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Addressing flow disruptions (FDs) in neurosurgery requires a multifaceted approach. Strategies like improved communication protocols, minimizing interruptions, improving coordination among team, optimizing operating room layout, and promoting user-centered design can help mitigate the challenges and enhance the overall flow and safety of neurosurgical procedures. Thirty neurosurgery cases were observed at two tertiary care facilities. The data collected were from wheels into the operating room to wheels out from the operating room. Data points were categorized using a human factors taxonomy known as RIPCHORD-TWA (Realizing Improved Patient Care Through Human-Centered Operating Room Design for Threat Window Analysis). Of the 541 total disruptions observed, coordination issues were the most prevalent (26.25%), followed by layout issues (26.06%), issues related to interruption (22.55%), communication (22.37%), equipment issues (2.40%) and usability issues (0.37%) comprised the remainder of the observations. This translated into one disruption every 2.7 min. Instead of focusing exclusively on errors and adverse events, we propose conceptualizing the accumulation of disruptions as "threat windows" to analyze potential threats to the integrity of the care system. This perspective allows for the improved identification of system weaknesses or threats, affording us the ability to address these inefficiencies and intervene before errors and adverse events may occur.

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The conventional Extended State Observer-Based Control (ESOBC) technique is mostly applicable to a class of Integral Chain Form (ICF) structure with the matched kind of single-channel lumped disturbances. However, the systems having the non-ICF structure with the multi-channel matched and mismatched lumped disturbances are widely prevailing in the control applications, where the conventional ESOBC scheme may no longer applicable. To this end, it is recommended to upgrade the conventional ESOBC scheme for enhancing the feasibility and the applicability. This research work addresses the above-discussed recommendations using hybridizing the ESOBC with the Generalized ESOBC (GESOBC) which termed as Hybrid Extended State Observer Based Control (HyESOBC) in this paper. The proposed scheme is capable of estimating and controlling the multi-channel lumped disturbances (i.e., matched and mismatched) for a wide range of practical applications including the systems with the non-ICF structure. Simulation results and comparative analysis of numerical and practical application examples with the dual-channel lumped disturbances are presented to confirm the feasibility and the applicability of the proposed scheme.

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OBJECTIVE: Each U.S. state and the District of Columbia has passed legislation expanding access to naloxone, the opioid overdose antidote. Most naloxone access laws allow for standing orders, whereby prescribers may authorize pharmacists to dispense naloxone without an outside prescription. A recent study from our group assessing naloxone accessibility via standing order identified continued access barriers. The present study assessed whether brief, in-person, student-led academic detailing of community pharmacists improved naloxone accessibility. METHODS: A telephone audit of all 2317 CVS, Walgreens, H-E-B, and Walmart pharmacies in Texas was conducted to determine naloxone accessibility under standing orders. Within 2 months following the initial audit, student pharmacists visited the Austin and San Antonio, Texas area pharmacies that indicated they would not dispense naloxone without a prescription, to provide brief (< 5 minutes) academic detailing to the pharmacist on duty. Students followed a scripted outline designed to inform pharmacists about naloxone standing orders and naloxone use for opioid overdose response. Then they provided a flyer and requested that it be displayed in the pharmacy to inform patients about naloxone. An identical telephone audit was conducted 1-2 weeks following the education. RESULTS: Of the 49 pharmacies receiving education, 37 (76%) responded that they would dispense naloxone without an outside prescription appropriately. When comparing each pharmacy before and after detailing, respectively, it was observed that 51% versus 71% (P = 0.008) stocked naloxone; 43% versus 71% (P = 0.002) would dispense naloxone to a third-party customer; and 12% versus 37% (P = 0.005) would submit a claim to the insurance of a third-party customer. CONCLUSION: Student-led academic detailing was effective in improving pharmacists' willingness to dispense naloxone under standing orders and increasing naloxone accessibility from community pharmacies. Studies beyond Texas chain pharmacies are warranted to validate the effectiveness of this technique on a larger scale.

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Intracranial pseudoaneurysms secondary to traumatic birth are a rare finding in infants. Definitive diagnosis of such findings is challenging, and no standard management is delineated for management of pseudoaneurysms in the pediatric population. Commonly attempted treatments include endovascular embolization or surgical clipping. A 5-week-old female presented with a two day history of right hand focal seizures. The patient was found to have a dysplastic superficial intra-axial aneurysm arising from the distal left middle cerebral artery (MCA) branch in the setting of a left posterior frontal lobe hemorrhage noted on brain magnetic resonance imaging/magnetic resonance angiography (MRI/MRA). The patient underwent diagnostic cerebral angiogram demonstrating a left distal MCA pseudoaneurysm, which was treated with Onyx embolization. Post-embolization period was complicated by recurrent left central localized seizures and a left hemispheric temporoparietal hemorrhagic infarction. The patient was managed on levetiracetam, phenytoin, phenobarbital with stable seizure control. Herein, we highlight the youngest case to date of a 5-week-old infant with a left distal MCA pseudoaneurysm treated with Onyx embolization. Pseudoaneurysmal incidence, diagnosis and accepted management is discussed.

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Background and Purpose- Mechanical thrombectomy has been shown to improve clinical outcomes in patients with acute ischemic stroke. However, the impact of balloon guide catheter (BGC) use is not well established. Methods- STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever as first-line therapy. In this study, an independent core laboratory, blinded to the clinical outcomes, reviewed all procedures and angiographic data to classify procedural technique, target clot location, recanalization after each pass, and determine the number of stent retriever passes. The primary clinical end point was functional independence (modified Rankin Scale, 0-2) at 3 months as determined on-site, and the angiographic end point was first-pass effect (FPE) success rate from a single device attempt (modified Thrombolysis in Cerebral Infarction, ≥2c) as determined by a core laboratory. Achieving modified FPE (modified Thrombolysis in Cerebral Infarction, ≥2b) was also assessed. Comparisons of clinical outcomes were made between groups and adjusted for baseline and procedural characteristics. All participating centers received institutional review board approval from their respective institutions. Results- Adjunctive technique groups included BGC (n=445), distal access catheter (n=238), and conventional guide catheter (n=62). The BGC group had a higher rate of FPE following first pass (212/443 [48%]) versus conventional guide catheter (16/62 [26%]; P=0.001) and distal access catheter (83/235 [35%]; P=0.002). Similarly, the BGC group had a higher rate of modified FPE (294/443 [66%]) versus conventional guide catheter (26/62 [42%]; P<0.001) and distal access catheter (129/234 [55%]; P=0.003). The BGC group achieved the highest rate of functional independence (253/415 [61%]) versus conventional guide catheter (23/55 [42%]; P=0.007) and distal access catheter (113/218 [52%]; P=0.027). Final revascularization and mortality rates did not differ across the groups. Conclusions- BGC use was an independent predictor of FPE, modified FPE, and functional independence, suggesting that its routine use may improve the rates of early revascularization success and good clinical outcomes. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

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BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (P<0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06-1.79; P=0.02). Likewise, excellent outcome (modified Rankin Score 0-1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13-1.92; P=0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P=0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640.

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BACKGROUND AND PURPOSE: Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials. METHODS: STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis. RESULTS: A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab-adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2. CONCLUSIONS: This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.

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BACKGROUND: Epirubicin-HCl is highly efficient for breast cancer management at a concentration of 60-90 mg/m(2). However, its application is limited due to cumulative dose-dependent cardio-toxicity. PURPOSE: The main aim of this study was to formulate breast cancer-targeted liposomal carrier by surface conjugation of transferrin to minimize cardio-toxicity of drug along with improved pharmacokinetic profile. METHOD: Liposomes were formulated by ethanol injection method using HSPC, cholesterol and DSPG and later loaded with drug by the ammonium sulfate gradient method. The formulation was characterized for physicochemical properties like size, zeta potential, entrapment efficiency, TEM; in vitro tests like electro-flocculation, hemolysis and drug release; cell line study (MCF-7 cells); in vivo studies including LD50 determination, pharmacokinetic analysis, myocardial toxicity determination and stability. RESULTS AND DISCUSSION: Optimized formulation had molar ratio of 60:30:8:2 (HSPC:Chol:DSPG:mPEG-DSPE) with entrapment efficiency ∼83%, particle size below 200 nm and zeta potential about -20 mV. In vitro studies proved non-interfering property and drug release character of formulation while cell line studies demonstrated improvement in cell uptake and thereby increased cytotoxicity of targeted formulation. The IC50 value obtained for epirubicin solution, non-targeted and targeted liposomes was 0.675, 0.532 and 0.192 µg/ml, respectively. Furthermore, in vivo tests validated safety and distribution profile of prepared formulations. CONCLUSION: Apt properties of prepared Epirubicin-HCl liposomal formulation warrant its clinical application in breast cancer treatment after further studies.

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Pulmonary drug delivery system facilitates local instillation of anticancer drugs to lungs which has proven to be pioneering approach for treatment of lung cancer. This approach led the groundwork for delivering liposomal formulation directly to lungs. Gemcitabine-HCl is currently considered as most effective drug for management of lung cancer. However, its application is limited owing to its metabolism by enzymes present in plasma resulting in reduced efficacy and higher toxicity. In present study, lyophilisation technique was used to convert liposomes into dry powder inhaler, which was formulated using emulsification solvent evaporation technique. The physicochemical properties including size, morphology, entrapment efficiency, loading efficiency etc. of formulated liposomes were evaluated. The prepared liposomal DPI (LDPI) formulations were then examined for solid state characteristics and aerosol performance using cascade impactor. From all the formulations prepared, the LDPI formulated using trehalose as cryoprotectant presented required properties along with desirable deposition pattern. Finally, the optimized formulation was selected for in vitro cell line studies; in vivo studies and stability study. This formulated inhalable particles offers a promising approach for the management of lung cancer through regional chemotherapy.

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Despite the use of advanced microsurgical techniques, resection of intramedullary tumors may result in significant postoperative deficits because of the vicinity or invasion of important functional tracts. Intraoperative monitoring of somatosensory evoked potentials and transcranial electrical motor evoked potentials has been used previously to limit such complications. Electromyography offers an opportunity for the surgeon to map the eloquent tissue associated with the tumor using intraoperative motor fiber stimulation. Similar to the use of cortical simulation in the resection of supratentorial gliomas, this technique can potentially advance the safety of intramedullary spinal cord tumor resection. The authors describe the use of intraoperative motor fiber tract stimulation to map the corticospinal tracts associated with an intramedullary tumor. This technique led to protection of these tracts during resection of the tumor.

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Receptor-targeted drug delivery has been extensively explored for active targeting. However, the scarce clinical applications of such delivery systems highlight the implicit hurdles in development of such systems. These hurdles begin with lack of knowledge of differential expression of receptors, their accessibility and identification of newer receptors. Similarly, ligand-specific challenges range from proper choice of ligand and conjugation chemistry, to release of drug/delivery system from ligand. Finally, nanocarrier systems, which offer improved loading, biocompatibility and reduced premature degradation, also face multiple challenges. This review focuses on understanding these challenges, and means to overcome such challenges to develop efficient, targeted drug-delivery systems.

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OBJECT: A wide variety of spinal intradural pathology traditionally has been treated from a midline posterior laminectomy using standard microsurgical techniques. This approach has been successful in treating the pathology; however, it carries a risk of postoperative complications including CSF leakage, wound infection, and spinal instability. The authors describe a minimally invasive surgical (MIS) approach to treating spinal intradural pathology with a low rate of postoperative complications. METHODS: Through a retrospective review of a prospectively collected surgical database, the authors identified 26 patients who underwent 27 surgeries via an MIS approach for intradural pathology of the spine. Using a tubular retractor system and an operative microscope, the authors were able to treat all patients with a unilateral, paramedian, and muscle-splitting technique. They then collected data regarding operative blood loss, length of stay, imaging characteristics, and outcomes. RESULTS: Eight cervical, 8 thoracic, and 11 lumbar intradural pathological entities, which included 14 oncological lesions, 4 Chiari I malformations, 4 arachnoid cysts, 3 tethered cords, 1 syrinx, and 1 chronic visceral pain, were treated via an MIS approach. The average blood loss was 197 ml and the average hospital stay was 3 days. One patient had to return to the operating room for noninfectious wound dehiscence. One patient required reoperation 18 months after the initial surgery for recurrence of the initial pathology. There was no CSF leak, no infection, and no spinal instability associated with the initial surgery on follow-up. CONCLUSIONS: Intradural spinal pathology can be safely and effectively treated with MIS approaches without an increased risk of neurological injury. This approach may also offer a reduced postoperative length of stay, risk of CSF leak, and risk of future spinal instability.

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INTRODUCTION: Aneurysms arising from the cavernous internal carotid artery (CCAs) pose technical challenges for surgical management and such patients are frequently referred for endovascular treatment. These aneurysms often produce a variety of neurological deficits, primarily those related to oculoparesis. Our purpose was to determine the visual and neurological outcome of patients with treated CCAs. METHODS: We reviewed the medical records and angiograms for patients who underwent endovascular treatment for CCAs at three academic medical centers. The following outcomes were analyzed: angiographic assessment, visual improvement and outcome at 3 months using Glasgow Outcome Scale (GOS). RESULTS: Thirty-four patients (mean age 54.7 years) were treated for CCAs. The mean aneurysm size was 14.2 mm (range: 3-45 mm), and fourteen patients (41.2%) required stent assistance. Twenty-one aneurysms (61.8%) were completely occluded; nine aneurysms (26.6%) had near-complete occlusion; 4 aneurysms (11.8%) had partial occlusion. Seven patients (20.6%) required retreatment. Fifteen of the 34 patients (44.1%) presented with visual symptoms, while only eight patients had residual visual symptomatology at follow-up (44.1% vs. 23.5%; p=0.02). Patients that presented with visual symptoms (N=15) had a mean aneurysm size of 24.5 mm, while those without visual symptoms (N=19) had a size of 7.5 mm (p=0.001). Follow-up GOS was good (4-5) in 29 patients (90.6%). No thromboembolic complications were observed. One patient died (3.1%) of an unrelated cause. CONCLUSIONS: Most patients in this multicenter series improved or remained stable after treatment. The results of this study indicate that endovascular treatment may improve the outcome of visual symptoms in patients with large cavernous aneurysms with low periprocedural morbidity. COMPETING INTERESTS: MJA is a consultant for Stryker and Codman. AC receives a Cordis Endovascular Fellowship Training Grant and a Stryker Endovascular Neurosurgery Post-graduate Fellow Grant. JUSTIFICATION OF AUTHORSHIP: Dr. Drazin: Conception and Design, Drafting the Article and Critically Revising the Article Dr. Choulakian: Analysis and Interpretation of Data and Drafting the Article Dr. Nuno: Analysis and Interpretation of Data Dr. Gandhi: Analysis and Interpretation of Data and Drafting the Article Dr. Edgell: Analysis and Interpretation of Data and Drafting the Article Dr. Alexander: Critically Revising the Article and Conception and Design.

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Epithelioid hemangioendothelioma (EH) is a rare, vascular neoplasm that can affect any age group and has been reported previously in sites including bone, liver, lung, breast, and brain. We describe a case of EH located in the mastoid, which appears to be the first report of EH in this site. The patient was 62 years old when they presented with dizziness and nausea. A suboccipital surgical approach was utilized to resect the tumor. After 18-month followup, the patient was symptom-free; however, imaging demonstrated a recurrence and the patient was taken back to the operating room for a resection. There is no evidence of recurrence after 8 years of followup. This paper aims to reinforce the need for a timely radical excision and aggressive clinical followup as the best hope for cure. Here, we describe an illustrative case and review the pertinent literature.

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OBJECT: Recent randomized trials have demonstrated a positive role (improved survival) in patients treated with cranial decompression for malignant cerebral infarction. However, many variables regarding operative decompression in this setting remain to be determined. Hinge craniotomy is an alternative to decompressive craniectomy, but its role in space-occupying cerebral infarctions has not been delineated. The objective of this study was to compare the authors' experiences with these 2 procedures in the management of space-occupying cerebral infarctions to determine the efficacy of each. METHODS: The authors conducted a retrospective review of 28 cases involving patients who underwent cranial decompression (hinge craniotomy in 9 cases, decompressive craniectomy in 19) for treatment of malignant intracranial hypertension after ischemic cerebral infarction. RESULTS: No significant differences were identified in baseline demographics, neurological examination, or Rotterdam score between the hinge craniotomy and decompressive craniectomy groups. Both treatments resulted in adequate control of intracranial pressure (ICP). The need for reoperation for persistent intracranial hypertension and duration of mechanical ventilation and intensive care unit stay were similar. Hospital survival was significantly higher in the decompressive craniectomy group (89% vs 56%), whereas long-term functional outcome was better in the hinge craniotomy group. Cranial defect size was comparable in the 2 groups. Postoperative imaging revealed a higher rate of subarachnoid hemorrhage, contusion/hematoma progression, and subdural effusions/hygromas after decompressive craniectomy. The requirement for cranial revision in survivors was higher for patients undergoing decompressive craniectomy (100%) than those undergoing hinge craniotomy (20%). CONCLUSIONS: Hinge craniotomy appears to be at least as good as decompressive craniectomy in providing postoperative ICP control at a similar therapeutic index. Although the in-hospital mortality was higher in patients treated with hinge craniotomy, that procedure resulted in superior long-term functional outcomes and may help limit postoperative complications.

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OBJECT: The optimal management of a ventriculoperitoneal shunt in the setting of acute, non-shunt related abdominal and pelvic infections is unknown. In the literature, distal shunt catheter reimplantation with or without a variable period of externalization has been recommended to prevent ascending ventriculitis. While this strategy is effective, there is little to almost no published data suggesting that it is necessary in all cases. Furthermore, it is not clear that shunt externalization to an external drainage bag during the treatment of non-shunt related peritonitis is any less likely to lead to ventriculitis than leaving the catheter in place. In the authors' experience, shunt externalization or revision during an episode of acute, non-shunt related peritonitis is unnecessary to prevent ventriculitis or chronic peritonitis. METHODS: In the present case series, the authors report on 7 patients whose shunts were left in the abdomen while they were treated for acute peritonitis. The patients were followed clinically for up to 21 months after the diagnosis to assess for evidence of recurrent abdominal infections, shunt infections, or shunt failure. RESULTS: In a follow-up period ranging from 13 to 22 months, no patient developed ventriculitis, required a shunt revision, or was unable to clear the peritoneal infection. CONCLUSIONS: The results of this small series suggest that leaving the distal end of a shunt catheter in place in a patient with acute peritonitis is a reasonably safe choice in specific patients, provided the source of infection is aggressively treated with systemic antibiotics and local debridement when necessary.

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Inflammatory pseudotumors (IP) are non-neoplastic lesions characterized by collagenous stroma and polyclonal mononuclear infiltrates. It is best characterized in the lung, but can occur in the CNS, mimicking a neoplastic process. We discuss the available literature and our cases in order to elucidate best medical practices when confronted with such a lesion. We report on two cases of intraventricular inflammatory pseudotumor in patients who presented with symptoms of CSF obstruction. Both patients were treated surgically with significant clinical improvement. Histopathologically, both specimens revealed a plasma cell granuloma variant of IP. A Medline search for English articles identified 46 cases of CNS IP, only eight of which were located within the ventricle. As with our case, most patients presented due to CSF obstruction or mass effect. Radiographically, the lesions have a variable appearance although most enhanced with gadolinium. Complete resection was achieved in 67% with a 12% rate of recurrence. With incomplete resection or biopsy alone, progression is seen despite steroid or radiation administration. Malignant transformation was only reported once. CNS IP is a rare pathological entity that cannot be diagnosed through clinical presentation or radiographic characteristics, but rather through a careful neuropathological inspection. The available literature suggests that complete resection with close follow-up is necessary.

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