Cephalic arch restenosis rates in hemodialysis patients with brachiocephalic fistulae: a retrospective multicenter analysis of 3301 patients.

BACKGROUND: We evaluated restenosis rates at the cephalic arch after percutaneous angioplasty and stenting procedures in patients with brachial artery to cephalic vein arteriovenous fistula (BCAVF) hemodialysis access. METHODS: We used data from adult hemodialysis patients treated at a national network of 44 outpatient interventional facilities during Oct 2011-2015. We included data from patients with BCAVF who received an exclusive angioplasty, or stent with angioplasty, for treatment of cephalic arch stenosis and had ≥1 subsequent evaluation of the cephalic arch. Median percent restenosis per month at cephalic arch and days between encounters was calculated from the 1st index to 2nd procedure, and for up to 4 subsequent encounters. Analyses were stratified by intervention and device types. RESULTS: We identified a cohort of 3301 patients (mean age 62.2 ± 13.9 years, 58.5% male, 33.2% white race) with a BCAVF who had an angioplasty, or stent, at the cephalic arch for an index and ≥ 1 follow-up procedure. Between the 1st index to 2nd procedure, patients who received an angioplasty (n = 2663) or stent (n = 933) showed a median decrease of 18.9 and 16.5% in luminal diameter per month and a median time of 93 and 91 days between encounters, respectively. Restenosis and day rates were similar for standard versus high-pressure angioplasties. Bare metal stents showed 10.1 percentage point higher restenosis rate compared to stent grafts. Restenosis rates and time to restenosis were relatively consistent across subsequent encounters. CONCLUSIONS: Findings suggest hemodialysis patients with a BCAVF who require an angioplasty or stent to treat a stenosis at the cephalic arch will have stenosis reformed at a rate of 18.9 and 16.5% per month after the first intervention, respectively. Findings suggest patients are at risk of having significant lesions at the cephalic arch within 3 months after the previous intervention.

Orthopedic uses of stem cell therapy.

The treatment of musculoskeletal disorders is gaining importance as the population ages. In addition to the complications brought on by prolonged life expectancy, the growing epidemic of obesity is contributing to joint degradation. Cell-based tissue engineering has the potential to advance the current treatment for musculoskeletal disorders. This article reviews the various forms of arthritis and describes stem cell therapy as a promising treatment option.

Sellar Masses that Present with Severe Hyponatremia.

OBJECTIVE: Hyponatremia is a known but underrecognized presentation of sellar lesions. Herein, we present a series of patients who presented with single or multiple episodes of hyponatremia. METHODS: Over 5 years, patients undergoing endonasal surgery for a de novo sellar mass with hyponatremia as an initial presentation were included. Pathology, sodium levels, pituitary hormonal status, and treatment course were documented. RESULTS: Of 282 patients, 16 (5.7%) (9 males, 7 females, age 32 to 84 years) presented with severe hyponatremia, with a mean serum sodium level of 115 ± 6 mmol/L (range, 101 to 125 mmol/L), and 3 patients had 2 or more episodes. Severe hyponatremia was a presenting sign in 0, 4.1, 14.3, and 37.5% of patients with craniopharyngiomas (n = 10), pituitary adenomas (n = 243), Rathke's cleft cysts (RCCs) (n = 21), and sellar arachnoid cysts (n = 8), respectively (P<.01). Half of the patients presenting with hyponatremia, including 6 of 10 patients with adenomas and 2 of 3 patients with RCCs, had pituitary apoplexy or cyst rupture. All patients had anterior pituitary gland dysfunction, including 81% with hypoadrenalism and 69% with hypothyroidism. Following surgery, hormonal status was unchanged or improved in 15 patients (median follow-up, 14 months). No patient had tumor/cyst recurrence or recurrent hyponatremia. CONCLUSION: Severe hyponatremia was a presenting sign in 5.7% of patients with sellar pathology, most frequently in patients with arachnoid cysts, RCCs, and pituitary apoplexy. Patients with new-onset severe hyponatremia and no obvious pharmacologic or systemic cause should undergo pituitary hormonal evaluation and brain imaging. Surgical resection and correction of hormonal deficiencies are associated with resolution of recurrent hyponatremic episodes.

Contemporary health care economics: an overview.

Economic evaluations provide a decision-making framework in which outcomes (benefits) and costs are assessed for various alternative options. Although the interest in complete and partial economic evaluations has increased over the past 2 decades, the quality of studies has been marginal due to methodological challenges or incomplete cost determination. This paper provides an overview of the main types of complete and partial economic evaluations, reviews key methodological elements to be considered for any economic evaluation, and reviews concepts of cost determination. The goal is to provide the clinician neurosurgeon with the knowledge and tools needed to appraise published economic evaluations and to direct high-quality health economic evaluations.

Time-driven activity-based costing: a driver for provider engagement in costing activities and redesign initiatives.

OBJECT: To date, health care providers have devoted significant efforts to improve performance regarding patient safety and quality of care. To address the lagging involvement of health care providers in the cost component of the value equation, UCLA Health piloted the implementation of time-driven activity-based costing (TDABC). Here, the authors describe the implementation experiment, share lessons learned across the care continuum, and report how TDABC has actively engaged health care providers in costing activities and care redesign. METHODS: After the selection of pilots in neurosurgery and urology and the creation of the TDABC team, multidisciplinary process mapping sessions, capacity-cost calculations, and model integration were coordinated and offered to engage care providers at each phase. RESULTS: Reviewing the maps for the entire episode of care, varying types of personnel involved in the delivery of care were noted: 63 for the neurosurgery pilot and 61 for the urology pilot. The average cost capacities for care coordinators, nurses, residents, and faculty were $0.70 (range $0.63-$0.75), $1.55 (range $1.28-$2.04), $0.58 (range $0.56-$0.62), and $3.54 (range $2.29-$4.52), across both pilots. After calculating the costs for material, equipment, and space, the TDABC model enabled the linking of a specific step of the care cycle (who performed the step and its duration) and its associated costs. Both pilots identified important opportunities to redesign care delivery in a costconscious fashion. CONCLUSIONS: The experimentation and implementation phases of the TDABC model have succeeded in engaging health care providers in process assessment and costing activities. The TDABC model proved to be a catalyzing agent for cost-conscious care redesign.

Assessing the cost of contemporary pituitary care.

OBJECT: Knowledge of the costs incurred through the delivery of neurosurgical care has been lagging, making it challenging to design impactful cost-containment initiatives. In this report, the authors describe a detailed cost analysis for pituitary surgery episodes of care and demonstrate the importance of such analyses in helping to identify high-impact cost activities and drive value-based care. METHODS: This was a retrospective study of consecutively treated patients undergoing an endoscopic endonasal procedure for the resection of a pituitary adenoma after implementation and maturation of quality-improvement initiatives and the implementation of cost-containment initiatives. RESULTS: The cost data pertaining to 27 patients were reviewed. The 2 most expensive cost activities during the index hospitalization were the total operating room (OR) and total bed-assignment costs. Together, these activities represented more than 60% of the cost of hospitalization. Although value-improvement initiatives contributed to the reduction of variation in the total cost of hospitalization, specific cost activities remained relatively variable, namely the following: 1) OR charged supplies, 2) postoperative imaging, and 3) use of intraoperative neuromonitoring. These activities, however, each contributed to less than 10% of the cost of hospitalization. Bed assignment was the fourth most variable cost activity. Cost related to readmission/reoperation represented less than 5% of the total cost of the surgical episode of care. CONCLUSIONS: After completing a detailed assessment of costs incurred throughout the management of patients undergoing pituitary surgery, high-yield opportunities for cost containment should be identified among the most expensive activities and/or those with the highest variation. Strategies for safely reducing the use of the targeted resources, and related costs incurred, should be developed by the multidisciplinary team providing care for this patient population.

Acute and chronic compartment syndromes: know when to act fast.

Compartment syndrome is a fairly common condition noted in patients with fractures or crush injuries to the extremities (acute compartment syndrome) and in athletes (chronic compartment syndrome). Compartments bound by fascia are found in the extremities, buttocks, and abdomen; conditions that cause intracompartmental swelling and hypertension can lead to ischemia and limb loss. This article reviews diagnosis of the problem, monitoring of compartment pressure, and appropriate treatment.

Corticospinal tractography as a prognosticator for motor improvement after brainstem cavernoma resection.

Given their highly eloquent location, surgical morbidity of brainstem cavernomas (BSCs) remain significant. Currently, there are no clinical factors or imaging techniques that can reliably predict post-operative motor improvement. Diffusion-tensor imaging (DTI) might have some prognostic value. We present a case supporting the use of DTI as predictor of motor recovery following brainstem surgery.

University of California, Los Angeles, surgical time-out process: evolution, challenges, and future perspective.

Since the development of the WHO Safe Surgery Saves Lives initiative and Surgical Safety Checklist, numerous hospitals across the globe have adopted the use of a surgical checklist. The UCLA Health System developed its first extended Surgical Safety Checklist in 2008. Authors of the present paper describe how the time-out checklist used before skin incision was implemented and how it progressed to its current form. Compliance with the most recent version of the checklist has been closely monitored via documentation and observance audits. In addition, the surgical team's appreciation of the current time-out has been assessed. Cultural, practice, and human resource challenges are discussed, as are potential future avenues for innovations in the emerging field of the surgical checklist in neurosurgery.

Impact of antibiotic-impregnated catheters on the timing of cerebrospinal fluid infections in non-traumatic subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) has been recognized as a risk factor for ventriculostomy-related infections (VRI). In addition to the hemorrhagic cerebrospinal fluid (CSF), the potential need for prolonged catheterization may contribute to the increased CSF infection rate in this population. The use of antibiotic-impregnated catheters (AIC) has effectively reduced the risk of VRI. Herein, we examined specifically the impact of systematic insertion of AIC on the timing of CSF infections in SAH patients. METHODS: Retrospective review of patients admitted between April 2006 to March 2009 with a non-traumatic SAH who required an external ventriculostomy. Only patients with AIC were included. A meningitis or ventriculitis was diagnosed according to the published criteria of the Center for Disease Control and Prevention. RESULTS: This study includes 75 patients in which 97 drains were inserted. Seven infections (7/75 = 9.3%) occurred over 1,024 drainage days (DD), resulting in a rate of 6.8 infections/1,000 DD. The mean drainage time was 15.4 days in the infected AIC group compared with 10.2 days in the non-infected AIC group. No infection occurred before day 9 of drainage and 71% (5/7) occurred after more than 2 weeks of drainage. The observed timing of infections is delayed in comparison with that reported in series using non-AIC, which typically occur prior to the 10th day of drainage. CONCLUSIONS: In the high-risk population of non-traumatic SAH, the use of AIC delays the occurrence of infection compared with that reported with non-antibiotic-impregnated catheters. This may orient management strategies in SAH patients requiring a ventriculostomy.

Management of Cushing's disease after failed surgery--a review.

Selective transsphenoidal adenomectomy is generally recommended for initial treatment of Cushing's disease (CD) because it achieves a high (70-85%) rate of remission. However, if initial surgery is not successful, the approach to persistent or recurrent CD is more complex. Because residual or recurrent adenoma is typically found at the site of the original adenoma, repeat transsphenoidal surgery is recommended including selective adenomectomy, hemihypophysectomy or total hypophysectomy. If repeat pituitary surgery does not achieve remission, then possible adjuvant therapies include radiosurgery or stereotactic radiotherapy, bilateral adrenalectomy, and/or medical therapy. In all cases of persistent or recurrent CD, successful treatment requires close collaboration of endocrinologists, radiation oncologists and neurosurgeons.

Unruptured cerebral aneurysms presenting with ischemic events.

BACKGROUND: Patients harboring an unruptured cerebral aneurysm may present with ischemic events. The goal of this study is to assess the clinical and radiological characteristics and the outcome following treatment of these patients. METHODS: The study population included 463 patients with unruptured cerebral aneurysms treated between January 2000 and November 2006. Patients with aneurysms manifesting with ischemic events were included. Outcome was assessed 12 months following aneurysm treatment using the modified Rankin scale. RESULTS: Eleven patients were included in this series. An acute ischemic lesion in the symptomatic territory was demonstrated in six patients. The aneurysms were located on the internal carotid artery (n=4), middle cerebral artery (n=4), superior cerebellar artery (n=2) and basilar artery (n=1). They measured 10 mm or less (n=7); 11-20 mm (n=2); more than 21 mm (n=2). Five aneurysms were partially thrombosed on imaging. Five patients were referred for coiling. Of these, one patient had an unsuccessful coiling attempt, one had a residual neck, and three presented an aneurysm recurrence. Six patients were treated surgically. Symptomatic thromboembolism occurred after surgery in three patients. Complete aneurysm exclusion was documented in five of six operated patients. Nine of the ten treated patients had a favorable outcome. CONCLUSION: Even though aneurysms presenting with ischemic events are often small and located on the anterior circulation, in this series the risk of thromboembolic events following aneurysm treatment is noteworthy. This information is relevant given the possible benign natural history in terms of stroke and risk of bleeding for some of these aneurysms.

Infraoptic course of anterior cerebral arteries associated with abnormal gyral segmentation. Case report.

The authors report the case of a 34-year-old woman who presented with increasing headaches. Neuroimaging revealed bilateral anomalous vessels arising at the level of each ophthalmic artery, coursing rostromedially to join the anterior communicating artery (ACA), which harbored an aneurysm. Intraoperatively, the authors identified an abnormal gyral segmentation of the frontoorbital region, with a median gyrus separated from the olfactory tracts on each side by the gyrus rectus. No interhemispheric fissure was observed in the exposed area. This is the first report in the literature of an abnormal gyral segmentation in association with an infraoptic course of an ACA. Recognition of this possible gyral abnormality in association with this vascular anomaly is relevant for surgical exposure and treatment of aneurysms by clip placement.

Diffusion tensor imaging analysis of long association bundles in the presence of an arteriovenous malformation.

OBJECT: Conventional imaging demonstrates intertwined fibers of the cerebral white matter as a homogeneous substrate. Recently, diffusion tensor imaging has allowed 3D reconstruction of these fiber bundles. The goal of this study was to analyze the modifications of the association fibers induced by an arteriovenous malformation (AVM) in the parietotemporooccipital (PTO) associative area and their clinical significance. METHODS: The authors analyzed the long association fibers in seven patients harboring an AVM in or near the PTO region in relation with the fibers' clinical manifestation. The fibers include the arcuate fasciculus (AF), the occipitofrontal fasciculus (OFF), and the inferior longitudinal fasciculus (ILF). These structures were compared with the contralateral bundles. RESULTS: The modification of the tracts could establish a pattern signature depending on the specific location of the vascular malformation. There was a positive correlation between the degree of modifications of OFF and ILF fiber tracts and visual deficits. Alteration of the AF correlated with a speech disorder and the risk of postoperative deficits. CONCLUSIONS: Diffusion tensor imaging enables in vivo dissection of fiber tracts coursing through the PTO area. Depending on the location of the AVMs, long association fibers are variously modified. These findings correlate with clinical manifestations and may predict outcome after surgery.

The response to brain tumor-derived growth factors is altered in radioresistant human brain endothelial cells.

INTRODUCTION: Radioresistant brain tumor vasculature is thought to hamper the efficiency of adjuvant cancer therapies. However, little is known regarding the signalling pathways involved in the angiogenic response to brain tumor-derived growth factors in irradiated human brain microvascular endothelial cells (HBMEC). The goal of this study is to assess the effect of ionizing radiation (IR) on HBMEC survival, migration and tubulogenesis. METHODS: HBMEC were cultured and irradiated at sublethal single doses. Cell survival was assessed by nuclear cell counting and flow cytometry. HBMEC migration in response to brain tumor-derived growth factors (U-87 GF) and tubulogenesis were assayed using modified Boyden chambers and Matrigel, respectively. RESULTS: We observed that single administration of 3-10 Gy IR doses only reduced cell survival by 30%. Radioresistant HBMEC overexpressed RhoA, a small GTPase protein regulating cellular adhesion and migration, and Rho-kinase (ROK), a serine-threonine protein kinase and one of RhoA's major targets. HBMEC migration was induced by vascular endothelial growth factor (VEGF), but even more so in response to sphingo-sine-1-phosphate (S1P) and to U-87 GF. Following IR exposure, HBMEC basal migration increased more than two-fold, whereas the response to S1P and to U-87 GF was significantly diminished. Similarly, the inhibitor of ROK Y-27632 decreased HBMEC migration in response to S1P and U-87 GF. Overexpression of RhoA decreased tubulogenesis, an effect also observed in irradiated HBMEC. CONCLUSION: Our results suggest that radioresistant HBMEC migration response to tumor-secreted growth factors and tubulogenesis are altered following IR. The RhoA/ROK signalling pathway is involved in the IR-altered angiogenic functions and may represent a potential molecular target for enhancing the impact of radiotherapy on tumor-associated endothelial cells.

The Survivin-mediated radioresistant phenotype of glioblastomas is regulated by RhoA and inhibited by the green tea polyphenol (-)-epigallocatechin-3-gallate.

INTRODUCTION: Glioblastoma multiforme's (GBM) aggressiveness is potentiated in radioresistant tumor cells. The combination of radiotherapy and chemotherapy has been envisioned as a therapeutic approach for GBM. The goal of this study is to determine if epigallocatechin-3-gallate (EGCg), a green tea-derived anti-cancer molecule, can modulate GBMs' response to ionizing radiation (IR) and whether this involves mediators of intracellular signaling and inhibitors of apoptosis proteins. MATERIAL AND METHODS: U-87 human GBM cells were cultured and transfected with cDNAs encoding for Survivin, RhoA or Caveolin-1. Mock and transfected cells were irradiated at sublethal single doses. Cell proliferation was analyzed by nuclear cell counting. Apoptosis was detected using a fluorometric caspase-3 assay. Analysis of protein expression was accomplished by Western immunoblotting. RESULTS: IR (10 Gy) reduced control U-87 cell proliferation by 40% through a caspase-independent mechanism. The overexpression of Survivin induced a cytoprotective effect against IR, while the overexpression of RhoA conferred a cytosensitizing effect upon IR. Control U-87 cells pretreated with EGCg exhibited a dose-dependent decrease in their proliferation rate. The growth inhibitory effect of EGCg was not antagonized by overexpressed Survivin. However, Survivin -transfected cells pretreated with EGCg became sensitive to IR, and their RhoA expression was downregulated. A potential therapeutic effect of EGCg targeting the prosurvival intracellular pathways of cancer cells is suggested to act synergistically with IR. CONCLUSION: The radioresistance of GBM is possibly mediated by a mechanism dependent on Survivin in conjunction with RhoA. The combination of natural anti-cancerous molecules such as EGCg with radiotherapy could improve the efficacy of IR treatments.