Jose Binongo

Cholecalciferol (Vitamin D3) Therapy and Vitamin D Insufficiency in Patients with Chronic Kidney Disease: A Randomized Controlled Pilot Study

OBJECTIVE To investigate the efficacy of cholecalciferol (vitamin D3) in raising serum 25-hydroxyvitamin D (25[OH)]D) levels and reducing parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD). METHODS In this double-blind, randomized controlled pilot study, participants with CKD stage 3 and 4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m2), vitamin D insufficiency (serum 25[OH]D <30 ng/mL), and serum intact PTH levels >70 pg/mL were randomly assigned to receive either 50 000 IU of cholecalciferol or placebo once weekly for 12 weeks. Primary outcomes (25[OH]D and PTH levels) were measured at baseline, week 6, and week 12. Secondary outcomes (1,25-dihydroxvitamin D and bone turnover markers) were measured at baseline and week 12. Because of skewed data distribution, statistical analyses were performed on a logarithmic scale. The difference between the group means was exponentiated to provide the geometric mean ratio. A linear mixed model using an unstructured variance-covariance matrix was used to examine change in the primary and secondary outcomes over time. RESULTS Geometric mean serum 25(OH)D concentrations of the study groups were similar at baseline (P = .77). At week 6, a significant difference between the treatment and placebo groups was detected (P = .001); this difference was maintained at week 12 (P = .002). Among cholecalciferol-treated participants, serum 25(OH)D concentration increased on average from 17.3 ng/mL (95% confidence interval [CI], 11.8-25.2) at baseline to 49.4 ng/mL (95% CI, 33.9-72.0) at week 12. As-treated analysis indicated a trend toward lower PTH levels among cholecalciferol-treated participants (P = .07). CONCLUSION Weekly cholecalciferol supplementation appears to be an effective treatment to correct vitamin D status in patients with CKD.

Association of coronary wall shear stress with atherosclerotic plaque burden, composition, and distribution in patients with coronary artery disease.

Background Extremes of wall shear stress (WSS) have been associated with plaque progression and transformation, which has raised interest in the clinical assessment of WSS. We hypothesized that calculated coronary WSS is predicted only partially by luminal geometry and that WSS is related to plaque composition. Methods and Results Twenty‐seven patients with coronary artery disease underwent virtual histology intravascular ultrasound and Doppler velocity measurement for computational fluid dynamics modeling for WSS calculation in each virtual histology intravascular ultrasound segment (N=3581 segments). We assessed the association of WSS with plaque burden and distribution and with plaque composition. WSS remained relatively constant across the lower 3 quartiles of plaque burden (P=0.08) but increased in the highest quartile of plaque burden (P<0.001). Segments distal to lesions or within bifurcations were more likely to have low WSS (P<0.001). However, the majority of segments distal to lesions (80%) and within bifurcations (89%) did not exhibit low WSS. After adjustment for plaque burden, there was a negative association between WSS and percent necrotic core and calcium. For every 10 dynes/cm2 increase in WSS, percent necrotic core decreased by 17% (P=0.01), and percent dense calcium decreased by 17% (P<0.001). There was no significant association between WSS and percent of fibrous or fibrofatty plaque components (P=NS). Conclusions In patients with coronary artery disease: (1) Luminal geometry predicts calculated WSS only partially, which suggests that detailed computational techniques must be used to calculate WSS. (2) Low WSS is associated with plaque necrotic core and calcium, independent of plaque burden, which suggests a link between WSS and coronary plaque phenotype. (J Am Heart Assoc. 2012;1:e002543 doi: 10.1161/JAHA.112.002543.)

Racial differences in arterial stiffness and microcirculatory function between Black and White Americans.

Background Compared with whites, black Americans suffer from a disproportionate burden of cardiovascular disease (CVD). We hypothesized that racial differences in the prevalence of CVD could be attributed, in part, to impaired vascular function in blacks after adjustment for differences in risk factor burden. Methods and Results We assessed vascular function in 385 black and 470 white subjects (mean age, 48±11 years; 45% male). Using digital pulse amplitude tonometry (EndoPAT) we estimated the reactive hyperemia index (RHI), a measure of microvascular endothelial function, and peripheral augmentation index (PAT‐AIx). Central augmentation index (C‐AIx) and pulse‐wave velocity (PWV) were measured as indices of wave reflections and arterial stiffness, respectively, using applanation tonometry (Sphygmocor). Compared with whites, blacks had lower RHI (2.1±0.6 versus 2.3±0.6, P<0.001), greater arterial wave reflections assessed as both PAT‐AIx (20.4±21.5 versus 17.0±22.4, P=0.01) and CAIx (20.8±12.3 versus 17.5±13.3, P=0.001), and greater arterial stiffness, measured as PWV (7.4±1.6 versus 7.1±1.6 m/s, P=0.001). After adjustment for traditional CVD risk factors, black race remained a significant predictor of lower RHI and higher PAT‐AIx and CAIx (all P<0.001) in all subjects and of higher PWV in men (P=0.01). Furthermore, these associations persisted in a subgroup analysis of “healthy” individuals free of CVD risk factors. Conclusion Black race is associated with impaired microvascular vasodilatory function, and greater large arterial wave reflections and stiffness. Because impairment in these vascular indices may be associated with worse long‐term outcomes, they may represent underlying mechanisms for the increased CVD risk in blacks.

Minimalist transcatheter aortic valve replacement: The new standard for surgeons and cardiologists using transfemoral access?

BACKGROUND A minimalist approach for transcatheter aortic valve replacement (MA-TAVR) utilizing transfemoral access under conscious sedation and transthoracic echocardiography is increasing in popularity. This relatively novel technique may necessitate a learning period to achieve proficiency in performing a successful and safe procedure. This report evaluates our MA-TAVR cohort with specific characterization between our early, midterm, and recent experience. METHODS We retrospectively reviewed 151 consecutive patients who underwent MA-TAVR with surgeons and interventionists equally as primary operator at Emory University between May 2012 and July 2014. Our institution had performed 300 TAVR procedures before implementation of MA-TAVR. Patient characteristics and early outcomes were compared using Valve Academic Research Consortium 2 definitions among 3 groups: group 1 included the first 50 patients, group 2 included patients 51 to 100, and group 3 included patients 101 to 151. RESULTS Median age for all patients was 84 years and similar among groups. The majority of patients were men (56%) and the median ejection fraction for all patients was 55% (interquartile range, 38.0%-60.0%). The majority of patients were high-risk surgical candidates with a median Society of Thoracic Surgeons Predicted Risk of Mortality of 10.0% and similar among groups. The overall major stroke rate was 3.3%, major vascular complications occurred in 3% of patients, and greater-than-mild paravalvular leak rate was 7%. In-hospital mortality and morbidity were similar among all 3 groups. CONCLUSIONS In a high-volume TAVR center, transition to MA-TAVR is feasible with acceptable outcomes and a diminutive procedural learning curve. We advocate for TAVR centers to actively pursue the minimalist technique with equal representation by cardiologists and surgeons.

The Expanding Role of Endoscopic Robotics in Mitral Valve Surgery: 1,257 Consecutive Procedures

BACKGROUND The role of robotic instruments in mitral valve (MV) surgery continues to evolve. The purpose of this study was to assess the safety, efficacy, and scope of MV surgery using a lateral endoscopic approach with robotics (LEAR) technique. METHODS From 2006 to 2013, a dedicated LEAR team performed 1,257 consecutive isolated MV procedures with or without tricuspid valve repair or atrial ablation. The procedures were performed robotically through five right-side chest ports with femoral artery or ascending aortic perfusion and balloon occlusion. Operative videos and data were recorded on all procedures and reviewed retrospectively. RESULTS The mean age of all patients was 59.3 ± 20.5 years, and 8.4% (n = 105) had previous cardiac surgery. The MV repair was performed in 1,167 patients (93%). The MV replacement was performed in 88 patients (7%), and paravalvular leak repair in 2 patients. Concomitant atrial ablation was performed in 226 patients (18%), and tricuspid valve repair in 138 patients (11%). Operative mortality occurred in 11 patients (0.9%) and stroke in 9 patients (0.7%). Predischarge echocardiograms demonstrated mild or less mitral regurgitation in 98.3% of MV repair patients. At mean follow-up of 50 ± 26 months, 44 patients (3.8%) required MV reoperation. Application of the LEAR technique to all institutional isolated MV procedures increased from 46% in the first year to more than 90% in the last 3 years. CONCLUSIONS Mitral valve repair or replacement, including concomitant procedures, can be performed safely and effectively using the LEAR technique. With a dedicated robotic team, the vast majority of patients with MV disorders, either isolated or with concomitant problems, can be treated using the LEAR technique.

Vitamin D status is independently associated with plasma glutathione and cysteine thiol/disulphide redox status in adults

Redox status and inflammation are important in the pathophysiology of numerous chronic diseases. Epidemiological studies have linked vitamin D status to a number of chronic diseases. We aimed to examine the relationships between serum 25‐hydroxyvitamin D [25(OH)D] and circulating thiol/disulphide redox status and biomarkers of inflammation.

Effect of progenitor cell mobilization with granulocyte-macrophage colony-stimulating factor in patients with peripheral artery disease: a randomized clinical trial.

IMPORTANCE Many patients with peripheral artery disease (PAD) have walking impairment despite therapy. Experimental studies in animals demonstrate improved perfusion in ischemic hind limb after mobilization of bone marrow progenitor cells (PCs), but whether this is effective in patients with PAD is unknown. OBJECTIVE To investigate whether therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) improves exercise capacity in patients with intermittent claudication. DESIGN, SETTING, AND PARTICIPANTS In a phase 2 double-blind, placebo-controlled study, 159 patients (median [SD] age, 64 [8] years; 87% male, 37% with diabetes) with intermittent claudication were enrolled at medical centers affiliated with Emory University in Atlanta, Georgia, between January 2010 and July 2012. INTERVENTIONS Participants were randomized (1:1) to received 4 weeks of subcutaneous injections of GM-CSF (leukine), 500 μg/day 3 times a week, or placebo. Both groups were encouraged to walk to claudication daily. MAIN OUTCOMES AND MEASURES The primary outcome was peak treadmill walking time (PWT) at 3 months. Secondary outcomes were PWT at 6 months and changes in circulating PC levels, ankle brachial index (ABI), and walking impairment questionnaire (WIQ) and 36-item Short-Form Health Survey (SF-36) scores. RESULTS Of the 159 patients randomized, 80 were assigned to the GM-CSF group. The mean (SD) PWT at 3 months increased in the GM-CSF group from 296 (151) seconds to 405 (248) seconds (mean change, 109 seconds [95% CI, 67 to 151]) and in the placebo group from 308 (161) seconds to 376 (182) seconds (change of 56 seconds [95% CI, 14 to 98]), but this difference was not significant (mean difference in change in PWT, 53 seconds [95% CI, -6 to 112], P = .08). At 3 months, compared with placebo, GM-CSF improved the physical functioning subscore of the SF-36 questionnaire by 11.4 (95% CI, 6.7 to 16.1) vs 4.8 (95% CI, -0.1 to 9.6), with a mean difference in change for GM-CSF vs placebo of 7.5 (95% CI, 1.0 to 14.0; P = .03). Similarly, the distance score of the WIQ improved by 12.5 (95% CI, 6.4 to 18.7) vs 4.8 (95% CI, -0.2 to 9.8) with GM-CSF compared with placebo (mean difference in change, 7.9 [95% CI, 0.2 to 15.7], P = .047). There were no significant differences in the ABI, WIQ distance and speed scores, claudication onset time, or mental or physical component scores of the SF-36 between the groups. CONCLUSIONS AND RELEVANCE Therapy with GM-CSF 3 times a week did not improve treadmill walking performance at the 3-month follow-up. The improvements in some secondary outcomes with GM-CSF suggest that it may warrant further study in patients with claudication. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01041417.

Consumption of less than 10% of total energy from added sugars is associated with increasing HDL in females during adolescence: a longitudinal analysis.

Background Atherosclerotic changes associated with dyslipidemia and increased cardiovascular disease risk are believed to begin in childhood. While previous studies have linked added sugars consumption to low high‐density lipoprotein (HDL), little is known about the long‐term impact of this consumption. This study aims to assess the association between added sugars intake and HDL cholesterol levels during adolescence, and whether this association is modified by obesity. Methods and Results We used data from the National Heart Lung and Blood Institutes Growth and Health Study, a 10‐year cohort study of non‐Hispanic Caucasian and African‐American girls (N=2379) aged 9 and 10 years at baseline recruited from 3 sites in 1987‐1988 with biennial plasma lipid measurement and annual assessment of diet using a 3‐day food record. Added sugars consumption was dichotomized into low (0% to <10% of total energy) and high (≥10% of total energy). In a mixed model controlling for obesity, race, physical activity, smoking, maturation stage, age, and nutritional factors, low compared with high added sugar consumption was associated with a 0.26 mg/dL greater annual increase in HDL levels (95% CI 0.48 to 0.04; P=0.02). Over the 10‐year study period, the model predicted a mean increase of 2.2 mg/dL (95% CI 0.09 to 4.32; P=0.04) among low consumers, and a 0.4 mg/dL decrease (95% CI −1.32 to 0.52; P=0.4) among high consumers. Weight category did not modify this association (P=0.45). Conclusion Low added sugars consumption is associated with increasing HDL cholesterol levels throughout adolescence.

Diagnostic Performance of an Expert System for Interpretation of 99mTc MAG3 Scans in Suspected Renal Obstruction

The purpose of the study was to compare diuresis renography scan interpretation generated by a renal expert system with the consensus interpretation of 3 expert readers. Methods: The expert system was evaluated in 95 randomly selected furosemide-augmented patient studies (185 kidneys) obtained for suspected obstruction; there were 55 males and 40 females with a mean age ± SD of 58.6 ± 16.5 y. Each subject had a baseline 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) scan followed by furosemide administration and a separate 20-min acquisition. Quantitative parameters were automatically extracted from baseline and furosemide acquisitions and forwarded to the expert system for analysis. Three experts, unaware of clinical information, independently graded each kidney as obstructed/probably obstructed, equivocal, and probably nonobstructed/nonobstructed; experts resolved differences by a consensus reading. These 3 expert categories were compared with the obstructed, equivocal, and nonobstructed interpretations provided by the expert system. Agreement was assessed using weighted κ, and the predictive accuracy of the expert system compared with expert readers was assessed by the area under receiver-operating-characteristic (ROC curve) curves. Results: The expert system agreed with the consensus reading in 84% (101/120) of nonobstructed kidneys, in 92% (33/36) of obstructed kidneys, and in 45% (13/29) of equivocal kidneys. The weighted κ between the expert system and the consensus reading was 0.72 and was comparable with the weighted κ between experts. There was no significant difference in the areas under the ROC curves when the expert system was compared with each expert using the other 2 experts as the gold standard. Conclusion: The renal expert system showed good agreement with the expert interpretation and could be a useful educational and decision support tool to assist physicians in the diagnosis of renal obstruction. To better mirror the clinical setting, algorithms to incorporate clinical data must be designed, implemented, and tested.

Lopinavir/Ritonavir Pharmacokinetic Profile: Impact of Sex and Other Covariates Following a Change From Twice-Daily to Once-Daily Therapy

The aim of this study was to determine the impact of sex on the pharmacokinetics of lopinavir/ritonavir. Interaction between lopinavir/ritonavir and tenofovir was also evaluated. Steady‐state plasma samples were obtained from virologically suppressed HIV‐infected patients on lopinavir/ritonavir 800/200‐mg soft gel capsule taken once daily. Drug assays were performed by high‐performance liquid chromatography. Pharmacokinetic parameters estimated by noncompartmental method were reported as 90% confidence intervals (CIs) about the geometric mean ratio (GMR). There were 9 males and 11 females. No sex differences were observed in lopinavir/ritonavir pharmacokinetics profile. The GMRsex (women compared with men) for lopinavir area under the concentration‐time curve (AUC24), maximum concentration (Cmax), and minimum concentration (Cmin) was 0.95 (90% CI, 0.70–1.29), 0.88 (90% CI, 0.67–1.15), and 1.27 (90% CI, 0.60–2.66), respectively. Similarly, the GMRsex for ritonavir AUC24, Cmax, and Cmin was 0.84 (90% CI, 0.57–1.24), 0.79 (90% CI, 0.50–1.22), and 1.02 (90% CI, 0.58–1.80), respectively. Tenofovir coadministration led to a reduction in lopinavir/ritonavir plasma exposure, giving a lopinavir GMRtenofovir for Cmax of 0.72 (90% CI, 0.57–0.93) and AUC24 of 0.74 (90% CI, 0.56–0.98), respectively. No difference in lopinavir/ritonavir plasma concentrations between sexes was demonstrated in this study. However, tenofovir coadministration lowered lopinavir/ritonavir plasma exposure.