ORL

Vaccinations against glioma CD40/CD40L expression correlates with the survival of patients with glioblastomas and an augmentation in CD40 signaling enhances the efficacy of vaccinations against glioma models Chonan, M., Saito, R., Shoji, T., Shibahara, I., Kanamori, M., Sonoda, Y., Watanabe, M., Kikuchi, T., Ishii, N., Tominaga, T., 2015-10-16 08:28:34 AM Background The prognosis of glioblastoma (GBM) remains poor; therefore, effective therapeutic strategies need to be developed. CD40 is a costimulatory molecule whose agonistic antibody has been shown to activate antitumor effects. Recently, CD40 has been extensively targeted for immunotherapeutic purposes. Methods Expressions of CD40/CD40L mRNAs were examined in 86 cases of World Health Organization grade IV GBM and 36 cases of grade III gliomas and correlated with outcomes. CD40 signaling was employed to augment the efficacy of immunotherapy against gliomas. The efficacy of FGK45, an agonistic antibody for CD40, was examined by adding it to a tumor lysate–based subcutaneous vaccination against a GL261 glioma model and an NSCL61 glioma-initiating cell–like cell tumor model. Results We demonstrated for the first time using quantitative PCR that grade III gliomas express higher levels of CD40/CD40L than does grade IV GBM. The higher expression of CD40/CD40L was associated with good prognoses in patients with GBM. Addition of FGK45 to the subcutaneous tumor cell lysate–based vaccination significantly prolonged survival in both tumor models. However, the efficacy was modest in NSCL61-model mice. Therefore, we established combination immunotherapeutic strategies using FGK45 and OX86, an agonistic antibody for OX40. Combination immunotherapy significantly prolonged survival with synergistic effects. Apoptosis increased and proliferation decreased in tumors treated with combination immunotherapy. Conclusions The high expression of CD40/CD40L can be used as a biomarker for better prognoses in patients with gliomas. Immunotherapy using FGK45 significantly prolonged survival and represents a potential therapeutic strategy for gliomas including glioma-initiating cells. Read More » PET in patients with brain tumors From the clinician's point of view - What is the status quo of positron emission tomography in patients with brain tumors? Galldiks, N., Langen, K.-J., Pope, W. B., 2015-10-16 08:28:34 AM The most common type of primary brain tumor is malignant glioma. Despite intensive therapeutic efforts, the majority of these neoplasms remain incurable. Imaging techniques are important for initial tumor detection and comprise indispensable tools for monitoring treatment. Structural imaging using contrast-enhanced MRI is the method of choice for brain tumor surveillance, but its capacity to differentiate tumor from nonspecific tissue changes can be limited, particularly with posttreatment gliomas. Metabolic imaging using positron-emission-tomography (PET) can provide relevant additional information, which may allow for better assessment of tumor burden in ambiguous cases. Specific PET tracers have addressed numerous molecular targets in the last decades, but only a few have achieved relevance in routine clinical practice. At present, PET studies using radiolabeled amino acids appear to improve clinical decision-making as these tracers can offer better delineation of tumor extent as well as improved targeting of biopsies, surgical interventions, and radiation therapy. Amino acid PET imaging also appears useful for distinguishing glioma recurrence or progression from postradiation treatment effects, particularly radiation necrosis and pseudoprogression, and provides information on histological grading and patient prognosis. In the last decade, the tracers O-(2-[18F]fluoroethyl)-L-tyrosine (FET) and 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (FDOPA) have been increasingly used for these indications. This review article focuses on these tracers and summarizes their recent applications for patients with brain tumors. Current uses of tracers other than FET and FDOPA are also discussed, and the most frequent practical questions regarding PET brain tumor imaging are reviewed. Read More » Anti-angiogenic therapy for gliomas Current status and future directions of  Wick, W., Platten, M., Wick, A., Hertenstein, A., Radbruch, A., Bendszus, M., Winkler, F., 2015-10-16 08:28:36 AM Molecular targets for the pathological vasculature are the vascular endothelial growth factor (VEGF)/VEGF receptor axis, integrins, angiopoietins, and platelet-derived growth factor receptor (PDGFR), as well as several intracellular or downstream effectors like protein kinase C beta and mammalian target of rapamycin (mTOR). Besides hypoxic damage or tumor cell starvation, preclinical models imply vessel independent tumor regression and suggest differential effects of anti-angiogenic treatments on tumorous and nontumorous precursor cells or the immune system. Despite compelling preclinical data and positive data in other cancers, the outcomes of clinical trials with anti-angiogenic agents in gliomas by and large have been disappointing and include VEGF blockage with bevacizumab, integrin inhibition with cilengitide, VEGF receptor inhibition with sunitinib or cediranib, PDGFR inhibition with imatinib or dasatinib, protein kinase C inhibition with enzastaurin, and mTOR inhibition with sirolimus, everolimus, or temsirolimus. Importantly, there is a lack of real understanding for this negative data. Anti-angiogenic therapies have stimulated the development of standardized imaging assessment and the integration of functional MRI sequences into daily practice. Here, we delineate directions in the identification of molecularly or image-based defined subgroups, anti-angiogenic cotreatment for immunotherapy, and the potential of ongoing trials or modified targets to change the game. Read More » Brain and CNS tumors relative to other cancers : Years of potential life lost (YPLL) Years of potential life lost for brain and CNS tumors relative to other cancers in adults in the United States, 2010 Rouse, C., Gittleman, H., Ostrom, Q. T., Kruchko, C., Barnholtz-Sloan, J. S., 2015-10-16 08:28:36 AM Background Years of potential life lost (YPLL) complement incidence and survival rates by measuring how much a patient's life is likely to be shortened by his or her cancer. In this study, we examine the impact of death due to brain and other central nervous system (CNS) tumors compared to other common cancers in adults by investigating the YPLL of adults in the United States. Methods Mortality and life table data were obtained from the Centers for Disease Control and Prevention's National Center for Health Statistics Vital Statistics Data for 2010. The study population included individuals aged 20 years or older at death who died from one of the selected cancers. YPLL was calculated by taking an individual's age at death and finding the corresponding expected remaining years of life using life table data. Results The cancers with the greatest mean YPLL were other malignant CNS tumors (20.65), malignant brain tumors (19.93), and pancreatic cancer (15.13) for males and malignant brain tumors (20.31), breast cancer (18.78), and other malignant CNS tumors (18.36) for females. For both sexes, non-Hispanic whites had the lowest YPLL, followed by non-Hispanic blacks, and Hispanics. Conclusion Malignant brain and other CNS tumors have the greatest mean YPLL, thereby reflecting their short survival time post diagnosis. These findings will hopefully motivate more research into mitigating the impact of these debilitating tumors. Read More » Sleep health disparities research Mentoring junior URM scientists to engage in sleep health disparities research: experience of the NYU PRIDE institute Girardin Jean-Louis, Indu Ayapa, David Rapoport, Ferdinand Zizi, Collins Airhienbuwa, Kola Okuyemi, Gbenga Ogedegbe DOI: http://dx.doi.org/10.1016/j.sleep.2015.09.010 • Implementing training programs tailored to address specific needs of URM scientists is paramount in empowering them to address sleep-related cardiovascular diseases that disproportionately burden their communities. • The specific goals of the PRIDE Institute are to: select qualified junior URM faculty with potential to contribute to current knowledge of translational models to reduce sleep-related cardiovascular risk; increase mentees' knowledge, skills, and motivation to pursue a career in implementation of translational behavioral sciences; provide continuous mentorship to mentees and facilitate achievement of career independence; and dispense individualized coaching in acquiring proficiency in grant writing and understanding of the NIH review process. Highlights • Implementing training programs tailored to address specific needs of URM scientists is paramount in empowering them to address sleep-related cardiovascular diseases that disproportionately burden their communities. • The specific goals of the PRIDE Institute are to: select qualified junior URM faculty with potential to contribute to current knowledge of translational models to reduce sleep-related cardiovascular risk; increase mentees' knowledge, skills, and motivation to pursue a career in implementation of translational behavioral sciences; provide continuous mentorship to mentees and facilitate achievement of career independence; and dispense individualized coaching in acquiring proficiency in grant writing and understanding of the NIH review process. • Overall the institute accomplished its main goal: to build an infrastructure enabling junior URM faculty to network with one another as well as with senior investigators, serving as role models, in a supportive academic environment. • Exposure to the PRIDE Institute enables junior URM faculty to develop important research and leadership skills to compete nationally for funding to support their academic career. Abstract Purpose The purpose of this study was to evaluate the NIH-funded Program to Increase Diversity (PRIDE) in Behavioral Medicine and Sleep Disorders Research at NYU Langone Medical Center. The NYU PRIDE Institute provides intensive didactic and mentored research training to junior underrepresented minority (URM) faculty. Method The Kirkpatrick model, a mixed-methods program evaluation tool, was used to gather data on participant's satisfaction and program outcomes. Quantitative evaluation data were obtained from all 29 mentees using the PRIDE REDcap-based evaluation tool. Additionally, in-depth interviews and focus groups were conducted with 17 mentees to learn about their experiences at the institute and their professional development activities. Quantitative data were examined, and emerging themes from in-depth interviews and focus groups were studied for patterns of connection and grouped into broader categories based on grounded theory. Results Overall, mentees rated all programmatic and mentoring aspects of the NYU PRIDE Institute very highly (80-100%). They identified the following areas as critical to their development: research and professional skills, mentorship, structured support and accountability, peer support, and continuous career development beyond the summer institute. Indicators of academic self-efficacy showed substantial improvement over time. Areas for improvement included tailoring programmatic activities to individual needs, greater assistance with publications and identifying local mentors when K awards are sought. Conclusions Numerous factors that uniquely impact URM investigators' ability to succeed should be addressed in order to promote their career development. The NYU PRIDE Institute, which provides exposure to a well-resourced academic environment, leadership, didactic skills building, and intensive individualized mentorship proved successful in enabling URM mentees to excel in the academic environment. Overall the institute accomplished its goals: to build an infrastructure enabling junior URM faculty to network with one another as well as with senior investigators, serving as role models, in a supportive academic environment. Keywords: PRIDE, mentorship, training, workforce diversity, sleep, behavioral medicine Read More » Quantifying the Turbulent Noise Portion of Voice Signals An Objective Parameter for  Liyu Lin, William Calawerts, Keith Dodd, Jack J. Jiang DOI: http://dx.doi.org/10.1016/j.jvoice.2015.08.017 Currently, there are no objective measures capable of distinguishing between all four voice signal types proposed by Titze in 1995 and updated by Sprecher in 2010. We propose an objective metric that distinguishes between voice signal types based on the aperiodicity present in a signal. Summary Objectives Currently, there are no objective measures capable of distinguishing between all four voice signal types proposed by Titze in 1995 and updated by Sprecher in 2010. We propose an objective metric that distinguishes between voice signal types based on the aperiodicity present in a signal. Study design One hundred fifty voice signal samples were randomly selected from the Disordered Voice Database and subjectively sorted into the appropriate voice signal category on the basis of the classification scheme presented in Sprecher 2010. Methods Short-time Fourier transform was applied to each voice sample to produce a spectrum for each signal. The spectrum of each signal was divided into 250 time segments. Next, these segments were compared to each other and used to calculate an outcome named spectrum convergence ratio (SCR). Finally, the mean SCR was calculated for each of the four voice signal types. Results SCR was capable of significantly differentiating between each of the four voice signal types (P < 0.001). Additionally, this new parameter proved equally as effective at distinguishing between voice signal types as currently available parameters. Conclusion SCR was capable of objectively distinguishing between all four voice signal types. This metric could be used by clinicians to quickly and efficiently diagnose voice disorders and monitor improvements in voice acoustical signals during treatment methods. Key Words: Turbulence, Signal spectrum analysis, Short time Fourier transform, Voice signal classification, Spectrum convergence ratio Read More » There are four types of signals that are typical representations of vocal fold vibratory patterns Vibratory Dynamics of Four Types of Excised Larynx Phonations Lin Li, Yu Zhang, William Calawerts, Jack J. Jiang DOI: http://dx.doi.org/10.1016/j.jvoice.2015.08.012 There are four types of signals that are typical representations of vocal fold vibratory patterns. Type 1 signals are nearly periodic, type 2 signals contain subharmonic properties, type 3 signals are chaotic, and type 4 signals are characterized as white noise. High-speed imaging allows detailed observation of these vocal fold vibratory patterns. Therefore, high-speed imaging can explore the vibratory mechanism behind each of the four types of signals. Summary Objectives There are four types of signals that are typical representations of vocal fold vibratory patterns. Type 1 signals are nearly periodic, type 2 signals contain subharmonic properties, type 3 signals are chaotic, and type 4 signals are characterized as white noise. High-speed imaging allows detailed observation of these vocal fold vibratory patterns. Therefore, high-speed imaging can explore the vibratory mechanism behind each of the four types of signals. Methods The glottal area time series of the four types of vocal fold vibrations were calculated from high-speed images of 10 excised canine larynges. Nonlinear dynamic parameters of correlation dimension (D2) and Kolmogorov entropy (K2) were used to quantify the characteristics of the glottal areas and acoustical signals for each voice signal type. Results The correlation dimension and Kolmogorov entropy of the glottal areas and acoustical signals for type 1, 2, and 3 voice signals were consistent with the results of previous studies. Interestingly, there was a difference between the glottal area and acoustical signals of type 4 voice signals (P < 0.001). Both the correlation dimension and Kolmogorov entropy of the type 4 glottal area were close to 0. In contrast, the type 4 acoustical signals had an infinite correlation dimension and a Kolmogorov entropy that was close to 1. Conclusions Turbulence in the vocal tract creates high-frequency breathiness, causing noise in the acoustical signal of type 4 voice, proving that the acoustical signal does not represent the motion mechanism behind type 4 voice. The results of this study demonstrate that high-speed imaging can provide a more accurate representation of the type 4 vocal fold vibratory pattern, and a more effective method to explore the mechanism of type 4 signals. Read More » Giant aneurysms arising from the vertebral artery (VA) are often associated with thrombosis and present as mass lesions with slow progression of symptoms and signs Vasa vasorum and the growing of thrombosed giant aneurysm of the vertebral artery: a case report via World Neurosurgery Publication date: Available online 13 October 2015 Source:World Neurosurgery Author(s): Felix Hendrik Pahl, Eduardo de Arnaldo Silva Vellutini, Alberto Carlos Capel Cardoso, Matheus Fernandes de Oliveira BackgroundGiant aneurysms arising from the vertebral artery (VA) are often associated with thrombosis and present as mass lesions with slow progression of symptoms and signs. A consensus is still to be established on the underlying growth mechanisms and surgical management of thrombosed giant aneurysms of the vertebral artery.Clinical presentationHere we report the case of a 54-year-old man who searched neurosurgical care after 3 months of progressive cervical axial pain. He underwent cervical magnetic resonance imaging (MRI) and cerebral angiography, which revealed a giant VA aneurysm with thrombosed component. After failure of proximal and distal endovascular treatment, it was decided to perform surgical approach, which revealed a markedly developed vasa vasorum in aneurismal walls, raising the possibility of intraaneurismal nutrition from vasa vasorum. Patient recovered progressively and almost completely after surgery.Discussion and conclusionsAnother report have already described the case of a 58-year-old woman harboring a partially thrombosed giant aneurysm of VA. Interestingly, at the time of resection, a marked development of vasa vasorum on the occluded VA and the neck of the aneurysm was noted. We highlight the need to comprehend vasa vasorum as potential sources for aneurismal growth. Read More » Serum B-Type Natriuretic Peptide: A Potential Marker for Neoplastic Edema in Brain Tumor Patients? Serum B-Type Natriuretic Peptide: A Potential Marker for Neoplastic Edema in Brain Tumor Patients? via World Neurosurgery Publication date: Available online 13 October 2015 Source:World Neurosurgery Author(s): Xi Chen, Yu Yao, Liang-Fu Zhou Read More » Neoplastic Edema in Brain Tumor : Serum B-Type Natriuretic Peptide a Potential Marker Serum B-Type Natriuretic Peptide: A Potential Marker for Neoplastic Edema in Brain Tumor Patients? via World Neurosurgery Publication date: Available online 13 October 2015 Source:World Neurosurgery Author(s): Xi Chen, Yu Yao, Liang-Fu Zhou Clin Med Res. 2007 Dec; 5(4): 228–237. doi:  10.3121/cmr.2007.762 PMCID: PMC2275758 Tumor-Related Hyponatremia Adedayo A. Onitilo, MD, MSCR, FACP, Ebenezer Kio, MD, and Suhail A. R. Doi, MBBS, FRCP, PhD Adedayo A. Onitilo, MD, MSCR, FACP, Department of Hematology/Oncology Marshfield Clinic Weston Center 3501 Cranberry Boulevard Weston, Wisconsin Ebenezer Kio, MD, Southern Ohio Medical Center Cancer Center 1121 Kinneys Lane Portsmouth, Ohio Suhail A. R. Doi, MBBS, FRCP, PhD, Department of Medicine Mubarak Al Kabeer Teaching Hospital Jabriya, Kuwait and Department of Medicine, Kuwait University Kuwait Adedayo Onitilo, MD, MSCR, FACP, Marshfield Clinic, Weston Center, 3501 Cranberry Boulevard, Weston, WI 54476, Tel: 715-393-1400, Fax: 715-393-1399, Email: gro.cinilcdleifhsram@oyadeda.olitino ABSTRACT Hyponatremia is an important and common electrolyte disorder in tumor patients and one that has been reported in association with a number of different primary diagnoses. The correct diagnosis of the pathophysiological basis for each patient is important because it significantly alters the treatment approach. In this article, we review the epidemiology and presentation of patients with hyponatremia, the pathophysiologic groups for the disorder with respect to sodium and water balance and the diagnostic measures for determining the correct pathophysiologic groups. We then present the various treatment options based on the pathophysiologic groups including a mathematical approach to the use of hypertonic saline in management. In cancer patients, hyponatremia is a serious comorbidity that requires particular attention as its treatment varies by pathophysiologic groups, and its consequences can have a deleterious effect on the patient's health. Keywords: Antidiuretic hormone, Arginine vasopressin, Cancer, Hypertonic saline, Hyponatremia, Malignancy, SIADH, Sodium Hyponatremia, a serious electrolyte disorder associated with life-threatening neurological complications, is one of the most common electrolyte disorders associated with tumor-related conditions.1 Mild hyponatremia is defined as a serum sodium concentration <135, moderate <132, severe <130 mmol/L and life threatening <125 or abnormal sodium concentration with clinical signs.2 It usually accompanies, but can also precede the diagnosis of the tumor with an incidence of about 3.7% to 5%3 and may result from medical4 or surgical intervention.5 Hyponatremia develops most often when the ability of the kidney to excrete free water is impaired; hence it is primarily a disorder of water metabolism without impact on intravascular volume status.6 However, when the former is associated with loss or gain of total body sodium, features of changes in intravascular volume are also associated.6 This review focuses on hyponatremia in tumor-related conditions and tries to provide a state-of-the-art understanding of presentation, management and outcome. Major causes of tumor-related hyponatremia. Group Mechanism Causes Clinical presentation I. Normal sodium balance Ia Excess ADH Excess ADH As SIADH with normal extracellular fluid volume     Paraneoplastic syndrome     Antineoplastic agents         Cyclophosphamide         Vinca alkaloids Glucocorticoid deficiency Thyroid hormone deficiency Ib Excess intake of free water or pseudohyponatremia Tumor products Pseudohyponatremia or true water excess not due to SIADH     Immunoglobulin     Paraproteins Excess of hypotonic solutions II. Impaired sodium balance IIa Renal solute conservation Decreased true circulating blood volume Hypervolemic or hypovolemic with increased or decreased extracellular fluid volume, respectively but hyponatremia not due to disturbed renal handling of Na.     Gastrointestinal causes         Reduced salt and water intake         GI losses (vomiting and diarrhea)     Third spacing Decreased effective circulating blood volume     Heart failure     Liver cirrhosis IIb Renal solute loss Adrenocortical insufficiency Volume depleted with decreased extracellular fluid volume due to disturbed renal handling of Na. Excess ANP or BNP     Ectopic ANP     Cerebral salt wasting Renal salt wasting     Anticancer drugs         Cisplatin         Carboplatin ADH, antidiuretic hormone; ANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; SIADH, syndrome of inappropriate secretion of antidiuretic hormone. Go to: ABSTRACT Hyponatremia is an important and common electrolyte disorder in tumor patients and one that has been reported in association with a number of different primary diagnoses. The correct diagnosis of the pathophysiological basis for each patient is important because it significantly alters the treatment approach. In this article, we review the epidemiology and presentation of patients with hyponatremia, the pathophysiologic groups for the disorder with respect to sodium and water balance and the diagnostic measures for determining the correct pathophysiologic groups. We then present the various treatment options based on the pathophysiologic groups including a mathematical approach to the use of hypertonic saline in management. In cancer patients, hyponatremia is a serious comorbidity that requires particular attention as its treatment varies by pathophysiologic groups, and its consequences can have a deleterious effect on the patient's health. Keywords:  Read More » Stereotactic Radiosurgery for Partially Resected Cerebral Arteriovenous Malformations Stereotactic Radiosurgery for Partially Resected Cerebral Arteriovenous Malformations via World Neurosurgery Publication date: Available online 13 October 2015 Source:World Neurosurgery Author(s): Dale Ding, Zhiyuan Xu, Han-Hsun Shih, Robert M. Starke, Chun-Po Yen, Jason P. Sheehan ObjectiveIncomplete microsurgical resection of cerebral arteriovenous malformations (AVM) occurs uncommonly. However, such patients harboring postoperative residual nidi remain exposed to the risk of AVM hemorrhage and are, therefore, reasonable candidates for further intervention. The goals of this retrospective case-control study are to analyze the radiosurgery outcomes for partially resected AVMs and determine the effect of prior resection on AVM radiosurgery outcomes.MethodsWe evaluated a prospective database of AVM patients treated with radiosurgery from 1989-2013. Previously resected AVMs with radiologic follow-up ≥2 years or nidus obliteration were selected for analysis and matched, in a 1:1 fashion and blinded to outcome, to previously unresected AVMs. Statistical analyses were performed to assess relationship between prior resection and AVM radiosurgery outcomes.ResultsThe matching process yielded 88 patients in each of the previously resected and unresected AVM cohorts. In the resected AVM cohort, the actuarial AVM obliteration rates at 3 and 5 years were 47% and 75%, respectively; the rates of radiologic and symptomatic radiation-induced changes (RIC) were 10% and 3%, respectively; and the annual post-radiosurgery hemorrhage risk was 1.1%. The lack of prior AVM resection (P<0.001) and superficial AVM location (P=0.009) were independent predictors of radiologic RIC. The actuarial rates of obliteration (P=0.849) and post-radiosurgery hemorrhage (P=0.548) were not significantly different between the resected and unresected AVM cohorts.ConclusionsRadiosurgery affords a reasonable risk to benefit profile for incompletely resected AVMs. For those with a small volume residual nidus after resection, radiosurgery should be considered an effective alternative to repeat resection. Read More » Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), and surgical outcomes in patients with motor cortical arteriovenous malformations (AVMs) Preoperative functional findings and surgical outcomes in patients with motor cortical arteriovenous malformation via World Neurosurgery Publication date: Available online 13 October 2015 Source:World Neurosurgery Author(s): Fuxin Lin, Jun Wu, Bing Zhao, Xianzeng Tong, Zhen Jin, Yong Cao, Shuo Wang ObjectiveThe relationship between preoperative functional findings, derived from functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), and surgical outcomes in patients with motor cortical arteriovenous malformations (AVMs) has not been determined. The aim of this study was to determine the relationship between preoperative functional findings and surgical outcomes in patients with motor cortical AVM.Materials and MethodsFifteen patients with AVM involving precentral knob and/or paracentral lobule were reviewed. Each involved motor function was examined as an independent object. Preoperative functional findings included cortical reorganization, activation around the nidus, corticospinal tract (CST) reorganization, nidus involving the CST and the involved level of CST. The relationship between preoperative functional findings and surgical outcomes was statistically analyzed. A muscle strength≤grade 3 was defined as a poor outcome after surgery, and a muscle strength≥grade 4 was defined as a good outcome.ResultsEighteen objects were created and analyzed. Cortical reorganization (p=1.000) was not correlated with surgical outcomes. However, nidus involving the CST was significantly associated with poor short-term outcomes (1week after surgery) (p=0.028) and permanent muscle strength deficit (p=0.042). Most of the objects had good outcomes (16/18, 88.9%) at 6 months after surgery (long-term outcomes). Only one patient with CST ruptured at the corona radiata level and one patient who suffered from postoperative hemorrhage obtained poor long-term outcomes.ConclusionsNidus involving the CST and the involved level of the CST, rather than cortical reorganization, may be associated with surgical outcomes in patients with motor cortical AVM. Read More » Ruptured Infantile Myofibroma of the Head  Presenting in a Neonate: Case Report and Review of the Literature via World Neurosurgery Publication date: Available online 13 October 2015 Source:World Neurosurgery Author(s): Paul F. Koch, Tamara Fierst, Austin J. Heuer, Mariarita Santi, Gregory G. Heuer BackgroundInfantile myofibroma/myofibromatosis (IM/M) is a myofibroblastic proliferative disorder often seen in infants and children. IM/M can result in congenital tumors of the head and neck and may occasionally present to the neurosurgeon.Case DescriptionWe report a case of a solitary ruptured myofibroma of the head in a newborn patient. The lesion was initially suggestive of encephalocele. We describe the presentation and management of this patient, including relevant imaging, histopathological evaluation and surgical technique. We subsequently review the literature of IM/M of the head and neck, highlighting the three forms of the condition, each requiring a distinct management strategy.ConclusionWhile this tumor rarely presents to the neurosurgeon, it may do so in the process of ruling out other more dangerous conditions. It is therefore important to consider this diagnosis in masses that occur in the head and neck of newborns. Read More » Intensive Treatment for Geriatric Traumatic Brain Injury Outcome and Refractory Factor of Intensive Treatment for Geriatric Traumatic Brain Injury: Analysis of 1,165 cases registered in the Japan Neurotrauma Data Bank via World Neurosurgery Publication date: Available online 13 October 2015 Source:World Neurosurgery Author(s): Shoji Yokobori, Masahiro Yamaguchi, Yutaka Igarashi, Kohei Hironaka, Hidetaka Onda, Kentaro Kuwamoto, Takashi Araki, Akira Fuse, Hiroyuki Yokota Highlights • We assessed the intensive treatments and its' refractory factor in geriatric TBI. • We analyzed the data of 1,165 geriatric TBIs from latest Japanese national data (JNTDB) • Severely disabled dependent survivors increased with intensive treatment. • Not the patient's age but the existence of IVH was the strongest refractory factor (OR 5.762) against the intensive treatment. • Progress of aging biomarker, rehabilitation and treatment strategy will be needed for this cohort. Read More » Occurrence of Herpes Simplex Virus Reactivation Suggests a Mechanism of Trigeminal Neuralgia Surgical Efficacy World Neurosurgery Volume 84, Issue 2,2015, Pages 279–282 Original Article Occurrence of Herpes Simplex Virus Reactivation Suggests a Mechanism of Trigeminal Neuralgia Surgical Efficacy Richard B. Tenser, Departments of Neurology and Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA doi:10.1016/j.wneu.2015.03.022 Common to the types of surgery that are effective for the treatment of trigeminal neuralgia (TN) is reactivation of herpes simplex virus (HSV). It is likely that such HSV reactivation following surgery indicates altered trigeminal ganglion neuron function, which was caused by the surgery. It is not thought that HSV infection is related to the cause of TN or that HSV reactivation is important for surgical treatment efficacy. Rather, it is thought that HSV reactivation is a marker of altered trigeminal ganglion neuron function resulting from the TN surgery. It is suggested that HSV reactivation is a surrogate marker of ganglion neuron injury. The correlation between effective types of surgery and evidence that they alter ganglion neuron function suggests that altered trigeminal ganglion neuron function may be the basis of the surgical efficacy. Key words Herpes simplex virus reactivation; Trigeminal neuralgia surgery Abbreviations and Acronyms CNS, Central nervous system; HSV, Herpes simplex virus; MS, Multiple sclerosis; PCR, Polymerase chain reaction; TN, Trigeminal neuralgia Conflict of interest statement: RBT has received honoraria from the following pharmaceutical companies over the past 2 years: Biogen Idec, Novartis, Pfizer/Serono, and Teva. To whom correspondence should be addressed: Richard B. Tenser, M.D. Copyright © 2015 Elsevier Inc. All rights reserved. Read More » Ruptured basilar tip aneurysm in a patient with bilateral internal carotid artery occlusion  successfully treated with bilateral superficial temporal artery–middle cerebral artery anastomoses: case report via World Neurosurgery Publication date: Available online 13 October 2015 Source:World Neurosurgery Author(s): Masahiro Indo, Soichi Oya, Toru Matsui Highlights • A case of ruptured basilar top aneurysm with bilateral ICA occlusion is presented. • The blood supply relied on the posterior circulation via bilateral p-com arteries. • We opted for bilateral direct STA-MCA bypass to alleviate the hemodynamic stress. • The patient has been stable for the following 4 years and the aneurysm shrank. • Flow reduction may be effective for ruptured aneurysm under special circumstances. Read More » Low-flow related ischemic complications and neurological worsening in patients with complex internal carotid artery aneurysm treated by EC-IC high-flow bypass Risk factors for  via World Neurosurgery Publication date: Available online 13 October 2015 Source:World Neurosurgery Author(s): Hidetoshi Matsukawa, Rokuya Tanikawa, Hiroyasu Kamiyama, Toshiyuki Tsuboi, Kosumo Noda, Nakao Ota, Shiro Miyata, Go Suzuki, Rihee Takeda, Sadahisa Tokuda BackgroundThe revascularization technique has remained to be indispensable for complex aneurysms. However, risk factors for low-flow related ischemic complications (LRICs) and neurological worsening (NW) have been less well documented. We evaluated the risk factors for LRICs and NW in 67 patients treated with extracranial to intracranial (EC-IC) bypass graft using radial artery or saphenous vein graft for complex internal carotid artery (ICA) aneurysm with ICA occlusion.MethodsIntraoperative middle cerebral artery pressure (MCAP) by backup superficial temporal artery to middle cerebral artery bypass was measured. The MCAP ratio (MCAPR) was the ratio of the MCAP after release of the graft bypass to the initial MCAP. LRICs were defined as new neurological deficits and ipsilateral cerebral blood flow reduction in single photon emission computed tomography. Early and late NW were defined as an increase in 1 or more modified Rankin Scale at discharge and at the 12-month follow-up examination.ResultsDuring a median follow-up period of 13.3 months, LRICs were observed in 7 patients (10%). The Cox proportional hazards model showed a MCAPR ≦0.80 was significantly related to LRICs. Multivariate logistic regression analysis revealed perforating artery ischemia was significantly associated with early NW (n=13, 19%) and late NW (n=7, 13%). It also showed that LRICs were also significantly related to late NW.ConclusionsThe present study showed that regardless of the graft type, the MCAPR was associated with LRICs, which were related to late NW in patients with complex ICA aneurysms treated by EC-IC high-flow bypass graft. Read More » Metastases of the spine and cranium from retroperitoneal paraganglioma En bloc resection and reconstruction using a frozen tumor-bearing bone for metastases of the spine and cranium from retroperitoneal paraganglioma via World Neurosurgery Publication date: Available online 13 October 2015 Source:World Neurosurgery Author(s): Ryo Kitagawa, Hideki Murakami, Satoshi Kato, Mitsutoshi Nakada, Satoru Demura, Hiroyuki Tsuchiya BackgroundParagangliomas are neuroendocrine tumors that originate from autonomic nervous system-associated paraganglia, and are rare tumor accounting for only 0.3% of all neoplasms. Malignant paragangliomas frequently spread to the skeleton. The authors present a case of malignant paraganglioma with bone metastases to the spine and cranium, and excellent local control achieved with en bloc tumor resection and reconstruction using frozen tumor-bearing bone for the sites of the metastases.CaseThe patient was a 61-year-old woman underwent retroperitoneal paraganglioma resection 12 years previously. Nine years after the primary surgery, she began to experience back pain. Magnetic resonance imaging revealed an isolated metastasis in T6, and the following evaluation detected another metastasis in the left temporal bone. We performed curative surgeries for the metastases, including total en bloc spondylectomy of T6, and partial craniectomy for the cranial metastasis, and spinal and cranial reconstruction using frozen tumor-bearing bone for the sites of the metastases. At the 24-months follow-up examination, bone fusion was achieved between the frozen bone and the adjacent healthy bone in the spine and cranium. At 36 months postoperatively, an asymptomatic metastatic lesion was found in the pelvis. Nevertheless, no local recurrences at the surgical sites were detected. Her quality of life and performance in activities of daily living were well preserved. To the author's knowledge, this is the first report to present a case of cranioplasty achieved using a liquid nitrogen frozen, tumor-bearing autologous bone flap in a single-stage operation. Read More » Surgical-treated Jugular Foramen Schwannoma Long-term Functional and Recurrence Outcomes of Surgical-treated Jugular Foramen Schwannoma: a 20-year Experience via World Neurosurgery Publication date: Available online 13 October 2015 Source:World Neurosurgery Author(s): Xiao-Jun Zeng, Da Li, Shu-Yu Hao, Liang Wang, Jie Tang, Xin-Ru Xiao, Guo-Lu Meng, Gui-Jun Jia, Li-Wei Zhang, Zhen Wu, Jun-Ting Zhang Hightlights 1. The R/R-free survival and overall survival at 15 years was 84.8% and 90.1%. 2. More than 85% of patients were improved/stabilized and lead a normal life. 3. Swallowing function was improved/unchanged in 95.5% patients. 4. Non-GTR and pathological mitosis were independent risk factors for tumor R/R. 5. Decreased preoperative KPS was independent risk factor for poor outcomes. Read More » 3D Endoscopy for Ventral Skull Base Pathology Efficacy of Three-Dimensional Endoscopy for Ventral Skull Base Pathology: A systematic review of the literature via World Neurosurgery Publication date: Available online 14 October 2015 Source:World Neurosurgery Author(s): Hasan A. Zaidi, Aqib Zehri, Timothy R. Smith, Peter Nakaji, Edward R. Laws ObjectThe three-dimensional (3D) endoscope is a novel tool that provides stereoscopic vision and may allow for improved dexterity and safety during surgical resection of ventral skull base lesions. We describe here the cumulative experience available in the neurosurgical literature.MethodsA PubMed literature review was performed to identify and analyze all studies pertaining to 3D endoscopic endonasal skull base surgery.ResultsTwenty-six articles were identified: 14 clinical articles, 5 simulated environment studies, 5 human cadaveric studies, and 2 expert opinions. Among clinical studies, a total of 262 patients were treated for the following 257 pathologies listed in the articles: 190 suprasellar/parasellar lesions (73.9%), 41 ventral skull base lesions (16.0%), 19 sinonasal pathologies (7.4%), and 7 CSF leak repairs (2.7%). Complication rates, operative time, length of hospital stay, and extent of tumor resection were equivalent between 2D and 3D endoscopy. However, all studies report that subjective depth perception and spatial orientation were markedly improved with 3D technology. Three studies (11.5%) concluded that there was no clinically significant surgical benefit in switching from 2D to 3D endoscopy. All cadaveric studies and expert opinions concluded that 3D endoscopy improved identification of key anatomical structures and was superior to 2D endoscopy. Simulated environment studies demonstrated that 3D endoscopy improves speed and accuracy of endonasal tasks, more so in novice surgeons.ConclusionsOur findings suggest that this modality provides improved surgical dexterity by affording the surgeon with depth perception when manipulating tissue and maneuvering the endoscope in the endonasal corridor. Read More » Spektrografische Stimmtypenklassifizierung zur Beurteilung der Stimmqualität Spektrografische Stimmtypenklassifizierung zur Beurteilung der Stimmqualität by Barsties, B. via Laryngo-Rhino-Otologie Laryngo-Rhino-Otol DOI: 10.1055/s-0035-1559678 Hintergrund: Neben der auditiv-perzeptiven Beurteilung, zählen auch objektiv-akustische Methoden als valides Evaluationsmittel für die Beurteilung der Stimmqualität. Die Spektrografie wird seit ca. 50 Jahren eingesetzt und kürzlich wurde ein neues Verfahren zur spektrografischen Stimmtypenklassifizierung nach Sprecher et al. (2010) vorgestellt. Das Ziel dieser Studie ist die Überprüfung der externen Validität beider Messverfahren mit einer größeren Stimmenanzahl. Material und Methoden: Es wurden 300 Stimmaufzeichnungen vom Vokal [a:] verwendet. 270 Aufnahmen stammten von Stimmpatienten mit unterschiedlichen Schweregraden einer Dysphonie und 30 Stimmgesunde. Alle Stimmen wurden von 7 Logopädinnen nach der RBH-Skala beurteilt und 2 Beurteiler analysierten die Stimmen nach der spektrografischen Stimmtypenklassifizierung. Ergebnisse: Die Intra- und Inter-Beurteiler-Zuverlässigkeit der RBH Parameter ergab nur eine durchschnittlich leichte Zuverlässigkeit (kappa=0,234–0,383). Die spektrografische-Beurteiler-Zuverlässigkeit war mäßig (kappa=0,457). Die Übereinstimmungsvalidität zwischen den auditiv-perzeptiven Parameter H und B und der spektrografischen Stimmtypenklassifizierung war hoch (H: r=0,746, p=0,000; B: r=0,746, p=0,000), jedoch für den Parameter R ergab sich nur eine leichte Übereinstimmung (r=0,370, p=0,000). Schlussfolgerung: Die spektrografische Stimmtypenklassifizierung nach Sprecher et al. (2010) scheint eine sinnvolle Ergänzung zur Beurteilung von Heiserkeit und Behauchtheit und bestätigt die Ergebnisse nach Sprecher et al. (2010). Das Verfahren ermöglicht eine objektivere Beurteilung von Stimmqualität für die angehaltene Phonation im klinischen Alltag sowie für die wissenschaftliche Arbeit. Read More » Therapie von Blutungen bei Patienten unter oraler Antikoagulation Therapie von Blutungen bei Patienten unter oraler Antikoagulation by Riess, Hanno via Laryngo-Rhino-Otologie Laryngo-Rhino-Otol 2015; 94: 697-709 DOI: 10.1055/s-0034-1564071 Sowohl unter einer Therapie mit klassischen Antikoagulanzien wie auch unter den direkten oralen Antikoagulanzien sind Blutungen die wichtigste klinische Komplikation. Deren Therapie unterscheidet sich zwischen den Substanzgruppen erheblich. Read More » Die Sinusvenenthrombose – eine seltene Komplikation der akuten Mastoiditis und des Cholesteatoms Die Sinusvenenthrombose – eine seltene Komplikation der akuten Mastoiditis und des Cholesteatoms by Graß, S. K. via Laryngo-Rhino-Otologie Laryngo-Rhino-Otol DOI: 10.1055/s-0035-1555914 Hintergrund: Die Sinusvenenthrombose (SVT) ist eine seltene Komplikation der akuten Mastoiditis und des infizierten Cholesteatoms. In der internationalen Literatur wurde bisher wenig über die systematische Untersuchung bei V.a. eine SVT dokumentiert. In dieser Untersuchung wurden die klinischen, intraoperativen und therapeutischen Befunde der Patienten diskutiert. Patienten und Methoden: Es werden retrospektiv 7 Patienten mit radiologischem V.a. eine SVT dargestellt. Bei allen Patienten erfolgte eine Mastoidektomie mit Darstellung des Hirnsinus und Überprüfung dessen Blutführung. Ergebnisse: 4 Patienten hatten eine Thrombose des Sinus sigmoideus und 3 Patienten hatten eine Phlebitis des Sinus. Patienten mit einer SVT hatten zusätzlich zur Otalgie Schwindel, Cephalgien, Meningismus, Surditas oder eine Facialisparese. Postoperative MRT-Untersuchungen zeigten eine Rekanalisation des Sinus in allen Fällen. 2 Patienten entwickelten einen 2-zeitigen Kleinhirnabszess. Schlussfolgerung: Die Symptome der SVT sind unspezifisch. Neurologische Beschwerden können bei einer Mastoiditis hinweisend sein. Die Therapie besteht in der intravenösen Antibiotikagabe und der operativen Fokussanierung. Immer sollte im Rahmen der Mastoidektomie die Darstellung des Sinus erfolgen und dessen Blutführung überprüft werden. Im Falle einer Thrombose ist kann überdies die Antikoagulantientherapie indiziert sein. Zum Ausschluss eines 2-zeitigen Hirnabszesses empfiehlt sich eine Kontroll-MRT 7–14 Tage postoperativ. Read More » Genexpressionsanalysen und ihr möglicher klinischer Nutzen in der Betrachtung der KHK Kopf-Hals-Karzinome via HNO Zusammenfassung Systembiologische Ansätze für Mutationen (Exomanalysen und „targeted sequencing") und Genexpressionsanalysen (transkriptomweites „Genexpressions-Profiling") stellen in der Kopf-Hals-Onkologie ein neues wachsendes Gebiet dar, das neben medizinisch biologischer Kompetenz auch zunehmend bioinformatisches Spezialwissen erfordert. Für die Plattenepithelkarzinome des Kopf-Hals-Bereichs („head and neck squamous cell carcinoma", HNSCC) stellen die bisherigen molekulargenetischen Einzel-Gen- und Signalwegbetrachtungen Grundlagenforschung dar. Diese hat mittlerweile an verschiedenen Stellen wesentliche Erweiterungen durch systembiologische Ansätze, welche zu relevanten translationalen klinischen Forschungsfeldern herangewachsen sind. Heutzutage ist bekannt, dass Humanpapillomvirus(HPV)16 an verschiedenen Stellen mit genetischen Veränderungen assoziiert ist, aber auch auf der Methylierungsebene funktionellen Einfluss auf nicht in ihrer Basensequenz alterierte Gene ausübt. Verschiedene Konsortien fanden in Transkriptomanalysen übereinstimmende Cluster der Genexpression und HPV16-Assoziationen mit dem Spektrum somatischer Mutationen. Die bei HPV16-getriebenen HNSCC ermittelte differenzielle Methylierung von Genpromotoren erwies sich als prädiktiv für das Überleben auch bei HNSCC-Patienten ohne HPV-Nachweis. Die Autoren stellen eine Übersicht einiger translational relevanter Erkenntnisse dar und wagen einen Ausblick auf mögliche zukünftige klinische Entwicklungen. Read More » The nervus intermedius and the facial and vestibulocochlear nerves in the cerebellopontine angle Neural connections between the nervus intermedius and the facial and vestibulocochlear nerves in the cerebellopontine angle: an anatomic study via Latest Results for Surgical and Radiologic Anatomy Abstract Purpose Unexpected clinical outcomes following transection of single nerves of the internal acoustic meatus have been reported. Therefore, this study aimed to investigate interneural connections between the nervus intermedius and the adjacent nerves in the cerebellopontine angle. Methods On 100 cadaveric sides, dissections were made of the facial/vestibulocochlear complex in the cerebellopontine angle with special attention to the nervus intermedius and potential connections between this nerve and the adjacent facial or vestibulocochlear nerves. Results A nervus intermedius was identified on all but ten sides. Histologically confirmed neural connections were found between the nervus intermedius and either the facial or vestibulocochlear nerves on 34 % of sides. The mean diameter of these small interconnecting nerves was 0.1 mm. The fiber orientation of these nerves was usually oblique (anteromedial or posterolateral) in nature, but 13 connections traveled anteroposteriorly. Connecting fibers were single on 81 % of sides, doubled on 16 %, and tripled on 3 %, six sides had connections both with the facial nerve anteriorly and the vestibular nerves posteriorly. On 6.5 % of sides, a connection was between the nervus intermedius and cochlear nerve. For vestibular nerve connections with the nervus intermedius, 76 % were with the superior vestibular nerve and 24 % with the inferior vestibular nerve. Conclusions Knowledge of the possible neural interconnections found between the nervus intermedius and surrounding nerves may prove useful to surgeons who operate in these regions so that inadvertent traction or transection is avoided. Additionally, unanticipated clinical presentations and exams following surgery may be due to such neural interconnections. Read More » Brain Imaging in Idiopathic Intracranial Hypertension Brain Imaging in Idiopathic Intracranial Hypertension. by Bidot, Samuel; Saindane, Amit M.; Peragallo, Jason H.; Bruce, Beau B.; Newman, Nancy J.; Biousse, Valérie via The North American Neuro-Ophthalmology Society Background: The primary role of brain imaging in idiopathic intracranial hypertension (IIH) is to exclude other pathologies causing intracranial hypertension. However, subtle radiologic findings suggestive of IIH have emerged with modern neuroimaging. This review provides a detailed description of the imaging findings reported in IIH and discusses their possible roles in the pathophysiology and the diagnosis of IIH. Evidence Acquisition: References were identified by searches of PubMed from 1955 to January 2015, with the terms "idiopathic intracranial hypertension," "pseudotumor cerebri," "intracranial hypertension," "benign intracranial hypertension," "magnetic resonance imaging," "magnetic resonance venography," "computed tomography (CT)," "CT venography," "imaging," and "cerebrospinal fluid (CSF) leak." Additional references were identified by hand search of relevant articles. When possible, we extracted the number of patients and control subjects from each study for each radiological finding. When at least 2 studies used the same criteria to define a radiological finding, all patients from these studies were pooled to obtain a mean sensitivity and specificity with 95% confidence interval. Results: Specific neuroimaging findings may suggest long-standing IIH, including empty sella, flattening of the posterior globes, optic nerve head protrusion, distention of the optic nerve sheaths, tortuosity of the optic nerve, cerebellar tonsillar herniation, meningoceles, CSF leaks, and transverse venous sinus stenosis. Conclusion: Although IIH remains a diagnosis of exclusion, the most recently proposed diagnostic criteria have included neuroimaging findings to suggest IIH when major diagnostic criteria are not fulfilled. However, these findings are not diagnostic of IIH, and their presence is not required for the diagnosis of definite IIH. Their incidental discovery on brain imaging should not prompt invasive procedures, unless other signs of IIH, such as papilledema, are present. (C) 2015 by North American Neuro-Ophthalmology Society Read More » Dressing with epigallocatechin gallate-nanoparticles for wound regeneration Dressing with epigallocatechin gallate-nanoparticles for wound regeneration by Yu-Hsin Lin, Jui-Hsiang Lin, Tzong-Shiun Li, Shih-Hao Wang, Chun-Hsu Yao, Wan-Yu Chung, Tse-Hao Ko via Wound Repair and Regeneration Abstract Several reagents have been studied to overcome the problems encountered with anti-septic use, such as moderate cutaneous wound cytotoxicity and skin thinning. We successfully prepared a gelatin/chitosan/epigallocatechin gallate nanoparticle incorporated in a poly(γ-glutamic acid)/gelatin hydrogel, which comprised activated carbon fibers with gentamicin, to fabricate a sandwiched dressing to enhance wound regeneration. The inner-layer of activated carbon fibers with gentamicin was designed to prevent bacterial infection, and the outer-layer of gelatin/chitosan/epigallocatechin gallate nanoparticles incorporated in a poly(γ-glutamic acid)/gelatin hydrogel was designed to prevent inflammation and facilitate re-epithelialization. An in vitro study demonstrated that the dressing effectively inhibited target microorganisms, and scanning electron microscope and confocal laser scanning microscope indicated that the nanoparticles were homogeneously dispersed and migrated into the hydrogel. The in vivo study reported that the sandwiched dressing, comprising the poly(γ-glutamic acid)/gelatin hydrogel, was easy to remove from the wound and facilitated wound tissue regeneration and accelerated healing process. This article is protected by copyright. All rights reserved. Read More » Low Grade Fibromyxoid Sarcoma of the Palate : A Case Report Srikanth Soma, Shriram Bhat, Sunil Kumar Shetty Correspondence Dr. Srikanth Soma, B-404, Amsri Residency, Ameerpet, Hyderabad, Telangana-500016, India. E-mail: soma_986@yahoo.co.in Low-grade fibromyxoid sarcoma (LGFMS) are rare soft-tissue sarcomas that usually come to attention as slow growing masses. Males and females are affected approximately equally and typically arising in the soft tissue of the proximal extremities. Primary occurrence within the head and neck is exceedingly rare. We report a case arising from the hard palate of a 40-year-old male and according to our knowledge this is the first ever case of LGFMS involving the palate to be reported. [ FULL TEXT ] | [ PDF ] Read More » Antifungal activities of five antipsychotic drugs In vitro antifungal activity of antipsychotic drugs and their combinations with conventional antifungals against Scedosporium and Pseudallescheria isolates by Homa, M., Galgoczy, L., Toth, E., Toth, L., Papp, T., Chandrasekaran, M., Kadaikunnan, S., Alharbi, N. S., Vagvolgyi, C. viaMedical Mycology - current issue In the present study, in vitro antifungal activities of five antipsychotic drugs (i.e., chlorpromazine hydrochloride, CPZ; trifluoperazine hydrochloride, TPZ; amantadine hydrochloride; R-(-)-deprenyl hydrochloride, and valproic acid sodium salt) and five conventional antifungal drugs (i.e., amphotericin B, AMB; caspofungin, CSP; itraconazole; terbinafine, TRB and voriconazole, VRC) were investigated in broth microdilution tests against four clinical and five environmentalScedosporium and Pseudallescheria isolates. When used alone, phenothiazines CPZ and TPZ exerted remarkable antifungal effects. Thus, their in vitro combinations with AMB, CSP, VRC, and TRB were also examined against the clinical isolates. In combination with antifungal agents, CPZ was able to act synergistically with AMB and TRB in cases of one and two isolates, respectively. In all other cases, indifferent interactions were revealed. Antagonism was not observed between the tested agents. These combinations may establish a more effective and less toxic therapy after further in vitro and in vivo studies for Scedosporium and Pseudallescheria infections. Read More » Evaluation eines Klassifikationsmodells horizontaler Gefäßveränderungen der Stimmlippen Evaluation eines Klassifikationsmodells horizontaler Gefäßveränderungen der Stimmlippen by Schossee, A. via Laryngo-Rhino-Otologie Laryngo-Rhino-Otol DOI: 10.1055/s-0035-1559677 Hintergrund: Derzeit existiert keine valide Klassifikation von beginnenden Gefäßveränderungen der Stimmlippen. Wir testeten deshalb ein neues Klassifikationsmodell sichtbarer, beginnender, vaskulärer Veränderungen der Stimmlippen. Material und Methoden: 3 Gutachtern wurden 168 indirekte larynxendoskopische Aufnahmen der Stimmlippen als 84 Weißlicht-(WL) und 84 Narrow-Band-Imaging-Bilder (NBI) in zufälliger Reihenfolge zur Klassifikation vorgelegt (Graduierung in normal, leicht-, mittel-, hochgradig der Gefäßmerkmale Ektasie, Mäander, Gefäßkonvolut, Gefäßhäufigkeit, Grad der Verästelung und Richtungswechsel). Zudem mussten sie mittels Numerischer Rating-Skala ihre Sicherheit bei der Bewertung angeben. Die Validität der Gutachterangaben wurde anhand zufällig erneut angebotener WL- und NBI-Bilder überprüft. Ergebnisse: Eine Klassifizierung beginnender Gefäßmerkmale ist grundsätzlich möglich. Ektasie, Mäander, Gefäßhäufigkeit, Grad der Verästelung und Richtungswechsel eignen sich dafür (p<0,0001). NBI-Bilder zeigen die Gefäßmerkmale insgesamt höhergradig als die WL-Bilder (p<0,0001). Die Sicherheit bei der Bewertung der Gefäßmerkmale unterscheidet sich nicht signifikant (p=0,3529), differiert jedoch zwischen den Gutachtern höchst signifikant (p<0,0001). Bei dem Bewertungslaien ist der Zuwachs bei der Lernkurve am höchsten. Die Intra- sowie Interratervariabilität unterscheiden sich zwischen WL und NBI nur gering. Schlussfolgerungen: Beginnende, horizontale Gefäßmerkmale der Stimmlippen lassen sich sicher klassifizieren. Larynxendoskopische NBI-Bilder stellen die untersuchten Gefäßmerkmale nachweislich besser dar als WL-Bilder. Die Vertrautheit mit dem Klassifikationsmodell und der larynxendoskopischen Methode bestimmt die Sicherheit bei der Gefäßbeurteilung. Read More » Headache as a predictor for dementia : The HUNT Study by Ane Røttereng via The Journal of Headache and Pain - Latest Articles Background: The impact of headache on dementia is largely unknown. This study examined the association between headache and dementia using data from a large population-based study. Methods: This population-based study used data from the Nord-Trøndelag Health Surveys performed in 1995–1997 (HUNT2) and 2006–2008 (HUNT3). The reference group (controls) was participants aged ≥55 years who answered the headache questions in HUNT2 and later participated in HUNT3 (n = 15,601). The association with headache status in HUNT2 was investigated in sample of confirmed non-demented elderly evaluated with psychometric tests after HUNT3 (n = 96), and HUNT2 participants later diagnosed with dementia during 1997–2011 (n = 746). The association with headache was evaluated by logistical regression with adjustment for age, gender, level of education, comorbidity, smoking, and anxiety and depression. Results: Any headache was more likely to be reported in HUNT2 among those who later were included in the dementia registry (OR 1.24; 95 % CI 1.04–1.49) compared to the reference group, but less likely among the confirmed non-demented individuals (OR 0.62; 95 % CI 0.39–0.98). This relationship was even stronger for non-migrainous headache, whereas such association was not found for migraine. Conclusions: Compared to the reference group, individuals with dementia were more likely to report non-previous migrainous headache in HUNT2, whereas a sample of confirmed non-demented were less likely to report previous non-migrainous headache. Read More » Patterns of Pediatric Mandible Fractures  in the United States by Owusu JA, Bellile E, Moyer JS, et al. via JAMA Facial Plastic Surgery Online First This database analysis of mandible fractures among children and adolescents reports that patients younger than 12 years and female patients tend to have condyle fractures caused more commonly by falls, while teenaged patients and male patients tend to have angle fractures caused by assault. Importance  The mandible is arguably the most frequently fractured facial bone in children. However, facial fractures are rare in children compared with adults, resulting in few large studies on patterns of pediatric facial fractures. Objective  To report the patterns, demographics, and cause of pediatric mandible fractures across the United States. Design, Setting, and Participants  A retrospective analysis was conducted of the Healthcare Cost and Utilization Project's National Emergency Department Sample from January 1 to December 31, 2012, using the International Classification of Disease, Ninth Revision, codes for mandible fractures (802.20-802.39) among patients 18 years and younger who presented to emergency departments. Demographics, fracture site, and fracture mechanism were analyzed to identify factors associated with fractures. Analysis was conducted from July 9 to July 28, 2015. Results  There were 1984 records, representing a weighted estimate of 8848 cases of pediatric mandible fracture. The mean patient age was 14.0 years (95% CI, 13.6-14.3). The male to female ratio was 4:1 and females were comparatively younger, with a mean age of 12.5 years (95% CI, 11.8-13.1; P < .001). The most frequently fractured sites were the condyle, in 1288 patients (14.6% [95% CI, 12.6%-16.5%]), and the angle, in 1252 patients (14.1% [12.4%-15.9%]). Associated intracranial injuries occurred in 756 patients (8.5% [7.1%-10.0%]), and cervical spine fractures occurred in 393 (4.4% [3.5%-5.4%]). The fracture site and mechanism of injury varied with age and sex. For patients 12 years and younger, the most frequent fracture site was the condyle, accounting for 636 fractures (27.9% [24.2%-31.6%]), and the most frequent cause was falls, accounting for 692 fractures (30.3% [25.9%-34.8%]). In teenaged patients (13-18 years), the angle was the most frequent fracture site, accounting for 1157 fractures (17.6% [15.6%-19.6%]), and the most frequent cause was assault, accounting for 2619 fractures (39.9% [36.4%-43.3%]). For male patients, the angle was the predominant site, accounting for 1053 fractures (15.0% [13.1%-16.8%]), and the leading cause was assault, accounting for 2360 fractures (33.5% [30.2%-36.9%]). For female patients, the condyle was the most frequent site, accounting for 369 fractures (20.3% [16.0%-24.6%]), and the leading cause was falls, accounting for 422 fractures (23.2% [18.6%-28.0%]). Conclusions and Relevance  In this study, age and sex disparities among pediatric mandible fractures were identified. Younger patients and female patients tend to have condyle fractures caused more commonly by falls while older patients and male patients tend to have angle fractures caused by assault. Level of Evidence  NA. Facial fractures are a rare occurrence in children compared with adults. However, traumatic injuries account for significant morbidity and mortality in children. Recent data from the Centers for Disease Control and Prevention report trauma as the leading cause of pediatric mortality in the United States.1 Anatomical differences between the craniofacial skeleton of adults and children contribute to the differences in the rate of facial fractures. In young children, the cranium accounts for a higher proportion of the craniofacial skeleton than in adults and the cranium protects the facial skeleton from trauma. The cranium to face ratio is 8:1 at birth and decreases to 2.5:1 in adulthood.2Thus, the risk of facial fractures increases with age owing to the increasing proportion of the facial skeleton. In addition, children in general are less likely to be involved in activities associated with traumatic injuries seen commonly in adults. The mandible is the most commonly fractured facial bone in children. In an analysis of the National Trauma Data Bank by Imahara et al,3 the mandible accounted for 32.7% of all facial fractures in children. Given the rarity of pediatric facial fractures, most studies on this subject have been limited to single institutional experiences.4 A broader understanding of the cause and epidemiological characteristics of facial fractures in children will help improve prevention and management strategies. Sponsored by the Agency for Healthcare Research and Quality, the Healthcare Cost and Utilization Project (HCUP) has gathered the largest collection of longitudinal hospital care data in the United States, to our knowledge. These data have enabled studies on conditions that could not previously be easily studied at the national level. The purpose of this study was to examine the cause and epidemiological characteristics of pediatric mandible fracture using the 2012 HCUP Nationwide Emergency Department Sample (NEDS). The 2012 NEDS contains 31 million records from a 20% stratified sample of hospital-based emergency departments (EDs). Weights are provided in the database to allow calculation of national estimates.5 The NEDS does not contain any identifiable patient information. Following approval from the University of Michigan Institutional Review Board, we analyzed mandible fractures recorded in the 2012 NEDS (data from January 1 to December 31, 2012). Records of children 18 years and younger were selected using the International Classification of Diseases, Ninth Revision (ICD-9), codes for mandible fractures (802.20-802.39). The database included the following mechanism of injures: motor vehicle collision (MVC), assault, and falls. Sports injuries were determined using ICD-9 Ecode (E8494) and other causes of injury were categorized as other. The mechanism of injury and fracture type (anatomical site) were analyzed by age and sex. For age group analysis, patients were stratified into 2 categories based on dentition development. Patients 6 years and younger (primary dentition) were combined into 1 group with those aged 7 to 12 years (mixed dentition). The second group consisted of patients aged 13 to 18 years (secondary dentition). The primary and mixed dentition groups were combined to comply with the HCUP data use agreement that prohibits reporting categories with fewer than 10 records. Likewise, owing to their low numbers, coronoid fractures were combined with unspecified fractures to comply with the HCUP data use agreement. Associated cervical spine and intracranial injuries were identified using Clinical Classification Software codes. This software is used by HCUP to conglomerate clinically relevant ICD-9 codes in diagnostic groups. The Clinical Classification Software codes 233 and 231 (ICD-9 codes 805.00-805.18) correspond with intracranial injury and cervical spine fractures, respectively. Analysis was conducted between July 9 and July 28, 2015. Weighted statistics for national estimates with 95% CIs were calculated using the discharge weights, strata, and cluster elements of the sampling design provided in the database for a domain analysis of the subset of pediatric mandible fractures. Age and sex were compared across fracture type and cause of injury using linear and logistic regression models, respectively, adjusted for the complex survey design (PROC SURVEYREG and SURVEYLOGISTIC procedures in SAS). All statistical analyses were performed using SAS, version 9.4 (SAS Institute). Prior studies on pediatric facial fractures have been limited to single institutional experiences.4,6- 8Our study presents a focused national analysis of pediatric mandible fractures. Consistent with previous studies, our analysis showed that mandible fractures are rare in younger children. We found that more than 74% of fractures occurred in children aged 13 to 18 years. This finding is likely a result of the protection of the facial skeleton by increased plasticity of the facial bones and a proportionally larger skull in younger children.2 In addition, younger children are less likely to be involved in activities associated with trauma and accidental injuries. Our analysis also revealed a predominance in males, which is consistent with other reports.3,4,9 In females, fractures occurred at a younger age, a finding that has previously been reported by Hoppe et al.4 Significant sex- and age-related variations were noted in the cause of fractures. In males, assault is the predominant cause of fractures, whereas falls and MVCs predominate in females. Fractures in younger children are largely owing to falls and MVCs, while assault is the most common cause in older children. These findings reflect the varying behavior patterns seen between the different age and sex groups. Studies have shown that males are more likely than females to be involved in high-risk activities associated with trauma and accidental injuries.10 Younger children are also typically protected from high-risk activities through close adult supervision that declines with age.11 Reports on the cause of pediatric mandible fractures in the literature have been inconsistent. Some studies have reported violence-related injuries as the leading cause of fractures4,12 while others point to sports-related incidents13 and MVC3 as the leading cause of pediatric mandible fractures. Our analysis supports assault as the leading cause of pediatric mandible fractures. Age, sex, and etiologic differences in the anatomical fracture site were also seen in our analysis. In younger children (≤12 years), the condyle appears to be the most vulnerable site. This finding is consistent with other reports in the literature.14- 16 Older children trend toward an adult fracture pattern, with the angle being the most frequently fractured site. The cause also contributes to the fracture pattern. Angle fractures predominantly result from assault whereas MVCs and falls commonly cause condyle fractures. This observation corresponds to the fracture patterns seen in the different age and sex groups in our study. In younger children and in females, where the leading cause of fracture is falls and MVCs, the most common fracture site is the condyle. Angle and condyle fractures were most likely to be associated with intracranial injuries, seen in 8.5% of the study population. The weaknesses of this study are those inherent to retrospective database reviews. Overall accuracy is dependent on correct coding practices. In addition, since the NEDS is a sampling of records of visits to hospital-based EDs, patients seen in non–hospital-based EDs are not captured in the sampling. Despite these shortcomings, this analysis provides a national view on the patterns of pediatric mandible fractures that, to our knowledge, has not been previously described on such a large scale. Significant age and sex disparities exist in the patterns and cause of pediatric mandible fractures. Fractures predominantly occur in older male children, with assault as the main mechanism of injury. The main causes of mandible fractures in females and younger children are falls and MVCs. Fractures can be associated with intracranial and cervical spine injuries; children presenting with mandible fractures should be carefully assessed for these injuries. National database analyses, such as those presented in our study, play an essential role in the creation of diagnostic, treatment, and prevention protocols for rare pediatric injuries. Read More » Psychological Traits of Female Patients Undergoing Cosmetic Surgery Psychological Traits of Female Patients Undergoing Cosmetic Surgery by Yin Z, Wang D, Ma Y, et al. via JAMA Facial Plastic Surgery Online First This comparative study of young, female, Chinese patients reports that self-esteem and self-efficacy mediate the negative effects of self-assessment on the decision to undergo facial cosmetic surgery. Importance  The psychological traits of cosmetic surgery patients (CSP) are important for selecting patients and postoperative patient satisfaction. A patient's self-esteem, self-efficacy, and self-assessment affect his or her motivation for cosmetic surgery, but the association among these traits remains unclear, especially in the Asian population. Objective  To clarify the association of a patient's psychological traits, decision to undergo cosmetic surgery, and the effectiveness of facial cosmetic surgery on the psychological conditions of young, female Chinese patients. Design, Setting, and Participants  Three different groups of young women (aged 18-30 years) from the Plastic Surgery Hospital, Chinese Academy of Medical Sciences, and 7 universities were enrolled from January 1, 2012, through December 31, 2014: CSPs (n = 161), general population controls (GPCs) (n = 355), and facial appearance raters (FARs) (n = 268). The last date of follow-up was January 20, 2015. Patient data from questionnaires were obtained preoperatively and 6 months postoperatively, and the data from the control groups were obtained immediately after enrollment. Front-view facial images of the study participants were taken and then shown to independent raters to assess the participants' facial appearances on a rating scale. Main Outcomes and Measures  Evaluation of self-esteem and self-efficacy, subjective and objective assessment of facial appearance, and structural equation models. Results  A total of 163 CSPs and 387 GPCs were recruited for the study, and complete and valid data were obtained from 161 CSPs and 355 GPCs. All responses from the 268 FARs met the criteria for subsequent analysis. Of the questionnaires issued to the CSPs 6 months postoperatively, 126 valid responses were returned (response rate, 78.3%). Self-esteem and self-efficacy decreased significantly in preoperative patients compared with controls (P < .001) (mean [SD] scores, 22.60 [1.80] for CSPs and 27.39 [2.11] for GPCs for self-esteem and 21.50 [2.40] for CSPs and 28.59 [4.23] for GPCs for self-efficacy) and were found to be at nearly normal levels 6 months postoperatively (mean [SD] scores, 25.88 [3.65] and 26.38 [2.45] for self-esteem and self-efficacy, respectively). The patients' objective assessments of facial appearance did not differ significantly from those of the control group participants (mean [SD] scores, 4.51 [0.77] and 4.55 [0.74] for CSPs and GPCs, respectively; P = .86); however, a significant decrease in patient self-assessment was noted (mean [SD scores], 6.45 [1.15] and 7.31 [1.42] for CSPs and GPCs, respectively; P = .01). Moreover, the structural equation models revealed a path from low self-esteem and self-efficacy after decreased self-assessment to decision for cosmetic surgery. Conclusions and Relevance  Self-esteem and self-efficacy mediate the negative effects of self-assessment on the decision of young women to undergo facial cosmetic surgery. The impairment of self-esteem and self-efficacy may indicate the need for preoperative psychological intervention. Facial cosmetic surgery can have positive effects on self-esteem and self-efficacy. Level of Evidence  2. Read More » Delayed Complications After Cochlear Implantation Delayed Complications After Cochlear Implantation by Terry B, Kelt RE, Jeyakumar A. via JAMA Otolaryngology–Head & Neck Surgery Online First This systematic review describes the reported rates and types of delayed complications after cochlear implantation in adults and children. Importance  Surgeons should understand the potential long-term complications in patients who undergo cochlear implantation (CI) and should be able to facilitate counseling. Objectives  To review the delayed complications after CI and some of the management plans used to treat these complications. Evidence Acquisition  The PubMed and OVID databases were searched for articles published from January 1, 2003, through December 31, 2013, using the search terms cochlear implant andcomplications. Seven hundred sixty-six articles were identified and searched for reports of delayed complications (>3 days after surgery). Exclusion criteria consisted of a language other than English, no long-term follow-up or report of delayed complications, small case series with fewer than 10 patients, and CI in patients with cochlear malformations. Additional articles were identified with specific search criteria consisting of cochlear implant combined with mastoiditis, meningitis complication, otitis media, hematoma, cholesteatoma, and facial nerve injury. Data were collected from January 1 through April 1, 2014, and analyzed from April 30 to May 1, 2014. Findings  A total of 88 individual articles were analyzed for this study. These articles included a total of 22 842 patients. Of 8519 patients with data in regard to sex, 4319 (50.7%) were male. The patients' ages ranged from 0.2 to 94.9 years, with a mean age of 19.0 years. The duration of follow-up ranged from 1 month to 17 years. The total number of delayed complications was 1302 (5.7%), with vestibular complications (181 of 4655 patients [3.9%]) being the most common; device failure (507 of 14 704 patients [3.4%]), the second most common; and taste problems (22 of 776 patients [2.8%]), the third most common. Less common complications included cholesteatoma (40 of 8579 patients [0.5%]) and facial nerve palsy (31 of 4785 patients [0.6%]). Conclusions and Relevance  Cochlear implantation continues to be a reliable and safe procedure, with a low percentage of severe complications when performed by experienced surgeons. The patients should receive lifetime follow-up. These patients need lifetime follow-up to monitor for potential complications and to facilitate their care if complications occur. Read More » Complications After Oral Cavity Cancer Risk Estimation for  by Awad MI, Palmer FL, Kou L, et al. via JAMA Otolaryngology–Head & Neck Surgery Online First The authors of this retrospective case series describe their development and validation of a statistical tool to predict an individual patient's risk of developing a major complication after surgery for oral cavity cancer. Importance  Postoperative complications after head and neck surgery carry the potential for significant morbidity. Estimating the risk of complications in an individual patient is challenging. Objective  To develop a statistical tool capable of predicting an individual patient's risk of developing a major complication after surgery for oral cavity squamous cell carcinoma. Design, Setting, and Participants  Retrospective case series derived from an institutional clinical oncologic database, augmented by medical record abstraction, at an academic tertiary care cancer center. Participants were 506 previously untreated adult patients with biopsy-proven oral cavity squamous cell carcinoma who underwent surgery between January 1, 2007, and December 31, 2012. Main Outcomes and Measures  The primary end point was a major postoperative complication requiring invasive intervention (Clavien-Dindo classification grades III-V). Patients treated between January 1, 2007, and December 31, 2008 (354 of 506 [70.0%]) comprised the modeling cohort and were used to develop a nomogram to predict the risk of developing the primary end point. Univariable analysis and correlation analysis were used to prescreen 36 potential predictors for incorporation in the subsequent multivariable logistic regression analysis. The variables with the highest predictive value were identified with the step-down model reduction method and included in the nomogram. Patients treated between January 1, 2007, and December 31, 2008 (152 of 506 [30.0%]) were used to validate the nomogram. Results  Clinical characteristics were similar between the 2 cohorts for most comparisons. Thirty-six patients in the modeling cohort (10.2%) and 16 patients in the validation cohort (10.5%) developed a major postoperative complication. The 6 preoperative variables with the highest individual predictive value were incorporated within the nomogram, including body mass index, comorbidity status, preoperative white blood cell count, preoperative hematocrit, planned neck dissection, and planned tracheotomy. The nomogram predicted a major complication with a validated concordance index of 0.79. Inclusion of surgical operative variables in the nomogram maintained predictive accuracy (concordance index, 0.77). Conclusions and Relevance  A statistical tool was developed that accurately estimates an individual patient's risk of developing a major complication after surgery for oral cavity squamous cell carcinoma. Read More » What is the diagnosis? Elderly Woman With Left-Sided Acute Epistaxis by Yi C, Tabaee A, Wang B. via JAMA Otolaryngology–Head & Neck Surgery Online First An elderly woman presented with new-onset, left-sided acute epistaxis occurring multiple times per day, and noncontrast paranasal sinus CT showed a 1ovoid soft-tissue mass opacifying the posterior aspect of the left nasal vestibule.  Read More » Immediate and Short-Term Therapeutic Results Between Direction-Changing Positional Nystagmus  with Short- and Long-Duration Groups. by Ban, Jae Ho; Kim, Min-Beom; Hong, Seok Min via Ear and Hearing - Published Ahead-of-Print Objectives: Clinicians sometimes treat patients with relatively long-duration geotropic direction-changing positional nystagmus (DCPN), without latency. Recently, the concept of a "light cupula" in the lateral canal that reveals persistent geotropic DCPN has been introduced. In the present study, we investigated the immediate and short-term therapeutic findings in long-duration DCPN. Design: The authors prospectively compared the therapeutic efficacy of a canalith-repositioning procedure (CRP) in short- and long-duration geotropic DCPN. Results: In patients with long-duration DCPN, the authors found no immediate therapeutic effect, and the number of patients showing short-term effects (on the next day) was very low compared with the comparable figure among those with short-duration DCPN. In addition, no cases exhibited canal conversion after the CRP. Conclusion: Our results suggest that CRP is not useful in patients with long-duration geotropic DCPN, and the pathogenesis of long-duration geotropic DCPN may not originate from free-floating debris but from deflection of the cupula. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. Read More » Single nucleotide polymorphism rs11669203 in TGFBR3L is associated with the risk of neuroblastoma  in a Chinese population via Tumor Biology Abstract With a primary mortality, neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Amplification of the MYCN (v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog) oncogene is observed in 20–30 % of NB cases, a feature which also characterizes a highly aggressive subtype of the disease. However, the systematic study of association between single nucleotide polymorphisms (SNPs) in MYCN-regulated genes and the risk of NB has not been investigated. In the current study, we scanned a set of 16 SNPs located within known or predicted MYCN binding sites in a cohort of 247 patients of Chinese origin with neuroblastic family tumors, including neuroblastoma (NB), ganglioneuroma (GN), and ganglioneuroblastoma (GNB), and in 290 cancer-free controls to determine whether any of the tested SNPs are associated with neuroblastic family tumors. We found that the rs11669203 G>C polymorphism, located in TGFBR3L promoter, is significantly associated with the risk of NB. Further, we found that this association is site specific to adrenal NB compared to non-adrenal NB. In addition, transcriptome analysis indicated that increased expression of TGFBR3L is strongly correlated with poor survival. The SNP rs11669203 located at the MYCN binding site of TGFBR3L is significantly associated with elevated risk of NB, and abnormal MYCN-regulated TGFBR3L expression may contribute to NB oncogenesis. Read More » The angioformative initiation of neovascularisation in human haemangioblastoma CD41 and CD45 expression marks  via Tumor Biology Abstract The initiation and formation of haemangioblastoma (HB) neovascularisation remain unknown, with concomitant controversy on its cytological origin. We detected HB-derived specific haematopoietic progenitors identified by surface expression of CD41 and CD45, which are similar to human embryonic vasculogenesis. CD41/CD45 cells expressed mesodermal markers, including SCL, Flk1 and c-kit. CD41 also seemed to appear before CD45 on haematopoietic progenitors. In vitro analysis showed that the CD41+/CD45 subpopulation gave rise to occasional primitive erythroid activity and endothelial marker expression. Meanwhile, kinetic investigation of the CD41+/CD45+ subpopulation showed that some molecules, including SCL, Flk1 and c-kit, were involved in vascular formation. The CD45+/c-kit+population that lacked primitive haematopoiesis came from CD41+ cells. Acquisition of CD45 expression by the haematopoietic progenitors was associated with advanced differentiation towards the vascular cell lineage. Taken together, the present data suggested that CD41 and CD45 expression marked the onset of HB neovascularisation and the stepwise development of the angioformative period. Our findings provide new insights into the mechanisms of HB neovascularisation and the underlying therapeutic targets of anti-vascular treatment. Read More » Are Episodic and Chronic Migraine One Disease or Two? Are Episodic and Chronic Migraine One Disease or Two? via Latest Results for Current Pain and Headache Reports Abstract Migraine is a debilitating headache disorder that has a significant impact on the world population, in both economic and sociologic capacities. Migraine has two main categories: (1) chronic migraine (CM), defined as the patient having 15 or more headache days per month, with at least five attacks fulfilling measures for EM with aura or EM without aura, and (2) episodic migraine (EM), defined as less than 15 headache days per month. With this definition, CM can only exist in the presence of EM, and it questions whether the two are separate diseases. Migraine has a significant impact on the population, as each year, about 2.5 % of patients with EM develop new-onset CM (Manack et al., Curr Pain Headache Rep 15:70–78, 2011) (Loder et al. Headache 55:214–228, 2015), with certain risk factors being evident only with CM. In addition, there are comorbid diseases that are only associated with CM, suggesting two separate diseases rather than one. Differentiation in response to treatments, both preventive and abortive, demonstrates both a similarity and a difference in EM versus CM. Also, comparing the two processes based upon functional imaging has been a recent development, beginning to show a physiological difference in regional cortical thickness, cortical surface area, and regional volumes in patients with EM and CM. Evidence regarding whether EM and CM demonstrate one disease with a significant level of complication or if two independent processes is inconclusive, and additional research must be performed to further characterize their relationship. Read More » TSCC : ROCK inhibitor Y-27632 inhibits the growth,migration,and invasion of Tca8113 and CAL-27 cells  in tongue squamous cell carcinoma via Tumor Biology Abstract The objective of this study is to determine the effects of Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor Y-27632 on the growth, invasion, and migration of Tca8113 and CAL-27 cells in tongue squamous cell carcinoma (TSCC). The methods of the study are as follows: After being routinely cultured for 24 h, Tca8113 and CAL-27 cells were treated with Y-27632 solution. The morphological change of Y-27632-treated cells was observed under an optical microscope and an inverted microscope; MTT assay was performed to measure the optical density (OD) of cells and calculate cell growth inhibition rate; the change of apoptosis was detected by AnnexinV-FITC/PI assay; cell invasion and migration were measured by Transwell assay. The results were as follows: (1) With increasing concentration of Y-27632, cell morphology changed and cell apoptosis appeared; (2) MTT assay showed that inhibition effect of Y-27632 on Tca8113 and CAL-27 cells was enhanced with increasing concentrations and time (all P < 0.01); (3) Apoptosis showed that, compared with controls, the number of apoptosis cells in experimental groups was significantly increased (all P < 0.01). Apoptosis rate was elevated with increasing concentrations of Y-27632; (4) Transwell assay showed, after a treatment with Y-27632, the number of migrated and invaded Tca8113 and CAL-27 cells in each group was statistically different (all P < 0.01); compared with controls, the number of migrated cell in groups treated with Y-27632 was decreased and less Tca8113 and CAL-27 cells in experimental groups passed through polycarbonate membrane (all P < 0.05). The study concludes that Y-27632 can inhibit the growth, invasion, and migration of Tca8113 and CAL-27 cells, suggesting that Y-27632 may be therapeutically useful in TSCC. Read More » Chronic HBV infection (CHB) : Down-expression of miR-152 lead to impaired anti-tumor effect of NK via upregulation of HLA-G Down-expression of miR-152 lead to impaired anti-tumor effect of NK via upregulation of HLA-G via Tumor Biology Abstract It is known that chronic HBV infection (CHB) is the major risk factor for hepatocellular carcinoma (HCC) because CHB could not only cause liver tumorigenesis but also lead to change of local microenviroment and lower immune response to infected and cancerous cells (immune tolerance). Human leucocyte antigen-G (HLA-G) belongs to a non-classic MHC-I family and was considered to be an immune tolerance molecule, which could bind to immunosuppressive receptors of natural killer cell (NK) and T cells and trigger immunosuppressive signaling. Recently, numerous studies highlighted that microRNAs (miRNAs) were significantly differentially expressed in HCC tumorigenesis, and the expression was tissue-specific, indicating that miRNAs may cause great epigenetic changes in HCC tumorigenesis. In this study, we found that the expression of HLA-G was upregulated by hepatitis B virus (HBV) infection and miR-152; a HLA-G-targeting miRNA was downregulated by HBV infection. And high expression of HLA-G further suppressed NK against cancer cells, providing a new concept that miR-152 was involved in HBV-induced hepatocellular carcinoma. Read More » Aspergillus and aspergilloses in wild and domestic animals : a global health concern with parallels to human disease by Seyedmousavi, S., Guillot, J., Arne, P., de Hoog, G. S., Mouton, J. W., Melchers, W. J. G., Verweij, P. E. via Medical Mycology - current issue The importance of aspergillosis in humans and various animal species has increased over the last decades.Aspergillus species are found worldwide in humans and in almost all domestic animals and birds as well as in many wild species, causing a wide range of diseases from localized infections to fatal disseminated diseases, as well as allergic responses to inhaled conidia. Some prevalent forms of animal aspergillosis are invasive fatal infections in sea fan corals, stonebrood mummification in honey bees, pulmonary and air sac infection in birds, mycotic abortion and mammary gland infections in cattle, guttural pouch mycoses in horses, sinonasal infections in dogs and cats, and invasive pulmonary and cerebral infections in marine mammals and nonhuman primates. This article represents a comprehensive overview of the most common infections reported by Aspergillus species and the corresponding diseases in various types of animals. Read More » Antifungal synergy between amphiphilic aminoglycoside K20 and azoles In vitro antifungal synergy between amphiphilic aminoglycoside K20 and azoles against Candida species and Cryptococcus neoformans by Shrestha, S. K., Grilley, M., Anderson, T., Dhiman, C., Oblad, J., Chang, C.-W. T., Sorensen, K. N., Takemoto, J. Y. via Medical Mycology - current issue Several azoles are widely used to treat human fungal infections. Increasing resistance to these azoles has prompted exploration of their synergistic antifungal activities when combined with other agents. The amphiphilic aminoglycoside, K20, was recently shown to inhibit filamentous fungi, yeasts and heterokonts, but not bacteria. In this study, in vitrosynergistic growth inhibition by combinations of K20 and azoles (fluconazole, itraconazole, voriconazole, clotrimazole, or posaconazole) were examined against Candida species and Cryptococcus neoformans. Checkerboard microbroth dilution, time-kill curve, and disk diffusion assays revealed that K20 has synergistic inhibitory activities with all five azoles against C. albicans including azole-resistant C. albicans strains ATCC 64124 and ATCC 10231. Four (fluconazole, itraconazole, clotrimazole, posaconazole) and three (fluconazole, itraconazole, voriconazole) azoles were synergistically inhibitory with K20 against C. lusitaniae and C. tropicalis, respectively. Only posaconazole showed synergy with K20 against two Cryptococcus neoformans strains (90–26 and VR-54). Time-kill curves with azole-resistant C. albicans 64124 and azole-sensitive C. albicans MYA-2876 confirmed the K20-azole synergistic interactions with a ≥ 2 log10 decrease in colony-forming units (CFU)/ml compared with the corresponding azoles alone. These results suggest that combinations of K20 and azoles offer a possible strategy for developing therapies against candidiasis. Read More » Molecular epidemiology of invasive Candida albicans at a tertiary hospital  in northern Taiwan from 2003 to 2011 by Wang, S.-H., Shen, M., Lin, H.-C., Sun, P.-L., Lo, H.-J., Lu, J.-J. via Medical Mycology - current issue Candida albicans is a common cause of bloodstream fungal infections in hospitalized patients. To investigate its epidemiology, multilocus sequence typing (MLST) was performed on 285 C. albicans bloodstream isolates from patients in Chang Gung Memorial Hospital at Linkou (CGMHL), Taiwan from 2003 to 2011. Among these isolates, the three major diploid sequence types (DSTs) were 693, 659, and 443 with 19, 16, and 13 isolates, respectively. The 179 DSTs were classified into 16 clades by unweighted pair-group method using arithmetic averages (UPGMA). The major ones were clades 1, 4, 3, and 17 (54, 49, 31, and 31 isolates, respectively). Further analyses with eBURST clustered the 285 isolates into 28 clonal complexes (CC). The most common complexes were CC8, CC20, and CC9. DST 693 that had the highest number of isolates was determined to be the cluster founder of CC20, which belonged to clade 3. So far, 33 isolates worldwide including 29 from Taiwan and 4 from Korea, are CC20, suggesting that CC20 is an Asian cluster. Two fluconazole-resistant isolates belonging to CC12 and CC19 were detected. All other CGMHL isolates were susceptible to 5-flucytosine, amphotericin B, anidulfungin, caspofungin, fluconazole, itraconazole, micafungin, posaconazole, and voriconazole. However, CC20 isolates exhibited significantly lower susceptibility to fluconazole. In conclusion, the 285 CGMHL C. albicans isolates displayed geographically clustering with Asian isolates, and most of them are susceptible to common antifungal drugs. Isolates of DST 693, a Taiwanese major genotype belonging to MLST clade 3, were more resistant to fluconazole than other isolates. Read More » Evaluation of two new enzyme immunoassay reagents for diagnosis of histoplasmosis  in a cohort of clinically characterized patients by Zhang, C., Lei, G.-S., Lee, C.-H., Hage, C. A. via Medical Mycology - current issue The performance characteristics of the recently available analyte-specific reagent based enzyme immunoassay (ASR-EIA) and in vitro diagnostic (IVD) kit for urine Histoplasma antigen detection were evaluated in a cohort of 50 clinically characterized patients with histoplasmosis and 50 control patients. Overall sensitivity and specificity of the ASR-EIA were significantly improved compared with those of the IVD kit (sensitivity 72% vs. 22%, P<.001, specificity 98% vs. 84%, P = .014). Fourteen specimens from patients with clinically characterized histoplasmosis (five with pulmonary histoplasmosis and nine with progressive disseminated histoplasmosis) were falsely negative by ASR-EIA. All 10 specimens from patients with severe symptoms of progressive disseminated histoplasmosis were positive by ASR-EIA, although the average reading value of these 10 specimens was not significantly different from that of others with positive results. Compared to the MiraVista antigen assay, both the IVD kit and the ASR-EIA were significantly less sensitive in detecting Histoplasma antigen in the urine of patients with histoplasmosis. The ASR-EIA and MiraVista assay had comparable specificity. In conclusion, the ASR-EIA has improved performance compared with the IVD kit in the detection of Histoplasma antigen in the urine. However, users should be aware of the potential for false negative results using the currently recommended cutoff value. Read More » Malignant sublingual gland tumors : demographics, prognostic factors, and treatment outcomes via Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Publication date: Available online 13 October 2015 Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Robert J. Lee, Elizabeth L. Tong, Riki Patel, Nihal Satyadev, Russell E. Christensen ObjectiveTo determine the demographics, prognostic factors, and optimal treatment modalities of patients diagnosed with malignant primary tumors of the sublingual gland.Materials and MethodsThe Surveillance, Epidemiology, and End Results (SEER) registry contains 210 patients diagnosed with sublingual gland tumors in the SEER database. Kaplan-Meier and multivariate Cox regression analysis were performed on age, sex, race, histologic subtype, stage, and treatment modality.ResultsKaplan-Meier analysis found an overall survival (OS) and disease-specific survival (DSS) at 5 years of 69% and 83% respectively. Multivariate analysis demonstrated that age, sex, stage, and surgery were predictors of OS, while stage was a predictor of DSS.ConclusionsHere we report, to our knowledge, the largest study to date investigating demographics, prognostic factors, and treatment modalities of patients diagnosed with primary malignant tumors of the sublingual gland. Increased age and stage correlated with decreased survival while female gender and surgical therapy correlated with increased survival in the overall population. Radiation therapy for patients diagnosed with adenoid cystic carcinoma in the sublingual gland was correlated with increased survival. Read More » Ameloblastic Carcinoma (Secondary Type) with Extensive Squamous Differentiation Areas and Dedifferentiated Regions Ameloblastic Carcinoma (Secondary Type) with Extensive Squamous Differentiation Areas and Dedifferentiated Regions via Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Publication date: Available online 13 October 2015 Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Felipe Paiva Fonseca, Oslei Paes de Almeida, Pablo Agustin Vargas, Fábio Gonçalves Júnior, Flávia Sirotheau Corrêa Pontes, Hélder Antônio Rebelo Pontes Ameloblastic carcinoma is rare, accounting for 1.5 to 2.0% of all odontogenic tumors. Few small series are available, but data upon its clinicopathological characteristics derive mainly from single case reports; therefore, description of new cases may help to better understand the biological characteristics of this rare odontogenic malignancy. In the current report we describe an ameloblastic carcinoma affecting a 27-year-old female patient that had a previous diagnosis of ameloblastoma seven years before. The carcinoma showed extensive areas of squamous differentiation resembling a primary intra-osseous squamous cell carcinoma, as well as areas of dedifferentiation, a poorly documented histological characteristic of ameloblastic carcinoma. This case provides new insights on the microscopic spectrum of ameloblastic carcinoma, permitting a critical discussion of the current WHO classification of this odontogenic tumor. Read More » A biphasic sessile mass of the buccal mucosa A biphasic sessile mass of the buccal mucosa via Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology    Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Tiffany M. Peters, Jose P. Zevallos, Brent A. Golden, Alice E. Curran Read More » Secondary syphilis with oral manifestations Clinicopathological features, microvessel density and immunohistochemical expression of ICAM-1 and VEGF in 15 cases of  via Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Publication date: Available online 13 October 2015 Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Fábio Ramôa Pires, Paulo José Souza da Silva, Renan Ferreira Natal, Fábio Abreu Alves, Clovis Antônio Lopes Pinto, Alícia Rumayor, Águida Maria Menezes Aguiar Miranda, Oslei Paes de Almeida Several studies have reported the clinical aspects of oral syphilis, but few papers have considered the involved immunoinflammatory mechanisms. Objective: to analyze the clinicopathological features and expression of immunoinflammatory and vascular proteins in oral secondary syphilis. Study Design: fifteen patients with oral secondary syphilis were included; histological features were analyzed using HE-stained histological slides and immunohistochemical reactions were performed against ICAM-1, VEGF and CD34. Results: lesions presented as multiple plaques and ulcers mostly located on the tongue, lips and palate. They were covered by a stratified epithelium of irregular thickness showing exocytosis associated with a subjacent plasma cell infiltrate arranged in perivascular and perineural patterns. ICAM-1 and VEGF were expressed on endothelial cells and leukocytes and microvessel density was similar on the superficial and deep regions of the connective tissue. Conclusion: expression of immunoinflammatory and vascular proteins was intense, suggesting their participation on the pathogenesis of oral secondary syphilis. Read More » The relationship between speech segment duration and vowel centralization  in a group of older speakers by Annalise R. Fletcher, Megan J. McAuliffe, Kaitlin L. Lansford and Julie M. Liss via The Journal of the Acoustical Society of America This study examined the relationship between average vowel duration and spectral vowel quality across a group of 149 New Zealand English speakers aged 65 to 90 yr. The primary intent was to determine whether participants who had a natural tendency to speak slowly would also produce more spectrally distinct vowel segments. As a secondary aim, this study investigated whether advancing age exhibited a measurable effect on vowel quality and vowel durations within the group. In examining vowel quality, both flexible and static formant extraction points were compared. Two formantmeasurements, from selected [ɐ:], [ ], and [ ] vowels, were extracted from a standard passage and used to calculate twomeasurements of vowel space area (VSA) for each speaker. Average vowel duration was calculated from segments across the passage. The study found a statistically significant relationship between speakers' average vowel durations and VSA measurements indicating that, on average, speakers with slower speech rates produced more acoustically distinct speech segments. As expected, increases in average vowel duration were found with advancing age. However, speakers' formant values remained unchanged. It is suggested that the use of a habitually slower speaking rate may assist speakers in maintaining acoustically distinct vowels. Read More » Reciprocal measurement of acoustic feedback paths in hearing aids Reciprocal measurement of acoustic feedback paths in hearing aids by Tobias Sankowsky-Rothe, Matthias Blau, Henning Schepker and Simon Doclo via The Journal of the Acoustical Society of America: JASA EXPRESS LETTERS A reciprocal measurement procedure to measure the acoustic feedback path in hearing aids is investigated. The advantage of the reciprocal measurement compared to the direct measurement is a significantly reduced sound pressure in the ear. The direct and reciprocal measurements are compared using measurements on a dummy head with adjustable ear canals, different earmolds, and variations in the outer sound field. The results show that the reciprocal measurement procedure can be used to obtain plausible feedback paths, while reducing the sound pressure in the ear canal by 30 to 40 dB. Read More » Electrical stimulation and exercise for dysphagia Efficacy of electrical stimulation and exercise for dysphagia in patients with head and neck cancer: A randomized clinical trial by Susan E. Langmore, Timothy M. McCulloch, Gintas P. Krisciunas, Cathy L. Lazarus, Douglas J. Daele, Barbara Roa Pauloski, Denis Rybin, Gheorghe Doros via Head & Neck Abstract Background Neuromuscular electrical stimulation (NMES) is a highly sought after but poorly studied treatment for dysphagia among patients with head and neck cancer with dysphagia. This study investigated the efficacy of NMES in this patient population. Methods In this double-blinded, randomized controlled trial, 170 patients with head and neck cancer experiencing posttreatment dysphagia were randomized into active NMES + swallow exercise versus sham NMES + swallow exercise groups. Outcomes after a 12-week program included changes in fluoroscopy measures, diet, and quality of life. Results After the 12-week program, the active NMES group had significantly worse Penetration Aspiration Scale scores than the sham group. Both groups reported significantly better diet and quality of life. No other measures were significant. Conclusion NMES did not add benefit to traditional swallow exercises. Unfortunately, swallow exercises were not effective by themselves either. For patients with head and neck cancer with moderate to severe dysphagia caused by radiation therapy, current behavioral therapies are of limited help in reversing long-term dysphagia. © 2015 Wiley Periodicals,Head Neck, 2015 Read More » Dosing intervals in intralymphatic immunotherapy Dosing intervals in intralymphatic immunotherapy by Ásdís Hjálmsdóttir, Ying Wäckerle-Men, Agathe Duda, Thomas M. Kündig, Pål Johansen via Clinical & Experimental Allergy Abstract Allergen-specific subcutaneous (SCIT) as well as sublingual (SLIT) immunotherapy both confer long-term protection against the highly prevalent IgE-mediated allergies, such as allergic rhino-conjunctivitis and asthma. Since both SCIT and SLIT are both very laborious and time-consuming treatments, we and others have investigated whether the immunotherapy could be enhanced by so-called intralymphatic immunotherapy (ILIT), which aims at improving treatment efficacy and safety and to reduce treatment duration, thereby making allergen immunotherapy (AIT) more patient friendly. In the original studies made by us (1, 2) and by Cardell et al (3), ILIT was administered three times with four week intervals. In 2013, Witten et al. questioned the efficacy of ILIT with grass pollen, based on the results of a clinical study of their in 38 adult hay-fever patients (4). While promising immunological changes such as increased IgG4 and Treg responses were observed, they concluded that the clinical outcome was at odds with that measured by us in 165 hay fever and 20 cat-dander allergic patients as well as in Cardell's study with 28 hay-fever patients. Read More » Endoscopic Treatment of Bronchial Carcinoids  in Comparison to Surgical Resection: A Retrospective Study by Neyman, Kirill; Sundset, Arve; Naalsund, Anne; Espinoza, Andreas; Solberg, Steinar; Kongerud, Johny; Fosse, Erik via Journal of Bronchology & Interventional Pulmonology - Most Popular Articles Background: Surgery is the gold standard of lung carcinoid treatment. However, bronchoscopic treatment may provide a complete cure in selected patients. The aim of the study was to review the results of laser treatment of bronchial carcinoids and to compare the outcome after laser resection against the outcome after surgical resection. Methods: Seventy-three patients, 29 men and 44 women, median age 53 years (range, 23 to 78 y), with bronchial carcinoids were treated by surgical resection (n=48) or endobronchial ablation (n=25). Bronchoscopic treatment was also performed in 5 of 48 surgical patients as a part of the surgical treatment strategy. Results: Among 25 patients treated endoscopically, 16 were successfully treated with laser, whereas 9 were operated subsequently. One major complication was registered, as an inadvertent ventilation caused a nonfatal fire of the bronchoscope during Nd:YAG laser procedure. Forty-eight patients underwent surgical resection. Most of the patients underwent lobectomy and bilobectomy (30 and 5 patients, respectively). Four of the patients were dead by the end of the study, 1 was treated with laser, and 3 treated with surgical resection. The overall survival was 94.5% in the surgical group and 94.4% in the group treated with endoscopic ablation (P=0.9). None of the 69 survivors had any sign of recurrence on computed tomographic scans and bronchoscopy by the end of the study. Conclusions: This is a retrospective study and no randomization has been performed. However, the results add evidence to the view that transbronchial laser treatment may be offered as a safe, stand-alone procedure in the treatment of typical carcinoid tumor in the central airways. Read More » Are stents beneficial in endoscopic choanal atresia repair of newborns and children?  Case series of 11 patients by Axel Wolf, Doris Lang-Loidolt, Wolfgang Koele, Gerald Wolf, Dietmar Thurnher, Heinz Stammberger, Peter V. Tomazic viaClinical Otolaryngology Abstract Although commonly used, the use of stents after endonasal, endoscopic choanal atresia and choanal stenosis repair is not clearly defined yet. The aim of the present work was to report about our experience of choanal stent application. Excellent postoperative results can be achieved with both, stent- and non-stent surgical techniques. Choanal stents may be used in newborns in order to avoid immediate postoperative restenosis and subsequent potential live threatening complications. Due to possible stent associated complications, we do not recommend the application of choanal stents in older patients (> 1 year) with mild symptoms. Read More »