Stable Clinical Condition Research Articles

HMGB1 Is Increased by CFTR Loss of Function, Is Lowered by Insulin, and Increases In Vivo at Onset of CFRD.

Cystic fibrosis-related diabetes (CFRD) is associated with worsening of inflammation and infections, and the beginning of insulin treatment is debated. To verify high-mobility group box 1 protein (HMGB1) levels in CF patients according to glucose tolerance state, and analyze relationships with insulin secretion and resistance. To verify, in an in vitro model, whether HMGB1 gene expression and protein content were affected by insulin administration and whether these changes were dependent on CF transmembrane conductance regulator (CFTR) loss of function. Forty-three patients in stable clinical conditions and 35 age- and sex-matched controls were enrolled. Glucose tolerance was established in patients based on a 5 point oral glucose tolerance test (OGTT). Fasting glucose to insulin ratio (FGIR), HOMA-IR index, whole-body insulin sensitivity index (WIBISI), and the areas under the curve for glucose (AUCG) and insulin (AUCI) were calculated. HMGB1 was assayed in serum, in cell lysates and conditioned media using a specific ELISA kit. For the in vitro study we used CFBE41o- cells, homozygous for the F508del mutation, and 16HBE14o- as non-CF control. HMGB1 gene expression was studied by real-time RT-PCR. Cells were stimulated with insulin at 2.5 and 5 ng/mL. The CFTR inhibitor 172 and CFTR gene silencing were used to induce CFTR loss of function in 16HBE14o- cells. HMGB1 levels were increased at onset of CFRD (5.04 ± 1.2 vs 2.7 ± 0.3 ng/mL in controls; P < .05) and correlated with FGIR (R = +0.43; P = .038), and AUCI (R = +0.43; P = .013). CFTR loss of function in the 16HBE14o- cells increased HMGB1 and was lowered by insulin. HMGB1 was increased in CF patients with deranging glucose metabolism and showed relationships with indexes of glucose metabolism. The increase in HMGB1 was related to CFTR loss of function, and insulin lowered HMGB1. Further research is required to verify whether HMGB1 could potentially be a candidate marker of onset of CFRD and to establish when to start insulin treatment.

ICU Pad Project: application of modern computer technology in pediatric postoperative cardiac intensive care. Pilot study.

ICU Pad Project: application of modern computer technology in pediatric postoperative cardiac intensive care. Pilot study.

Relationship between mean platelet volume and ischemic stroke in patients with patent foramen ovale.

Patent foramen ovale (PFO) is commonly encountered in patients with cryptogenic stroke. Mean platelet volume (MPV), an indicator of platelet reactivity, has been reported in recent trials to be higher in patients with PFO than in normal population. The aim of this study was to investigate whether there is a difference in MPV between patients with PFO and stroke or transient ischemic attack (TIA) and that of patients with asymptomatic PFO. Patients with PFO who were younger than 55 years of age were enrolled in this retrospective study. Hemogram parameters of patients with ischemic stroke or TIA (symptomatic group) were obtained during hospitalization once they had stable clinical status. Total of 108 patients, 51 of whom were symptomatic, were included in the study. MPV was determined to be higher in symptomatic group compared with asymptomatic group (median 10.0 fl [25th-75th percentile: 9.0-11.0] vs median 8.56 fl [25th-75th percentile: 8.0-9.0], respectively; p<0.001,. Cut-off point of 9.0 fl for MPV had 70% sensitivity and 86% specificity in predicting symptomatic PFO patients. MPV is higher in symptomatic than in asymptomatic PFO patients. This finding may be a subsidiary risk factor to identify patients with PFO and high risk of cardioembolic stroke.

"Next Door" intraoperative magnetic resonance imaging for awake craniotomy: Preliminary experience and technical note.

Background:During glioma surgery “maximal safe resection” must be the main goal. Intraoperative magnetic resonance imaging (iMRI) associated with awake craniotomy (AC) is a valuable tool to achieve this objective. In this article, AC with a “next-door” iMRI concept is described in a stepwise protocol.Methods:This is a retrospective analysis of 18 patients submitted to AC using iMRI; a stepwise protocol is also discussed.Results:The mean age was 41.7 years. Hemiparesis, aphasia, and seizures were the main initial symptoms of the patients. Sixty-six percent of the tumors were located in the left hemisphere. All tumors were near or within eloquent areas. Fifty-three percent of the cases were glioblastomas multiforme and 47% of the patients had low grade gliomas. The mean surgical time and iMRI time were 4 h 4 min and 30 min, respectively. New resection was performed in 33% after iMRI. Extent of resection (EOR) higher than 95% was possible in 66.7% of the patients. The main reason of EOR lower than 95% was positive mapping of eloquent areas (6 patients). Eighty percent of the patients experienced improvement of their deficits immediately after the surgery or had a stable clinical status whereas 20% had neurological deterioration, however, all of them improved after 30 days.Conclusion:AC associated with “next-door” iMRI is a complex procedure, but if performed using a meticulous technique, it may improve the overall tumor resection and safety of the patients.

Galectin-3 Serum Levels Are Independently Associated With Microalbuminuria in Chronic Heart Failure Outpatients.

Background:Galectin-3 (Gal-3) is a novel biomarker reflecting inflammation status and fibrosis involving worsening of both cardiac and renal functions.Objectives:The aim of this study was to evaluate the relationship between Gal-3 serum levels and microalbuminuria in a group of chronic heart failure (CHF) outpatients.Patients and Methods:We enrolled CHF outpatients having stable clinical conditions and receiving conventional therapy. All patients underwent clinical evaluation, routine chemistry analysis, echocardiography, and evaluation of the urinary albumin/creatinine ratio (UACR).Results:Among the patients enrolled, 61 had microalbuminuria (UACR, 30-299) and 133 normoalbuminuria (UACR, < 30). Patients with normoalbuminuria showed significantly higher levels of Gal-3 than those without (19.9 ± 8.8 vs. 14.6 ± 5.5 ng/mL). The stepwise regression analysis indicated that Gal-3 was the first determinant of microalbuminuria (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.02 - 1.14, P = 0.012), followed by diabetes (OR 2.14; 95% CI: 1.00 - 4.57; P = 0.049) and high central venous pressure (OR 2.80; 95% CI: 1.04 - 7.58; P= 0.042).Conclusions:Our findings indicate an independent association between Gal-3 levels and microalbuminuria, an early marker of altered renal function. This suggests the possible role of Gal-3 in the progression of cardiorenal syndrome in CHF outpatients.

Role of a multidisciplinary program in improving outcomes in cognitively impaired heart failure older patients

Cognitive impairment (CI) frequently complicates Heart failure (HF) and is associated with increased mortality and morbidity. Previous studies reported that nurse-lead home-based multidisciplinary program (MP) may not improve the prognosis of this high-risk group. In the present study, we analysed the relative effectiveness of an integrated hospital-based MP in patients with cognitive impairment. Consecutive (n = 173) community-living outpatients aged > 70 years (mean 77 +/- 6, 48% women) randomized to a MP (n = 86) or usual care (UC) (n = 87) were enrolled in stable clinical conditions. Cognitive status was assessed by means of Folstein Mini Mental State Examination (MMSE). CI (MMSE < or = 24) was present in 41.6% (42,5% UC vs 40.7% MP p =ns). The variables independently associated to CI were: older age, education level <5 years, anemia and severe renal dysfunction. During a 2-year follow-up, 59 patients died (31.4%) with no significant difference between intervention group. At multivariate analysis, in the entire cohort, CI was independently associated to death (HR 2,07 7[95%CI 1,097-3,931]), HF admissions (2,133[1,346-3,381]), death/HF admissions (1,784[1,132-2,811]) and all-cause admissions (1,473[1,008-2,153]. When considered according to intervention groups, CI was independently associated to all-cause death (3,603 [1,553-8,358], death/HF admissions (2,029[1,200-3,432]) and HF admissions (2,474[1,406-4,353]) but not to all-cause admissions. The assignment of patients with CI to MP was associated to a significant reduction in HF admissions vs UC (0,503[0,253-0,999] (all interaction tests p = ns). This study suggests that CI is very common and associated to worse prognosis in heart failure and that hospital-based MP seems to improve outcomes in these patients through reduction of heart failure hospital admission.

Pulmonary Hypertension in the Preterm Infant with Chronic Lung Disease can be Caused by Pulmonary Vein Stenosis: A Must-Know Entity.

Pulmonary hypertension (PHT) in the preterm infant is frequently due to chronic lung disease. Rarely, PHT can be caused by pulmonary vein (PV) stenosis that has been described to be associated with prematurity. This study is a retrospective analysis of all premature infants <37 weeks of gestation with PV stenosis and PHT in two French pediatric congenital cardiac centers from 1998 till 2015. Diagnosis, hemodynamics and outcome are described. Sixteen patients met the inclusion criteria. Median gestational age was 28 weeks (25 + 6-35) with a median birth weight of 842 g (585-1500). The majority of infants (87.5 %) had chronic lung disease and associated cardiac defects. Median age at diagnosis was 6.6 months (1.5-71). Fifty-six percentage (n = 9) had initially unilateral PV stenosis affecting in 89 % the left PV. Median initial invasive mean pulmonary artery pressure was 42 mmHg (25-70). Treatment options included surgical intervention (n = 6), interventional cardiac catheter (n = 3) and/or targeted therapy for pulmonary arterial hypertension (n = 5). In six patients, decision of nonintervention was taken. Global mortality was 44 %. All deaths occurred within 7 months after diagnosis regardless of chosen treatment option. Mean follow-up was 6 years (4.9 months-12 years). At last visit, all eight survivors were in stable clinical condition with five of them receiving targeted therapy for pulmonary arterial hypertension. PV stenosis is an unusual cause of PHT in the premature infant with chronic lung disease. Diagnosis is challenging since initial echocardiography can be normal and the disease is progressive. Treatment options are numerous, but prognosis remains guarded.

Adding Sarcosine to Antipsychotic Treatment in Patients with Stable Schizophrenia Changes the Concentrations of Neuronal and Glial Metabolites in the Left Dorsolateral Prefrontal Cortex.

The glutamatergic system is a key point in pathogenesis of schizophrenia. Sarcosine (N-methylglycine) is an exogenous amino acid that acts as a glycine transporter inhibitor. It modulates glutamatergic transmission by increasing glycine concentration around NMDA (N-methyl-d-aspartate) receptors. In patients with schizophrenia, the function of the glutamatergic system in the prefrontal cortex is impaired, which may promote negative and cognitive symptoms. Proton nuclear magnetic resonance (1H-NMR) spectroscopy is a non-invasive imaging method enabling the evaluation of brain metabolite concentration, which can be applied to assess pharmacologically induced changes. The aim of the study was to evaluate the influence of a six-month course of sarcosine therapy on the concentration of metabolites (NAA, N-acetylaspartate; Glx, complex of glutamate, glutamine and γ-aminobutyric acid (GABA); mI, myo-inositol; Cr, creatine; Cho, choline) in the left dorso-lateral prefrontal cortex (DLPFC) in patients with stable schizophrenia. Fifty patients with schizophrenia, treated with constant antipsychotics doses, in stable clinical condition were randomly assigned to administration of sarcosine (25 patients) or placebo (25 patients) for six months. Metabolite concentrations in DLPFC were assessed with 1.5 Tesla 1H-NMR spectroscopy. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS). The first spectroscopy revealed no differences in metabolite concentrations between groups. After six months, NAA/Cho, mI/Cr and mI/Cho ratios in the left DLPFC were significantly higher in the sarcosine than the placebo group. In the sarcosine group, NAA/Cr, NAA/Cho, mI/Cr, mI/Cho ratios also significantly increased compared to baseline values. In the placebo group, only the NAA/Cr ratio increased. The addition of sarcosine to antipsychotic therapy for six months increased markers of neurons viability (NAA) and neurogilal activity (mI) with simultaneous improvement of clinical symptoms. Sarcosine, two grams administered daily, seems to be an effective adjuvant in the pharmacotherapy of schizophrenia.

Supplementation of antipsychotic treatment with sarcosine – GlyT1 inhibitor – causes changes of glutamatergic 1NMR spectroscopy parameters in the left hippocampus in patients with stable schizophrenia

Glutamatergic system, the main stimulating system of the brain, plays an important role in the pathogenesis of schizophrenia. Hippocampus, a structure crucial for memory and cognitive functions and rich in glutamatergic neurons, is a natural object of interest in studies on psychoses. Sarcosine, a glycine transporter (GlyT-1) inhibitor influences the function of NMDA receptor and glutamate-dependent transmission.The aim of the study was to assess the effects of sarcosine on metabolism parameters in the left hippocampus in patients with schizophrenia. Assessments were performed using proton nuclear magnetic resonance (1H NMR) spectroscopy (1.5T).Fifty patients diagnosed with schizophrenia (DSM-IV-TR), with dominant negative symptoms, in stable clinical condition and stable antipsychotics doses were treated either with sarcosine (n=25) or placebo (n=25). Spectroscopic parameters were evaluated within groups and between two groups before and after 6-month intervention. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS).In the sarcosine group, after 6-month treatment, we found significant decrease in hippocampal Glx/Cr (Glx-complex of glutamate, glutamine and GABA, Cr-creatine) and Glx/Cho (Cho-choline), while N-acetylaspartate (NAA), myo-inositol (mI), Cr and Cho parameters remained stable along the study and also did not differ significantly between both groups.This is the first study showing that a pharmacological intervention in schizophrenia, particularly augmentation of the antypsychotic treatment with sarcosine, may reverse the pathological increase in glutamatergic transmission in the hippocampus. The results confirm involvement of glutamatergic system in the pathogenesis of schizophrenia and demonstrate beneficial effects of GlyT-1 inhibitor on the metabolism in the hippocampus and symptoms of schizophrenia.

Levosimendan improves exercise performance in patients with advanced chronic heart failure.

AimsCardiopulmonary exercise test (CPET) provides parameters such as peak VO2 and ventilation/CO2 production (VE/VCO2) slope, which are strong prognostic predictors in patients with stable advanced chronic heart failure (ADHF). The study aim was to evaluate the effects of the inodilator levosimendan on CPET in patients with ADHF under stable clinical conditions.Methods and resultsWe enrolled patients with ADHF (peak VO2 < 12 mL/min/kg) in a double‐blind, placebo‐controlled protocol. Patients were randomly assigned to i.v. infusion of placebo (500 mL 5% glucose; n = 19) or levosimendan (in 500 mL 5% glucose; n = 23). Before and 24 h after the end of the infusion, patients underwent determination of New York Heart Association class, B‐type natriuretic peptide (BNP), haemoglobin, serum creatinine, and blood urea nitrogen levels, as well as CPET, standard spirometry, and alveolar capillary gas diffusion. BNP showed no change with placebo (1042 ± 811 to 1043 ± 867 pg/mL), but it was decreased with levosimendan (1163 ± 897 to 509 ± 543 pg/mL, P < 0.001). No changes were observed for haemoglobin, creatinine, and blood urea nitrogen in either group. With levosimendan, a minor improvement was observed in spirometry measurements, but not in alveolar capillary gas diffusion. Peak VO2 showed a small, non‐significant increase with placebo (9.5 ± 1.7 to 10.0 ± 2.1 mL/kg/min, P = 0.12), and a greater increase with levosimendan (9.8 ± 1.7 to 11.0 ± 1.9 mL/kg/min, P < 0.005). The VE/VCO2 slope showed no change (44.0 ± 11 vs. 43.4 ± 10.3, P = 0.44), and a decrease (41.9 ± 10 vs. 36.6 ± 6.4, P < 0.001) in the placebo and in the levosimendan group, respectively.ConclusionLevosimendan treatment significantly improves peak VO2 and reduces VE/VCO2 slope and BNP in patients with ADHF.

Administration of Anesthesia to Patients with Renal Failure.

1. Never place a central line in the same extremity where the arteriovenous access (primary AV fistula or GORE-TEX® graft) is present. 2. Do not administer large amounts of intravenous (IV) fluids to patients with end-stage renal disease (ESRD) or acute renal failure (ARF)-oliguric patients (i.e., no more than 1 mL/kg) for minor procedures and during stable clinical conditions. 3. Choose the proper IV solution during anesthesia (0.9% or 0.45% NaCl) according to the following serum electrolyte levels: • normal saline (NS) if NA + 140 mEq/L or in patients receiving large amounts of exogenous NA + in the form of fresh, frozen plasma. May alternate one liter of each during prolonged surgical procedures, particularly if large amounts of volume are needed. Add 5% dextrose in NS or 1⁄2 NS in nondiabetic patients or in diabetics who receive pre-op insulin. 4. Severe intraoperative hyponatremia can frequently happen while receiving hypotonic solutions ( 200 mg/dL. Use regular insulin alone; correction of hyperglycemia results in improvement of hyperkalemia. May use sliding scale for blood sugar as follows (using Accu-Chek® every 15 min): • 201-250 mg/dL 3 U regular insulin IV • 251-300 mg/dL 5 U regular insulin IV • 301-350 mg/dL 7 U regular insulin IV • 351-400 mg/dL 10 U regular insulin IV • 400 mg/dL 15 U regular insulin IV Conversely, if blood sugar 7.48), in which case do not administer. c. Calcium gluconate 1 gm IVP, particularly if EKG findings of hyperkalemia are present. Watch for hyperkalemia intra-op if: • radiographic contrast is used (particularly in ARF-oliguric patients, as a consequence of “solvent drag effect”), • large amounts of mannitol are given under the same circumstances as above, or • cardiovascular collapse develops with ensuing lactic acidosis (resulting in acidemia, “shifting,” and hyperkalemia). 6. For intra-op hypertension in ESRD and ARF patients, avoid ACE inhibitors and beta-blockers as antihypertensive drugs since they can lead to hyperkalemia. Instead use calcium channel blockers, which may have a nephroprotective effect in ARF patients. 7. In patients with acute ongoing metabolic acidosis and acidemia (pH 150 mEq/L), tris-hydroxymethyl aminomethane (THAM) is the preferred solution to provide buffer and prevent further worsening hypernatremia obligated by NaHCO3 infusion. 8. Large amounts of citrate administered via multiple blood transfusions can lower Ca++ levels, for which calcium gluconate 1 gm IV should be administered for every 3 U of blood. Ca++ levels need to be followed closely to prevent high calciumphosphorus double product and risk for calcium-phosphorus precipitation in vital organs. 9. In the unusual event of severe hypophosphatemia (P < 2.0 mg%), replace NaHPO4 10 mmol IV over 1 hour or KHPO4 10 mmol over 1 hour according to the situation. 10. Avoid drugs with potential nephrotoxicity in ARF patients; modify doses of medications according to reduced renal function (glomerular filtration rate (GFR) < 5 mL in ESRD). Formulas such as MDRD eGFR and Cockroft-Gault (140 – age in years) x (weight in kg)/SCr x 72 are of no use in ARF to calculate GFR since anuria is GFR 0 regardless of serum creatinine levels; this formula is only useful when renal function is at a steady state and not changing daily as with ARF. P O I N T S T O R E M E M B E R

Heart failure is the strongest predictor of acute kidney injury in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction.

ST elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PCI) are at higher risk of acute kidney injury (AKI) than patients undergoing PCI in stable clinical conditions. This fact suggests that mechanisms other than contrast nephrotoxicity are involved. To evaluate the incidence, risk factors, and consequences of AKI in patients undergoing primary PCI for STEMI in current daily practice. Analysis of all consecutive patients who underwent primary PCI over a one-year period. AKI was defined as an increase in serum creatinine ≥ 50% or 26.5 μmol/L (AKIN criteria) from the baseline within 48 h. A total of 202 patients were included. AKI occurred in 25 (12.4%) subjects. Baseline characteristics and in-hospital complications of the patients with and without AKI did not differ significantly except for age (69 ± 13 vs. 62 ± 12; p = 0.003), female gender (48.0% vs. 26.6%; p = 0.035), hypertension (88.0% vs. 62.7%; p = 0.013), left ventricular ejection fraction (40% ± 12% vs. 49% ± 14%; p = 0.002), cardiogenic shock (44.0% vs. 5.1%; p < 0.0001), use of intravenous diuretics (76.0% vs. 26.0%; p < 0.0001), ventricular arrhythmias (24.0% vs. 3.4%; p = 0.001), and in-hospital mortality (24.0% vs. 3.4%; p = 0.001). In multivariate analysis heart failure remained the only independent correlate of AKI. AKI was an frequent and serious complication of STEMI in patients treated by primary PCI. Heart failure was the strongest predictor of AKI. Other risk factors including contrast medium volume, baseline renal function, diabetes, and age failed to predict AKI.

EPS02.1 Anti-Aspergillus fumigatus antibodies in cystic fibrosis (CF) patients: A comparison of three methods

Objectives The aim of the study is to compare data from an ELISA ( A. fumigatus – Bordier Affinity Products SA, CH) and a Western Blot kit (WB Aspergillus IgG – LDBio Diagnostics, France) with double diffusion (DD) method in agar gel (Ouchterlony). Methods 91 sera from CF pediatric and adult patients followed at our hospital were tested retrospectively. DD, a semi-quantitative method, was performed using somatic and metabolic extracts of A. fumigatus (BioRad and FSK, Microgen Bioproducts Ltd). The interpretation is based on the absence/presence and number of precipitation arcs. ELISA and WB were performed according to manufacturer's instructions. Conclusion The 91 sera were classified, according to the DD results, in negative (29), positive (49) and uncertain (13). Six out of the 29 negative sera were positive by ELISA, two out of the 6 were also positive to the WB, both belonging to patients with positive cultures. Notably, one of the two patients was affected by allergic bronchopulmonary aspergillosis. Among the 49 DD positive sera, 3 belonged to patients with positive culture but with stable clinical conditions and were negative for ELISA and WB. Statistical analysis of the data (excluding the doubtful cases) suggests that the distribution of inconsistent outcomes between the ELISA vs DD is compatible with the hypothesis of random variability (p = 0.508). The greatest number of positive results by ELISA compared to WB is not compatible with the hypothesis of random variability (p = 0.022). These assessments suggest that the replacement of DD with the ELISA test does not involve a deviation between the results obtained and that ELISA test confirms its validity as screening test.

Clinical course, laboratory parameters and outcome of TTP pediatric patients presenting with posterior reversible encephalopathy syndrome

Aim: The clinical course and outcome of children with thrombotic thrombocytopenic purpura and posterior reversible encephalopathy has not been observed and studied till date. The aim of the present study was to know the clinical course and outcome of children with thrombotic thrombocytopenic purpura and posterior reversible encephalopathy. Results from our observation invite potential insight for further research on this subject. Methods: From January 2005 to February 2013, seven children diagnosed with thrombotic thrombocytopenic purpura and posterior reversible encephalopathy syndromes were admitted in a tertiary care hospital in Srinagar, Kashmir. The demographic parameters, clinical characteristics and laboratory data were noted. The outcome was defined in the form of complete recovery or death. Thrombotic thrombocytopenic purpura was diagnosed on clinical grounds, laboratory parameters and renal biopsy. The diagnosis was established after an expert opinion from a hematologist. Posterior reversible encephalopathy syndrome was defined on neuroimaging. Results: The common clinical parameters which were shared by all the patients were hypertension and altered sensorium. Four (57.1%) patients showed clinical deterioration and died within one week of admission even after intensive management. Three (42.8%) patients improved clinically and recovered fully and were discharged in stable clinical condition. Repeat imaging on discharge was normal. Conclusion: This series of seven pediatric patients is the first series on this subject. The presence of posterior reversible encephalopathy syndrome in pediatric patients with thrombotic thrombocytopenic purpura complicates the clinical course and worsens the prognosis.

SUCCESSFUL APPLICATION OF PERIPHERAL VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION FOR CARDIAC ALLOGRAFT ANTIBODY-MEDIATED REJECTION WITH SEVERE HEMODYNAMIC COMPROMISE

Introduction . Acute antibody-mediated rejection (AMR) is one of the severe complications of early and late period after heart transplantation (HT). Only few case reports and studies presented of mechanical circulatory support (MCS) application for refractory acute rejection causing hemodynamic compromise. Aim . We report the case of a woman with cardiogenic shock caused by severe AMR that was successfully treatment by peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO). Material and methods. In december 2014, a 60-year-old woman with dilated cardiomyopathy was operated for HT. The patient had a good initial cardiac allograft function and no and was discharged from ICU on the 4 th day after HT. 1 st endomyocardial biopsy (EMB) (the 7 th day after HT) showed absence of acute cellular and antibody-mediated rejection. On the 11 th day after HT patient aggravated and presented clinical signs of life-threatening acute cardiac allograft dysfunction: arterial blood pressure 78/49/38 mm Hg, HR 111 in min, CVP 20 mm Hg, PAP 47/34/25 mm Hg, PCWP 25 mm Hg, CI 1.5 l/min/m 2 , adrenalin 110 ng/kg/min, dopamine 15 mcg/kg/min. ECG showed impairment of systolic left (LVEF 25%) and right (RVEF 15%) ventricle function, left and right ventricle diffuse hypokinesis, thickness of IVS, LV and RV wall 1.7, 1.4 and 0.8 cm, tricuspid and mitral valve regurgitation 2–3 degrees. EMB presented AMR. In conscience peripheral VA ECMO was installed. We used peripheral transcutaneous cannulation technique via femoral vessels – arterial cannula 15 F, venous cannula – 23 F, vascular catheter 14 G for anterograde leg’s perfusion. ACT 130–150 sec. AMR therapy included: methylprednisolon pulse-therapy (10 mg/kg for 5 day), IgG, plasmapheresis (No 7), rituximab. Results. Under MCS by VA ECMO we noted quick improvement of hemodynamic, metabolic homeostasis and organ functions. On the 6 th day of VA ECMO (blood flow 1.8 l/min): arterial blood pressure 133/81/54 mm Hg, CVP 5 mm Hg, PAP 31/21/12 mm Hg, PCWP 12 mm Hg, CI 3,4 l/min/м 2 , HR 85 in min, LVEF 53%, IVS 1.3 cm, mitral valve regurgitation <1 degree, inotropic support was discontinued. Control EMB showed resolution of AMR. Duration of VA ECMO was 7 days. Patient was discharged from ICU on the 2 nd and 26 th day after VA ECMO in stable clinical status. Conclusion. VA ECMO should be crucial component of treatment of cardiac allogaft antibody-mediated rejection with severe hemodynamic compromise.

Systemic cytokine signaling via IL-17 in smokers with obstructive pulmonary disease: a link to bacterial colonization?

We examined whether systemic cytokine signaling via interleukin (IL)-17 and growth-related oncogene-α (GRO-α) is impaired in smokers with obstructive pulmonary disease including chronic bronchitis (OPD-CB). We also examined how this systemic cytokine signaling relates to bacterial colonization in the airways of the smokers with OPD-CB. Currently smoking OPD-CB patients (n=60, corresponding to Global initiative for chronic Obstructive Lung Disease [GOLD] stage I–IV) underwent recurrent blood and sputum sampling over 60 weeks, during stable conditions and at exacerbations. We characterized cytokine protein concentrations in blood and bacterial growth in sputum. Asymptomatic smokers (n=10) and never-smokers (n=10) were included as control groups. During stable clinical conditions, the protein concentrations of IL-17 and GRO-α were markedly lower among OPD-CB patients compared with never-smoker controls, whereas the asymptomatic smoker controls displayed intermediate concentrations. Notably, among OPD-CB patients, colonization by opportunistic pathogens was associated with markedly lower IL-17 and GRO-α, compared with colonization by common respiratory pathogens or oropharyngeal flora. During exacerbations in the OPD-CB patients, GRO-α and neutrophil concentrations were increased, whereas protein concentrations and messenger RNA for IL-17 were not detectable in a reproducible manner. In smokers with OPD-CB, systemic cytokine signaling via IL-17 and GRO-α is impaired and this alteration may be linked to colonization by opportunistic pathogens in the airways. Given the potential pathogenic and therapeutic implications, these findings deserve to be validated in new and larger patient cohorts.

Treatment options for lactic acidosis and metabolic crisis in children with mitochondrial disease.

The mitochondrial pyruvate oxidation route is a tightly regulated process, which is essential for aerobic cellular energy production. Disruption of this pathway may lead to severe neurometabolic disorders with onset in early childhood. A frequent finding in these patients is acute and chronic lactic acidemia, which is caused by increased conversion of pyruvate via the enzyme lactate dehydrogenase. Under stable clinical conditions, this process may remain well compensated and does not require specific therapy. However, especially in situations with altered energy demands, such as febrile infections or longer periods of fasting, children with mitochondrial disorders have a high risk of metabolic decompensation with exacerbation of hyperlactatemia and severe metabolic acidosis. Unfortunately, no controlled studies regarding therapy of this critical condition are available and clinical outcome is often unfavorable. Therefore, the aim of this review was to formulate expert-based suggestions for treatment of these patients, including dietary recommendations, buffering strategies and specific drug therapy. However, it is important to keep in mind that a specific therapy for the underlying metabolic cause in children with mitochondrial diseases is usually not available and symptomatic therapy especially of severe lactic acidosis has its ethical limitations.

Impact of left ventricular late enhancement on pulmonary arterial hypertension in idiopathic dilated cardiomyopathy

Methods 71 consecutive patients (p) with DCM, left ventricular systolic dysfunction (LVEF<35%) and normal coronary angiography followed in an outpatient HF clinic, were prospectively enrolled in two institutions. All p had to be in stable clinical condition in the last month. Exclusion criteria were: contraindications for contrast-enhanced cardiac MR (ce-CMR), significant impairment of lung function by clinical criteria or spirometry and history of thromboembolic disease. All patients underwent ECG, echo, blood test and a ce-CMR study in a Philips Intera ® 1.5 T scanner, which included cine imaging, phase contrast in the main pulmonary artery and aorta and late enhancement (LE). Postprocessing was performed with QMASS 7.2 ® (Medis, The Netherlands). PVR was calculated following the equation: 19.38 -(4.62*Ln pulmonary artery average velocity) (0.08 x RVEF %)

Hormonal Profile in Patients With Dilated Cardiomyopathy.

Background:There is increasing evidence that endocrine system may be dysfunctional in patients with heart failure.Objectives:In the present study, we investigated hormonal abnormalities in heart failure and the effect of disturbed hormonal balance on prognostic outcomes of patients with systolic heart failure.Patients and Methods:Among patients followed in Heart Failure and Transplantation Clinic, 33 men with a diagnosis of idiopathic dilated cardiomyopathy receiving guidelines-directed medical therapies and with New York Heart Association Class II-III were enrolled. Serum concentrations of growth hormone (GH), insulin-like growth factor 1 (IGF-1), thyroid hormones, free testosterone, high-sensitive C-reactive protein (hs-CRP), and N-terminal pro-brain natriuretic peptide (NT Pro-BNP) were measured in all the patients. The physical performance of patients was assessed by six-minute walk test (6MWT). The patients were subsequently followed for a year and the data regarding their death, transplantation, or hospitalizations due to acute heart failure were recorded.Results:Except for testosterone level, the levels of GH, IGF-1, T3, and T4 concentrations in the patients were significantly lower than the normal values (P < 0.05). Among different hormone, only GH had correlation with NT Pro-BNP, hs-CRP, and 6MWT. There was no association between the occurrence of the combined events and different hormonal levels in multivariate analysis.Conclusions:The hormonal levels were low in patients with idiopathic dilated cardiomyopathy. However, the prognostic significance of different hormonal deficiencies was not clear in our study populations who were receiving standard therapies for heart failure and had a relatively stable clinical condition.

0449: Prognostic value of right ventricle echocardiographic parameters in children with idiopathic pulmonary hypertension

Echocardiography is the most common modality used for assessment and serial follow-up of right (RV) and left ventricle (LV) function in children with PAH. However, its role as predictors of outcome value has been poorly characterized. We aimed to characterize RV function in children with idiopathic PAH (iPAH) according their clinical status, and to assess the prognostic value of several echocardiographic indices of cardiac function. Clinical, biological and echocardiographic variables were assessed in 39 children (28 girls) with iPAH (type 1, Dana Point classification). Patient’s median age at inclusion was 5.8 years old 95%CI [2.9 -10.4] and the median follow-up was 12.8 months. Forty-seven echocardiographic scans were performed in children at time of worsening defined by NYHA=III or IV and/ or history of syncope and/or RV failure, and 226 echocardiographic scans were performed in stable clinical status defined by NYHA≤II, without syncope and without RV failure. Outcome events were defined as changing from stable to worsening clinical status, death, transplantation, and Potts intervention. Patients in worsening status were significantly younger and had lower body mass index (median age 5.7 years old, BMI=15 kg/m2; p<0.01). TAPSE, RV peak systolic myocardial velocity, pulmonary ejection time, aortic and pulmonary velocity-time integral were significantly reduced in this group (p<0.01). LV filling was also impaired in worsening status group: mitral early (E)/late(A) ratio and LV myocardial early diastolic velocities (mitral E’) were significantly reduced (respectively p=0.02 and p<0.01). TAPSE was the strongest predictor of events in multivariate Cox regression analysis (HR=0,80, 95%CI[0,75 to 0,86, p<0,01), and a TAPSE value ≤18mm was strongly predictive of clinical outcomes (area under curve 0,82). Echocardiographic parameters of RV function and LV filling were impaired in children with iPAH. TAPSE can predict adverse cardiovascular events. These parameters could be used in the follow-up of children with iPAH, by comparing serially within a given patient.