Median Z-score Research Articles

Evaluating perinatal and neonatal outcomes among children with vascular Ehlers-Danlos syndrome.

Birth outcomes data for patients with vascular Ehlers-Danlos syndrome (VEDS) are limited. Patients with a pathogenic or likely pathogenic COL3A1 variant were included. Outcomes included gestational age (GA), birthweight (BW), and maternal complications. Birth outcomes were first compared with that of US population data, then compared by sex, maternal affected status, and COL3A1 genotype. A total of 41 children were included (70.7% male), including 32 with high-risk (missense and splice site) variants. Preterm birth (<37 weeks) was more common in patients with VEDS than in the US population (48.8% vs 12.2%, P < .0001). Low BW (<2.5 kg) was also more common in patients with VEDS than in the US population (P < .0001), although, it was appropriate after GA adjustment (median GA-adjusted z-score 0.01 vs z-score 0.0, P= .26). No differences in GA or BW were observed by sex or maternal affected status. Those with high-risk variants were more likely to be born preterm than those with haploinsufficient variants, although this did not meet significance criteria (53% vs 33%, P=.35). Of the 6 affected mothers, 5 had perinatal complications. Preterm birth is more common in children with VEDS than in the general population. Maternal affected status is not associated with preterm birth, suggesting that risk is conferred by the fetal VEDS diagnosis alone.

A single-centre study on predictors and determinants of pubertal delay and growth impairment in Epidermolysis Bullosa.

BackgroundDelayed puberty is a possible complication of Epidermolysis Bullosa (EB), though the actual incidence is still unknown. In chronic illnesses delayed puberty should be correctly managed since, if untreated, can have detrimental effects on adult height attainment, peak bone mass achievement and psychological health.Aims and methodsThis is a single-centre study on pubertal development, growth and bone status in EB. Auxological, densitometric (areal Bone Mineral Density-aBMD Z-score, Bone Mineral Apparent Density-BMAD Z-score, Trabecular Bone Score-TBS and Bone Strain Index-BSI at Lumbar spine) and body composition data (Total Body DXA scans) were collected. Disease severity was defined according to Birmingham Epidermolysis Bullosa Severity (BEBS) score.ResultsTwenty-one patients (12 Recessive Dystrophic EB-RDEB, 3 Dominant Dystrophic EB, 3 Junctional EB-JEB, 2 EB Simplex and one Kindler EB) aged 13 years (females) or 14 years (males) and above were enrolled (age 16.2±2.5 years, M/F 11/10). Short stature was highly prevalent (57%, mean height -2.12±2.05 SDS) with 55% patients with height <-2SD their mid-parental height. 7/21 patients (33%, 6 RDEB and 1 JEB) had delayed puberty with a median BEBS of 50 (range 29 to 63), a height SDS of -2.59 SDS (range -5.95 to -2.22) and a median lumbar BMAD Z-score of -4.0 SDS (range -5.42 to -0.63 SDS). Pubertal status was negatively associated with BEBS, skin involvement, inflammatory state and positively with height SDS and BMI SDS.ConclusionsPubertal delay is highly prevalent in EB, especially in patients with RDEB and JEB, high severity score and inflammatory state. Moreover, pubertal delay worsens growth impairment and bone health. A study on pubertal induction is ongoing to enlighten possible beneficial effects on adult height attainment and peak bone mass accrual.

Vext - A Virtual Exercise Training Program For Pediatric Solid Organ Transplant Recipients: A Feasibility Study.

Pediatric solid organ transplant (SOT) recipients report lower strength and physical activity levels than their healthy peers. Virtual exercise programs may reduce barriers to exercise and allow for additional access to specialized care. PURPOSE: To determine the feasibility of an 8-week virtual exercise program (VEXT) in pediatric solid organ transplant recipients. METHODS: A strength-based program was designed by a clinical exercise physiologist (AD). A treadmill exercise stress test was completed prior to starting the program. Self-report surveys were used to assess quality of life (Pediatric Quality of Life Inventory, PedsQL), fatigue (Pediatric Quality of Life Multidimensional Fatigue Scale, PedsQL-Fatigue), and physical activity (Physical Activity Questionnaire for Children and Adolescents, PAQ-C/A) prior to and after completion of the program. The strength sub-test of the Bruininks-Oseretsky Test of Motor Proficiency (BOT-2) was administered virtually. Classes were conducted via Zoom (Zoom Video Communications Inc, San Jose, CA), 3 times per week for 30 minutes. Weekly engagement with the study team was provided by a web-based text messaging platform (WelTel Inc., Vancouver, BC). Medians (inter-quartile range, IQR) are reported. RESULTS: Baseline findings are reported for 12 participants (4 liver, 5 kidney, 3 heart SOT recipients; 58% females). The median age was 12 (11-14) years. PedsQL score was [69.57 (55.98-79.89); Normal: 85.66 ± 11.99]. PedsQL-Fatigue score was [66.67 (45.84-76.89); Normal: 82.19 ± 12.27]. PAQ-C/A score was [Females: 1.72 (1.27-2.11); Normal: 2.70 ± 0.63, Males: 2.87 (2.60-2.87); Normal: 3.01 ± 0.72]. The median strength subtest Z-score was -1.00 (-1.35 to -0.60). Exercise times for 10 of the participants who followed the BCCH protocol was 7.04 minutes [(5.68 - 8.86); Controls: 15.25 (13.82 - 16.75)]. The remaining 2 participants followed a modified protocol due to physical limitations. CONCLUSIONS: At baseline, pediatric SOT recipients report a lower quality of life, higher fatigue, and lower physical activity levels than healthy children. Eleven of twelve participants have a low strength score. A virtual exercise program may help to increase strength, increase physical activity levels and, in turn, may improve quality of life in these children.

1470P Transcriptomic signature and immune infiltrate in metastatic collecting duct renal cell carcinoma patients treated with first-line cabozantinib: Results of exploratory endpoints from BONSAI trial (Meeturo 2)

The prospective phase II BONSAI trial (n=25; NCT03354884) met its primary endpoint demonstrating cabozantinib effects in untreated metastatic collecting duct carcinoma (mCDC). We aimed at investigating if baseline mCDC transcriptome is associated with outcome and/or predictive immune signatures. FFPE samples from 18 mCDC patients from BONSAI trial were sequenced and the data processed with STAR and htseq. Globaltest and edgeR in R were used to assess the correlation between transcriptional and survival data, and GSVA to estimate variation of gene sets enrichment. Patients were divided into high and low groups based on the median gene expression z-score. A 22-gene signature (BONSAI) clusters patients into a first group (n=6) with increased expression of 19/22 genes (BONSAIhigh) and longer PFS and OS, and a second group (n=12) with opposite expression trend associated with disease progression. BONSAIhigh patients exhibit best response rate to cabozantinib, while no clear association with metastasis localization, tumor mutational burden and LOH state is observed. BONSAIhigh tumors display enrichment of the predictive “angiogenesis” and “T-cell immunity” IMmotion150 trial (McDermott 2018). Conversely tumors from BONSAIlow patients are enriched in CDC-specific gene signature (Gargiuli 2021), myeloid genes associated with therapy resistance and poor outcome, as well as specific immunosuppressive signature linked to myeloid derived suppressor cells (MDSC) activity in progressive clear-cell renal carcinoma (ccRCC; Rinchai 2021). mCDC is featured by a prognostic signature associating T cell immunity and angiogenesis with good clinical outcome and sensitivity to cabozantinib, differently from ccRCC. MDSC signatures linked with drug resistance and poor prognosis may warrant using myeloid-targeting drugs to achieve disease control. The study of blood MDSC of these patients is ongoing and will provide insights of role of MSDC in mCDC. A further validation of this signature will be performed in the ongoing CICERONE trial.

Outcome of humanitarian patients with late complete repair of tetralogy of Fallot: A 13-year long single-center experience

BackgroundSurgical repair of tetralogy of Fallot is usually performed between 3 and 6 months of age with pulmonary valve-sparing repair promoted for the best long-term result. Through a humanitarian program from developing countries, late complete surgical repair of tetralogy of Fallot has been performed at our institution for many years. MethodsRetrospective analysis of pre- and perioperative data, as well as 30-days outcome of patients older than one year with a confirmed diagnosis of tetralogy of Fallot who had a complete surgical repair between 2005 and 2018 at our institution. ResultsOne hundred sixty-five patients were included with a median age of 4.5 years [3.0–6.3], median weight of 13.5 kg [10.9 to 16.5], median transcutaneous oximetry of 78% [70 to 85] and median pulmonary valve annulus Z-score of −1.8 [-3.4 to −0.8]. There was no early surgical mortality. By multivariate analysis, only severe right ventricular hypertrophy, severe right ventricle outflow tract obstruction, and hypoplasia of the main pulmonary artery were independent predictors of failure to preserve the pulmonary annulus at surgical repair. ConclusionsLate complete surgical repair of tetralogy of Fallot has low mortality and morbidity even when pulmonary valve-sparing repair cannot be successfully performed. The preservation of the pulmonary valve function is significantly associated with shorter ventilation time, ICU and hospital lengths of stay. In the analyzed group of patients, a pulmonary valve-sparing repair cannot be predicted exclusively based on the dimension of the pulmonary valve annulus.

Short- and medium-term outcomes for patent ductus arteriosus stenting in neonates ≤2.5 kg with duct-dependent pulmonary circulation.

Morbidity with surgical systemic-to-pulmonary artery shunting (SPS) in infants ≤2.5 kg has remained high. Patent ductus arteriosus (PDA) stenting may be a valid alternative. The objective of this study isto evaluate outcomes following PDA stenting in patients ≤2.5 kg from four large tertiary centers. Retrospective review of all neonates ≤2.5 kg with duct-dependent pulmonary circulation who underwent PDA stenting. Procedural details, pulmonary arterial growth, reinterventions, surgery type, and outcomes were assessed. PDA stents were implanted in 37 of 38 patients attempted (18 female) at a median procedural weight of 2.2 kg (interquartile range[IQR], 2-2.4 kg). Seven patients (18%) had a genetic abnormality and 16 (42%) had associated comorbidities. The median intensive care unit stay was 4 days (IQR, 2-6.75 days), and the median hospital stay was 20 days (IQR, 16-57.25). One patient required a rescue shunt procedure, with three others requiring early SPS (<30 days postprocedure). Twenty patients (54%) required reintervention with either balloon angioplasty, restenting, or both. At 6-month follow-up, right pulmonary artery growth (median z-score -1.16 to 0.01, p = 0.05) was greater than the left pulmonary artery (median z-score -0.9 to -0.64, p = 0.35). Serious adverse effects (SAEs) were seen in 18% (N = 7) of our cohort. One patient developed an SAE during planned reintervention There were no intraprocedural deaths, with one early procedure-related mortality, and three interstage mortalities not directly related to PDA stenting. PDA stenting in infants ≤2.5 kg is feasible and effective, promoting pulmonary artery growth. Reintervention rates are relatively high, though many are planned to allow for optimal growth before a definitive operation.

Parallel transmit (pTx) with online pulse design for task-based fMRI at 7 T

PurposeParallel transmission (pTx) is an approach to improve image uniformity for ultra-high field imaging. In this study, we modified an echo planar imaging (EPI) sequence to design subject-specific pTx pulses online. We compared its performance against EPI with conventional circularly polarised (CP) pulses. MethodsWe compared the pTx-EPI and CP-EPI sequences in a short EPI acquisition protocol and for two different functional paradigms in six healthy volunteers (2 female, aged 23–36 years, mean age 29.2 years). We chose two paradigms that are typically affected by signal dropout at 7 T: a visual objects localiser to determine face/scene selective brain regions and a semantic-processing task. ResultsAcross all subjects, pTx-EPI improved whole-brain mean temporal signal-to-noise ratio (tSNR) by 11.0% compared to CP-EPI. We also compared the ability of pTx-EPI and CP-EPI to detect functional activation for three contrasts over the two paradigms: face > object and scene > object for the visual objects localiser and semantic association > pattern matching for the semantic-processing paradigm. Across all three contrasts, pTx-EPI showed higher median z-scores and detected more active voxels in relevant areas, as determined from previous 3 T studies. ConclusionWe have demonstrated a workflow for EPI acquisitions with online per-subject pulse calculations. We saw improved performance in both tSNR and functional acquisitions from pTx-EPI. Thus, we believe that online calculation pTx-EPI is robust enough for future fMRI studies, especially where activation is expected in brain areas liable to significant signal dropout.

Visual versus quantitative analysis of muscle ultrasound in neuromuscular disease.

Introduction/AimsVisual and quantitative muscle ultrasound are both valid diagnostic tools in neuromuscular diseases. To optimize muscle ultrasound evaluation and facilitate its use in neuromuscular disease, we examined the correlation between visual and quantitative muscle ultrasound analysis and their pitfalls.MethodsRetrospective data from 994 patients with 13,562 muscle ultrasound images were analyzed. Differences in echogenicity z‐score distribution per Heckmatt grade and corresponding correlation coefficients were calculated.ResultsOverall, there was a correlation of 0.60 between the two scoring systems, with a gradual increase in z‐score with increasing Heckmatt grades and vice versa. Patients with a neuromuscular disorder had higher Heckmatt grades (p < 0.001) and z‐scores (median z‐score = 0.30, p < 0.001) than patients without. The highest Heckmatt grades and z‐scores were found in patients with either a dystrophy or inflammatory myopathy (both median Heckmatt grade of 2 and median z score of 0.74 and 1.20, respectively). Discrepant scores were infrequent (<2%), but revealed important pitfalls in both grading systems.DiscussionVisual and quantitative muscle ultrasound are complementary techniques to evaluate neuromuscular disease and have a moderate positive correlation. Importantly, we identified specific pitfalls for visual and quantitative muscle ultrasound and how to overcome them in clinical practice.

Physical Fitness and Frailty in Males after Allogeneic Hematopoietic Stem Cell Transplantation in Childhood: A Long-Term Follow-Up Study.

Simple SummaryThe prevalence of frailty is increased among young adult childhood cancer survivors and is associated with early morbidity and mortality. The aim of our study was to analyze physical fitness, physical activity and the prevalence of frailty in male long-term survivors of pediatric allogeneic hematopoietic stem cell transplantation. We observed significantly lower muscle strength and muscle endurance in the hand-grip and sit-to-stand tests compared to the age and sex matched normative reference values of the tests. Furthermore, 30% of the survivors were considered pre-frail or frail. Chronic graft-versus-host disease, shorter stature, higher body fat mass and hazardous drinking predicted prefrail/frail status. Common cardiovascular risk factors were associated with poor physical fitness and low physical activity level. These results indicate a need for cardiometabolic follow up as well as health education in the decades following HSCT.Purpose and methods: To analyze physical fitness, physical activity and the prevalence of frailty in male long-term survivors of pediatric allogeneic hematopoietic stem cell transplantation (HSCT). We performed a Nordic two-center study of 98 male survivors (mean age 28.7 years, range 18.5–47.0) treated with pediatric allogeneic hematopoietic stem cell transplantation (HSCT) 1980–2010 in denmark or finland. physical fitness was evaluated by the dominant hand grip-strength, timed up-and-go, sit-to-stand, gait speed and two-minute walk tests. Results: Survivors presented significantly lower muscle strength and muscle endurance in the dominant hand-grip strength (median Z-score −0.7, range −4.3–3.9) and sit-to-stand tests (median Z-score −1.5, range −3.5–2.5) compared to age and sex matched normative values of the tests. However, mobility and gait speed were not affected on a group level. The prevalence of frailty (pre-frail 20% or frail 10%) was high among the survivors. In multiple regression analysis, chronic graft-versus-host disease, shorter stature, higher body fat mass and hazardous drinking predicted prefrail/frail status. Common cardiovascular risk factors, such as increased levels of serum triglycerides, higher resting heart rate and diastolic blood pressure, were associated with lower physical fitness. Conclusion: Low muscle strength and a high incidence of frailty were observed in survivors of pediatric HSCT. There is a predominant risk of cardiovascular and metabolic diseases in the long-term.

Evolution of Pulmonary Valve Management During Repair of Tetralogy of Fallot: A 14-year Experience

BackgroundThe optimal repair strategy for tetralogy of Fallot remains controversial. This report presents a 14-year evolution of management of the pulmonary valve (PV) from transannular patch to valve-sparing repair to neovalve creation using living right atrial appendage tissue. MethodsA retrospective review of 172 consecutive patients undergoing complete repair for TOF between January 2007 and June 2021 was performed. Clinical and follow-up data were analyzed by repair group. Neopulmonary valve (NPV) creation using right atrial appendage tissue was introduced in 2019. Failure of valve-sparing repair was defined as needing reintervention for recurrent right ventricular outflow tract obstruction (RVOTO). ResultsMedian age and weight at repair were 4.9 months and 6 kg, respectively. Median preoperative PV size and z-score were 6.4 mm (5.2-8.3 mm) and −3.2 (−4.1 to −2.1), respectively. Patients who underwent valve-sparing repair had larger PV size and z-score compared with patients who underwent transannular patch procedures (8 mm vs 5.6 mm; −2.1 vs −3.2; both P < .001). There were no hospital mortalities. Overall follow-up was 44 months. At last follow-up, 10% of patients who underwent valve-sparing repair had repeat intervention for recurrent RVOTO. Patients who had failed valve-sparing repair had significantly lower PV z-scores (−2.6 vs −1.9; P = .01). An NPV was used in 8 patients with a median PV z-score of −4 (−4.7 to −3.9). At 6 months, 6 patients (75%) had mild or trivial pulmonary insufficiency after NPV placement. ConclusionsRepair of tetralogy of Fallot is a safe operation with excellent outcomes. Valve-sparing repair avoids right ventricular dilation but may fail for RVOTO at a PV z-score <−2. NPV creation offers an alternative option in patients with a small PV.

Single-stage off-pump repair of coarctation of the aorta and ventricular septal defects in children.

OBJECTIVESThe appropriate approach for surgical repair of coarctation of the aorta with a ventricular septal defect (VSD) remains controversial. This study evaluated the outcomes of primary repair of VSDs with periventricular device closure without cardiopulmonary bypass through a left thoracotomy in patients without arch hypoplasia.METHODSWe selected 21 patients aged <1 year, including 7 neonates, who underwent repair of coarctation of the aorta with periventricular device closure of a VSD.RESULTSThe median occluder size was 6 (range, 5–8) mm. The median mechanical ventilation time was 14 (range, 2–68) h, and the median duration of hospital stay was 11 (range, 7–16) days. No reoperations were required to correct VSD shunting, and the median residual shunt size was 1 (range, 1–2) mm. The median follow-up period was 13 (range, 4–31) months. No late deaths were reported, and no haemodynamically significant pressure gradient at the anastomotic site was observed. The median distal aortic arch z-score was 0.39 (range, −0.1–to 0.9). Only 1 patient had a permanent pacemaker implanted towards the end of the follow-up period.CONCLUSIONSPeriventricular device closure can be used safely for closure of VSD in children with coarctation of the aorta without a hypoplastic aortic arch, even in neonates, to reduce the risk of prolonged cardiopulmonary bypass. This hybrid approach can be performed with a low incidence of rhythm disturbances and residual shunting. However, a meticulous assessment of the VSD anatomy is essential to avoid any unfavourable events.

A comparison of nutritional status in patients with neuroblastoma in Rwanda and United Kingdom: a cross-sectional observational study conducted by the OxPLORE collaboration

BackgroundCancer is a major global health concern and a leading cause of death in paediatric populations worldwide. Malnutrition contributes to a poor prognosis and remains the most common comorbidity leading to death in children with cancer. This retrospective study was developed through Oxford Paediatrics Linking Oncology Research with Electives (OxPLORE)—a medical student-led collaboration of paediatric surgeons and oncologists from low- and middle-income (LMIC) and high-income (HIC) countries. The aim of this study was twofold; firstly, to investigate the nutritional status and outcomes of neuroblastoma paediatric patients in two OxPLORE centres. Secondly, to facilitate the development of research skills of medical students as part of the OxPLORE initiative.ResultsNine neuroblastoma patients were identified (YY, n = 4, XX, n = 5) over the study period. Nutritional status was poorer in YY patients (median z-score − 1.57 cf. − 0.7, t = 1.16, p = 0.28), which correlated with poorer survival in the YY cohort (75%), as compared to the XX cohort (100%). YY patients were older at presentation than the XX cohort (57 cf. 13 months, t = 1.959 p = 0.09). Further, tumour presentation was at a later stage in the YY group (75% stage IV).ConclusionThis collaboration has shown a correlation in disparities in nutritional status and outcome of neuroblastoma in paediatric populations in YY and XX. These findings can inform institutional quality improvement. Further, this pilot study has highlighted the potential for medical students to undertake international research collaborations.

Efficacy and safety of recombinant human growth hormone therapy in pediatric intestinal transplant recipients.

Recombinant human growth hormone (rhGH) is widely used to treat growth retardation in children. We aimed to examine the effect of rhGH therapy on growth and its impact on allograft function in children with growth retardation after intestinal transplant (IT). We retrospectively included children younger than 19 years who had received an IT with or without the liver, were diagnosed with growth retardation, and have received rhGH between January 2010 and January 2021. Changes in the patient's anthropometric parameters between baseline and various time points were compared using the paired t-test or Wilcoxon signed-rank test, as appropriate. Seven patients (all males and prepubertal) received rhGH for the median duration of 2.3 years. The median age at rhGH start was 9.5 years. The median growth velocity z-score improved from -0.95 before treatment to 2.3 (p= .04) and 1.9 (p= .06) after 1 and 2 years of treatment, respectively. The median height-for-age z-score significantly improved from -3.4 at rhGH start to -1.3 (p= .005) at rhGH stop and remained above baseline at the last visit (-2.4, p= .002). The change in the first-year growth velocity was negatively correlated with the change in the second-year growth velocity (r= -.90, p= .04). No serious adverse effects or worsening allograft function were observed. Severely growth retarded children after IT could benefit from rhGH treatment. A larger, longitudinal study would be warranted to monitor the long-term effect and safety of rhGH and examine predictors of growth response to rhGH therapy in these pediatric IT recipients.

Technique of Coronary Button Transfer Has no Impact on Neoaortic Root Size in Simple Transposition

We studied the effect of various coronary transfer techniques (CTT) on neo-aortic root size after an arterial switch operation (ASO) in simple transposition by excluding the impact of recognized predisposing factors. One hundred and seventy-eight patients with simple transposition were reviewed retrospectively (January 2004-December 2018) and grouped as Punch Hole (n=83/178), Nonpunch Hole (n=65/178; Trapdoor or Standard) and Mixed (n=30/178). Factors predicting the neo-aortic root z-scores- annulus, mid-sinus, and sinotubular junction (STJ) were analyzed by uni/multivariable linear regression. Follow-up was 6 years, Interquartile range (IQR) 3.4,10.6. Preoperative aortic (7.4 mm, IQR 6.9,8) and pulmonary annulus (7.5 mm, IQR 6.8,8.1) sizes were identical (P=0.831). The changes in preoperative, postoperative, and latest median z-scores for neo-aortic annulus (-0.2, IQR -1.2,0.9; 0.0, IQR -0.9,0.9; 0.9, IQR -0.4,2.6; P < 0.001), mid-sinus (1.1, IQR-0.1,2; 2.6, IQR 1.6,3.7; 2.9, IQR 1.8,4.3; P < 0.001) and STJ (-0.1, IQR -0.8,1.1; 2.1, IQR 0.7,3; 2.4, IQR 1,3.5; P < 0.001) were significant. On multivariate analysis, preoperative pulmonary annulus z-score predicted the latest neo-aortic annulus z-score [Beta estimate (BE)=0.32, 95% confidence interval (CI)=0.03,0.62; P=0.03] and STJ z-score (BE= 0.45, 95% CI= 0.20,0.70; P < 0.0001). CTT did not predict any of the latest neo-aortic z-scores (all P > 0.05). Mild plus neo-aortic regurgitation (neoAR) was not significantly different across CTT groups [punch hole 20% (n=15/74), mixed 37% (n=11/30), nonpunch hole 21% (n=13/62); Fisher-exact P=0.186], one patient required valve replacement for severe neoAR. The neo-aortic root enlarges significantly over time at all 3 levels following an ASO in simple transposition, however, this is not significantly influenced by the CTT utilized.

Clinical Features and Natural History of Preadolescent Nonsyndromic Hypertrophic Cardiomyopathy

BackgroundUp to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized. ObjectivesThe aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years. MethodsData from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years. ResultsAt baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age. ConclusionsEarly-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages.

MP46-10 ELUCIDATING THERAPEUTIC OPTIONS FOR TREATMENT-NAÏVE AND CISPLATIN-RESISTANT TESTICULAR CANCER

You have accessJournal of UrologyCME1 May 2022MP46-10 ELUCIDATING THERAPEUTIC OPTIONS FOR TREATMENT-NAÏVE AND CISPLATIN-RESISTANT TESTICULAR CANCER Julie-Ann Cavallo, Daniel Ranti, Elliot Merritt, Anna Tocheva, John P. Sfakianos, and Benjamin Hopkins Julie-Ann CavalloJulie-Ann Cavallo More articles by this author , Daniel RantiDaniel Ranti More articles by this author , Elliot MerrittElliot Merritt More articles by this author , Anna TochevaAnna Tocheva More articles by this author , John P. SfakianosJohn P. Sfakianos More articles by this author , and Benjamin HopkinsBenjamin Hopkins More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002612.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Platinum-based chemotherapy is the standard of care (SOC) for patients with advanced testicular cancer (TC). However, outcomes for platinum-refractory tumors remain poor. This project seeks to use functional diagnostic approach to both predict therapeutic response for patients with testicular cancer and evaluate the utility of alternate therapeutic strategies that may improve responses for patients with platinum-refractory disease. METHODS: Using an IRB-approved protocol, we obtained tissue from platinum-sensitive and -resistant TC patients. Tissue specimens were obtained from 13 tumors: 10 primary, 2 post-treatment, and 1 lymph node. To functionally model therapeutic responses for patients with TC, we used our RAPiDS (Rapid Assessment of Patient Drug Sensitivity) screens on primary patient-derived organoids (PDOs) to stratify patient response to SOC therapies and evaluate the relative sensitivity of the tumors to alternative therapeutic regimens. For these studies, we conducted screens with nine therapeutics in a clinically relevant range of concentrations to extract correlative drug response data within two weeks from dissociation. RESULTS: Using the RAPiDS protocol, we developed and evaluated drug sensitivities in five PDOs (Figure 1A). Normalized luminescence from Cell-TiterGlo cell viability assays were used to determine Area Under the Curve (AUC) as a function of drug concentration (Figure 1A and B). Heatmaps show the median centered z-score for these AUC values across the therapeutics screened in each patient to gauge relative sensitivity (Figure 1A). All of our screened TC cases showed sensitivity to one or more alternative therapies tested, regardless of PDO response to first- or second-line SOC (Figure 1B). CONCLUSIONS: This data suggests that RAPiDS could be used on TC PDOs to help guide the selection of treatment options within clinically relevant timelines, which has the potential to be useful, especially in metastatic and rare cancer settings where therapeutic options are limited. Additionally, we are currently investigating the utility of RAPiDS in refractory and metastatic TC. Source of Funding: Mount Sinai School of Medicine seed funds © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e776 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Julie-Ann Cavallo More articles by this author Daniel Ranti More articles by this author Elliot Merritt More articles by this author Anna Tocheva More articles by this author John P. Sfakianos More articles by this author Benjamin Hopkins More articles by this author Expand All Advertisement PDF DownloadLoading ...

Hypertension: An Important but Reversible Cause of Systolic Dysfunction in Pediatrics

<h3>Purpose</h3> Cardiac dysfunction due to hypertension (CDHTN) in pediatrics is not well described. The purpose of the study is to describe the presentation and outcomes of pediatric CDHTN. <h3>Methods</h3> Patients ≤ 21 years with CDHTN between January 2005 and September 2020 at our institution were reviewed. Inclusion criteria were systolic dysfunction (shortening fraction (SF) <28% or ejection fraction <50%) without another cause of dysfunction, blood pressure (BP) >95th %ile for age and height within 3 months of diagnosis and physician judgment that dysfunction was secondary to hypertension. Demographics, clinical characteristics, echocardiographic findings and outcomes were described and examined using Chi-squared and Wilcoxon rank-sum tests. <h3>Results</h3> There were 34 patients included, with median age 10.9 (IQR 0.3-17.0) years. Due to a bimodal age distribution, patients were divided into groups <1 year (n=12) and >1 year (n=22) for outcome analysis. Causes of hypertension included medical renal disease (n=20, 59%), renovascular disease (n=6, 17%), essential (n=5, 15%), multifactorial (n=2, 6%) and medication effect (n=1, 3%). Peak systolic and diastolic BP at diagnosis was >99th %ile in 97% and 68% of patients, respectively. Echocardiography demonstrated mild LV dilation (median LV end diastolic z-score 2.6) and mild LV hypertrophy (median LV mass z-score 2.3). Patients were often symptomatic at diagnosis (n=21, 62%) and required admission (n=28, 82%), but a minority required intubation (n=9, 26%) or inotropic support (n=15, 44%). No patients received mechanical circulatory support (MCS), and only one patient was listed for transplant. Survival was high (n=33, 97%) over 3.5 (IQR 2.0-6.3) years follow up. Despite a trend toward worse function at diagnosis (SF 19% vs 23%, p=0.07), patients <1 year had shorter duration of dysfunction (12 vs 218 days, p=0.003) and better function at last follow up (SF 36% vs 29%, p=0.002). Overall, 92% of infants and 68% of older patients had resolution of systolic dysfunction. <h3>Conclusion</h3> Hypertension is an important cause of systolic dysfunction with a bimodal age distribution in children. Outcomes are favorable with low mortality and a high proportion of patients with resolution of systolic dysfunction, particularly those <1 year. Identification of hypertension as the cause of dysfunction is vital, as these patients do not often require MCS or transplantation.

Right Ventricular Outflow Tract Stenting as the First Option for Palliation of Neonates with Severe Tetralogy of Fallot

Background: Neonates with Tetralogy of Fallot (TOF) might be prostaglandin dependent and cannot be discharged from the hospital except after complete correction or palliation. Palliation could be achieved by modified Blalock-Taussig Shunt (BTS), ductal stenting, or right ventricular outflow tract (RVOT) stenting. Objective: The objective of this study was to present our experience of palliating neonates with severe TOF who require augmentation of the pulmonary blood flow by RVOT stenting. Methods: This study was conducted on a series of patients who had RVOT stenting in PSCC-Qassim, Saudi Arabia, from August 2016 till December 2019. Cases that had RVOT stenting are included. The patient's clinical data, echocardiography, cardiac catheterization, and follow-up data were recorded. Data were analyzed using The Microsoft Excel data analysis tool. Results: During the study period, four consecutive patients with a diagnosis of TOF with significant cyanosis underwent RVOT stenting. The mean age and weight were 2.8±1.7 days and 2.9±0.1 kg respectively. All were on prostaglandin infusion before the intervention. The mean saturation before and after RVOT stenting was 63% (±11%) and 82% (±4%) respectively (p = 0.018). One patient required RVOT stent dilatation after 4 months. All patients are alive and had complete TOF repair at a median age of 6.5 months (range 6 to 12 months). The median follow-up period is 13 months. The median branch PAs diameter and Z-score before RVOT stenting and immediately before complete TOF repair were 2.8 mm (Z score: -2.5) and 5.5 mm (Z score: -0.5 to -1.16) respectively (p = 0.001). Conclusion: RVOT stenting is a reasonable alternative palliation for patients with severe TOF. The technique of stent deployment in the RVOT is challenging and requires pre-intervention planning and discussion. Using soft catheters, coronary wires, and the premounted coronary stents facilitate crossing of the RVOT and pulmonary valve and then stent deploymen

Nutrient Intake with Early Progressive Enteral Feeding and Growth of Very Low-Birth-Weight Newborns.

Early nutrition is one of the most modifiable factors influencing postnatal growth. Optimal nutrient intakes for very preterm infants remain unknown, and poor postnatal growth is common in this population. The aim of this study was to assess nutrient intake during the first 4 weeks of life with early progressive enteral feeding and its impact on the in-hospital growth of very low-birth-weight (VLBW) infants. In total, 120 infants with birth weights below 1500 g and gestational ages below 35 weeks were included in the study. Nutrient intakes were assessed daily for the first 28 days. Growth was measured weekly until discharge. Median time of parenteral nutrition support was 6 days. Target enteral nutrient and energy intake were reached at day 10 of life, and remained stable until day 28, with slowly declining protein intake. Median z-scores at discharge were −0.73, −0.49, and −0.31 for weight, length, and head circumference, respectively. Extrauterine growth restriction was observed in 30.3% of the whole cohort. Protein, carbohydrates, and energy intakes correlated positively with weight gain and head circumference growth. Early progressive enteral feeding with human milk is well tolerated in VLBW infants. Target enteral nutrient intake may be reached early and improve in-hospital growth.

Changes in body mass index, weight, and height in children with acute myeloid leukemia and the associations with outcome

AbstractLittle is known about body composition changes in patients with acute myeloid leukemia (AML) during and after treatment or their associations with outcomes. Z-scores for body mass index (BMI), weight, and height at diagnosis, their longitudinal changes from diagnosis to 5 years off therapy, and their associations with adverse effects and outcomes were evaluated in 227 pediatric patients with AML enrolled in the AML02 and AML08 trials at St. Jude Children's Research Hospital between 2002-2017. The median Z-scores for baseline weight, height, and BMI were 0.193, 0.209, and 0.170, respectively, and those for weight and height decreased significantly during therapy to −0.038 and −0.163, respectively, at off-therapy (P < .001 for both). At 5 years off therapy, the Z-scores for weight and BMI had increased significantly to 0.492 (P = .003) and 0.911 (P < .001), respectively, whereas the height Z-score remained significantly lower at −0.066 (P < .001) compared with baseline. The height Z-score of transplant recipients decreased further from −0.211 at transplant to −0.617 12 months later (P < .001). Baseline BMI category and Z-score were not associated with outcomes, but higher weight Z-scores were associated with lower incidences of refractory or relapsed disease (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.67-0.99) and higher incidences of death in remission (HR, 1.31; 95% CI, 1.01-1.70). Furthermore, weight Z-score decrease during induction therapy was associated with gastrointestinal, hepatic, and infection toxicities during subsequent therapy and with death in remission (HR, 2.66; 95% CI, 1.11-6.45). Multidisciplinary monitoring for weight changes and short stature is required from diagnosis to the off-therapy period.