Current status and recommendations for biomarkers and biobanking in neurofibromatosis.

Objective: Clinically validated biomarkers for neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis (SWN) have not been identified to date. The biomarker working group's goals are to (1) define biomarker needs in NF1, NF2, and SWN; (2) summarize existing data on biomarkers in NF1, NF2, and SWN; (3) outline recommendations for sample collection and biomarker development; and (4) standardize sample collection and methodology protocols where possible to promote comparison between studies by publishing standard operating procedures (SOPs).

Methods: The biomarker group reviewed published data on biomarkers in NF1, NF2, and SWN and on biobanking efforts outside these diseases via literature search, defined the need for biomarkers in NF, and developed recommendations in a series of consensus meetings.

Current whole-body MRI applications in the neurofibromatoses: NF1, NF2, and schwannomatosis.

Objectives: The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration Whole-Body MRI (WB-MRI) Working Group reviewed the existing literature on WB-MRI, an emerging technology for assessing disease in patients with neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN), to recommend optimal image acquisition and analysis methods to enable WB-MRI as an endpoint in NF clinical trials.

Methods: A systematic process was used to review all published data about WB-MRI in NF syndromes to assess diagnostic accuracy, feasibility and reproducibility, and data about specific techniques for assessment of tumor burden, characterization of neoplasms, and response to therapy.

Results: WB-MRI at 1.

Sleep and pulmonary outcomes for clinical trials of airway plexiform neurofibromas in NF1.

Objective: Plexiform neurofibromas (PNs) are complex, benign nerve sheath tumors that occur in approximately 25%-50% of individuals with neurofibromatosis type 1 (NF1). PNs that cause airway compromise or pulmonary dysfunction are uncommon but clinically important. Because improvement in sleep quality or airway function represents direct clinical benefit, measures of sleep and pulmonary function may be more meaningful than tumor size as endpoints in therapeutic clinical trials targeting airway PN.

A Phase 1 Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimera Vaccines in Cytomegalovirus-Seronegative Men.

Background:  Human cytomegalovirus (HCMV) infection causes disease in newborns and transplant recipients. A HCMV vaccine (Towne) protects transplant recipients.

Methods:  The genomes of Towne and the nonattenuated Toledo strain were recombined, yielding 4 Towne/Toledo chimera vaccines.

Mind-body therapy via videoconferencing in patients with neurofibromatosis: An RCT.

Objective: To test, within a single-blind randomized controlled trial, the feasibility, acceptability, efficacy, and durability of a mind-body program (the Relaxation Response Resiliency Program for neurofibromatosis [3RP-NF]) vs an attention placebo control (Health Enhancement Program for NF [HEP-NF]), both delivered via group videoconferencing.

Methods: Sixty-three patients completed baseline assessments and were randomized. Primary outcomes were physical health and psychological quality of life (QoL), measured by the WHOQOL-BREF (World Health Organization QoL abbreviated instrument).

An in-vitro evaluation of three types of drug-eluting microspheres loaded with irinotecan.

To compare the mechanical and chemical properties of three commercially available microspheres loaded with irinotecan. LifePearl (200 µm), DC Bead (100-300 µm), and Tandem (100 µm) microspheres were loaded with irinotecan. For loading, elution, and stability determinations, irinotecan concentrations were quantified using validated high-performance liquid chromatography methods.

An In Vitro Evaluation of Four Types of Drug-Eluting Microspheres Loaded with Doxorubicin.

Purpose: To compare in vitro properties of 4 drug-eluting embolic agents loaded with doxorubicin.

Materials And Methods: DC Bead (100-300 µm), LifePearl (200 µm), HepaSphere (30-60 µm), and Tandem (100 µm) microspheres were loaded with 40 mg/20 mL of doxorubicin per milliliter of microspheres. Loading, elution, diameter changes after loading, changes in the amount of doxorubicin loaded over 2 weeks in storage, and time in suspension were evaluated.

The Fourth International Symposium on Genetic Disorders of the Ras/MAPK pathway.

The RASopathies are a group of disorders due to variations of genes associated with the Ras/MAPK pathway. Some of the RASopathies include neurofibromatosis type 1 (NF1), Noonan syndrome, Noonan syndrome with multiple lentigines, cardiofaciocutaneous (CFC) syndrome, Costello syndrome, Legius syndrome, and capillary malformation-arteriovenous malformation (CM-AVM) syndrome. In combination, the RASopathies are a frequent group of genetic disorders.

Health-related Quality of Life of Individuals With Neurofibromatosis Type 2: Results From the NF2 Natural History Study.

Objective: To explore health-related quality of life (HRQoL) reported by individuals with neurofibromatosis type 2 (NF2) and to assess for correlations between HRQoL and objective measures of disease manifestations.

Study Design: Prospective observational study.

Setting: Seven international NF2 centers.

Efficacy and Biomarker Study of Bevacizumab for Hearing Loss Resulting From Neurofibromatosis Type 2-Associated Vestibular Schwannomas.

Purpose: Neurofibromatosis type 2 (NF2) is a tumor predisposition syndrome characterized by bilateral vestibular schwannomas (VSs) resulting in deafness and brainstem compression. This study evaluated efficacy and biomarkers of bevacizumab activity for NF2-associated progressive and symptomatic VSs.

Patients And Methods: Bevacizumab 7.

Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis.

Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded byNF1) and merlin (encoded byNF2) have led to therapeutic advances for patients with NF1 and NF2.

Laryngeal Manifestations of Neurofibromatosis.

Objectives: To describe the range of findings in patients with neurofibromatosis (NF) presenting to a laryngology clinic and to analyze the etiologic factors of vocal fold dysfunction in this cohort.

Study Design: Case series with chart review.

Setting: Tertiary laryngology practice.

Increased Risk of Cerebrovascular Disease Among Patients With Neurofibromatosis Type 1: Population-Based Approach.

Background And Purpose: Although neurofibromatosis type 1 (NF1) may be associated with an incompletely understood vasculopathy, relative odds of stroke in this population is not known.

Methods: Using the 1998 to 2009 US Nationwide Inpatient Sample, we performed a case-control study matching cases of NF1 to controls without such a diagnosis. We then compared the odds of stroke between the 2 groups.

Glioblastoma care in the elderly.

Glioblastoma is common among elderly patients, a group in which comorbidities and a poor prognosis raise important considerations when designing neuro-oncologic care. Although the standard of care for nonelderly patients with glioblastoma includes maximal safe surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide, the safety and efficacy of these modalities in elderly patients are less certain given the population's underrepresentation in many clinical trials. The authors reviewed the clinical trial literature for reports on the treatment of elderly patients with glioblastoma to provide evidence-based guidance for practitioners.

Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model.

Hearing loss is the main limitation of radiation therapy for vestibular schwannoma (VS), and identifying treatment options that minimize hearing loss are urgently needed. Treatment with bevacizumab is associated with tumor control and hearing improvement in neurofibromatosis type 2 (NF2) patients; however, its effect is not durable and its mechanism of action on nerve function is unknown. We modeled the effect anti-VEGF therapy on neurological function in the sciatic nerve model and found that it improves neurological function by alleviating tumor edema, which may further improve results by decreasing muscle atrophy and increasing nerve regeneration.

Global incidence of serogroup B invasive meningococcal disease: a systematic review.

Use of recently licensed vaccines against Neisseria meningitidis serogroup B (NmB) will depend partly on disease burden estimates. We systematically reviewed NmB incidence and mortality worldwide between January, 2000, and March, 2015, incorporating data from 37 articles and 12 websites. Most countries had a yearly invasive NmB incidence of less than 2 per 100,000 people.

Protein Transfer Free Energy Obeys Entropy-Enthalpy Compensation.

We have found significant entropy-enthalpy compensation for the transfer of a diverse set of two-state folding proteins from water into water containing a diverse set of cosolutes, including osmolytes, denaturants, and crowders. In extracting thermodynamic parameters from experimental data, we show the potential importance of accounting for the cosolute concentration-dependence of the heat capacity change upon unfolding, as well as the potential importance of the temperature-dependence of the heat capacity change upon unfolding. We introduce a new Monte Carlo method to estimate the experimental uncertainty in the thermodynamic data and use this to show by bootstrapping methods that entropy-enthalpy compensation is statistically significant, in spite of large, correlated scatter in the data.

Pertussis Across the Globe: Recent Epidemiologic Trends From 2000 to 2013.

Pertussis has reemerged as a problem across the world. To better understand the nature of the resurgence, we reviewed recent epidemiologic data and we report disease trends from across the world. Published epidemiologic data from January 2000 to July 2013 were obtained via PubMed searches and open-access websites.

Bevacizumab treatment for symptomatic spinal ependymomas in neurofibromatosis type 2.

Background: Neurofibromatosis type 2 (NF2) is a tumor suppressor syndrome associated with vestibular schwannomas, meningiomas, and spinal ependymomas. There have been anecdotal reports of radiographic response of spinal ependymomas in NF2 patients being treated for progressive vestibular schwannomas with bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF).

Aims: The aim of this study was to review the clinical effects of bevacizumab treatment for symptomatic, NF2-associated ependymomas

Methods: We conducted a retrospective review of all patients with NF2 treated with bevacizumab for symptomatic ependymoma at three NF2 specialty centers.

Epidemiological and virological characteristics of influenza B: results of the Global Influenza B Study.

Introduction: Literature on influenza focuses on influenza A, despite influenza B having a large public health impact. The Global Influenza B Study aims to collect information on global epidemiology and burden of disease of influenza B since 2000.

Methods: Twenty-six countries in the Southern (n = 5) and Northern (n = 7) hemispheres and intertropical belt (n = 14) provided virological and epidemiological data.

A high-throughput kinome screen reveals serum/glucocorticoid-regulated kinase 1 as a therapeutic target for NF2-deficient meningiomas.

Meningiomas are the most common primary intracranial adult tumor. All Neurofibromatosis 2 (NF2)-associated meningiomas and ~60% of sporadic meningiomas show loss of NF2 tumor suppressor protein. There are no effective medical therapies for progressive and recurrent meningiomas.

Increasing Complexity of Vaccine Development.

Vaccines already developed have been enormously successful. However, the development of future vaccines requires solution of a number of immunologic problems, including pathogen variability, short effector memory, evoking functional responses, and identification of antigens that generate protective responses. In addition, different populations may respond differently to the same vaccine because of genetic, age, or environmental factors.