Explore the vast range of titles available.

Hydrocephalus, characterized by cerebral ventricular dilatation, is routinely attributed to primary defects in cerebrospinal fluid (CSF) homeostasis. This fosters CSF shunting as the leading reason for brain surgery in children despite considerable disease heterogeneity. In this study, by integrating human brain transcriptomics with whole-exome sequencing of 483 patients with congenital hydrocephalus (CH), we found convergence of CH risk genes in embryonic neuroepithelial stem cells. Of all CH risk genes, TRIM71/lin-41 harbors the most de novo mutations and is most specifically expressed in neuroepithelial cells. Mice harboring neuroepithelial cell-specific Trim71 deletion or CH-specific Trim71 mutation exhibit prenatal hydrocephalus. CH mutations disrupt TRIM71 binding to its RNA targets, causing premature neuroepithelial cell differentiation and reduced neurogenesis. Cortical hypoplasia leads to a hypercompliant cortex and secondary ventricular enlargement without primary defects in CSF circulation. These data highlight the importance of precisely regulated neuroepithelial cell fate for normal brain–CSF biomechanics and support a clinically relevant neuroprogenitor-based paradigm of CH.Duy and Weise et al. combined human functional integrative genomics with mouse experimental biology to reveal a neuroprogenitor-based genetic subtype of human hydrocephalus with defective neurogenesis and altered brain–fluid biomechanics.

Malnutrition, common in the elderly, may adversely affect healthcare outcomes. In spine surgery, malnutrition is associated with higher rates of perioperative complications, unplanned readmission, and prolonged length of stay (LOS). The aim of this study was to determine the effect of malnutrition on adverse events (AEs), unplanned readmission, and LOS in patients undergoing spine surgery for spondylolisthesis. A retrospective cohort study was performed using the American College of Surgeons National Surgical Quality Improvement Program database from 2010 to 2016. Adult patients who underwent posterior decompression or fusion for spondylolisthesis were identified using the ICD-9-CM coding systems. Patients were divided into two cohorts based on preoperative serum albumin levels. propensity-score (PS) matching was used to create an age- and sex-matched Nourished cohort. Patient demographics, comorbidities, LOS, and postoperative complications were collected. Multivariate logistic regression analysis was performed to identify predictors of prolonged LOS, unplanned readmission, and AEs. Of the 2196 patients identified, 4.5% were malnourished. Patients in the Malnourished cohort were found to have significantly longer average LOS (Malnourished: 4.51 ± 3.1 days vs PS-Matched Not Nourished: 3.7 ± 3.7, p = 0.002), higher rates of AEs (Malnourished: 14.3% vs PS-Matched Nourished: 5.8%, p = 0.007), reoperation (Malnourished: 8.4% vs PS-Matched Nourished: 3.2%, p = 0.026), and unplanned readmission (Malnourished: 15.3% vs PS-Matched Nourished: 6.1%, p = 0.003). On multivariate analysis considering only preoperative data, malnutrition was a significant independent predictor of AEs [OR: 2.13, CI (1.02, 4.46), p = 0.045]. However, after correcting for the occurrence of AEs, malnutrition was not associated with total LOS [aRR: 0.29, CI (−0.37, 0.95), p = 0.392] or 30-day unplanned readmissions [aOR: 2.24, CI (0.89, 5.60), p = 0.086]. Our study found that malnourished patients undergoing lumbar fusion for spondylolisthesis have significantly higher rates of AEs, unplanned readmission, and prolonged LOS than nourished patients. Further studies are necessary to corroborate our findings. •Malnutrition is associated with poor postoperative outcomes in spine surgery.•Poor outcomes include prolonged LOS, costs, adverse events, and readmission.•We examined the impact of malnutrition on spondylolisthesis surgery outcomes.•We found that malnourishment was associated with worse postoperative outcomes.•Malnutrition may be a driver of AEs in spondylolisthesis patients.

Study Design Retrospective cohort study Objective The aim of this study was to determine the relative importance and predicative power of the Hospital Frailty Risk Score (HFRS) on unplanned 30-day readmission after surgical intervention for metastatic spinal column tumors. Methods All adult patients undergoing surgery for metastatic spinal column tumor were identified in the Nationwide Readmission Database from the years 2016 to 2018. Patients were categorized into 3 cohorts based on the criteria of the HFRS: Low(<5), Intermediate(5-14.9), and High(≥ 15). Random Forest (RF) classification was used to construct predictive models for 30-day patient readmission. Model performance was examined using the area under the receiver operating curve (AUC), and the Mean Decrease Gini (MDG) metric was used to quantify and rank features by relative importance. Results There were 4346 patients included. The proportion of patients who required any readmission were higher among the Intermediate and High frailty cohorts when compared to the Low frailty cohort (Low:33.9% vs. Intermediate:39.3% vs. High:39.2%, P < .001). An RF classifier was trained to predict 30-day readmission on all features (AUC = .60) and architecturally equivalent model trained using only ten features with highest MDG (AUC = .59). Both models found frailty to have the highest importance in predicting risk of readmission. On multivariate regression analysis, Intermediate frailty [OR:1.32, CI(1.06,1.64), P = .012] was found to be an independent predictor of unplanned 30-day readmission. Conclusion Our study utilizes machine learning approaches and predictive modeling to identify frailty as a significant risk-factor that contributes to unplanned 30-day readmission after spine surgery for metastatic spinal column metastases.

Hydrocephalus is the most common neurosurgical disorder worldwide and is characterized by enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles resulting from failed CSF homeostasis. Since the 1840s, physicians have observed inflammation in the brain and the CSF spaces in both posthaemorrhagic hydrocephalus (PHH) and postinfectious hydrocephalus (PIH). Reparative inflammation is an important protective response that eliminates foreign organisms, damaged cells and physical irritants; however, inappropriately triggered or sustained inflammation can respectively initiate or propagate disease. Recent data have begun to uncover the molecular mechanisms by which inflammation — driven by Toll-like receptor 4-regulated cytokines, immune cells and signalling pathways — contributes to the pathogenesis of hydrocephalus. We propose that therapeutic approaches that target inflammatory mediators in both PHH and PIH could address the multiple drivers of disease, including choroid plexus CSF hypersecretion, ependymal denudation, and damage and scarring of intraventricular and parenchymal (glia–lymphatic) CSF pathways. Here, we review the evidence for a prominent role of inflammation in the pathogenic mechanism of PHH and PIH and highlight promising targets for therapeutic intervention. Focusing research efforts on inflammation could shift our view of hydrocephalus from that of a lifelong neurosurgical disorder to that of a preventable neuroinflammatory condition.In this Review, Karimy et al. discuss the mechanisms by which inflammation can contribute to the pathogenesis of acquired hydrocephalus and highlight targets for therapeutic intervention.

Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to ~22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH. The largest whole-exome sequencing study of sporadic congenital hydrocephalus identities mutations associated with disrupted fetal neuro-gliogenesis as the primary pathophysiological event in a significant number of cases.

Fibrosis is a macrophage-driven process of uncontrolled extracellular matrix accumulation. Neuronal guidance proteins such as netrin-1 promote inflammatory scarring. We found that macrophage-derived netrin-1 stimulates fibrosis through its neuronal guidance functions. In mice, fibrosis due to inhaled bleomycin engendered netrin-1-expressing macrophages and fibroblasts, remodeled adrenergic nerves, and augmented noradrenaline. Cell-specific knockout mice showed that collagen accumulation, fibrotic histology, and nerve-associated endpoints required netrin-1 of macrophage but not fibroblast origin. Adrenergic denervation; haploinsufficiency of netrin-1's receptor, deleted in colorectal carcinoma; and therapeutic α1 adrenoreceptor antagonism improved collagen content and histology. An idiopathic pulmonary fibrosis (IPF) lung microarray data set showed increased netrin-1 expression. IPF lung tissues were enriched for netrin-1+ macrophages and noradrenaline. A longitudinal IPF cohort showed improved survival in patients prescribed α1 adrenoreceptor blockade. This work showed that macrophages stimulate lung fibrosis via netrin-1-driven adrenergic processes and introduced α1 blockers as a potentially new fibrotic therapy.

Background Pilomyxoid astrocytomas are an aggressive subtype of astrocytoma, not graded by WHO, frequently located in hypothalamic/chiasmatic region, affecting diencephalic structures, and characterized by shorter survival and high recurrence rates. Pilomyxoid astrocytoma management remains controversial, with pathologic tissue diagnosis and relief of mass effect being the main goals of surgery while avoiding treatment‐related morbidity, including vision loss, panhypopituitarism, and hypothalamic dysfunction. Chemotherapy (typically vincristine and carboplatin) in all pediatric patients and radiation therapy in pediatric patients over 5 years of age are used for treatment. Methods We report clinical presentation, surgical management, and whole exome sequencing results in a pediatric patient with the subtotally resected pilomyxoid astrocytoma. Results We identified two somatic activating missense mutations affecting FGFR1, including FGFR1 p.K656E and FGFR1 p.V561M. While the former is a known hotspot mutation that is both activating and transforming, the latter has been described as a gatekeeper mutation imparting resistance to FGFR inhibitors. Interestingly, both mutations were present with similar variant allele frequency within the tumor. Conclusion Similar variant allele frequencies of FGFR1 p.K656E and FGFR1 p.V561M mutations in our patient's tumor suggest that these mutations may have occurred at similar time points. Use of FGFR inhibitors in addition to STAT3 or PI3K/mTOR inhibition may prove a useful strategy in targeting our patient's pilomyxoid astrocytoma. Pilomyxoid astrocytomas are an aggressive subtype of astrocytoma, not graded by WHO, frequently located in hypothalamic/chiasmatic regions, affecting diencephalic structures, and characterized by shorter survival and high recurrence rates; their management remains controversial. We describe a pediatric patient with a pilomyxoid astrocytoma. We identified a known hotspot mutation FGFR1 p.K656E that is both activating and transforming, and a gatekeeper mutation FGFR1 p.V561M imparting resistance to FGFR inhibitors. Use of FGFR inhibitors in addition to STAT3 or PI3K/mTOR inhibition may prove a useful strategy in targeting our patient's pilomyxoid astrocytoma.

AimTo use the Hospital Frailty Risk Score (HFRS) to investigate the impact of frailty on complication rates and healthcare resource utilization in patients who underwent endovascular treatment of ruptured intracranial aneurysms (IAs).MethodsA retrospective cohort study was performed using the 2016–2019 National Inpatient Sample database. All adult patients (≥18 years) undergoing endovascular treatment for IAs after subarachnoid hemorrhage were identified using ICD-10-CM codes. Patients were categorized into frailty cohorts: low (HFRS <5), intermediate (HFRS 5–15) and high (HFRS >15). Patient demographics, adverse events, length of stay (LOS), discharge disposition, and total cost of admission were assessed. Multivariate logistic regression analysis was used to identify independent predictors of prolonged LOS, increased cost, and non-routine discharge.ResultsOf the 33 840 patients identified, 7940 (23.5%) were found to be low, 20 075 (59.3%) intermediate and 5825 (17.2%) high frailty by HFRS criteria. The rate of encountering any adverse event was significantly greater in the higher frailty cohorts (low: 59.9%; intermediate: 92.4%; high: 99.2%, p<0.001). There was a stepwise increase in mean LOS (low: 11.7±8.2 days; intermediate: 18.7±14.1 days; high: 26.6±20.1 days, p<0.001), mean total hospital cost (low: $62 888±37 757; intermediate: $99 670±63 446; high: $134 937±80 331, p<0.001), and non-routine discharge (low: 17.3%; intermediate: 44.4%; high: 69.4%, p<0.001) with increasing frailty. On multivariate regression analysis, a similar stepwise impact was found in prolonged LOS (intermediate: OR 2.38, p<0.001; high: OR 4.49, p<0.001)], total hospital cost (intermediate: OR 2.15, p<0.001; high: OR 3.62, p<0.001), and non-routine discharge (intermediate: OR 2.13, p<0.001; high: OR 4.17, p<0.001).ConclusionsOur study found that greater frailty as defined by the HFRS was associated with increased complications, LOS, total costs, and non-routine discharge.

Introduction Intraventricular hemorrhage (IVH) can ensue permanent neurologic dysfunction, morbidity, and mortality. While previous reports have identified disparities based on patient gender or weight, no prior study has assessed how race may influence in neonatal or infantile IVH patients. The aim of this study was to investigate the impact of race on adverse event (AE) rates, length of stay (LOS), and total cost of admission among newborns with IVH. Methods Using the 2016–2019 National Inpatient Sample database, newborns diagnosed with IVH were identified using ICD-10-CM codes. Patients were stratified based on race. Patient characteristics and inpatient outcomes were assessed. Multivariate logistic regression analyses were used to identify the impact of race on extended LOS and exorbitant cost. Results Of 1435 patients, 650 were White (45.3%), 270 African American (AA) (18.8%), 300 Hispanic (20.9%), and 215 Other (15.0%). A higher percentage of AA and Other patients than Hispanic and White patients were < 28 days old ( p  =  0.008 ). Each of the cohorts had largely similar presenting comorbidities and symptoms, although AA patients did have significantly higher rates of NEC ( p  <  0.001 ). There were no observed differences in rates of AEs, rates of mortality, mean LOS, or mean total cost of admission. Similarly, on multivariate analysis, no race was identified as a significant independent predictor of extended LOS or exorbitant cost. Conclusions Our study found that in newborns with IVH, race is not associated with proxies of poor healthcare outcomes like prolonged LOS or excessive cost. Further studies are needed to validate these findings.

Background Non-hypothalamic glioneural hamartomas are rare entities known to cause medically refractory epilepsy. Olfactory bulb hamartomas, in particular, are exceptionally rare. Methods We describe a case of an olfactory bulb hamartoma that was surgically resected at our institution. We also performed a literature review of all glioneural hamartomas and discuss the clinical presentation, diagnosis, and management of these lesions. Results Herein, we present the unusual case of a typically developing 17-year-old boy with a near life-long history of drug-resistant epilepsy, found to have a 0.8 × 1.0 cm right olfactory bulb hamartoma. Endoscopic endonasal trans-cribriform resection of the lesion led to seizure freedom in the 6-month follow-up period (Engel class 1 outcome). Comprehensive literature review revealed only one other sporadic case, which was also successfully treated with total surgical resection. Conclusions Our case of an olfactory bulb hamartoma adds to the limited literature currently available, illustrating key clinical characteristics of these exceedingly rare lesions and outlining an effective, minimally invasive, and low-morbidity treatment strategy.