Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage.

BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known. METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients' assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment. RESULTS: A total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and -0.013 (95% Bayesian credible interval, -0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration. CONCLUSIONS: Among patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.).

New dual peroxisome proliferator activated receptor agonist-Saroglitazar in diabetic dyslipidemia and non-alcoholic fatty liver disease: integrated analysis of the real world evidence.

BACKGROUND: Saroglitazar, a novel dual peroxisome proliferator activated receptor (PPAR) agonist, in clinical trials, has shown an improvement in lipid and glycemic parameters through the PPAR-α and γ agonist actions, respectively. It was granted marketing authorization in India in 2013 for diabetic dyslipidemia. This review was conducted to summarize the effects of Saroglitazar in patients with diabetic dyslipidemia in real world clinical studies conducted after marketing authorization in India. METHODS: In this review, we selected real world clinical studies of Saroglitazar published as manuscripts and abstracts presented at scientific conferences. In all these studies, patients with diabetic dyslipidemia were treated with Saroglitazar 4 mg once daily for at least 12 weeks and different lipid and glycemic parameters were measured at the baseline and end of the study. RESULTS: In 18 selected studies (5 published manuscripts and 13 abstracts), a total of 5824 patients with diabetic dyslipidemia were prescribed Saroglitazar 4 mg for a duration ranging from 12 to 58 weeks. Across all the studies, mean age of patients ranged from 49.6 to 59.1 years and the proportion of female patients ranged from 22% to 42%. Across all the studies, there was a consistent mean reduction in triglyceride levels (~ 45% to 62%), total cholesterol levels (~ 17% to 26%), non-high-density lipoprotein cholesterol levels (~ 21% to 36%), low-density lipoprotein cholesterol levels (~ 11% to 27%), and glycosylated hemoglobin levels (~ 0.7% to 1.6%) with an increase in mean high-density lipoprotein cholesterol levels (up to 9%) from baseline to end of the study. Saroglitazar also improved alanine aminotransferase levels and fatty liver (evaluated by FibroScan™) in non-alcoholic fatty liver disease patients with diabetic dyslipidemia. Body weight remained unchanged and no significant adverse events (AEs) were reported in the studies. CONCLUSION: Saroglitazar effectively improved lipid and glycemic parameters without significant AEs in patients with diabetic dyslipidemia in real-world clinical studies of up to 58 weeks duration.

Intraoperative detection of isocitrate dehydrogenase mutations in human gliomas using a miniature mass spectrometer.

Knowledge of the isocitrate dehydrogenase (IDH) mutation status of glioma patients could provide insights for decision-making during brain surgery. However, pathology is not able to provide such information intraoperatively. Here we describe the first application of a miniature mass spectrometer (MS) to the determination of IDH mutation status in gliomas intraoperatively. The instrumentation was modified to be compatible with use in the operating room. Tandem MS was performed on the oncometabolite, 2-hydroxyglutarate, and a reference metabolite, glutamate, which is not involved in the IDH mutation. Ratios of fragment ion intensities were measured to calculate an IDH mutation score, which was used to differentiate IDH mutant and wild-type tissues. The results of analyzing 25 biopsies from 13 patients indicate that reliable determination of IDH mutation status was achieved (p = 0.0001, using the Kruskal-Wallis non-parametric test). With its small footprint and low power consumption and noise level, this application of miniature mass spectrometers represents a simple and cost-effective platform for an important intraoperative measurement. Graphical abstract.

Introduction: surgical management of skull base meningiomas.

Meningiomas represent the most common primary intracranial neoplasm treated by neurosurgeons. Although multimodal treatment of meningiomas includes surgery, radiation-based treatments, and occasionally medical therapy, surgery remains the mainstay of treatment for most symptomatic meningiomas. Because of the intricate relationship of the dura mater and arachnoid mater with the central nervous system and cranial nerves, meningiomas can arise anywhere along the skull base or convexities, and occasionally even within the ventricular system, thereby mandating a catalog of surgical approaches that neurosurgeons may employ to individualize treatment for patients. Skull base meningiomas represent some of the most challenging pathology encountered by neurosurgeons, on account of their depth, invasion, vascularity, texture/consistency, and their relationship to bony anatomy, cranial nerves, and blood vessels. Resection of complex skull base meningiomas often mandates adequate bony removal to achieve sufficient exposure of the tumor and surrounding region, in order to minimize brain retraction and optimally identify, protect, control, and manipulate sensitive neurovascular structures. A variety of traditional skull base approaches has evolved to address complex skull base tumors, of which meningiomas are considered the paragon in terms of both complexity and frequency. In this supplemental video issue of Neurosurgical Focus, contributing authors from around the world provide instructional narratives demonstrating resection of a variety of skull base meningiomas arising from traditionally challenging origins, including the clinoid processes, tuberculum sellae, dorsum sellae, petroclival region, falco-tentorial region, cerebellopontine angle, and foramen magnum. In addition, two cases of extended endoscopic endonasal approaches for tuberculum sellae and dorsum sellae meningiomas are presented, representing the latest evolution in accessing the skull base for selected tumors. Along with key pearls for safe tumor resection, an equally important component of open and endoscopic skull base operations for meningiomas addressed by the contributing authors is the reconstruction aspect, which must be performed meticulously to prevent delayed cerebrospinal fluid leakage and/or infections. This curated assortment of instructional videos represents the authors' optimal treatment paradigms pertaining to the selection of approach, setup, exposure, and principles to guide tumor resection for a wide spectrum of complex meningiomas.

Cervical Spine Clearance in Pediatric Trauma Centers: The Need for Standardization and an Evidence-based Protocol.

BACKGROUND: Cervical spine clearance in the pediatric trauma patient represents a particularly challenging task. Unfortunately, standardized clearance protocols for pediatric cervical clearance are poorly reported in the literature and imaging recommendations demonstrate considerable variability. With the use of a web-based survey, this study aims to define the methods utilized by pediatric trauma centers throughout North America. Specific attention was given to the identification of personnel responsible for cervical spine care, diagnostic imaging modalities used, and the presence or absence of a written pediatric cervical spine clearance protocol. METHODS: A 10-question electronic survey was given to members of the newly formed Pediatric Cervical Spine Study Group, all of whom are active POSNA members. The survey was submitted via the online service SurveyMonkey (https://www.surveymonkey.com/r/7NVVQZR). The survey assessed the respondent's institution demographics, such as trauma level and services primarily responsible for consultation and operative management of cervical spine injuries. In addition, respondents were asked to identify the protocols and primary imaging modality used for cervical spine clearance. Finally, respondents were asked if their institution had a documented cervical spine clearance protocol. RESULTS: Of the 25 separate institutions evaluated, 21 were designated as level 1 trauma centers. Considerable variation was reported with regards to the primary service responsible for cervical spine clearance. General Surgery/Trauma (44%) is most commonly the primary service, followed by a rotating schedule (33%), Neurosugery (11%), and Orthopaedic Surgery (8%). Spine consults tend to be seen most commonly by a rotating schedule of Orthopaedic Surgery and Neurosurgery. The majority of responding institutions utilize computed tomographic imaging (46%) as the primary imaging modality, whereas 42% of hospitals used x-ray primarily. The remaining institutions reported using a combination of x-ray and computed tomographic imaging. Only 46% of institutions utilize a written, standardized pediatric cervical spine clearance protocol. CONCLUSIONS: This study demonstrates a striking variability in the use of personnel, imaging modalities and, most importantly, standardized protocol in the evaluation of the pediatric trauma patient with a potential cervical spine injury. Cervical spine clearance protocols have been shown to decrease the incidence of missed injuries, minimize excessive radiation exposure, decrease the time to collar removal, and lower overall associated costs. It is our opinion that development of a task force or multicenter research protocol that incorporates existing evidence-based literature is the next best step in improving the care of children with cervical spine injuries. LEVEL OF EVIDENCE: Level 4-economic and decision analyses.

Ciliochoroidal ganglioneuroma in neurofibromatosis type 1: Report of a case and review of the literature.

Orbitofacial neurofibromatosis (OFNF) is considered a variant of neurofibromatosis type 1 (NF1). OFNF most often affects the eye, orbit and one side of the face. It is characterized by the development of relatively aggressive and disfiguring lesions, including plexiform and diffuse neurofibromas. Ciliochoroidal ganglioneuromas have not been previously reported in patients with this syndrome. We report the case of a 50-year-old man with OFNF, ciliochoroidal ganglioneuroma and a large ipsilateral frontoethmoidal encephalocele.

Outcomes in transcranial microsurgery versus extended endoscopic endonasal approach for primary resection of adult craniopharyngiomas.

OBJECTIVE Craniopharyngiomas have historically been resected via transcranial microsurgery (TCM). In the last 2 decades, the extended endoscopic endonasal (transtuberculum) approach to these tumors has become more widely accepted, yet there remains controversy over which approach leads to better outcomes. The purpose of this study is to determine whether differences in outcomes were identified between TCM and extended endoscopic endonasal approaches (EEEAs) in adult patients undergoing primary resection of suprasellar craniopharyngiomas at a single institution. METHODS A retrospective review of all patients who underwent resection of their histopathologically confirmed craniopharyngiomas at the authors' institution between 2005 and 2015 was performed. Pediatric patients, revision cases, and patients with tumors greater than 2 standard deviations above the mean volume were excluded. The patients were divided into 2 groups: those undergoing primary TCM and those undergoing a primary EEEA. Preoperative patient demographics, presenting symptoms, and preoperative tumor volumes were determined. Extent of resection, tumor histological subtype, postoperative complications, and additional outcome data were obtained. Statistical significance between variables was determined utilizing Student t-tests, chi-square tests, and Fisher exact tests when applicable. RESULTS After exclusions, 21 patients satisfied the aforementioned inclusion criteria; 12 underwent TCM for resection while 9 benefitted from the EEEA. There were no significant differences in patient demographics, presenting symptoms, tumor subtype, or preoperative tumor volumes; no tumors had significant lateral or prechiasmatic extension. The extent of resection was similar between these 2 groups, as was the necessity for additional surgery or adjuvant therapy. CSF leakage was encountered only in the EEEA group (2 patients). Importantly, the rate of postoperative visual improvement was significantly higher in the EEEA group than in the TCM group (88.9% vs 25.0%; p = 0.0075). Postoperative visual deterioration only occurred in the TCM group (3 patients). Recurrence was uncommon, with similar rates between the groups. Other complication rates, overall complication risk, and additional outcome measures were similar between these groups as well. CONCLUSIONS Based on this study, most outcome variables appear to be similar between TCM and EEEA routes for similarly sized tumors in adults. The multidisciplinary EEEA to craniopharyngioma resection represents a safe and compelling alternative to TCM. The authors' data demonstrate that postoperative visual improvement is statistically more likely in the EEEA despite the increased risk of CSF leakage. These results add to the growing evidence that the EEEA may be considered the approach of choice for resection of select confined primary craniopharyngiomas without significant lateral extension in centers with experienced surgeons. Further prospective, multiinstitutional collaboration is needed to power studies capable of fully evaluating indications and appropriate approaches for craniopharyngiomas.

Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis.

BACKGROUND: Current observational studies on warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation (AF) undergoing dialysis found conflicting results. METHODS AND RESULTS: We conducted a population-based retrospective cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF, in Quebec and Ontario, Canada from 1998 to 2007. The AF cohort was grouped into dialysis (hemodialysis and peritoneal dialysis) and nondialysis patients and into warfarin and no-warfarin users according to the first prescription filled for warfarin within 30 days after AF hospital discharge. We determined the association between warfarin use and the risk for stroke and bleeding in dialysis and nondialysis patients. The cohort comprised 1626 dialysis patients and 204 210 nondialysis patients. Among dialysis patients, 46% (756/1626) patients were prescribed warfarin. Among dialysis patients, warfarin users had more congestive heart failure and diabetes mellitus, but fewer prior bleeding events in comparison with the no-warfarin users. Among dialysis patients, warfarin use, in comparison with no-warfarin use, was not associated with a lower risk for stroke (adjusted hazard ratio, 1.14; 95% confidence interval, 0.78-1.67) but was associated with a 44% higher risk for bleeding (adjusted hazard ratio, 1.44; 95% confidence interval, 1.13-1.85) after adjusting for potential confounders. Propensity score-adjusted analyses yielded similar results. CONCLUSIONS: Our results suggest that warfarin use is not beneficial in reducing stroke risk, but it is associated with a higher bleeding risk in patients with AF undergoing dialysis.

Proton therapy for atypical meningiomas.

We report clinical outcomes of proton therapy in patients with World Health Organization grade 2 (atypical) meningiomas. Between 2005 and 2013, 22 patients with atypical meningiomas were treated to a median dose of 63 Gy (RBE) using proton therapy, as an adjuvant therapy after surgery (n = 12) or for recurrence or progression of residual tumor (n = 10). Six patients had presumed radiation-induced meningiomas, but none had received prior radiotherapy for their meningioma. The median follow-up time after radiation was 39 months (range 7-104) and all patients remain alive at last follow-up. The 5-year estimate of local control was 71.1% (95% CI 49.3-92.9%). The 5-year estimate of local control was 87.5% following a radiation dose >60 Gy (RBE), compared to 50.0% for ≤ 60 Gy (RBE) (p = 0.038). The 5-year estimate of neuraxis dissemination was 5% (95% CI 0-14.6%) and 6.2% (95% CI 0-18.2%) for metastases outside of the central nervous system. Radiation necrosis was observed in one patient with a history of prior cranial irradiation. Fractionated proton therapy was associated with favorable tumor control rates for grade 2 meningiomas. Prospective studies are needed to define the optimal radiation dose for high-grade meningiomas.

Association between angiotensin converting enzyme inhibitor or angiotensin receptor blocker use prior to major elective surgery and the risk of acute dialysis.

BACKGROUND: Some studies but not others suggest angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use prior to major surgery associates with a higher risk of postoperative acute kidney injury (AKI) and death. METHODS: We conducted a large population-based retrospective cohort study of patients aged 66 years or older who received major elective surgery in 118 hospitals in Ontario, Canada from 1995 to 2010 (n = 237,208). We grouped the cohort into ACEi/ARB users (n = 101,494) and non-users (n = 135,714) according to whether the patient filled at least one prescription for an ACEi or ARB (or not) in the 120 days prior to surgery. Our study outcomes were acute kidney injury treated with dialysis (AKI-D) within 14 days of surgery and all-cause mortality within 90 days of surgery. RESULTS: After adjusting for potential confounders, preoperative ACEi/ARB use versus non-use was associated with 17% lower risk of post-operative AKI-D (adjusted relative risk (RR): 0.83; 95% confidence interval (CI): 0.71 to 0.98) and 9% lower risk of all-cause mortality (adjusted RR: 0.91; 95% CI: 0.87 to 0.95). Propensity score matched analyses provided similar results. The association between ACEi/ARB and AKI-D was significantly modified by the presence of preoperative chronic kidney disease (CKD) (P value for interaction < 0.001) with the observed association evident only in patients with CKD (CKD - adjusted RR: 0.62; 95% CI: 0.50 to 0.78 versus No CKD: adjusted RR: 1.00; 95% CI: 0.81 to 1.24). CONCLUSIONS: In this cohort study, preoperative ACEi/ARB use versus non-use was associated with a lower risk of AKI-D, and the association was primarily evident in patients with CKD. Large, multi-centre randomized trials are needed to inform optimal ACEi/ARB use in the peri-operative setting.

Management of Fallopian Canal Spontaneous CSF Leaks, Implications of Elevated Intracranial Pressure: Case Report and Systematic Review of the Literature.

OBJECTIVES: Describe the diagnosis and management of a spontaneous cerebrospinal fluid leak (sCSF-L) through the facial nerve fallopian canal and determine the role of intracranial hypertension (IH). STUDY DESIGN: Retrospective case study and systematic review of the literature. METHODS: Reviewed patient characteristics, radiographic findings, and management of the facial nerve canal CSF leak and postoperative IH. Conducted systematic literature review according to the PRISMA guidelines for surgical management and rates of IH. RESULTS: A 50-year-old female with bilateral tegmen defects and temporal encephaloceles underwent left middle cranial fossa (MCF) repair. Intraoperative CSF egressed from the temporal bone tegmen defects. Facial nerve decompression revealed CSF leak from the labyrinthine segment. A nonocclusive temporalis muscle plug was placed in the fallopian canal, and tegmen repair was completed with bone cement. A ventriculoperitoneal shunt was placed for IH. Postoperative facial nerve function and hearing were normal. A total of 20 studies met inclusion criteria with a total of 25 unique patients. Of 13 total adult cases of fallopian canal CSF leak, there is a 46% recurrence rate, and 86% of patients had documented IH when tested. CONCLUSIONS: Fallopian canal CSF leaks are rare and challenging to manage. Assessment of intracranial hypertension and CSF diversion is recommended along with MCF skull base repair to preserve facial nerve function and conductive hearing.

Nail-plate Combination Treatment of Ipsilateral Humeral Shaft and Distal Humerus Fractures - A Case Report.

Introduction: Humeral shaft and distal humerus fractures have several different treatment options, including plate fixation and intramedullary nailing. Each has its own benefits, but typically, they are not used in conjunction. While nail-plate combinations (NPCs) have become more common in the lower extremity, literature on their use in upper extremity fractures remains scarce. Case Report: A 74-year-old right-hand dominant male presented after a fall with a closed left transverse midshaft humerus fracture and an associated supracondylar distal humerus fracture with intercondylar extension through a medial column. Due to the segmental nature of his injury, medial column plating was used in conjunction with a retrograde intramedullary nail to obtain anatomic reduction and fixation of the articular injury while stabilizing the midshaft humerus fracture with minimal soft tissue disruption. The patient was recommended non-weight bearing through his left arm for 6 weeks, at which point he returned to weight bearing as tolerated. He was allowed to range his left elbow after 2 weeks. His left elbow range of motion at the 4-month follow-up was 20-135 degrees, and he reported minimal pain. Conclusion: The retrograde NPC should be considered in segmental humeral fractures involving the distal articular surface and midshaft humerus fractures as it limits violation of the soft tissue while avoiding iatrogenic disruption of the articular surface at the shoulder or elbow.

Preoperative stereotactic radiosurgery for patients with 1-4 brain metastases: A single-arm phase 2 trial outcome analysis (NCT03398694).

Background: Stereotactic radiosurgery (SRS) following surgical resection is the standard of care for patients with symptomatic oligo brain metastasis (BM), however, it is associated with 10-15% local failure. Targeting a resection cavity is imprecise, thus preoperative radiosurgery where the target is well-defined may be superior, however, the efficacy of preoperative SRS has not yet been tested in a clinical trial. Methods: We conducted a phase 2, single-arm trial of preoperative SRS followed by surgical resection in patients with 1-4 symptomatic oligo BMs (NCT03398694) with the primary objective of measuring 6-month local control (LC). SRS was delivered to all patients utilizing a gamma knife or linear accelerator as per RTOG-9005 dosing criteria [Shaw E, Scott C, Souhami L, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000;47(2):291-298] based on tumor diameter with the exception that the largest lesion diameter treated was 5 cm with 15 Gy with all SRS treatment given in single fraction dosing. Results: The trial screened 50 patients, 48 patients were treated under the protocol and 32 patients completed the entire follow-up period. Of all the patients who completed the follow-up period, the primary endpoint of 6-month LC was 100% (95% CI: 0.891-1.000; P = .005). Secondary endpoints, presented as medians, were overall survival (17.6 months), progression-free survival (5.3 months), distant in-brain failure (40.8% at 1 year), leptomeningeal failure (4.8% at 1 year), and radiation necrosis (7.7% at 1 year). Conclusions: Our data confirms superior local control in patients who received preoperative SRS when compared to historical controls. Further study with a larger randomized cohort of patients is warranted to fully understand the benefits of preoperative SRS.

Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure.

Stereotactic radiosurgery (SRS) has been shown to be efficacious for the treatment of limited brain metastasis (BM); however, the effects of SRS on human brain metastases have yet to be studied. We performed genomic analysis on resected brain metastases from patients whose resected lesion was previously treated with SRS. Our analyses demonstrated for the first time that patients possess a distinct genomic signature based on type of treatment failure including local failure, leptomeningeal spread, and radio-necrosis. Examination of the center and peripheral edge of the tumors treated with SRS indicated differential DNA damage distribution and an enrichment for tumor suppressor mutations and DNA damage repair pathways along the peripheral edge. Furthermore, the two clinical modalities used to deliver SRS, LINAC and GK, demonstrated differential effects on the tumor landscape even between controlled primary sites. Our study provides, in human, biological evidence of differential effects of SRS across BM's.

The risk of perioperative bleeding in patients with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Worldwide, millions of patients with chronic kidney disease undergo surgery each year. Although chronic kidney disease increases the risk of bleeding in nonoperative settings, the risk of perioperative bleeding is less clear. We conducted a systematic review and meta-analysis to summarize existing information and quantify the risk of perioperative bleeding from chronic kidney disease. METHODS: We screened 9376 citations from multiple databases for cohort studies published between 1990 and 2011. Studies that met our inclusion criteria included patients undergoing any major surgery, with a sample size of at least 100 patients with chronic kidney disease (as defined by the primary study authors with an elevated preoperative serum creatinine value or a low estimated glomerular filtration rate). Their outcomes had to be compared with a reference group of at least 100 patients without chronic kidney disease. Our primary outcomes were (1) receipt of perioperative blood transfusions and (2) need for reoperation for reasons of bleeding. RESULTS: Twenty-three studies met our criteria for review (20 cardiac surgery, 3 non-cardiac surgery). Chronic kidney disease was associated with a greater risk of requiring blood transfusion (7 studies in cardiac surgery, totaling 22,718 patients) and weighted incidence in patients with normal kidney function was 53% and in chronic kidney disease was 73%; pooled odds ratio, 2.7 (95% confidence interval, 2.1-3.4). After adjustment for relevant factors, the association remained statistically significant in 4 studies. Chronic kidney disease was associated with more reoperation for reasons of bleeding (14 studies in cardiac surgery, totaling 569,715 patients) and weighted incidence in patients with normal kidney function was 2.4% and in chronic kidney disease was 2.7%; pooled odds ratio, 1.6 (95% confidence interval, 1.3-1.8). However, after adjustment for relevant factors (as done in 5 studies), the association was no longer statistically significant. CONCLUSIONS: Chronic kidney disease is associated with perioperative bleeding but not bleeding that required reoperation. Further studies should stage chronic kidney disease with the modern system, better define bleeding outcomes, and guide intervention to improve the safety of surgery in this at-risk population.

Spinous process fixation devices for instrumented spinal fusion.

Lumbar spinal fusion is a well-established surgical procedure for many spinal conditions. Posterior instrumentation may be added to provide immediate stabilization and improve fusion rates. Spinous process fixation, a type of posterior fixation, offers a less-invasive option to pedicle or facet screws with quantitative evidence of similar biomechanical stabilization; however, little has been published on the use of these devices. Further, there has been confusion about the use of spinous process fixation devices versus spinous process spacers. Spinous process fixation devices provide spine surgeons with another option for instrumented fusion, offering potential advantages for select patients. Biomechanical data suggest that relative to pedicle screws, modern spinous process fixation devices provide equivalent stability with reduced clinical risk and a less-invasive surgical procedure. These devices need to be distinguished from spacers, which are non-fixation devices.

Evaluation of the Posterior Tilt Angle in Predicting Failure of Nondisplaced Femoral Neck Fractures After Internal Fixation: A Systematic Review.

OBJECTIVE: To evaluate the posterior tilt angle (PTA) in predicting treatment failure after internal fixation of nondisplaced femoral neck fractures as graded by the Garden classification, which is based solely on anterior-posterior radiographic evaluation. DATA SOURCES: A search was conducted of all published literature in the following databases from inception to December 20, 2021: PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov . STUDY SELECTION: We included English-language randomized controlled trials, prospective and retrospective cohort studies that reported malunion/nonunion, avascular necrosis, fixation failure, or reoperations in patients with nondisplaced femoral neck fractures treated with internal fixation who were evaluated for PTA using either lateral radiograph or computed tomography. DATA EXTRACTION: All abstract, screening, and quality appraisal was conducted independently by 2 authors. Data from included studies were extracted manually and summarized. The Methodological Index for Non-Randomized Studies criteria was used for quality appraisal. DATA SYNTHESIS: Odds ratios with 95% confidence intervals were calculated for treatment failure, defined as nonunion/malunion, avascular necrosis, fixation failure, or reoperation, in cases involving preoperative PTA ≥20-degrees and <20-degrees. Statistical significance was set at P < 0.05. RESULTS: Nondisplaced femoral neck fractures with PTA >20-degrees had a 24% rate of treatment failure compared with 12% for those <20-degrees [odds ratios, 3.21 (95% confidence intervals, 1.95-5.28); P < 0.001]. CONCLUSION: PTA is a predictor of treatment failure in nondisplaced femoral neck fractures treated with internal fixation. Nondisplaced femoral neck fractures with a PTA >20-degrees may warrant alternative treatment modalities. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Dosimetric Impact of Source Displacement in GammaTile Surgically Targeted Radiation Therapy for Gliomas.

Background This study aims to evaluate dosimetric changes that happened during the first month after GammaTile surgically targeted radiation therapy (STaRT) for gliomas due to Cesium-131 (Cs-131) seed displacement caused by cavity shrinkage in brain brachytherapy. Methodology In this study, 10 glioma patients had 4-11 GammaTiles placed along the resection bed after maximal safe resection during craniotomy. Each GammaTile is composed of four Cs-131 seeds embedded in a biodegradable collagen sponge to minimize seed movement and maintain seed-to-cavity surface distance. The Cs-131 seed positions were identified using VariSeed on day one. On day 30, post-implant computed tomography (CT) images and dosimetry parameters were calculated. An iterative closest point (ICP) algorithm was used to compute rigid transformation between the day one and day 30 seed clouds. The seed displacement was calculated after registration. The volume receiving 100% of the prescription dose (V100), the dose received by 90% of the planning target volume (D90_PTV), the planning target volume receiving 100% of the prescription dose (V100_PTV), and the dose to organs at risk (OARs) were calculated for both CT images to determine the dosimetric changes from any seed displacement. Results The mean seed displacement of 1.8 ± 1.0 mm for all patients was observed between day one and day 30. The maximum seed displacement for each patient ranged from 2.3 mm to 7.3 mm. The mean V100 difference between day one and day 30 was 2.5 cc (range = 0.5-6.5 cc). The mean D90_PTVs were 95.5% (range = 69.0%-131.0%) and 98.1% (range = 19.9%-149.0%) on day one and day 30, respectively. The mean V100_PTVs were 88.4% (range = 81.3%-99.1%) and 87.9% (range = 47.0%-99.7%) on day one and day 30, respectively. On day one, the brainstem dose was 63.5 Gy for one case and 28.1 Gy for another case; while on day 30, the brainstem dose was 55.8 Gy and 20.6 Gy for the same patients, contributing to 7.7 Gy (12.8%) and 7.5 Gy (12.5%) dose reductions to brainstem for these patients, respectively. Only two patients received a dose to the optic nerves (34.1 Gy and 5.2 Gy). There were small changes (1.8 Gy and 0.5 Gy, respectively) in the dose to optic nerves when comparing the dose calculated on day one and the dose calculated on day 30 CT images. The same two patients received 30.4 Gy and 6.8 Gy to the chiasm, respectively. Small changes in the dose to the chiasm (≤1.1 Gy) were noted between day one and day 30. Conclusions A maximum seed displacement of up to 7.3 mm and a mean seed displacement of 1.8 mm caused by cavity shrinkage were observed during the first month after GammaTile STaRT for gliomas. There were noticeable changes in dosimetry parameters. Changes in the doses to OARs, particularly the brainstem, were large (up to 12.8% of the prescription dose). These changes in dosimetry should be considered when evaluating treatment outcomes and planning future GammaTile treatments.

Facial Nerve Preservation With Inferior Long-Axis Dissection of Large Vestibular Schwannomas.

OBJECTIVE: To describe a tumor resection using the inferior long-axis (ILA) technique for cisternal facial nerve dissection in large vestibular schwannomas (VS). STUDY DESIGN: Retrospective case series from 2018 to 2021. SETTING: Tertiary academic medical center. PATIENTS: Patients who underwent surgical resection with ILA facial nerve dissection of VS (>2.0 cm measured parallel to the petrous ridge) and had at least 3-month follow-up. INTERVENTIONS: Cisternal facial nerve dissection during retrosigmoid or translabyrinthine approach using standardized ILA technique developed by author R.N. MAIN OUTCOME MEASURES: Immediate postoperative and last follow-up facial nerve function with House-Brackmann scores of I to II defined as "good" facial nerve function and House-Brackmann scores III to VI defined as "poor" function. Extent of resection was also assessed. RESULTS: A total of 48 patients underwent large VS resection with ILA dissection of tumor off of the facial nerve from 2018 to 2021. Mean (standard deviation) tumor size was 3.11 (0.76) cm. Mean (standard deviation) follow-up was 9.2 (9.0) months. Gross-total resection or near-total resection were achieved in 75% (radiographic estimate) to 83% (surgeon estimate) of cases. End-of-case facial nerve stimulation at 0.05 mAmp with a response of at least 240 mV was achieved in 80.4% of patients. Good facial nerve function was observed in 72% immediately postoperatively, 70% 1-month postoperatively, and 82% of patients at last follow-up. CONCLUSIONS: The ILA technique is now the method of choice of the senior surgeon (R.N.) when performing microsurgical dissection of the cisternal facial nerve, with which he has achieved high rates of total or near-total resection with excellent facial nerve preservation.

Genomic Analysis of Human Brain Metastases Treated with Stereotactic Radiosurgery Under the Phase-II Clinical Trial (NCT03398694) Reveals DNA Damage Repair at the Peripheral Tumor Edge.

Stereotactic Radiosurgery (SRS) is one of the leading treatment modalities for oligo brain metastasis (BM), however no comprehensive genomic data assessing the effect of radiation on BM in humans exist. Leveraging a unique opportunity, as part of the clinical trial (NCT03398694), we collected post-SRS, delivered via Gamma-knife or LINAC, tumor samples from core and peripheral-edges of the resected tumor to characterize the genomic effects of overall SRS as well as the SRS delivery modality. Using these rare patient samples, we show that SRS results in significant genomic changes at DNA and RNA levels throughout the tumor. Mutations and expression profiles of peripheral tumor samples indicated interaction with surrounding brain tissue as well as elevated DNA damage repair. Central samples show GSEA enrichment for cellular apoptosis while peripheral samples carried an increase in tumor suppressor mutations. There are significant differences in the transcriptomic profile at the periphery between Gamma-knife vs LINAC.