Taldefgrobep Alfa and the Phase 3 RESILIENT Trial in Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a rare, genetic neurodegenerative disorder caused by insufficient production of survival motor neuron (SMN) protein. Diminished SMN protein levels lead to motor neuron loss, causing muscle atrophy and weakness that impairs daily functioning and reduces quality of life. SMN upregulators offer clinical improvements and increased survival in SMA patients, although significant unmet needs remain. Myostatin, a TGF-ß superfamily signaling molecule that binds to the activin II receptor, negatively regulates muscle growth; myostatin inhibition is a promising therapeutic strategy for enhancing muscle. Combining myostatin inhibition with SMN upregulation, a comprehensive therapeutic strategy targeting the whole motor unit, offers promise in SMA. Taldefgrobep alfa is a novel, fully human recombinant protein that selectively binds to myostatin and competitively inhibits other ligands that signal through the activin II receptor. Given a robust scientific and clinical rationale and the favorable safety profile of taldefgrobep in patients with neuromuscular disease, the RESILIENT phase 3, randomized, placebo-controlled trial is investigating taldefgrobep as an adjunct to SMN upregulators in SMA (NCT05337553). This manuscript reviews the role of myostatin in muscle, explores the preclinical and clinical development of taldefgrobep and introduces the phase 3 RESILIENT trial of taldefgrobep in SMA.

Early Ophthalmology Findings in Nonsyndromic Craniosynostosis.

Craniosynostosis (CS) occurs 1 in 2500 births and surgical intervention is indicated partly due to risk for elevated intracranial pressure (EICP). Ophthalmological examinations help identify EICP and additional vision concerns. This study describes preoperative and postoperative ophthalmic findings in CS patients (N=314) from chart review. Patients included nonsyndromic CS: multisuture (6.1%), bicoronal (7.3%), sagittal (41.4%), unicoronal (22.6%), metopic (20.4%), and lambdoidal (2.2%). Preoperative ophthalmology visits were at M =8.9±14.1 months for 36% of patients and surgery was at M =8.3±4.2 months. Postoperative ophthalmology visits were at age M =18.7±12.6 months for 42% with follow-up at M =27.1±15.1 months for 29% of patients. A marker for EICP was found for a patient with isolated sagittal CS. Only a third of patients with unicoronal CS had normal eye exams (30.4%) with hyperopia (38.2%) and anisometropia (16.7%) at higher rates than the general population. Most children with sagittal CS had normal exams (74.2%) with higher than expected hyperopia (10.8%) and exotropia (9.7%). The majority of patients with metopic CS had normal eye exams (84.8%). About half of patients with bicoronal CS had normal eye exams (48.5%) and findings included: exotropia (33.3%), hyperopia (27.3%), astigmatism (6%), and anisometropia (3%). Over half of children with nonsyndromic multisuture CS had normal exams (60.7%) with findings of: hyperopia (7.1%), corneal scarring (7.1%), exotropia (3.6%), anisometropia (3.6%), hypertropia (3.6%), esotropia (3.6%), and keratopathy (3.6%). Given the range of findings, early referral to ophthalmology and ongoing monitoring is recommended as part of CS care.

Critical Emergency Department Interventions and Clinical Deterioration in Children With Nonsevere Traumatic Intracranial Hemorrhage.

OBJECTIVE: Substantial practice variation exists in the management of children with nonsevere traumatic intracranial hemorrhage (tICH). A comprehensive understanding of rates and timing of clinically important tICH, including critical interventions and deterioration, along with associated clinical and neuroradiographic characteristics, will inform accurate risk stratification. METHODS: We conducted a single-center retrospective cohort study of children aged younger than 18 years evaluated in the emergency department (ED) from May 1, 2014 to February 28, 2020 with tICH and initial Glasgow Coma Scale (GCS) score of higher than 8. We determined rates of clinically important tICH after injury and within 96 hours of ED arrival, defined as immediate ED interventions (intubation, hyperosmotic agents, or neurosurgery within 4 hours of arrival) or clinically important deterioration (signs/symptoms with change in management). Associations between outcome and clinical and neuroradiographic characteristics were calculated using individual logistic regression models. RESULTS: Our sample included 135 children. Clinically important tICH was observed in 13.3% (n = 18); 9 (6.7%) underwent immediate ED interventions and 9 (6.7%) developed deterioration. Most (93.3%, n = 127) presented with an initial GCS ≥ 14, including all children who later deteriorated. Initial GCS (P = 0.001) and nonaccidental trauma (P = 0.024) mechanism were associated with the outcome. None of the 71 (52.6%) children with initial GCS ≥ 14, isolated, nonepidural hemorrhage after accidental injury developed clinically important tICH. CONCLUSIONS: Clinically important tICH occurred in 13% of children with nonsevere tICH, and 7% of children who did not undergo immediate ED interventions later deteriorated, all of whom had an initial GCS ≥ 14. However, a subgroup of children was identified as low risk based on clinical and neuroradiographic characteristics.

Management of Isolated Skull Fractures in Pediatric Patients: A Systematic Review.

OBJECTIVES: Isolated skull fractures (ISFs) in children are one of the most common emergency department injuries. Recent studies suggest these children may be safely discharged following ED evaluation with little risk of delayed neurological compromise. The aim of this study was to propose an evidence-based protocol for the management of ISF in children in an effort to reduce medically unnecessary hospital admissions. METHODS: Using PubMed and The Cochrane Library databases, a literature search using the search terms (pediatric OR child) AND skull fracture AND (isolated OR linear) was performed. Three hundred forty-three abstracts were identified and screened based on the inclusion criteria: (1) linear, nondepressed ISF; (2) no evidence of intracranial injury; (3) age 18 years or younger; and (4) data on patient outcomes and management. Data including age, Glasgow Coma Scale score on arrival, repeat imaging, admission rates, need for neurosurgical intervention, and patient outcome were collected. Two authors reviewed each study for data extraction and quality assessment. RESULTS: Fourteen articles met the eligibility criteria. Data including admission rates, outcomes, and necessity of neurosurgical intervention were analyzed. Admission rates ranged from 56.8% to 100%; however, only 8 of more than 5000 patients developed new imaging findings after admission, all of which were nonsurgical. Only 1 patient required neurosurgical intervention for a finding evident upon initial evaluation. CONCLUSIONS: Pediatric ISF patients with a presenting Glasgow Coma Scale score of 15 who are neurologically intact and tolerating feeds without concern for nonaccidental trauma or an unstable social environment can safely be discharged following ED evaluation to a responsible caregiver.

A sex-dependent change in behavioral temperature regulation in African house snakes (Lamprophis fuliginosus) challenged with different pathogens.

Behavioral fever in reptiles is often considered an adaptive response used to eliminate pathogens, yet empirical data showing the wide-spread use of this response is mixed. This behavioral change can be beneficial by enhancing the host's immune response and increasing the animal's chance of survival, but it can also be detrimental in terms of host energetic requirements and enzymatic performance. Thus, we examined whether captive-bred African house snakes (Lamprophis fuliginosus) employed behavioral fever in response to pathogen stimulus. Twenty-one African house snakes were injected separately with three different strains of ultraviolet (UV) light-killed bacteria (Escherichia coli, Staphylococcus aureus, Salmonella enterica). We found an increased variance of hourly cloacal temperatures following exposure to pathogens in male but not female house snakes. We did not, however, find a significant febrile response to pathogen exposure as measured via mean cloacal temperature. This research adds critical information to the field of reptilian physiology as this field remains understudied. Reptilian immune function and its relationship with thermal biology is ever more pertinent as new challenges arise, such as novel pathogens and changing climate.

Corticosteroid responses of snakes to toxins from toads (bufadienolides) and plants (cardenolides) reflect differences in dietary specializations.

Toads are chemically defended by cardiotonic steroids known as bufadienolides. Resistance to the acute effects of bufadienolides in snakes that prey on toads is conferred by target-site insensitivity of the toxin's target enzyme, the Na+/K+-ATPase. Previous studies have focused largely on the molecular mechanisms of resistance but have not investigated the physiological mechanisms or consequences of exposure to the toxins. Adrenal enlargement in snakes often is associated with specialization on a diet of toads. These endocrine glands are partly composed of interrenal tissue, which produces the corticosteroids corticosterone and aldosterone. Corticosterone is the main hormone released in response to stress in reptiles, and aldosterone plays an important role in maintaining ion balance through upregulation of Na+/K+-ATPase. We tested the endocrine response of select species of snakes to acute cardiotonic steroid exposure by measuring circulating aldosterone and corticosterone concentrations. We found that Rhabdophis tigrinus, which specializes on a diet of toads, responds with lower corticosterone and higher aldosterone compared to other species that exhibit target-site resistance to the toxins but do not specialize on toads. We also found differences between sexes in R. tigrinus, with males generally responding with higher corticosterone and aldosterone than females. This study provides evidence of physiological adaptations, beyond target-site resistance, associated with tolerance of bufadienolides in a specialized toad-eating snake.

Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial.

BACKGROUND: Src kinase-mediated interactions between prostate cancer cells and osteoclasts might promote bone metastasis. Dasatinib inhibits tyrosine kinases, including Src kinases. Data suggests that dasatinib kinase inhibition leads to antitumour activity, affects osteoclasts, and has synergy with docetaxel, a first-line chemotherapy for metastatic castration-resistant prostate cancer. We assessed whether dasatinib plus docetaxel in chemotherapy-naive men with metastatic castration-resistant prostate cancer led to greater efficacy than with docetaxel alone. METHODS: In this double-blind, randomised, placebo-controlled phase 3 study, we enrolled men of 18 years or older with chemotherapy-naive, metastatic, castration-resistant prostate cancer, and adequate organ function from 186 centres across 25 countries. Eligible patients were randomly assigned (1:1) via an interactive voice response system to receive docetaxel (75 mg/m(2) intravenously every 3 weeks, plus oral prednisone 5 mg twice daily), plus either dasatinib (100 mg orally once daily) or placebo until disease progression or unacceptable toxicity. Randomisation was stratified by Eastern Cooperative Oncology Group performance status (0-1 vs 2), bisphosphonate use (yes vs no), and urinary N-telopeptide (uNTx) value (<60 µmol/mol creatinine vs ≥60 µmol/mol creatinine). All patients, investigators, and personnel involved in study conduct and data analyses were blinded to treatment allocation. The primary endpoint was overall survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00744497. FINDINGS: Between Oct 30, 2008, and April 11, 2011, 1522 eligible patients were randomly assigned to treatment; 762 patients were assigned to dasatinib and 760 to placebo. At final analysis, median follow-up was 19·0 months (IQR 11·2-25·1) and 914 patients had died. Median overall survival was 21·5 months (95% CI 20·3-22·8) in the dasatinib group and 21·2 months (20·0-23·4) in the placebo group (stratified hazard ratio [HR] 0·99, 95·5% CI 0·87-1·13; p=0·90). The most common grade 3-4 adverse events included diarrhoea (58 [8%] patients in the dasatinib group vs 27 [4%] patients in the placebo group), fatigue (62 [8%] vs 42 [6%]), and asthenia (40 [5%] vs 23 [3%]); grade 3-4 pleural effusions were uncommon (ten [1%] vs three [<1%]). INTERPRETATION: The addition of dasatinib to docetaxel did not improve overall survival for chemotherapy-naive men with metastatic castration-resistant prostate cancer. This study does not support the combination of dasatinib and docetaxel in this population of patients. FUNDING: Bristol-Myers Squibb.

Gender Differences in the Pediatric Neurosurgical Workforce: Professional Practice, Work-Life Balance, and Beyond.

BACKGROUND AND OBJECTIVES: Evidence suggests that female neurosurgeons experience unique challenges in the workplace including lack of academic advancement, challenges with work-life balance, harassment, and discrimination. How these factors influence the gender gap in neurosurgery remains unclear. This analysis investigated gender differences in pediatric neurosurgeons in professional and nonprofessional activities and responsibilities. METHODS: A survey examining professional activities, work-life balance, family dynamics, career satisfaction, and workplace discrimination and harassment was administered to 495 pediatric neurosurgeons. Response rate was 49% (n = 241). RESULTS: One-third of the pediatric neurosurgical workforce is female. There were no gender differences in race/ethnicity, American Board of Neurological Surgery/American Board of Pediatric Neurological Surgery certification rates, or pediatric neurosurgery fellowship completion. No gender differences were found in operative caseload, weekly hours worked, or working after 8 pm or weekends. Women took call more frequently than men ( P = .044). Men were more likely to work in academia ( P = .004) and have salary subsidization from external sources ( P = .026). Women were more likely to anticipate retirement by age 65 years ( P = .044), were less happy with call commitments ( P = .012), and worked more hours at home while off ( P = .050). Women more frequently reported witnessing and experiencing racial discrimination ( P = .008; P < .001), sexual harassment ( P = .002, P < .001), and feeling less safe at work ( P < .001). Men were more likely married ( P = .042) with 1 ( P = .004) or more children ( P = .034). Women reported significantly greater responsibility for child and domestic care ( P < .001). There were no gender differences in work-life balance, feeling supported at work, or having enough time to do things outside of work. CONCLUSION: Despite little difference in workload and professional responsibilities, women held more domestic responsibilities and experienced and witnessed more racial and sexual discrimination in the workplace. Surprisingly, there were no reported differences in work-life balance or feeling supported at work between genders. These findings suggest that factors unique to female neurosurgeons may contribute to continued gender disparity in the field.

Quantitative noninvasive measurement of cerebrospinal fluid flow in shunted hydrocephalus.

OBJECTIVE: Standard MRI protocols lack a quantitative sequence that can be used to evaluate shunt-treated patients with a history of hydrocephalus. The objective of this study was to investigate the use of phase-contrast MRI (PC-MRI), a quantitative MR sequence, to measure CSF flow through the shunt and demonstrate PC-MRI as a useful adjunct in the clinical monitoring of shunt-treated patients. METHODS: The rapid (96 seconds) PC-MRI sequence was calibrated using a flow phantom with known flow rates ranging from 0 to 24 mL/hr. Following phantom calibration, 21 patients were scanned with the PC-MRI sequence. Multiple, successive proximal and distal measurements were gathered in 5 patients to test for measurement error in different portions of the shunt system and to determine intrapatient CSF flow variability. The study also includes the first in vivo validations of PC-MRI for CSF shunt flow by comparing phase-contrast-measured flow rate with CSF accumulation in a collection burette obtained in patients with externalized distal shunts. RESULTS: The PC-MRI sequence successfully measured CSF flow rates ranging from 6 to 54 mL/hr in 21 consecutive pediatric patients. Comparison of PC-MRI flow measurement and CSF volume collected in a bedside burette showed good agreement in a patient with an externalized distal shunt. Notably, the distal portion of the shunt demonstrated lower measurement error when compared with PC-MRI measurements acquired in the proximal catheter. CONCLUSIONS: The PC-MRI sequence provided accurate and reliable clinical measurements of CSF flow in shunt-treated patients. This work provides the necessary framework to include PC-MRI as an immediate addition to the clinical setting in the noninvasive evaluation of shunt function and in future clinical investigations of CSF physiology.

Sociodemographic Factors Associated with Delayed Presentation in Craniosynostosis Surgery at a Tertiary Children's Hospital.

Background: Craniosynostosis is a common diagnosis requiring early referral to a pediatric plastic surgeon; however, disparities in healthcare may influence presentation timing and affect treatment options and outcomes. This study aimed to explore sociodemographic factors contributing to delay in craniosynostosis surgical consultation. Methods: A retrospective cohort study of 694 California-based craniosynostosis patients at a tertiary children's hospital was performed from 2006 to 2023. State-specific Area Deprivation Index (ADI) and distance to the hospital were calculated using ZIP codes. Multivariate linear and logistic regressions considered race, insurance type, syndromic status, suture type, and ZIP code-based socioeconomic factors. Results: Median age of presentation was 4.5 [interquartile range: 2.6-7.6] months with racial/ethnic breakdown of Hispanic/Latinx (41.2%), White (23.6%), Asian (3.7%), Black/African American (2.0%), or other/unreported (29.5%) with 58.4% having public insurance and an average distance to the hospital of 48.3 km. Median ADI was 5.4 [interquartile range: 4.0-7.1]. By linear regression, public insurance (P < 0.001) and higher ADI decile (P < 0.001) independently contributed to an older age of presentation. Patients with public insurance (odds ratio 1.90; P = 0.002) were more likely to present after 4 months of age. Conclusions: Patients who had public insurance or resided in more disadvantaged areas presented later for craniosynostosis surgical consultation. Eliminating disparities in these populations ensures more equitable access to surgical options and can improve patient outcomes.

Surgical management of pediatric spinal aneurysmal bone cysts: patient series.

BACKGROUND: Aneurysmal bone cysts (ABCs) are rare, highly vascular osteolytic bone lesions that predominantly affect pediatric populations. This report evaluates the clinicopathological data of pediatric patients with spinal ABCs. The medical records for all patients at Children's Hospital Los Angeles with biopsy-proven ABCs of the spine between 1998 and 2018 were evaluated. OBSERVATIONS: Seventeen patients, 6 males and 11 females, were identified. The mean age at surgery was 10.4 years (range, 3.5-20 years). The most common presenting complaint was pain at the lesion site 16/17 (94%), followed by lower-extremity weakness 8/17 (47%). Resection and intralesional curettage were performed in all patients. Three (18%) of 17 patients underwent selective arterial embolization prior to resection. Spinal stability was compromised in 15 of 17 patients (88%), requiring instrumented fusion. Five (29%) of the 17 patients received additional therapy including radiation, calcitonin-methylprednisolone, or phenol. Four (23.5%) of 17 patients experienced a recurrence, and the mean time to recurrence was 15 months. The postoperative follow-up ranged from 6 to 108 months (median, 28 months). Reoperation occurred after an average of 35 months. At the recent follow-up, patients were free of disease. LESSONS: Gross-total resection by intralesional curettage with case-dependent instrumented spinal fusion for instability remains an effective strategy for managing pediatric spinal ABCs. Long-term follow-up is necessary to detect tumor recurrence.

The role of occipital condyle and atlas anomalies on occipital cervical fusion outcomes in Chiari malformation type I with syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF). METHODS: The authors analyzed the prevalence of condylar hypoplasia and atlas arch anomalies for patients in the Park-Reeves Syringomyelia Research Consortium database who underwent PFD+OCF. Condylar hypoplasia was defined by an atlanto-occipital joint axis angle (AOJAA) ≥ 130°. Atlas assimilation and arch anomalies were identified on presurgical radiographic imaging. This PFD+OCF cohort was compared with a control cohort of patients who underwent PFD alone. The control group was matched to the PFD+OCF cohort according to age, sex, and duration of symptoms at a 2:1 ratio. RESULTS: Clinical features and radiographic atlanto-occipital joint parameters were compared between 19 patients in the PFD+OCF cohort and 38 patients in the PFD-only cohort. Demographic data were not significantly different between cohorts (p > 0.05). The mean AOJAA was significantly higher in the PFD+OCF group than in the PFD group (144° ± 12° vs 127° ± 6°, p < 0.0001). In the PFD+OCF group, atlas assimilation and atlas arch anomalies were identified in 10 (53%) and 5 (26%) patients, respectively. These anomalies were absent (n = 0) in the PFD group (p < 0.001). Multivariate regression analysis identified the following 3 CVJ radiographic variables that were predictive of OCF occurrence after PFD: AOJAA ≥ 130° (p = 0.01), clivoaxial angle < 125° (p = 0.02), and occipital condyle-C2 sagittal vertical alignment (C-C2SVA) ≥ 5 mm (p = 0.01). A predictive model based on these 3 factors accurately predicted OCF following PFD (C-statistic 0.95). CONCLUSIONS: The authors' results indicate that the occipital condyle-atlas joint complex might affect the biomechanical integrity of the CVJ in children with CM-I and syringomyelia. They describe the role of the AOJAA metric as an independent predictive factor for occurrence of OCF following PFD. Preoperative identification of these skeletal abnormalities may be used to guide surgical planning and treatment of patients with complex CM-I and coexistent osseous pathology.

Orthotic (helmet) therapy in the treatment of plagiocephaly.

OBJECT: The goal of this study was to review the current literature on orthotic (helmet) therapy use in the treatment of deformational plagiocephaly. METHODS: PubMed was used to search English articles using the medical subject headings "deformational plagiocephaly" and "orthosis," and "deformational plagiocephaly" and "helmet." RESULTS: Forty-two articles were found. There were no Class I studies, 7 Class II studies, 1 Class III study, and 13 Class IV studies. Cranial orthoses have been shown to be effective in treating deformational plagiocephaly. It continues to be debated as to whether the statistical significance of treatment with cranial orthoses compared with conservative therapies is clinically significant. Children older than 12 months of age with deformational plagiocephaly may still benefit from orthotic therapy. The long-term effects of orthotic therapy are controversial. CONCLUSIONS: There is a lack of Class I literature evidence supporting the use of helmet therapy in deformational plagiocephaly. There are controversies surrounding the use of orthotic therapy such as appropriate use, cost, use in older children, and long-term outcomes. Clinical indications for orthotic therapy need to be better defined with further research studies.

Myelomeningocele repair at pediatric hospitals: association with routine discharge and shorter hospital stay.

OBJECTIVE: Postnatal repair for myelomeningocele (MMC) is a time-sensitive and technically challenging procedure. More experienced hospitals may provide improved outcomes for the complexity of care associated with these patients. No prior study has investigated the impact of MMC treatment at pediatric hospitals. The authors sought to examine the effect of pediatric hospital designation on patients undergoing postnatal MMC repair to identify factors associated with maximizing improved patient outcomes. METHODS: The Nationwide Readmissions Database records from 2010 to 2018 were analyzed retrospectively to determine the effect of hospital designation on patient outcomes after postnatal MMC repair. Univariate and multivariate regression analyses of patient and hospital characteristics were conducted to evaluate if MMC repair at a designated pediatric hospital was independently associated with patient outcomes of perinatal infection rates, discharge disposition, and length of stay. RESULTS: Of the total of 6353 pediatric patients who underwent postnatal MMC repair between 2010 and 2018, 2224 (35.0%) received care at a pediatric hospital. Those with an extreme level of disease burden as defined by the all patient refined diagnosis-related group severity of illness index were more likely to be treated at a pediatric hospital (p = 0.03). Patients undergoing repair at a pediatric hospital were also associated with a decreased likelihood of perinatal infection (OR 0.54, 95% CI 0.35-0.83, p = 0.005); greater likelihood of routine disposition (OR 4.85, 95% CI 2.34-10.06, p < 0.0001); and shorter length of stay (incidence rate ratio 0.88, 95% CI 0.77-0.995, p = 0.04). CONCLUSIONS: Pediatric patients requiring intervention for postnatal repair of MMC may benefit from the multidisciplinary subspeciality care offered at pediatric hospitals. The authors found that postnatal repair of MMC at pediatric hospitals was associated with a greater likelihood of improved patient outcomes.

Systematic Review of Racial, Socioeconomic, and Insurance Status Disparities in the Treatment of Pediatric Neurosurgical Diseases in the United States.

BACKGROUND: Increasing light is being shed on how race, insurance, and socioeconomic status (SES) may be related to outcomes from disease in the United States. To better understand the impact of these health care disparities in pediatric neurosurgery, we performed a systematic review of the literature. METHODS: We conducted a systematic review using PRISMA guidelines and MeSH terms involving neurosurgical conditions and racial, ethnic, and SES disparities. Three independent reviewers screened articles and analyzed texts selected for full analysis. RESULTS: Thirty-eight studies were included in the final analysis, of which all but 2 were retrospective database reviews. Thirty-four studies analyzed race, 22 analyzed insurance status, and 13 analyzed SES/income. Overall, nonwhite patients, patients with public insurance, and patients from lower SES were shown to have reduced access to treatment and greater rates of adverse outcomes. Nonwhite patients were more likely to present at an older age with more severe disease, less likely to undergo surgery at a high-volume surgical center, and more likely to experience postoperative morbidity and mortality. Underinsured and publicly insured patients were more likely to experience delay in surgical referral, less likely to undergo surgical treatment, and more likely to experience inpatient mortality. CONCLUSIONS: Health care disparities are present within multiple populations of patients receiving pediatric neurosurgical care. This review highlights the need for continued investigation into identifying and addressing health care disparities in pediatric neurosurgery patients.

An unusual cause of diaphragm pacer failure in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome is a rare genetic disorder affecting ventilatory response to hypercapnia and/or hypoxemia. We describe a case of diaphragm pacing (DP) failure in a 38-year-old woman with congenital central hypoventilation syndrome who used DP as ventilatory support only during sleep for 24 years. Diagnostic evaluation began with examination of external DP equipment, but adjustment did not elicit adequate diaphragm contractions. Clinical evaluation and transtelephonic monitoring showed absent function of the right pacer and diminished function of the left pacer. The patient had surgical exploration of her internal DP components. The operation revealed that the right pacer receiver had significant circumferential calcium accumulation. After replacement of the receivers in subcutaneous pockets closer to the skin surface, robust diaphragm contractions bilaterally occurred with stimulation. This case suggests DP failure can result from development of calcification and increased distance from the skin surface to the receivers due to weight gain. CITATION: Kwon A, Lodge M, McComb JG, et al. An unusual cause of diaphragm pacer failure in congenital central hypoventilation syndrome. J Clin Sleep Med. 2022;18(3):949-952.

Complications and outcomes of posterior fossa decompression with duraplasty versus without duraplasty for pediatric patients with Chiari malformation type I and syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM). METHODS: The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups. RESULTS: A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD. CONCLUSIONS: PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.

On the use of log-transformation vs. nonlinear regression for analyzing biological power laws.

Power-law relationships are among the most well-studied functional relationships in biology. Recently the common practice of fitting power laws using linear regression (LR) on log-transformed data has been criticized, calling into question the conclusions of hundreds of studies. It has been suggested that nonlinear regression (NLR) is preferable, but no rigorous comparison of these two methods has been conducted. Using Monte Carlo simulations, we demonstrate that the error distribution determines which method performs better, with NLR better characterizing data with additive, homoscedastic, normal error and LR better characterizing data with multiplicative, heteroscedastic, lognormal error. Analysis of 471 biological power laws shows that both forms of error occur in nature. While previous analyses based on log-transformation appear to be generally valid, future analyses should choose methods based on a combination of biological plausibility and analysis of the error distribution. We provide detailed guidelines and associated computer code for doing so, including a model averaging approach for cases where the error structure is uncertain.

Meeting the mental health needs of the aging veteran population.

The growth in the veterans population parallels the graying of America, accompanied by an increasing need for health care and mental health services from the U.S. Department of Veterans Affairs (VA) health care system. With the incidence of posttraumatic stress disorder (PTSD) rising in veterans of the wars in Iraq and Afghanistan and the already strained mental health resources in use by veterans with persistent PTSD from previous wars, the VA mental health system is and will continue to be in overload. In addition, recent research has noted an increased incidence of dementia in veterans with PTSD. The VA's long-term care facilities cannot meet their current demands, nevermind provide support for veterans with cognitive deficits who can no longer be cared for at home. It is imperative that immediate measures be taken to strengthen resources for research, manpower, and training to accommodate the future mental health needs of our aging veterans.