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Background After severe traumatic brain injury (sTBI), physicians use long-term prognostication to guide acute clinical care yet struggle to predict outcomes in comatose patients. Purpose To develop and evaluate a prognostic model combining deep learning of head CT scans and clinical information to predict long-term outcomes after sTBI. Materials and Methods This was a retrospective analysis of two prospectively collected databases. The model-building set included 537 patients (mean age, 40 years ± 17 [SD]; 422 men) from one institution from November 2002 to December 2018. Transfer learning and curriculum learning were applied to a convolutional neural network using admission head CT to predict mortality and unfavorable outcomes (Glasgow Outcomes Scale scores 1-3) at 6 months. This was combined with clinical input for a holistic fusion model. The models were evaluated using an independent internal test set and an external cohort of 220 patients with sTBI (mean age, 39 years ± 17; 166 men) from 18 institutions in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study from February 2014 to April 2018. The models were compared with the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model and the predictions of three neurosurgeons. Area under the receiver operating characteristic curve (AUC) was used as the main model performance metric. Results The fusion model had higher AUCs than did the IMPACT model in the prediction of mortality (AUC, 0.92 [95% CI: 0.86, 0.97] vs 0.80 [95% CI: 0.71, 0.88]

The recovery of severe traumatic brain injury (TBI) survivors with long-term favorable outlook is understudied. Time to follow commands varies widely in this patient population but has important clinical implications.To (1) evaluate time to follow commands in severe patients with TBI with favorable outcomes, (2) characterize their trajectory of recovery, and (3) identify predictors associated with delayed cognitive improvement.Participants were recruited prospectively at a Level I trauma center through the Brain Trauma Research Center from 2003 to 2018. Inclusion criteria were age 16 to 80 years, Glasgow Coma Scale score ≤8 and motor scorelt;6, and Glasgow Outcome Scale-Extended measure ≥4 at 2 years postinjury.In 580 patients, there were 229 (39.5%) deaths and 140 (24.1%) patients had favorable outcomes at 2 years. The mean age was 33.7 ± 14.5 years, median Glasgow Coma Scale was 7 (IQR 6-7), and median Injury Severity Score was 30 (IQR 26-38). The mean time to follow commands was 12.7 ± 11.8 days. On multivariable linear regression, the presence of diffuse axonal injury (B = 9.2 days [4.8, 13.7], Plt; .0001) or intraventricular hemorrhage (B = 6.4 days [0.5, 12.3], Plt; .035) was associated with longer time before following commands and patients who developed nosocomial infections (B = 6.5 days [1.6-11.4], Plt; .01).In severe TBI survivors with favorable outcomes, time to follow commands varied widely. Most patients began to follow commands within 2 weeks. Evidence of diffuse axonal injury, intraventricular hemorrhage, and infections can delay cognitive improvement in the acute period. Patients make considerable recovery up to 2 years after their injury.

Background: Mild traumatic brain injury (MTBI) causes morbidity and disability worldwide. Pediatric patients are uniquely vulnerable due to developmental and psychosocial factors. Reduced healthcare access in rural/underserved communities impair management and outcome. A knowledge update relevant to current gaps in care is critically needed to develop targeted solutions. Methods: The National Library of Medicine PubMed database was queried using comprehensive search terms ((“mild traumatic brain injury” or “concussion”) and (“rural” or “low-income” or “underserved”) and (“pediatric” or “child/children”)) in the title, abstract, and Medical Subject Headings through December 2022. Fifteen articles on rural/underserved pediatric MTBI/concussion not covered in prior reviews were examined and organized into four topical categories: epidemiology, care practices, socioeconomic factors, and telehealth. Results: Incidences are higher for Individuals in rural regions, minorities, and those aged 0–4 years compared to their counterparts, and are increasing over time. Rural healthcare utilization rates generally exceed urban rates, and favor emergency departments (vs. primary care) for initial injury assessment. Management guidelines require customization to resource-constrained settings for implementation and adoption. Decreased community recognition of the seriousness of injury is a consensus challenge to care provision by clinicians. Low parental education and income were correlated with decreased MTBI knowledge and worse outcome. Telehealth protocols for triage/consultation and rehabilitation were feasible in improving care delivery to rural and remote settings. Conclusions: Pediatric MTBI/concussion patients in rural/underserved regions experience increased risks of injury, geographic and financial healthcare barriers, and poorer outcomes. Globally, under-reporting of injury has hindered epidemiological understanding. Ongoing MTBI education should be implemented for rural caregivers, schools, and low-income populations to improve community awareness. Telehealth can improve care delivery across acuity settings, and warrants judicious inclusion in triage and treatment protocols.

Traumatic brain injury (TBI) remains a leading cause of death and disability worldwide, and its incidence is increasing [...]

Introduction: The benefits of performing open and endovascular procedures in a hybrid neuroangiography surgical suite include confirmation of treatment results and reduction in number of procedures, leading to improved efficiency of care. Combined procedural suites are infrequently used in pediatric facilities due to technical and logistical limitations. We report the safety, utility, and lessons learned from a single-institution experience using a hybrid suite equipped with biplane rotational digital subtraction angiography and pan-surgical capabilities. Methods: We conducted a retrospective review of consecutive cases performed at our institution that utilized the hybrid neuroangiography surgical suite from February 2020 to August 2021. Demographics, surgical metrics, and imaging results were collected from the electronic medical record. Outcomes, interventions, and nuances for optimizing preoperative/intraoperative setup and postoperative care were presented. Results: Eighteen procedures were performed in 17 patients (mean age 13.4 years, range 6–19). Cases included 14 arteriovenous malformations (AVM; 85.7% ruptured), one dural arteriovenous fistula, one mycotic aneurysm, and one hemangioblastoma. The average operative time was 416 min (range 321–745). There were no intraoperative or postoperative complications. All patients were alive at follow-up (range 0.1–14.7 months). Five patients had anticipated postoperative deficits arising from their hemorrhage, and 12 returned to baseline neurological status. Four illustrative cases demonstrating specific, unique applications of the hybrid angiography suite are presented. Conclusion: The hybrid neuroangiography surgical suite is a safe option for pediatric cerebrovascular pathologies requiring combined surgical and endovascular intervention. Hybrid cases can be completed within the same anesthesia session and reduce the need for return to the operating room for resection or surveillance angiography. High-quality intraoperative angiography enables diagnostic confirmation under a single procedure, mitigating risk of morbidity and accelerating recovery. Effective multidisciplinary planning enables preoperative angiograms to be completed to inform the operative plan immediately prior to definitive resection.

BACKGROUND Spinal granulomas form from infectious or noninfectious inflammatory processes and are rarely present intradurally. Intradural granulomas secondary to hematoma are unreported in the literature and present diagnostic and management challenges. OBSERVATIONS A 70-year-old man receiving aspirin presented with encephalopathy, subacute malaise, and right lower extremity weakness and was diagnosed with polysubstance withdrawal and refractory hypertension requiring extended treatment. Seven days after admission, he reported increased bilateral lower extremity (BLE) weakness. Magnetic resonance imaging showed T2–3 and T7–8 masses abutting the pia, with spinal cord compression at T2–3. He was transferred to the authors’ institution, and work-up showed no vascular shunting or malignancy. He underwent T2–3 laminectomies for biopsy/resection. A firm, xanthochromic mass was resected en bloc. Pathology showed organizing hematoma without infection, vascular malformation, or malignancy. Subsequent coagulopathy work-up was unremarkable. His BLE strength significantly improved, and he declined resection of the inferior mass. He completed physical therapy and was cleared for placement in a skilled nursing facility. LESSONS Spinal granulomas can mimic vascular lesions and malignancy. The authors present the first report of paraparesis caused by intradural granuloma secondary to organizing hematoma, preceded by severe refractory hypertension. Tissue diagnosis is critical, and resection is curative. These findings can inform the vigilant clinician for expeditious treatment.

The effects of traumatic brain injury (TBI) are difficult to measure in longitudinal cohort studies, because disparate pre-injury characteristics and injury mechanisms produce variable impairment profiles and recovery trajectories. In preparation for the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, which followed patients with injuries ranging from uncomplicated mild TBI to coma, we designed a multi-dimensional Flexible outcome Assessment Battery (FAB). The FAB relies on a decision-making algorithm that assigns participants to a Comprehensive (CAB) or Abbreviated Assessment Battery (AAB) and guides test selection across all phases of recovery. To assess feasibility of the FAB, we calculated the proportion of participants followed at 2 weeks (2w) and at 3, 6, and 12 months (3m, 6m, 12m) post-injury who completed the FAB and received valid scores. We evaluated utility of the FAB by examining differences in 6m and 12m Glasgow Outcome Scale-Extended (GOSE) scores between participant subgroups derived from the FAB-enabled versus traditional approach to outcome assessment applied at 2w. Among participants followed at 2w (

Adult patients with mild traumatic brain injury (mTBI) exhibit distinct phenotypes of emotional and cognitive functioning identified by latent profile analysis of clinical neuropsychological assessments. When discerned early after injury, these latent clinical profiles have been found to improve prediction of long-term outcomes from mTBI. The present study hypothesized that white matter (WM) microstructure is better preserved in an emotionally resilient (ER) mTBI phenotype compared with a neuropsychiatrically distressed (ND) mTBI phenotype.The present study used diffusion MRI to investigate and compare WM microstructure in major association, projection, and commissural tracts between the two phenotypes and over time. Diffusion MR images from 172 mTBI patients were analyzed to compute individual diffusion tensor imaging (DTI) maps at 2 weeks and 6 months postinjury.By comparing the DTI parameters between the two phenotypes at global, regional, and voxel levels, the present study showed that the ER patients have higher axial diffusivity (AD) compared to their ND counterparts early after mTBI. Longitudinal analysis revealed greater compromise of WM microstructure in ND patients, with greater decrease of global AD and more widespread decrease of regional AD during the first 6 months after injury compared to their ER counterparts.These results provide neuroimaging evidence of WM microstructural differences underpinning mTBI phenotypes identified from neuropsychological assessments and show differing longitudinal trajectories of these biological effects. These findings suggest diffusion MRI can provide short- and long-term imaging biomarkers of resilience.

Traumatic brain injury (TBI) affects millions of people in the US each year. Most patients with TBI seen in emergency departments (EDs) have a Glasgow Coma Scale (GCS) score of 15 and a head computed tomography (CT) scan showing no acute intracranial traumatic injury (negative head CT scan), yet the short-term and long-term functional outcomes of this subset of patients remain unclear.To describe the 2-week and 6-month recovery outcomes in a cohort of patients with mild TBI with a GCS score of 15 and a negative head CT scan.This cohort study analyzed participants who were enrolled from January 1, 2014, to December 31, 2018, in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective, observational cohort study of patients with TBI that was conducted in EDs of 18 level I trauma centers in urban areas. Of the total 2697 participants in the TRACK-TBI study, 991 had a GCS score of 15 and negative head CT scan and were eligible for inclusion in this analysis. Data were analyzed from September 1, 2021, to May 30, 2022.The primary outcome was the Glasgow Outcome Scale-Extended (GOS-E) score, which was stratified according to functional recovery (GOS-E score, 8) vs incomplete recovery (GOS-E score,8), at 2 weeks and 6 months after the injury. The secondary outcome was severity of mild TBI-related symptoms assessed by the Rivermead Post Concussion Symptoms Questionnaire (RPQ) total score.A total of 991 participants (mean [SD] age, 38.5 [15.8] years; 631 male individuals [64%]) were included. Of these participants, 751 (76%) were followed up at 2 weeks after the injury: 204 (27%) had a GOS-E score of 8 (functional recovery), and 547 (73%) had a GOS-E scores less than 8 (incomplete recovery). Of 659 participants (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery. Most participants with incomplete recovery reported that they had not returned to baseline or preinjury life (88% [479 of 546]; 95% CI, 85%-90%). Mean RPQ score was 16 (95% CI, 14-18; P .001) points lower at 2 weeks (7 vs 23) and 18 (95% CI, 16-20; P .001) points lower at 6 months (4 vs 22) in participants with a GOS-E score of 8 compared with those with a GOS-E score less than 8.This study found that most participants with a GCS score of 15 and negative head CT scan reported incomplete recovery at 2 weeks and 6 months after their injury. The findings suggest that emergency department clinicians should recommend 2-week follow-up visits for these patients to identify those with incomplete recovery and to facilitate their rehabilitation.

Hospital length of stay (HLOS) after traumatic brain injury (TBI) is an important metric of injury severity, resource utilization, and access to post-acute care services. Risk factors for protracted HLOS after TBI require further characterization.Data regarding adult inpatients admitted to a single U.S. level 1 trauma center with a diagnosis of acute TBI between August 1, 2019, and April 1, 2022, were extracted from the electronic health record. Patients with extreme HLOS (XHLOS,99th percentile of institutional TBI HLOS) were compared with those without XHLOS. Socioeconomic status (SES), clinical/injury factors, and discharge disposition were analyzed.In 1638 patients, the median HLOS was 3 days (interquartile range [IQR]: 2-8 days). XHLOS threshold was70 days (N = 18; range: 72-146 days). XHLOS was associated with younger age (XHLOS/non-XHLOS: 50.4/59.6 years; P = 0.042) and greater proportions with severe TBI (55.6%/11.4%; P0.001), low SES (72.2%/31.4%; P0.001), and Medicaid insurance (77.8%/30.1%; P0.001). XHLOS patients were more likely to die in hospital (22.2%/8.1%) and discharge to post-acute facility (77.8%/16.3%; P0.001). No XHLOS patients were discharged to home. In XHLOS patients alive at discharge, medical stability was documented at median 39 days (IQR: 28-58 days) and were hospitalized for another 56 days (IQR: 26.5-78.5 days).XHLOS patients were more likely to have severe injuries, low SES, and Medicaid. XHLOS is associated with in-hospital mortality and need for post-acute placement. XHLOS patients often demonstrated medical stability long before placement, underscoring complex relationships between SES, health insurance, and outcome. These findings have important implications for quality improvement and resource utilization at acute care hospitals and await validation from larger trials.

Lynch Syndrome (LS) is an autosomal dominant disease conferring a high risk of colorectal cancer due to germline heterozygous mutations in a DNA mismatch repair (MMR) gene. Although cancers in LS patients show elevated somatic mutation burdens, information on mutation rates in normal tissues and understanding of the trajectory from normal to cancer cell is limited. Here we whole genome sequence 152 crypts from normal and neoplastic epithelial tissues from 10 LS patients. In normal tissues the repertoire of mutational processes and mutation rates is similar to that found in wild type individuals. A morphologically normal colonic crypt with an increased mutation burden and MMR deficiency-associated mutational signatures is identified, which may represent a very early stage of LS pathogenesis. Phylogenetic trees of tumour crypts indicate that the most recent ancestor cell of each tumour is already MMR deficient and has experienced multiple cycles of clonal evolution. This study demonstrates the genomic stability of epithelial cells with heterozygous germline MMR gene mutations and highlights important differences in the pathogenesis of LS from other colorectal cancer predisposition syndromes.

Our objective was to examine the construct validity of the Brief Test of Adult Cognition by Telephone (BTACT) and its relationship to traumatic brain injury (TBI) of differing severities. Data were analyzed on 1422 patients with TBI and 170 orthopedic trauma controls (OTC) from the multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Participants were assessed at 6 months post-injury with the BTACT and an in-person neuropsychological battery. We examined the BTACT's factor structure, factorial group invariance, convergent and discriminant validity, and relationship to TBI and TBI severity. Confirmatory factor analysis supported both a 1-factor model and a 2-factor model comprising correlated Episodic Memory and Executive Function (EF) factors. Both models demonstrated strict invariance across TBI severity and OTC groups. Correlations between BTACT and criterion measures suggested that the BTACT memory indices predominantly reflect verbal episodic memory, whereas the BTACT EF factor correlated with a diverse range of cognitive tests. Although the EF factor and other BTACT indices showed significant relationships with TBI and TBI severity, some group effect sizes were larger for more comprehensive in-person cognitive tests than the BTACT. The BTACT is a promising, brief, phone-based cognitive screening tool for patients with TBI. Although the BTACT's memory items appear to index verbal Episodic Memory, items that purport to assess EFs may reflect a broader array of cognitive domains. The sensitivity of the BTACT to TBI severity is lower than domain-specific neuropsychological measures, suggesting it should not be used as a substitute for comprehensive, in-person cognitive testing at 6 months post-TBI.

Torticollis is a clinical diagnosis with heterogeneous causes. We present an unusual case of acquired torticollis in an 8-month-old female infant with a large cerebellopontine angle arachnoid cyst. Symptoms resolved after surgical fenestration. Non-traumatic acquired or new-onset torticollis requires brain imaging, and posterior fossa lesions are an important entity in the differential for pediatric clinicians.

Background Currently, most basilar artery aneurysms (BAAs) are treated endovascularly. Surgery remains an appropriate therapy for a subset of all intracranial aneurysms. Whether open microsurgery would be required or utilized, and to what extent, for BAAs treated by a surgeon who performs both endovascular and open procedures has not been reported. Methods Retrospective analysis of prospectively maintained, single-surgeon series of BAAs treated with endovascular or open surgery from the first 5 years of practice. Results Forty-two procedures were performed in 34 patients to treat BAAs—including aneurysms arising from basilar artery apex, trunk, and perforators. Unruptured BAAs accounted for 35/42 cases (83.3%), and the mean aneurysm diameter was 8.4 ± 5.4 mm. Endovascular coiling—including stent-assisted coiling—accounted for 26/42 (61.9%) treatments and led to complete obliteration in 76.9% of cases. Four patients in the endovascular cohort required re-treatment. Surgical clip reconstruction accounted for 16/42 (38.1%) treatments and led to complete obliteration in 88.5% of cases. Good neurologic outcome (mRS ≤ 2) was achieved in 88.5% and 75.0% of patients in endovascular and open surgical cohorts, respectively (p = 0.40). Univariate logistic regression analysis demonstrated that advanced age (OR 1.11[95% CI 1.01–1.23]) or peri-procedural adverse event (OR 85.0 [95% CI 6.5–118.9]), but not treatment modality (OR 0.39[95% CI 0.08–2.04]), was the predictor of poor neurologic outcome. Conclusions Complementary implementation of both endovascular and open surgery facilitates individualized treatment planning of BAAs. By leveraging strengths of both techniques, equivalent clinical outcomes and technical proficiency may be achieved with both modalities.

Introduction: Tumor-associated intracranial aneurysms are rare and not well understood. Case Presentation: We describe a 4-year-old female with multiple intracranial aneurysms intimately associated with a suprasellar germ cell tumor (GCT). We provide the clinical history, medical, and surgical treatment course, as well as a comprehensive and concise synthesis of the literature on tumor-associated aneurysms. Discussion: We discuss mechanisms for aneurysm formation with relevance to the current case, including cellular and paracrine signaling pertinent to suprasellar GCTs and possible molecular pathways involved. We review the complex multidisciplinary treatment required for complex tumor and cerebrovascular interactions.

EBioMedicine 77, 103933 (2022). doi:10.1016/j.ebiom.2022.103933, Published by Elsevier, Amsterdam [u.a.]

Coccidioidomycosis exposure is common in the southwest United States and northern Mexico. Dissemination to the meninges is the most severe form of progression. Although ischemic strokes are well-reported in these patients, other cerebrovascular complications of coccidioidomycosis meningitis (CM), as well as their treatment options and outcomes, have not been systematically studied. We present a uniquely severe case of CM with several cerebrovascular complications. We also systematically queried PubMed and EMBASE databases, including articles published before April 2020 reporting human patients with CM-induced cerebrovascular pathology other than ischemic infarcts. Sixteen articles met inclusion criteria, which describe 6 patients with aneurysmal hemorrhage, 10 with non-aneurysmal hemorrhage, one with vasospasm, and one with transient ischemic attacks. CM-associated aneurysms invariably presented with hemorrhage. These were universally fatal until the past decade, when advances in surgical clipping and/or combined surgical and endovascular treatment have improved outcomes. We found that non-aneurysmal intracranial hemorrhages were limited to male patients, involved a diverse set of intracranial vasculature, and had a mortality rate surpassing 80%. Vasospasm was reported once, and was treated with percutaneous transluminal angioplasty. Transient ischemic attacks were reported once, and were successfully treated with fluconazole and dexamethasone. This review suggests that CM can present with a wide array of cerebrovascular complications, including ischemic infarcts, aneurysmogenesis, non-aneurysmal intracranial hemorrhage, vasospasm, and transient ischemic attacks. Mortality has improved over time due to advances in surgical and endovascular treatment modalities. The exception is non-aneurysmal intracranial hemorrhage, which remains associated with high mortality rates and few targeted therapeutic options.

We present a new experimental method for measuring inner-shell ionization cross sections of low-charged ions colliding with hydrogen gas target in a storage ring. The method is based on a calibration by the well-known differential cross sections of proton elastic scattering on nuclei. K-shell ionization cross section of 1047(100) barn for the 95 MeV/u 58Ni19+ ions colliding with hydrogen atoms was obtained in this work. Compared to the measured ionization cross section, a good agreement is achieved with the prediction by the Relativistic Ionization CODE Modified program (RICODE-M).

Polytrauma and traumatic brain injury (TBI) frequently co-occur and outcomes are routinely measured by the Glasgow Outcome Scale-Extended (GOSE). Polytrauma may confound GOSE measurement of TBI-specific outcomes. Adult patients with TBI from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study had presented to a Level 1 trauma center after injury, received head computed tomography (CT) within 24 h, and completed the GOSE at 3 months and 6 months post-injury. Polytrauma was defined as an Abbreviated Injury Score (AIS) ≥3 in any extracranial region. Univariate regressions were performed using known GOSE clinical cutoffs. Multi-variable regressions were performed for the 3- and 6-month GOSE, controlling for known demographic and injury predictors. Of 361 subjects (age 44.9 ± 18.9 years, 69.8% male), 69 (19.1%) suffered polytrauma. By Glasgow Coma Scale (GCS) assessment, 80.1% had mild, 5.8% moderate, and 14.1% severe TBI. On univariate logistic regression, polytrauma was associated with increased odds of moderate disability or worse (GOSE ≤6; 3 month odds ratio [OR] = 2.57 [95% confidence interval (CI): 1.50-4.41; 6 month OR = 1.70 [95% CI: 1.01-2.88]) and death/severe disability (GOSE ≤4; 3 month OR = 3.80 [95% CI: 2.03-7.11]; 6 month OR = 3.33 [95% CI: 1.71-6.46]). Compared with patients with isolated TBI, more polytrauma patients experienced a decline in GOSE from 3 to 6 months (37.7 vs. 24.7%), and fewer improved (11.6 vs. 22.6%). Polytrauma was associated with greater univariate ordinal odds for poorer GOSE (3 month OR = 2.79 [95% CI: 1.73-4.49]; 6 month OR = 1.73 [95% CI: 1.07-2.79]), which was conserved on multi-variable ordinal regression (3 month OR = 3.05 [95% CI: 1.76-5.26]; 6 month OR = 2.04 [95% CI: 1.18-3.42]). Patients with TBI with polytrauma are at greater risk for 3- and 6-month disability compared with those with isolated TBI. Methodological improvements in assessing TBI-specific disability, versus disability attributable to all systemic injuries, will generate better TBI outcomes assessment tools.

Deep brain stimulation (DBS) is being increasingly utilized to treat movement disorders including Parkinson's disease (PD), essential tremor (ET), and dystonia. An improved understanding of national trends in safety and cost is necessary. Herein, our objectives are to (1) characterize complication, mortality, and cost profiles of patients undergoing DBS for movement disorders in the United States, (2) identify predictors of morbidity and mortality, and (3) evaluate impact of complications on cost.DBS surgeries were extracted from the National Inpatient Sample (NIS) 2002-2014 for the clinical indications of PD, ET, and dystonia. Patient characteristics and eight complication categories (hardware malfunction, infection, neurological, other haemorrhagic, thromboembolic, cardiac, pulmonary, and renal/urinary) were reviewed. Outcomes included complications, mortality, hospitalization length, and inflation-adjusted cost.There were 44,866 weighted admissions (PD-73.5%, ET-22.7%, dystonia-3.8%). The number of procedures increased 2.22-fold from 2002 to 2014 (Increased DBS utilization for adult movement disorders in the United States from 2002 to 2014 was attributed to rapid adoption by teaching hospitals for PD. DBS remains a safe procedure with low overall complications and stable inpatient costs from 2002 to 2014. Complication risks vary by type of movement disorder, and although rare, multiple complications increase morbidity and cost of care.

Refuge floors are fire safety requirements for tall buildings in many Asia-Oceania cities. However, there are concerns on the adequate provision of cross-ventilation and drencher system to openings on refuge floors. To review the existing situation, a survey of 44 building developments involving 51 blocks of both residential and non-residential tall buildings was conducted. A new fire safety parameter, i.e. the ratio of external wall openings areas to the nominal total wall areas of refuge floors (wall opening area ratio, or WOAR), was introduced to provide a quantitative measure in analysing fire safety level of tall buildings. To study how the ventilation provision is affected by WOAR, numerical simulations for the effect of natural ventilation on fire growth on the refuge floor were conducted by incorporating the wind data collected from the tallest building in Hong Kong. In the simulations, an office layout was adopted on both upper and lower floors for the sake of illustrating the possible smoke and heat spread from lower floor to upper floor (refuge floor). Finally, fire safety issues in relation to natural ventilation on fire in tall buildings were discussed. Suggestions in improving the fire safety design of tall buildings are proposed.

The increasing competitiveness of the neurosurgical residency match has made it progressively difficult for foreign medical graduates (FMGs) to match in neurosurgery. We compared FMG to U.S. medical graduate (USMG) match rates in neurosurgery and identified factors associated with match outcomes for FMGs in neurosurgery.Retrospective review of American Association of Neurological Surgeons membership data and Association of American Medical Colleges Charting the Outcomes match reports (2007-2017).Across 1857 neurosurgical residents (USMG: 91.1%, FMG: 8.9%), average FMG match rates were 24% (range, 15%-35%) versus 83% (range, 75%-94%; P0.001) for USMG. FMGs were more male (89.5% vs. 82.0%, P = 0.016), older (33.9 vs. 31.8 years, P = 0.008), and more likely to take research year(s) before matching (95.8% vs. 78.5%, P0.001). FMGs had greater publications (5 vs. 2, P0.001) and H-indices (3 vs. 1, P0.001). The number of matched USMGs increased by 3.3 annually, whereas that of matched FMGs remained unchanged (β = 0.07). Compared with USMGs, FMGs were less likely to match to National Institutes of Health (NIH) Top 40 (32.7% vs. 47.5%, P0.001) and Doximity Top 20 (20.0% vs. 29.0%, P = 0.014) programs. FMGs with prior U.S. neurosurgery program affiliation were more likely to match at NIH and Doximity Top 20 programs (P0.05). For NIH programs, FMGs were older (35.3 vs. 32.0, P = 0.011), had higher H-indices (5 vs. 2, P0.001), publications (7 vs. 2, P0.001), and were more likely to take research year(s) (94.4% vs. 76.0%, P = 0.002) than USMGs. FMGs had similar patterns for matching into Doximity Top 20 programs.Although FMGs have lower match rates into U.S. neurosurgery residencies than USMGs, several demographic, professional, and academic factors could increase the chances of successful FMG neurosurgical match.

ObjectiveSporadic early-onset colorectal cancer (EOCRC) has bad prognosis, yet is poorly represented by cell line models. We examine the key mutational and transcriptomic alterations in an organoid biobank enriched in EOCRCs.DesignWe established paired cancer (n=32) and normal organoids (n=18) from 20 patients enriched in microsatellite-stable EOCRC. Exome and transcriptome analysis was performed.ResultsWe observed a striking diversity of molecular phenotypes, including PTPRK-RSPO3 fusions. Transcriptionally, RSPO fusion organoids resembled normal colon organoids and were distinct from APC mutant organoids, with high BMP2 and low PTK7 expression. Single cell transcriptome analysis confirmed the similarity between RSPO fusion organoids and normal organoids, with a propensity for maturation on Wnt withdrawal, whereas the APC mutant organoids were locked in progenitor stages. CRISPR/Cas9 engineered mutation of APC in normal human colon organoids led to upregulation of PTK7 protein and suppression of BMP2, but less so with an engineered RNF43 mutation. The frequent co-occurrence of RSPO fusions with SMAD4 or BMPR1A mutation was confirmed in TCGA database searches. RNF43 mutation was found in organoid from a leukaemia survivor with a novel mutational signature; and organoids with POLE proofreading mutation displayed ultramutation. The cancer organoid genomes were stable over long culture periods, while normal human colon organoids tended to be subject to clonal dominance over time.ConclusionsThese organoid models enriched in EOCRCs with linked genomic data fill a gap in existing CRC models and reveal distinct genetic profiles and novel pathway cooperativity.

Background Type 2 diabetes diagnosed during youth and early adulthood is aggressive and associated with a high burden of vascular complications. The increase in complications is often attributed to long disease duration and poor metabolic control. Whether people with young‐onset type 2 diabetes are inherently more susceptible to long‐term complications than those diagnosed in later adulthood is unclear. Methods Prospective data from 3322 individuals, diagnosed between the age of 15 and 70 years and collected 10–25 years after diabetes diagnosis, were analysed. The cross‐sectional associations between age at diagnosis and microvascular and macrovascular complications were analysed using logistic regression models, adjusted for duration of diabetes exposure and metabolic risk factors including blood pressure, cholesterol and updated mean HbA1c. Results The prevalence of retinopathy was highest in those with young‐onset type 2 diabetes (diagnosed at age 15 to, What's new? Young‐onset type 2 diabetes is an aggressive disease, associated with a higher burden of complications than that seen in older‐onset diabetes.It is not known whether young people have an underlying increased susceptibility to complications or whether their long‐term excess risk of complications can be explained by glycaemia and longer duration of disease exposure.Unlike other complications, risk of retinopathy in young‐onset type 2 diabetes (or those with a younger current age) is twofold higher than in older‐onset type 2 diabetes, after adjustment for duration of diabetes exposure, glycaemia and other known risk factors. This finding supports an underlying increased susceptibility to retinal complications for young people.This increased risk of retinopathy indicates a need for more frequent surveillance and aggressive management of known risk factors, and supports a reconsideration of the diabetic retinopathy guidelines for young people and those with a younger age at diagnosis.A search for as yet unidentified contributing factors for retinopathy risk in young people is warranted.

OBJECTIVE Surgical site infection (SSI) following spine surgery causes major morbidity and greatly impedes functional recovery. In the modern era of advanced operative techniques and improved perioperative care, SSI remains a problematic complication that may be reduced with institutional practices. The objectives of this study were to 1) characterize the SSI rate and microbial etiology following spine surgery for various thoracolumbar diseases, and 2) identify risk factors that were associated with SSI despite current perioperative management. METHODS All patients treated with thoracic or lumbar spine operations on the neurosurgery service at the University of California, San Francisco from April 2012 to April 2016 were formally reviewed for SSI using the National Healthcare Safety Network (NHSN) guidelines. Preoperative risk variables included age, sex, BMI, smoking, diabetes mellitus (DM), coronary artery disease (CAD), ambulatory status, history of malignancy, use of preoperative chlorhexidine gluconate (CHG) showers, and the American Society of Anesthesiologists (ASA) classification. Operative variables included surgical pathology, resident involvement, spine level and surgical technique, instrumentation, antibiotic and steroid use, estimated blood loss (EBL), and operative time. Multivariable logistic regression was used to evaluate predictors for SSI. Odds ratios and 95% confidence intervals were reported. RESULTS In total, 2252 consecutive patients underwent thoracolumbar spine surgery. The mean patient age was 58.6 ± 13.8 years and 49.6% were male. The mean hospital length of stay was 6.6 ± 7.4 days. Sixty percent of patients had degenerative conditions, and 51.9% underwent fusions. Sixty percent of patients utilized presurgery CHG showers. The mean operative duration was 3.7 ± 2 hours, and the mean EBL was 467 ± 829 ml. Compared to nonfusion patients, fusion patients were older (mean 60.1 ± 12.7 vs 57.1 ± 14.7 years, p II (48.0% vs 36.0%, p < 0.001), and experienced longer operative times (252.3 ± 120.9 minutes vs 191.1 ± 110.2 minutes, p < 0.001). Eleven patients had deep SSI (0.49%), and the most common causative organisms were methicillin-sensitive Staphylococcus aureus and methicillin-resistant S. aureus. Patients with CAD (p = 0.003) or DM (p = 0.050), and those who were male (p = 0.006), were predictors of increased odds of SSI, and presurgery CHG showers (p = 0.001) were associated with decreased odds of SSI. CONCLUSIONS This institutional experience over a 4-year period revealed that the overall rate of SSI by the NHSN criteria was low at 0.49% following thoracolumbar surgery. This was attributable to the implementation of presurgery optimization, and intraoperative and postoperative measures to prevent SSI across the authors’ institution. Despite prevention measures, having a history of CAD or DM, and being male, were risk factors associated with increased SSI, and presurgery CHG shower utilization decreased SSI risk in patients. ABBREVIATIONS ASA = American Society of Anesthesiologists; CAD = coronary artery disease; CHG = chlorhexidine gluconate; CI = confidence interval; DM = diabetes mellitus; EBL = estimated blood loss; LOS = length of stay; MIS = minimally invasive surgery; MRSA = methicillin-resistant Staphylococcus aureus; MRSE = methicillin-resistant Staphylococcus epidermidis; MSSA = methicillin-sensitive S. aureus; MSSE = methicillin-sensitive S. epidermidis; NHSN = National Healthcare Safety Network; OR = odds ratio; SSI = surgical site infection.

The insulin-like peptide relaxin (RLX), an endogenous peptide hormone produced in human for pregnancy and reproduction, is also known to exert a range of physiological and pathological effects. Its use is banned in human sports, horseracing, and equestrian competitions due to its potential performance enhancing effect through vasodilation resulting in the increase of blood and oxygen supplies to muscles. Little is known about the biotransformation and elimination of RLX in horses. This paper describes an administration study of rhRLX-2 and its elimination in horses, and the development of sensitive methods for the detection and confirmation of rhRLX-2 in both horse plasma and urine by nano-liquid chromatography/high resolution mass spectrometry (nano-LC/HRMS) after immunoaffinity extraction with the objective of controlling the abuse of rhRLX-2 in horses. The limits of detection in plasma and urine are 2 pg/mL and 5 pg/mL, respectively. Two thoroughbred geldings were each administered one dose of 10 mg rhRLX-2 subcutaneously daily for 3 consecutive days. The rhRLX-2 could be detected and confirmed in the plasma and urine samples collected 105 h and 80 h, respectively, after the last dose of administration. For doping control purposes, rhRLX-2 ELISA could be used as a screening test to identify potential positive samples for further investigation using the nano-LC/HRMS methods.

We sought to report the safety of implementation of a novel standard of care protocol using spinal cord perfusion pressure (SCPP) maintenance for managing traumatic spinal cord injury (SCI) in lieu of mean arterial pressure goals at a U.S. Level I trauma center.Starting in December 2017, blunt SCI patients presenting24 hours after injury with admission American Spinal Injury Association Impairment Scale (AIS) A-C (or AIS D at neurosurgeon discretion) received lumbar subarachnoid drain (LSAD) placement for SCPP monitoring in the intensive care unit and were included in the TRACK-SCI (Transforming Research and Clinical Knowledge in Spinal Cord Injury) data registry. This SCPP protocol comprises standard care at our institution. SCPPs were monitored for 5 days (goal ≥65 mm Hg) achieved through intravenous fluids and vasopressor support. AISs were assessed at admission and day 7.Fifteen patients enrolled to date were aged 60.5 ± 17 years. Injury levels were 93.3% (cervical) and 6.7% (thoracic). Admission AIS was 20.0%/20.0%/26.7%/33.3% for A/B/C/D. All patients maintained mean SCPP ≥65 mm Hg during monitoring. Fourteen of 15 cases required surgical decompression and stabilization with time to surgery 8.8 ± 7.1 hours (71.4%12 hours). At day 7, 33.3% overall and 50% of initial AIS A-C had an improved AIS. Length of stay was 14.7 ± 8.3 days. None had LSAD-related complications. There were 7 respiratory complications. One patient expired after transfer to comfort care.In our initial experience of 15 patients with acute SCI, standardized SCPP goal-directed care based on LSAD monitoring for 5 days was feasible. There were no SCPP-related complications. This is the first report of SCPP implementation as clinical standard of care in acute SCI.

Background Mild-traumatic brain injury (mTBI) and concussions cause significant morbidity. To date, synthesis of specific health care disparities and gaps in care for rural mTBI/concussion patients remains needed. Methods A comprehensive literature search was performed using PubMed database for English articles with keywords “rural” and (“concussion” or “mild traumatic brain injury”) from 1991 to 2019. Eighteen articles focusing on rural epidemiology (n = 5), management/cost (n = 5), military (n = 2), and concussion prevention/return to play (n = 6) were included. Results mTBI/concussion incidence was higher in rural compared with urban areas. Compared with urban patients, rural patients were at increased risk for vehicular injuries, lifetime number of concussions, admissions for observation without neuroimaging, and injury-related costs. Rural patients were less likely to utilize ambulatory and mental health services following mTBI/concussion. Rural secondary schools had decreased access to certified personnel for concussion evaluation, and decreased use of standardized assessment instruments/neurocognitive testing. While school coaches were aware of return-to-play laws, mTBI/concussion education rates for athletes and parents were suboptimal in both settings. Rural veterans were at increased risk for postconcussive symptoms and posttraumatic stress. Telemedicine in rural/low-resource areas is an emerging tool for rapid evaluation, triage, and follow-up. Conclusions Rural patients are at unique risk for mTBI/concussions and health care costs. Barriers to care include lower socioeconomic status, longer distances to regional medical center, and decreased availability of neuroimaging and consultants. Due to socioeconomic and distance barriers, rural schools are less able to recruit personnel certified for concussion evaluation. Telemedicine is an emerging tool for remote triage and evaluation.