Midwave resonant cavity infrared detectors (RCIDs) with suppressed background noise.

We report a resonant cavity infrared detector (RCID) with an InAsSb/InAs superlattice absorber with a thickness of only ≈ 100 nm, a 33-period GaAs/Al0.92Ga0.08As distributed Bragg reflector bottom mirror, and a Ge/SiO2/Ge top mirror. At a low bias voltage of 150 mV, the external quantum efficiency (EQE) reaches 58% at the resonance wavelength λres ≈ 4.6 µm, with linewidth δλ = 19-27 nm. The thermal background current for a realistic system scenario with f/4 optic that views a 300 K scene is estimated by integrating the photocurrent generated by background spanning the entire mid-IR spectral band (3-5 µm). The resulting specific detectivity is a factor of 3 lower than for a state-of-the-art broadband HgCdTe device at 300 K, where dark current dominates the noise. However, at 125 K where the suppression of background noise becomes critical, the estimated specific detectivity D* of 5.5 × 1012 cm Hz½/W is more than 3× higher. This occurs despite a non-optimal absorber cut-off that causes the EQE to decrease rapidly with decreasing temperature, e.g., to 33% at 125 K. The present RCID's advantage over the broadband device depends critically on its low EQE at non-resonance wavelengths: ≤ 1% in the range 3.9-5.5 µm. Simulations using NRL MULTIBANDS indicate that impact ionization in the bottom contact and absorber layers dominates the dark current at near ambient temperatures. We expect future design modifications to substantially enhance D* throughout the investigated temperature range of 100-300 K.

Treatment of hydrocephalus following posterior fossa tumor resection: a multicenter collaboration from the Hydrocephalus Clinical Research Network.

OBJECTIVE: Persistent hydrocephalus following posterior fossa brain tumor (PFBT) resection is a common cause of morbidity in pediatric brain tumor patients, for which the optimal treatment is debated. The purpose of this study was to compare treatment outcomes between VPS and ETV in patients with persistent hydrocephalus following surgical resection of a PFBT. METHODS: A post-hoc analysis was performed of the Hydrocephalus Clinical Research Network (HCRN) prospective observational study evaluating VPS and ETV for pediatric patients. Children who experienced hydrocephalus secondary to PFBT from 2008 to 2021 were included. Primary outcomes were VPS/ETV treatment failure and time-to-failure (TTF). RESULTS: Among 241 patients, the VPS (183) and ETV (58) groups were similar in age, extent of tumor resection, and preoperative ETV Success Score. There was no difference in overall treatment failure between VPS and ETV (33.9% vs 31.0%, p = 0.751). However, mean TTF was shorter for ETV than VPS (0.45 years vs 1.30 years, p = 0.001). While major complication profiles were similar, compared to VPS, ETV patients had relatively higher incidence of minor CSF leak (10.3% vs. 1.1%, p = 0.003) and pseudomeningocele (12.1% vs 3.3%, p = 0.02). No ETV failures were identified beyond 3 years, while shunt failures occurred beyond 5 years. Shunt infections occurred in 5.5% of the VPS cohort. CONCLUSIONS: ETV and VPS offer similar overall success rates for PFBT-related postoperative hydrocephalus. ETV failure occurs earlier, while susceptibility to VPS failure persists beyond 5 years. Tumor histology and grade may be considered when selecting the optimal means of CSF diversion.

Same-day versus staged revascularization of bilateral moyamoya arteriopathy in pediatric patients.

PURPOSE: To compare the outcomes of conducting left and right hemisphere surgical revascularization on the same day versus different days for bilateral pediatric moyamoya arteriopathy patients. METHODS: We retrospectively analyzed mortality, stroke, and transient neurologic event (TNE) rates in North American bilateral pediatric moyamoya arteriopathy patients who underwent bilateral cerebral revascularization. RESULTS: A total of 38 pediatric (≤ 18 years old) patients at our institution underwent bilateral cerebral revascularization for moyamoya arteriopathy. Of these patients, 24 (63.2%) had both operations on the same day and 14 (36.8%) had the two operations on different days. The average length of stay for patients who underwent same-day bilateral revascularization was 6.9 ± 2.0 days and the average length of stay for each operation for patients who underwent staged bilateral revascularization was 4.5 ± 1.4 days, p = 0.001. While there were 7 (14.6%) postoperative strokes in patients who had both hemispheres revascularized on the same day, 0 (0%) strokes occurred in hemispheres after they had been operated on in the staged cohort, p = 0.042. Additionally, the postoperative stroke-free survival time in the ipsilateral hemisphere and TNE-free survival time were significantly longer in patients in the staged revascularization cohort. CONCLUSION: Same-day bilateral revascularization was associated with longer length of stay per operation, higher rate of ipsilateral stroke, and shorter postoperative TNE-free and stroke-free survival time in the revascularized hemisphere.

Postnatal Progressive Craniosynostosis in Syndromic Conditions: Two Patients With Saethre-Chotzen Due to TWIST1 Gene Deletions and Review of the Literature.

Saethre-Chotzen syndrome (SCS) is a known craniosynostosis syndrome with a variable presentation of craniofacial and somatic involvement. Congenital coronal craniosynostosis is most commonly observed in SCS; however, progressive postnatal craniosynostosis of other sutures has been reported. The authors present 2 infants with progressive postnatal craniosynostosis and SCS caused by chromosome 7p deletions including the TWIST1 gene. The evolution of their clinical features and a literature review of patients with syndromic, postnatal progressive craniosynostosis illustrate the importance of longitudinal observation and management of these patients.

Weighing the Risk Profile of Cervical Spine MRI in Evaluating Pediatric Cervical Spine Injuries.

OBJECTIVE: Screening for cervical spine injury after blunt trauma is common, but there remains varied practice patterns and clinical uncertainty regarding adequate radiographic evaluation. An oft-cited downside of MRI is the added risk compared to CT in the pediatric population; however, these specific risks have not yet been reported. This study examines the risks of cervical spine MRI in pediatric trauma patients in the context of what value MRI adds. METHODS: This was a retrospective observational study of all pediatric blunt trauma patients who were evaluated with a cervical spine MRI over a 4-year period at a level 1 pediatric trauma center. Clinical and radiographic data were abstracted, as well as anesthesia requirements and MRI-related major adverse events. CT and MRI results were compared for their ability to detect clinically unstable injuries - those requiring halo or surgery. RESULTS: There was one major adverse event related to MRI among the 269 patients who underwent cervical spine MRI - a rate of 0.37%. While 55% of children had an airway and anesthesia for MRI, only 57% of these airways were newly placed for the MRI. None of the 85 patients newly intubated for MRI developed aspiration pneumonitis or ventilator-associated pneumonia, and no patients had a significant neurologic event while at MRI. Another area of the body was imaged concurrently with the cervical spine MRI in 64% of patients and 83% of MRIs were performed within 48 h. CT and MRI were both 100% sensitive for injuries requiring halo or operative intervention. Eighty-three patients had an MRI performed after a negative CT, 11% (9/83) of these patients had a clinically stable injury detected on subsequent MRI, and none of these patients presented for delayed cervical spine complications. CONCLUSIONS: Overall, the safety profile of MRI in this setting is excellent and less than one-third of patients need new airway and anesthesia solely for MRI. In this clinical scenario, MRIs can happen relatively quickly and many patients require another body part to be imaged concurrently anyway. MRI and CT were both 100% sensitive for clinically unstable injuries. In the appropriate patients, MRI remains a safe and radiation-free alternative to CT.

Caregiver Preferences for Three-Dimensional Printed or Augmented Reality Craniosynostosis Skull Models: A Cross-Sectional Survey.

BACKGROUND: Recent advances in three-dimensional (3D) printing and augmented reality (AR) have expanded anatomical modeling possibilities for caregiver craniosynostosis education. The purpose of this study is to characterize caregiver preferences regarding these visual models and determine the impact of these models on caregiver understanding of craniosynostosis. METHODS: The authors constructed 3D-printed and AR craniosynostosis models, which were randomly presented in a cross-sectional survey. Caregivers rated each model's utility in learning about craniosynostosis, learning about skull anatomy, viewing an abnormal head shape, easing anxiety, and increasing trust in the surgeon in comparison to a two-dimensional (2D) diagram. Furthermore, caregivers were asked to identify the fused suture on each model and indicate their preference for generic versus patient-specific models. RESULTS: A total of 412 craniosynostosis caregivers completed the survey (mean age 33 years, 56% Caucasian, 51% male). Caregivers preferred interactive, patient-specific 3D-printed or AR models over 2D diagrams (mean score difference 3D-printed to 2D: 0.16, P < 0.05; mean score difference AR to 2D: 0.17, P < 0.01) for learning about craniosynostosis, with no significant difference in preference between 3D-printed and AR models. Caregiver detection accuracy of the fused suture on the sagittal model was 19% higher with the 3D-printed model than with the AR model (P < 0.05) and 17% higher with the 3D-printed model than with the 2D diagram (P < 0.05). CONCLUSIONS: Our findings indicate that craniosynostosis caregivers prefer 3D-printed or AR models over 2D diagrams in learning about craniosynostosis. Future craniosynostosis skull models with increased user interactivity and patient-specific components can better suit caregiver preferences.

Machine learning predicts risk of cerebrospinal fluid shunt failure in children: a study from the hydrocephalus clinical research network.

PURPOSE: While conventional statistical approaches have been used to identify risk factors for cerebrospinal fluid (CSF) shunt failure, these methods may not fully capture the complex contribution of clinical, radiologic, surgical, and shunt-specific variables influencing this outcome. Using prospectively collected data from the Hydrocephalus Clinical Research Network (HCRN) patient registry, we applied machine learning (ML) approaches to create a predictive model of CSF shunt failure. METHODS: Pediatric patients (age < 19 years) undergoing first-time CSF shunt placement at six HCRN centers were included. CSF shunt failure was defined as a composite outcome including requirement for shunt revision, endoscopic third ventriculostomy, or shunt infection within 5 years of initial surgery. Performance of conventional statistical and 4 ML models were compared. RESULTS: Our cohort consisted of 1036 children undergoing CSF shunt placement, of whom 344 (33.2%) experienced shunt failure. Thirty-eight clinical, radiologic, surgical, and shunt-design variables were included in the ML analyses. Of all ML algorithms tested, the artificial neural network (ANN) had the strongest performance with an area under the receiver operator curve (AUC) of 0.71. The ANN had a specificity of 90% and a sensitivity of 68%, meaning that the ANN can effectively rule-in patients most likely to experience CSF shunt failure (i.e., high specificity) and moderately effective as a tool to rule-out patients at high risk of CSF shunt failure (i.e., moderately sensitive). The ANN was independently validated in 155 patients (prospectively collected, retrospectively analyzed). CONCLUSION: These data suggest that the ANN, or future iterations thereof, can provide an evidence-based tool to assist in prognostication and patient-counseling immediately after CSF shunt placement.

Clinical Indicators of Pediatric Shunt Malfunction: A Population-Based Study From the Nationwide Emergency Department Sample.

OBJECTIVES: The majority of the previous literature on clinical predictors of shunt malfunction is from the neurosurgical data, looking at the symptoms of patients who had surgery. Because common childhood illnesses are filtered from these samples, the prevalence of shunt malfunction is markedly higher than it would be for the pediatrician's office or emergency department (ED). Clinical predictive values obtained from a representative population can better inform clinical judgment in these environments. METHODS: A retrospective analysis of the Nationwide Emergency Department Sample (2006-2015) was performed. International Classification of Diseases, Ninth Revision, Clinical Modification Diagnosis/Procedure Codes were used to identify pediatric (≤20 years of age) ED visits with the presence of a cerebrospinal fluid (CSF) shunt (V45.2). Shunt malfunction was defined as any condition resulting in surgical revision (02.41, 02.42, 02.43). Multivariable logistic regression was used to examine the associations between shunt malfunction, demographic factors, and clinical presentation. RESULTS: There were 74,552 observations for ED visits by pediatric patients with a CSF shunt between 2006 and 2015, of which 12.8% (9,560) required shunt revision. Positive predictive values for clinical indicators were reported along with the results of multivariable logistic regression. CONCLUSIONS: We identified peritonitis, papilledema, and oculomotor palsies as the strongest clinical indicators for shunt malfunction in pediatric ED visits with a CSF shunt. We found that patients presenting with headache, nausea/vomiting, convulsions, or fever were more likely to have an etiology other than shunt malfunction. Thus, after an appropriate shunt evaluation, other sources of symptoms should be investigated.

Nonviral polymeric nanoparticles for gene therapy in pediatric CNS malignancies.

Together, medulloblastoma (MB) and atypical teratoid/rhabdoid tumors (AT/RT) represent two of the most prevalent pediatric brain malignancies. Current treatment involves radiation, which has high risks of developmental sequelae for patients under the age of three. New safer and more effective treatment modalities are needed. Cancer gene therapy is a promising alternative, but there are challenges with using viruses in pediatric patients. We developed a library of poly(beta-amino ester) (PBAE) nanoparticles and evaluated their efficacy for plasmid delivery of a suicide gene therapy to pediatric brain cancer models-specifically herpes simplex virus type I thymidine kinase (HSVtk), which results in controlled apoptosis of transfected cells. In vivo, PBAE-HSVtk treated groups had a greater median overall survival in mice implanted with AT/RT (P = 0.0083 vs. control) and MB (P < 0.0001 vs. control). Our data provide proof of principle for using biodegradable PBAE nanoparticles as a safe and effective nanomedicine for treating pediatric CNS malignancies.

Resonant-cavity infrared detector with five-quantum-well absorber and 34% external quantum efficiency at 4 µm.

We report resonant-cavity infrared detectors with 34% external quantum efficiency at room temperature at the resonant wavelength of 4.0 µm, even though the absorber consists of only five quantum wells with a total thickness of 50 nm. The full width at half maximum (FWHM) linewidth is 46 nm, and the peak absorption is enhanced by nearly a factor of 30 over that for a single pass through the absorber. In spite of an unfavorable Shockley-Read lifetime in the current material, the dark current density is at the level of state-of-the-art HgCdTe detectors as quantified by "Rule 07." The Johnson-noise limited detectivity (D*) at 21°C is 7 × 109 cm Hz½/W. We expect that future improvements in the device design and material quality will lead to higher quantum efficiency, as well as a significant reduction of the dark current density consistent with the very thin absorber.

Trauma Bay Disposition of Infants and Young Children With Mild Traumatic Brain Injury and Positive Head Imaging.

OBJECTIVES: To describe the disposition of infants and young children with isolated mild traumatic brain injury and neuroimaging findings evaluated at a level 1 pediatric trauma center, and identify factors associated with their need for ICU admission. DESIGN: Retrospective cohort. SETTING: Single center. PATIENTS: Children less than or equal to 4 years old with mild traumatic brain injury (Glasgow Coma Scale 13-15) and neuroimaging findings evaluated between January 1, 2013, and December 31, 2015. Polytrauma victims and patients requiring intubation or vasoactive infusions preadmission were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-hundred ten children (median age/weight/Glasgow Coma Scale: 6 mo/7.5 kg/15) met inclusion criteria. Most neuroimaging showed skull fractures with extra-axial hemorrhage/no midline shift (30%), nondisplaced skull fractures (28%), and intracranial hemorrhage without fractures/midline shift (19%). Trauma bay disposition included ICU (48%), ward (38%), intermediate care unit and home (7% each). Overall, 1% required intubation, 4.3% seizure management, and 4.3% neurosurgical procedures; 15% were diagnosed with nonaccidental trauma. None of the ward/intermediate care unit patients were transferred to ICU. Median ICU/hospital length of stay was 2 days. Most patients (99%) were discharged home without neurologic deficits. The ICU subgroup included all patients with midline shift, 62% patients with intracranial hemorrhage, and 20% patients with skull fractures. Across these imaging subtypes, the only clinical predictor of ICU admission was trauma bay Glasgow Coma Scale less than 15 (p = 0.018 for intracranial hemorrhage; p < 0.001 for skull fractures). A minority of ICU patients (18/100) required neurocritical care and/or neurosurgical interventions; risk factors included neurologic deficit, loss of consciousness/seizures, and extra-axial hemorrhage (especially epidural hematoma). CONCLUSIONS: Nearly half of our cohort was briefly monitored in the ICU (with disposition mostly explained by trauma bay imaging, rather than clinical findings); however, less than 10% required ICU-specific interventions. Although ICU could be used for close neuromonitoring to prevent further neurologic injury, additional research should explore if less conservative approaches may preserve patient safety while optimizing healthcare resource utilization.

Use of Telemedicine During Interhospital Transport of Children With Operative Intracranial Hemorrhage.

OBJECTIVES: To analyze the impact of an intervention of using telemedicine during interhospital transport on time to surgery in children with operative intracranial hemorrhage. DESIGN: We performed a retrospective chart review of children with intracranial hemorrhage transferred for emergent neurosurgical intervention between January 1, 2011 and December 31, 2016. We identified those patients whose neuroimaging was transmitted via telemedicine to the neurosurgical team prior to arrival at our center and then compared the telemedicine and nontelemedicine groups. Mann-Whitney U and Fisher exact tests were used to compare interval variables and categorical data. SETTING: Single-center study performed at Johns Hopkins Hospital. PATIENTS: Patients less than or equal to 18 years old transferred for operative intracranial hemorrhage. INTERVENTIONS: Pediatric transport implemented routine telemedicine use via departmental smart phones to facilitate transfer of information and imaging and reduce time to definitive care by having surgical services available when needed. MEASUREMENTS AND MAIN RESULTS: Fifteen children (eight in telemedicine group; seven in nontelemedicine group) met inclusion criteria. Most had extraaxial hemorrhage (87.5% telemedicine group; 85.7% nontelemedicine group; p = 1.0), were intubated pre transport (62.5% telemedicine group; 71.4% nontelemedicine group; p = 1.0), and arrived at our center's trauma bay during night shift or weekend (87.5% telemedicine group; 57.1% nontelemedicine group; p = 0.28). Median trauma bay Glasgow Coma Scale scores did not differ (eight in telemedicine group; seven in nontelemedicine group; p = 0.24). Although nonsignificant, when compared with the nontelemedicine group, the telemedicine group had decreased rates of repeat preoperative neuroimaging (37.5% vs 57%; p = 0.62), shorter median times from trauma bay arrival to surgery (33 min vs 47 min; p = 0.22) and from diagnosis to surgery (146.5 min vs 157 min; p = 0.45), shorter intensive care stay (2.5 vs 5 d) and hospitalization (4 vs 5 d), and higher home discharge rates (87.5% vs 57.1%; p = 0.28). CONCLUSIONS: Telemedicine use during interhospital transport appears to expedite definitive care for children with intracranial hemorrhage requiring emergent neurosurgical intervention, which could contribute to improved patient outcomes.

Shunt revision requirements after posthemorrhagic hydrocephalus of prematurity: insight into the time course of shunt dependency.

PURPOSE: Intraventricular hemorrhage (IVH) is a common affliction of preterm infants and often results in posthemorrhagic hydrocephalus (PHH). These patients typically eventually require permanent CSF diversion and are presumed to be indefinitely shunt-dependent. To date, however, there has been no study of long-term shunt revision requirements in patients with PHH. METHODS: We analyzed retrospectively collected data for 89 preterm patients diagnosed with grades III and IV IVH and PHH at our institution from 1998 to 2011. RESULTS: Sixty-nine out of 89 patients (77.5%) underwent ventriculoperitoneal (VP) shunt placement, and 33 (47.8%) required at least one shunt revision and 18 (26.1%) required multiple revisions. The mean ± standard deviation follow-up time for shunted patients was 5.0 ± 3.3 years. The majority of early failures were due to proximal catheter malfunction, while later failures were mostly due to distal catheter problems. There was a significant difference in the number of patients requiring revisions in the first 3 years following initial VP shunt insertion compared after 3 years, with 28 revisions versus 10 (p < 0.004). In 8 out of 10 patients who underwent shunt revisions after 3 years, evidence of obstructive hydrocephalus was found on imaging either in the form of an isolated fourth ventricular cyst or aqueductal stenosis. CONCLUSIONS: Our results suggest that in a distinct subset of patients with PHH, obstructive hydrocephalus may develop, resulting in long-term dependence on CSF diversion. Further study on the factors associated with long-term shunt dependence and revision requirements within the PHH group is warranted.

Clinical and socioeconomic predictors of shunt malfunction in the pediatric emergency department.

OBJECTIVE: The aim of this study was to delineate the clinical and socioeconomic variables associated with shunt revision in pediatric patients presenting to the emergency department (ED) with concerns of ventricular shunt malfunction. METHODS: A retrospective analysis of pediatric ED consultations for shunt malfunction over a 1-year period was conducted, examining clinical symptoms, radiographic findings, and socioeconomic variables. Sensitivities, specificities, and positive and negative predictive values were calculated for each presenting symptom collected. Logistic regression models were used to estimate the odds ratios for shunt revision based on these variables, and multivariate analyses were used to adjust for potential confounders. RESULTS: Of the 271 ED visits from 137 patients, 19.2% resulted in shunt revision. Increased ventricle size on imaging (OR 11.38, p < 0.001), shunt site swelling (OR 9.04, p = 0.01), bradycardia (OR 7.08, p < 0.001), and lethargy (OR 5.77, p < 0.001) were significantly associated with shunt revision. Seizure-like activity was inversely related to revision needs (OR 0.24, p < 0.001). Patients with private or self-pay insurance were more likely to undergo revision compared with those with public insurance (p = 0.028). Multivariate analysis further confirmed the significant associations of increased ventricle size, lethargy, and bradycardia with shunt revision, while also revealing that seizure-like activity inversely affected the likelihood of revision. Patients with severe cognitive and language disabilities were more likely to be admitted to the hospital from the ED but were not more likely to undergo revision. CONCLUSIONS: Clinical signs such as increased ventricle size, shunt site swelling, bradycardia, and lethargy may be strong predictors of the need for shunt revision in pediatric patients presenting to the ED with concerns of shunt malfunction. Socioeconomic factors play a less clear role in predicting shunt revision and admission from the ED; however, the nature of their influence is unclear. These findings can help inform clinical decision-making and optimize resource utilization in the ED.

Evaluation of cervical spine clearance scores in children younger than 3 years with blunt trauma.

OBJECTIVE: The PEDSPINE I and PEDSPINE II scores were developed to determine when patients require advanced imaging to rule out cervical spine injury (CSI) in children younger than 3 years of age with blunt trauma. This study aimed to evaluate these scores in an institutional cohort. METHODS: The authors identified patients younger than 3 years with blunt trauma who received cervical spine MRI from their institution's prospective database from 2012 to 2015. Patient demographics, injury characteristics, and imaging were compared between patients with and without CSI using chi-square and Wilcoxon rank-sum tests. RESULTS: Eighty-eight patients were identified, 8 (9%) of whom had CSI on MRI. The PEDSPINE I system had a higher sensitivity (50% vs 25%) and negative predictive value (93% vs 92%), whereas PEDSPINE II had a higher specificity (91% vs 65%) and positive predictive value (22% vs 13%). Patients with CSI missed by the scores had mild, radiologically significant ligamentous injuries detected on MRI. Both models would have recommended advanced imaging for the patient who required halo-vest fixation (risk profile: no CSI, 81.9%; ligamentous, 10.1%; osseous, 8.0%). PEDSPINE I would have prevented 52 (65%) of 80 uninjured patients from receiving advanced imaging, whereas PEDSPINE II would have prevented 73 (91%). Using PEDSPINE I, 10 uninjured patients (13%) could have avoided intubation for imaging. PEDSPINE II would not have spared any patients intubation. CONCLUSIONS: Current cervical spine clearance algorithms are not sensitive or specific enough to determine the need for advanced imaging in children. However, these scores can be used as a reference in conjunction with physicians' clinical impressions to reduce unnecessary imaging.

Unraveling the complexity of the senescence-associated secretory phenotype in adamantinomatous craniopharyngioma using multimodal machine learning analysis.

BACKGROUND: Cellular senescence can have positive and negative effects on the body, including aiding in damage repair and facilitating tumor growth. Adamantinomatous craniopharyngioma (ACP), the most common pediatric sellar/suprasellar brain tumor, poses significant treatment challenges. Recent studies suggest that senescent cells in ACP tumors may contribute to tumor growth and invasion by releasing a senesecence-associated secretory phenotype. However, a detailed analysis of these characteristics has yet to be completed. METHODS: We analyzed primary tissue samples from ACP patients using single-cell, single-nuclei, and spatial RNA sequencing. We performed various analyses, including gene expression clustering, inferred senescence cells from gene expression, and conducted cytokine signaling inference. We utilized LASSO to select essential gene expression pathways associated with senescence. Finally, we validated our findings through immunostaining. RESULTS: We observed significant diversity in gene expression and tissue structure. Key factors such as NFKB, RELA, and SP1 are essential in regulating gene expression, while senescence markers are present throughout the tissue. SPP1 is the most significant cytokine signaling network among ACP cells, while the Wnt signaling pathway predominantly occurs between epithelial and glial cells. Our research has identified links between senescence-associated features and pathways, such as PI3K/Akt/mTOR, MYC, FZD, and Hedgehog, with increased P53 expression associated with senescence in these cells. CONCLUSIONS: A complex interplay between cellular senescence, cytokine signaling, and gene expression pathways underlies ACP development. Further research is crucial to understand how these elements interact to create novel therapeutic approaches for patients with ACP.

A re-evaluation of the Endoscopic Third Ventriculostomy Success Score: a Hydrocephalus Clinical Research Network study.

OBJECTIVE: The Hydrocephalus Clinical Research Network (HCRN) conducted a prospective study 1) to determine if a new, better-performing version of the Endoscopic Third Ventriculostomy Success Score (ETVSS) could be developed, 2) to explore the performance characteristics of the original ETVSS in a modern endoscopic third ventriculostomy (ETV) cohort, and 3) to determine if the addition of radiological variables to the ETVSS improved its predictive abilities. METHODS: From April 2008 to August 2019, children (corrected age ≤ 17.5 years) who underwent a first-time ETV for hydrocephalus were included in a prospective multicenter HCRN study. All children had at least 6 months of clinical follow-up and were followed since the index ETV in the HCRN Core Data Registry. Children who underwent choroid plexus cauterization were excluded. Outcome (ETV success) was defined as the lack of ETV failure within 6 months of the index procedure. Kaplan-Meier curves were constructed to evaluate time-dependent variables. Multivariable binary logistic models were built to evaluate predictors of ETV success. Model performance was evaluated with Hosmer-Lemeshow and Harrell's C statistics. RESULTS: Seven hundred sixty-one children underwent a first-time ETV. The rate of 6-month ETV success was 76%. The Hosmer-Lemeshow and Harrell's C statistics of the logistic model containing more granular age and etiology categorizations did not differ significantly from a model containing the ETVSS categories. In children ≥ 12 months of age with ETVSSs of 50 or 60, the original ETVSS underestimated success, but this analysis was limited by a small sample size. Fronto-occipital horn ratio (p = 0.37), maximum width of the third ventricle (p = 0.39), and downward concavity of the floor of the third ventricle (p = 0.63) did not predict ETV success. A possible association between the degree of prepontine adhesions on preoperative MRI and ETV success was detected, but this did not reach statistical significance. CONCLUSIONS: This modern, multicenter study of ETV success shows that the original ETVSS continues to demonstrate good predictive ability, which was not substantially improved with a new success score. There might be an association between preoperative prepontine adhesions and ETV success, and this needs to be evaluated in a future large prospective study.

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.

The Neurodevelopmental and Molecular Landscape of Medulloblastoma Subgroups: Current Targets and the Potential for Combined Therapies.

Medulloblastoma is the most common malignant pediatric brain tumor and is associated with significant morbidity and mortality in the pediatric population. Despite the use of multiple therapeutic approaches consisting of surgical resection, craniospinal irradiation, and multiagent chemotherapy, the prognosis of many patients with medulloblastoma remains dismal. Additionally, the high doses of radiation and the chemotherapeutic agents used are associated with significant short- and long-term complications and adverse effects, most notably neurocognitive delay. Hence, there is an urgent need for the development and clinical integration of targeted treatment regimens with greater efficacy and superior safety profiles. Since the adoption of the molecular-based classification of medulloblastoma into wingless (WNT) activated, sonic hedgehog (SHH) activated, group 3, and group 4, research efforts have been directed towards unraveling the genetic, epigenetic, transcriptomic, and proteomic profiles of each subtype. This review aims to delineate the progress that has been made in characterizing the neurodevelopmental and molecular features of each medulloblastoma subtype. It further delves into the implications that these characteristics have on the development of subgroup-specific targeted therapeutic agents. Furthermore, it highlights potential future avenues for combining multiple agents or strategies in order to obtain augmented effects and evade the development of treatment resistance in tumors.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Patients With Chiari Malformation: Surgical Interventions.

BACKGROUND: Chiari malformation type I (CIM) diagnoses have increased in recent years. Controversy regarding the best operative management prompted a review of the literature to offer guidance on surgical interventions. OBJECTIVE: To assess the literature to determine (1) whether posterior fossa decompression or posterior fossa decompression with duraplasty is more effective in preoperative symptom resolution; (2) whether there is benefit from cerebellar tonsillar resection/reduction; (3) the role of intraoperative neuromonitoring; (4) in patients with a syrinx, how long should a syrinx be observed for improvement before additional surgery is performed; and 5) what is the optimal duration of follow-up care after preoperative symptom resolution. METHODS: A systematic review was performed using the National Library of Medicine/PubMed and Embase databases for studies on CIM in children and adults. The most appropriate surgical interventions, the use of neuromonitoring, and clinical improvement during follow-up were reviewed for studies published between 1946 and January 23, 2021. RESULTS: A total of 80 studies met inclusion criteria. Posterior fossa decompression with or without duraplasty or cerebellar tonsil reduction all appeared to show some benefit for symptom relief and syrinx reduction. There was insufficient evidence to determine whether duraplasty or cerebellar tonsil reduction was needed for specific patient groups. There was no strong correlation between symptom relief and syringomyelia resolution. Many surgeons follow patients for 6-12 months before considering reoperation for persistent syringomyelia. No benefit or harm was seen with the use of neuromonitoring. CONCLUSION: This evidence-based clinical guidelines for the treatment of CIM provide 1 Class II and 4 Class III recommendations. In patients with CIM with or without syringomyelia, treatment options include bone decompression with or without duraplasty or cerebellar tonsil reduction. Improved syrinx resolution may potentially be seen with dural patch grafting. Symptom resolution and syrinx resolution did not correlate directly. Reoperation for a persistent syrinx was potentially beneficial if the syrinx had not improved 6 to 12 months after the initial operation. The full guidelines can be seen online at https://www.cns.org/guidelines/browse-guidelines-detail/3-surgical-interventions .