: A pilot study.

OBJECTIVE: Temporomandibular disorder (TMD) is a multifactorial condition and the most common cause of orofacial pain, affecting mostly women, which points to a female hormone predilection. Therefore, the aim of this study was to analyze the association between TMD and estrogen receptor alpha 1 expression in disks of patients with TMD and condyle fracture (CFx). STUDY DESIGN: Forty specimens (from 27 patients) included n = 8 CFx, n = 21 anterior disk displacement with reduction (ADDwR), and n = 11 anterior disk displacement without reduction (ADDwoR). Age, area, and intensity of immunostaining were statistically compared between CFx, ADDwR, and ADDwoR groups using analysis of variance and Kruskal-Wallis analysis (P < .05). RESULTS: No significant difference between CFx, ADDwR, and ADDwoR groups with respect to age and expression of estrogen receptor alpha 1 was observed on immunohistochemical examination. CONCLUSION: No association of estrogen receptor alpha 1 expression and age was found in the CFx, ADDwR, and ADDwoR groups.

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.

Efeito cardiovascular superior do modelo periodizado para prescrição de exercícios comparado ao convencional em coronariopatas / Superior cardiovascular effect of the periodized model for prescribed exercises as compared to the conventional one in coronary diseases

O exercício físico melhora a sobrevida e a qualidade de vida de pacientes coronarianos, mas a maneira ideal de prescrevê-lo é ainda controversa. Criar um modelo periodizado para prescrição de exercícios para pacientes coronarianos e compará-lo com o modelo convencional. Randomização de 62 pacientes coronarianos em tratamento farmacológico em dois grupos: treinamento convencional, não periodizado (GNP, n = 33) e periodizado (GP, n = 29). Os dois grupos foram submetidos aos mesmos exercícios durante as 36 sessões do programa, mas prescritos de maneira diferente. Todos os pacientes foram submetidos à seguinte avaliação: consulta médica admissional, teste de esforço cardiopulmonar, teste de 1 repetição máxima (1RM) e avaliação da composição corporal. O VO2 pico melhorou nos dois grupos, embora de maneira mais efetiva no GP (4% versus 1,7%, p < 0,001). Além disso, a capacidade funcional do GP aumentou em 13%, tendo havido significativa redução no percentual de gordura corporal (2,1%, p < 0,005) e no peso corporal (1,9 kg, p < 0,005). A força muscular nos dois grupos melhorou como diagnosticado pelo teste de 1RM para seis diferentes grupos musculares (quádriceps, isquiotibiais, bíceps, tríceps braquial, peitoral e grande dorsal), mas sem diferença significativa entre os grupos, tendo os dois modelos a mesma eficiência. O presente estudo mostrou que a periodização do treinamento de pacientes cardíacos pode melhorar a capacidade cardiorrespiratória e reduzir a porcentagem de gordura corporal mais efetivamente do que o modelo convencional

Physical exercise improves the survival and quality of life of coronary patients, but the ideal way of prescribing these exercises is still controversial. To create a new periodized model for the prescription of exercises for coronary patients and compare it with a conventional model. 62 coronary patients under pharmacological treatment were randomized into two groups: conventional (NPG, n = 33) and periodized (PG, n = 29) training. The two groups were submitted to the same exercises during the 36 sessions making up the program, but prescribed in different ways. All patients underwent an evaluation consisting of: medical admission consultancy, cardiopulmonary endurance testing, 1 maximum repetition test (1MR) and body composition evaluation. The VO2 peak improved in both groups, although more effectively in the PG (4% against 1.7%, p < 0.001). In addition, the functional capacity of this group improved by 13%, and there was a significant reduction in the percent body fat (2.1%, p < 0.005) and body weight (1.9 kg, p < 0.005). The muscle strength of both groups improved as diagnosed by the 1RM test for six different muscle groups (quadriceps, hamstrings, brachial biceps, brachial triceps, pectoral and large dorsal), and showed no significant difference between the groups, evidencing that the two models had the same efficiency. The present study showed that periodization of the training of cardiac patients can improve their cardiorespiratory capacity and reduce the percent body fat more effectively than the conventional one

Expanded CD133+ Cells from Human Umbilical Cord Blood Improved Heart Function in Rats after Severe Myocardial Infarction.

Pharmacological approaches are partially effective in limiting infarct size. Cell therapies using a cell population enriched with endothelial progenitor cells (EPCs) CD133+ have opened new perspectives for the treatment of ischemic areas after infarction. This preclinical study evaluated the effect of intramyocardial transplantation of purified or expanded human umbilical cord blood-derived CD133+ cells on the recovery of rats following acute myocardial infarction (AMI). Histology studies, electrocardiogram, and fluorescence in situ hybridization (FISH) were used to evaluate heart recovery. Purified CD133+ cells, enriched in endothelial progenitor cells, when expanded in vitro acquired an endothelial-like cell phenotype expressing CD31 and von Willebrand factor (vWF). The group of infarcted rats that received expanded CD133+ cells had a more significant recovery of contraction performance and less heart remodeling than the group that received purified CD133+ cells. Either purified or expanded CD133+ cells were able to induce neovascularization in the infarcted myocardium in an equivalent manner. Few human cells were detected in the infarcted myocardium of the rats 28 days after transplantation suggesting that the effects observed might be related primarily to paracrine activity. Although both cell populations ameliorated the infarcted heart and are suitable for regeneration of the vascular system, expanded CD133+ cells are more beneficial and promising candidates for vascular regeneration.

Regeneration of Tracheal Tissue in Partial Defects Using Porcine Small Intestinal Submucosa.

BACKGROUND: Surgical correction of tracheal defects is a complex procedure when the gold standard treatment with primary end-to-end anastomosis is not possible. An alternative treatment may be the use of porcine small intestinal submucosa (SIS). It has been used as graft material for bioengineering applications and to promote tissue regeneration. The aim of this study was to evaluate whether SIS grafts improved tracheal tissue regeneration in a rabbit model of experimental tracheostomy. METHODS: Sixteen rabbits were randomized into two groups. Animals in the control group underwent only surgical tracheostomy, while animals in the SIS group underwent surgical tracheostomy with an SIS graft covering the defect. We examined tissues at the site of tracheostomy 60 days after surgery using histological analysis with hematoxylin and eosin (H&E) staining and analyzed the perimeter and area of the defect with Image-Pro® PLUS 4.5 (Media Cybernetics). RESULTS: The average perimeter and area of the defects were smaller by 15.3% (p = 0.034) and 21.8% (p = 0.151), respectively, in the SIS group than in the control group. Histological analysis revealed immature cartilage, pseudostratified ciliated epithelium, and connective tissue in 54.5% (p = 0.018) of the SIS group, while no cartilaginous regeneration was observed in the control group. CONCLUSIONS: Although tracheal SIS engraftment could not prevent stenosis in a rabbit model of tracheal injury, it produced some remarkable changes, efficiently facilitating neovascularization, reepithelialization, and neoformation of immature cartilage.

Prevalence of high cholesterol levels suggestive of familial hypercholesterolemia in Brazilian adolescents: Data from the study of cardiovascular risk in adolescents.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder with an estimated worldwide prevalence ranging from 1 in 200 individuals to 1 in 500 individuals in its heterozygous form. Individuals with FH exhibit high low-density lipoprotein cholesterol (LDLc) levels from birth, which leads to premature cardiovascular events. In Brazil, like in most countries around the world, FH is considered a public health problem but remains underdiagnosed and undertreated. OBJECTIVE: The aim of this study was to evaluate the prevalence of LDLc or non-high-density lipoprotein cholesterol (non-HDLc) levels suggestive of FH among Brazilian adolescents. METHODS: The Study of Cardiovascular Risk in Adolescents (ERICA) was a nationwide, school-based, cross-sectional study that assessed the prevalence of cardiovascular risk factors in approximately 75,000 adolescents between 12 and 17 years old. Data were analyzed according to sex, age, type of school (public or private), and geographic regions of Brazil. Adolescents with untreated fasting LDLc levels of 160 mg/dL or higher or non-HDLc levels of 190 mg/dL or higher were suspected to have FH. We also evaluated the prevalence of LDLc levels of 190 mg/dL or higher, which is highly suggestive of a diagnosis of FH in this age group. RESULTS: A total of 38,069 adolescents were evaluated; more than half (59.9%) were female and most (74%) attended public schools. The prevalence of LDLc levels of 160 mg/dL or higher or non-HDLc levels of 190 mg/dL or higher among the adolescents was 0.49% (95% confidence interval: 0.34-0.71; n = 209). Moreover, 0.12% of the adolescents (95% confidence interval: 0.04-0.34; n = 44) had LDLc levels of 190 mg/dL or higher. We estimate that approximately 100,000 (1 in 200) Brazilian adolescents aged 12 to 17 years are suspected to have FH on the basis of LDLc and non-HDLc levels. CONCLUSION: We identified a significant prevalence of cholesterol levels suggestive of FH among Brazilian adolescents. Further evaluation is needed to confirm the diagnoses among the students. Our results reinforce the importance of universal screening as a critical tool for early diagnosis and treatment of FH.