Off-pump versus on-pump coronary bypass in high-risk subgroups

BACKGROUND: Cardiopulmonary bypass (CPB) has pathophysiologic sequelae that may be more severe in high-risk subsets. We wanted to determine whether off-pump coronary bypass (OPCAB) could optimize outcomes. METHODS: Our database of 242 OPCAB patients undergoing complete revascularization was compared to a base of 483 CABG patients undergoing CPB. Results were compared for the overall series and in the following high-risk subsets: 80 years of age or older, ventricular dysfunction (ejection fraction (EF) < or = 0.25), prior neurologic event or renal failure, chronic obstructive pulmonary disease (COPD), and reoperation. RESULTS: In the overall series, OPCAB significantly reduced the incidence of intraoperative transfusion requirements and showed a trend toward reduced morbidity in terms of postoperative neurologic and renal complications, prolonged ventilator requirement greater than 3 days, and bleeding requiring reexploration. Mortality was less in the OPCAB group (0.4% versus 2.7%, p = not significant). Similar results were achieved in the following high-risk subgroups (n = off-pump/on-pump): 80 years of age or older (n = 28/58), EF less than or equal to 25% (n = 13/26), preoperative neurologic event (n = 25/36), preoperative renal failure (n = 27/46), COPD (n = 33/43), and reoperation (n = 28/76). OPCAB decreased the incidence of prolonged ventilation in COPD patients (0/33 [0%] versus 4/43 [9.3%] p = not significant) and decreased the incidence of renal complications in the elderly (1/28 [3.6%] versus 9/58 [15.5%] p = not significant). Off-pump coronary bypass reduced but did not eliminate neurologic events in the elderly (2/28 [7.1%] versus 8/58 [13.8%] p = not significant). CONCLUSION: Off-pump coronary bypass significantly reduced the incidence of transfusion requirement compared to the CPB counterparts and had a consistent trend in reducing morbidity and mortality overall and in all high-risk subsets. Neurologic events are not eliminated in OPCAB.     

Cognitive impairment correlates with hypothalamo-pituitary-adrenal axis dysregulation in multiple sclerosis

Hypothalamo-pituitary-adrenal (HPA) dysregulation has recently been demonstrated in multiple sclerosis (MS) by means of combined dexamethasone corticotropin-releasing hormone (Dex-CRH) suppression tests. Authors found a correlation with course of disease and to a lesser extent with depressive symptoms. In this study, we aimed to further evaluate whether HPA disturbances in MS are correlated with cognitive impairment, disability status, and fatigue. Dex-CRH tests were performed in a total of 40 patients and 11 healthy controls. Concomitantly, cognitive impairment was evaluated using the symbol digit modalities test and fatigue was assessed by different fatigue severity scales.When comparing patient subpopulations to healthy subjects, Dex-CRH stimulation tests indicated an HPA hyperactivity in primary and secondary progressive MS, while relapsing-remitting patients had response patterns similar to controls. However, results were only significant for one of the six analysed parameters, i.e. area under the curve calculations of ACTH stimulation. Within the patient sample, clear-cut differences emerged between groups of different cognitive impairment, being significant for all ACTH response parameters. Our results suggest an HPA hyperactivation related to increased cognitive impairment. Indicators of HPA axis activation further correlated substantially with neurologic disability, but only moderately with duration of disease and even less with depressive symptoms and fatigue. We conclude that the observed dysregulation is more likely a secondary effect of the extent of brain damage rather than primarily involved in the pathogenesis of MS.     

Association between diabetic retinopathy and polymorphisms of cytokine genes: a systematic review and meta-analysis

International Ophthalmology - Diabetic retinopathy (DR) is a medical condition caused by damage to the blood vessels of retina tissue due to diabetes mellitus. DR leads to injury in neural and...     

Finding genetic contributions to sporadic disease: a recessive locus at 12q24 commonly contributes to patent ductus arteriosus

The causes of many sporadic diseases are unexplained; the contribution of recessive loci with reduced penetrance is one possibility that has been difficult to explore. We describe an approach to this problem by first searching for diseases with higher prevalence in populations with high rates of consanguinity, then determining whether disease cases are more commonly the product of consanguinous union than controls in such populations, followed by analysis of genetic linkage in consanguinous cases. We demonstrate the utility of this approach by investigation of congenital heart disease in Iran. We found that patent ductus arteriosus (PDA), a common congenital heart disease, accounts for a higher fraction of congenital heart disease in Iran (15%) than in the United States (2-7%). Moreover, Iranian PDA cases demonstrated a marked increase of parental consanguinity (63%), compared with the general Iranian population (25%) or control cases with tetralogy of Fallot (30%). The recurrence of PDA among siblings was 5%. A genomewide analysis of linkage in 21 unrelated consanguinous PDA cases demonstrated a multipoint logarithm of odds score of 6.27 in favor of linkage of PDA to a 3-centimorgan interval of chromosome 12q24, with 53% of kindreds linked. These findings together establish a recessive component to PDA and implicate a single locus, PDA1, in one third or more of all PDA cases in Iran; they further suggest a role for this locus in PDA worldwide. Finally, these results suggest a general approach to the identification of recessive contributions to sporadic diseases.     

Cardiac sodium channelopathies

Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (I_Na) during phase 0 of the cardiac action potential. The importance of I_Na for normal cardiac electrical activity is reflected by the high incidence of arrhythmias in cardiac sodium channelopathies, i.e., arrhythmogenic diseases in patients with mutations in SCN5A, the gene responsible for the pore-forming ion-conducting α-subunit, or in genes that encode the ancillary β-subunits or regulatory proteins of the cardiac sodium channel. While clinical and genetic studies have laid the foundation for our understanding of cardiac sodium channelopathies by establishing links between arrhythmogenic diseases and mutations in genes that encode various subunits of the cardiac sodium channel, biophysical studies (particularly in heterologous expression systems and transgenic mouse models) have provided insights into the mechanisms by which I_Na dysfunction causes disease in such channelopathies. It is now recognized that mutations that increase I_Na delay cardiac repolarization, prolong action potential duration, and cause long QT syndrome, while mutations that reduce I_Na decrease cardiac excitability, reduce electrical conduction velocity, and induce Brugada syndrome, progressive cardiac conduction disease, sick sinus syndrome, or combinations thereof. Recently, mutation-induced I_Na dysfunction was also linked to dilated cardiomyopathy, atrial fibrillation, and sudden infant death syndrome. This review describes the structure and function of the cardiac sodium channel and its various subunits, summarizes major cardiac sodium channelopathies and the current knowledge concerning their genetic background and underlying molecular mechanisms, and discusses recent advances in the discovery of mutation-specific therapies in the management of these channelopathies.     

Importance of Mean Platelet Volume in Predicting Cardiac Mechanics Parameters and Carotid‐Intima Media Thickness in Children With End‐Stage Renal Disease and Comparison With Healthy Children

Cardiovascular disease (CVD) is the major cause of death in children with ESRD. Echocardiography and Doppler ultrasound are useful devices for diagnosing cardiovascular abnormalities in such patients. However, they are expensive, difficult to perform as a routine, and not available in many centers. Therefore, finding a more accessible and inexpensive method for CVD evaluation biomarkers is needed. The aim of this study was to evaluate the relationship between mean platelet volume (MPV) as a routine hematological parameter with cardiac mechanics characteristics in children with ESRD. Forty‐two children under dialysis and 60 age‐ and sex‐matched healthy subjects as control group were enrolled in the study. Carotid‐intima media thickness (CIMT) and echocardiographic parameters were measured in both groups. In addition, hematological and biochemical variables were evaluated in blood samples of participants. MPV was significantly higher in patients than in controls. CIMT, left ventricular mass index (LVMI), end diastolic diameter, strain rate, and global longitudinal strain were significantly different between the two groups. MPV was positively correlated with LVMI and inversely with ejection fraction. In receiver operating characteristic (ROC) curve analysis, the area under the ROC curve (AUC) values for MPV in predicting left ventricular hypertrophy (LVH) and abnormal CIMT were 0.65 (P = 0.07) and 0.53 (P = 0.74), respectively. MPV was correlated with some cardiac abnormalities in children with ESRD. However, it could not show appropriate predictive values in diagnosing LVH and subclinical atherosclerosis. Further studies with prospective design could shed more light in this topic.     

Pulmonary <Superscript>18</Superscript>F-FDG uptake helps refine current risk stratification in idiopathic pulmonary fibrosis (IPF)

Purpose

There is a lack of prognostic biomarkers in idiopathic pulmonary fibrosis (IPF) patients. The objective of this study is to investigate the potential of ¹⁸F-FDG-PET/ CT to predict mortality in IPF.

Methods

A total of 113 IPF patients (93 males, 20 females, mean age?±?SD: 70?±?9 years) were prospectively recruited for ¹⁸F-FDG-PET/CT. The overall maximum pulmonary uptake of ¹⁸F-FDG (SUV_max), the minimum pulmonary uptake or background lung activity (SUV_min), and target-to-background (SUV_max/ SUV_min) ratio (TBR) were quantified using routine region-of-interest analysis. Kaplan–Meier analysis was used to identify associations of PET measurements with mortality. We also compared PET associations with IPF mortality with the established GAP (gender age and physiology) scoring system. Cox analysis assessed the independence of the significant PET measurement(s) from GAP score. We investigated synergisms between pulmonary ¹⁸F-FDG-PET measurements and GAP score for risk stratification in IPF patients.

Results

During a mean follow-up of 29 months, there were 54 deaths. The mean TBR?±?SD was 5.6?±?2.7. Mortality was associated with high pulmonary TBR (p?=?0.009), low forced vital capacity (FVC; p?=?0.001), low transfer factor (TLCO; p?<?0.001), high GAP index (p?=?0.003), and high GAP stage (p?=?0.003). Stepwise forward-Wald–Cox analysis revealed that the pulmonary TBR was independent of GAP classification (p?=?0.010). The median survival in IPF patients with a TBR < 4.9 was 71 months, whilst in those with TBR?> 4.9 was 24 months. Combining PET data with GAP data (“PET modified GAP score”) refined the ability to predict mortality.

Conclusions

A high pulmonary TBR is independently associated with increased risk of mortality in IPF patients.

     

Effects of short- and long-term estrogen and progesterone replacement on behavioral responses and c-fos mRNA levels in female rats after acute cocaine administration

It is well established that there are estrous cycle differences in cocaine-induced behavioral activity, implicating fluctuations in levels of estrogen and progesterone throughout the cycle in these alterations in behavior. However, the mechanisms by which steroids alter cocaine-induced behavioral responses have yet to be determined. The aim of this study was to determine whether short- or long-term estrogen and progesterone administration differentially alters behavioral responses to cocaine. Estrogen (50 microg) was administered 30 min or 48 h before cocaine (15 mg/kg, i.p.) administration; progesterone (500 microg) was administered 30 min or 24 h before cocaine. Short-term estrogen replacement decreased cocaine-induced ambulations. Short-term progesterone decreased rearing, whereas long-term progesterone decreased ambulations. Although cocaine increased levels of c-fos mRNA, none of the estrogen or progesterone replacement paradigms affected this measure. Because long-term estrogen replacement has been shown to have no effect on locomotor activity after acute cocaine administration, our observations suggest that short-term estrogen may underlie behavioral alterations. These findings suggest that after acute cocaine administration, while estrogen may activate only membrane receptors to alter behavioral responses to cocaine, progesterone activates both nuclear and membrane receptors.