Transradial access for anterior circulation deployment of pipeline embolization device: A case report, literature review, and technical note.

Common femoral artery (CFA) transfemoral access (TFA) has been the traditional route for neuroendovascular intervention with flow diversion including the pipeline embolization device (PED) for the treatment of wide-necked aneurysms. Successful deployment requires significant catheter support, thus making alternative access challenging. A 56-year-old-female presented with subarachnoid hemorrhage secondary to a large ruptured posterior communicating artery (PCOM) aneurysm as well as found to have an unruptured left superior cerebellar artery (SCA) aneurysm. Endovascular embolization of PCOM aneurysm via TFA was complicated by a right CFA pseudoaneurysm. The SCA aneurysm was treated 8 weeks later via left TFA with consequent development of a left CFA pseudoaneurysm. Contrasted magnetic resonance angiography revealed recurrence at the neck of the PCOM aneurysm at 4-month follow-up, treated via transradial access (TRA) PED flow diversion to avoid additional groin complications. Anatomic, procedural, and clinical considerations for TRA anterior circulation flow diversion using the PED are reviewed.

Caudal Regression Syndrome-A Review Focusing on Genetic Associations.

Caudal regression syndrome (CRS) represents a spectrum of clinical phenotypes with varying degrees of malformation of the lower body with involvement of structures deriving from all 3 layers of the trilaminar embryo. We review areas of active investigation in the diagnosis, etiology, epidemiology, and treatment of the disease with a focus on underlying genetics. CRS pathobiology is complex and multifactorial with a significant contribution from environmental factors as evidenced in twin studies. Contemporary genomic and genetic investigations in both human primary tissue and murine in vitro and in vivo models implicate various genes associated with caudal differentiation and neural cell migration in embryogenesis. A large number of identified targets center around the metabolic regulation of retinoic acid and its derivatives. Dysregulation of retinoic acid homeostasis has been associated with abnormal embryonic cell migration, differentiation, and organogenesis with resulting malformations and agenesis in both a laboratory and a clinical setting. There appears to be a significant overlap in potential genetic targets with CRS and other developmental syndromes with similar presentations, such as VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) association. CRS represents a spectrum of caudal developmental abnormalities with treatment options limited to mild and moderate expressions of disease. Continued research is necessary to further clarify mechanisms of disease pathobiology and complex polygenetic and environmental interaction. Despite this, progress has been made in identifying genetic targets and downstream effectors contributing to preclinical and clinical progression.

Relationship of the Obturator Nerve and Psoas Major: Anatomic Study with Application to Avoiding Iatrogenic Injuries.

BACKGROUND: The proximal course of the obturator nerve as related to the psoas major has been described differently among various authors. Because this relationship is important for better understanding of clinical presentations and during surgical approaches, this study aimed to elucidate this anatomy via cadaveric dissection. METHODS: Twenty obturator nerves from 10 white cadaveric specimens underwent dissection. Observations were made of the relationship between the nerve and psoas major muscle. RESULTS: On all sides, the obturator nerve descended posterior to the psoas major and never through it. CONCLUSIONS: These results might be important to clinicians who interpret radiology of this region, to clinicians who treat patients with presumed obturator compression syndromes, or to surgeons who operate near the intracavitary part of the obturator nerve.

Cryptogenic stroke: clinical consideration of a heterogeneous ischemic subtype.

BACKGROUND: Cryptogenic stroke can be subdivided into 3 distinct categories: stroke of no determined cause (CyNC), stroke due to multiple etiologies (Cy >1), and stroke etiology unclear due to incomplete evaluation. Although these subdivisions may be very different from one another with respect to baseline features and outcomes, they are often reported as a composite group in clinical trials. METHODS: Patients treated at our academic institution between July 2008 and June 2013 for acute ischemic stroke were retrospectively assessed in our prospective registry. CyNC and Cy >1 patients were compared to other Trial of Org 10172 in Acute Stroke Treatment (TOAST) stroke subtypes and to each other using univariate analyses and multivariate logistic regression. The primary outcome of interest was good functional outcome, defined as a discharge modified Rankin Scale score of 0-2. RESULTS: Of the 1311 included patients, 260 (19.8%) experienced a CyNC and 49 (3.7%) experienced a Cy >1. Cy >1 classification was associated with history of atrial fibrillation (odds ratio [OR], 3.17; 95% confidence interval [CI], 1.16-6.12; P = .001). In comparison to other TOAST classifications, CyNC strokes were more likely to have good functional outcome (OR, 1.97; 95% CI, 1.38-2.82; P < .001) after adjusting for baseline National Institutes of Health Stroke Scale, admission glucose, age, and intravenous tissue plasminogen activator (IV tPA). CONCLUSIONS: Even after adjusting for higher IV tPA treatment rates, ischemic stroke patients with no identified cause had better outcomes than other TOAST groups. Conversely, patients coded as cryptogenic with more than 1 likely cause represent a different patient subpopulation. These data argue against the consolidation of cryptogenic stroke subcategories in future investigations.

Biomarkers of bone remodeling in multiple myeloma patients to tailor bisphosphonate therapy.

BACKGROUND: Patients with multiple myeloma may be susceptible to osteonecrosis of the jaw (ONJ) and stress fractures due to long-term aminobisphosphonate (aBP) therapy. However, it is unknown whether urinary N-telopeptide (NTX) or other bone biomarkers are predictive of skeletal-related events (SRE) or the impact of cessation of aBP therapy on bone remodeling. METHODS: We studied markers of bone turnover over a 6-month period after a single dose of zoledronic acid in 29 patients with multiple myeloma in remission who previously received 8 to 12 doses of pamidronate or zoledronate (NCT00577642). Our primary objective was to determine the duration of time urinary NTX levels remain suppressed after a single dose of zoledronate. A secondary objective was to identify and correlate other markers of bone remodeling with NTX changes. Thirty cytokines, based on their possible role in bone remodeling, were tested using cytokine arrays. Candidates were confirmed by ELISA. RESULTS: All patients had continued suppression of NTX levels, except 1 patient who had an increase in NTX levels associated with an SRE. GDF-15 and decorin were found to decrease, whereas bone-specific alkaline phosphatase (BSALP) increased. Although not significant in aggregate, osteopontin and osteoprotegerin levels increased in at least half of the patients. CONCLUSION: Our data show that NTX levels continue to be suppressed after aBP therapy, and suggest that suppressed NTX levels may be predictive of freedom from SRE in this patient population. Furthermore, osteoblast suppression by aBP may be reversible in myeloma. These data provide the basis for less frequent dosing of aBPs.

Outcomes in patients with relapsed or refractory multiple myeloma in a phase I study of everolimus in combination with lenalidomide.

Everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor, has been studied in multiple myeloma (MM) but lacks significant single agent activity. Based on preclinical studies showing synergistic activity of mTOR inhibitors with lenalidomide, we studied the combination of lenalidomide and everolimus in relapsed or refractory MM in a phase I clinical trial. We assessed patient samples using gene expression, Western blotting and immunohistochemistry to probe the mTOR pathway. Twenty-six patients were evaluable for toxicity. Dose-limiting toxicities included grade 4 neutropenia and thrombocytopenia. The maximum tolerated dose was lenalidomide 15 mg and everolimus 5 mg for 21 d with a 7 d rest period. Grade 3/4 adverse events included thrombocytopenia (35%) and neutropenia (42%). The overall response rate was 65% (1 complete response + 4 partial response + 10 minimal response). The median progression-free survival was 5·5 months and median overall survival was 29·5 months. Biomarker data demonstrated downregulation of phosphorylated p70S6K. Gene expression profiling suggested activation of mTOR in responders versus non-responders. The combination of lenalidomide and everolimus was well tolerated with predictable toxicities and showed responses in a heavily pretreated population. When confirmed with larger patient numbers, this analysis may guide patient selection for future clinical trials of mTOR inhibition in MM.