UMA POLIFONIA DA EDUCAÇÃO FÍSICA PARA O DIA QUE NASCERÁ: sonhar mais, crer no improvável, desejar coisas bonitas que não existem e alargar fronteiras

Pensar a vida dos sujeitos-estudantes é condição para pensar o impacto da pandemia na Educação Física e fortalecer uma escolha inadiável: a potência política e cultural contida no alargamento das fronteiras da Educação Física para reconhecer em seu programa os saberes de povos diversos que constituem o povo brasileiro (povos originários, povos afro-ameríndios, povos latino-americanos, povos do campo) e também os saberes produzidos pelos sujeitos coletivos em espaços diversos das cidades, pois foram esses povos que a pandemia mais atingiu e mais matou. A Educação Física da Escola não pode ficar indiferente, seu tributo é uma resposta histórica para o dia que nascerá: acolher suas culturas tornando-as vivas e visíveis em seu programa de ensino ­ uma Educação Física polifônica.

To think about the life of the subjects-Students is a condition to think about the impact of the pandemic in Physical Education and it reinforces an unavoidable choice: the political and cultural potential contained in the enlargement of the frontiers of Physical Education so as to recognize in its content the knowledge of the different peoples which constitute the Brazilian people (original people, Afro-American and native peoples, Latin-Americans, rural peoples) as well as the knowledge produced by the collective subjects in various city structures. For these are the peoples the pandemic hit the most, and killed the most. The Physical Education at School cannot be indifferent. Its tribute is a historic response to the day that shall come: to harbor their cultures by making them come to life and light in its teaching program ­ a polyphonic Physical Education.

Pensar la vida de los sujetos-Estudiantes es una condición para pensar el impacto de la pandemia en la Educación Física y fortalecer una elección inevitable: la potencia política y cultural contenida en la ampliación de las fronteras de la Educación Física para reconocer en su programa los saberes de pueblos diversos que constituyen el pueblo brasileño (pueblos originarios, pueblos afroamerindios, pueblos latinoamericanos, pueblos del campo) así como los saberes producidos por los sujetos colectivos en los diversos espacios de las ciudades. Pues fueron estos pueblos que la pandemia más atingió y mató. La Educación Física en la Escuela no puede quedarse indiferente. Su tributo es una respuesta histórica para el día que nacerá: acoger sus culturas haciéndolas vivas y visibles en su programa de enseñanza ­ una Educación Física polifónica.

Uma polifonia da Educação Física para o dia que nascerá: sonhar mais, crer no improvável, desejar coisas bonitas que não existem e alargar fronteiras / A POLYPHONY OF PHYSICAL EDUCATION FOR THE DAY THAT WILL BE BORN: dream more, believe in the improbable, wish for beautiful things that do not exist and expand borders

Pensar a vida dos sujeitos-estudantes é condição para pensar o impacto da pandemia na Educação Física e fortalecer uma escolha inadiável: a potência política e cultural contida no alargamento das fronteiras da Educação Física para reconhecer em seu programa os saberes de povos diversos que constituem o povo brasileiro (povos originários, povos afro-ameríndios, povos latino-americanos, povos do campo) e também os saberes produzidos pelos sujeitos coletivos em espaços diversos das cidades, pois foram esses povos que a pandemia mais atingiu e mais matou. A Educação Física da Escola não pode ficar indiferente, seu tributo é uma resposta histórica para o dia que nascerá: acolher suas culturas tornando-as vivas e visíveis em seu programa de ensino ­ uma Educação Física polifônica (AU).

To think about the life of the subjects-Students is a condition to think about the impact of the pandemic in Physical Education and it reinforces an unavoidable choice: the political and cultural potential contained in the enlargement of the frontiers of Physical Education so as to recognize in its content the knowledge of the different peoples which constitute the Brazilian people (original people, Afro-American and native peoples, Latin-Americans, rural peoples) as well as the knowledge produced by the collective subjects in various city structures. For these are the peoples the pandemic hit the most, and killed the most. The Physical Education at School cannot be indifferent. Its tribute is a historic response to the day that shall come: to harbor their cultures by making them come to life and light in its teaching program ­ a polyphonic Physical Education (AU).

Pensar la vida de los sujetos-Estudiantes es una condición para pensar el impacto de la pandemia en la Educación Física y fortalecer una elección inevitable: la potencia política y cultural contenida en la ampliación de las fronteras de la Educación Física para reconocer en su programa los saberes de pueblos diversos que constituyen el pueblo brasileño (pueblos originarios, pueblos afroamerindios, pueblos latinoamericanos, pueblos del campo) así como los saberes producidos por los sujetos colectivos en los diversos espacios de las ciudades. Pues fueron estos pueblos que la pandemia más atingió y mató. La Educación Física en la Escuela no puede quedarse indiferente. Su tributo es una respuesta histórica para el día que nacerá: acoger sus culturas haciéndolas vivas y visibles en su programa de enseñanza ­ una Educación Física polifónica (AU).

Placental ESRRG-CYP19A1 Expressions and Circulating 17-Beta Estradiol in IUGR Pregnancies.

Introduction: Sex steroids are regulating factors for intrauterine growth. 17-ß Estradiol (E2) is particularly critical to a physiological pregnancy, as increased maternal E2 was correlated to lower fetal weight at delivery. The placenta itself is a primary source of estrogens, synthetized from cholesterol precursors. Cytochrome P450 aromatase (encoded by CYP19A1 gene) is a rate-limiting enzyme for E2 biosynthesis. CYP19A1 transcription is supported by Estrogen Related-Receptor Gamma (ERRγ- ESRRG gene), which thus has an indirect role in placental steroidogenesis. Here we investigated maternal E2 levels and placental CYP19A1 and ESRRG expressions in pregnancies with IntraUterine Growth Restriction (IUGR). Methods: Singleton pregnancies were studied. E2 was measured in maternal plasma by electrochemiluminescence in 16 term controls and 11 IUGR (classified by umbilical artery doppler pulsatility index) at elective cesarean section, and also in 13 controls during pregnancy at a gestational age comparable to IUGR. CYP19A1 and ESRRG expressions were analyzed in placental tissue. Maternal/fetal characteristics, placental and molecular data were compared among study groups and tested for correlations. Results: Maternal E2 plasma concentrations were significantly decreased in IUGR compared to controls at delivery. When analyzing normal pregnancies at a gestational age similar to IUGR, E2 levels were not different to pathological cases. However, E2 levels at delivery positively correlated with placental efficiency. Placental CYP19A1 levels were significantly higher in IUGR placental tissue vs. controls, and specifically increased in female IUGR placentas. ESRRG expression was not different among groups. Discussion: We report a positive correlation between 17-ß Estradiol levels and placental efficiency, that might indicate a disrupted steroidogenesis in IUGR pregnancies. Moreover, we show alterations of CYP19A1 expression in IUGR placentas, possibly indicating a compensatory effect to the adverse IUGR intrauterine environment, also depending on fetal sex. Further studies are needed to deeper investigate IUGR alterations in the complex interaction among molecules involved in placental steroidogenesis.

Ileal interposition coupled with duodenal diverted sleeve gastrectomy versus standard medical treatment in type 2 diabetes mellitus obese patients: long-term results of a case-control study.

BACKGROUND: Randomized controlled trials have demonstrated that bariatric surgery is effective in obtaining remission of type 2 diabetes mellitus (T2DM) in obese patients, yet no data exist in the literature from prospective studies with ileal interposition with duodenal diversion sleeve gastrectomy (II-DD-SG). The aim of this case-control study is to investigate if II-DD-SG is superior to medical treatment in T2DM obese patients. METHODS: Thirty obese patients (BMI > 30) affected by T2DM were recruited for surgery (II-DD-SG) between 2008 and 2011 and were matched with an equal control group which received standard medical treatment. Anthropometric measures, glucose metabolism, cardiovascular risk factors were determined baseline and during follow-up. The primary end point was T2DM remission; reduction of body weight, BMI, and cardiovascular risk factors were secondary end-points. RESULTS: Shortly after II-DD-SG, normalization of glucose plasma levels and glycated hemoglobin was observed followed by a significant decrease in body weight and BMI. At one-year follow-up, insulin resistance strongly declined as did insulin plasma levels. Complete remission was observed in 26 patients (86%); 2 (6.6%) had partial remission, and two (6.6%) were still diabetic. After 5 years, 17 of 25 patients on follow-up (68%) showed complete remission of T2DM and 56% had remission of cardiovascular risk factors. Only two patients receiving medical treatment showed complete remission of T2DM (p < 0.0001 versus II-DD-SG). No significant changes of anthropometric parameters and lipid metabolism were recorded. CONCLUSIONS: II-DD-SG is an effective surgical procedure, able to induce complete and prolonged remission of T2DM in obese patients as opposed to medical treatment.

Measurement of Serum Klotho in Systemic Sclerosis.

BACKGROUND: The aim of our study was to evaluate the serum concentration of klotho in a cohort of systemic sclerosis (SSc) patients compared to that of healthy controls and to correlate its levels with the degree and the kind of organ involvement. METHODS: Blood samples obtained from both patients and controls were collected and analysed by an ELISA test for the determination of human soluble klotho. Scleroderma patients were evaluated for disease activity through clinical, laboratory, and instrumental assessment. RESULTS: Our cohort consisted of 81 SSc patients (74 females, mean age 63.9 ± 13.1 years) and 136 healthy controls (78 females, mean age 50.5 ± 10.7 years). When matched for age, serum klotho concentration significantly differed between controls and patients (p < 0.001). However, in SSc patients, we did not find any significant association between serum klotho and clinical, laboratory, and instrumental findings. Lower serum levels of klotho were detected in 4 patients who were anticitrullinated peptide antibody (ACPA) positive (p = 0.005). CONCLUSIONS: Our data show a lower concentration of klotho in the serum of SSc patients compared to that of healthy controls, without any significant association with clinical manifestations and laboratory and instrumental findings. The association between serum klotho and ACPA positivity requires further investigation.

Para a sanidade do corpo: ginástica e educação física nas Actas e Pareceres do Congresso de Instrucção Publica - Rio de Janeiro, 1883 / For the sanity of the body: gymnastics and physical education in the Proceedings and Opinions of the Congress of Public Instruction - Rio de Janeiro, 1883

O Brasil vivia então um tempo e seus tumultos. Assim foram os últimos anos do império. Na educação, em 1882, o jurista, então deputado pela Bahia, Ruy Barbosa expressava o desejo de reformas ao apresentar, como relator, proposta para a instrução pública na qual uma parte era dedicada à educação física, com obrigatoriedade da ginástica nas escolas...

Lung ultrasound and short-term prognosis in heart failure patients.

BACKGROUND: Heart failure (HF) is the leading cause of hospitalization for patients older than 65years, with a 30-day readmission rate of 20-25%. Although several markers have been evaluated to stratify timing of follow-up after an acute decompensation is mostly based on clinical judgment. Lung ultrasound (LUS) has been demonstrated to be a valid tool for the assessment and monitoring of pulmonary congestion. Aim of our study was to evaluate if LUS performed in HF patients at discharge could predict 100-day hospital readmission or death. METHODS: One-hundred fifty patients were enrolled. The anterolateral chest was scanned to evaluate the presence of B-lines. A sonographic score was calculated attributing 1 to each positive (≥3 B-lines) sector. Clinical, biochemical and echocardiographic data were recorded. A Cox proportional hazard regression analysis was performed to evaluate the association between variables and 100-day events. RESULTS: Follow-up was obtained in 149 patients. Thirty-four events were recorded. Sonographic score was significantly associated with events (HR 1.19; CI 1.05 to 1.34; p=0.005). On average, the increase of 1 point in the sonographic score was associated with an increase of approximately 24% in the risk of event within 100days. At multivariate analysis NTproBNP remained the only independent prognostic factor. CONCLUSIONS: We confirmed that B-lines at discharge are a prognostic marker for hospital readmission and death at 100days in HF patients. Nevertheless, further randomized clinical studies are needed to definitely support the routine use of LUS in the clinical management of HF patients, in combination or not with NT-proBNP.

Sequential N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin Measurements During Albumin Replacement in Patients With Severe Sepsis or Septic Shock.

OBJECTIVES: Myocardial dysfunction is a frequent complication in patients with severe sepsis and can worsen the prognosis. We investigated whether circulating biomarkers related to myocardial function and injury predicted outcome and were associated with albumin replacement. DESIGN: A multicenter, randomized clinical trial about albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis trial). SETTING: Forty ICUs in Italy. PATIENTS: Nine hundred and ninety-five patients with severe sepsis or septic shock. INTERVENTIONS: Randomization to albumin and crystalloid solutions or crystalloid solutions alone. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of N- terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T were measured 1, 2, and 7 days after enrollment. We tested the relationship of single marker measurements or changes over time with clinical events, organ dysfunctions, albumin replacement, and ICU or 90-day mortality in the overall population and after stratification by shock. N-terminal pro-B-type natriuretic peptide levels were abnormal in 97.4% of the patients and high-sensitivity cardiac troponin T in 84.5%, with higher concentrations in those with shock. After extensive adjustments, N-terminal pro-B-type natriuretic peptide concentrations predicted ICU or 90-day mortality, better than high-sensitivity cardiac troponin T. Early changes in N-terminal pro-B-type natriuretic peptide or high-sensitivity cardiac troponin T concentrations were independently associated with subsequent mortality in patients with shock. Patients given albumin had significantly higher N-terminal pro-B-type natriuretic peptide levels; in addition, early rise in N-terminal pro-B-type natriuretic peptide was associated with a better outcome in this subgroup. CONCLUSIONS: Circulating N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T are frequently elevated in severe sepsis or septic shock and have relevant prognostic value, which may be important in monitoring the clinical efficacy of supporting therapy.

Cardiac Remodeling, Circulating Biomarkers and Clinical Events in Patients with a History of Atrial Fibrillation. Data from the GISSI-AF Trial.

PURPOSE: Atrial fibrillation (AF) is the most common arrhythmia and has an increasing impact on public health because of its morbidity and mortality. Clinical and diagnostic tests to predict the recurrence of arrhythmia and clinical events before AF becomes permanent are still an open issue. METHODS: 307 out of 1442 patients in sinus rhythm, at high risk of recurrence of AF enrolled in the GISSI-AF study, participated in a substudy with echocardiographic and biohumoral evaluation at baseline and at 12-month follow-up. The relations between biomarker concentrations and echocardiographic parameters with study endpoints in 1 year, were analysed by a stepwise multivariable Cox model (entry criteria p < 0.5 and stay criteria p < 0.2). RESULTS: The echocardiographic variables, cardiac markers and clinical variables considered in the statistical model indicated a higher concentration of NT-proBNP at baseline as the strongest factor related to time of first AF recurrence (HR 1.42; 95 %CI 1.23-1.46), first CV hospitalization (HR 1.58; 95 %CI 1.31-1.92) and increasing duration of recurrent AF (OR 2.16; 95 %CI 1.52-3.08). Valsartan treatment was not related to clinical events. CONCLUSIONS: In patients in sinus rhythm with a history of AF a higher concentration of NT-proBNP at baseline was the strongest independent risk factor for first AF recurrence and its duration, and for the first hospital admission for cardiovascular reasons.

Duodenal diverted sleeve gastrectomy with ileal interposition does not cause biliary salt malabsorption.

BACKGROUND: Duodenal diverted sleeve gastrectomy with ileal interposition (DDSG-II) is a bariatric-metabolic operation designed to treat type 2 diabetes mellitus (T2DM). It is restrictive (SG) but also acts on the small bowel with functional effects. The objective of the present study was to investigate whether or not it is also a malabsorptive operation. METHODS: Twelve obese patients (9 female and 3 male) affected by T2DM had DDSG-II. Follow-up was every 3 months, and the results after 1 year are reported here. Clinical conditions, related to diabetes and malnutrition, changes in weight, body mass index, fasting glucose plasma levels, HbA1c (glycated hemoglobin %), basal insulin, vitamin B12, folic acid, vitamin D, total proteins, albumin, and hemoglobin were recorded. Basal plasma levels of FGF19 (pg/mL) and of 7α-hydroxy-4-cholesten-3-one (C4) (µg/dL) were also determined for the diagnosis of biliary salt malabsorption. The results were expressed as mean±SEM, and the differences between times compared by the Mann Whitney U test; P<.05 was considered significant. RESULTS: After 1 year, all patients had a significant weight loss (-33.2±3 kg) with T2DM remission according to the American Diabetes Association criteria (11), criteria. No significant changes in total proteins, albumin, hemoglobin, and vitamins (B6, B12, and D) were detected. C4 did not change after the operation (2±.5 µg/dL versus 1.6±.5 µg/dL), whereas FGF19 significantly increased (from 85±11.2 pg/mL to 166.4±28.2 pg/mL, P<.04). Only 2 patients had mild symptoms of malabsorption. CONCLUSIONS: DDSG-II is effective for treatment of T2DM obese patients, increases the enterokine FGF19, and does not cause biliary salt malabsorption.

Circulating cardiac biomarkers and postoperative atrial fibrillation in the OPERA trial.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and predicts increased morbidity and mortality. Identification of patients at high risk of POAF with the help of circulating biomarkers may enable early preventive treatment but data are limited, especially in contemporary surgical patients. METHODS: Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured at enrollment, on the morning of cardiac surgery, at end surgery, and 2 days postsurgery in 562 patients undergoing cardiac surgery, randomized to perioperative supplementation with oral fish oil or placebo in the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation trial (OPERA). The primary endpoint was incident POAF lasting ≥ 30 s, centrally adjudicated and confirmed electrocardiographically. RESULTS: Higher levels of NT-proBNP and hs-cTnT before surgery were associated with older age, renal or cardiac dysfunction and EuroSCORE. NT-proBNP peaked on postoperative day 2 (2172 [1238-3758] ng/L, median [Q1-Q3]), while hs-cTnT peaked at the end of surgery (373 [188-660] ng/L). Fish oil supplementation did not alter the time course of the cardiac biomarkers (P > 0.05). Concentrations of NT-proBNP or hs-cTnT, on the morning of surgery, or changes in their level between morning of surgery and postsurgery, were not significantly associated with POAF after adjustment for clinical and surgical characteristics. CONCLUSION: Among patients undergoing cardiac surgery, NT-proBNP and hs-cTnT are related to clinical and surgical characteristics, have different perioperative time courses but are not independently associated with risk of POAF.

Postresuscitation treatment with argon improves early neurological recovery in a porcine model of cardiac arrest.

INTRODUCTION: Effects of postresuscitation treatment with argon on neurologic recovery were investigated in a porcine model of cardiac arrest (CA) with an underlying acute myocardial infarction. METHODS: The left anterior descending coronary artery was occluded in 12 pigs, and CA was induced. After 8 min of untreated CA, cardiopulmonary resuscitation was performed for 5 min before defibrillation. Following resuscitation, animals were subjected to 4-h ventilation with 70% argon/30% oxygen or 70% nitrogen/30% oxygen. Myocardial function was echocardiographically assessed, and serum neuron-specific enolase was measured. Animals were observed up to 72 h for assessment of survival and neurologic recovery. RESULTS: All the animals were resuscitated and survived for 72 h, except for a control pig. Ventilation with argon did not have any detrimental effects on hemodynamics and respiratory gas exchange. All the six argon-treated animals had a fast and complete 72-h neurologic recovery, in contrast to only two of the six controls (P < 0.05). Seventy-two-hour neurologic alertness score and neurologic deficit score were, respectively, 100 and 0 in the argon group and 79 and 29 in the control one (P < 0.01 and P < 0.05). Significantly lower increases in serum neuron-specific enolase (12% vs. 234%) and minimal histological brain injury (neuronal degeneration: 0 vs. 1) were also observed in argon-treated animals, in comparison to controls. CONCLUSIONS: In this model, postresuscitation treatment with argon allowed for a faster and complete neurologic recovery, without detrimental effects on hemodynamics and respiratory gas exchanges.

Usefulness of N-terminal pro-B-type natriuretic Peptide increase as a marker for cardiac arrhythmia in patients with syncope.

B-type natriuretic peptides (BNPs) have been investigated as biomarkers for risk stratification of patients with syncope. Their concentration can be influenced by age and co-morbidities. In the present study, we compared the change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels within 6 hours in patients with vasovagal and arrhythmic syncope to determine whether this change can predict arrhythmic syncope. Using a case-control design, 33 patients were enrolled. Of the 33 patients, 18 with arrhythmic syncope, as they underwent controlled ventricular tachycardia or ventricular fibrillation (VF) during device safety testing of an implantable cardioverter defibrillator implantation or battery replacement, were compared with 15 patients, who during a tilt-table test were diagnosed with vasovagal syncope (VS). For each patient, a blood sample for NT-proBNP evaluation was collected at baseline and 6 hours after the episode of ventricular tachycardia, VF, or VS. We calculated the percentage of increase in the 6-hour NT-proBNP concentration between the 2 groups using nonparametric techniques. We also calculated the area under a receiver operating characteristic curve with the 95% confidence intervals. The 6-hour change in the NT-proBNP concentrations between patients who had had an episode of ventricular tachycardia or VF and patients with VS was significantly different, with a median increase of 32% in the ventricular tachycardia or VF group versus 5% in the VS group (p <0.01). The area under a receiver operating characteristic curve to predict arrhythmic syncope was 0.8 (95% confidence interval 0.65 to 0.95). In conclusion, the results of the present study suggest that a 6-hour NT-proBNP increase might be able to predict arrhythmic syncope. Future work is needed to confirm these findings in undifferentiated emergency department patients who present with syncope.

Pentraxin-3 predicts functional recovery and 1-year major adverse cardiovascular events after rehabilitation of cardiac surgery patients.

BACKGROUND: Inflammatory and vascular markers have proved to be predictors of outcome in myocardial infarction and heart failure. We evaluated several circulating markers of cardiac stress, inflammation, and endothelial function to investigate their ability to predict short-term functional recovery and long-term clinical outcome in heart surgery patients undergoing inpatient rehabilitation. METHODS: This prospective, multicenter study enrolled 223 patients after heart surgery, included in a 3-week program of standardized and supervised physical training. The association between biomarkers (pentraxin-3 [PTX3], brain natriuretic peptide, high-sensitivity cardiac troponin-T [hs-cTnT] and C-reactive protein [hsCRP], creatine kinase, myoglobin, and urinary albumin excretion [UACR]) and exercise capacity (6-minute walk test, 6MWT) or 1-year incidence of major adverse cardiovascular events (MACE) was tested in models that included biohumoral markers, and clinical and instrumental variables. RESULTS: The patients (69.5% men, mean age of 67 ± 11 years) were enrolled after valvular surgery (52.7%) and 58.6% after coronary artery bypass grafting (CABG). Exercise capacity improved during rehabilitation (6MWT distance from 279 ± 95 to 386 ± 91 m; P < .0001); concentrations of most biomarkers decreased (hsCRP: 79% [P < .0001]; hs-cTnT: 57% [P < .0001]; UACR: 36% [P = .05]). Among the tested markers, PTX3 showed the closest association with 6MWT distance (P = .01) and was the only predictor of MACE, also in the subgroup of CABG patients (OR [95% CI] = 1.14 [1.03-1.27]; P = .015). CONCLUSION: PTX3, a marker of vascular inflammation and cardiovascular damage, is a predictor of short-term functional recovery and 1-year MACE in patients undergoing rehabilitation after cardiac surgery, regardless of clinical and instrumental parameters.

Serial measurement of cardiac troponin T using a highly sensitive assay in patients with chronic heart failure: data from 2 large randomized clinical trials.

BACKGROUND: Cardiac troponins are emerging as important prognostic markers in chronic cardiovascular conditions like stable coronary artery disease or chronic heart failure (HF). Less is known about the relation between serial measurements of high-sensitivity cardiac troponin T (hs-cTnT) and future events in HF. We determined the association between changes over time in hs-cTnT and outcome in patients with chronic HF. METHODS AND RESULTS: We analyzed 5284 patients with chronic HF from 2 independent randomized clinical trials, the Valsartan Heart Failure Trial (Val-HeFT) (n=4053) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) trial (n=1231). hs-cTnT was measured at randomization and after 3 months (GISSI-HF) or 4 months of follow-up (Val-HeFT). The association between changes over time of hs-cTnT and various outcomes was tested in multivariable models. In both studies, increases in hs-cTnT levels over time were associated with age, diabetes mellitus, worsening of renal function (reduction in estimated glomerular filtration rate), and baseline and increases in N-terminal pro-brain natriuretic peptide concentrations. Increases in hs-cTnT concentrations were associated with all-cause mortality (incidence rates, 8.19 [7.51-8.88] and 6.79 [5.98-7.61] per 100 person-years in Val-HeFT and GISSI-HF, respectively, with hazard ratios [95% confidence intervals] of 1.59 [1.39-1.82] and 1.88 [1.50-2.35]) after adjustment for conventional risk factors and baseline levels of hs-cTnT and N-terminal pro-brain natriuretic peptide. Changes in hs-cTnT concentration modestly improved prognostic discrimination beyond baseline values for fatal outcomes only. CONCLUSIONS: Despite very low circulating concentrations, changes in hs-cTnT concentrations over time are robust predictors of future cardiovascular events in patients with chronic HF but add limited prognostic discrimination. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00336336.

Comparison of the temporal release pattern of copeptin with conventional biomarkers in acute myocardial infarction.

BACKGROUND: Early detection of acute myocardial infarction (AMI) using cardiac biomarkers of myocardial necrosis remains limited since these biomarkers do not rise within the first hours from onset of AMI. We aimed to compare the temporal release pattern of the C-terminal portion of provasopressin (copeptin) with conventional cardiac biomarkers, including creatine kinase isoenzyme (CK-MB), cardiac troponin T (cTnT), and high-sensitivity cTnT (hs-cTnT), in patients with ST-elevation AMI. METHODS: We included 145 patients undergoing successful primary percutaneous coronary intervention (PCI) for a first ST-elevation AMI presenting within 12 h of symptom onset. Blood samples were taken on admission and at four time points within the first 24 h after PCI. RESULTS: In contrast to all other markers, copeptin levels were already elevated on admission and were higher with a shorter time from symptom onset to reperfusion and lower systolic blood pressure. Copeptin levels peaked immediately after symptom onset at a maximum of 249 pmol/L and normalized within 10 h. In contrast, CK-MB, cTnT, and hs-cTnT peaked after 14 h from symptom onset at a maximum of 275 U/L, 5.75 µg/L, and 4.16 µg/L, respectively, and decreased more gradually. CONCLUSIONS: Copeptin has a distinct release pattern in patients with ST-elevation AMI, peaking within the first hour after symptom onset before conventional cardiac biomarkers and falling to normal ranges within the first day. Further studies are required to determine the exact role of copeptin in AMI suspects presenting within the first hours after symptom onset.

Adiponectin in chronic heart failure: influence of diabetes and genetic variants.

BACKGROUND: We hypothesized that, besides type 2 diabetes (T2D) and body mass index (BMI), circulating adiponectin concentration would be associated with variants of the ADIPOQ gene in patients with chronic heart failure (CHF). We also assessed the influence of these confounders on the prognostic value of adiponectin. METHODS: Plasma adiponectin was measured at entry and after 3 months in approximately 1200 patients with CHF enrolled in the GISSI-HF trial. Four common single-nucleotide polymorphisms (SNPs) spanning the ADIPOQ gene were studied: rs17300539 (-11391G→A), rs266729 (-11377C→G), rs2241766 (+45T→G) and rs1501299 (+276G→T). Associations with clinical characteristics and mortality were evaluated in patients with or without T2D. RESULTS: Adiponectin concentrations were negatively related to BMI, higher in women and older persons, but lower in patients with diabetes. T-allele carriers for rs1501299 and A-allele carriers for rs17300539 had significantly elevated adiponectin concentrations. Irrespective of diabetes, baseline plasma adiponectin was independently associated with mortality (adjusted HR [95%CI] per 1 SD increase in adiponectin concentration = 1·24[1·12-1·37], P < 0·0001) and improved prognostic discrimination beyond clinical risk factors (integrated discrimination improvement, P = 0·005). Patients with increasing adiponectin concentration over 3 months had worse outcome than those with stable levels (unadjusted HR = 1·46[1·09-1·96], P = 0·01); this relation was attenuated by the genetic variants examined and by robust confounders like age, diabetes, BMI or NT-proBNP (adjusted HR = 1·37[0·97-1·94], P = 0·075). CONCLUSIONS: Although diabetes and genetic variants at the ADIPOQ gene influence the circulating levels of adiponectin in CHF, higher plasma adipokine levels, but not genetic variants, are consistently associated with a poor prognosis.

Liver-related factors associated with low vitamin D levels in HIV and HIV/HCV coinfected patients and comparison to general population.

OBJECTIVES: Low 25-Hydroxyvitamin D (25[OH]D) was associated with severe fibrosis and low sustained virological response (SVR) after interferon (IFN)-based therapy in chronic hepatitis C. Furthermore, hypovitaminosis D was reported in HIV-infected individuals, but its role in liver disease progression in HIV/HCV coinfection is unknown. METHODS: 25(OH)D was retrospectively measured in 237 HIV-infected patients (93 with HCV coinfection) and 76 healthy controls. Multivariate analysis included season, immuno-virological data, combined antiretroviral therapy (cART) and, in a subgroup of 51 HIV/HCV-genotype 1 coinfected patients, factors influencing SVR to pegylated-IFN and ribavirin. In a group of 20 patients, liver expression of cytochrome (CY)-P27A1 and CYP2R1, 25-hydroxylating enzymes, was assessed by immunohistochemistry. RESULTS: Median 25(OH)D levels were 23.4 (interquartile range 16.7-33.7) ng/mL in the HIV-infected population and 24 ng/mL (18.3-29.5) in healthy controls (p=0.9). At multiple regression analysis, only winter/spring measurements correlated with lower 25(OH)D levels. No correlation with HCV coinfection, nor with cART regimens was found. Low 25(OH)D was independently associated with advanced fibrosis in HIV/HCV coinfected patients (p=0.023), whereas no association emerged with SVR to IFN-based therapy. CYP27A1 and CYP2R1 expression was associated neither with 25(OH)D serum levels nor with HCV-infection, liver histology, or cART. CONCLUSIONS: In our experience, despite the high prevalence of 25(OH)D insufficiency, HIV and HCV-infection did not seem to influence vitamin D status. The role of HIV, HCV and cART on hypovitaminosis D needs further validation in larger cohorts that account for the vitamin levels in general populations and for seasonal and regional variability.