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Authors' Contributions 1.JF -Substantial contributions to acquisition, analysis and interpretation of data, drafting the work, final approval of the version to be published and agreement to be accountable for all aspects of the work. 2.AO -Substantial contributions to the conception and design of the work, analysis and interpretation of data, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 3.TP -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 4.SW -Substantial contributions to the conception and design of the work, analysis and interpretation of data, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 5.AL -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 6.NL -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 7.AB -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 8.RP -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 9.LK -Substantial revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 10.SG -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 11.IP -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 12.IQ -Substantial contributions to revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 13.RJ -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable ...

A B S T R A C T PurposeWe conducted a prospective trial to evaluate late effects in pediatric patients with low-grade glioma (LGG) treated with conformal radiation therapy (CRT). Patients and MethodsBetween August 1997 and August 2006, 78 pediatric patients with LGG (mean age, 9.7 years; standard deviation, Ϯ4.4 years) received 54 Gy of CRT with a 10-mm clinical target volume margin. Tumor locations were diencephalon (n ϭ 58), cerebral hemisphere (n ϭ 3), and cerebellum (n ϭ 17). Baseline and serial evaluations were performed to identify deficits in cognition, endocrine function, and hearing. Deficits were correlated with clinical factors and radiation dose within specific normal tissue volumes. ResultsCognitive effects of CRT through 5 years after CRT correlated with patient age, neurofibromatosis type 1 status, tumor location and volume, extent of resection, and radiation dose. The effect of age exceeded that of radiation dose; patients younger than 5 years experienced the greatest decline in cognition. Before CRT, growth hormone (GH) secretion abnormality was diagnosed in 24% of tested patients, and 12% had precocious puberty. The 10-year cumulative incidence of GH replacement was 48.9%; of thyroid hormone replacement, 64.0%; of glucocorticoid replacement, 19.2%; and of gonadotropin-releasing hormone analog therapy, 34.2%. The mean Ϯ standard errors of the cumulative incidence of hearing loss at 10 years did not exceed 5.7% Ϯ 3.3% at any frequency. ConclusionTo our knowledge, this is the largest series of prospectively followed children with LGG to undergo irradiation. Adverse effects are limited and predictable for most patients; however, this study provides additional evidence that CRT should be delayed for young patients and identifies the potential benefits of reducing radiation dose to normal brain.

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Background - Left bundle branch pacing (LBBP) is a novel pacing method and has been observed to have low and stable pacing thresholds in prior small short-term studies. The objective of this study was to evaluate the feasibility and safety of LBBP in a large consecutive diverse group of patients with long-term follow up. Methods - This study prospectively enrolled 632 consecutive pacemaker patients with attempted LBBP from April 2017 to July 2019. Pacing parameters, complications, ECG, and echocardiographic measurements were assessed at implant, and during follow-up of 1, 6, 12 and 24 months. Results - LBBP was successful in 618/632 (97.8%) patients according to strict criteria for LBB capture. Mean follow-up time was 18.6±6.7 months. 231 patients had follow-up over 2 years. LBB capture threshold at implant was 0.65±0.27 mV@0.5ms and 0.69±0.24 mV@0.5ms at 2-year follow-up. A significant decrease in QRS duration was observed in patients with LBBB (167.22 ± 18.99ms vs. 124.02 ± 24.15ms, p<0.001). Post implantation left ventricular ejection fraction improved in patients with QRS≥120ms (48.82±17.78 % vs. 58.12±13.04 %, p<0.001). The number of patients with moderate and severe tricuspid regurgitation decreased at 1-year. Permanent right bundle branch injury occurred in 55 (8.9%) patients. LBB capture threshold increased to more than 3 V or loss of bundle capture in 6 patients (1%), 2 patients of them had loss of conduction system capture. Two patients required lead revision due to dislodgement. Conclusions - This large observational study suggests that LBBP is feasible with high success rates and low complication rates during long term follow up. Therefore, LBBP appears to be a reliable method for physiological pacing for patients with either a bradycardia or heart failure pacing indication.

pHBP improved LVEF, LVESV and NYHA Class in patients with HF with typical LBBB.

Hypothalamic obesity is a devastating complication in children surviving brain tumors and/or cranial irradiation. These subjects are thought to exhibit autonomic dysregulation of the beta-cell, with insulin hypersecretion in response to oral glucose tolerance testing (OGTT). We report the results of a randomized, double-blind, placebo-controlled trial of octreotide therapy for pediatric hypothalamic obesity. Eighteen subjects [weight, 100.6 +/- 5.6 kg; body mass index (BMI), 37.1 +/- 1.3 kg/m(2)] received octreotide (5-15 microg/kg x d s.c.) or placebo for 6 months. With octreotide, Delta weight (mean +/- SEM) was +1.6 +/- 0.6 vs. +9.1 +/- 1.7 kg for placebo (P < 0.001). Delta BMI was -0.2 +/- 0.2 vs. +2.2 +/- 0.5 kg/m(2), respectively (P < 0.001). OGTT documented Delta insulin response (peak - basal) of -417 +/- 304 pM after octreotide vs. +216 +/- 215 pM after placebo (P = 0.034). Improvement in physical activity by parent report was noted with octreotide, but not placebo (P = 0.03). For the octreotide group, changes in quality of life positively correlated with changes in insulin response (P = 0.041). Complications and adverse events were mild and self-limited. These data demonstrate the beneficial effects of octreotide in pediatric hypothalamic obesity. Octreotide suppressed insulin, and stabilized weight and BMI. Improved quality of life correlated with the degree of insulin suppression. Octreotide was safe and well tolerated.