Effects of chronic moderate alcohol consumption on right ventricle and pulmonary remodelling.

NEW FINDINGS: What is the central question of this study? Does the consumption of a moderate amount of alcohol differentially impact the heart ventricles and pulmonary vasculature. What is the main finding and its importance? Moderate alcohol consumption for a short period of time impaired pulmonary vascular cellular renewal through an apoptosis resistance pattern that ultimately affected the right ventricular function and structure. These findings support the need for a deeper understanding of effects of moderate alcohol consumption on the overall cardiovascular and pulmonary systems. ABSTRACT: Over the past decades, observational studies have supported an association between moderate alcohol consumption and a lower risk of cardiovascular disease and mortality. However, recent and more robust meta-analyses have raised concerns around the robustness of the evidence for the cardioprotective effects of alcohol. Also, studies of the functional, structural and molecular changes promoted by alcohol have focused primarily on the left ventricle, ignoring the fact that the right ventricle could adapt differently. The aim of this study was to evaluate the bi-ventricular impact of daily moderate alcohol intake, during a 4-week period, in a rodent model. Male Wistar rats were allowed to drink water (Control) or a 5.2% ethanol mixture (ETOH) for 4 weeks. At the end of the protocol bi-ventricular haemodynamic recordings were performed and samples collected for further histological and molecular analysis. ETOH ingestion did not impact cardiac function. However, it caused right ventricle hypertrophy, paralleled by an activation of molecular pathways responsible for cell growth (ERK1/2, AKT), proteolysis (MURF-1) and oxidative stress (NOX4, SOD2). Furthermore, ETOH animals also presented remodelling of the pulmonary vasculature with an increase in pulmonary arteries' medial thickness, which was characterized by increased expression of apoptosis-related proteins expression (BCL-XL, BAX and caspases). Moderate alcohol consumption for a short period of time impaired the lungs and the right ventricle early, before any change could be detected on the left ventricle. Right ventricular changes might be secondary to alcohol-induced pulmonary vasculature remodelling.

Abdominal aortic aneurysm calcification: trying to identify a reliable semiquantitative method.

BACKGROUND: The main objective of this study was to assess the correlation between three semiquantitative and one computerized method based on Agatston Score (AS), when measuring abdominal aortic calcification (AAC) in abdominal aortic aneurysm (AAA) patients. Secondary aim was to access differences in AAC upon clinical variables, when different methods of calcium scoring are used. METHODS: This was an observational, retrospective, cross-sectional study. A database of AAA patients consecutively submitted to elective repair between 2008 and 2015 was used. Patients were excluded if they did not have preoperative imaging or presented scans incompatible with at least one of the whole set of calcification methods tested. Calcification measures were performed using AS, Aortic Calcification Index (ACI), AAC-8 and AAC-24 methods. The Pearson's correlation was used for primary analysis. RESULTS: Study population comprised 102 patients, 95% males, with a median age of 71 (interquartile range, IQR 66-76) years. AAAs presented median aortic diameter of 60 (54-70) mm. Pearson's correlation with AS was 0.816 for ACI, 0.703 for AAC-8 and 0.648 for AAC-24. ACI also presented the highest ICC for intraobserver agreement (0.972) and for interobserver agreement (0.966). ACI was associated more often to demographic and clinical variables in the dataset that associated with the computerized method. CONCLUSIONS: ACI is suggested as a fast and easy-to-use method of assessing AAC in AAA patients. Its use should be encouraged to study AAC in AAA over other semiquantitative methods, in research settings.

Exercise preconditioning prevents left ventricular dysfunction and remodeling in monocrotaline-induced pulmonary hypertension.

BACKGROUND: Despite pulmonary arterial hypertension (PAH) directly affects the right ventricle (RV), important structural, functional, and molecular changes also occur in left ventricle (LV). The objective of our study was to analyze the hypothetical cardioprotective effects of exercise preconditioning on LV in rats with monocrotaline (MCT)-induced PAH. METHODS: Forty male Wistar rats were randomly separated in sedentary (SED) and trained group (EX; running sessions of 60 min/day, 5 days/wk, at 25 m/min, for 4 weeks). After 4 weeks, animals were injected with MCT (60 mg/kg; SED + MCT; EX + MCT) or vehicle (SED + V). Following an additional period of 4 weeks where all animals remained sedentary, we completed LV hemodynamic evaluation in baseline and isovolumic conditions and collected LV samples for histological and molecular analysis. RESULTS: Preconditioning with exercise was capable to restore LV systolic and diastolic dysfunction in both baseline and isovolumic conditions (P < .05). This improved was paralleled with prevention of LV cardiomyocytes atrophy, fibrosis, and endothelin 1 mRNA levels (P < .05). CONCLUSIONS: Our findings suggest that exercise preconditioning can prevent LV dysfunction secondary to MCT-induced PAH, which is of particular interest for the familial form of the disease that is manifested by greater severity or earlier onset.

Anti-Remodeling Effects of Xanthohumol-Fortified Beer in Pulmonary Arterial Hypertension Mediated by ERK and AKT Inhibition.

Polyphenols present in some alcoholic beverages have been linked to beneficial effects in preventing cardiovascular diseases. Polyphenols found in beer with anti-proliferative and anti-cancer properties are appealing in the context of the quasi-malignant phenotype of pulmonary arterial hypertension (PAH). Our purpose was to evaluate if the chronic ingestion of a xanthohumol-fortified beer (FB) would be able to modulate the pathophysiology of experimental PAH. Male Wistar rats with monocrotaline (MCT)-induced PAH (60 mg/kg) were allowed to drink either xanthohumol-fortified beer (MCT + FB) or 5.2% ethanol (MCT + SHAM) for a period 4 weeks. At the end of the protocol, cardiopulmonary exercise testing and hemodynamic recordings were performed, followed by sample collection for further analysis. FB intake resulted in a significant attenuation of the pulmonary vascular remodeling in MCT + FB animals. This improvement was paralleled with the downregulation in expression of proteins responsible for proliferation (ERK1/2), cell viability (AKT), and apoptosis (BCL-XL). Moreover, MCT + FB animals presented improved right ventricle (RV) function and remodeling accompanied by VEGFR-2 pathway downregulation. The present study demonstrates that a regular consumption of xanthohumol through FB modulates major remodeling pathways activated in experimental PAH.

Sigmoid Volvulus in Children: Diagnosis and Therapeutic Challenge.

BACKGROUND: Sigmoid volvulus is a rare condition in children. Early diagnosis increases the success of nonsurgical treatment in the emergency department, but posterior elective surgery is important due to the risk of recurrence. METHODS/CONCLUSIONS: We present the case of a healthy 16-year-old girl with recurrent volvulus and successful endoscopic treatment followed by elective surgery.

INTRODUÇÃO: A ocorrência de um vólvulo do sigmoide na criança ê raro, constituindo desta forma um desafio diagnóstico. A identificação precoce desta patologia é essencial pois permite que a redução do vólvulo seja efetuada numa primeira abordagem por métodos não cirú;rgicos, e quanto mais precoce na história da doença maior a taxa de sucesso e menor o risco de complicações associadas. MÉTODOS/CONCLUSÕES: No entanto a cirurgia eletiva posterior é mandatória pelo alto risco de recidiva. Os autores apresentam o caso de uma adolescente sem antecedentes patológicos de relevo com um vólvulo sigmoideu recorrente submetido a redução endoscópica com sucesso.

[Perspectives and research challenges in abdominal aortic aneurysm calcification]. / Perspetivas e desafios do estudo da calcificação no aneurisma da aorta abdominal.

Abdominal aortic aneurysm (AAA) remains a relevant cause of mortality in Western countries. There is a need for continuous identification of risk factors for aneurysmal progression and predictors of treatment response to optimize the therapeutic strategy to be offered to these patients. Vascular calcification has been studied in several capillary beds as a cardiovascular risk factor. However, the importance of abdominal aortic calcification (AC) in AAA remains incompletely clarified, and the available evidence is scattered and heterogeneous. The objective of this review is to describe the possible impact of AC on aneurysmal progression and rupture, as well as on the response to endovascular correction. It should be noted that the establishment of a validated, quick and easy to use method for assessing AC would be of great clinical and/or research utility.

O aneurisma da aorta abdominal (AAA) permanece uma causa relevante de mortalidade nos países ocidentais. É premente a contínua identificação de fatores de risco de progressão aneurismática bem como de preditores de resposta ao tratamento na otimização da estratégia terapêutica a oferecer a estes doentes. A calcificação vascular tem sido estudada em diversos leitos capilares como um fator de prognóstico cardiovascular. Contudo, a importância da calcificação da aorta abdominal (CA) no AAA permanece incompletamente esclarecida, sendo a prova científica disponível dispersa e heterogénea. O objetivo desta revisão é descrever o eventual impacto da CA na progressão e rutura aneurismática, bem como na resposta à correção endovascular do AAA. Salienta-se que o estabelecimento de um método validado, rápido e fácil de usar para avaliar a CA seria de grande utilidade clínica e/ou investigacional.

High Density of Periaortic Adipose Tissue in Abdominal Aortic Aneurysm.

OBJECTIVES: Perivascular adipose tissue (PVAT) is currently seen as a paracrine organ that produces vasoactive substances, including inflammatory agents, which may have an impact on the vasculature. In this study PVAT density was quantified in patients with an aortic aneurysm and compared with those with a non-dilated aorta. Since chronic inflammation, as the pathway to medial thinning, is a hallmark of abdominal aortic aneurysms (AAAs), it was hypothesised that PVAT density is higher in AAA patients. METHODS: In this multicentre retrospective case control study, three groups of patients were included: non-treated asymptomatic AAA (n = 140), aortoiliac occlusive disease (AIOD) (n = 104), and individuals without aortic pathology (n = 97). A Hounsfield units based analysis was performed by computed tomography (CT). As a proxy for PVAT, the density of adipose tissue 10 mm circumferential to the infrarenal aorta was analysed in each consecutive CT slice. Intra-individual PVAT differences were reported as the difference in PVAT density between the region of the maximum AAA diameter (or the mid-aortic region in patients with AIOD or controls) and the two uppermost slices of infrarenal non-dilated aorta just below the renal arteries. Furthermore, subcutaneous (SAT) and visceral (VAT) adipose tissue measurements were performed. Linear models were fitted to assess the association between the study groups, different adipose tissue compartments, and between adipose tissue compartments and aortic dimensions. RESULTS: AAA patients presented higher intra-individual PVAT differences, with higher PVAT density around the aneurysm sac than the healthy neck. This association persisted after adjustment for cardiovascular risk factors and diseases and other fat compartments (ß = 13.175, SE 4.732, p = .006). Furthermore, intra-individual PVAT differences presented the highest correlation with aortic volume that persisted after adjustment for other fat compartments, body mass index, sex, and age (ß = 0.566, 0.200, p = .005). CONCLUSION: The results suggest a relation between the deposition of PVAT and AAA pathophysiology. Further research should explore the exact underlying processes.

Mechanisms underlying the impact of exercise training in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive increases in pulmonary vascular resistance that can ultimately lead to right ventricle failure and death. Common symptoms include shortness of breath, fatigue, dizziness and chest pain, which negatively impact the functional capacity and quality of life. Despite the improvements in disease-targeted therapies, PAH remains incurable and with a high mortality rate, requiring effective therapeutic strategies. Exercise training is an important adjunct non-pharmacological treatment for patients with left heart failure and chronic obstructive pulmonary disease. Although exercise training was discouraged in PAH because of safety concerns, recent studies support that supervised exercise training is safe and beneficial in patients with stable PAH. However, the molecular mechanisms underlying these improvements are still poorly understood. This review summarizes and integrates the emerging clinical and experimental studies describing the molecular alterations related with exercise training in PAH.

Assessment in pediatrics clerkships: impact of strategies to solve item-sharing problems.

INTRODUCTION: Reusing multiple-choice questions in different examinations may lead to item sharing between students. Our aim was to analyze and solve an item-sharing problem during assessment of medical students in pediatrics clerkship. METHODS: This is a 3 years prospective analysis of 5th year medical students, submitted to an examination at the end of their Pediatrics' clerkship. In 2012, questions were reused across different clerkships. In 2013, no questions were reused in different clerkships. In 2014, no questions were reused and the review of the test was postponed to the end of the year, after all clerkships ended. RESULTS: In 2012, the mean score increased 1.36 points (in a scale of 0-20) per clerkship rotation, with the last clerkship having a difference of 9.5 points regarding the first one (P < .001). Fifty percent of this variation was due to the repetition of questions. In 2013, with a new question bank, the mean score increased 0.8 points per clerkship rotation, with a difference of 5.6 points between the last and the first rotations (P < .024). Finally, in 2014 there was no significant variation between clerkships.Tests' scores had a significant moderate correlation with students' average course grade (r = 0.39, r = 0.30, r = 0.48, for 2012, 2013, and 2014, respectively). The students' average course grade, however, did not confound the increase in tests' scores across different clerkships. CONCLUSION: The present work demonstrated an item-sharing problem among students during pediatric clerkships. An effective approach to correct this bias assessment was achieved by restricting the reuse of questions, by changing the time-point of test revision and by progressively adapting equating strategies.

Trans-umbilical laparoscopic-assisted appendectomy in the pediatric population: comparing single-incision and 2-trocar techniques.

INTRODUCTION: Trans-umbilical laparoscopic-assisted appendectomy (TULAA) combines advantages of open surgery with benefits of laparoscopy and can be performed either by single-incision or with two trocars; the present study aims to compare outcomes and cost of these techniques in a pediatric serie. MATERIAL AND METHODS: Patients undergoing TULAA between July 2013 and June 2014 were retrospectively reviewed. There were two groups: A (single-incision) - one umbilical trocar for a telescope with inbuilt working channel; and B (2-trocar) - one umbilical trocar for a 'standard' telescope plus a supra-pubic trocar for instruments. RESULTS: One-hundred and eighty-nine patients (112 males, age: 12[2-17] years) underwent TULAA; 32(17%) presented with perforated appendicitis. Group A encompassed 157 and group B 32 patients; age, gender, proportion of perforated appendicitis, and follow-up were similar. Operative time was 46 [21-145] min in group A, and 54.5[30-111] in group B (A vs B, p = 0.087). Length of hospital stay was 2 [1;22] days in group B, and 2 [0;24] in group A (A vs B, p = 0.136). The prevalence of post-operative complications was similar: 11 (7%) cases in group A and 2 (6.3%) intra-abdominal abscesses in group B. Using disposable trocars, the more expensive starting point of single-incision technique may be reversed after 27 procedures. CONCLUSION: Single-incision and 2-trocar TULAA are effective techniques with low complication rates and similar outcomes. Despite being technically more demanding, single incision may be advantageous because there are no visible scars, and potentially cheaper in hospitals where disposable trocars are used.

Ventricular arrhythmia solved by surgical correction of pectus excavatum.

Pectus excavatum is generally considered a benign problem with a wide spectrum of impact in body image. Some articles had highlighted that this deformity can be associated with important clinical problems. We report a case of a 14-year-old boy with a severe pectus excavatum associated with palpitations who was diagnosed with polymorphic ventricular arrhythmia. The arrhythmia was resolved after minimally invasive surgical correction of the pectus excavatum.

Fetal Cardiac Function in Maternal Diabetes: A Conventional and Speckle-Tracking Echocardiographic Study.

BACKGROUND: Intrauterine exposure to a diabetic environment is associated with adverse fetal myocardial remodeling. The aim of this study was to assess the biventricular systolic and diastolic function of fetuses exposed to maternal diabetes (MD) compared with control subjects, using a comprehensive cardiac functional assessment and exploring the role of speckle-tracking to assess myocardial deformation. The authors hypothesized that fetuses exposed to MD present signs of biventricular dysfunction, which can be detected by deformation analysis. METHODS: A cross-sectional study was conducted in 129 fetuses with structurally normal hearts, including 76 fetuses of mothers with diabetes and 53 of mothers without diabetes. Maternal baseline characteristics, standard fetoplacental Doppler indices, and conventional echocardiographic and myocardial deformation parameters were prospectively collected at 30 to 33 weeks of gestation. RESULTS: Fetuses of mothers with diabetes had a significantly thicker interventricular septum compared with control subjects (median, 4.25 mm [interquartile range (IQR), 3.87-4.50 mm] vs 3.67 mm [IQR, 3.40-3.93 mm), P < .001), but no effect modification was demonstrated on myocardial deformation analysis. No significant differences were found in conventional systolic and diastolic functional parameters for the left ventricle and right ventricle, except for lower left ventricular cardiac output in the MD group (median, 320 mL/min [IQR, 269-377 mL/min] vs 365 mL/min [IQR, 311-422 mL/min], P < .05]. Deformation analysis demonstrated a significantly lower early diastolic strain rate (SRe) and late diastolic strain rate (SRa) for both ventricles in the MD group (left ventricle: SRe 1.85 ± 0.72 vs 2.26 ± 0.68 sec-1, SRa 1.50 ± 0.52 vs 1.78 ± 0.57 sec-1; right ventricle: SRe 1.57 ± 0.73 vs 1.97 ± 0.73 sec-1, SRa 2 ± 0.77 vs 1.68 ± 0.79 sec-1; P < .05), suggesting biventricular diastolic impairment. Additionally, the right ventricle presented a lower global longitudinal strain in the study group (-13.67 ± 4.18% vs -15.52 ± 3.86%, P < .05). Multivariate analysis revealed that maternal age is an independent predictor of left and right ventricular global longitudinal strain (P < .05), with a significant effect only in MD after group stratification. CONCLUSIONS: Fetuses of mothers with diabetes present signs of biventricular diastolic dysfunction and right ventricular systolic dysfunction by deformation analysis in the third trimester of pregnancy. They may represent a special indication group for functional cardiac assessment, independently of septal hypertrophy. Two-dimensional speckle-tracking could offer an additional benefit over conventional echocardiography to detect subclinical unfavorable changes in myocardial function in this population.

Exercise Training in Pulmonary Hypertension and Right Heart Failure: Insights from Pre-clinical Studies.

Exercise training (ExT) is widely used for the prevention and treatment of several chronic cardiovascular diseases. However, only recently it started to be recognized as safe and beneficial in pulmonary arterial hypertension. Despite the consistency of its favorable effects on exercise tolerance and quality of life, the mechanisms underlying these meaningful clinical improvements remain unclear. Current studies emphasize the exercise-induced changes on skeletal muscle but the impact of ExT at the level of the pulmonary circulation and right ventricle should not be overlooked. In this chapter, we summarize the main findings from pre-clinical studies analyzing the impact of exercise in pulmonary hypertension and right heart failure.

Mini-Review on Cachexia-Related miRNA.

Cachexia, or muscle wasting, is a complex metabolic syndrome associated with an underlying illness and characterized by loss of muscle mass. It is a rather prevalent condition, with impacts on patient survival, response to treatment, and quality of life. Treatment options are sparse because of cachexia's multifactorial pathogenesis. Recently, attention has focused on microRNAs (miRNAs) as potential therapeutic targets of several diseases. miRNAs are small, 18- to 25-base-long constructs that regulate gene expression on a post-transcriptional level, selectively activating or repressing elements of specific signaling pathways. In this review, we investigated whether miRNAs play any role in cachexia's biochemical pathways and if miRNA targeting has any significant impact on preclinical models of cachexia.

Fetal programming as a predictor of adult health or disease: the need to reevaluate fetal heart function.

Epidemiologic and experimental evidence suggests that adverse stimuli during critical periods in utero permanently alters organ structure and function and may have persistent consequences for the long-term health of the offspring. Fetal hypoxia, maternal malnutrition, or ventricular overloading are among the major adverse conditions that can compromise cardiovascular development in early life. With the heart as a central organ in fetal adaptive mechanisms, a deeper understanding of the fetal cardiovascular physiology and of the echocardiographic tools to assess both normal and stressed pregnancies would give precious information on fetal well-being and hopefully may help in early identification of special risk groups for cardiovascular diseases later in life. Assessment of cardiac function in the fetus represents an additional challenge when comparing to children and adults, requiring advanced training and a critical approach to properly acquire and interpret functional parameters. This review summarizes the basic fetal cardiovascular physiology and the main differences from the mature postnatal circulation, provides an overview of the particularities of echocardiographic evaluation in the fetus, and finally proposes an integrated view of in utero programming of cardiovascular diseases later in life, highlighting priorities for future clinical research.

A new methodology for assessment of pectus excavatum correction after bar removal in Nuss procedure: Preliminary study.

PURPOSE: The objective is to present a new methodology to assess quantitatively the impact of bar removal on the anterior chest wall, among patients with pectus excavatum who have undergone the Nuss procedure, and present a preliminary study using this methodology. METHODS: We propose to acquire, for each patient, the surface of the anterior chest wall using a three-dimensional laser scanner at subsequent time points (short term: before and after surgery; long term: follow-up visit, 6months, and 12months after surgery). After surfaces postprocessing, the changes are assessed by overlapping and measuring the distances between surfaces. In this preliminary study, three time points were acquired and two assessments were performed: before vs after bar removal (early) and before vs 2-8weeks after bar removal (interim). In 21 patients, the signed distances and volumes between surfaces were computed and the data analysis was performed. RESULTS: This methodology revealed useful for monitoring changes in the anterior chest wall. On average, the mean, maximum, and volume variations, in the early assessment, were -0.1±0.1cm, -0.6±0.2cm, and 47.8±22.2cm3, respectively; and, in the interim assessment, were -0.5±0.2cm, -1.3±0.4cm, and 122.1±47.3cm3, respectively (p<0.05). Data analysis revealed that the time the bar was in situ was inversely and significantly correlated with postretraction and was a relevant predictor of its decrease following surgery (p<0.05). Additionally, gender and age suggested influencing the outcome. CONCLUSIONS: This methodology is novel, objective and safe, helping on follow-up of pectus excavatum patients. Moreover, the preliminary study suggests that the time the bar was in situ may be the main determinant of the anterior chest wall retraction following bar removal. Further studies should continue to corroborate and reinforce the preliminary findings, by increasing the sample size and performing long-term assessments. LEVELS OF EVIDENCE: III.

Vascular access in neonates.

The aim of this review was to provide updated and recent literature on vascular access in neonates in order to help neonatologists in their clinical practice, using as data sources textbooks, recent published articles from Pubmed, Cochrane reviews and web guidelines.

Prediction of cardiovascular risk in preterm neonates through urinary proteomics: An exploratory study.

HIGHLIGHTS: Urine proteomics allows the identification of the pathways modulated in neonates.Up-regulated pathways in preterm include immunity, metabolism and oxidative stress.Some of these pathways seem to be modulated by the nutritional support.AGT and RBP4 might be related to the development of cardiovascular diseases. ABSTRACT: Preterm birth has been associated with an increased risk of cardiovascular diseases (CVD) in adulthood. The goal of our study was to give new molecular insights on the relationship between prematurity and CVD risk and to identify putative biomarkers that would facilitate the development of effective screening and therapeutic strategies. In this sense, mass spectrometry (MS)-based proteomics was applied to the characterization of urine protein profile.GeLC-MS/MS analysis of urine (desalted and concentrated with a 10-kDa filter) followed by bioinformatics was applied for the characterization of preterm and full-term neonates. Urine proteome profiling retrieved 434 unique proteins, from which 126 were common to both groups, 37 were unique to preterm and 58 to full-term neonates. Protein-protein interaction analysis for unique proteins and common ones present in significant distinct levels retrieved immune system, metabolism, defense systems and tissue remodeling as the most representative clusters in preterm neonates.Metabolic adaptation along with the up-regulation of heart growth (identified by angiotensinogen and retinol-binding protein 4) may account for an increased CVD risk in preterm neonates. These proteins may have predictive value of CVD in adulthood of this specific group of neonates. The follow-up of urinary proteome dynamics of preterm and full-term neonates will be crucial for the validation of this hypothesis.