Challenges in the surgical treatment of a 8-year old child living with Prune Belly syndrome: case report / Desafios no tratamento tardio da síndrome de Prune Belly: relato de caso

Prune Belly syndrome, also known as Eagle-Barret syndrome, is a rare disease, with a prevalence of 3.8 live births per 100,000 births. Its main characteristic is the hypoplasia of the abdominal muscles, giving rise to the name "prune belly syndrome". The gold standard treatment is surgery, ideally with correction of cryptorchidism and phimosis between 6 to 18 months of life. Correction of urinary malformations and abdominoplasty should be performed up to 4 years of age. Little evidence exists in the literature about late treatment and its implications for prognosis. The context mentioned above led us to present an uncommon case of a six years old child in which a surgical approach was performed later than usual.

Introdução: A síndrome de Prune Belly é uma doença rara, com prevalência de 3,8 nascidos vivos a cada 100 mil nascimentos. Tem como principal caraterística a hipoplasia da musculatura abdominal gerando a origem do nome "síndrome da barriga de ameixa". O tratamento padrão ouro é cirúrgico, idealmente com correção da criptorquidia e fimose entre 6 a 18 meses e a correção das malformações urinárias e abdominoplastia devem ser realizadas até os 4 anos. Aqui descreve-se um caso ainda menos comum, em que foi realizada abordagem cirúrgica de forma mais tardia que o habitual. Há pouca evidência na literatura acerca do tratamento tardio e suas implicações em relação ao prognóstico.

Traffic accident mortality of motorcyclists, pedestrians and hospital costs in the city of São Paulo

Introduction: the United Nations recognizes traffic accidents as a serious public health problem all over the world, because they are accompanied by a high morbidity and mortality rate. Traffic causes the death of approximately 1.3 million people and the disability of millions more.Objective: to evaluate mortality from traffic accidents among motorcyclists, pedestrians and hospital costs that occurred in the city of São Paulo, Brazil, from 1999 to 2019.Methods: this is a retrospective time series study with official micro data, collected by place of occurrence among motorcycle drivers, pedestrians and hospital costs from 1999 to 2019, in the city of São Paulo, SP, Brazil.Results: in the city of São Paulo, from 1999 to 2019, there were 144,186 thousand deaths resulting from land transport accidents, projecting 5,293 thousand deaths specifically with motorcyclists. Proportional mortality from was higher in the mean age group of 29 years, predominantly in males, with emphasis on white race/skin color. The costs per death stand out for motorcyclists with an average of R$: 49,078.18, with regard to deaths by sex, male predominated in relation to female.Conclusion: there was a high death rate, both in motorcyclists and pedestrians, with the latter having a higher average. Thus, these findings provide relevant information on the magnitude of the public health problem to guide us on control strategies for these causes.

Impact of bariatric surgery in elderly patients with obesity.

INTRODUCTION: to evaluate the long-term impact of bariatric surgery in the elderly population. METHODS: a retrospective study including all patients older than 60 years who underwent Roux-en-Y gastric bypass (RYGB) at our center and maintained a follow-up longer than 1 year. Clinical and laboratory variables were studied to assess remission of obesity and its comorbidities, as well as variables directly related to the surgical procedure itself, including early and late complications. RESULTS: fifty-six patients were studied, mostly female (76,8%), with a mean age of 64.02 ± 3.34. A rate of complications of 37,5% was observed, with 10,7% requiring hospital admission and emergency surgery. The mean excess weight loss (%EWL) was 74.22% ± 26.76. The remission rates of hypertension and diabetes mellitus were 26.08% and 54.54%, respectively. There was significant difference in BMI reduction (12.25 ± 5.42, p<0.001), total cholesterol (31.37 ± 38.89 p<0,001), LDL cholesterol (23.45 ± 34.9, p=0.002), HDL cholesterol (5.14 ± 11.13, p=0,024), triglycerides (48.85 ± 56.15 p<0.001), HbA1C (1,81 ± 1,97, p<0,001) e PCR (1.43 ± 1.96, p<0.001). CONCLUSION: bariatric surgery was effective in weight loss and remission of comorbidities in the elderly obese population within the long term.

Analysis of cathepsin S expression in gastric adenocarcinoma and in Helicobacter pylori infection.

BACKGROUND: Recent experimental studies have suggested a potential link between cathepsin S (CTTS) and gastric adenocarcinoma progression. Herein, we aimed to evaluate the expression of CTTS in gastric adenocarcinoma in patients who underwent curative-intent surgical resection. METHODS: This was a cross-sectional study that included two groups: gastric adenocarcinoma (n = 42) and gastritis (n = 50). The gastritis group was then subdivided into H. pylori-positive (n = 25) and H. pylori-negative (n = 25) groups. Gastric tissue samples were analysed to determine CTTS expression through immunohistochemistry. Samples were obtained by oesophagogastroduodenoscopy or surgical specimens. RESULTS: In patients with gastritis, the age ranged from 18 to 78 years. Among them, 34% were male, and 66% were female. In patients with gastric adenocarcinoma, the age ranged from 37 to 85 years. Among them, 50% were male. When comparing the expression of CTTS between the two groups, only 16% of the gastritis samples had an expression higher than 25%. Alternatively, among patients with gastric adenocarcinoma, 19% had expression between 25-50%, 14.3% between 51-75%, and 26.2% had expression higher than 75% (p < 0.001). In the gastritis group, CTTS expression was significantly higher in patients with a positive test for H. pylori than negative test for H. pylori: 87.5% and 38.5%, respectively (p<0.001). There was no statistically significant association between CTTS positivity and clinicopathological variables, including tumour staging, histological type, angiolymphatic invasion, recurrence, current status and death. CONCLUSION: CTTS expression is higher in gastric adenocarcinoma samples. Patients with gastritis due to H. pylori also show a higher expression of CTTS than patients with negative results for this bacterium.

Impact of Three Methods of Ischemic Preconditioning on Ischemia-Reperfusion Injury in a Pig Model of Liver Transplantation.

BACKGROUND: Ischemic preconditioning (IPC), either direct (DIPC) or remote (RIPC), is a procedure aimed at reducing the harmful effects of ischemia-reperfusion (I/R) injury. OBJECTIVES: To assess the local and systemic effects of DIPC, RIPC, and both combined, in the pig liver transplant model. MATERIALS AND METHODS: Twenty-four pigs underwent orthotopic liver transplantation and were divided into 4 groups: control, direct donor preconditioning, indirect preconditioning at the recipient, and direct donor with indirect recipient preconditioning. The recorded parameters were: donor and recipient weight, graft-to-recipient weight ratio (GRWR), surgery time, warm and cold ischemia time, and intraoperative hemodynamic values. Blood samples were collected before native liver removal (BL) and at 0 h, 1 h, 3 h, 6 h, 12 h, 18 h, and 24 h post-reperfusion for the biochemical tests: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), creatinine, BUN (blood urea nitrogen), lactate, total and direct bilirubin. Histopathological examination of liver, gut, kidney, and lung fragments were performed, as well as molecular analyses for expression of the apoptosis-related BAX (pro-apoptotic) and Bcl-XL (anti-apoptotic) genes, eNOS (endothelial nitric oxide synthase) gene, and IL-6 gene related to inflammatory ischemia-reperfusion injury, using real-time polymerase chain reaction (RT-PCR). RESULTS: There were no differences between the groups regarding biochemical and histopathological parameters. We found a reduced ratio between the expression of the BAX gene and Bcl-XL in the livers of animals with IPC versus the control group. CONCLUSIONS: DIPC, RIPC or a combination of both, produce beneficial effects at the molecular level without biochemical or histological changes.

Impact of bariatric surgery in elderly patients with obesity / Impacto da cirurgia bariátrica em pacientes idosos portadores de obesidade

ABSTRACT Introduction: to evaluate the long-term impact of bariatric surgery in the elderly population. Methods: a retrospective study including all patients older than 60 years who underwent Roux-en-Y gastric bypass (RYGB) at our center and maintained a follow-up longer than 1 year. Clinical and laboratory variables were studied to assess remission of obesity and its comorbidities, as well as variables directly related to the surgical procedure itself, including early and late complications. Results: fifty-six patients were studied, mostly female (76,8%), with a mean age of 64.02 ± 3.34. A rate of complications of 37,5% was observed, with 10,7% requiring hospital admission and emergency surgery. The mean excess weight loss (%EWL) was 74.22% ± 26.76. The remission rates of hypertension and diabetes mellitus were 26.08% and 54.54%, respectively. There was significant difference in BMI reduction (12.25 ± 5.42, p<0.001), total cholesterol (31.37 ± 38.89 p<0,001), LDL cholesterol (23.45 ± 34.9, p=0.002), HDL cholesterol (5.14 ± 11.13, p=0,024), triglycerides (48.85 ± 56.15 p<0.001), HbA1C (1,81 ± 1,97, p<0,001) e PCR (1.43 ± 1.96, p<0.001). Conclusion: bariatric surgery was effective in weight loss and remission of comorbidities in the elderly obese population within the long term.

RESUMO Introdução: avaliar o impacto da cirurgia bariátrica na população idosa no longo prazo. Métodos: estudo retrospectivo que incluiu todos os pacientes com mais de 60 anos submetidos ao Bypass gástrico em Y de Roux (BGYR) em nosso centro e que mantiveram seguimento superior a 1 ano. Foram estudadas variáveis clínicas e laboratoriais para avaliação da remissão da obesidade e suas comorbidades, além de variáveis diretamente relacionados ao procedimento cirúrgico em si, incluindo complicações precoces e tardias. Resultados: foram estudados 56 pacientes, a maioria do sexo feminino (76,8%), com idade média de 64,02 ± 3,34. Foi observada uma taxa de complicações de 37,5%, com 10,7% requerendo internamento hospitalar e cirurgia de urgência. A média geral da perda do excesso de peso (%PEP) foi de 74,22% ± 26,76. As taxas de remissão de hipertensão e diabetes mellitus foram de 26,08% e 54,54%, respectivamente. Houve variação significativa no IMC (12,25 ± 5,42, p<0,001), colesterol total (31,37 ± 38,89 p<0,001), colesterol LDL (23,45 ± 34,9, p=0,002), colesterol HDL (5,14 ± 11,13, p=0,024), triglicerídeos (48,85 ± 56,15 p<0,001), HbA1C (1,81 ± 1,97, p<0,001) e PCR (1,43 ± 1,96, p<0,001). Conclusão: a cirurgia bariátrica se mostrou eficaz na perda de peso e na remissão de comorbidades na população de idosos com obesidade no longo prazo..

Mortality and case fatality rates of COVID-19 in the State of Goiás, Brazil / Taxas de mortalidade e fatalidade de casos da COVID-19 no Estado de Goiás, Brasil

INTRODUCTION: the initial spread of the pandemic in Brazil was mainly affected by patterns of socioeconomic vulnerability. It should be noted that the Central-West region of Brazil is one of the regions with the lowest number of cases, but the states of this region together have the highest mortality rate of COVID-19 in the country. Goiás was the most affected state of this region, with the highest number of deaths in the area. OBJECTIVE: to assess the incidence of mortality and lethality caused by COVID-19 from March 2020 to June 2021 in the State of Goiás, Brazil. METHODS: an ecological study, using a series of time series of public and official data of the Department of Health of the State of Goiás, Brazil. Information was collected on cases and deaths from COVID-19 from March 2020 to June 2021. Mortality, case fatality, and incidence rates were calculated. The Prais-Wisten regression model was used to build time series. The daily percent change (DPC) and the effective reproductive number (Rt) were estimated. RESULTS: Goiás had a predominance of a greater viral spread during the first and the beginning of the second wave, with Rt higher than 1. The second wave from December 2020 to June 2021 was more lethal and had higher mortality rates than the first wave. It was observed, higher scores of case fatality and mortality belonged to males and the elderly. CONCLUSION: an analysis of mortality and case fatality rates helps understand the COVID-19 pandemic behavior in Goiás. It is essential to monitor epidemiological indicators and strengthen intervention strategies to contain the pandemic in this state.

INTRODUÇÃO: a propagação inicial da pandemia no Brasil foi afetada principalmente por padrões de vulnerabilidade socioeconômica. Ressalta-se que a região Centro-Oeste do Brasil é uma das regiões com menor número de casos, mas os estados dessa região juntos apresentaram a maior taxa de mortalidade por COVID-19 do país. Goiás foi o estado mais afetado da região, com o maior número de óbitos. OBJETIVO: avaliar a incidência, mortalidade e letalidade por COVID-19 no Estado de Goiás, Brasil, no período de março de 2020 a junho de 2021. MÉTODO: estudo ecológico, utilizando séries temporais de dados públicos e oficiais da Secretaria de Saúde do Estado de Goiás, Brasil. As informações foram coletadas sobre casos e óbitos de COVID-19 de março de 2020 a junho de 2021. Mortalidade, letalidade e taxas de incidência foram calculadas. O modelo de regressão Prais-Wisten foi usado para construir séries temporais. A mudança percentual diária (DPC) e o número reprodutivo efetivo (Rt) foram estimados. RESULTADOS: Goiás teve predomínio de maior disseminação viral durante a primeira onda e o início da segunda onda, com Rt maior que 1. A segunda onda, dezembro de 2020 a junho de 2021, foi mais letal e apresentou taxas de mortalidade maiores que a primeira onda. Observou-se que os maiores escores de letalidade e mortalidade pertenciam ao sexo masculino e aos idosos CONCLUSÃO: uma análise das taxas de mortalidade e letalidade ajuda a entender o comportamento da pandemia do COVID-19 em Goiás. É fundamental monitorar indicadores epidemiológicos e fortalecer estratégias de intervenção para conter a pandemia neste estado.

Brugada syndrome: current concepts and genetic background / Síndrome de Brugada: conceitos atuais e antecedentes genéticos

BACKGROUNG: Brugada syndrome (BrS) is a hereditary clinical-electrocardiographic arrhythmic entity with low worldwide prevalence. The syndrome is caused by changes in the structure and function of certain cardiac ion channels and reduced expression of Connexin 43 (Cx43) in the Right Ventricle (RV), predominantly in the Right Ventricular Outflow Tract (VSVD), causing electromechanical abnormalities. The diagnosis is based on the presence of spontaneous or medicated ST elevation, characterized by boost of the J point and the ST segment ≥2 mm, of superior convexity "hollow type" (subtype 1A) or descending rectilinear model (subtype 1B). BrS is associated with an increased risk of syncope, palpitations, chest pain, convulsions, difficulty in breathing (nocturnal agonal breathing) and/or Sudden Cardiac Death (SCD) secondary to PVT/VF, unexplained cardiac arrest or documented PVT/VF or Paroxysmal atrial fibrillation (AF) in the absence of apparent macroscopic or structural heart disease, electrolyte disturbance, use of certain medications or coronary heart disease and fever. In less than three decades since the discovery of Brugada syndrome, the concept of Mendelian heredity has come undone. The enormous variants and mutations found mean that we are still far from being able to concretely clarify a genotype-phenotype relationship. There is no doubt that the entity is oligogenetic, associated with environmental factors, and that there are variants of uncertain significance, especially the rare variants of the SCN5A mutation, with European or Japanese ancestors, as well as a spontaneous type 1 or induced pattern, thanks to gnomAD (coalition) researchers who seek to aggregate and harmonize exome and genome sequencing data from a variety of large-scale sequencing projects and make summary data available to the scientific community at large). Thus, we believe that this in-depth analytical study of the countless mutations attributed to BrS may constitute a real cornerstone that will help to better understand this intriguing syndrome.

INTRODUÇÃO: A Síndrome de Brugada (SBr) é uma entidade arrítmica clínico-eletrocardiográfica hereditária com baixa prevalência mundial. A síndrome é causada por alterações na estrutura e função de certos canais iônicos cardíacos e redução da expressão da Connexina 43 (Cx43) no Ventrículo Direito (VD), predominantemente no Trato de Saída do Ventricular Direito (VSVD), causando anormalidades eletromecânicas. O diagnóstico é baseado na presença de supradesnivelamento de ST espontâneo ou medicamentoso caracterizado por supradesnivelamento do ponto J e do segmento ST ≥2 mm, de convexidade superior "tipo covado" (subtipo 1A) ou modelo retilíneo descendente (subtipo 1B). A SBr está associado a um risco aumentado de síncope, palpitações, dor precordial, convulsões, dificuldade em respirar (respiração agonal noturna) e/ou Morte Cardíaca Súbita (MSC) secundária a PVT/VF, parada cardíaca inexplicada ou PVT/VF documentado ou Fibrilação atrial paroxística (FA) na ausência de doença cardíaca macroscópica ou estrutural aparente, distúrbio eletrolítico, uso de certos medicamentos ou coração coronário e febre. Em menos de três décadas desde a descoberta da síndrome de Brugada, o conceito de hereditariedade mendeliana se desfez. As enormes variantes e mutações encontradas significam que ainda estamos longe de sermos capazes de esclarecer concretamente uma relação genótipo-fenótipo. Não há dúvida de que a entidade é oligogenética associada a fatores ambientais, e que há variantes de significado incerto, principalmente as raras variantes da mutação SCN5A, com ancestrais europeus ou japoneses, bem como padrão espontâneo tipo 1 ou induzido, graças ao gnomAD (coalizão de pesquisadores que buscam agregar e harmonizar dados de sequenciamento de exoma e genoma de uma variedade de projetos de sequenciamento em grande escala e disponibilizar dados resumidos para a comunidade científica em geral). As enormes variantes e mutações encontradas significam que ainda estamos longe de sermos capazes de esclarecer concretamente uma relação genótipo-fenótipo. Assim, acreditamos que este estudo analítico em profundidade das inúmeras mutações atribuídas à BrS pode constituir uma verdadeira pedra angular que ajudará a compreender melhor esta síndrome intrigante.

Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

The severe form of COVID-19 is marked by an abnormal and exacerbated immunological host response favoring to a poor outcome in a significant number of patients, especially those with obesity, diabetes, hypertension, and atherosclerosis. The chronic inflammatory process found in these cardiometabolic comorbidities is marked by the overexpression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumoral necrosis factor-alpha (TNF-α), which are products of the Toll-Like receptors 4 (TLR4) pathway. The SARS-CoV-2 initially infects cells in the upper respiratory tract and, in some patients, spread very quickly, needing respiratory support and systemically, causing collateral damage in tissues. We hypothesize that this happens because the SARS-CoV-2 spike protein interacts strongly with TLR4, causing an intensely exacerbated immune response in the host's lungs, culminating with the cytokine storm, accumulating secretions and hindering blood oxygenation, along with the immune system attacks the body, leading to multiple organ failure.

Primary hepatic neuroendocrine tumor: A case report and literature review.

INTRODUCTION: Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare, having less than 200 cases reported in the literature. PRESENTATION OF CASE: A 51-year-old woman presenting with mild intensity sharp pain in the upper abdomen that started 4 years ago. Preoperative Magnetic Resonance Imaging (MRI) suggested hepatocellular adenoma. Surgical exploration found a tumor occupying the whole segment IV of the liver, therefore a left hepatectomy was performed. Pathology and immunohistochemistry indicated to be a low-grade neuroendocrine tumor of the liver. The patient is enjoying a good quality of life, free of disease, presenting no signs of recurrence nor metastases 12 months after the procedure. CONCLUSION: The clinical presentation of PHNETs is non-specific and its radiologic features are intensely diversified, frequently leading to misdiagnosis of other hepatic neoplasms.

A durable murine model of spleen transplantation with arterial and venous anastomoses.

The spleen is a large lymphoid organ located in the abdomen that filters blood and regulates the immune system. The extent of mobilization of splenic immune cells to peripheral tissues in health and disease, however, remains poorly understood. This is due, in large part, to a lack of in vivo, spleen-specific lineage tagging strategies. Here, we describe a detailed practical protocol of spleen transplantation and its evaluation for long-term graft survival. Unlike implantation of splenic morsels in the great omentum, our approach uses arterial and venous anastomoses which rapidly restores blood flow and facilitates long-term survival of the graft. The use of congenic mouse strains permits the use of immunofluorescence and flow cytometry-based methodologies to unambiguously track the migration of spleen-derived cells to peripheral tissues.

[Subjective method for tracheal tube cuff inflation: performance of anesthesiology residents and staff anesthesiologists. Prospective observational study]. / Insuflação de balonete de tubo traqueal por método subjetivo: desempenho de médicos residentes e especialistas em anestesiologia. Estudo prospectivo observacional.

BACKGROUND AND OBJECTIVES: Poor monitoring of tracheal tube cuff pressure may result in patient complications. The objective method of using a manometer is recommended to keep safe cuff pressure values (20-30 cm H2O). However, as manometers are not readily available, anesthesiologists use subjective methods. We aimed to assess appropriateness of a subjective method for attaining cuff pressure and the expertise level of manometer handling among anesthesiology staff and residents in a university teaching hospital. METHODS: Prospective observational study, recruiting participants that performed tracheal intubation and the subjective method for tube cuff inflation. Patients with difficult airway, larynx and trachea anatomic abnormality and emergency procedures were not included. Up to 60 minutes after tracheal intubation, an investigator registered the cuff pressure using an aneroid manometer (AMBU®) connected to the tube pilot balloon. RESULTS: Forty-seven anesthesiologists were included in the study - 24 residents and 23 staff. Mean (SD) and medians (IQR) measured in cm H2O were, respectively, 52.5 (27.1) and 50 (30-70). We registered 83% of measurements outside the recommended pressure range, with no difference between specialists and residents. The level of expertise with the objective method was also similar in both groups. Pressure adjustments were performed in 76.6% of cases. CONCLUSION: The subjective method for inflating the tracheal tube cuff resulted in a high rate of inadequate cuff pressures, with no difference in performance between anesthesiology specialists and residents.

Cathepsin S as a target in gastric cancer.

Cathepsin S (Cat S) is a protein expressed in some epithelial cells, which appears to be associated with cancer metastasis and recurrence. The abnormal expression of Cat S has been reported to be associated with the progression of certain types of gastrointestinal neoplasms, including gastric cancer (GC). There is a need to identify novel biomarkers and therapeutic targets associated with the growth, invasion and migration of GC cells, in order to develop non-invasive diagnostic and prognostic procedures and design new therapeutic approaches. The aim of the present study was to assess the association between Cat S and oncogenic processes implicated in the development of GC, focusing on the diagnostic and therapeutic potential of this molecule in GC. A search was conducted through the PubMed and Cochrane Central Register of Controlled Trials electronic databases for relevant literature published between 2003 and 2018, using the mesh terms 'cathepsin S' and 'cancer' and 'gastric cancer'.

Multiorgan Systems Study Reveals Igfbp7 as a Suppressor of Gluconeogenesis after Gastric Bypass Surgery.

Roux-en-Y gastric bypass (RYGB) surgery reduces weight in obese patients. A marked decrease in blood glucose levels occurs before weight loss; however, key molecules that improve the glycemic profile remain largely unknown. Using a murine RYGB surgery model, we performed multiorgan proteomics and bioinformatics to monitor the proteins and molecular pathways that change in this early glycemic response. Multiplexed proteomic kinetics data analysis revealed that the Roux limb, biliopancreatic limb, liver, and pancreas each exhibited unique temporal and molecular responses to the RYGB surgery. In addition, protein-protein network analysis indicated that the changes to the microbial environment in the intestine may play a crucial role in the beneficial effects of RYGB surgery. Furthermore, insulin-like growth factor binding protein 7 (Igfbp7) was identified as an early induced protein in the Roux limb. Known secretory properties of Igfbp7 prompted us to further investigate its role as a remote organ regulator of glucose metabolism. Igfbp7 overexpression decreased blood glucose levels in diet-induced obese mice and attenuated gluconeogenic gene expression in the liver. Secreted Igfbp7 appeared to mediate these beneficial effects. These results demonstrate that organs responded differentially to RYGB surgery and indicate that Igfbp7 may play an important role in improving blood glucose levels.

The Effect of Sleeve Gastrectomy on the Hormonal Profile of Patients with Polycystic Ovary Syndrome.

PURPOSE: To prospectively evaluate the hormonal profile and weight loss of women with obesity and PCOS submitted to sleeve gastrectomy (SG). METHODS: A Prospective study carried out at the Hospital das Clínicas, Federal University of Pernambuco, Recife, Brazil, in 2018, where 18 patients with PCOS, whose age varied from 18 to 40 years, with an indication for bariatric surgery were evaluated. Plasma estradiol (E2), fasting insulin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured prior to bariatric surgery and 3 months after surgery. The LH/FSH ratio and BMI of the study participants were also calculated. RESULTS: Postoperative E2 levels were higher (preoperative mean of 63.4 pg/dL versus postoperative mean of 91.0 pg/dL), with no statistical significance then (p = 0.139). It was observed, at the postoperative period, statistically significant decreases in mean fasting insulin levels (24.4 mIU/mL vs. 9.0 mIU/mL; p < 0.001), LH levels (7.2 vs. 4.5; p = 0.047), and an inverted LH/FSH ratio (1.5 vs. 0.9; p = 0.008); relevant weight loss occurred (mean BMI, 40.5 kg/m2 vs. 33.4 kg/m2; p < 0.001). CONCLUSION: Relevant changes in the hormone profile and significant alterations in the gonadotropic and insulin patterns were seen. In addition to satisfactory weight loss, the observed endocrine alterations revealed an internal environment that was more homeostatic and conducive to reproduction, indicating that SG was able to produce attractive physiological outcomes for women with PCOS.

Dedifferentiated liposarcoma of the gallbladder: first reported case.

BACKGROUND: Liposarcoma of the gallbladder is an extremely rare sarcoma, with only five cases reported in the literature according to our knowledge. CASE PRESENTATION: A 71-year-old woman was referred to the Surgical Oncology Division of Napoleão Laureano Hospital (João Pessoa, PB, Brazil) due to a solid mass at the right side of the abdomen and fever, with no signs of jaundice. Abdominal ultrasonography and computed tomography (CT) evidenced an extensive gallbladder lobular formation adhered to the inferior border of the right hepatic lobe and cholelithiasis. The CT report suggested gallbladder liposarcoma. A cholecystectomy associated with resection of segments IV-B and V of the liver were performed. Intraoperative frozen sections were compatible with gallbladder sarcoma. Anatomopathological examination and immunohistochemistry confirmed dedifferentiated liposarcoma with foci of heterologous leiomyosarcomatous differentiation and undifferentiated fusocellular areas of high histological grade. CONCLUSION: This is the first case of dedifferentiated liposarcoma of the gallbladder to be reported.

Cathepsin S As an Inhibitor of Cardiovascular Inflammation and Calcification in Chronic Kidney Disease.

Cardiovascular disease (CVD) is responsible for the majority of deaths in the developed world. Particularly, in patients with chronic kidney disease (CKD), the imbalance of calcium and phosphate may lead to the acceleration of both vascular and valve inflammation and calcification. One in two patients with CKD are reported as dying from cardiovascular causes due to the resulting acceleration in the development of atherosclerosis plaques. In addition, CKD patients on hemodialysis are prone to aortic valve calcification and often need valve replacement before kidney transplantation. The lysosomal proteases, cathepsins, are composed of 11 cysteine members (cathepsin B, C, F, H, K, L, O, S, V, W, and Z), as well as serine proteases cathepsin A and G, which cleave peptide bonds with serine as the amino acid, and aspartyl proteases D and E, which use an activated water molecule bound to aspartate to break peptide substrate. Cysteine proteases, also known as thiol proteases, degrade protein via the deprotonation of a thiol and have been found to play a significant role in autoimmune disease, atherosclerosis, aortic valve calcification, cardiac repair, and cardiomyopathy, operating within extracellular spaces. This review sought to evaluate recent findings in this field, highlighting how among cathepsins, the inhibition of cathepsin S in particular, could play a significant role in diminishing the effects of CVD, especially for patients with CKD.

Cardiac sodium channel, its mutations and their spectrum of arrhythmia phenotypes

The mechanisms of cellular excitability and propagation of electrical signals in the cardiac muscle are very important functionally and pathologically. The heart is constituted by three types of muscle: atrial, ventricular, and specialized excitatory and conducting fibers. From a physiological and pathophysiological point of view, the conformational states of the sodium channel during heart function constitute a significant aspect for the diagnosis and treatment of heart diseases. Functional states of the sodium channel (closed, open, and inactivated) and their structure help to understand the cardiac regulation processes. There are areas in the cardiac muscle with anatomical and functional differentiation that present automatism, thus subjecting the rest of the fibers to their own rhythm. The rate of these (pacemaker) areas could be altered by modifications in ions, temperature and especially, the autonomic system. Excitability is a property of the myocardium to react when stimulated. Another electrical property is conductivity, which is characterized by a conduction and activation process, where the action potential, by the all-or-nothing law, travels throughout the heart. Heart relaxation also stands out as an active process, dependent on the energetic output and on specific ion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. In the gene mutation aspects that encode the rapid sodium channel (SCN5A gene), this channel is responsible for several phenotypes, such as Brugada syndrome, idiopathic ventricular fibrillation, dilated cardiomyopathy, early repolarization syndrome, familial atrial fibrillation, variant 3 of long QT syndrome, multifocal ectopic ventricular contractions originating in Purkinje arborizations, progressive cardiac conduction defect (Lenègre disease), sudden infant death syndrome, sick sinus syndrome, sudden unexplained nocturnal death syndrome, among other sodium channel alterations with clinical overlapping. Finally, it seems appropriate to consider the "sodium channel syndrome" (mutations in the gene of the alpha subunit of the sodium channel, SCN5A gene) as a single clinical entity that may manifest in a wide range of phenotypes, to thus have a better insight on these cardiac syndromes and potential outcomes for their clinical treatment.

Os mecanismos da excitabilidade celular e de propagação dos sinais elétricos no músculo cardíaco são de grande importância funcional e patológica. O coração é composto por três tipos de músculo: atrial, ventricular e das fibras especializadas excitatórias e condutoras. Do ponto de vista fisiológico e fisiopatológico os estados conformacionais do canal de sódio constitui-se um importante aspecto para o diagnóstico e tratamento de doenças cardíacas. A descrição dos estados funcionais do canal de sódio (fechado, aberto e inativado) e sua estrutura ajudam a compreensão dos processos de regulação cardíaca. Há áreas no músculo cardíaco com diferenciação anatômica e funcional que possuem automatismo submetendo as demais fibras ao seu próprio ritmo. A frequência dessas áreas (marca-passo) pode ser alterada por modificações iônicas, pela temperatura e, especialmente, do sistema autonômico. Já a excitabilidade é a propriedade que tem o miocárdio de reagir quando estimulado. A outra propriedade elétrica é a condutibilidade, que se caracteriza por um processo de condução e ativação, no qual o potencial de ação, pela ei do tudo ou nada, percorre todo o coração. Destaca-se que o relaxamento do coração também é um processo ativo, dependente de gasto energético e de ações iônicas e enzimáticas específicas, destacando o papel dos canais de sódio no processo funcional. Nos aspectos das mutações no gene que codifica o canal rápido de sódio (gene SCN5A), este é responsável por vários fenótipos, tais como a síndrome de Brugada; a fibrilação ventricular idiopática, a miocardiopatia dilatada; a síndrome de repolarização precoce; a fibrilação atrial familiar; a síndrome do QT longo variante 3; as contrações ventriculares ectópicas multifocais originadas nas arborizações de Purkinje; o distúrbio progressivo de condução intraventricular cardíaco (doença de Lenègre); a síndrome da morte súbita do recém-nascido; a síndrome do nódulo sinusal doente; a síndrome da morte súbita noturna inesperada, entre outras alterações do canal de sódio com sobreposições clínicas, as chamadas "overpping". Por fim, parece ser apropriado considerar a "síndrome do canal de sódio" (mutações no gene da subunidade alfa do canal de sódio, gene SCN5A) como uma entidade clínica única que pode manifestar-se com um amplo espectro de fenótipos e assim, prover um melhor entendimento destas síndromes cardíacas e potencial desfecho para seu tratamento clínico.

Pitavastatin Reduces Inflammation in Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice with Late Stage Renal Disease.

OBJECTIVES: Chronic renal disease (CRD) accelerates atherosclerosis and cardiovascular calcification. Statins reduce low-density lipoprotein-cholesterol levels in patients with CRD, however, the benefits of statins on cardiovascular disease in CRD remain unclear. This study has determined the effects of pitavastatin, the newest statin, on arterial inflammation and calcification in atherogenic mice with CRD. METHODS AND RESULTS: CRD was induced by 5/6 nephrectomy in cholesterol-fed apolipoprotein E-deficient mice. Mice were randomized into three groups: control mice, CRD mice, and CRD mice treated with pitavastatin. Ultrasonography showed that pitavastatin treatment significantly attenuated luminal stenosis in brachiocephalic arteries of CRD mice. Near-infrared molecular imaging and correlative Mac3 immunostaining demonstrated a significant reduction in macrophage accumulation in pitavastatin-treated CRD mice. Pitavastatin treatment reduced levels of osteopontin in plasma and atherosclerotic lesions in CRD mice, but did not produce a significant reduction in calcification in atherosclerotic plaques as assesses by histology. CRD mice had significantly higher levels of phosphate in plasma than did control mice, which did not change by pitavastatin. In vitro, pitavastatin suppressed the expression of osteopontin in peritoneal macrophages stimulated with phosphate or calcium/phosphate in concentrations similar to those found in human patients with CRD. CONCLUSION: Our study provides in vivo evidence that pitavastatin reduces inflammation within atherosclerotic lesions in CRD mice.

Macrophage Notch Ligand Delta-Like 4 Promotes Vein Graft Lesion Development: Implications for the Treatment of Vein Graft Failure.

OBJECTIVE: Despite its large clinical impact, the underlying mechanisms for vein graft failure remain obscure and no effective therapeutic solutions are available. We tested the hypothesis that Notch signaling promotes vein graft disease. APPROACH AND RESULTS: We used 2 biotherapeutics for Delta-like ligand 4 (Dll4), a Notch ligand: (1) blocking antibody and (2) macrophage- or endothelial cell (EC)-targeted small-interfering RNA. Dll4 antibody administration for 28 days inhibited vein graft lesion development in low-density lipoprotein (LDL) receptor-deficient (Ldlr(-/-)) mice, and suppressed macrophage accumulation and macrophage expression of proinflammatory M1 genes. Dll4 antibody treatment for 7 days after grafting also reduced macrophage burden at day 28. Dll4 silencing via macrophage-targeted lipid nanoparticles reduced lesion development and macrophage accumulation, whereas EC-targeted Dll4 small-interfering RNA produced no effects. Gain-of-function and loss-of-function studies suggested in vitro that Dll4 induces proinflammatory molecules in macrophages. Macrophage Dll4 also stimulated smooth muscle cell proliferation and migration and suppressed their differentiation. CONCLUSIONS: These results suggest that macrophage Dll4 promotes lesion development in vein grafts via macrophage activation and crosstalk between macrophages and smooth muscle cells, supporting the Dll4-Notch axis as a novel therapeutic target.