Implications of MTHFD2 expression in renal cell carcinoma aggressiveness.

Renal cell carcinoma (RCC) is the most common type of cancer in kidney and is often diagnosed in advanced stages. Until now, there is no reliable biomarker to assess tumor prognosis during histopathological diagnosis. The Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) overexpression has been suggested as prognostic indicator for RCC, however, its protein profile needs to be clarified. This study investigated the MTHFD2 expression in different RCC cohorts, associating it with tumor characteristics and prognostic factors. Gene expression comparisons between non-neoplastic (NN) and tumor samples, as well as patients' survival analysis, were assessed using KM-Plotter tool. MTHFD2 protein pattern was evaluated in 117 RCC by immunohistochemistry and associations with prognosis, clinical and pathological data were investigated. The tumors exhibited higher MTHFD2 transcript levels than NN, being even higher in the metastatic group. Opposite gene expression patterns were found among clear cell renal cell carcinoma (ccRCC) and pappilary renal cell carcinoma (pRCC) subtypes, showing higher and lower expressions compared to NN samples respectively. Overexpression was associated with shorter overall survival for ccRCC and pRCC subtypes, and shorter recurrence-free survival for pRCC. The immunolabeling profile varied according to tumor subtypes, with lower intensity and expression scores in ccRCC compared to pRCC and to chromophobe renal cell carcinoma (chRCC). MTHFD2 protein expression was associated with larger tumors and higher Fuhrman grades. Although prognostic value of protein immunostaining was not confirmed, patients with higher MTHFD2 tended to have lower survival rates in the pRCC group. The results highlight MTHFD2 different patterns according to RCC histological subtypes, revealing marked variations at both the genetic and protein levels. The mRNA indicated tumor prognosis, and greater expression in the tumor samples. Although MTHFD2 immunolabeling suggests tumor aggressiveness, it needs to be validated in other cohorts as potential prognostic factor.

Utrecht grief rumination scale (UGRS): Psychometric study of validation of the Portuguese version.

Grief rumination is characterized by recurring, repetitive, self-focused thoughts about the causes and consequences of loss and loss-related emotions. This cognitive process is a transdiagnostic risk factor for mental disorders, such as prolonged grief. The aim of this study was to analyze the psychometric properties of the Portuguese version of the Utrecht Grief Rumination Scale (UGRS). The sample consists of 242 bereaved adult participants with Portuguese nationality. Confirmatory Factor Analysis showed that the hierarchical model showed a better fit to the data. Average Variance Extracted was also calculated to measure convergent and divergent validity. Test-criterion validity was investigated by analyzing associations between grief rumination and measures of posttraumatic stress, prolonged grief, anxiety, and depression. Using McDonald's Omega and Cronbach's Alpha, all subscales showed adequate reliability. The UGRS showed acceptable psychometric properties, standing out as a valid instrument for practice and research in psychology in the area of ​​bereavement.

In situ assessment of Mindin as a biomarker of podocyte lesions in diabetic nephropathy.

Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal failure worldwide. Several mechanisms are involved in the pathogenesis of this disease, which culminate in morphological changes such as podocyte injury. Despite the complex diagnosis and pathogenesis, limited attempts have been made to establish new biomarkers for DN. The higher concentration of Mindin protein in the urine of patients with type 2 diabetes mellitus suggests that it plays a role in DN. Therefore, this study investigated whether in situ protein expression of Mindin can be considered a potential DN biomarker. Fifty renal biopsies from patients diagnosed with DN, 57 with nondiabetic glomerular diseases, including 17 with focal segmental glomerulosclerosis (FSGS), 14 with minimal lesion disease (MLD) and 27 with immunoglobulin A nephropathy (IgAN), and 23 adult kidney samples from autopsies (control group) were evaluated for Mindin expression by immunohistochemistry. Podocyte density was inferred by Wilms' tumor 1 (WT1) immunostaining, while foot process effacement was assessed by transmission electron microscopy. Receiver operative characteristic (ROC) analysis was performed to determine the biomarker sensitivity/specificity. Low podocyte density and increased Mindin expression were observed in all cases of DN, regardless of their class. In the DN group, Mindin expression was significantly higher than that in the FSGS, MCD, IgAN and control groups. Higher Mindin expression was significantly positively correlated with foot process effacement only in class III DN cases. Furthermore, Mindin protein presented high specificity in the biopsies of patients with DN (p < 0.0001). Our data suggest that Mindin may play a role in DN pathogenesis and is a promising biomarker of podocyte lesions.

In situ evaluation of podocytes in patients with focal segmental glomerulosclerosis and minimal change disease.

Podocyte injury in focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) results from the imbalance between adaptive responses that maintain homeostasis and cellular dysfunction that can culminate in cell death. Therefore, an in situ analysis was performed to detect morphological changes related to cell death and autophagy in renal biopsies from adult patients with podocytopathies. Forty-nine renal biopsies from patients with FSGS (n = 22) and MCD (n = 27) were selected. In situ expression of Wilms Tumor 1 protein (WT1), light chain microtubule 1-associated protein (LC3) and caspase-3 protein were evaluated by immunohistochemistry. The foot process effacement and morphological alterations related to podocyte cell death and autophagy were analyzed with transmission electronic microscopy. Reduction in the density of WT1-labeled podocytes was observed for FSGS and MCD cases as compared to controls. Foot process width (FPW) in control group was lower than in cases of podocytopathies. In FSGS group, FPW was significantly higher than in MCD group and correlated with proteinuria. A density of LC3-labeled podocytes and the number of autophagosomes in podocytes/ pedicels were higher in the MCD group than in the FSGS group. The number of autophagosomes correlated positively with the estimated glomerular filtration rate in cases of MCD. The density of caspase-3-labeled podocytes in FSGS and MCD was higher than control group, and a higher number of podocytes with an evidence of necrosis was detected in FSGS cases than in MCD and control cases. Podocytes from patients diagnosed with FSGS showed more morphological and functional alterations resulting from a larger number of lesions and reduced cell adaptation.

Renal expression of cytokines and chemokines in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Inflammatory mediators have been implicated in the pathogenesis of DN, thus considered an inflammatory disease. However, further studies are required to assess the renal damage caused by the action of these molecules. Therefore, the objective of this study was to analyze the expression of cytokines and chemokines in renal biopsies from patients with DN and to correlate it with interstitial inflammation and decreased renal function. METHODS: Forty-four native renal biopsies from patients with DN and 23 control cases were selected. In situ expression of eotaxin, MIP-1α (macrophage inflammatory protein-1α), IL-8 (interleukin-8), IL-4, IL-10, TNF-α (tumor necrosis factor-α), TNFR1 (tumor necrosis factor receptor-1), IL-1ß, and IL-6 were evaluated by immunohistochemistry. RESULTS: The DN group showed a significant increase in IL-6 (p < 0.0001), IL-1ß (p < 0.0001), IL-4 (p < 0.0001) and eotaxin (p = 0.0012) expression, and a decrease in TNFR1 (p = 0.0107) and IL-8 (p = 0.0262) expression compared to the control group. However, there were no significant differences in IL-10 (p = 0.4951), TNF-α (p = 0.7534), and MIP-1α (p = 0.3816) expression among groups. Regarding interstitial inflammation, there was a significant increase in IL-6 in scores 0 and 1 compared to score 2 (p = 0.0035), in IL-10 in score 2 compared to score 0 (p = 0.0479), and in eotaxin in score 2 compared to scores 0 and 1 (p < 0.0001), whereas IL-8 (p = 0.0513) and MIP-1α (p = 0.1801) showed no significant differences. There was a tendency for negative correlation between eotaxin and estimated glomerular filtration rate (eGFR) (p = 0.0566). CONCLUSIONS: Our results indicated an increased in situ production of cytokines and chemokines in DN, including IL-6, IL-1ß, IL-4, and eotaxin. It was observed that, possibly, eotaxin may have an important role in the progression of interstitial inflammation in DN and in eGFR decrease of these patients.

Analysis of serum inflammatory mediators in type 2 diabetic patients and their influence on renal function.

AIM: To evaluate the serum concentrations of inflammatory mediators in patients with type 2 diabetes mellitus (T2DM) with or without renal alteration (RA) function. METHODS: Serum samples from 76 patients with T2DM and 24 healthy individuals were selected. Patients with T2DM were divided into two groups according to eGFR (> or < 60mL/min/1.73m2). Cytokines, chemokines and adipokines levels were evaluated using the Multiplex immunoassay and ELISA. RESULTS: TNFR1 and leptin were higher in the T2DM group with RA than in the T2DM group without RA and control group. All patients with T2DM showed increased resistin, IL-8, and MIP-1α compared to the control group. Adiponectin were higher and IL-4 decreased in the T2DM group with RA compared to the control group. eGFR positively correlated with IL-4 and negatively with TNFR1, TNFR2, and leptin in patients with T2DM. In the T2DM group with RA, eGFR was negatively correlated with TNFR1 and resistin. TNFR1 was positively correlated with resistin and leptin, as well as resistin with IL-8 and leptin. CONCLUSION: Increased levels of TNFR1, adipokines, chemokines and decrease of IL-4 play important role in the inflammatory process developed in T2DM and decreased renal function. We also suggest that TNFR1 is a strong predictor of renal dysfunction in patients with T2DM.

Focal and Segmental Glomerulosclerosis and Membranous Nephropathy overlapping in a patient with Nephrotic Syndrome: a case report / Glomeruloesclerose Segmentar e Focal e Nefropatia Membranosa sobrepostas em paciente com Síndrome Nefrótica: relato de caso

Abstract Introduction: Some cases of membranous nephropathy (MGN) present focal segmental glomerulosclerosis (FSGS) typically associated with disease progression. However, we report a case of a patient who seemed to have MGN and FSGS, both primary. Case presentation: A 17-year-old female, Caucasian, presenting lower extremity edema associated with episodes of foamy urine and high blood pressure, had physical and laboratorial exams indicating nephrotic syndrome. A renal biopsy was performed and focal and segmental glomerulosclerosis were observed under light microscopy in some glomeruli presented as tip lesion, and in others it was accompanied by podocyte hypertrophy and podocyte detachment in urinary space, compatible with podocytopathy FSGS. Besides, there were thickened capillary loops with basement membrane irregularities due to "spikes" compatible with MGN stage II. Immunofluorescence showed finely granular IgG, IgG4, and PLA2R deposits in capillary loops and, in electron microscopy, subepithelial deposits and foot process effacement. These morphological findings are compatible with FSGS and MGN stage II. Conclusions: In the present case, clinical and morphological characteristics showed a possible overlap of primary FSGS and MGN as focal and segmental glomerulosclerosis does not seem to be related with MGN progression but with the podocytopathy FSGS.

Resumo Introdução: Alguns casos de nefropatia membranosa (NM) apresentam glomeruloesclerose segmentar e focal (GESF) tipicamente associada a progressão da doença. Contudo, relatamos o caso de uma paciente que parece ter NM e GESF, ambas primárias. Apresentação do caso: Uma jovem branca de 17 anos de idade com edema de membros inferiores associado a episódios de urina espumosa e hipertensão apresentou-se com achados físicos e laboratoriais sugestivos de síndrome nefrótica. Foi realizada biópsia renal. GESF foi observada por microscopia de luz em alguns glomérulos que apresentavam lesões de ponta, enquanto em outros o achado era acompanhado por hipertrofia podocitária e descolamento de podócitos no espaço urinário, compatíveis com podocitopatia GESF. Além disso, as alças capilares estavam espessadas com irregularidades na membrana basal devido a "espículas" compatíveis com NM estágio II. Imunofluorescência revelou depósitos finamente granulares de IgG, IgG4 e PLA2R nas alças capilares. Microscopia eletrônica exibiu depósitos subepiteliais e apagamento de pedicelos. Tais achados morfológicos são compatíveis com GESF e NM estágio II. Conclusões: No presente caso, as características clínicas e morfológicas revelaram uma possível sobreposição de GESF primária e NM, uma vez que a glomeruloesclerose segmentar e focal não parece estar relacionada com a progressão da NM, mas com a podocitopatia GESF.

Focal and Segmental Glomerulosclerosis and Membranous Nephropathy overlapping in a patient with Nephrotic Syndrome: a case report.

INTRODUCTION: Some cases of membranous nephropathy (MGN) present focal segmental glomerulosclerosis (FSGS) typically associated with disease progression. However, we report a case of a patient who seemed to have MGN and FSGS, both primary. CASE PRESENTATION: A 17-year-old female, Caucasian, presenting lower extremity edema associated with episodes of foamy urine and high blood pressure, had physical and laboratorial exams indicating nephrotic syndrome. A renal biopsy was performed and focal and segmental glomerulosclerosis were observed under light microscopy in some glomeruli presented as tip lesion, and in others it was accompanied by podocyte hypertrophy and podocyte detachment in urinary space, compatible with podocytopathy FSGS. Besides, there were thickened capillary loops with basement membrane irregularities due to "spikes" compatible with MGN stage II. Immunofluorescence showed finely granular IgG, IgG4, and PLA2R deposits in capillary loops and, in electron microscopy, subepithelial deposits and foot process effacement. These morphological findings are compatible with FSGS and MGN stage II. CONCLUSIONS: In the present case, clinical and morphological characteristics showed a possible overlap of primary FSGS and MGN as focal and segmental glomerulosclerosis does not seem to be related with MGN progression but with the podocytopathy FSGS.

A novel single amino acid deletion impairs fibronectin function and causes familial glomerulopathy with fibronectin deposits: case report of a family.

BACKGROUND: Glomerulopathy with fibronectin deposits is an autosomal dominant disease associated with proteinuria, hematuria, hypertension and renal function decline. Forty percent of the cases are caused by mutations in FN1, the gene that encodes fibronectin. CASE PRESENTATION: This report describes two cases of Glomerulopathy with fibronectin deposits, involving a 47-year-old father and a 14-year-old son. The renal biopsies showed glomeruli with endocapillary hypercellularity and large amounts of mesangial and subendothelial eosinophilic deposits. Immunohistochemistry for fibronectin was markedly positive. Whole exome sequencing identified a novel FN1 mutation that leads to an amino-acid deletion in both patients (Ile1988del), a variant that required primary amino-acid sequence analysis for assessment of pathogenicity. Our primary sequence analyses revealed that Ile1988 is very highly conserved among relative sequences and is positioned in a C-terminal FN3 domain containing heparin- and fibulin-1-binding sites. This mutation was predicted as deleterious and molecular mechanics simulations support that it can change the tertiary structure and affect the complex folding and its molecular functionality. CONCLUSION: The current report not only documents the occurrence of two GFND cases in an affected family and deeply characterizes its anatomopathological features but also identifies a novel pathogenic mutation in FN1, analyzes its structural and functional implications, and supports its pathogenicity.

Is it possible to predict parameters of the Oxford classification of primary IgA Nephropathy from clinical laboratory data? Focus on the role of segmental glomerulosclerosis subtypes.

INTRODUCTION: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world and has a broad range of histological and clinical manifestations, ranging from morphologically normal to globally sclerotic glomeruli with clinical manifestations varying from isolated hematuria to end stage renal disease. This study aims to assess sensitivity, specificity and accuracy of clinical data at the time of biopsy in predicting 2017 updated Oxford classification parameters and to investigate if subtypes of segmental sclerosis (FSGS) influence clinical presentation. MATERIAL AND METHODS: Renal biopsies from 103 patients with IgAN were analyzed. Oxford classification was updated and FSGS lesions were subclassified. ROC curves, univariate and multivariate logistic regression were used. RESULTS: In Oxford classification, the majority of patients had mesangial hypercellularity in less than a half of glomeruli (M0), did not have endocapillary hypercellularity (E0), had segmental glomerulosclerosis (S1), had interstitial fibrosis and tubular atrophy in more than a half of the sample (T2) and had no crescents (C0). Hypertension increases the chance of M1 in 2.54x (p = 0.02). For each unit of increased creatinine, 2.6x more chances of E1 (p = 0.001). S1 is predicted by proteinuria with 75% sensitivity and 90.9% specificity (p < 0.0001). For each unit of increase in GFR, there is a reduction of 6% in the chance of T2 in relation to T0 (p = 0.0001). If hypertension, there is 5x more chances of T2 than T0 (p = 0.01). For each unit of increase in creatinine, there are 2.8x more chances of crescents- C (p = 0.003). Creatinine also showed 75.8% sensitivity and 75% specificity for prediction of C (p = 0.002). Inversely, for each unit of GFR, the chance of C is reduced by 4% (p = 0.007). Other clinical data related with C are hypertension (p = 0.03) and proteinuria (p = 0.02). To determine the role of FSGS subtypes in clinical presentation, we divided patients in S0 and S1 groups. Proteinuria was the only clinical parameter with significative difference, respectively, 0.3 (0-2.1) and 1.6 (0.02-16.2) g/24 h (p < 0.0001). FSGS subtypes related to proteinuria were cellular (p = 0.03) and peri-hilar (p = 0.02). Subtypes classically related to podocytopathies showed no correlation with clinical data. CONCLUSION: In the future, with noninvasive methods for diagnosis of IgAN, it will be essential to predict Oxford classification parameters using clinical laboratory data for establishment of prognosis and therapeutics. We showed that Oxford classification parameters correspond to some clinical laboratory data, making this approach possible. FSGS lesions not specifically related to podocytopathies may also influence clinical parameters that affect renal disease progression.

Repeatability and Reproducibility of Postural Variables by Photogrammetry.

OBJECTIVE: This study aimed to examine the reliability of postural variables analyzed by photogrammetry obtained at different instances on the same day and between 2 different days. METHODS: A sample composed of 24 healthy adult individuals of both sexes was submitted to photogrammetric postural assessment. From 35 seconds of filming, 7 photographs (of time instance at 0 second, 05 seconds, 10 seconds, 15 seconds, 20 seconds, 25 seconds, and 30 seconds) were extracted and digitalized on digital image-based postural assessment software. One factor repeated-measures analysis of variance quantified the alterations in the magnitude of the variables within and between sessions (factor time and factor day, respectively). The intraclass correlation coefficient (ICC), standard error of measurement (SEM), and minimal detectable change (MDC) were calculated to verify the repeatability and reproducibility. RESULTS: The repeatability shows that postural variables did not present significant differences in the comparison among the 7 instances; all the variables had excellent and significant ICCs, and SEM and MDC values indicated measurement errors lower than 5%. The intrarater reproducibility shows that postural variables did not present significant differences between 2 days of evaluation; most of the variables had excellent and significant ICCs, and SEM and MDC values were between 0.9% and 12.5%. CONCLUSION: The results for repeatability and reproducibility show that most of the variables have excellent and significant ICCs. Postural evaluation by photogrammetry can be performed at any time within a 30-second interval counting from the positioning of the participant for assessment. Therefore, we conclude that a single photograph can represent the static posture of an individual in the postural evaluation, which is reliable enough and useful to determine the effects of an intervention either in clinical practice or in research.

Podocin and uPAR are good biomarkers in cases of Focal and segmental glomerulosclerosis in pediatric renal biopsies.

There are controversies whether Minimal Change Disease (MCD) and Focal and Segmental Glomerulosclerosis (FSGS) are distinct glomerular lesions or different manifestations within the same spectrum of diseases. The uPAR (urokinase-type plasminogen activator receptor) and some slit diaphragm proteins may be altered in FSGS glomeruli and may function as biomarkers of the disease in renal biopsies. Thus, this study aims to evaluate the diagnostic potential of uPAR and glomerular proteins for differentiation between MCD and FSGS in renal pediatric biopsy. Renal biopsies from 50 children between 2 and 18 years old were selected, with diagnosis of MCD (n = 29) and FSGS (n = 21). Control group consisted of pediatric autopsies (n = 15) from patients younger than 18 years old, with no evidences of renal dysfunction. In situ expressions of WT1, nephrin, podocin and uPAR were evaluated by immunoperoxidase technique. Renal biopsy of patients with MCD and FSGS expressed fewer WT1 (p≤0.0001, F = 19.35) and nephrin (p<0.0001; H = 21.54) than patients in the control group. FSGS patients expressed fewer podocin than control (p<0.0359, H = 6.655). FSGS cases expressed more uPAR than each of control and MCD (p = 0.0019; H = 12.57) and there was a positive and significant correlation between nephrin and podocin (p = 0.0026, rS = 0.6502) in these cases. Podocin had sensitivity of 73.3% and specificity of 86.7% (p = 0.0068) and uPAR had sensitivity of 78.9% and specificity of 73.3% (p = 0.0040) for diagnosis of FSGS patients. The main limitation of the study is the limited number of cases due to the difficulty in performing biopsy in pediatric patients. Podocin and uPAR are good markers for FSGS and differentiate these cases from MCD, reinforcing the theory of distinct glomerular diseases. These findings suggest that podocin and uPAR can be used as biomarkers in the routine analysis of renal biopsies in cases of podocytopathies when the lesion (sclerosis) is not sampled.

Evaluation of the Diagnostic Potential of uPAR as a Biomarker in Renal Biopsies of Patients with FSGS.

Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are primary glomerulopathies leading to proteinuria, known as podocytopathies, which share syndromic and morphological similarities. Morphological similarity occurs in cases of FSGS in which the sclerotic lesion was not sampled in renal biopsy, due to the focal nature of the disease. Differentiating these entities is very important, especially in cases of suspected FSGS but with sclerotic lesion not sampled, as they are diseases that apparently have different pathogenic mechanisms and prognosis. The difference in uPAR expression in situ among these two entities may be related to a distinct molecular mechanism involved in pathogenesis. Thus, finding biomarkers involved in the pathogenesis and that can also help in differential diagnosis is very relevant. The aim of this work was to evaluate the potential of urokinase-type plasminogen activator receptor (uPAR) as a biomarker in renal biopsies of patients with podocytopathies (n = 38). Immunohistochemistry showed that FSGS (n = 22) had increased uPAR expression in podocytes compared with both the MCD group (n = 16; p = 0.0368) and control group (n = 21; p = 0.0076). ROC curve (p = 0.008) showed that this biomarker has 80.95% of specificity in biopsies of patients with FSGS. Therefore, uPAR presented a high specificity in cases of podocytopathies associated with sclerosis and it can be considered a potential biomarker for FSGS.

Influência da posição do marcador maleolar sobre os parâmetros posturais no plano sagital / Influencia de la posición del marcador maleolar en los parámetros posturales del plano sagital / Influence of the malleolar marker position on postural parameters in the sagittal plane

RESUMO Fotogrametria é um método de avaliação postural que fornece informações baseadas no referencial de marcadores anatômicos. No plano sagital, uma das principais avaliações está relacionada ao fio de prumo, apresentando divergências a respeito da colocação do marcador de referência maleolar na bibliografia. Alguns defendem que seja feita exatamente sobre o centro do maléolo lateral, enquanto outros defendem a colocação um pouco à frente do maléolo lateral. O objetivo deste estudo foi identificar se a modificação da posição do marcador maleolar influencia os resultados do procedimento. Trata-se de um estudo observacional analítico transversal, com delineamento comparativo intrassujeitos. Foram avaliados 44 indivíduos saudáveis (25 mulheres e 19 homens; 27±6 anos; 170±11cm; 71±15Kg) utilizando o protocolo e software DIPA© para investigação das variáveis (teste do fio de prumo e pulsão da pelve) no plano sagital, com o marcador maleolar em duas posições: (1) no centro do maléolo lateral e (2) à frente do maléolo lateral. A análise realizada segundo os métodos estatístico, descritivo (distribuição de frequências, média e desvio padrão) e inferencial (testes de Shapiro Wilk, t de Student dependente e Wilcoxon, α=0,05). Para ambas as variáveis, a posição do marcador maleolar exerceu influência estatisticamente significativa (p<0,05) apenas no valor escalar, não afetando significativamente (p>0,05) a classificação postural. Os resultados sugerem que o ponto de referência vertical para a fotogrametria, baseado no marcador maleolar pode ser de escolha do avaliador.

RESUMEN La fotogrametría es un método de evaluación postural que proporciona información basada en los referenciales de los marcadores anatómicos. En el plano sagital, una de las principales evaluaciones se relaciona con la plomada, y demuestra divergencias en cuanto a la colocación del marcador de referencia maleolar en la bibliografía. Algunos autores argumentan que se lo hace exactamente en el centro del maléolo lateral, mientras que otros lo defienden colocando un poco delante del maléolo lateral. El estudio propone identificar si la modificación de la posición del marcador maleolar influye en los resultados del procedimiento. Se trata de un estudio observacional analítico transversal, de concepción comparativa intraindividual. Se evaluaron a 44 individuos sanos (25 mujeres y 19 hombres; 27±6 años; 170±11 cm, 71±15 kg) por medio del protocolo y el software DIPA© para analizar las variables (prueba de la plomada y pulsión de la pelvis) en el plano sagital, con el marcador maleolar en dos posiciones: (1) en el centro del maléolo lateral y (2) delante del maléolo lateral. Se realizó el análisis conforme los métodos estadístico, descriptivo (distribución de frecuencias, media y desviación estándar) y estadística inferencial (prueba de Shapiro-Wilk, prueba t de Student dependiente y de Wilcoxon, α=0,05). En ambas variables, la posición del marcador maleolar tuvo una influencia estadísticamente significativa (p<0,05) en el valor escalar, pero no afectó significativamente (p>0,05) a la clasificación postural. Los resultados revelaron que el punto de referencia vertical a la fotogrametría desde el marcador maleolar puede ser elegido por el evaluador.

ABSTRACT Photogrammetry is a postural evaluation method that provides information based on the reference of anatomical markers. In the sagittal plane, one of the main evaluations is related to the plumb line; however, the literature shows divergences regarding the placement of the malleolar reference marker. Some argue that it must be placed exactly on the center of the lateral malleolus, while others defend placing it slightly in front of the lateral malleolus. This study aimed to identify whether the modification of the position of the malleolar marker affects the results of the procedure. This is a cross-sectional analytical observational study, with comparative intrasubject design. Forty-four healthy subjects (25 women and 19 men; 27±6 years old; 170±11 cm; 71±15 kg) were evaluated using protocol and software DIPA© for investigation of the variables (plumb line test and pelvic version) in the sagittal plane, with the malleolar marker in two positions: (1) in the center of the lateral malleolus and (2) in front of the lateral malleolus. The analysis was carried out according to descriptive (frequency distribution, mean and standard deviation) and inferential (Shapiro-Wilk test, dependent Student's t-test, and Wilcoxon test, α=0.05) statistical methods. For both variables, the malleolar marker position presented statistically significant difference (p<0.05) only on the scalar value, not significantly affecting the posture classification. The results suggest that the vertical reference point for photogrammetry, based on the malleolar marker, can be chosen by the evaluator.

Da diretriz ao mundo real: o papel dos inibidores de PCSK9 / From the guideline to the real world: the role of PCSK9 inhibitors

INTRODUÇÃO: A hipercolesterolemia é um fator de risco para aterosclerose. Segundo a Atualização brasileira de dislipidemias e prevenção de aterosclerose - 2017, a meta terapêutica de LDL colesterol (LDL-c) em pacientes com muito alto risco cardiovascular é menor que 50 mg/dL. OBJETIVO: Apresentar a porcentagem de pacientes de muito alto risco que atingiram as metas es-tabelecidas de LDL-c, tratados no ambulatório de dislipidemias de um hospital terciário, onde o acesso à atorvastatina é livre e gratuito e verificar indicação de prescrição de inibi-dores de PCSK9 de acordo com os critérios NICE (LDL-c >160). MÉTODO: Trata-se de um estudo transversal em que foram coletados dados de pacientes de muito alto risco cardiovascular - aterosclerose clinicamente manifesta, todos em uso de atorvastatina de 40 mg e 80 mg/dia, atendidos em um período de 60 dias no ano de 2018. RESULTADOS: Foram incluídos 280 pacientes, 62% do sexo masculino, média de idade foi de 66 (des-vio padrão 10) anos, 96% hipertensos, 86% diabéticos. Apenas 14% estavam com valor de LDL-c dentro da meta. Entre os que estavam fora da meta terapêutica, o LDL-c estava acima de 100 mg/ dL em 34% dos casos e acima de 160 mg/dL em 9%. CONCLUSÕES: Na prática clínica, a taxa de pacientes que atingem a meta terapêutica de LDL-c recomendada com o uso de estatina de alta potência é baixa. Segundo as recomendações do National Institute foi Health and Care Excellence (NICE), é indicado o uso inibidores de PCSK9 para pacientes de muito alto risco cardiovascular com hipercolesterolemia já em uso de estatina, mas que mantêm níveis de LDL acima de 160 mg/dL. Dessa forma, 9% dos pacientes fora da meta de LDL deste hospital terciário analisado poderiam se beneficiar do uso desses anticorpos monoclonais. (AU)

Arrtimias nas cardiopatias congênitas no adulto ­ uma revisão de literatura / Arrtimias in congenital heart disease in adults - a literature review

INTRODUÇÃO: As cardiopatias congênitas são afecções comuns e, com avanço das técnicas diagnósticas e das abordagens cirúrgicas, tem prevalência crescente na população adulta. Enquanto o principal determinante da morbimortalidade na população pediátrica está relacionado ao resultado do seu tratamento cirúrgico, na população adulta, estão relacionadas a ocorrência de arritmias e mecanismos adaptativos a longo prazo. OBJETIVO: Almeja-se realizar revisão da literatura sobre as diferentes arritmias associadas a cardiopatias congênitas no adulto, além de detalhar seus diferentes mecanismos fisiopatológicos. METODOLOGIA: Tratase de revisão bibliográfica utilizando os descritores "arrhythmia", "adult congenital heart disease", utilizando plataformas Scielo, Lilacs e Pubmed de artigos publicados nos últimos 05 anos sobre o tema. RESULTADOS: As arritmias podem ser diferenciadas quando a sua origem em supraventriculares (mais comuns, cerca de 75% das arritmias) e ventriculares. A prevalência das arritmias varia com o tipo de cardiopatia estudada, além da idade, podendo chegar até 50% em cardiopatias mais complexas, como a Tetralogia de Fallot. Dentre as taquiarritmias supraventriculares, destacam-se a taquicardia atrial por reentrada intra-atrial (TRIA), fibrilação atrial, flutter atrial, taquicardia juncional. Já as taquiarritmias ventriculares, com grande associação a morte súbita cardíaca nesses pacientes, são, sobretudo, representadas pelas taquicardias ventriculares, em sua maioria não-sustentadas. Com relação as bradiarritmias, elas podem acometer todos os pontos do sistema de condução (nó sinusal, nó atrioventicular (AV), feixe de His, fibras de Purkinje), com destaque especial aos diferentes graus de bloqueios AV e disfunção do nó sinusal. Seus mecanismos fisiopatológicos têm origens diversas, podendo-se destacar diversos mecanismos pré e pós-cirúrgicos. Vale também salientar que não é incomum a ocorrência de mais de um tipo de arritmia, podendo seus diferentes subtipos coexistir frequentemente. CONCLUSÃO: A identificação, diagnóstico correto e manejo das arritmias cardíacas nas cardiopatias congênitas no adulto constituem desafio ao cardiologista. As cardiopatias congênitas conferem características especiais que devem ser conhecidas pelo cardiologista, para correta identificação e realização de conduta terapêutica adequada, uma vez que podem ter efeito profundo e adverso no desfecho dessa população de pacientes, cada vez mais prevalente nos dias atuais. (AU)

Estratificação de risco morte súbita em cardiopatias congênitas do adulto / Risk stratification sudden death in adult congenital heart disease

INTRODUÇÃO: Avanços no tratamento de crianças com cardiopatia congênita causou aumento dessa população em idade adulta, criando a necessidade de uma nova especialidade: Cardiopatia congênita em adultos (GUCH). Esta população é exposta a um maior risco de óbito, principalmente causada por morte súbita cardíaca (MSC), de origem arrítmica. OBJETIVOS: Definir os mais importantes aspectos de saúde dessa população, com ênfase nas complicações arritmicas tardias, principais causas de MSC. Objetiva-se estimular o investimento na área, para o manejo correto do GUCH. METODOS: Trata-se de revisão bibliográfica utilizando os descritores "GUCH", "sudden cardiac death", "estratificaçao de risco em GUCH", utilizando plataformas Scielo, Lilacs e Pubmed de artigos publicados nos últimos 5 anos sobre o tema. RESULTADOS: Sabendo-se que nos adultos com cardiopatias congênitas a morte súbita é causa de morte comum nos adultos com cardiopatias congênitas, sendo principalmente causada por arritmias, identificar os fatores de risco para tal condição é essencial para a melhor assistência desses pacientes. A anatomia, história da cirurgia, status hemodinâmico devem ser avaliados para definição do risco de arritmia e morte súbita, significando um maior desafio nos pacientes assintomáticos. Um estudo casocontrole multicêntrico conseguiu identificar fatores associados a MS nessa população. De maneira geral, a taquicardia supraventricular foi fator de risco ­ predominantemente flutter e fibrilação atrial, a duração e a dispersão do QT (odds ratio de 1.22 para cada aumento de 10ms). A redução da função ventricular é fator de risco para MS. Dessa forma, a estratificação de risco é indicada nos pacientes de maior risco ou naqueles em que na avaliação inicial, anamnese e exame físico, apresentarem achados que podem indicar risco aumentado e pior prognóstico: presença de palpitações rápidas, síncope inexplicada, presença de arritmia cardíaca, sopro cardíaco ou sinais de insuficiência cardíaca. O conhecimento de preditores e fatores de risco pode ajudar na decisão clínica de quais pacientes se beneficiaram com estabelecimento de terapias profiláticas. CONCLUSÃO: A alta prevalência de arritmias, a deteriorização funcional progressiva, e o risco de morte súbita como primeira manifestação clínica, força a realização de estratificação desses pacientes, para determinação de seguimento mais adequado , incluindo a profilaxia primária. (AU)

Atualização em reabilitação e o impacto na qualidade de vida do paciente falcêmico / Rehabilitation update and impact on sickle cell patient's quality of life

INTRODUÇÃO: A anemia falciforme é uma doença genética caracterizada pela produção de hemoglobina anormal, gerando estado pró-inflamatório, polimerização da HbS e posterior falcização, gerando as complicações agudas e crônicas da doença. Terapias atuais levam a uma maior expectativa de vida, porém ainda é causa de importante de morbidade, baixa qualidade de vida e intolerância ao exercício. A literatura diverge sobre o papel do exercício como potencializador das complicações agudas da doença falciforme ou como fator protetor de novas crises. As alterações metabólicas inerentes ao exercício, a depender da duração e intensidade, podem desencadear as complicações falcêmicas. Por outro lado, alguns trabalhos mostram segurança na realização de exercício de endurance moderado, sugerindo menor risco de disfunção endotelial. Atualmente, não existem recomendações, sobre prescrição da modalidade, intensidade ou duração de exercícios, que ajudem a modular alterações biológicas/previnam complicações agudas. OBJETIVOS: Definir as indicações do treinamento físico do paciente falcêmico através de uma ampla revisão bibliográfica. O conhecimento das limitações do exercício e da programação de reabilitação possui enorme relevância social e através do teste cardiopulmonar de exercício (TCPE), podese mensurar a real capacidade funcional de tais pacientes, e auxilia-los na prescrição do treinamento físico. Esses conhecimentos auxiliarão na retomada de atividades desses pacientes, podendo reinseri-los adequadamente na sociedade, além dos possíveis benefícios de sobrevida e qualidade de vida. METODOS: Trata-se de revisão bibliográfica utilizando os descritores "rehabilitation", "sickle cell anemia", "exercise and sickle cell disease", "cardiopulmonary exercise testing", utilizando plataformas Scielo, Lilacs e Pubmed de artigos publicados nos últimos 20 anos sobre o tema. CONCLUSÃO: Diversos estudos foram desenvolvidos com objetivo de determinar o impacto da exercícios na história natural da anemia falciforme. Para tal, o TCPE representa a modalidade mais acurada de avaliação da resposta ao exercício nesse grupo de pacientes. Os resultados demonstram que os pacientes com AF podem ser submetidos a estresse moderado sem complicações clínicas. Embora a literatura ainda seja escassa os estudos sugerem benefícios promovidos pelo treinamento físico que devem ser buscados em detrimento do baixo risco de complicações. (AU)

Sangramentos tardios após TAVI ­ o que já sabemos? Uma revisão de literatura / Late bleeding after TAVI - what do we already know? A literature review

INTRODUÇÃO: A estenose aórtica (EAo) constitui uma das principais valvopatias encontradas, estando associada a grande morbimortalidade ao iniciarem os seus sintomas. O implante de bioprótese aórtica transcateter (do inglês transcatheter aortic valve implantation ­ TAVI) constitui em modalidade mais recente no tratamento intervencionista da estenose aórtica, revolucionando a propedêutica de muitos pacientes antes considerados inoperáveis. Grande preocupação é dada as complicações de sangramento submetidos pós-TAVI. OBJETIVO: Fazer análise crítica sobre o papel do sangramento tardio e seu impacto prognóstico nos pacientes submetidos a TAVI. METODOLOGIA: Trata-se de revisão bibliográfica utilizando os descritores "late bleeding", "TAVI", "aortic stenosis", utilizando plataformas Scielo, Lilacs e Pubmed de artigos publicados nos últimos 05 anos sobre o tema. RESULTADOS: Enquanto os sangramentos precoces estão mais relacionados a complicações relacionadas ao procedimento (complicações em sítio de acesso ou complicações vasculares), os fatores relacionados ao sangramento tardio são pouco conhecidos. Sabe-se que o sangramento está associado a complicações vasculares maiores, uso de suporte hemodinâmico, maior necessidade de hemotransfusões, tendo grande impacto na morbimortalidade desses doentes. No único grande trial que avaliou o impacto do sangramento tardio, observou-se que a taxa de sangramentos chegou a 6% nessa população, estando associado a piores desfechos. Existem diversos trabalhos na literatura que tentam estabelecer um perfil de pacientes mais propensos a essa complicação, tendo fatores relacionados ao paciente, alterações ecocardiográficas que conferem maior risco ou ainda inerentes ao próprio procedimento em si, como tipo de prótese, técnica de abordagem. Fatores como o tempo de terapia antitrombótica e necessidade de anticoagulação oral também parecem ter papel importante na gênese dos sangramentos tardios, tendo resultados variados na literatura. CONCLUSÃO: o conhecimento dos fatores relacionados ao sangramento tardio são de grande importância na redução de efeitos adversos tardios, sendo a realização de mais estudos envolvendo sangramentos tardios e analisando a nossa população necessária para maior entendimento dessa complicação. (AU)

Efeitos anti-hipertensivos do aceturato de diminazeno: um ativador da enzima conversora de angiotensina 2 em ratos / Antihypertensive effects of diminazene aceturate: an activator of angiotensin-2 converting enzyme in rats

INTRODUÇÃO: O sistema renina-angiotensina-aldosterona desempenha importante papel cardiovascular. A enzima conversora de angiotensina 2 (ECA2) degrada a Angiotensina II em Angiotensina-(1-7), que se liga ao receptor Mas e há liberação de óxido nítrico (NO). Recentemente, foi descrito o aceturato de diminazeno (DIZE), ativador da ECA2. OBJETIVOS: Avaliar a ação do DIZE na pressão arterial (PA) e frequência cardíaca (FC) de ratos normotensos e hipertensos, além de explorar seu mecanismo de ação em vasos isolados. Métodos: Estudo de intervenção em ratos submetidos a implante de cânulas na artéria femoral para registrar PA e FC e na veia femoral para injeção de DIZE e salina (controle). O efeito no fluxo sanguíneo de arteríolas mesentéricas foi avaliado por microscopia intravital. Para induzir hipertensão arterial foi usado o modelo de hipertensão renovascular (2-kidney1clip; 2K1C). Após o procedimento, os animais foram tratados com DIZE, captopril ou salina e posteriormente feita análise histológica dos corações. No estudo in vitro de vasos isolados, o mecanismo de ação do DIZE foi avaliado usando o A-779, bloqueador do Mas, e o L-NAME, inibidor da NO sintase. RESULTADOS e CONCLUSÕES: O DIZE causou redução na PA com aumento compensatório da FC de maneira dose-dependente em ratos normotensos (Fig.1). O efeito hipotensor do DIZE foi semelhante ao do captopril em ratos hipertensos e não houve alteração na FC (Fig.1). Houve diminuição na velocidade do fluxo nas arteríolas no leito vascular mesentérico em ratos normotensos. A vasodilatação foi dependente do Mas e da liberação de NO. O DIZE preveniu o desenvolvimento de hipertrofia cardíaca em ratos hipertensos. Conclui-se que o DIZE tem efeito hipotensor em ratos normotensos e hipertensos devido a liberação de NO após ativação do Mas. (AU)