Citations

Abstract BACKGROUND Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis. Up to 50% of patients develop central nervous system involvement, and a subset of these patients can present with isolated tumor-like masses. OBJECTIVE To describe the skull base manifestations of ECD with an emphasis on aspects most pertinent to surgeons who may be referred such patients for primary evaluation. METHODS Scopus, Web of Science, and PubMed were searched from database inception to May 1, 2018 for articles reporting skull base ECD. An institutional retrospective analysis of all patients treated at the authors’ institution since January 1, 1996 was also performed to supplement these data. RESULTS Of 465 retrieved articles, 18 studies totaling 20 patients met inclusion criteria. Institutional review identified an additional 7 patients. Collectively, the median age at diagnosis was 49 yr (interquartile range, 42-58) with a 4:1 male-to-female ratio. Patients frequently presented with diplopia (48%), headache (30%), dysarthria (22%), and vertigo or imbalance (22%), though trigeminal hypesthesia (11%), facial nerve paresis (7%), hearing loss (7%), and trigeminal neuralgia (7%) were also observed. ECD commonly mimicked meningioma (33%), trigeminal schwannoma (8%), neurosarcoidosis (8%), and skull base lymphoma (8%). CONCLUSION Discrete skull base lesions frequently mimic more common pathology such as meningioma or cranial nerve schwannomas. Medical therapy comprises the initial treatment for symptomatic skull base disease. Surgical resection is not curative and the utility of surgical intervention is largely limited to biopsy to establish diagnosis and/or surgical debulking to relieve mass effect.

Background Age, tumor size and location, overall health, and patient preference are primary considerations driving treatment decision-making for intracranial meningiomas. However, even for the same individual patient, treatment recommendations may vary between centers and providers. Objective To study associations between geography, disease presentation, and management of intracranial meningioma in the United States. Methods The population-based Surveillance, Epidemiology, and End Results(SEER) data were queried between 2004 and 2014 for cases of intracranial meningioma. Results A total of 65,808 patients with intracranial meningioma were identified. Univariate analyses demonstrated strong associations between geographic location, age, and size of tumor at presentation. The mean age for all registries was 64.2 years, with a range from 62.0 (Utah registry) to 66.6 (Detroit registry). The greatest proportion of small tumors (<1 cm) were identified in the Utah registry (13.9% of tumors), while the greatest proportion of large tumors (> 4cm) were noted in the Hawaii registry (30.7% of tumors). Multivariable analysis demonstrated that the impact of geography on treatment selection was just as important as other established variables. For example, the distribution in tumor size between New Mexico and Greater California registries is nearly identical; however, the odds ratio for surgery was 1.5 times greater for the New Mexico population. Conclusion These data suggest that disease presentation and treatment are significantly influenced by regional referral patterns, provider or institutional treatment preferences, and regional availability of subspecialty expertise. Understanding such biases is important for patients, referring physicians, and treatment providers in an effort to provide balanced counseling and treatment.

Objective/Hypothesis The aim of the study was to determine the impact of race on disease presentation and treatment of intracranial meningioma in the United States. Study Design This study comprised of the analysis of a national population-based tumor registry. Methods Analysis of the surveillance, epidemiology, and end results (SEER) database was performed, including all patients identified with a diagnosis of intracranial meningioma. Associations between race, disease presentation, treatment strategy, and overall survival were analyzed in a univariate and multivariable model. Results A total of 65,973 patients with intracranial meningiomas were identified. Of these, 45,251 (68.6%) claimed white, 7,796 (12%) black, 7,154 (11%) Hispanic, 4,902 (7%) Asian, and 870 (1%) patients reported “other-unspecified” or “other-unknown.” The median annual incidence of disease was lowest among black (3.43 per 100,000 persons) and highest among white (9.52 per 100,000 persons) populations (p < 0.001). Overall, Hispanic patients were diagnosed at the youngest age and white patients were diagnosed at the oldest age (mean of 59 vs. 66 years, respectively; p < 0.001). Compared with white populations, black, Hispanic, and Asian populations were more likely to present with larger tumors (p < 0.001). After controlling for tumor size, age, and treatment center in a multivariable model, Hispanic patients were more likely to undergo surgery than white, black, and Asian populations. Black populations had the poorest disease specific and overall survival rates at 5 years following surgery compared with other groups. Conclusion Racial differences among patients with intracranial meningioma exist within the United States. Understanding these differences are of vital importance toward identifying potential differences in the biological basis of disease or alternatively inequalities in healthcare delivery or access Further studies are required to determine which factors drive differences in tumor size, age, annual disease incidence, and overall survival between races.

Abstract Background: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer–metabolite associations using two-sample Mendelian randomization (MR). Methods: The case–control portion of the study was conducted in nine UK centers with men ages 50–69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Results: Thirty-five metabolites were strongly associated with prostate cancer (P &lt; 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal. Conclusions: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk. Impact: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

Abstract BACKGROUND More than a million Americans harbor a cerebral cavernous angioma (CA), and those who suffer a prior symptomatic hemorrhage have an exceptionally high rebleeding risk. Preclinical studies show that atorvastatin blunts CA lesion development and hemorrhage through inhibiting RhoA kinase (ROCK), suggesting it may confer a therapeutic benefit. OBJECTIVE To evaluate whether atorvastatin produces a difference compared to placebo in lesional iron deposition as assessed by quantitative susceptibility mapping (QSM) on magnetic resonance imaging in CAs that have demonstrated a symptomatic hemorrhage in the prior year. Secondary aims shall assess effects on vascular permeability, ROCK activity in peripheral leukocytes, signal effects on clinical outcomes, adverse events, and prespecified subgroups. METHODS The phase I/IIa placebo-controlled, double-blinded, single-site clinical trial aims to enroll 80 subjects randomized 1-1 to atorvastatin (starting dose 80 mg PO daily) or placebo. Dosing shall continue for 24-mo or until reaching a safety endpoint. EXPECTED OUTCOMES The trial is powered to detect an absolute difference of 20% in the mean percent change in lesional QSM per year (2-tailed, power 0.9, alpha 0.05). A decrease in QSM change would be a signal of potential benefit, and an increase would signal a safety concern with the drug. DISCUSSION With firm mechanistic rationale, rigorous preclinical discoveries, and biomarker validations, the trial shall explore a proof of concept effect of a widely used repurposed drug in stabilizing CAs after a symptomatic hemorrhage. This will be the first clinical trial of a drug aimed at altering rebleeding in CA.

AbstractEnd‐stage renal disease (ESRD) patients receiving hemodialysis are typically anemic due to a lack of erythropoietin (EPO), a hormone required for red blood cell (RBC) production. EPO replacement therapy is complex, often resulting in oscillating hemoglobin (Hb) levels. EPO dosing protocols do not account for endogenous delays and appear to contribute to, if not cause, Hb variability. The Mayo Clinic Anemia Management System (MCAMS) is based on a physiological simulation of the production and lifespan of RBCs, driven by EPO dosage schedules. Patient‐specific parameters were found such that simulated Hb levels matched historical Hb levels in response to historical EPO doses. The calibrated model was used to identify new dosing regimens that stabilize Hb. MCAMS has been used to recommend individualized EPO dosage regimens to maintain stable Hb levels within a desired target range for more than 600 patients, improving patient outcomes while reducing medication costs by about 40 percent.© 2018 System Dynamics Society

Objectives: To highlight superior semicircular canal dehiscence (SSCD) involving the superior petrosal sinus (SPS), and to propose a novel classification system for SPS associated SSCD with potential surgical implications. Study Design: Multicenter retrospective review. Setting: Three tertiary referral centers. Patients: All patients diagnosed with SPS associated SSCD (1/2000 to 8/2016). Radiographic findings and clinical symptoms were analyzed. Intervention: Surgical repair or observation. Main Outcome Measure: Radiographic findings and clinical symptoms were analyzed. Results: Thirty-three dehiscences (30 patients) involving the SPS were identified. The average age at the time of presentation was 52.5 years (median, 56.9; range, 4.9–75.3 yr), and 53.3% of patients were men. Three patients had bilateral SPS associated SSCD. The most common associated symptoms at presentation were episodic vertigo (63.6%), subjective hearing loss (60.6%), and aural fullness (57.6%). Four distinct types of dehiscence were identified: class Ia. SSCD involving a single dehiscence into an otherwise normal appearing SPS; class Ib. SSCD involving a single dehiscence into an apparent venous anomaly of the SPS; class IIa. SSCD involving two distinct dehiscences into the middle cranial fossa and the SPS; class IIb. SSCD involving a single confluent dehiscence into the middle cranial fossa and the SPS. Conclusions: SSCD involving the SPS represents a small but distinct subset of SSCD cases. This scenario can create a unique set of symptoms and surgical challenges when intervention is sought. Clinical findings and considerations for surgical intervention are provided to facilitate effective diagnosis and management.