Assessment of Anomalous Coronary Arteries by Imagers and Surgeons: Comparison of Imaging Modalities.

BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) is associated with sudden cardiac death. High-risk characteristics are most commonly assessed using a 2-dimensional (2D) echocardiogram (echo) or cardiac computed tomography (CT). We hypothesize that these characteristics will be more accurately assessed when they are presented in the form of a 3D digital model. METHODS: Fourteen participants, including cardiothoracic surgeons and cardiac imaging specialists, assessed image representations, including echo, CT images, and a 3D digital model, from 6 patients who had undergone AAOCA repair. Accuracy of assessment was evaluated by comparing responses with operative findings (the gold standard). RESULTS: The reported type of AAOCA was most accurately assessed on CT (100%) and 3D models (92.31%) compared with echo (80.77%). The accuracy of the AAOCA course was highest on CT (91.03%), followed by the 3D model (80.77%), and lowest on echo (61.54%). The accuracy of intramurality was low across all imaging modalities (17.95% echo, 29.49% CT, and 21.79% 3D model). Accurate assessment of a separate AAOCA ostium was highest on 3D models (97.40%). Ostial stenosis was more accurately assessed on 3D models (56.41%). When accuracy was separated by subspecialty, CT and 3D models were more accurately assessed by all participants regardless of training. CONCLUSIONS: Cardiac imagers and congenital cardiothoracic surgeons most accurately assessed AAOCA presence, type, and course on cardiac CT and 3D models. 3D models were superior in representation of ostial characteristics. CT and 3D models are overall more accurately assessed by specialists regardless of training.

Targeted Therapy for Pulmonary Hypertension in Premature Infants.

Pulmonary hypertension (PH) is common in premature infants with bronchopulmonary dysplasia (BPD) and is associated with significant mortality. Despite expert consensus suggesting the use of targeted therapies such as phosphodiesterase inhibitors, endothelin receptor antagonists, and prostanoids, there is little data on safety and outcomes in infants with BPD-associated PH (BPD-PH) treated with these medications. We sought to describe the pharmacologic management of BPD-PH and to report outcomes at our institution. Premature infants with BPD-PH born between 2005 and 2016 were included. Follow-up data were obtained through January 2020. A total of 101 patients (61 male, 40 female) were included. Of these, 99 (98.0%) patients were treated with sildenafil, 13 (12.9%) with bosentan, 35 (34.7%) with inhaled iloprost, 12 (11.9%) with intravenous epoprostenol, and nine (8.9%) with subcutaneous treprostinil. A total of 33 (32.7%) patients died during the study period and 10 (9.9%) were secondary to severe to pulmonary hypertension. Of the surviving patients, 57 (83.8%) had follow-up data at a median of 5.1 (range 0.38-12.65) years and 44 (77.2%) were weaned off PH medications at a median 2.0 (range 0-8) years. Mortality for BPD-PH remains high mostly due to co-morbid conditions. However, for those patients that survive to discharge, PH therapies can frequently be discontinued in the first few years of life.

Sildenafil Use in Children with Pulmonary Hypertension.

OBJECTIVE: To assess the demographics, treatment algorithm, and outcomes in a large cohort of children treated with sildenafil. STUDY DESIGN: A retrospective cohort study of children with pulmonary hypertension (PH) treated with sildenafil at a single institution between 2004 and 2015. Baseline and follow-up data collected by chart review. RESULTS: There were 269 children included in this study: 47 with idiopathic pulmonary arterial hypertension, 53 with congenital heart disease, 135 with bronchopulmonary dysplasia, 24 with congenital diaphragmatic hernia, and 7 with other causes. Sildenafil was initial monotherapy in 84.8% and add-on therapy in 15.2%. Median follow-up time was 3.1 years (2 weeks-12.4 years). On follow-up, 99 (37%) remained on sildenafil or transitioned to tadalafil, 93 (35%) stopped sildenafil for improvement in PH, 54 (20%) died, and 20 (7%) were lost to follow-up. PH was most likely to improve in those with bronchopulmonary dysplasia, allowing for the discontinuation of sildenafil in 45%. Eighteen deaths were related to PH and 36 from other systemic causes. Two patients stopped sildenafil owing to airway spasm with desaturation. Overall survival was significantly lower in World Health Organization group 3 PH (bronchopulmonary dysplasia and congenital diaphragmatic hernia) vs group 1 (idiopathic pulmonary arterial hypertension and congenital heart disease), P = .02. CONCLUSIONS: In this retrospective experience in children with mainly World Health Organization groups 1 and 3 PH, low-dose sildenafil was well-tolerated, safe, and had an acceptable side effect profile. Although patients with group 3 PH have high mortality, survivors have a high likelihood of PH improving.

Patients with anomalous aortic origin of the coronary artery remain at risk after surgical repair.

OBJECTIVES: Anomalous aortic origin of a coronary artery (AAOCA) from the opposite sinus of Valsalva is a rare cardiac anomaly associated with sudden cardiac death (SCD). Single-center studies describe surgical repair as safe, although medium- and long-term effects on symptoms and risk of SCD remain unknown. We sought to describe outcomes of surgical repair of AAOCA. METHODS: We reviewed institutional records for patients who underwent AAOCA repair, from 2001 to 2016, at 2 affiliated institutions. Patients with associated heart disease were excluded. RESULTS: In total, 60 patients underwent AAOCA repair. Half of the patients (n = 30) had an anomalous left coronary artery arising from the right sinus of Valsalva and half had an anomalous right. Median age at surgery was 15.4 years (interquartile range, 11.9-17.9 years; range, 4 months to 68 years). The most common presenting symptoms were chest pain (n = 38; 63%) and shortness of breath (n = 17; 28%); aborted SCD was the presenting symptom in 4 patients (7%). Follow-up data were available for 54 patients (90%) over a median of 1.6 years. Of 53 patients with symptoms at presentation, 34 (64%) had complete resolution postoperatively. Postoperative mild or greater aortic insufficiency was present in 8 patients (17%) and moderate supravalvar aortic stenosis in 1 (2%). One patient required aortic valve replacement for aortic insufficiency. Two patients required reoperation for coronary stenosis at 3 months and 6 years postoperatively. CONCLUSIONS: Surgical repair of AAOCA is generally safe and adverse events are rare. Restenosis, and even sudden cardiac events, can occur and long-term surveillance is critical. Multi-institutional collaboration is vital to identify at-risk subpopulations and refine current recommendations for long-term management.

Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction treated with dextranomer/hyaluronic acid copolymer (Deflux).

OBJECTIVE: There has been hesitancy to use dextranomer/hyaluronic acid copolymer (DHXA, Deflux for vesicoureteral reflux (VUR) in the setting of lower urinary tract (LUT) dysfunction because of the limited number of published studies, the possibility of less success, and the manufacturer's recommendations contraindicating its use in patients with active LUT dysfunction. We report on our experience using DXHA in this subset of patients whose VUR persisted despite targeted therapy for their LUT condition. MATERIALS AND METHODS: We reviewed patients diagnosed with both a LUT condition and VUR who underwent subureteric DXHA while still undergoing treatment for their LUT dysfunction. Persistence of VUR was confirmed by videourodynamic studies (VUDS)/VCUG (voiding cystourethrogram) and all patients were on targeted treatment (TT) and antibiotic prophylaxis prior to and during DXHA injection. VUR was reassessed post-injection. RESULTS: Fifteen patients (22 ureters; 21F,1M) met inclusion criteria (mean age 6.1 years, range 4-12). Following one to three DXHA injections, VUR resolved in 17 ureters (77%) including eight of nine ureters in dysfunctional voiding (DV) patients, five of nine in idiopathic detrusor overactivity disorder (IDOD), and four of four in detrusor underutilization disorder (DUD) patients. CONCLUSIONS: DXHA is safe and effective in resolving VUR in children with associated LUT dysfunction, even before their LUT condition has fully resolved. Highest resolution rates were noted in patients with either DV or DUD or who were least symptomatic prior to injection.

Use of complementary and alternative medicine among children, adolescent, and young adult cancer survivors: a survey study.

PURPOSE: The main objective of this study was to investigate the prevalence of complementary and alternative medicine (CAM) use, types and reasons for use, and determinants of use among survivors of childhood cancer. METHODS: An interviewer-based survey of CAM use was administered to 197 survivors or their guardians. Demographic data, CAM therapies used, purpose and referral for use, and communication about use was collected. RESULTS: A total of 115 (58%) survivors reported using CAM in survivorship, 72% of which used biologically based therapies. The majority of therapies were used for relaxation and stress management (15%), referred for use by the parent (25%), reported as very effective (62%), and initiated 0 to 4 years after completion of cancer treatment (41%). Among CAM users, young adults used manipulative and body-based therapies [odds ratio (OR)=3.3; 95% confidence interval (CI), 1.4-7.8] and mind-body therapies (OR=2.8, 95% CI: 1.2-6.4) more than children. Use of mind-body therapies was associated with not attending religious services regularly (OR=2.4; P<0.01). Half (51%) of all CAM therapies were disclosed to the physician. CONCLUSIONS: Survivors of childhood cancer frequently use CAM for health promotion and mitigation of physical and psychological conditions. Clinicians should consider the role of CAM in the adoption of healthy lifestyles among this population.

Incidence, significance and natural history of persistent retrograde venous flow after varicocelectomy in children and adolescents: correlation with catch-up growth.

PURPOSE: Varying incidences and levels of persistent retrograde venous flow have been reported following adult and adolescent varicocelectomy but the significance remains unclear. We sought to determine the incidence and natural history of persistent flow and whether it had any effect on postoperative testicular catch-up growth. MATERIALS AND METHODS: We retrospectively analyzed pre-varicocelectomy and post-varicocelectomy Doppler duplex ultrasound findings. Peak retrograde venous flow, maximum vein diameter, flow quality and varicocele grade were recorded at each visit. Catch-up growth was defined as less than 15% testicular asymmetry at final visit. RESULTS: Of 330 patients (median age 15.4 years) undergoing varicocelectomy (laparoscopic in 247, open in 83) 145 had residual retrograde venous flow after Valsalva maneuver with a mean peak of 13.3 cm per second. Of 290 patients with repeat Doppler duplex ultrasound (median followup 2.6 years) 124 had initial peak retrograde venous flow less than 20 cm per second (43%) and only 17 (6%) had flow 20 cm per second or greater. Incidence of post-varicocelectomy retrograde venous flow at last visit (48%) was similar to that at initial postoperative visit (49%). Of 330 boys 20 had recurrence of palpable varicocele (grade 2 or 3), of whom 18 (90%) had initial retrograde venous flow. Catch-up growth was more likely in patients with no retrograde venous flow, and rates of catch-up growth decreased as peak retrograde venous flow increased. All 5 patients with initial testicular asymmetry and persistent retrograde venous flow at levels greater than 30 cm per second had continued testicular asymmetry (ie none had catch-up growth). CONCLUSIONS: Retrograde venous flow is frequently present after varicocelectomy and is almost always associated with peak retrograde venous flow rates significantly lower than those seen in patients who are recommended for initial varicocelectomy. Retrograde venous flow tends to persist during followup at stable peak retrograde venous flow rates. Palpable recurrence and persistent testicular asymmetry are most often associated with postoperative peak retrograde venous flow rates 20 cm per second or greater.

Outcomes of targeted treatment for vesicoureteral reflux in children with nonneurogenic lower urinary tract dysfunction.

PURPOSE: There is a known association between nonneurogenic lower urinary tract conditions and vesicoureteral reflux. Whether reflux is secondary to the lower urinary tract condition or coincidental is controversial. We determined the rate of reflux resolution in patients with lower urinary tract dysfunction using targeted treatment for the underlying condition. MATERIALS AND METHODS: Patients diagnosed and treated for a lower urinary tract condition who had concomitant vesicoureteral reflux at or near the time of diagnosis were included. Patients underwent targeted treatment and antibiotic prophylaxis, and reflux was monitored with voiding cystourethrography or videourodynamics. RESULTS: Vesicoureteral reflux was identified in 58 ureters in 36 females and 5 males with a mean age of 6.2 years. After a mean of 3.1 years of treatment reflux resolved with targeted treatment in 26 of 58 ureters (45%). All of these patients had a history of urinary tract infections before starting targeted treatment. Resolution rates of vesicoureteral reflux were similar for all reflux grades. Resolution or significant improvement of reflux was greater in the ureters of patients with dysfunctional voiding (70%) compared to those with idiopathic detrusor overactivity disorder (38%) or detrusor underutilization (40%). CONCLUSIONS: Vesicoureteral reflux associated with lower urinary tract conditions resolved with targeted treatment and antibiotic prophylaxis in 45% of ureters. Unlike the resolution rates reported in patients with reflux without a coexisting lower urinary tract condition, we found that there were no differences in resolution rates among grades I to V reflux in patients with lower urinary tract conditions. Patients with dysfunctional voiding had the most improvement and greatest resolution of reflux. Additionally grade V reflux resolved in some patients.

Proprotein convertase subtilisin/kexin type 9 potentially influences cholesterol uptake in macrophages and reverse cholesterol transport.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of low-density lipoprotein receptor (LDLRs) molecules expressed on the cell surface. Gene inactivation of PCSK9 reduces the areas of atherosclerotic lesions in mice, and the effect is mainly dependent on LDLRs. Furthermore, a positive relationship between PCSK9 and cholesterol accumulation in the wall of the aorta has been established. However, the mechanism remains unknown. As PCSK9 is mainly expressed in atherosclerotic plaque and in the liver, we hypothesize that PCSK9 might increase oxidized LDL uptake and impair macrophage-mediated reverse cholesterol transport, contributing to the development of atherosclerosis.

Intratesticular varicoceles: are they significant?

OBJECTIVE: Varicoceles occur in 15% of adult and adolescent males and are generally considered to be an extratesticular phenomenon. However, an intratesticular component has been reported in up to 2% of adult and 2% of adolescent varicoceles. We sought to determine the incidence of intratesticular varicoceles (ITV) in adolescents in our practice, its significance, associated findings and response to treatment. MATERIALS AND METHODS: We retrospectively reviewed 684 adolescent males who were diagnosed with varicoceles and had at least one Doppler ultrasound (DUS) prior to any surgery to identify those with an intratesticular component. Testicular volumes, maximum vein diameter (MVD) and peak retrograde flow (PRF) were determined by DUS and recorded. RESULTS: A total of 6 (0.9%) patients were found to have an intratesticular component with a mean PRF of 43.7 cm/s, mean MVD of 3.3 mm and mean asymmetry of 20%. Mean PRF, MVD, and asymmetry of those without an intratesticular component who underwent surgery was 44.8 cm/s, 2.9 mm, and 21.8%, respectively (PNS for all parameters). Four of the 6 patients had 2 or more DUS, and all 4 had worsening testicular asymmetry and PRF over time. Five patients underwent laparoscopic varicocelectomy and all five had catch-up testicular growth. One patient refused surgical repair and has had subsequent worsening testicular asymmetry and softening of the testicle. CONCLUSIONS: Our findings suggest that adolescents who present with an intratesticular varicocele in association with testicular asymmetry will develop worse asymmetry over time. Therefore, adolescents with intratesticular varicoceles and initial asymmetry should be scheduled for surgery rather than followed.

Observations on hydroceles following adolescent varicocelectomy.

PURPOSE: There is wide variation in the reported incidence of hydrocele after varicocelectomy (0% to 29%). We determined the incidence of hydroceles and hydrocelectomy following adolescent varicocelectomy, the time it took for them to manifest, and the results of aspiration and surgical correction. MATERIALS AND METHODS: Our adolescent varicocele registry was reviewed to identify patients with a post-varicocelectomy hydrocele. We evaluated physical examination and ultrasound findings, postoperative interval to development and treatment results. RESULTS: A total of 400 patients with at least 6 months of postoperative followup underwent 521 varicocelectomies (16 redo, 1 right, 104 bilateral) from 1987 to 2010. Mean followup was 32 months (range 6 to 182). Hydrocele was detected in 80 of 521 (15.4%) at a mean of 2 years after surgery. The incidence of hydrocele was higher in open vs laparoscopic (p <0.001), bilateral vs unilateral (p = 0.013), nonlymphatic sparing vs lymphatic sparing (p = 0.043) and Palomo vs laparoscopic nonlymphatic sparing (p = 0.001) procedures. Eight patients underwent aspiration for a large postoperative hydrocele. In all 8 patients fluid returned to pre-aspiration status. There were 29 patients (5.6%) who underwent Jaboulay bottleneck hydrocelectomy and none had recurrence. CONCLUSIONS: Hydroceles are a common sequela of varicocelectomy, with the fewest hydroceles occurring after laparoscopic lymphatic sparing varicocelectomy. Patients should be followed for at least 2 years after varicocelectomy to examine for the presence of hydroceles. Although there have been reports on the use of aspiration for post-varicocelectomy hydrocele, we have not had success in those with a single aspiration. Jaboulay bottleneck hydrocelectomy had a 100% success rate in this select group.