Repeated sprint training in hypoxia induces specific skeletal muscle adaptations through S100A protein signaling.

Athletes increasingly engage in repeated sprint training consisting in repeated short all-out efforts interspersed by short recoveries. When performed in hypoxia (RSH), it may lead to greater training effects than in normoxia (RSN); however, the underlying molecular mechanisms remain unclear. This study aimed at elucidating the effects of RSH on skeletal muscle metabolic adaptations as compared to RSN. Sixteen healthy young men performed nine repeated sprint training sessions in either normoxia (FIO2 = 0.209, RSN, n = 7) or normobaric hypoxia (FIO2 = 0.136, RSH, n = 9). Before and after the training period, exercise performance was assessed by using repeated sprint ability (RSA) and Wingate tests. Vastus lateralis muscle biopsies were performed to investigate muscle metabolic adaptations using proteomics combined with western blot analysis. Similar improvements were observed in RSA and Wingate tests in both RSN and RSH groups. At the muscle level, RSN and RSH reduced oxidative phosphorylation protein content but triggered an increase in mitochondrial biogenesis proteins. Proteomics showed an increase in several S100A family proteins in the RSH group, among which S100A13 most strongly. We confirmed a significant increase in S100A13 protein by western blot in RSH, which was associated with increased Akt phosphorylation and its downstream targets regulating protein synthesis. Altogether our data indicate that RSH may activate an S100A/Akt pathway to trigger specific adaptations as compared to RSN.

Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications. METHODS: We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not. RESULTS: Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46). CONCLUSION: Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.

Impact of mechanical circulatory support on survival in pediatric heart transplantation.

Evidence on the impact of MCS on pediatric heart transplant survival is still scarce related to congenital heart disease patients including univentricular physiology as well as the risk factors for complications. We performed a retrospective review of all urgent pediatric (aged ≤16 years) HT from 2004 to 2014 in the Spanish Pediatric Heart Transplant Registry Group. Patients were stratified into two groups: urgent 0 (MCS at HT) and urgent 1 (non-MCS at HT). The primary outcome measure was post-transplant survival; secondary outcome measures were complications and absence of infections and rejection during the first post-transplant year. One hundred twenty-one pediatric patients underwent urgent HT, 58 (47.9%) urgent 0 and 63 (52%) urgent 1. There were 30 (24.8%) deaths: 12 in the urgent 0 group and 18 in the urgent 1 group, P = n.s. Regarding the type of MCS, patients on ECMO had the highest rate of complications (80%) and mortality (40%). Patients in the urgent 1 group showed a higher risk of hospital re-admission for infection during the first year after transplantation (OR 2.31 [1.1-4.82]), P = .025. We did not identify a risk factor for mortality. MCS does not impact negatively on survival after HT. However, there is a significant increase in 30-day and 1-year mortality and complications in ECMO patients compared with VAD patients. Infants, congenital heart disease, and PediMACS were not found to be risk factors for mortality.

Thigh and abdominal adipose tissue depot associations with testosterone levels in postmenopausal females.

OBJECTIVE: Research findings on the relationship between serum androgens and adipose tissue in older females are inconsistent. We aimed to clarify the relationship using state-of-the-art techniques to evaluate associations between body fat distribution and plasma testosterone (T) levels in older postmenopausal women. DESIGN: Observational, cross-sectional study of healthy, community dwelling postmenopausal women. PATIENTS AND MEASUREMENTS: Postmenopausal women (60-80 years old) were included in this study. Overall body composition was evaluated by dual-energy X-ray absorptiometry. Abdominal and thigh fat depots were measured by magnetic resonance imaging. Circulating T concentrations were analysed by liquid chromatography-tandem mass spectrometry. RESULTS: Thirty-five women (66.6 ± 0.8 years) participated in this study. T levels were positively associated with clinical proxy measures of adiposity including weight (ρ = 0.39), BMI (ρ = 0.43) and waist circumference (ρ = 0.39) (all P < 0.05). Fat mass and % body fat were correlated with T levels (ρ = 0.42 and 0.38 respectively, both P < 0.05). T correlated with overall and superficial abdominal fat (ρ = 0.34 and 0.37 respectively, both P < 0.05) but not with visceral adipose tissue. T increased with greater thigh fat (ρ = 0.49, P < 0.05) in both superficial and deep depots (ρ = 0.50 and 0.35 respectively, both P < 0.05). CONCLUSION: Our results suggest that postmenopausal women with higher circulating T levels have both higher regional and overall body adiposity. These findings underscore the sexual dimorphism in the relationship between serum androgen levels and adiposity.

Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication.

BACKGROUND & AIMS: The risk of hepatocellular carcinoma (HCC) is reduced but not eradicated among patients with hepatitis C virus (HCV)-induced advanced hepatic fibrosis who attained sustained viral response (SVR). We aimed to assess the risk of cirrhosis-related complications in this specific group of patients. METHODS: Data from previously reported Western cohort studies including patients with chronic HCV infection and bridging fibrosis or cirrhosis who attained SVR were pooled for survival analyses on the individual patient level. The primary endpoint was HCC and the secondary endpoint was clinical disease progression, defined as liver failure, HCC or death. RESULTS: Included were 1000 patients with SVR. Median age was 52.7 (IQR 45.1-59.7) years, 676 (68%) were male and 842 (85%) had cirrhosis. Median follow-up was 5.7 (IQR 2.9-8.0) years. Fifty-one patients developed HCC and 101 had clinical disease progression. The cumulative 8-year HCC incidence was 1.8 (95% CI 0.0-4.3) among patients with bridging fibrosis and 8.7% (95% CI 6.0-11.4) among those with cirrhosis (p=0.058). Within the cirrhosis group, the 8-year HCC incidence was 2.6% (95% CI 0.0-5.5) among patients <45years, 9.7% (95% CI 5.8-13.6) among patients from 45-60years, and 12.2% (95% CI 5.3-19.1) among patients >60years of age at start of therapy (p=0.006). Multivariable Cox analyses indicated that higher age, lower platelet count and diabetes mellitus were independently associated with development of HCC. After 8years 4.2% (95% CI 0.1-8.3) of patients with bridging fibrosis and 15.8% (95% CI 12.3-19.3) of patients with cirrhosis experienced clinical disease progression (p=0.007). CONCLUSIONS: Patients with HCV-induced cirrhosis and SVR showed an annual risk of approximately 1% for HCC and 2% for clinical disease progression. Therefore, to prevent HCC surveillance, chronic HCV infection should preferably be treated before cirrhosis has developed. LAY SUMMARY: Patients with cirrhosis who were able to eradicate their chronic HCV infection remain at substantial risk of primary liver cancer. The risk of liver cancer increases with higher age, laboratory makers suggesting more severe liver disease, and presence of diabetes mellitus. Also after successful antiviral therapy patients with HCV-induced cirrhosis should thus remain included in follow-up for early detection of liver cancer.

Upcoming pharmacological developments in chronic hepatitis B: can we glimpse a cure on the horizon?

BACKGROUND: Hepatitis B virus (HBV) chronic infection affects up to 240 million people in the world and it is a common cause of cirrhosis and hepatocellular carcinoma (HCC). HBV covalently closed circular DNA (cccDNA) plays an essential role in HBV persistence and replication. Current pharmacological treatment with nucleos(t)ide analogues (NA) may suppress HBV replication with little or no impact on cccDNA, hence lifelong treatment is required in the vast majority of patients. Clearances of intrahepatic cccDNA and/or HBsAg are critical endpoints for future antiviral therapy in chronic HBV. Recent promising developments targeting different molecular HBV life cycle steps are being pre-clinically tested or have moved forward in early clinical trials. METHODS: We review the current state of the art of these pharmacological developments, mainly focusing on efficacy and safety results, which are expected to lay the ground for future HBV eradication. An inclusive literature search on new treatments of HBV using the following electronic databases: Pubmed/MEDLINE, AMED, CINAHL and the Cochrane Central Register of Controlled Trials. Full-text manuscripts and abstracts published over the last 12 years, from 2005 to March 2011 were reviewed for relevance and reference lists were crosschecked for additional applicable studies regarding new HBV antiviral treatment. RESULTS: HBV entry inhibitors, HBV core inhibitors, HBV cccDNA transcripts RNA interference, HBV cell apoptosis inducers, HBV RNA, viral proteins and DNA knock down agents, HBV release inhibitors, anti-sense nucleosides, exogenous interferon stimulation, interferon response stimulation and HBV therapeutic vaccines were reviewed. CONCLUSION: This review will provide readers with an updated vision of current and foreseeable therapeutic developments in chronic hepatitis B.

Successful cardiac transplantation in a patient with congenital generalized lipodystrophy.

We report a case of a 12-yr-old boy referred to our unit with congenital generalized lipodystrophy and dilated cardiomyopathy related to a lamin gene mutation. He progressively developed end-stage heart failure and was referred for heart transplant evaluation. The patient's lipid profile, glucose level, and renal function were normal, and vascular retinopathy was ruled out. He underwent orthotopic bicaval HT and had an uneventful recovery. He was discharged home two wk after surgery with good graft function. During follow-up, he developed hyperglycemia and dyslipidemia, which were controlled by increasing leptin dose and starting oral antidiabetic drugs. The patient is currently doing well two yr after transplantation.

Randomized clinical trial comparing high versus standard dose of ribavirin plus peginterferon alfa-2a in hepatitis C genotype 3 and high viral load. Dargen-3 study.

INTRODUCTION: Less than half of patients with chronic hepatitis C genotype 3 (G3) and high viral load (HVL) without a rapid virological response (RVR) achieve a sustained virological response (SVR) when treated with peginterferon plus ribavirin (RBV). OBJECTIVES: To assess the impact of high doses of RBV on SVR in patients with G3 and HVL. METHODS: Ninety-seven patients were randomized to receive peginterferon α-2a+RBV 800 mg/day (A; n=42) or peginterferon α-2a+RBV 1600 mg/day+epoetin ß 400 IU/kg/week SC (B; n=55). Patients allocated to group B who achieved RVR continued on RBV (800mg/day) for a further 20 weeks (B1; n=42) while non-RVR patients received a higher dose of RBV (1600 mg/day)+epoetin ß (B2; n=13). RESULTS: RVR was observed in 64.3% of patients in A and in 76.4% in B (p=0.259). Intention-to-treat (ITT) analysis showed SVR rates of 64.3% (A) and 61.8% (B), with a reduction of -2.5% (-21.8% to 16.9%) (p=0.835). The SVR rate was 61.9% in arm B1 and 61.5% in arm B2. No serious adverse events were reported, and the rate of moderate adverse events was < 5%. CONCLUSIONS: G3 patients with high viral load without RVR did not obtain a benefit from a higher dose of RBV. Higher doses of RBV plus epoetin ß were safe and well tolerated (Clin Trials Gov NCT00830609).

CT-derived liver and spleen volume accurately diagnose clinically significant portal hypertension in patients with hepatocellular carcinoma.

Background & Aims: Clinically significant portal hypertension (CSPH) is a landmark in the natural history of cirrhosis, influencing clinical decisions in patients with hepatocellular carcinoma (HCC). Previous small series suggested that splanchnic volume measurements may predict portal hypertension. We aimed to evaluate whether volumetry obtained by standard multidetector computerised tomography (MDCT) can predict CSPH in patients with HCC. Methods: We included 175 patients with HCC, referred for hepatic venous pressure gradient (HVPG) evaluation, in whom contemporary MDCT was available. Liver volume, spleen volume (SV) and liver segmental volume ratio (LSVR: volume of the segments I-III/volume of the segments IV-VIII) were calculated semi-automatically from MDCT. Other non-invasive tests (NITs) were also employed. Results: Volume parameters could be measured in almost 100% of cases with an excellent inter-observer agreement (intraclass correlation coefficient >0.950). SV and LSVR were independently associated with CSPH (HVPG ≥10 mmHg) and did not interact with aetiology. The volume Index (VI), calculated as the product of SV and LSVR, predicted CSPH (AUC 0.83; 95% CI 0.77-0.89). Similar results were observed in an external cohort (n = 23) (AUC 0.87; 95% CI 0.69-1.00). Setting a sensitivity and specificity of 98%, VI could have avoided 35.9% of HVPG measurements. The accuracy of VI was similar to that of other NITs. VI also accurately predicted HVPG greater than 12, 14, 16 and 18 mmHg (AUC 0.81 [95% CI 0.74-0.88], 0.84 [95% CI 0.77-0.91], 0.85 [95% CI 0.77-0.92] and 0.87 [95% CI 0.79-0.94], respectively). Conclusions: Quantification of liver and spleen volumes by MDCT is a simple, accurate and reliable method of CSPH estimation in patients with compensated cirrhosis and HCC. Impact and implications: An increase in portal pressure strongly impacts outcomes after surgery in patients with early hepatocellular carcinoma (HCC). Direct measurement through hepatic vein catheterization remains the reference standard for portal pressure assessment, but its invasiveness limits its application. Therefore, we evaluated the ability of CT scan-based liver and spleen volume measurements to predict portal hypertension in patients with HCC. Our results indicate that the newly described index, based on quantification of liver and spleen volume, accurately predicts portal hypertension. These results suggest that a single imaging test may be used to diagnose and stage HCC, while providing an accurate estimation of portal hypertension, thus helping to stratify surgical risks.

Nutrition in congenital heart disease: consensus document.

INTRODUCTION: The prevalence of malnutrition among infants with congenital heart disease (CHD) is high. Early nutritional assessment and intervention contribute significantly to its treatment and improve outcomes. Our objective was to develop a consensus document for the nutritional assessment and management of infants with CHD. MATERIAL AND METHODS: We employed a modified Delphi technique. Based on the literature and clinical experience, a scientific committee prepared a list of statements that addressed the referral to paediatric nutrition units (PNUs), assessment, and nutritional management of infants with CHD. Specialists in paediatric cardiology and paediatric gastroenterology and nutrition evaluated the questionnaire in 2 rounds. RESULTS: Thirty-two specialists participated. After two evaluation rounds, a consensus was reached for 150 out of 185 items (81%). Cardiac pathologies associated with a low and high nutritional risk and associated cardiac or extracardiac factors that carry a high nutritional risk were identified. The committee developed recommendations for assessment and follow-up by nutrition units and for the calculation of nutritional requirements, the type of nutrition and the route of administration. Particular attention was devoted to the need for intensive nutrition therapy in the preoperative period, the follow-up by the PNU during the postoperative period of patients who required preoperative nutritional care, and reassessment by the cardiologist in the case nutrition goals are not achieved. CONCLUSIONS: These recommendations can be helpful for the early detection and referral of vulnerable patients, their evaluation and nutritional management and improving the prognosis of their CHD.

Liver and spleen volumes are associated with prognosis of compensated and decompensated cirrhosis and parallel its natural history.

OBJECTIVE: Cirrhosis is characterized by the complex interplay among biological, histological and haemodynamic events. Liver and spleen remodelling occur throughout its natural history, but the prognostic role of these volumetric changes is unclear. We evaluated the relationship between volumetric changes assessed by multidetector computerised tomography (MDCT) and landmark features of cirrhosis. METHODS: We included consecutive cirrhotic patients who underwent liver transplantation (LT) or hepatocellular carcinoma (HCC) resection in whom dynamic MDCT was available. Different volumetric indices were calculated. Fibrosis was evaluated by the collagen proportional area and Laennec sub-stages. Correlation and logistic regression analysis were performed to explore associations of volumetric indexes and fibrosis with key prognostic features across the clinical stages of cirrhosis. RESULTS: 185 patients were included (146 LT; 39 HCC); the predominant aetiology was viral hepatitis (51.35%); 65.9% had decompensated disease and 85.08% clinically significant portal hypertension (CSPH). The standardised liver volume and liver-spleen volume ratio negatively correlated with Model for End-stage Liver Disease (MELD), albumin and hepatic venous pressure gradient (HVPG) and were significantly lower in decompensated patients. The liver segmental volume ratio (segments I-III/segments IV-VIII) best captured the characteristic features of the compensated phase, showing a positive correlation with HVPG and a good discrimination between patients with and without CSPH and varices. Volumetric changes and fibrosis severity were independently associated with key prognostic events, with no association between these two parameters. CONCLUSIONS: Liver and spleen volumetric indices evolve differently along the natural history of cirrhosis and are associated with key prognostic factors in each phase, regardless of fibrosis severity and portal hypertension.

Peginterferon plus ribavirin and sustained virological response in HCV-related cirrhosis: outcomes and factors predicting response.

OBJECTIVES: Patients with hepatitis C virus (HCV) cirrhosis are difficult to treat and have a high risk of liver decompensation or hepatocellular carcinoma. We sought to identify factors that could predict treatment response. METHODS: Collaborating centers (n=26) provided data for patients (n=568) with HCV cirrhosis undergoing treatment with peginterferon-α plus ribavirin (RBV). Univariate and multivariate analyses were used to evaluate factors predicting treatment outcomes. RESULTS: Sustained viral response (SVR) in naive patients was 30.7%, with no significant differences between centers. Median follow-up was 35 months (range: 1-81). Factors predicting SVR were: non-genotype 1 (odds ratio (OR)=4.183; 95% confidence interval (CI): 2.353-7.438) overall dose and ≥80% of the scheduled time of treatment (OR=3.177; 95% CI: 1.752-5.760); serum γ-glutamyl transpeptidase (GGT) <76 IU per ml (OR=4.092; 95% CI: 2.418-6.927); baseline viral load <6 × 10(5) (OR=2.597; 95% CI: 1.583-4.262); absence of ultrasound signs of portal hypertension (OR=2.067; 95% CI: 1.26-3.39). No patient with a HCV-RNA decline <1 log(10) at week 4 achieved SVR. Event-free survival at 5 years was 91% in patients with SVR vs. 59% in non-responders (P<0.001). Overall survival in patients with SVR was 98% vs. 86% in non-responders (P=0.005). Independent factors predicting events were absence of SVR (hazard ratio (HR)=2.66; 95% CI: 1.32-5.54), baseline serum albumin <3.9 g per 100 ml (HR=3.06; 95% CI: 1.81-5.15), presence of esophageal varices on endoscopy (HR=2.489; 95% CI: 1.546-4). Improved outcome was more evident in responders with less advanced disease at baseline. CONCLUSIONS: SVR can be achieved in approximately one-third of patients with HCV-related cirrhosis. SVR independently reduces the likelihood of clinical decompensation and improves survival.

Pericardial single-patch repair of right coronary artery from aorto-left ventricular tunnel.

Aortico-left ventricular tunnel (ALVT) is a rare congenital paravalvar communication between the aorta and the left ventricle. This anomaly has been associated with the right coronary artery (RCA) arising directly from the tunnel. Surgical repair of this later condition is challenging and is usually undertaken by closure of the ventricular and aortic ends of the tunnel and transfer of the RCA. Regardless of the surgical technique, development of early and late aortic regurgitation (AR) remains a concern. We report a neonate with ALVT and the RCA coming off the tunnel that was successfully managed by closure of both ends of the tunnel, reinforcement of the annulus with autologous pericardium, and leaving the RCA perfused by way of the tunnel. After 6 months of follow-up, no AR has been shown on echocardiography.

Alterations to neuromuscular properties of skeletal muscle are temporally dissociated from the oxygen uptake slow component.

To assess if the alteration of neuromuscular properties of knee extensors muscles during heavy exercise co-vary with the SCV ([Formula: see text] slow component), eleven healthy male participants completed an incremental ramp test to exhaustion and five constant heavy intensity cycling bouts of 2, 6, 10, 20 and 30 minutes. Neuromuscular testing of the knee extensor muscles were completed before and after exercise. Results showed a significant decline in maximal voluntary contraction (MVC) torque only after 30 minutes of exercise (-17.01% ± 13.09%; p < 0.05) while single twitch (PT), 10 Hz (P10), and 100 Hz (P100) doublet peak torque amplitudes were reduced after 20 and 30 minutes (p < 0.05). Voluntary activation (VA) and M-wave were not affected by exercise, but significant correlation was found between the SCV and PT, MVC, VA, P10, P100, and P10/P100 ratio, respectively (p < 0.015). Therefore, because the development of the SCV occurred mainly between 2-10 minutes, during which neuromuscular properties were relatively stable, and because PT, P10 and P100 were significantly reduced only after 20-30 minutes of exercise while SCV is stable, a temporal relationship between them does not appear to exist. These results suggest that the development of fatigue due to alterations of neuromuscular properties is not an essential requirement to elicit the SCV.

The metabolic profiles of different fiber type populations under the emergence of the slow component of oxygen uptake.

To investigate the influence of different metabolic muscle fiber profiles on the emergence of the slow component of oxygen uptake ([Formula: see text]SC), 12 habitually active males completed four sessions of different combinations of work-to-work transition exercises up to severe intensity. Each transition was modeled to analyze the different kinetic parameters. Using a new approach, combining Henneman's principle and superposition principle, a reconstructed kinetics was built by temporally aligning the start of each new transition and summing them. The primary phase time constant significantly slowed and the gain at the end (GainEnd) significantly increased when transitions started from a higher intensity (p < 0.001). Kinetic parameters from the reconstructed curve ([Formula: see text], time delay of primary phase, [Formula: see text]End and GainEnd) were not significantly different from one transition to severe exercise. These results suggest that the appearance of the [Formula: see text]SC is at least related to, if not the result of, the different metabolic properties of muscle fibers.

Hybrid fiber alterations in exercising seniors suggest contribution to fast-to-slow muscle fiber shift.

BACKGROUND: Human skeletal muscle is composed of a functional and metabolic continuum of slow (Type I) and fast fibers (IIa and IIx). Hybrid fibers co-expressing different myosin heavy chains are also present and seem to be more prominent in aging muscle. Their role is debated; hybrid fibers were reported either in a transitional state, between slow and fast fibers, or as fixed individual entities. This study examined the fate of hybrid fibers with an endurance exercise intervention in an elderly sedentary population. METHODS: Twenty-two sedentary healthy elderly men and women underwent a 16-week supervised endurance exercise intervention. Eighteen endurance-trained age- and gender-matched volunteers served as controls. Fiber type distribution was determined by immunohistochemistry on vastus lateralis muscle biopsies pre-intervention and post-intervention. RESULTS: A total of 13840 fibers were analyzed. At baseline, a Type II dominant fiber profile was observed compared with the control group, with more Type IIa (P = 0.0301) and Type IIx fibers (P = 0.0328). Hybrid fibers represented almost 5% of total muscle fibers in both groups. There was no significant difference between groups (I-IIa, P = 0.6719 and IIa-IIx, P = 0.0998). Intervention triggered qualitative dynamics towards an increase in Type I, and decrease in Type II fibers, paralleled by an increase in I-IIa hybrids (P = 0.0301). CONCLUSIONS: The present study is, to our knowledge, the first to examine hybrid muscle fiber type adaptations to an endurance exercise intervention in the elderly. Hybrid fiber proportions did not differ between chronic sedentary state and chronic endurance-trained state. Exercise intervention increased Type I-IIa hybrid fibers along with shift dynamics in other fiber types suggesting the contribution of hybrid fiber to a fast-to-slow fiber type transition, eventually serving as intermediate reservoir from one monomorphic myosin heavy chain expressing fiber type to another. This finding favours the transitional theory regarding hybrid muscle fibers and exercise, crucial to understanding reversible mechanisms of sarcopenia and development of prevention measures.

Distinct patterns of skeletal muscle mitochondria fusion, fission and mitophagy upon duration of exercise training.

AIM: Healthy ageing interventions encompass regular exercise to prevent mitochondrial dysfunction, key player in sarcopenia pathogenesis. Mitochondrial biogenesis has been well documented, but mitochondrial remodelling in response to exercise training is poorly understood. Here we investigated fusion, fission and mitophagy before and after an exercise intervention in older adults. METHODS: Skeletal muscle biopsies were collected from 22 healthy sedentary men and women before and after 4 months of supervised training. Eight lifelong trained age- and gender-matched volunteers served as positive controls. Transmission electron microscopy was used to estimate mitochondrial content. Western blotting and qRT-PCR were used to detect changes in specific proteins and transcripts. RESULTS: After intervention, mitochondrial content increased to levels of controls. While enhancement of fusion was prevalent after intervention, inhibition of fission and increased mitophagy were dominant in controls. Similarly to PARKIN, BCL2L13 content was higher in controls. The observed molecular adaptations paralleled long-term effects of training on physical fitness, exercise efficiency and oxidative capacity. CONCLUSIONS: This study describes distinct patterns of molecular adaptations in human skeletal muscle under chronic exercise training. After 16 weeks of exercise, the pattern was dominated by fusion to increase mitochondrial content to the metabolic demands of exercise. In lifelong exercise, the pattern was dominated by mitophagy synchronized with increased fusion and decreased fission, indicating an increased mitochondrial turnover. In addition to these temporally distinct adaptive mechanisms, this study suggests for the first time a specific role of BCL2L13 in chronic exercise that requires constant maintenance of mitochondrial quality.

La nutrición en las cardiopatías congénitas: Documento de consenso / Nutrition in congenital heart disease: Consensus document

Introducción: La tasa de desnutrición entre los lactantes con cardiopatías congénitas (CC) es elevada. Una evaluación e intervención nutricional tempranas ayudan a su tratamiento y mejoran el pronóstico. El objetivo fue elaborar un documento de consenso para la evaluación y el tratamiento nutricional del lactante con CC. Material y métodos: Se utilizó una técnica Delphi modificada. Con base en la literatura y en su experiencia clínica, un comité científico elaboró un listado de afirmaciones que abordaban la derivación a unidades de nutrición pediátrica (UNP), la evaluación y el manejo nutricional de los lactantes con CC. Especialistas en cardiología pediátrica, y gastroenterología y nutrición pediátrica evaluaron el cuestionario en dos rondas. Resultados: Participaron 32 especialistas. Tras dos rondas de evaluación, se consensuaron 150 de 185 ítems (81%). Se determinaron patologías cardiacas de bajo y alto riesgo nutricional y factores asociados cardiacos o extracardiacos que confieren riesgo nutricional alto. Se elaboraron recomendaciones para la evaluación y seguimiento en unidades de nutrición y sobre el cálculo de los requerimientos nutricionales, el tipo de nutrición y la vía de administración. Se enfatiza la necesidad de un tratamiento nutricional intensivo en el preoperatorio, del seguimiento por la UNP en el postoperatorio cuando se haya necesitado intervención preoperatoria, y de la reevaluación por el cardiólogo cuando no se alcancen los objetivos nutricionales. Conclusiones: Estas recomendaciones pueden ser de ayuda para la detección precoz y derivación temprana de población vulnerable, su evaluación y tratamiento nutricional y para mejorar el pronóstico de su CC. (AU)

Introduction: The prevalence of malnutrition among infants with congenital heart disease (CHD) is high. Early nutritional assessment and intervention contribute significantly to its treatment and improve outcomes. Our objective was to develop a consensus document for the nutritional assessment and management of infants with CHD. Material and methods: We employed a modified Delphi technique. Based on the literature and clinical experience, a scientific committee prepared a list of statements that addressed the referral to paediatric nutrition units (PNUs), assessment, and nutritional management of infants with CHD. Specialists in paediatric cardiology and paediatric gastroenterology and nutrition evaluated the questionnaire in 2 rounds. Results: Thirty-two specialists participated. After two evaluation rounds, a consensus was reached for 150 out of 185 items (81%). Cardiac pathologies associated with a low and high nutritional risk and associated cardiac or extracardiac factors that carry a high nutritional risk were identified. The committee developed recommendations for assessment and follow-up by nutrition units and for the calculation of nutritional requirements, the type of nutrition and the route of administration. Particular attention was devoted to the need for intensive nutrition therapy in the preoperative period, the follow-up by the PNU during the postoperative period of patients who required preoperative nutritional care, and reassessment by the cardiologist in the case nutrition goals are not achieved. Conclusions: These recommendations can be helpful for the early detection and referral of vulnerable patients, their evaluation and nutritional management and improving the prognosis of their CHD. (AU)