Search

Vishal Madaan, Venkata Kolli, Durga P Bestha, Manan J ShahDepartment of Psychiatry and Neurobehavioral Sciences, Division of Child and Family Psychiatry, University of Virginia Health System, Charlottesville, VA, USAAbstract: Lisdexamfetamine (LDX) has been a recent addition to the treatment armamentarium for Attention Deficit Hyperactivity Disorder (ADHD). It is unique among stimulants as it is a prodrug, and has been found to be safe and well-tolerated medication in children older than 6 years, adolescents and adults. It has a smooth onset of action, exerts its action up to 13 hours and may have less rebound symptoms. LDX has proven to be effective in the treatment of ADHD in placebo controlled trials, and improved performance in simulated academic and work environments have been noticed. Both stimulant naïve and stimulant-exposed patients with ADHD appear to benefit from LDX. It has also shown some promise in improving emotional expression and executive function of patients with ADHD. Adverse effects such as decrease in sleep, loss of appetite and others have been reported with LDX use, just as with other stimulant formulations. Since most such studies exclude subjects with preexisting cardiac morbidity, prescribing precautions should be taken with LDX in such subjects, as with any other stimulant. Study subjects on LDX have been reported to have low scores on drug likability scales, even with intravenous use; as a result, LDX may have somewhat less potential for abuse and diversion. There is a need for future studies comparing other long acting stimulants with LDX in ADHD; in fact clinical trials comparing LDX with OROS (osmotic controlled-release oral delivery system) methylphenidate are currently underway. Furthermore, the utility of this medication in other psychiatric disorders and beyond ADHD is being investigated.Keywords: lisdexamfetamine, ADHD, functional impairment, pharmacotherapy

A 1-year-old child weighing 8 kg with familial congenital junctional ectopic tachycardia that was difficult to treat with antiarrhythmic medications underwent successful cryoablation with preservation of atrioventricular (AV) nodal function. This report describes a strategy of cryoablation in conjunction with a 3-D mapping system and the use of atrial overdrive pacing during cryothermal application to assess AV nodal function. [ABSTRACT FROM AUTHOR]

Various techniques and electrode catheters have been developed for effective and safe temporary transvenous cardiac pacing. In neonates and children, lead dislodgment and myocardial perforation have been attendant risks with passive fixation leads. We report our experience with the recently introduced Medtronic 6416 active fixation bipolar lead in a small group of children. Between January 2000 and February 2002, 4 children (2 boys, 2 girls) underwent temporary transvenous pacing with the Medtronic 6416 lead. The median age at implantation was 4.25 years (range: 5 days-13 years), median weight was 14.5 kg (range: 2.5 kg-54 kg) and the median duration of temporary pacing was 19.5 days (range: 5-38 days). The indication for temporary pacing was AV block (n = 2), sinus arrest (n = 1) and sinus node dysfunction (n = 1). The acute pacing threshold was <1.5 mA with no significant rise in the follow-up period. The venous access for lead placement was femoral vein (n = 2), internal jugular vein (n = 1), and subclavian vein (n = 1). There were no complications related to implantation or in the follow-up period. The Medtronic 6416 lead appears to be a safe and effective tool in temporary transvenous pacing in neonates and children. [ABSTRACT FROM AUTHOR]

The rapid growth in consumer-facing mobile and sensor technologies has created tremendous opportunities for patient-driven personalized health management. The diagnosis and management of cardiac arrhythmias are particularly well suited to benefit from these easily accessible consumer health technologies. In particular, smartphone-based and wrist-worn wearable electrocardiogram (ECG) and photoplethysmography (PPG) technology can facilitate relatively inexpensive, long-term rhythm monitoring. Here we review the practical utility of the currently available and emerging mobile health technologies relevant to cardiac arrhythmia care. We discuss the applications of these tools, which vary with respect to diagnostic performance, target populations, and indications. We also highlight that requirements for successful integration into clinical practice require adaptations to regulatory approval, data management, electronic medical record integration, quality oversight, and efforts to minimize the additional burden to health care professionals., (© 2024. The Author(s).)

Background and Objectives: Spinal cerebrospinal fluid (CSF) leaks may cause a myriad of clinical symptoms, the most common being orthostatic headache. Lateral leaks (Type II) and direct CSF-venous fistulas (Type III) are a subgroup of spinal CSF leaks, representing about 1/3 of spinal CSF leaks. This study aimed to analyze the risk and efficacy of nerve root clipping in patients with Type II and Type III CSF leaks., Methods: All consecutive patients with Type II and Type III CSF fistulas treated with nerve root clipping at our institution from May 2018 to December 2022 were included. Patients were evaluated for postoperative sensory motor deficits and neuropathic pain using the "Douleur Neuropathique 4" questionnaire, and the outcome was evaluated using the "Patient Global Impression of Change" and the return-to-work rate., Results: A total of 40 patients were included, and the mean follow-up time was 22 months. According to the Patient Global Impression of Change, significant symptoms improvement was reported in 85% of patients. Over 87% of patients returned to work fully or partially. One patient experienced a low-grade motor deficit after T1-nerve root clipping. 2.5% of patients developed postoperative neuropathic pain requiring medical treatment under which they fully improved. Over 80% of patients developed dermatomal hypoesthesia, with no reported effect on quality of life., Conclusion: The surgical strategy of noneloquent nerve root clipping shows favorable outcomes and return-to-work rates. There are instances of neuropathic pain and dermatomal hypoesthesia with no significant morbidity. Despite the favorable outcome and low recurrence rate, nerve root-sparing surgical techniques should be further explored., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Congress of Neurological Surgeons.)

Introduction: Patients with spontaneous intracranial hypotension (SIH) frequently present with several symptoms and impaired mental health. This study systematically investigates the somatic and mental symptom burden of SIH and the effect of surgical treatment., Methods: In this single-center retrospective study, patients with surgical closure of a spinal cerebrospinal fluid leak between September 2022 and July 2023 completed the Somatic Symptom Scale (SSS-8), the Somatic Symptom Disorder - B Criteria Scale (SSD-12), and the Patient Health Questionnaire (PHQ-8) preoperatively and three and 6 months postoperatively., Results: Fifty-seven patients were included. All three scores showed clearly pathological values before surgery (SSS-8: 12 [IQR 6.5-16], SSD-12: 26 [IQR 19.5-33.5], PHQ-8: 11 [IQR 6.5-15]) representing a high somatic symptom burden and relevant current depression. After surgery, there was a significant and sustainable improvement (SSS-8: 8 [IQR 3-11.75], SSD-12: 12.5 [IQR 5-21.75], PHQ-8: 4.5 [IQR 2-9], p  < 0.001, respectively) that exceeded the minimal clinically important difference for every score., Conclusion: SIH presents with high somatic and mental symptom burden. Surgical treatment leads to a relevant improvement of somatic and depressive symptoms. However, even after surgical success some patients still exhibit elevated depressive scores. Depressive symptoms might be added to the typical symptomatology of SIH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Volz, Lahmann, Wolf, Fung, Shah, Lützen, Urbach, Zander, Beck and El Rahal.)

Background: Implantable cardioverter-defibrillators last longer, and interest in reliable leads with targeted lead placement is growing. The OmniaSecure defibrillation lead is a novel, small-diameter, catheter-delivered lead designed for targeted placement, based on the established SelectSecure SureScan MRI Model 3830 lumenless pacing lead platform., Objective: This trial assessed safety and efficacy of the OmniaSecure defibrillation lead., Methods: The worldwide LEADR pivotal clinical trial enrolled patients indicated for de novo implantation of a primary or secondary prevention implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator, all of whom received the study lead. The primary efficacy end point was successful defibrillation at implantation per protocol. The primary safety end point was freedom from study lead-related major complications at 6 months. The primary efficacy and safety objectives were met if the lower bound of the 2-sided 95% credible interval was >88% and >90%, respectively., Results: In total, 643 patients successfully received the study lead, and 505 patients have completed 12-month follow-up. The lead was placed in the desired right ventricular location in 99.5% of patients. Defibrillation testing at implantation was completed in 119 patients, with success in 97.5%. The Kaplan-Meier estimated freedom from study lead-related major complications was 97.1% at 6 and 12 months. The trial exceeded the primary efficacy and safety objective thresholds. There were zero study lead fractures and electrical performance was stable throughout the mean follow-up of 12.7 ± 4.8 months (mean ± SD)., Conclusion: The OmniaSecure lead exceeded prespecified primary end point performance goals for safety and efficacy, demonstrating high defibrillation success and a low occurrence of lead-related major complications with zero lead fractures., Competing Interests: Disclosures G.H.C.: speaker at Medtronic and Philips; consultant for Medtronic and Boston Scientific. P.S.: reports having served on the advisory boards of Medtronic, Abbott, Boston Scientific, PaceMate, and CathRx; the University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic, Abbott, and Boston Scientific; and the University of Adelaide has received on his behalf research funding from Medtronic, Abbott, Boston Scientific, and Becton-Dickson. B.H.: reports funding from Medtronic and CVRx. P.D.F.: consultant fees and travel support from Medtronic, Boston Scientific, Abbott, and Biotronik as well as honoraria and advisory board participation for Medtronic, Abbott, and Biotronik. M.J.S.: consultant for Medtronic and Tenaya Therapeutics. M.S.: speaker honorarium from Medtronic Japan and financial endowments to our clinical research division from Biotronik Japan, Medtronic Japan, Boston Scientific Japan, and Abbott Japan. S.K.K.: member of the speakers bureau for Bayer/Schering Pharma, Boston Scientific, Medtronic, and Pfizer; speaker fees, honoraria, consultancy, advisory board fees, investigator, committee member for Novartis, Medtronic, Boehringer-Ingelheim, Boston Scientific, and Bayer. T.D.R.: consultant for Medtronic, Johnson and Johnson, and Philips; research funding from Medtronic and Abbott. F.P.: speaker at Medtronic and Boston Scientific; consultant for Medtronic and Boston Scientific; research funding from Medtronic and Boston Scientific. J.S.Z.: consultant for Medtronic. H.F.T.: consultant and speaker fee and research grant from Abbott, BMS/Pfizer, Bayer, Boehringer Ingelheim, Boston Scientific, Daiichi-Sankyo, Medtronic, and Sanofi. D.P.S.: institutional funding from Medtronic. C.S.: received scientific grants from Medtronic. R.K.P.: reports that Canberra Heart Rhythm Foundation has received on his behalf lecture and/or consulting fees from Medtronic, Abbott Medical, Boston Scientific, and Biotronik. G.M.: received honoraria from Medtronic. J.S.C.: consultant for Medronic, Biosense Webster, and Boston Scientific. B.T.: honorarium from Boston scientific. M.B.W.: consultant for Medtronic. B.M.R.: consultant for Medtronic. X.H.: consultant for Medtronic. B.B.: consultant for Medtronic. R.C., M.L.P., A.K.H., T.G, and A.E.T.: employees of Medtronic, Inc. P.K.M.: consultant for Medtronic, Boston Scientific, and Cook as well as honoraria from Medtronic and Cook., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Youth and adult participation in sports continues to increase, and athletes may be diagnosed with potentially arrhythmogenic cardiac conditions. This international multidisciplinary document is intended to guide electrophysiologists, sports cardiologists, and associated health care team members in the diagnosis, treatment, and management of arrhythmic conditions in the athlete with the goal of facilitating return to sport and avoiding the harm caused by restriction. Expert, disease-specific risk assessment in the context of athlete symptoms and diagnoses is emphasized throughout the document. After appropriate risk assessment, management of arrhythmias geared toward return to play when possible is addressed. Other topics include shared decision-making and emergency action planning. The goal of this document is to provide evidence-based recommendations impacting all areas in the care of athletes with arrhythmic conditions. Areas in need of further study are also discussed., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Selection of radiofrequency ablation (RF) or cryoablation (Cryo) for atrioventricular nodal re-entrant tachycardia (AVNRT) in children remains controversial due to a lack of contemporary comparison studies in this population., Objectives: This study sought to compare outcomes of RF and Cryo for AVNRT in the pediatric population., Methods: AVNRT ablation outcomes were retrospectively analyzed utilizing the National Cardiovascular Data Registry IMPACT (Improving Pediatric and Adult Congenital Treatment) Registry from April 2016 to March 2019. Data from subjects 1 to 21 years of age undergoing elective first-time slow pathway (SP) modification for AVNRT were included. Exclusion criteria included <1 year of age, congenital heart disease, and >1 ablation target. Cases were analyzed by ablation energy: 1) RF only; 2) Cryo only; 3) radiofrequency ablation switching to cryoablation (RF→Cryo); and 4) cryoablation switching to radiofrequency ablation (Cryo→RF). The primary outcome was acute ablation failure. Secondary outcomes included in-hospital adverse events., Results: Among 2,448 patients (mean age 13.6 ± 3.4 years, 60% female), RF only was employed in 43% (n = 1,046), Cryo only in 49% (n = 1,201), RF→Cryo in 6% (n = 135), and Cryo→RF in 66 (3%). Acute ablation failure occurred in 1.3% (n = 33), with no difference by energy source (1% in RF only, 1.5% in Cryo only, 1.5% in RF→Cryo, 3% in Cryo→RF; P = 0.5). Atrioventricular (AV) block requiring permanent pacemaker did not occur in any group; transient AV block occurred in 0.4% of the cohort, with no difference by group., Conclusions: In this largest pediatric study of AVNRT ablation, RF and Cryo demonstrated comparable high acute success and rare documentation of AV block that did not result in temporary or permanent pacing. Longitudinal data are important for further comparison of these modalities with regard to recurrence risk and late complications., Competing Interests: Funding Support and Author Disclosures The specific analysis described in this manuscript was funded by the American College of Cardiology and National Cardiovascular Data Registry. The proposed project and manuscript were reviewed by the IMPACT Research and Publications Committee. The funding agencies had no role in the drafting of the manuscript or influencing its content. The views expressed in this manuscript represent those of the author(s), and do not necessarily represent the official views of the NCDR or its associated professional societies identified at CVQuality.ACC.org/ NCDR. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Defibrillation leads remain the Achilles heel of implantable cardioverter-defibrillators. As patients with implantable cardioverter-defibrillators are living longer and battery longevity increases, more durable leads are needed. The LEADR trial evaluated the novel, lumenless, small-diameter, OmniaSecure defibrillation lead and demonstrated favorable safety and efficacy profile as well as zero fractures through 12.7 ± 4.8 months and remains in clinical follow-up. To augment the clinical trial, advanced cardiac lead reliability modeling was used to project long-term lead durability., Objective: We aimed to project the 10-year fracture-free survival of the OmniaSecure defibrillation lead using reliability modeling., Methods: The validated reliability model, which incorporates patient and bench test data, was used to project the 10-year fracture-free survival of the OmniaSecure lead. A subset of LEADR trial patients underwent biplane fluoroscopy imaging during cardiac and patient motion to evaluate the lead's bending curvature in vivo. Bench tests then reproduced these use conditions with greater bending curvatures than observed in patients to exaggerate stress on the lead and to evaluate the lead fatigue strength., Results: The reliability modeling projects a 98.2% fracture-free survival rate of the OmniaSecure lead at 10 years, including a 10-year fracture-free survival rate of 97.9% in adolescents, exceeding both the modeled and clinical 10-year performance of the highly reliable, larger diameter Sprint Quattro lead., Conclusion: Consistent with early clinical trial experience, modeling projects highly durable 10-year performance of the OmniaSecure lead, including within the active adolescent pediatric population, which may uniquely benefit from a novel 4.7F defibrillation lead designed for reliability., Gov Identifier: NCT04863664., Competing Interests: Disclosures G.H.C.: speaker at Medtronic and Philips; consultant for Medtronic and Boston Scientific. P.K.M.: consultant for Medtronic, Boston Scientific, and Cook as well as honoraria from Medtronic and Cook. B.H.: reports funding from Medtronic and CVRx. P.D.F.: consultant fees and travel support from Medtronic, Boston Scientific, Abbott, and Biotronik; honoraria and advisory board participation for Medtronic, Abbott, and Biotronik. M.J.S.: consultant for Medtronic and Tenaya Therapeutics. F.P.: speaker at Medtronic and Boston Scientific; consultant for Medtronic and Boston Scientific; research funding from Medtronic and Boston Scientific. D.S.: institutional funding from Medtronic. T.D.R.: consultant for Medtronic, Johnson and Johnson, and Philips; research funding from Medtronic and Abbott. M.B.W.: consultant for Medtronic. JayD.: consultant for Boston Scientific, Abbott, and Medtronic. J.D., A.H., L.S., and A.E.T: employees of Medtronic, Inc. P.S.: reports having served on the advisory boards of Medtronic, Abbott, Boston Scientific, PaceMate, and CathRx; the University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic, Abbott, and Boston Scientific; and the University of Adelaide has received on his behalf research funding from Medtronic, Abbott, Boston Scientific, and Becton-Dickson., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Standard neoadjuvant chemotherapy (NACT) for locally advanced esophageal/gastroesophageal junction squamous cancer (LAEGSC), 5-fluorouracil (5FU)+platinum, is toxic and logistically challenging; alternative regimens are needed., Patients and Methods: Phase III randomized open-label non-inferiority trial at Tata Memorial Center, India, in resectable LAEGSC. Patients were randomized 1:1 to three cycles of 3-weekly platinum (cisplatin 75 mg/m2 or carboplatin AUC 6) with paclitaxel 175 mg/m2 (day 1) or 5FU 1000 mg/m2 continuous infusion (days 1-4), followed by surgery., Results: Between August 2014 and June 2022, we enrolled 420 patients; 210 to each arm. Significantly more patients on paclitaxel + platinum (194 (92.3%)] received all 3 chemotherapy cycles than on 5FU+platinum (170 [85.9%]), P = .009. 5FU + platinum caused more grade ≥ 3 toxicities (124 [69.7%]) than paclitaxel + platinum (97 [51.9%]), P = .001. Surgery was performed in 131 (62.4%) patients on 5FU + platinum vs 139 (66.2%) on paclitaxel + platinum, P = .415. Paclitaxel + platinum resulted in higher pathologic primary tumor clearance (33 [25.8%]) vs 17 [15%]; P = .04), and pathologic complete responses in 21.9% compared to 12.4% from 5FU + platinum, P = .053. Median OS was 27.5 months (95% CI, 18.6-43.5) from paclitaxel + platinum, which was non-inferior to 27.1 months (95% CI, 18.8-40.7) from 5FU + platinum; HR, 0.89 (95% CI, 0.72-1.09); P = .346., Conclusion: Neoadjuvant paclitaxel + platinum chemotherapy is safer, and results in similar R0 resections, higher pathologic tumor clearance and non-inferior survival, compared to 5FU + platinum. Paclitaxel + platinum should replace 5FU + platinum as NACT for resectable LAEGSC., Clinical Trials Registry India Number: CTRI/2014/04/004516., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The complexity of child behavioral health and the importance of transitioning from the most restrictive to an intermediate level of care such as a partial hospitalization program (PHP) for high-risk youth is highlighted in this study. While inpatient hospitalization stabilizes youth in imminent danger, PHPs offer intensive treatment of those requiring more support than traditional outpatient care but less intensive than inpatient hospitalization. The transition between levels of care is determined by the severity of symptoms, high-risk behaviors, and clinical progress with planned step-downs from inpatient settings to a PHP and crisis-driven step-ups from a PHP to inpatient., Competing Interests: Disclosure Dr M.J. Shah reports no commercial or financial conflicts of interest, no funding sources. This author has nothing to disclose. Dr R.V. Tumuluru reports no conflicts and receives research funding support from NIA, United States, NIH, United States, PCORI, United States, and La-Roche Hoffman., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Published guidelines provide recommendations for risk stratification in pediatric Wolff-Parkinson-White (WPW). There are no data on provider concordance with these guidelines. We hypothesized that significant practice variation exists between pediatric cardiologists (PC) and electrophysiologists (EP)., Method: The records of all patients, age 8 to 21 years, with a new ECG diagnosis of WPW between 1/1/2013 and 12/31/2018, from a single center, were retrospectively reviewed. Subjects were categorized on the basis of symptoms and resting ECG findings as one of the following: asymptomatic intermittent WPW, asymptomatic persistent WPW, or symptomatic WPW. The performance and results of diagnostic testing, including Holter monitor, event monitor, exercise stress test (EST), and electrophysiology study (EPS), were recorded. The primary outcome was concordance with published guidelines. A secondary outcome was documentation of a discussion of sudden cardiac death (SCD) risk., Results: 615 patient encounters were analyzed in 231 patients with newly diagnosed WPW pattern on ECG (56% male; mean age at diagnosis 13.9 ± 2.5 years). EP were observed to have a significantly higher rate of guideline concordance than PC (95% vs. 71%, p < 0.001). There was significant practice variation between PC and EP in the documentation of a discussion of SCD risk: 96% in EP vs. 39% in PC (p < 0.001)., Conclusion: Significant practice variation exists in the non-invasive and invasive risk stratification of pediatric WPW, with lower concordance to published guidelines amongst PC, when compared to EP. This report highlights the need to promote awareness of current WPW guidelines in the pediatric cardiology community at large., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This review provides a comprehensive overview of cone beam computed tomography (CBCT) in dentistry. It covers the basic principles, various applications, advantages, limitations, considerations, and future prospects of CBCT in the field of dentistry., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Background: Orthodontic treatment is known to significantly impact facial esthetics, but there is a lack of long-term studies examining its effects, particularly in conjunction with the natural aging process. This study aims to fill this gap by investigating the enduring effects of orthodontic treatment on facial esthetics and aging over a 15-year period., Materials and Methods: Three hundred orthodontic patients aged 12 to 25 at the start of treatment were included. Dental alignment, soft tissue transformations, skeletal changes, and patient-reported outcomes were measured objectively. Statistical analyses were conducted to compare pretreatment and post-treatment measurements., Results: Significant improvements were observed across various aspects following orthodontic treatment. Dental alignment showed a marked reduction in crowding, with an average decrease of 5.2 mm. Soft tissue transformations revealed notable advancements in lip positioning, averaging 3.8 mm, along with increased lip thickness. Skeletal changes were relatively modest, characterized by subtle alterations in chin positioning and mandibular angles. Patients reported high levels of satisfaction, reflected by an average score of 9.2 on the satisfaction scale. Despite treatment efficacy, the aging process continued to manifest natural changes in skin elasticity and fat distribution over the 15-year follow-up period. These findings underscore the multifaceted nature of orthodontic outcomes and highlight the importance of considering long-term effects on facial esthetics and aging., Conclusion: This longitudinal study provides valuable insights into the long-term effects of orthodontic treatment on facial esthetics and aging. It highlights significant improvements in dental alignment and soft tissue transformations, along with sustained patient satisfaction. However, modest skeletal changes and the ongoing aging process emphasize the need for managing patient expectations. These findings can guide practitioners and patients in making informed decisions regarding orthodontic interventions., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Background and Objective: Spontaneous intracranial hypotension (SIH) is an underdiagnosed disease. To depict the accurate diagnosis can be demanding; especially the detection of CSF-venous fistulas poses many challenges. Potential dynamic biomarkers have been identified through non-invasive phase-contrast MRI in a limited subset of SIH patients with evidence of spinal longitudinal extradural collection. This study aimed to explore these biomarkers related to spinal cord motion and CSF velocities in a broader SIH cohort., Methods: A retrospective, monocentric pooled-data analysis was conducted of patients suspected to suffer from SIH who underwent phase-contrast MRI for spinal cord and CSF velocity measurements at segment C2/C3 referred to a tertiary center between February 2022 and June 2023. Velocity ranges (mm/s), total displacement (mm), and further derivatives were assessed and compared to data from the database of 70 healthy controls., Results: In 117 patients, a leak was located (54% ventral leak, 20% lateral leak, 20% CSF-venous fistulas, 6% sacral leaks). SIH patients showed larger spinal cord and CSF velocities than healthy controls: e.g., velocity range 7.6 ± 3 mm/s vs. 5.6 ± 1.4 mm/s, 56 ± 21 mm/s vs. 42 ± 10 mm/s, p < 0.001, respectively. Patients with lateral leaks and CSF-venous fistulas exhibited an exceptionally heightened level of spinal cord motion (e.g., velocity range 8.4 ± 3.3 mm/s; 8.2 ± 3.1 mm/s vs. 5.6 ± 1.4 mm/s, p < 0.001, respectively)., Conclusion: Phase-contrast MRI might become a valuable tool for SIH diagnosis, especially in patients with CSF-venous fistulas without evidence of spinal extradural fluid collection., (© 2024. The Author(s).)

Competing Interests: Disclosures The authors have no conflicts of interest to disclose.

Background: The Apple Watch™ (AW) offers heart rate (HR) tracking by photoplethysmography (PPG) and single-lead electrocardiographic (ECG) recordings. The accuracy of AW-HR and diagnostic performance of AW-ECGs among children during both sinus rhythm and arrhythmias have not been explored., Objective: The purposes of this study were to assess the accuracy of AW-HR measurements compared to gold standard modalities in children during sinus rhythm and arrhythmias and to identify non-sinus rhythms using AW-ECGs., Methods: Subjects ≤18 years wore an AW during (1) telemetry admission, (2) electrophysiological study (EPS), or (3) exercise stress test (EST). AW-HRs were compared to gold standard modality values. Recorded AW-ECGs were reviewed by 3 blinded pediatric electrophysiologists., Results: Eighty subjects (median age 13 years; interquartile range 1.0-16.0 years; 50% female) wore AW (telemetry 41% [n = 33]; EPS 34% [n = 27]; EST 25% [n = 20]). A total of 1090 AW-HR measurements were compared to time-synchronized gold standard modality HR values. Intraclass correlation coefficient (ICC) was high 0.99 (0.98-0.99) for AW-HR during sinus rhythm compared to gold standard modalities. ICC was poor comparing AW-HR to gold standard modality HR in tachyarrhythmias (ICC 0.24-0.27) due to systematic undercounting of AW-HR values. A total of 126 AW-ECGs were reviewed. Identification of non-sinus rhythm by AW-ECG showed sensitivity of 89%-96% and specificity of 78%-87%., Conclusions: We found high levels of agreement for AW-HR values with gold standard modalities during sinus rhythm and poor agreement during tachyarrhythmias, likely due to hemodynamic effects of tachyarrhythmias on PPG-based measurements. AW-ECGs had good sensitivity and moderate specificity in identification of non-sinus rhythm in children., Competing Interests: Disclosures Dr Shah serves as a consultant for Medtronic. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Precise preoperative localization of anterior skull base defects is important to plan surgical access, increase the success rate and reduce complications. A stable closure of the defect is vital to prevent recurrence of cerebrospinal fluid (CSF) rhinorrhea. The purpose of this retrospective case series was to evaluate the reliability of a new high-resolution gadolinium-enhanced compressed-sensing SPACE technique (CS T1 SPACE) for magnetic resonance (MR) cisternography to detect cerebrospinal fluid leaks of the anterior skull base and to assess the long-term success rate of the gasket-seal technique for closure of skull base defects., Method: All patients with spontaneous or postoperative cerebrospinal fluid rhinorrhea and defects of the anterior skull base presenting to the Departments of Otorhinolaryngology and Neurosurgery between 2019 and 2020, receiving a computed tomography (CT) cisternography and MR cisternography (on a 3T whole-body MR scanner using a 64-channel head and neck coil) with CS T1 SPACE sequence and closure of the defect with the gasket-seal technique, were enrolled in the study. For the cisternography, iodinated contrast agent (15 ml Solutrast 250 M®), saline (4 mL) mixed with a 0.5 mL of gadoteridol was injected into the lumbar subarachnoid space., Results: A total of four patients were included in the study and MR cisternography with CS T1 SPACE sequence was able to precisely localize CSF leaks in all patients. The imaging results correlated with intraoperative findings. All defects could be successfully closed with the gasket-seal technique. The mean follow-up was 35.25 months (range 33-37 months)., Conclusion: MR cisternography with CS T1 SPACE sequence could be a promising technique for precise localization of CSF leaks and the gasket-seal technique resulted in good closure of the CSF fistula in this case series., (© 2023. The Author(s).)

The innate immune compartment of the human central nervous system (CNS) is highly diverse and includes several immune-cell populations such as macrophages that are frequent in the brain parenchyma (microglia) and less numerous at the brain interfaces as CNS-associated macrophages (CAMs). Due to their scantiness and particular location, little is known about the presence of temporally and spatially restricted CAM subclasses during development, health and perturbation. Here we combined single-cell RNA sequencing, time-of-flight mass cytometry and single-cell spatial transcriptomics with fate mapping and advanced immunohistochemistry to comprehensively characterize the immune system at human CNS interfaces with over 356,000 analyzed transcriptomes from 102 individuals. We also provide a comprehensive analysis of resident and engrafted myeloid cells in the brains of 15 individuals with peripheral blood stem cell transplantation, revealing compartment-specific engraftment rates across different CNS interfaces. Integrated multiomic and high-resolution spatial transcriptome analysis of anatomically dissected glioblastoma samples shows regionally distinct myeloid cell-type distributions driven by hypoxia. Notably, the glioblastoma-associated hypoxia response was distinct from the physiological hypoxia response in fetal microglia and CAMs. Our results highlight myeloid diversity at the interfaces of the human CNS with the periphery and provide insights into the complexities of the human brain's immune system., (© 2023. The Author(s).)

Introduction: The outcomes in advanced NSCLC have improved owing to the availability of more effective systemic and improved supportive care. This has increased the number of patients who seek treatment in the third line and beyond setting. We conducted this study to compare the quality of life (QoL), toxicity, and outcomes in patients receiving chemotherapy and EGFR tyrosine kinase inhibitors (TKIs) in this setting., Methods: In this phase 3, randomized, open-label study, patients with stage III or IV NSCLC with disease progression on at least two prior lines of chemotherapy, with a life expectancy of at least 3 months, without prior EGFR TKI exposure, and stable brain metastases (if any) were included. Patients were randomized to receive chemotherapy (gemcitabine or docetaxel or paclitaxel or vinorelbine) or an EGFR TKI (erlotinib or gefitinib). The primary end point was the change in QoL at 8 to 10 weeks; the secondary outcomes were safety and overall survival (OS). Patients underwent clinical evaluation at every visit, and toxicity was assessed as per Common Terminology Criteria for Adverse Events version 4.03. A radiological tumor response assessment was done every 8 to 12 weeks from the start of therapy. The QoL was assessed using the EORTC QLQ C30 and LC13 questionnaires. The change in QoL scores was calculated as the difference between scores at baseline and scores at 8 to 10 weeks (Δ) for each QoL domain. The Mann-Whitney U test was used to compare the mean difference (Δ) for each domain. OS and progression-free survival (PFS) were determined using the Kaplan-Meier method and Cox proportional regression analysis., Results: A total of 246 patients were enrolled in the study, with 123 in each arm. There was a male predominance with 69.1% male patients in the chemotherapy arm and 70.7% in the EGFR TKI arm. The median age of patients in the chemotherapy arm was 54 years and 55 years in the chemotherapy and EGFR TKI arms, respectively. There was no significant difference in the change in QoL at baseline and the second visit (Δ) in both arms in all domains of EORTC QLQ C30 except cognitive function ( p  = 0.0045) and LC13 except alopecia (0.01249). The mean Δ Global Health Status was -28 in the chemotherapy arm and -26.8 in the EGFR TKI arm; this was not statistically significant ( p  = 0.973). The median follow-up was 88.1 months (95% confidence interval [CI]: 39.04-137.15). On the intention-to-treat analysis, the median PFS was 3.13 months (95% CI: 2.15-4.11) in the chemotherapy arm and 2.26 months (95% CI: 2.1-2.43) in the EGFR TKI arm, with hazard ratio at 1.074 (95% CI: 0.83-1.38) ( p  = 0.58). There were 120 deaths in each arm. The median OS was 7.63 months (95% CI: 5.96-9.30) in the chemotherapy arm and 7.5 months in the EGFR TKI arm (95% CI: 5.85-9.14); hazard ratio at 1.033 (95% CI: 0.80-1.33) ( p  = 0.805). The toxicity profile was similar in both arms except for a significantly higher incidence of fatigue ( p  = 0.043), peripheral neuropathy (0.000), alopecia, hypokalemia (0.037), and pedal edema (0.007) in the chemotherapy arm and dry skin ( p  = 0.000) and skin rash ( p  = 0.019) in the EGFR TKI arm., Conclusions: There was no significant difference in most QoL scales (except cognitive function and alopecia), OS, and PFS of patients with advanced NSCLC receiving an EGFR TKI as compared with chemotherapy TKI in the third-line setting. The toxicity profile is consistent with the known toxicities of the agents., (© 2024 The Authors.)

Objectives: Despite their life-saving capabilities, cerebrospinal fluid (CSF) shunts exhibit high failure rates, with a large fraction of failures attributed to the regulating valve. Due to a lack of methods for the detailed analysis of valve malfunctions, failure mechanisms are not well understood, and valves often have to be surgically explanted on the mere suspicion of malfunction. The presented pilot study aims to demonstrate radiological methods for comprehensive analysis of CSF shunt valves, considering both the potential for failure analysis in design optimization, and for future clinical in-vivo application to reduce the number of required shunt revision surgeries. The proposed method could also be utilized to develop and support in situ repair methods (e.g. by lysis or ultrasound) of malfunctioning CSF shunt valves., Materials and Methods: The primary methods described are contrast-enhanced radiographic time series of CSF shunt valves, taken in a favorable projection geometry at low radiation dose, and the machine-learning-based diagnosis of CSF shunt valve obstructions. Complimentarily, we investigate CT-based methods capable of providing accurate ground truth for the training of such diagnostic tools. Using simulated test and training data, the performance of the machine-learning diagnostics in identifying and localizing obstructions within a shunt valve is evaluated regarding per-pixel sensitivity and specificity, the Dice similarity coefficient, and the false positive rate in the case of obstruction free test samples., Results: Contrast enhanced subtraction radiography allows high-resolution, time-resolved, low-dose analysis of fluid transport in CSF shunt valves. Complementarily, photon-counting micro-CT allows to investigate valve obstruction mechanisms in detail, and to generate valid ground truth for machine learning-based diagnostics. Machine-learning-based detection of valve obstructions in simulated radiographies shows promising results, with a per-pixel sensitivity >70%, per-pixel specificity >90%, a median Dice coefficient >0.8 and <10% false positives at a detection threshold of 0.5., Conclusions: This ex-vivo study demonstrates obstruction detection in cerebro-spinal fluid shunt valves, combining radiological methods with machine learning under conditions compatible to future in-vivo application. Results indicate that high-resolution contrast-enhanced subtraction radiography, possibly including time-series data, combined with machine-learning image analysis, has the potential to strongly improve the diagnostics of CSF shunt valve failures. The presented method is in principle suitable for in-vivo application, considering both measurement geometry and radiological dose. Further research is needed to validate these results on real-world data and to refine the employed methods. In combination, the presented methods enable comprehensive analysis of valve failure mechanisms, paving the way for improved product development and clinical diagnostics of CSF shunt valves., Competing Interests: Declaration of competing interest This work was supported by a hardware loan of DECTRIS AG of Baden-Daettwil, Switzerland, who provided the photon-counting detectors employed in the current study. Martin Pichotka: Shareholder of speCTive GmbH, Freiburg, Germany. Moritz Weigt: Shareholder of speCTive GmbH, Freiburg, Germany. Christopher L. Schlett: Speaker Bureau by Siemens Healthineers and Bayer Healthcare. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Transcatheter leadless pacemakers have benefits in congenital heart disease because they eliminate the risks of lead malfunction, venous occlusions, and pocket complications. This newest pacemaker's utility in this population has been limited by the large sheath and delivery system, need for atrioventricular synchronous pacing, lack of explantation options, and possible lack of adequate access to the subpulmonary ventricle. With careful planning, leadless pacing can be successfully performed in these patients. Consideration of nonfemoral access, alternative implant sites to avoid myocardial scar or prosthetic material, anticoagulation for patients with persistent intracardiac shunts or systemic ventricular implantation, and operator experience are critical., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Guidelines addressing magnetic resonance imaging (MRI) in patients with cardiac implantable electronic devices (CIEDs) provide algorithms for imaging pediatric and congenital heart disease (CHD) patients. Guideline acceptance varies by institution. Guidelines also do not support routine MRI scans in patients with epicardial or abandoned leads, common in pediatric and CHD patients., Objective: The purpose of this study was to determine the incidence of MRI-related complications in pediatric and CHD patients with CIEDs, including epicardial and/or abandoned leads., Methods: A multicenter retrospective review included patients with CIEDs who underwent any MRI between 2007 and 2022 at congenital cardiac centers. The primary outcome was any patient adverse event or clinically significant CIED change after MRI, defined as pacing lead capture threshold increase >0.5 V with output change, P- or R- wave amplitude decrease >50% with sensitivity change, or impedance change >50%., Results: Across 14 institutions, 314 patients (median age 18.8 [1.3; 31.4] years) underwent 389 MRIs. There were 288 pacemakers (74%) and 87 implantable cardioverter-defibrillators (22%); 52% contained epicardial leads, and 14 (4%) were abandoned leads only. Symptoms or CIED changes occurred in 4.9% of MRI scans (6.1% of patients). On 9 occasions (2%), warmth or pain occurred. Pacing capture threshold or lead impedance changes occurred in 1.4% and 2.0% of CIEDs post-MRI and at follow-up., Conclusion: Our data provide evidence that MRIs can be performed in pediatric and CHD patients with CIEDs, including non-MRI-conditional CIEDs and epicardial and/or abandoned leads, with rare minor symptoms or CIED changes but no other complications., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)