Citations

Congenital heart diseases, including single ventricle circulations, are clinically challenging due to chronic pressure overload and the inability of the myocardium to compensate for lifelong physiological demands. To determine the clinical relevance of autologous umbilical cord blood–derived mononuclear cells (UCB-MNCs) as a therapy to augment cardiac adaptation following surgical management of congenital heart disease, a validated model system of right ventricular pressure overload due to pulmonary artery banding (PAB) in juvenile pigs has been employed. PAB in a juvenile porcine model and intramyocardial delivery of UCB-MNCs was evaluated in three distinct 12-week studies utilizing serial cardiac imaging and end-of-study pathology evaluations. PAB reproducibly induced pressure overload leading to chronic right ventricular remodeling including significant myocardial fibrosis and elevation of heart failure biomarkers. High-dose UCB-MNCs (3 million/kg) delivered into the right ventricular myocardium did not cause any detectable safety issues in the context of arrhythmias or abnormal cardiac physiology. In addition, this high-dose treatment compared with placebo controls demonstrated that UCB-MNCs promoted a significant increase in Ki-67-positive cardiomyocytes coupled with an increase in the number of CD31+ endothelium. Furthermore, the incorporation of BrdU-labeled cells within the myocardium confirmed the biological potency of the high-dose UCB-MNC treatment. Finally, the cell-based treatment augmented the physiological adaptation compared with controls with a trend toward increased right ventricular mass within the 12 weeks of the follow-up period. Despite these adaptations, functional changes as measured by echocardiography and magnetic resonance imaging did not demonstrate differences between cohorts in this surgical model system. Therefore, this randomized, double-blinded, placebo-controlled pre-clinical trial establishes the safety of UCB-MNCs delivered via intramyocardial injections in a dysfunctional right ventricle and validates the induction of cardiac proliferation and angiogenesis as transient paracrine mechanisms that may be important to optimize long-term outcomes for surgically repaired congenital heart diseases.

Background: The first instance of a robotic-assisted surgery occurred in neurosurgery; however, it is now more common in other fields such as urology and gynecology. This study aims to characterize the prevalence of robotic surgery among current neurosurgery programs as well as identify trends in clinical trials pertaining to robotic neurosurgery. Methods: Each institution’s website was analyzed for the mention of a robotic neurosurgery program and procedures. The future potential of robotics in neurosurgery was assessed by searching for current clinical trials pertaining to neurosurgical robotic surgery. Results: Of the top 100 programs, 30 offer robotic cranial and 40 offer robotic spinal surgery. No significant differences were observed with robotic surgical offerings between geographic regions in the US. Larger programs (faculty size 16 or over) had 20 of the 30 robotic cranial programs (66.6%), whereas 21 of the 40 robotic spinal programs (52.5%) were at larger programs. An initial search of clinical trials revealed 223 studies, of which only 13 pertained to robotic neurosurgery. Spinal fixation was the most common intervention (six studies), followed by Deep Brain Stimulation (DBS, two studies), Cochlear implants (two studies), laser ablation (LITT, one study), and endovascular embolization (one study). Most studies had industry sponsors (9/13 studies), while only five studies had hospital sponsors. Conclusion: Robotic neurosurgery is still in its infancy with less than half of the top programs offering robotic procedures. Future directions for robotics in neurosurgery appear to be focused on increased automation of stereotactic procedures such as DBS and LITT and robot-assisted spinal surgery.

Background: Although lower back injuries (LBIs) are common among National Collegiate Athletic Association (NCAA) female volleyball athletes, their incidence and etiology has not been well-defined. Purpose: To describe the epidemiology of LBIs in collegiate female volleyball athletes over a 5-year period from the academic years 2009 to 2010 and 2013 to 2014. Study Design: Descriptive epidemiology study. Methods: The incidence and characteristics of spine injuries were identified utilizing the NCAA Injury Surveillance Program database. Rates of injury were calculated as the number of injuries by the total number of athlete-exposures (AEs). AEs were defined as any student participation in any single NCAA-sanctioned practice or competition. The injury rate was computed as the number of injuries per the total number of AEs and reported as a ration of injuries per 10,000 exposures. The ratio was then reported as overall number as well as stratified for event, time of season, and athletic NCAA division. Incidence rate ratios were then calculated to compare rates between event type. Results with 95% CIs that did not include 1.0 were considered statistically significant. Results: An estimated 3384 LBIs occurred in NCAA female volleyball players during this 5-year time frame. These LBIs occurred at a rate of 4.89 injuries per 10,000 AEs. LBIs were 2.76 times more likely in preseason when compared with regular season. More injuries occurred in practice (85%) when compared with competition (15%). The outside hitter and middle blocker were the most commonly position to sustain an LBI. Almost 70% of injuries were new injuries, and another 29% were recurrent injuries. The most common mechanism of injury was equally split between contact (50.4%) and overuse (45.5%) injuries, whereas the remaining mechanisms of injury were secondary for unknown reasons (4.14%). Most players returned to play within 24 hours (72.3%) followed by 1 to 6 days (16.4%), and finally 7 to 12 days (11.3%). No patient required surgical intervention. Conclusion: The rate of LBIs was high (4.89/10,000 AEs) and injuries commonly recurred (29.2%). Most injuries were new, with most athletes returning to play with 24 hours.

Background: Hypoplastic left heart syndrome (HLHS) with risk of poor outcome has been linked to MYH6 variants, implicating overlap in genetic etiologies of structural and myopathic heart disease. Methods: Whole genome sequencing was performed in 197 probands with HLHS, 43 family members, and 813 controls. Data were filtered for rare, segregating variants in 3 index families comprised of an HLHS proband and relative(s) with cardiomyopathy. Whole genome sequencing data from cases and controls were compared for rare variant burden across 56 cardiomyopathy genes utilizing a weighted burden test approach, accounting for multiple testing using a Bonferroni correction. Results: A pathogenic MYBPC3 nonsense variant was identified in the first proband who underwent cardiac transplantation for diastolic heart failure, her father with left ventricular noncompaction, and 2 fourth-degree relatives with hypertrophic cardiomyopathy. A likely pathogenic RYR2 missense variant was identified in the second proband, a second-degree relative with aortic dilation, and a fourth-degree relative with dilated cardiomyopathy. A pathogenic RYR2 exon 3 in-frame deletion was identified in the third proband diagnosed with catecholaminergic polymorphic ventricular tachycardia and his father with left ventricular noncompaction and catecholaminergic polymorphic ventricular tachycardia. To further investigate HLHS-cardiomyopathy gene associations in cases versus controls, rare variant burden testing of 56 genes revealed enrichment in MYH6 ( P =0.000068). Rare, predicted-damaging MYH6 variants were identified in 10% of probands in our cohort—4 with familial congenital heart disease, 4 with compound heterozygosity (3 with systolic ventricular dysfunction), and 4 with MYH6 – FLNC synergistic heterozygosity. Conclusions: Whole genome sequencing in multiplex families, proband-parent trios, and case-control cohorts revealed defects in cardiomyopathy-associated genes in patients with HLHS, which may portend impaired functional reserve of the single-ventricle circulation.

Ebstein anomaly has a breadth of presentations, including “typical” and “atypical,” and can be confused with congenital tricuspid dysplasia. We summarize how to differentiate within this spectrum of disease. Both typical and atypical Ebstein have an underlying failure of delamination, but atypical Ebstein does not have ≥8mm/m 2 apical septal leaflet displacement. In congenital tricuspid dysplasia, delamination is normal, while the leaflets and subvalvar apparatus are abnormal. To summarize, the sine qua non feature of Ebstein anomaly, present in both typical and atypical, is the failure of delamination. These are distinct from congenital tricuspid valve dysplasia in which the pathology is in the leaflet itself.

Abstract Background (+)‐Epicatechin (EPI) induces mitochondrial biogenesis and antioxidant metabolism in muscle fibers and neurons. We aimed to evaluate safety and efficacy of (+)‐EPI in pediatric subjects with Friedreich's ataxia (FRDA). Methods This was a phase II, open‐label, baseline‐controlled single‐center trial including 10 participants ages 10 to 22 with confirmed FA diagnosis. (+)‐EPI was administered orally at 75 mg/d for 24 weeks, with escalation to 150 mg/d at 12 weeks for subjects not showing improvement of neuromuscular, neurological or cardiac endpoints. Neurological endpoints were change from baseline in Friedreich's Ataxia Rating Scale (FARS) and 8‐m timed walk. Cardiac endpoints were changes from baseline in left ventricular (LV) structure and function by cardiac magnetic resonance imaging (MRI) and echocardiogram, changes in cardiac electrophysiology, and changes in biomarkers for heart failure and hypertrophy. Results Mean FARS/modified (m)FARS scores showed nonstatistically significant improvement by both group and individual analysis. FARS/mFARS scores improved in 5/9 subjects (56%), 8‐m walk in 3/9 (33%), 9‐peg hole test in 6/10 (60%). LV mass index by cardiac MRI was significantly reduced at 12 weeks ( P = .045), and was improved in 7/10 (70%) subjects at 24 weeks. Mean LV ejection fraction was increased at 24 weeks ( P = .008) compared to baseline. Mean maximal septal thickness by echocardiography was increased at 24 weeks ( P = .031). There were no serious adverse events. Conclusion (+)‐EPI was well tolerated over 24 weeks at up to 150 mg/d. Improvement was observed in cardiac structure and function in subset of subjects with FRDA without statistically significant improvement in primary neurological outcomes. Synopsis A (+)‐epicatechin showed improvement of cardiac function, nonsignificant reduction of FARS/mFARS scores, and sustained significant upregulation of muscle‐regeneration biomarker follistatin.