Intradural cervical chordoma with diffuse spinal leptomeningeal spread: case report and review of the literature

Abstract

Purpose

Chordoma is a low-grade malignant bone tumor derived from embryonic notochord remnants along the axial skeleton. About 50% of chordomas occur in the sacral vertebrae and 35% in the skull base. Most chordomas are extradural and cause extensive bone destruction. Intradural spinal tumors without bone involvement are rare.

Methods

We herein describe the clinical features of a patient with a chordoma as well as the imaging and pathological manifestations of the tumor.

Results

We encountered an unusual presentation of a C6 and C7 spinal intradural chordoma in a 23-year-old man. He presented with a 5-day history of discomfort over the lumbosacral region. Magnetic resonance imaging and enhanced scanning of the cervical spine showed an intradural soft tissue mass at C6 and C7 and linear enhancement of the spinal meninges. The tumor was excised because the patient had been previously misdiagnosed with an intraspinal neurogenic tumor with spinal meningitis. Postoperative pathological examination confirmed the diagnosis of chordoma. On postoperative day 7, the patient underwent brain magnetic resonance imaging because of severe headache. The images showed multiple soft tissue nodules in the skull base cistern. To the best of our knowledge, this is the first case report of an entirely extraosseous and spinal intradural chordoma with diffuse spinal leptomeningeal spread. The patient died 2 months postoperatively.

Conclusions

An intradural spinal chordoma is difficult to distinguish from a neurogenic tumor by imaging. When the lesion is dumbbell-shaped, it is easily misdiagnosed as a schwannoma. In the present case, the tumor was intradural and located at the level of the C6 and C7 vertebrae. Preoperative diagnosis was difficult, and the final diagnosis required pathological examination.

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Edmonton obesity staging system among pediatric patients: a validation and obesogenic risk factor analysis

Abstract

Purpose

The Edmonton Obesity Staging System for Pediatrics (EOSS-P) is a useful tool, delineating different obesity severity tiers associated with distinct treatment barriers. The aim of the study was to apply the EOSS-P on a Greek pediatric cohort and assess risk factors associated with each stage, compared to normal weight controls.

Methods

A total of 361 children (2–14 years old), outpatients of an Athenian hospital, participated in this case–control study by forming two groups: the obese (n = 203) and the normoweight controls (n = 158). Anthropometry, blood pressure, blood and biochemical markers, comorbidities and obesogenic lifestyle parameters were recorded and the EOSS-P was applied. Validation of EOSS-P stages was conducted by juxtaposing them with IOTF-defined weight status. Obesogenic risk factors' analysis was conducted by constructing gender-and-age-adjusted (GA) and multivariate logistic models.

Results

The majority of obese children were stratified at stage 1 (46.0%), 17.0% were on stage 0, and 37.0% on stage 2. The validation analysis revealed that EOSS-P stages greater than 0 were associated with diastolic blood pressure and levels of glucose, cholesterol, LDL and ALT. Reduced obesity odds were observed among children playing outdoors and increased odds for every screen time hour, both in the GA and in the multivariate analyses (all P < 0.05). Although participation in sports > 2 times/week was associated with reduced obesity odds in the GA analysis (OR = 0.57, 95% CI = 0.33–0.98, P linear = 0.047), it lost its significance in the multivariate analysis (P linear = 0.145). Analogous results were recorded in the analyses of the abovementioned physical activity risk factors for the EOSS-P stages. Linear relationships were observed for fast-food consumption and IOTF-defined obesity and higher than 0 EOSS-P stages. Parental obesity status was associated with all EOSS-P stages and IOTF-defined obesity status.

Conclusions

Few outpatients were healthy obese (stage 0), while the majority exhibited several comorbidities. Since each obesity tier entails different impacts to disease management, the study herein highlights modifiable factors facilitating descend to lower stages, and provides insight for designing tailored approaches tackling the high national pediatric obesity rates.

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Websites on Bladder Cancer: an Appropriate Source of Patient Information?

Abstract

A growing number of patients search for health information online. An early investigation of websites about bladder cancer (BCa) revealed mostly incomplete and particularly inaccurate information. We analyzed the quality, readability, and popularity of the most frequented websites on BCa. An Internet search on www.google.com was performed for the term "bladder cancer." After selecting the most frequented websites for patient information, HONcode quality certification, Alexa popularity rank, and readability scores (according to US grade levels) were investigated. A 36-point checklist was used to assess the content according to the EAU guidelines on BCa, which was categorized into seven topics. The popularity of the 49 websites analyzed was average, with a median Alexa popularity rank of 41,698 (interquartile range [IQR] 7–4,671,246). The readability was rated difficult with 11 years of school education needed to understand the information. Thirteen (27%) websites were HONcode certified. Out of 343 topics (seven EAU guideline topics each on 49 websites), 79% were mentioned on the websites. Of these, 10% contained incorrect information, mostly outdated or biased, and 34% contained incomplete information. Publically provided websites mentioned more topics per website (median [IQR] 7 [5.5–7] vs. 5.5 [3.3–7]; p = 0.022) and showed less incorrect information (median [IQR] 0 [0–1] vs. 1 [0–1]; p = 0.039) than physician-provided websites. Our study revealed mostly correct but partially incomplete information on BCa websites for patients. Physicians and public organizations should strive to keep their website information up-to-date and unbiased to optimize patients' health literacy.

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The Effect of Educational Intervention Based on Health Belief Model and Social Support on Promoting Skin Cancer Preventive Behaviors in a Sample of Iranian Farmers

Abstract

Skin cancer is one of the most common cancers in Iran. Farmers are exposed to the sun's ultraviolet radiation due to their job and are susceptible to skin cancer. The aim of this study is to survey the effect of educational intervention based on health belief model and social support on promoting skin cancer preventive behaviors in farmers of Fasa City, Fars province, Iran. In this quasi-experimental study, 200 farmers (100 in experimental group and 100 in control group) in Fasa City, Fars, Iran, were selected in 2017. The educational intervention for the experimental group consisted of eight training sessions (introduction to skin cancer, risk factors, complications, benefits and barriers to proper use of sunscreen, UV sunglasses and physical protection, self-efficacy in applying preventive behaviors, role of social support). A questionnaire consisting of demographic information, knowledge, HBM constructs (perceived susceptibility, severity, benefits, barriers, self-efficacy and cues to action), and social support was used to measure skin cancer preventive behaviors before, 3 months after the intervention, and 6 months later. Data were analyzed using SPSS-22 via chi-squared, independent samples t test, Mann-Whitney, and repeated measures ANOVA at a significance level of 0.5. The mean age of the farmers was 42.21 ± 10.52 years in the experimental group and 44.28 ± 10.16 years in the control group. Three months after the intervention and 6 months after the intervention, the experimental group showed a significant increase in the knowledge, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, cues to action, social support, and skin cancer preventive behaviors compared to the control group. This study showed the effectiveness of the intervention based on the HBM constructs and social support in adoption of skin cancer preventive behaviors in 3 and 6 months post intervention in farmers. Hence, these models can act as a framework for designing and implementing educational interventions for the prevention of skin cancer.

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CD146 positive human dental pulp stem cells promote regeneration of dentin/pulp-like structures

Abstract

CD146 and STRO-1 are endothelial biomarkers that are co-expressed on the cellular membranes of blood vessels within human dental pulp tissue. This study characterized the percentage of dentin-like structures produced by CD146-positive (CD146⁺) human dental pulp stem cells (DPSCs), compared with their CD146-negative (CD146⁻) counterparts. DPSC populations were enriched using magnetic-activated cell sorting (MACS), yielding CD146⁺ and CD146⁻ cells, as well as mixtures composed of 25% CD146⁺ cells and 75% CD146⁻ cells (CD146^+/−). Cell growth assays indicated that CD146⁺ cells exhibit an approximate 3–4 h difference in doubling time, compared with CD146⁻ cells. Cell cycle distributions were determined by flow cytometry analysis. The low percentage of CD146⁺ cells' DNA content in G₀/G₁ phase were compared with CD146⁻ and non-separated cells. In contrast to CD146⁻ and non-separated cells, prompt mineralization was observed in CD146⁺ cells. Subsequently, qRT-PCR revealed high mRNA expression of CD146 and Alkaline phosphatase in mineralization-induced CD146⁺ cells. CD146⁺ cells were also observed high adipogenic ability by Oil red O staining. Histological examinations revealed an increased area of dentin/pulp-like structures in transplanted CD146⁺ cells, compared with CD146⁻ and CD146^+/− cells. Immunohistochemical studies detected dentin matrix protein-1 (DMP1) and dentin sialophosphoprotein (DSPP), as well as human mitochondria, in transplanted DPSCs. Co-expression of CD146 and GFP indicated that CD146 was expressed in transplanted CD146⁺ cells. CD146⁺ cells may promote mineralization and generate dentin/pulp-like structures, suggesting a role in self-renewal of stem cells and dental pulp regenerative therapy.

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A Case Report of Abdominal Desmoplastic Small Round Cell Tumor in a Young Tunisian Woman

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Defining the phenotypic spectrum of SLC6A1 mutations

Summary

Objective

Pathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in a larger cohort of SCL6A1-mutated patients.

Methods

We collected 24 SLC6A1 probands and 6 affected family members. Four previously published cases were included for further electroclinical description. In total, we reviewed the electroclinical data of 34 subjects.

Results

Cognitive development was impaired in 33/34 (97%) subjects; 28/34 had mild to moderate ID, with language impairment being the most common feature. Epilepsy was diagnosed in 31/34 cases with mean onset at 3.7 years. Cognitive assessment before epilepsy onset was available in 24/31 subjects and was normal in 25% (6/24), and consistent with mild ID in 46% (11/24) or moderate ID in 17% (4/24). Two patients had speech delay only, and 1 had severe ID. After epilepsy onset, cognition deteriorated in 46% (11/24) of cases. The most common seizure types were absence, myoclonic, and atonic seizures. Sixteen cases fulfilled the diagnostic criteria for MAE. Seven further patients had different forms of generalized epilepsy and 2 had focal epilepsy. Twenty of 31 patients became seizure-free, with valproic acid being the most effective drug. There was no clear-cut correlation between seizure control and cognitive outcome. Electroencephalography (EEG) findings were available in 27/31 patients showing irregular bursts of diffuse 2.5-3.5 Hz spikes/polyspikes-and-slow waves in 25/31. Two patients developed an EEG pattern resembling electrical status epilepticus during sleep. Ataxia was observed in 7/34 cases. We describe 7 truncating and 18 missense variants, including 4 recurrent variants (Gly232Val, Ala288Val, Val342Met, and Gly362Arg).

Significance

Most patients carrying pathogenic SLC6A1 variants have an MAE phenotype with language delay and mild/moderate ID before epilepsy onset. However, ID alone or associated with focal epilepsy can also be observed.

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Cytotoxic edema at onset in West syndrome of unknown etiology: A longitudinal diffusion tensor imaging study

Summary

Objective

To clarify longitudinal changes in white matter microstructures from the onset of disease in patients with West syndrome (WS) of unknown etiology.

Methods

Diffusion tensor imaging (DTI) was prospectively performed at onset and at 12 and 24 months old in 17 children with WS of unknown etiology. DTI was analyzed using tract-based spatial statistics (TBSS) and tract-specific analysis (TSA) of 13 fiber tracts, and fractional anisotropy (FA) and mean diffusivity (MD) were compared with those of 42 age-matched controls. Correlations of FA and MD with developmental quotient (DQ) at age 24 months were analyzed. Multiple comparisons were adjusted for using the false discovery rate (q-value).

Results

TBSS analysis at onset showed higher FA and lower MD in the corpus callosum and brainstem in patients. TSA showed lower MD in bilateral uncinate fasciculi (UF) (right: q < 0.001; left: q = 0.03) at onset in patients. TBSS showed a negative correlation between FA at onset and DQ in the right frontal lobe, whereas FA at 24 months old exhibited a positive correlation with DQ in the diffuse white matter. MD for bilateral UF at 24 months old on TSA correlated positively with DQ (q = 0.04, both).

Significance

These findings may indicate the existence of cytotoxic edema in the immature white matter and dorsal brainstem at onset, and subsequent alterations in the diffuse white matter in WS of unknown etiology. Microstructural development in the UF might play important roles in cognitive development in WS.

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Websites on Bladder Cancer: an Appropriate Source of Patient Information?

Abstract

A growing number of patients search for health information online. An early investigation of websites about bladder cancer (BCa) revealed mostly incomplete and particularly inaccurate information. We analyzed the quality, readability, and popularity of the most frequented websites on BCa. An Internet search on www.google.com was performed for the term "bladder cancer." After selecting the most frequented websites for patient information, HONcode quality certification, Alexa popularity rank, and readability scores (according to US grade levels) were investigated. A 36-point checklist was used to assess the content according to the EAU guidelines on BCa, which was categorized into seven topics. The popularity of the 49 websites analyzed was average, with a median Alexa popularity rank of 41,698 (interquartile range [IQR] 7–4,671,246). The readability was rated difficult with 11 years of school education needed to understand the information. Thirteen (27%) websites were HONcode certified. Out of 343 topics (seven EAU guideline topics each on 49 websites), 79% were mentioned on the websites. Of these, 10% contained incorrect information, mostly outdated or biased, and 34% contained incomplete information. Publically provided websites mentioned more topics per website (median [IQR] 7 [5.5–7] vs. 5.5 [3.3–7]; p = 0.022) and showed less incorrect information (median [IQR] 0 [0–1] vs. 1 [0–1]; p = 0.039) than physician-provided websites. Our study revealed mostly correct but partially incomplete information on BCa websites for patients. Physicians and public organizations should strive to keep their website information up-to-date and unbiased to optimize patients' health literacy.

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The Effect of Educational Intervention Based on Health Belief Model and Social Support on Promoting Skin Cancer Preventive Behaviors in a Sample of Iranian Farmers

Abstract

Skin cancer is one of the most common cancers in Iran. Farmers are exposed to the sun's ultraviolet radiation due to their job and are susceptible to skin cancer. The aim of this study is to survey the effect of educational intervention based on health belief model and social support on promoting skin cancer preventive behaviors in farmers of Fasa City, Fars province, Iran. In this quasi-experimental study, 200 farmers (100 in experimental group and 100 in control group) in Fasa City, Fars, Iran, were selected in 2017. The educational intervention for the experimental group consisted of eight training sessions (introduction to skin cancer, risk factors, complications, benefits and barriers to proper use of sunscreen, UV sunglasses and physical protection, self-efficacy in applying preventive behaviors, role of social support). A questionnaire consisting of demographic information, knowledge, HBM constructs (perceived susceptibility, severity, benefits, barriers, self-efficacy and cues to action), and social support was used to measure skin cancer preventive behaviors before, 3 months after the intervention, and 6 months later. Data were analyzed using SPSS-22 via chi-squared, independent samples t test, Mann-Whitney, and repeated measures ANOVA at a significance level of 0.5. The mean age of the farmers was 42.21 ± 10.52 years in the experimental group and 44.28 ± 10.16 years in the control group. Three months after the intervention and 6 months after the intervention, the experimental group showed a significant increase in the knowledge, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, cues to action, social support, and skin cancer preventive behaviors compared to the control group. This study showed the effectiveness of the intervention based on the HBM constructs and social support in adoption of skin cancer preventive behaviors in 3 and 6 months post intervention in farmers. Hence, these models can act as a framework for designing and implementing educational interventions for the prevention of skin cancer.

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Issue Information

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Prenatal exposure to Chernobyl fallout in Norway: neurological and developmental outcomes in a 25-year follow-up

Abstract

Ionizing radiation at high doses early in life may cause neurodevelopmental problems. Possible effects of lower doses are, however, controversial. We use carefully collected exposure data for Norway following the Chernobyl accident in April 1986 combined with population-based registries to assess long-term effects of fetal exposure on neurodevelopmental outcomes. Radiation doses were estimated for each Norwegian municipality for each calendar month from May 1986 to April 1989. We established a cohort of all Norwegian pregnancies during the three-year period of radiation measurement and compared them with appropriate unexposed groups. All cohorts were followed into adulthood. Risks of cerebral palsy, mental retardation, schizophrenia, epilepsy, vision or hearing problems, school dropout, and low income were estimated. We also conducted an analysis of mathematics and language grades using siblings born after the exposure period as comparison. There was little evidence of associations between radiation exposure and cerebral palsy, mental retardation, schizophrenia, epilepsy, or hearing or vision problems associated with radiation exposure. (p-values for trend with exposure dose were 0.27, 0.14, 0.83, 0.35 and 0.42.) Slightly more of the exposed failed to complete high school (p = 0.05), but there was no increase in the proportion with low income (p = 0.38). The natural advantage of older siblings over younger siblings in mathematics grades was diminished with exposure of older siblings (p = 0.003), but there was no association of exposure with Norwegian language grades (p = 0.37). There is scant evidence that the low-dose fallout from Chernobyl in Norway increased the risk for serious neurodevelopmental problems. We cannot exclude the possibility of lower mathematics grades with exposure, similar to a report from Sweden.

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Prenatal exposure to Chernobyl fallout in Norway: neurological and developmental outcomes in a 25-year follow-up

Abstract

Ionizing radiation at high doses early in life may cause neurodevelopmental problems. Possible effects of lower doses are, however, controversial. We use carefully collected exposure data for Norway following the Chernobyl accident in April 1986 combined with population-based registries to assess long-term effects of fetal exposure on neurodevelopmental outcomes. Radiation doses were estimated for each Norwegian municipality for each calendar month from May 1986 to April 1989. We established a cohort of all Norwegian pregnancies during the three-year period of radiation measurement and compared them with appropriate unexposed groups. All cohorts were followed into adulthood. Risks of cerebral palsy, mental retardation, schizophrenia, epilepsy, vision or hearing problems, school dropout, and low income were estimated. We also conducted an analysis of mathematics and language grades using siblings born after the exposure period as comparison. There was little evidence of associations between radiation exposure and cerebral palsy, mental retardation, schizophrenia, epilepsy, or hearing or vision problems associated with radiation exposure. (p-values for trend with exposure dose were 0.27, 0.14, 0.83, 0.35 and 0.42.) Slightly more of the exposed failed to complete high school (p = 0.05), but there was no increase in the proportion with low income (p = 0.38). The natural advantage of older siblings over younger siblings in mathematics grades was diminished with exposure of older siblings (p = 0.003), but there was no association of exposure with Norwegian language grades (p = 0.37). There is scant evidence that the low-dose fallout from Chernobyl in Norway increased the risk for serious neurodevelopmental problems. We cannot exclude the possibility of lower mathematics grades with exposure, similar to a report from Sweden.

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APOBEC mutagenesis in drug resistance and immune escape in HIV and cancer evolution

Abstract

The APOBEC mutational signature has only recently been detected in a multitude of cancers through next-generation sequencing. In contrast, APOBEC has been a focus of virology research for over a decade. Many lessons learnt regarding APOBEC within virology are likely to be applicable to cancer. In this review, we explore the parallels between the role of APOBEC enzymes in HIV and cancer evolution. We discuss data supporting the role of APOBEC mutagenesis in creating HIV genome heterogeneity, drug resistance, and immune escape variants. We hypothesize similar functions of APOBEC will also hold true in cancer.

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PD-1 blockade with nivolumab in endemic Kaposi sarcoma

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Outcome in colorectal cancer – tumour, stroma and so much more

colorectal cancerprognosisinflammationtumour microenvironment

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The T-cell Receptor {beta}-Chain Is an Immunotherapy Target for Lymphomas [Lymphoma]

Targeting the TRBC gene expressed by T-cell malignancies mitigates severe immunosuppression.

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Suppression of Adaptive Responses to Targeted Cancer Therapy by Transcriptional Repression [Research Briefs]

Acquired drug resistance is a major factor limiting the effectiveness of targeted cancer therapies. Targeting tumors with kinase inhibitors induces complex adaptive programs that promote the persistence of a fraction of the original cell population, facilitating the eventual outgrowth of inhibitor-resistant tumor clones. We show that the addition of a newly identified CDK7/12 inhibitor, THZ1, to targeted therapy enhances cell killing and impedes the emergence of drug-resistant cell populations in diverse cellular and in vivo cancer models. We propose that targeted therapy induces a state of transcriptional dependency in a subpopulation of cells poised to become drug tolerant, which THZ1 can exploit by blocking dynamic transcriptional responses, promoting remodeling of enhancers and key signaling outputs required for tumor cell survival in the setting of targeted therapy. These findings suggest that the addition of THZ1 to targeted therapies is a promising broad-based strategy to hinder the emergence of drug-resistant cancer cell populations.

Significance: CDK7/12 inhibition prevents active enhancer formation at genes, promoting resistance emergence in response to targeted therapy, and impedes the engagement of transcriptional programs required for tumor cell survival. CDK7/12 inhibition in combination with targeted cancer therapies may serve as a therapeutic paradigm for enhancing the effectiveness of targeted therapies. Cancer Discov; 8(1); 59–73. ©2017 AACR.

See related commentary by Carugo and Draetta, p. 17.

This article is highlighted in the In This Issue feature, p. 1

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First-Line Osimertinib Beneficial in Advanced NSCLC [News in Brief]

Osimertinib is more effective as first-line therapy than other EGFR inhibitors for patients with advanced EGFR-mutated non–small cell lung cancer—notably Asians, who have a higher incidence of the disease compared with Western populations. The conclusion is based on data from a subgroup analysis of the phase III FLAURA trial.

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The DNA Transposase PGBD5 Sensitizes Tumors to Inhibition of DNA Repair [Pediatric Cancers]

PGBD5 expression in pediatric solid tumors confers sensitivity to inhibitors of DNA damage signaling.

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Dasatinib Approved for Pediatric CML [News in Brief]

The FDA approved dasatinib to treat pediatric chronic myeloid leukemia. This drug is the second tyrosine kinase inhibitor, alongside imatinib, approved for this indication and represents an important new option for first- and second-line treatment.

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PMN-MDSC Infiltration Blocks the Antitumor Effects of CSF1R Inhibition [Immunology]

CSF1R inhibition both reduces protumorigenic TAMs and recruits protumorigenic PMN-MDSCs.

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Blocking IDO1 Helps Shrink Bladder, Cervical Tumors [News in Brief]

Findings from a phase I/IIa study indicate that combining the investigational indoleamine 2,3-dioxygenase 1 inhibitor BMS-986205 with nivolumab is safe and boosts response rates among patients with bladder and cervical cancers.

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PD-1 Functions as a Tumor Suppressor in T-cell Lymphoma [Lymphoma]

Oncogenic T-cell signaling upregulates PD-1, which increases PTEN expression to suppress oncogenesis.

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People [News in Brief]

Josep Tabernero, MD, PhD, and Alexis A. Thompson, MD, MPH, are featured.

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BLU-285 Targets KIT/PDGFRA Conformation and Activating Loop Mutations [Targeted Therapy]

The small-molecule inhibitor BLU-285 inhibits clinically relevant KIT and PDGFRA mutations.

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Basket Study Yields Approval for Rare Cancer [News in Brief]

The FDA, in a regulatory first, approved a targeted therapy based on a basket study. The move, which expanded the indications for the BRAF inhibitor vemurafenib to include Erdheim–Chester disease, points to a new approval pathway for drugs that treat rare cancers.

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In This Issue [In This Issue]

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JCAR015 in ALL: A Root-Cause Investigation [News in Brief]

After conducting an internal probe of the five deaths that halted JCAR015's development for acute lymphoblastic leukemia, Juno Therapeutics has concluded that multiple factors were at play. A surge in inflammatory cytokine levels from rapid, early T-cell proliferation may have provoked the blood–brain barrier disruption seen in these patients, inducing fatal cerebral edema.

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NFS1 Expression Protects Lung Tumor Cells from Ferroptosis [Lung Cancer]

NFS1 activity is essential for maintenance of iron–sulfur cluster biosynthesis in response to oxidative stress.

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Poziotinib Shows Promise for Rare Lung Cancer [News in Brief]

Poziotinib, an EGFR inhibitor that was previously shelved as ineffective against non–small cell lung cancer, is showing promising activity in a subset of patients with EGFR exon 20 insertions. According to preliminary data from a phase II trial, the drug led to a 73% overall response rate in patients with this disease subtype, which is typically highly resistant to standard therapy.

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Osteoblasts Promote Release of Tumor-Promoting SiglecFhi Neutrophils [Lung Cancer]

Lung tumors activate OCN⁺ osteoblasts in distant bone stroma to supply tumor-infiltrating neutrophils.

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FDA Approves Second CAR T-cell Therapy [News in Brief]

The FDA approved the chimeric antigen receptor T-cell therapy axicabtagene ciloleucel, making it the second such treatment for blood cancers in the United States. The therapy is indicated for adults with certain non-Hodgkin lymphomas who have tried at least two other treatments.

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Introduction to the Naida CI All-In-One Solution

This course on the Naída CI All-In-One Solution includes information about the system components, features, benefits, wireless accessories, and programming.

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Health care disparities among octogenarians and nonagenarians with stage III lung cancer

BACKGROUND

To the authors' knowledge, the practice patterns for patients aged more than 80 years with stage III non-small cell lung cancer (NSCLC) is not well known. The purpose of the current study was to investigate factors predictive of and the impact on overall survival (OS) after concurrent chemoradiation (CRT) among patients aged ≥80 years with American Joint Committee on Cancer stage III NSCLC in the National Cancer Data Base (NCDB).

METHODS

In the NCDB, patients aged ≥80 years who were diagnosed with stage III NSCLC from 2004 to 2013 with complete treatment records were identified. Multivariable logistic regression and Cox proportional hazard models were generated and propensity score-matched analysis was used.

RESULTS

A total of 12,641 patients met the entry criteria: 6018 (47.6%) had stage IIIA disease and 6623 (52.4%) had stage IIIB disease. The median age at the time of diagnosis was 83.0 years (range, 80-91 years). A total of 7921 patients (62.7%) received no therapy. Black race (odds ratio [OR], 1.23; 95% confidence interval [95% CI], 1.06-1.43) and living in a lower educated census tract of residence (OR, 1.20; 95% CI, 1.03-1.40) were found to be associated with not receiving care, whereas treatment at an academic center (OR, 0.80; 95% CI, 0.70-0.92) was associated with receiving cancer-directed therapy. Receipt of no treatment (hazard ratio [HR], 2.69; 95% CI, 2.57-2.82) or definitive radiation alone (HR, 1.15; 95% CI, 1.07-1.24) compared with CRT was associated with worse OS. On propensity score matching, not receiving CRT was found to be associated with worse OS (HR, 1.58; 95% CI, 1.44-1.72).

CONCLUSIONS

In this NCDB analysis, approximately 62.7% of patients aged ≥80 years with stage III NSCLC received no cancer-directed care. Black race and living in a lower educated census tract were associated with not receiving cancer-directed care. OS was found to be improved in patients receiving CRT. Cancer 2018. © 2018 American Cancer Society.

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The assessment of Buerger’s exercise on dorsal foot skin circulation in patients with vasculopathic diabetic foot ulcer by using wireless near-infrared spectroscope: a cohort prospective study

Abstract

The improvement of peripheral circulation is crucial for the care of vasculopathic diabetic foot ulcer (DFU). Near-infrared spectroscopy (NIRS) was used to investigate the effects of Buerger's exercise on dorsal foot skin circulation with novel technique of measuring the absorption difference in wavelength of light between oxy-hemoglobin (HbO₂) and deoxy-hemoglobin (HbR). Patients with vasculopathic DFU who could tolerate Buerger's exercise three times a day at home for at least 8 weeks were enrolled (group A). They were divided into two subgroups: without previous percutaneous transluminal angioplasty (PTA) (group A1) vs. with previous PTA (group A2). Wireless NIRS were applied on patients' dorsal foot to assess the peripheral circulation in follow-up clinics. The patients' wound condition, follow-up time, and concentration of HbO₂ and total hemoglobin (HbT) before and after exercise rehabilitation program were documented. From May 2015 to February 2016, 14 patients with average age of 70.2 ± 11.2 were enrolled in this study (group A), including eight without previous PTA (group A1), and six with previous PTA (group A2). The concentration of HbO2 and HbT were significantly increased after exercise rehabilitation program training in group A (p = 0.024 in HbO₂, p = 0.02 in HbT, n = 14) and group A2 (p = 0.021 in HbO₂, p = 0.028 in HbT, n = 6), while the concentration in group A1 were improved with borderline significance after exercise (p = 0.055 in HbO₂, p = 0.058 in HbT, n = 8). The majority of the ulcers were either completely healed (11/14 = 78.57%) or improving (3/14 = 21.43%). Buerger's exercise improved the peripheral circulation and wound condition in patients with vasculopathic DFU. The wireless apparatus is a novel and efficient tool to monitor rehabilitation program.

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Histopathological and immunohistochemical characterization of Burkholderia pseudomallei lesions in an acute model of infection with BALB/c mice

Summary

Organ tissue damage is a key contributor to host morbidity and mortality following infection with microbial agents. Severe immune responses, excessive cellular recruitment and necrosis of cells all play a role in disease pathology. Understanding the pathogenesis of disease can aid in identifying potential new therapeutic targets or simply act as a diagnostic tool. Burkholderia pseudomallei is a Gram-negative bacterium that can cause acute and chronic diseases. The BALB/c mouse has been shown to be highly susceptible to aerosol challenge with B. pseudomallei and hence acts as a good model to study the acute and potentially lethal form of the disease melioidosis. In our study, BALB/c mice were challenged and culled at predetermined time points to generate a pathological time course of infection. Lung, liver and spleen were subjected to pathological and immunohistochemical analysis. The number and type of microscopic lesions within each organ, as well as the location and the mean percentage of neutrophils, B cells, T cells and Burkholderia capsule antigen within the lesions, were all characterized during the time course. Neutrophils were determined as the key player in tissue pathology and generation of lesions, with B cells playing an insignificant role. This detailed pathological assessment increases our understanding of B. pseudomallei disease.

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Rabdocoestin B exhibits antitumor activity by inducing G2/M phase arrest and apoptosis in esophageal squamous cell carcinoma

Abstract

Purpose

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive squamous cell carcinomas and is generally resistant to chemotherapy. In the present study, the cytotoxic activity of Rabdocoestin B (Rabd-B) against ESCC and the underlying mechanisms were investigated.

Methods

The inhibitory effect of Rabd-B on KYSE30 and KYSE450 was evaluated by Cell Counting Kit-8 (CCK8) and colony formation assays in vitro. The cell cycle distribution and apoptosis of cells treated with Rabd-B were determined by flow cytometry. The mechanisms underlying the effects of Rabd-B were systematically examined by Western blot. The in vivo anti-tumor ability of Rabd-B was measured in mouse xenograft models and cisplatin (DDP) was used as positive control.

Results

Rabd-B efficiently induced G2/M phase arrest in ESCC cells by upregulating the Chk1/Chk2-Cdc25C axis to inhibit the G2→M transition facilitated by Cdc2/Cyclin B1. Furthermore, Rabd-B suppressed ATM/ATR phosphorylation, thereby inhibiting BRCA1-mediated DNA repair, which resulted in mitotic catastrophe and induced cell apoptosis. Rabd-B also decreased the activity of the Akt and NF-κB survival signaling pathways and ultimately initiated the caspase-9-dependent intrinsic apoptotic pathway in ESCC cells. The apoptosis induced by Rabd-B could be partially reversed by a caspase-9-specific inhibitor (Z-LEHD-FMK) and a pan-caspase inhibitor (Z-VAD-FMK). Moreover, Rabd-B effectively suppressed tumor growth in mouse xenografts which was comparable to that of DDP without significant injuries to the mice.

Conclusion

Taken together, these findings indicate that Rabd-B is a promising precursor compound that may be useful as a treatment for ESCC and thus warrants further investigation.

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Evaluation of sex hormones and sperm parameters in male epileptic patients

Objectives

The aim of this study was to investigate the effect of carbamazepine (CBZ) and sodium valproate (VPA) monotherapy on sexual functions, sex hormones, and semen analysis and quality in male patients with epilepsy.

Methods

A total of 59 male patients with epilepsy, of which 30 were on VPA monotherapy and 29 were on CBZ monotherapy, were included in the study between January 2015 and March 2016. A control group was established with 30 healthy males. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), free testosterone (fT), estradiol (E2), sex hormone-binding globulin (SHBG) levels and bioactive testosterone (BAT)/bioactive estradiol (BAE), and BAT/LH ratio were studied in groups. All groups received semen analysis and International Index of Erectile Function Scale (IIEF-5) test for erectile dysfunction.

Results

E2 and DHEAS levels were higher in VPA and CBZ groups compared to control group (P < .001, P = .014). The decrease in fT levels in the VPA group was statistically significant (P = .038). No significant difference was detected in levels of SHBG, LH, and FSH (P > .05). BAT/BAE ratios were low both in VPA and CBZ groups (P < .001; P < .001), while BAT/LH ratios were low only in CBZ group (P = .033). In semen analysis, semen volume and number of normal sperms were found to be significantly lower in patients receiving antiepileptic drugs compared to control group (P < .05). There were no differences between the groups in rates of abnormal sperm morphology. IIEF-5 scores were found to be significantly lower in VPA and CBZ groups (P < .001).

Conclusion

VPA or CBZ therapy may lead to dysregulation of sex hormones, sexual dysfunction, and alterations in semen analysis in male patients with epilepsy. This must be considered for the selection of antiepileptic drugs in young male patients.

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Serum cystatin C and anti-N-methyl-D-aspartate receptor encephalitis

Background

Cystatin C (CysC) is associated with many neurodegenerative disorders and autoimmune diseases, but its relationship with anti-N-Methyl-D-aspartate receptor (anti-NMDAR) encephalitis is unknown.

Methods

Serum levels of CysC were determined in 66 patients with anti-NMDAR encephalitis and 115 healthy controls. Of the 66 patients, 30 had a follow-up evaluation at 3 months after admission. Association of CysC with anti-NMDAR encephalitis and its clinical parameters were evaluated in the patients.

Results

The serum levels of CysC were significantly lower in patients with anti-NMDAR encephalitis than in controls (0.70 ± 0.13 vs 0.83 ± 0.17 mg/mL, P < .001). Disease severity and disease duration were significantly associated with CysC levels. Furthermore, a follow-up evaluation revealed that after treatment anti-NMDAR encephalitis patients had significantly increased serum CysC levels (P < .001) and significantly decreased modified Rankin Scale (mRS) scores (P < .001) compared with before treatment. In addition, a significant negative correlation was observed between the change in CysC levels and the change in mRS scores (r = −.700, P < .001).

Conclusion

Our results show that the serum levels of CysC are associated with anti-NMDAR encephalitis and its clinical parameters and that the changes in CysC levels correlate with therapeutic effect. Therefore, our findings provide new insights into the association between serum CysC and anti-NMDAR encephalitis.

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Pretherapeutic functional neuroimaging predicts tremor arrest after thalamotomy

Objective

Essential tremor (ET) represents the most common movement disorder. Drug-resistant ET can benefit from standard stereotactic procedures (deep brain stimulation or radiofrequency thalamotomy) or alternatively minimally invasive high-focused ultrasound or radiosurgery. All aim at same target, thalamic ventro-intermediate nucleus (Vim).

Methods

The study included a cohort of 17 consecutive patients, with ET, treated only with left unilateral stereotactic radiosurgical thalamotomy (SRS-T) between September 2014 and August 2015. The mean time to tremor improvement was 3.32 months (SD 2.7, 0.5-10). Neuroimaging data were collected at baseline (n = 17). Standard tremor scores, including activities of daily living (ADL) and tremor score on treated hand (TSTH), were completed pretherapeutically and 1 year later. We further correlate these scores with baseline inter-connectivity in twenty major large-scale brain networks.

Results

We report as predictive three networks, with the interconnected statistically significant clusters: primary motor cortex interconnected with inferior olivary nucleus, bilateral thalamus interconnected with motor cerebellum lobule V² (ADL), and anterior default-mode network interconnected with Brodmann area 10³ (TSTH). For all, more positive pretherapeutic interconnectivity correlated with higher drop in points on the respective scores. Age, disease duration, or time-to-response after SRS-T were not statistically correlated with pretherapeutic brain connectivity measures (P > .05). The same applied to pretherapeutic tremor scores, after using the same methodology described above.

Conclusions

Our findings have clinical implications for predicting clinical response after SRS-T. Here, using pretherapeutic magnetic resonance imaging and data processing without prior hypothesis, we show that pretherapeutic network(s) interconnectivity strength predicts tremor arrest in drug-naïve ET, following stereotactic radiosurgical thalamotomy.

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No excess of autoimmune diseases in multiple sclerosis families from the Netherlands

Objectives

Autoimmune diseases (AIDs) cluster in families; however, to what extent AIDs co-occur in MS multiplex families with two or more affected individuals is still controversial. The study aimed to evaluate coexisting AIDs in this type of families from the Netherlands.

Materials and methods

A total of 155 MS multiplex families (155 MS probands, 959 first-degree relatives and 212 spouses) were characterized for a history of 11 AIDs by means of a self-administered questionnaire.

Results

In 43.2% of MS multiplex families, at least one AID was present in the first-degree relatives. Overall, the frequency of AIDs was not significantly different between patients with MS (11%), their first-degree family members (11%) and controls (5.2%). After correction for age at inclusion and gender, the odds ratios (OR) for AIDs were not significant for patients with MS (OR = 1.8 [0.77-4.34], P = .17) and first-degree family members (OR = 2.0 [0.98-4.10], P = .06) when both compared to spouses. The frequency of AIDs in mothers did not differ from that in fathers after correction for sex bias (19% vs 8%, P = .51). A presence of AID was more often reported in maternal than paternal second-degree relatives (23% vs 10%, P = .0020).

Conclusion

Although nearly half of the Dutch MS multiplex families reported an AID, no excess of AIDs was present in patients with MS from multiplex families or their first-degree family members compared to the spouses.

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Effects of task demands on olfactory, auditory and visual event-related potentials suggest similar top-down modulation across senses

Abstract

A widely held view is that top-down modulation of sensory information relies on an amodal control network that acts through the thalamus to regulate incoming signals. Olfaction lacks a direct thalamic projection, which suggests that it may differ from other modalities in this regard. We investigated the late positive complex (LPC) amplitudes of event-related potentials (ERP) from 28 participants, elicited by intensity-matched olfactory, auditory and visual stimuli, during a condition of focused attention, a neutral condition, and a condition in which stimuli were to be actively ignored. Amplitudes were largest during the attend condition, lowest during the ignore condition, with the neutral condition in between. A Bayesian analysis resulted in strong evidence for similar effects of task across sensory modalities. We conclude that olfaction, despite its unique neural projections, does not differ from audition and vision in terms of task-dependent neural modulation of the LPC.

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Contact heat evoked potentials: reliable acquisition from lower extremities

Publication date: Available online 7 January 2018
Source:Clinical Neurophysiology
Author(s): J Rosner, M Hubli, P Hostettler, PS Scheuren, J Rinert, JLK Kramer, M Hupp, A Curt, CR Jutzeler
ObjectiveTo investigate test-retest reliability of contact heat evoked potentials (CHEPs) from lower extremities using two different stimulation protocols, i.e., normal and increased baseline temperature.MethodsA total of 32 able-bodied subjects were included and a subset (N=22) was retested. CHEPs were recorded from three different dermatomes of the lower extremity (i.e., L2, L5, and S2). Test-retest reliability of CHEPs acquisition after simulation in various lower limb dermatomes using different stimulation protocolswas analyzed.ResultsThe study revealed an improved acquisition of CHEPS employing the increased baseline protocol, particularly when stimulating more distal sites, i.e., dermatome L5 and S2. Based on repeatability coefficients, CHEP latency (N2 potential) emerged as the most robust CHEP parameter. Although CHEP amplitudes (N2P2 complex) and pain ratings were decreased in the retest, amplitudes still showed fair to excellent intraclass correlation coefficients (ICCs) using normal baseline or increased baseline temperature, respectively.ConclusionsThis is the first study to demonstrate that CHEPs acquisition from the lower extremities is improved by increasing the baseline temperature of the thermode.SignificanceThis study highlights the usability of CHEPs as a viable diagnostic method to study small fiber integrity.



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Viruses, bacteria, and parasites – oh my! a resurgence of interest in microbial-based therapy for cancer

Abstract

As infections and cancer are two of the most common maladies affecting human beings, a concerted effort is needed to better understand their potential interactions and to further explore their use in microbial-based cancer treatments. Studies focusing on the interaction between pathogens and cancer began over 4000 years ago, but therapeutic application of pathogens has often been bypassed as other cancer therapies have gained wider interest. To many, the field of microbial-based cancer treatment may feel antiquated and already sufficiently explored. However, closer examination reveals that our current knowledge is but a series of dim reflections amongst many yet-unexplored shadows. Particularly, with our increased understanding of pathogen entry, replication, and senescence, coupled with our quickly increasing knowledge regarding cancer initiation, growth, and metastasis, and capped by our realization of the complexity and plasticity of the immune response, we are just now beginning to realize the vastness of the undiscovered area encompassing this field. At the same time, we are now uniquely poised with gained knowledge and discovered tools to join together across disciplines, uncover new positive and negative interactions between pathogens and cancer, and make important progress toward saving cancer patient lives.

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Contact heat evoked potentials: reliable acquisition from lower extremities

Contact heat evoked potentials (CHEPs) reflect cortical responses of Aδ-nociceptors activated by noxious heat stimuli (Greffrath et al. 2007; Baumgartner et al. 2012). In addition to Aδ-fibers, C-fibers are also known to be involved in the perception of contact heat. The reliable recording of C-fiber volley is, however, extremely challenging (Magerl et al. 1999).

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Heparin-Bridging Therapy and Risk of Bleeding After Endoscopic Submucosal Dissection for Gastric Neoplasms: a Meta-Analysis

Abstract

Purpose

Peri-procedural heparin is recommended as bridging therapy for patients with high thromboembolic risk who need to withhold anticoagulant for endoscopic submucosal dissection (ESD) for gastric neoplasms. However, little is known about the bleeding risk from heparin-bridging therapy itself.

Methods

MEDLINE and EMBASE databases were searched through August 2017 for studies that compared the risk of post-ESD bleeding in patients who received heparin-bridging therapy in lieu of anticoagulant for gastric neoplasms and those who discontinued anticoagulant without receiving heparin. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effect model, generic inverse variance method. The between-study heterogeneity was quantified using the Q statistic and I².

Results

A total of four studies consisting of 350 patients were identified. A significantly increased risk of post-ESD bleeding among the bridged patients compared with the non-bridged patients was observed with the pooled RR of 2.99 (95% CI, 1.51 to 5.92). The statistical heterogeneity was insignificant with I² of 0%.

Conclusions

A significantly increased risk of post-ESD bleeding among patients who received heparin-bridging therapy in lieu of anticoagulant compared to patients who did not receive it was demonstrated in this study.

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Reference centile curves for wrist circumference for Indian children aged 3–18 years

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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A rare unbalanced Y:autosome translocation in a Turner syndrome patient

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Management of thyrotoxicosis in children and adolescents: 35 years’ experience in 304 patients

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Four novel mutations of the BCKDHA, BCKDHB and DBT genes in Iranian patients with maple syrup urine disease

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Decrease in serum chemerin through aerobic exercise plus dieting and its association with mitigation of cardio-metabolic risk in obese female adolescents

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Comparison between two inhibin B ELISA assays in 46,XY testicular disorders of sex development (DSD) with normal testosterone secretion

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Modification of the measurement of the major variables in mandibular condylar fractures: angulation of sidewards displacement and shortening of the height of the ramus

Publication date: Available online 5 January 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): S.P. Chang, Y. Yang, L.Q. Shi, Y.W. Liu, Y. Liu, Q. Ma
Our aim was to improve the accuracy of measurement of the angulation and the shortening of the height of the ramus in fractures of the mandibular condyle using modified methods. We analysed spiral computed tomography (CT) of 67 unilateral fractures with the OsiriX v 5.0 (©Pixmeo Sarl) and Mimics 19.0 (©2016 Materialise NV, Belgium) and analysed them with SPSS (version 24.0, IBM^® SPSS^®). Angulation was measured using both the traditional method and our modified method. The results showed significant difference (p = 0.000), and the values measured with the traditional method were lower, which is consistent with geometric analysis. We repositioned the condylar fragment with computer-aided surgical simulation and measured the shortened ramus. We were unable to find a significant difference between these values and those measured with our modified method (p = 0.053), so the accuracy of the modified method is acceptable. The measurement of the height of the ramus by our modified method is applicable to patients with unilateral, and those with bilateral, fractures. The accuracy in measurement of the major variables of condylar fractures is acceptable in both theory and practice. On the basis of such accurate measurement, more prospective clinical study is needed to find out the most appropriate treatment for condylar fractures.



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The value of detection of S100A8 and ASAH1 in predicting the chemotherapy response for breast cancer patients

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Yu-hong Li, Hai-ting Liu, Jing Xu, Ai-yan Xing, Jie Zhang, Ya-wen Wang, Gang Yin, Peng Gao
Chemotherapy plays an important role in the treatment of breast cancer. However, chemoresistance remains the main obstacle for effective treatment, leading to poor prognosis. This study aims to investigate the value of detection of S100A8 and ASAH1 in predicting the chemotherapy response. Miller and Payne grades were used to assess the chemotherapy response in breast cancers. The expression of S100A8 and ASAH1, as well as ER, PR, HER-2 and Ki-67 were assessed by immunohistochemical staining in 120 cases of non-special type invasive ductal carcinoma (IDC-NOS). S100A8 expression was higher in chemosensitive breast cancers than chemoresistant ones. Moreover, S100A8 expression was significantly correlated with the molecular subtypes and histological grade, but not with patients' age, tumor size and lymph nodes status. However, there was no significant difference in ASAH1 expression between chemoresistant and chemosensitive group. We also found that higher ASAH1 expression was correlated with positive lymph nodes status, but not with age, tumor size, molecular subtypes and histological grade. S100A8 was valuable in predicting chemotherapy response in breast cancers. The expression of ASAH1 was associated significantly with lymph nodes metastasis, indicating that ASAH1 may serve as a biomarker to predict patients' lymph nodes status in breast cancers.



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Atypical multivacuolated lipoblasts and atypical mitoses are not compatible with the diagnosis of spindle cell/pleomorphic lipoma—reply

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Michael Michal, Dmitry V. Kazakov, Kvetoslava Michalova, Michal Michal




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Characteristics of cribriform morular variant of papillary thyroid carcinoma in post-Chernobyl affected region

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Alfred King-yin Lam, Mikhail Fridman
The aim is to study the characteristics of cribriform morular variant of papillary thyroid carcinoma (CMV-PTC) in patients living in radiation-affected area of Belarus. The clinical and pathological features of 35 patients with CMV-PTC from Belarus were studied and compared with those of conventional papillary thyroid carcinoma diagnosed in the same period. The patients with CMV-PTC were all females and were younger at presentation (mean age = 24) than those with conventional papillary thyroid carcinoma. Familial adenomatous polyposis (FAP) was identified in 20% of the patients with CMV-PTC. The majority of the CMV-PTCs (29/35; 83%) were staged as pT1 and were less advanced than conventional papillary thyroid carcinoma. There was no evidence of lymph node metastases or distant metastases. CMV-PTCs were positive for beta-catenin, APC (adenomatous polyposis coli) and p53 proteins. No psammoma bodies were identified on microscopic examination. Over a median follow-up of 9 years, all the patients were alive, there were no cancer recurrence or mortality related to the thyroid cancer. To conclude, patients with CMV-PTC in radiation-affected region behave in an indolent fashion. They had distinctive features that are different from patients with conventional papillary thyroid carcinoma living in the same region.



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Downregulated SASH1 Expression Indicates Poor Clinical Prognosis in Gastric Cancer

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Nan Zhou, Can Liu, Xudong Wang, Qinsheng Mao, Qin Jin, Peng Li
SASH1 (SAM- and SH3-domain containing 1), a novel candidate tumor suppressor, has attracted attention due to its role in intracellular signal transduction and its tumor prognostic value in diverse cancers. Reports have demonstrated that reduced SASH1 expression correlates with tumor proliferation, invasion, and metastasis. However, the expression and prognostic significance of SASH1 in gastric cancer (GC) remain unclear. In this study, 8 paired fresh-frozen GC tissues and corresponding gastric mucosal tissues were examined by Western blot to analyze the protein expression of SASH1. 726 formalin-fixed, paraffin-embedded (FFPE) gastric tissue samples were evaluated by immunohistochemical (IHC) to determine the correlations of SASH1 expression with clinicopathological factors and prognosis. Compared with adjacent noncancerous tissues, SASH1 was significantly downregulated in GC specimens. Analysis using the χ test revealed that low SASH1 expression was significantly associated with advanced TNM stage (P<0.001) in GC. Cox regression multivariable analyses demonstrated that SASH1 expression (P<0.001), TNM stage (P<0.001), preoperative CEA level (P=0.003) and preoperative CA19-9 level (P=0.002) were independent prognostic factors. Our clinical findings suggest that downregulated SASH1 expression could be used as an independent biomarker for poor prognosis in GC.



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Prognostic significance of S100A16 sub-cellular localization in lung adenocarcinoma

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Makoto Kobayashi, Ryo Nagashio, Keita Saito, Clemente Aguilar-Bonavides, Shinichiro Ryuge, Ken Katono, Satoshi Igawa, Benio Tsuchiya, Shi-Xu Jiang, Masaaki Ichinoe, Yoshiki Murakumo, Makoto Saegusa, Yukitoshi Satoh, Yuichi Sato
To discover novel tumor markers for lung adenocarcinoma (AC), we performed proteomics analysis and reported a correlation between S100A16 membranous expression in AC tissues and a poor prognosis. However, some patients with a good prognosis also showed S100A16 membranous staining. We re-evaluated immunohistochemically stained tissues, and found membrane-positive and nucleus- negative expressions to be significantly higher in the presence of the following: male, smoker, positive nodal metastasis, higher p-TNM stage, larger tumor, poorer differentiation, positive for lymphatic invasion, positive for vascular invasion, and positive for pleural invasion (all factors P < 0.05). This pattern of staining was also an independent prognostic factor. Furthermore, we analyzed S100A16 mRNA expression using TCGA and Kaplan-Meier plotter databases, and found that higher S100A16 mRNA expression in AC was significantly correlated with poorer survival. To our knowledge, there has been no comprehensive study focused on both S100A16 protein and mRNA expression levels in AC patients. Our results suggest that the sub-cellular localization of S100A16 and S100A16 mRNA expression levels are promising prognostic markers for AC.



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Uterine Rhabdomyosarcoma in Adults

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Andre Pinto, Ryan M. Kahn, Andrew E. Rosenberg, Brian Slomovitz, Charles Matthew Quick, Michella K. Whisman, Marilyn Huang
Rhabdomyosarcoma (RMS) is an aggressive mesenchymal tumor most commonly diagnosed in the pediatric population, and when occurring in adults, tends to develop in the deep soft tissue of the limbs. Primary uterine RMS comprises an even more restricted subset, with little known or reported when compared to most other gynecologic sarcomas. Our goal with this study was to retrospectively evaluate cases from two academic institutions and describe the main histopathologic findings of this rare gynecologic malignancy. A total of eight cases were identified, consisting of four pleomorphic rhabdomyosarcomas (PRMS), two alveolar rhabdomyosarcomas (ARMS), and two embryonal rhabdomyosarcomas (ERMS). They occurred in patients ranging from 22 to 70 years old, and the most common presenting symptom was vaginal bleeding. Most patients presented with advanced stage at diagnosis, including metastatic disease to lymph nodes and to distant sites. The masses were mostly (6/8) centered in the myometrium, while two cases arose in the cervix (2/8). Histologic characteristics of the tumors were dependent of the RMS subtype, although all cases demonstrated a similar immunohistochemical profile regardless of their subclassification. RMS of the uterus has a very poor prognosis, and data regarding treatment of this rare malignancy is limited, and usually extrapolated from non-uterine sites.



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The Many Faces of Intestinal Tract Gastric Heterotopia; A Series of Four Cases Highlighting Clinical and Pathological Heterogeneity

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Aqsa Nasir, Stuart K. Amateau, Sabina Khan, Ross W. Simpson, Dale C. Snover, Khalid Amin
Gastric heterotopia of the intestinal tract can have a diverse clinicopathologic presentation, resulting in a diagnostic dilemma. We present a series of four cases, two male and two female patients with age range of 31-82 year, found in the duodenum, jejunum, and transverse colon. The most common and rather unusual clinical presentation was iron deficiency anemia, seen in three cases, while one patient presented with abdominal pain. Endoscopically two cases were visualized as pedunculated polyps and two as sessile/plaques like lesions. Polypectomy was performed in three patients and one patient underwent biopsy followed by resection. Two cases showed oxyntic-type epithelium and two cases exhibited pylorictype gastric epithelium. Three patients were relieved of their presenting symptoms after therapeutic procedure with no evidence of recurrence noted on follow-up. Follow-up was not available on one patient. This case series highlights diverse clinicopathologic spectrum of gastric heterotopia. Accurate diagnosis is essential for proper management.



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Effects of Rhinovirus (RV) 39 Infection on Airway Hyper-responsiveness (AHR) to Carbachol in Human Airways Precision Cut Lung Slices (PCLS)

Publication date: Available online 6 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Joshua L. Kennedy, Cynthia J. Koziol-White, Susanne Jeffus, Mallikarjuna R. Rettiganti, Paige Fisher, Megan Kurten, Anthony Eze, Suzanne House, James D. Sikes, Emily Askew, Claire Putt, Reynold A. Panettieri, Stacie M. Jones, Richard C. Kurten




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Cluster Analysis of Vulnerable Groups in Acute TBI Rehabilitation

Publication date: Available online 6 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Erkut N. Kucukboyaci, Coralynn Long, Michelle Smith, Joseph F. Rath, Tamara Bushnik
ObjectiveTo analyze the complex relationship between various social indicators that contribute to socioeconomic status and healthcare barriers.DesignCluster analysis of historical patient data obtained from inpatient visits.SettingSetting: Inpatient rehabilitation unit in a large, urban university hospitalParticipantsAdult patients receiving acute inpatient care, predominantly for closed head injury.InterventionsNot applicableMain outcome measuresWe examined the membership of TBI patients in various "vulnerable group" (VG) clusters (e.g., homeless, unemployed, racial/ethnic minority) and characterized the rehabilitation outcomes of the patients (e.g., duration of stay, changes in Functional Independence Measure [FIM] scores between admission to inpatient stay and discharge).ResultsAnalysis revealed four major clusters (i.e., Clusters A-D) separated by VG memberships, with distinct durations of stay and FIM gains during their stay. Cluster B, the largest cluster and also consisting of mostly racial/ethnic minorities, had the shortest duration of hospital stay and one of the lowest FIM improvements among the four clusters despite higher FIM scores at admission. In cluster C, also consisting of mostly ethnic minorities with multiple SES vulnerabilities, patients were characterized by low cognitive FIM scores at admission and the longest duration of stay, and they showed good improvement in FIM scores.ConclusionsApplication of clustering techniques to inpatient data identified distinct clusters of patients who may experience differences in their rehabilitation outcome due to their membership in various "at-risk" groups. Results identified patients (i.e., cluster B, with minority patients and Cluster D, with elderly patients) who attain below-average gains in brain injury rehabilitation. Results also suggested that systemic (e.g., duration of stay) or clinical service improvements (e.g., staff's language skills, ability to offer substance abuse therapy, provide appropriate referrals or liaise with intensive social work services or plan subacute rehabilitation phase) could be beneficial for acute settings. Stronger recruitment, training and retention initiatives for bilingual and multiethnic professionals may also be considered to optimize gains from acute inpatient rehabilitation following traumatic brain injury.



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Determining Reliability of a Dual-task Functional Mobility Protocol for Individuals with Lower Extremity Amputations

Publication date: Available online 6 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Courtney Frengopoulos, Michael WC. Payne, Jeffrey Holmes, Ricardo Viana, Susan W. Hunter
ObjectivesTo determine the relative and absolute reliability of a dual-task functional mobility assessment.DesignCross-sectional study.SettingAcademic Rehabilitation Hospital.ParticipantsSixty individuals with lower extremity amputation (LEA) attending an outpatient amputee clinic (age= 58.21±12.59; 80.0% male). Subjects were stratified into three groups: 1) transtibial amputations of vascular etiology (TTA-vas), transtibial amputations of non-vascular etiology (TTA-nonvas); transfemoral or bilateral amputees (TFA/bilat) of any etiology.InterventionsN/AMain Outcome MeasuresTime to complete the L Test measured functional mobility under single- and dual-task conditions. Addition of a cognitive task (serial subtractions by 3s) created dual-task conditions. Single task performance on the cognitive task was also reported. Intra-class correlation coefficients (ICC) measured relative reliability; standard error of measurement (SEM) and minimal detectable change with a 95% confidence interval (MDC95) measured absolute reliability. Bland and Altman plots measured agreement between assessments.ResultsRelative reliability results were excellent for all three groups. Values for the dual-task L Test for those with TTA-vas (n=20, age=60.36±7.84, 90.0% male) were ICC=0.98 (95% CI, 0.94-0.99), with SEM=1.36s and MDC95 of 3.76s; for those with TTA-nonvas (n=20, age=55.85±14.08, 85.0% male), were ICC=0.93 (95% CI, 0.80-0.98), SEM=1.34s and MDC95 of 3.71s; and for those with TFA/bilat group (n=20, age=58.21±14.88, 65.0% male) were ICC=0.998 (95% CI, 0.996-0.999), SEM=1.03s and an MDC95 of 2.85s. Bland-Altman plots indicated that assessments did not vary systematically for each group.ConclusionsThis dual-task assessment protocol achieved approved levels of relative reliability values for the three groups tested. This protocol may be used clinically or in research settings to assess the interaction between cognition and functional mobility in the LEA population.



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Issue Information

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Development of stereotaxic recording system for awake marmosets (Callithrix jacchus)

Publication date: Available online 6 January 2018
Source:Neuroscience Research
Author(s): Masahiro Wakabayashi, Daisuke Koketsu, Hideki Kondo, Shigeki Sato, Kiichi Ohara, Zlata Polyakova, Satomi Chiken, Nobuhiko Hatanaka, Atsushi Nambu
The common marmoset has been proposed as a potential alternative to macaque monkey as a primate model for neuroscience and medical research. Here, we have newly developed a stereotaxic neuronal recording system for awake marmosets under the head-fixed condition by modifying that for macaque monkeys. Using this system, we recorded neuronal activity in the cerebral cortex of awake marmosets and successfully identified the primary motor cortex by intracortical microstimulation. Neuronal activities of deep brain structures, such as the basal ganglia, thalamus, and cerebellum, in awake marmosets were also successfully recorded referring to magnetic resonance images. Our system is suitable for functional mapping of the brain, since the large recording chamber allows access to arbitrary regions over almost the entire brain, and the recording electrode can be easily moved stereotaxically from one site to another. In addition, our system is desirable for neuronal recording during task performance to assess motor skills and cognitive function, as the marmoset sits in the marmoset chair and can freely use its hands. Moreover, our system can be used in combination with cutting-edge techniques, such as two-photon imaging and optogenetic manipulation. This recording system will contribute to boosting neuroscience and medical research using marmosets.



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Presynaptic Calcium Channels

Publication date: Available online 6 January 2018
Source:Neuroscience Research
Author(s): Sumiko Mochida
At the presynaptic terminal, neuronal firing activity induces membrane depolarization and subsequent Ca²⁺ entry through voltage-gated Ca²⁺ (CaV) channels triggers neurotransmitter release from the active zone. Presynaptic Ca²⁺ channels form a large signaling complex, which targets synaptic vesicles to Ca²⁺ channels for efficient release and mediates Ca²⁺ channel regulation. The presynaptic CaV2 channel family (comprising CaV2.1, CaV2.2 and CaV2.3 isoforms) encode the pore-forming α1 subunit. The cytoplasmic regions are the target of regulatory proteins for channel modulation. Modulation of presynaptic Ca²⁺ channels has a powerful influence on synaptic transmission. This article overviews spatial and temporal regulation of Ca²⁺ channels by effectors and sensors of Ca²⁺ signaling, and describes the emerging evidence for a critical role of Ca²⁺ channel regulation in control of synaptic transmission and presynaptic plasticity. Sympathetic superior cervical ganglion neurons in culture expressing CaV2.2 channels represent a well-characterized system for investigating synaptic transmission. The exogenously expressed α1 subunit of the CaV2.1 as well as endogenous CaV2.2 was examined for modulation of channel activity, and thereby regulation of synaptic transmission. The constitutive and Ca²⁺-dependent modulation of CaV2.1 channels coordinately act as spatial and temporal molecular switches to control synaptic efficacy.



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Exposure- and flux-based assessment of ozone risk to sugarcane plants

Publication date: March 2018
Source:Atmospheric Environment, Volume 176
Author(s): Bárbara Baêsso Moura, Yasutomo Hoshika, Rafael Vasconcelos Ribeiro, Elena Paoletti
Ozone (O3) is a toxic oxidative air pollutant, with significant detrimental effects on crops. Sugarcane (Saccharum spp.) is an important crop with no O3 risk assessment performed so far. This study aimed to assess O3 risk to sugarcane plants by using exposure-based indices (AOT40 and W126) based on O3 concentrations in the air, and the flux-based index (PODy, where y is a threshold of uptake) that considers leaf O3 uptake and the influence of environmental conditions on stomatal conductance (gsto). Two sugarcane genotypes (IACSP94-2094 and IACSP95-5000) were subjected to a 90-day Free-Air Controlled Experiment (FACE) exposure at three levels of O3 concentrations: ambient (Amb); Amb x1.2; and Amb x1.4. Total above-ground biomass (AGB), stalk biomass (SB) and leaf biomass (LB) were evaluated and the potential biomass production in a clean air was estimated by assuming a theoretical clean atmosphere at 10 ppb as 24 h O3 average. The Jarvis-type multiplicative algorithm was used to parametrize gsto including environmental factors i.e. air temperature, light intensity, air vapor pressure deficit, and minimum night-time temperature. Ozone exposure caused a negative impact on AGB, SB and LB. The O3 sensitivity of sugarcane may be related to its high gsto (∼535 mmol H2O m⁻² s⁻¹). As sugarcane is adapted to hot climate conditions, gsto was restricted when the current minimum air temperature (Tmin) was below ∼14 °C and the minimum night-time air temperature of the previous day (Tnmin) was below ∼7.5 °C. The flux-based index (PODy) performed better than the exposure-based indices in estimating O3 effect on biomass losses. We recommend a y threshold of 2 nmol m⁻² s⁻¹ to incorporate O3 effects on both AGB and SB and 1 nmol m⁻² s⁻¹ on LB. In order not to exceed 4% reduction in the growth of these two sugarcane genotypes, we recommend the following critical levels: 1.09 and 1.04 mmol m⁻² POD2 for AGB, 0.91 and 0.96 mmol m⁻² POD2 for SB, and 3.00 and 2.36 mmol m⁻² POD1 for LB of IACSP95-5000 and IACSP94-2094, respectively.



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iSepsis – The Lactate Myths

Lactate the Myths. Lactate is good for the patient and not bad.

EMCrit Project by Paul Marik.

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The River of Aural Serenity: selected papers from the 2017 Annual Conference of the National Hearing Conservation Association.

Related Articles

The River of Aural Serenity: selected papers from the 2017 Annual Conference of the National Hearing Conservation Association.

Int J Audiol. 2018 Jan 05;:1-2

Authors: Tufts JB, Giguère C

PMID: 29304562 [PubMed - as supplied by publisher]

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Hearing impairment and hearing aid usage in Singapore.

Related Articles

Hearing impairment and hearing aid usage in Singapore.

Int J Audiol. 2018 Jan 05;:1-11

Authors: Ho EC, Zhang H, Ong WMW, Li K, Bei YTE, Medapati SVR, Seneviratna A

Abstract
OBJECTIVE: To examine the epidemiological and audiological profile, pattern of hearing aid (HA) fitting and usage among HA users in Singapore.
DESIGN: Retrospective cross-sectional study.
STUDY SAMPLE: Cohort of 1068 subjects issued with HAs at a tertiary hospital between 2001 and 2013.
RESULTS: Mean age was 70 years with 50.8% male. Mean hearing loss (HL) was 63.1 dB and 69.5% had at least moderate-severe HL. Sensorineural HL was present in 66.4% and 69.8% had symmetrical HL. "Behind-the-Ear" HAs were cheaper than "In-Ear" HAs. Standard "Behind-The-Ear" HAs were also cheaper than "Receiver-in-Canal" HAs. Among In-Ear HAs, "In-the-Canal" and "Completely-in-Canal" were more popular than "In-the-Ear" HAs despite costing more. HA was used ≥4 days/week by 85.6% but >7 h per day by only 35.7%. Only 18% received bilateral first HA fitting. In multivariate analysis, younger age and symmetrical HL were predictors of bilateral HA uptake while better Pure-Tone-Audiometry of aided ear and >7 h of daily HA usage were predictors of successive HA fitting.
CONCLUSIONS: HA users in Singapore were elderly and presented with advanced HL. Bilateral HA adoption and average daily use were low compared to other developed countries. Future research on understanding the suboptimal HA usage should explore patients motivation, hearing disability, and HA effectiveness.

PMID: 29304553 [PubMed - as supplied by publisher]

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The River of Aural Serenity: selected papers from the 2017 Annual Conference of the National Hearing Conservation Association.

Related Articles

The River of Aural Serenity: selected papers from the 2017 Annual Conference of the National Hearing Conservation Association.

Int J Audiol. 2018 Jan 05;:1-2

Authors: Tufts JB, Giguère C

PMID: 29304562 [PubMed - as supplied by publisher]

from #ENT-PubMed via ola Kala on Inoreader http://ift.tt/2m6vwxc

Hearing impairment and hearing aid usage in Singapore.

Related Articles

Hearing impairment and hearing aid usage in Singapore.

Int J Audiol. 2018 Jan 05;:1-11

Authors: Ho EC, Zhang H, Ong WMW, Li K, Bei YTE, Medapati SVR, Seneviratna A

Abstract
OBJECTIVE: To examine the epidemiological and audiological profile, pattern of hearing aid (HA) fitting and usage among HA users in Singapore.
DESIGN: Retrospective cross-sectional study.
STUDY SAMPLE: Cohort of 1068 subjects issued with HAs at a tertiary hospital between 2001 and 2013.
RESULTS: Mean age was 70 years with 50.8% male. Mean hearing loss (HL) was 63.1 dB and 69.5% had at least moderate-severe HL. Sensorineural HL was present in 66.4% and 69.8% had symmetrical HL. "Behind-the-Ear" HAs were cheaper than "In-Ear" HAs. Standard "Behind-The-Ear" HAs were also cheaper than "Receiver-in-Canal" HAs. Among In-Ear HAs, "In-the-Canal" and "Completely-in-Canal" were more popular than "In-the-Ear" HAs despite costing more. HA was used ≥4 days/week by 85.6% but >7 h per day by only 35.7%. Only 18% received bilateral first HA fitting. In multivariate analysis, younger age and symmetrical HL were predictors of bilateral HA uptake while better Pure-Tone-Audiometry of aided ear and >7 h of daily HA usage were predictors of successive HA fitting.
CONCLUSIONS: HA users in Singapore were elderly and presented with advanced HL. Bilateral HA adoption and average daily use were low compared to other developed countries. Future research on understanding the suboptimal HA usage should explore patients motivation, hearing disability, and HA effectiveness.

PMID: 29304553 [PubMed - as supplied by publisher]

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The River of Aural Serenity: selected papers from the 2017 Annual Conference of the National Hearing Conservation Association.

Related Articles

The River of Aural Serenity: selected papers from the 2017 Annual Conference of the National Hearing Conservation Association.

Int J Audiol. 2018 Jan 05;:1-2

Authors: Tufts JB, Giguère C

PMID: 29304562 [PubMed - as supplied by publisher]

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2m6vwxc

Hearing impairment and hearing aid usage in Singapore.

Related Articles

Hearing impairment and hearing aid usage in Singapore.

Int J Audiol. 2018 Jan 05;:1-11

Authors: Ho EC, Zhang H, Ong WMW, Li K, Bei YTE, Medapati SVR, Seneviratna A

Abstract
OBJECTIVE: To examine the epidemiological and audiological profile, pattern of hearing aid (HA) fitting and usage among HA users in Singapore.
DESIGN: Retrospective cross-sectional study.
STUDY SAMPLE: Cohort of 1068 subjects issued with HAs at a tertiary hospital between 2001 and 2013.
RESULTS: Mean age was 70 years with 50.8% male. Mean hearing loss (HL) was 63.1 dB and 69.5% had at least moderate-severe HL. Sensorineural HL was present in 66.4% and 69.8% had symmetrical HL. "Behind-the-Ear" HAs were cheaper than "In-Ear" HAs. Standard "Behind-The-Ear" HAs were also cheaper than "Receiver-in-Canal" HAs. Among In-Ear HAs, "In-the-Canal" and "Completely-in-Canal" were more popular than "In-the-Ear" HAs despite costing more. HA was used ≥4 days/week by 85.6% but >7 h per day by only 35.7%. Only 18% received bilateral first HA fitting. In multivariate analysis, younger age and symmetrical HL were predictors of bilateral HA uptake while better Pure-Tone-Audiometry of aided ear and >7 h of daily HA usage were predictors of successive HA fitting.
CONCLUSIONS: HA users in Singapore were elderly and presented with advanced HL. Bilateral HA adoption and average daily use were low compared to other developed countries. Future research on understanding the suboptimal HA usage should explore patients motivation, hearing disability, and HA effectiveness.

PMID: 29304553 [PubMed - as supplied by publisher]

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Vestibulo-cochlear function in inflammatory neuropathies.

Related Articles

Vestibulo-cochlear function in inflammatory neuropathies.

Clin Neurophysiol. 2017 Dec 20;:

Authors: Blanquet M, Petersen JA, Palla A, Veraguth D, Weber KP, Straumann D, Tarnutzer AA, Jung HH

Abstract
OBJECTIVE: We aimed to quantify peripheral-vestibular deficits that may contribute to imbalanced stance/gait in patients with inflammatory neuropathies.
METHODS: Twenty-one patients (58 ± 15 y [mean age ± 1SD]; chronic-inflammatory-demyelinating-polyneuropathy = 10, Guillain-Barré Syndrome = 5, Anti-MAG peripheral neuropathy = 2, multifocal-motor-neuropathy = 4) were compared with 26 healthy controls. All subjects received video-head-impulse testing (vHIT), caloric irrigation and cervical/ocular vestibular-evoked myogenic-potentials (VEMPs). The Yardley vertigo-symptom-scale (VSS) was used to rate vertigo/dizziness. Postural stability was assessed using the functional gait-assessment (FGA). Pure-tone audiograms (n = 18), otoacoustic emissions (n = 12) and auditory brainstem responses were obtained (n = 12).
RESULTS: Semicircular-canal hypofunction was noted in 9/21 (43%) patients (vHIT = 6; caloric irrigation = 5), whereas otolith function was impaired in 12/21 (57%) (oVEMPs = 8; cVEMPs = 5), resulting in vestibular impairment of at least one sensor in 13/21 (62%). On average, 2.4 ± 1.1 vestibular end organs (each side: anterior/posterior/horizontal canal, utriculus, sacculus; total = 10) were affected. The VSS-scores were higher in patients (16.8 ± 8.6 vs. 9.5 ± 6.2, p = 0.002) but did not correlate with the number of affected organs. Auditory neuropathy was found in 1/12 (8%) patients.
CONCLUSION: Impairment of one or more vestibular end organs was frequent, but usually mild, possibly contributing to imbalance of stance/gait in inflammatory neuropathies.
SIGNIFICANCE: While our data does not support routine vestibular testing in inflammatory neuropathies, this may be considered in selected cases.

PMID: 29305208 [PubMed - as supplied by publisher]

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The River of Aural Serenity: selected papers from the 2017 Annual Conference of the National Hearing Conservation Association.

Related Articles

The River of Aural Serenity: selected papers from the 2017 Annual Conference of the National Hearing Conservation Association.

Int J Audiol. 2018 Jan 05;:1-2

Authors: Tufts JB, Giguère C

PMID: 29304562 [PubMed - as supplied by publisher]

from #ENT-PubMed via ola Kala on Inoreader http://ift.tt/2m6vwxc

Hearing impairment and hearing aid usage in Singapore.

Related Articles

Hearing impairment and hearing aid usage in Singapore.

Int J Audiol. 2018 Jan 05;:1-11

Authors: Ho EC, Zhang H, Ong WMW, Li K, Bei YTE, Medapati SVR, Seneviratna A

Abstract
OBJECTIVE: To examine the epidemiological and audiological profile, pattern of hearing aid (HA) fitting and usage among HA users in Singapore.
DESIGN: Retrospective cross-sectional study.
STUDY SAMPLE: Cohort of 1068 subjects issued with HAs at a tertiary hospital between 2001 and 2013.
RESULTS: Mean age was 70 years with 50.8% male. Mean hearing loss (HL) was 63.1 dB and 69.5% had at least moderate-severe HL. Sensorineural HL was present in 66.4% and 69.8% had symmetrical HL. "Behind-the-Ear" HAs were cheaper than "In-Ear" HAs. Standard "Behind-The-Ear" HAs were also cheaper than "Receiver-in-Canal" HAs. Among In-Ear HAs, "In-the-Canal" and "Completely-in-Canal" were more popular than "In-the-Ear" HAs despite costing more. HA was used ≥4 days/week by 85.6% but >7 h per day by only 35.7%. Only 18% received bilateral first HA fitting. In multivariate analysis, younger age and symmetrical HL were predictors of bilateral HA uptake while better Pure-Tone-Audiometry of aided ear and >7 h of daily HA usage were predictors of successive HA fitting.
CONCLUSIONS: HA users in Singapore were elderly and presented with advanced HL. Bilateral HA adoption and average daily use were low compared to other developed countries. Future research on understanding the suboptimal HA usage should explore patients motivation, hearing disability, and HA effectiveness.

PMID: 29304553 [PubMed - as supplied by publisher]

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Transauricular vagus nerve stimulation at auricular acupoints Kindey (CO10), Yidan (CO11), Liver (CO12) and Shenmen (TF4) can induce auditory and limbic cortices activation measured by fMRI.

Transauricular vagus nerve stimulation at auricular acupoints Kindey (CO10), Yidan (CO11), Liver (CO12) and Shenmen (TF4) can induce auditory and limbic cortices activation measured by fMRI.

Hear Res. 2017 Dec 24;:

Authors: Peng L, Mu K, Liu A, Zhou L, Gao Y, Shenoy IT, Mei Z, Chen Q

Abstract
The purpose of this study was to explore the central mechanism of transauricular vagus nerve stimulation (taVNS) to human by fMRI and to find a suitable taVNS site for potential tinnitus treatment. 24 healthy subjects aged between 28 and 38 years were enrolled in the experiment. 8 subjects were stimulated in the auricular acupoints Kindey (CO10), Yidan (CO11), Liver (CO12) and Shenmen (TF4) in the left ear, 8 subjects were stimulated at the anterior wall of the auditory canal and left lower limb as an anterior stimulation group; 8 persons who were arranged in a sham group received taVNS at the left ear lobe and tail of the helix. Functional magnetic resonance imaging (fMRI) data from the cortices was collected and an Alphasim analysis was performed. We found that taVNS at auricular acupoints CO10-12, TF4 can instantly and effectively generate blood oxygenation level dependent (BOLD) signal changes in the prefrontal, auditory and limbic cortices of healthy subjects by fMRI. When comparing the acupoints group and the sham group in the left brain, the signals from the prefrontal cortex, the auditory ascending pathway including superior temporal gyrus, middle temporal gyrus, thalamus and limbic system regions such as putamen, caudate, posterior cingulate cortex, amygdala and parahippocampal gyrus were increased under our stimulation. The difference of the BOLD signal in the left brain between acupoints group and anterior group was in the superior temporal gyrus. We could also find signal differences in several regions of right brain among the groups. In conclusion, taVNS at acupoints CO10-12, TF4 could activate the prefrontal, auditory and limbic cortices of healthy brain and this scheme could be a promising tool for tinnitus treatment.

PMID: 29305037 [PubMed - as supplied by publisher]

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Persistent postural-perceptual dizziness: a useful new syndrome.

Persistent postural-perceptual dizziness: a useful new syndrome.

Pract Neurol. 2018 Jan 04;:

Authors: Seemungal BM, Passamonti L

PMID: 29305493 [PubMed - as supplied by publisher]

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Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib.

Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib.

Acta Neuropathol. 2018 Jan 05;:

Authors: Verginelli F, Perconti S, Vespa S, Schiavi F, Prasat SC, Lanuti P, Cama A, Tramontana L, Esposito DL, Guarnieri S, Sheu A, Pantalone MR, Florio R, Morgano A, Rossi C, Bologna G, Marchisio M, D'Argenio A, Taschin E, Visone R, Opocher G, Veronese A, Paties CT, Rajasekhar VK, Söderberg-Nauclér C, Sanna M, Lotti LV, Mariani-Costantini R

Abstract
Tumours can be viewed as aberrant tissues or organs sustained by tumorigenic stem-like cells that engage into dysregulated histo/organogenetic processes. Paragangliomas, prototypical organoid tumours constituted by dysmorphic variants of the vascular and neural tissues found in normal paraganglia, provide a model to test this hypothesis. To understand the origin of paragangliomas, we built a biobank comprising 77 cases, 18 primary cultures, 4 derived cell lines, 80 patient-derived xenografts and 11 cell-derived xenografts. We comparatively investigated these unique complementary materials using morphofunctional, ultrastructural and flow cytometric assays accompanied by microRNA studies. We found that paragangliomas contain stem-like cells with hybrid mesenchymal/vasculoneural phenotype, stabilized and expanded in the derived cultures. The viability and growth of such cultures depended on the downregulation of the miR-200 and miR-34 families, which allowed high PDGFRA and ZEB1 protein expression levels. Both tumour tissue- and cell culture-derived xenografts recapitulated the vasculoneural paraganglioma structure and arose from mesenchymal-like cells through a fixed developmental sequence. First, vasculoangiogenesis organized the microenvironment, building a perivascular niche which in turn supported neurogenesis. Neuroepithelial differentiation was associated with severe mitochondrial dysfunction, not present in cultured paraganglioma cells, but acquired in vivo during xenograft formation. Vasculogenesis was the Achilles' heel of xenograft development. In fact, imatinib, that targets endothelial-mural signalling, blocked paraganglioma xenograft formation (11 xenografts from 12 cell transplants in the control group versus 2 out of 10 in the treated group, P = 0.0015). Overall our key results were unaffected by the SDHx gene carrier status of the patient, characterized for 70 out of 77 cases. In conclusion, we explain the biphasic vasculoneural structure of paragangliomas and identify an early and pharmacologically actionable phase of paraganglioma organization.

PMID: 29305721 [PubMed - as supplied by publisher]

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Endoscope holders in Cranial Neurosurgery: Part 2 - An international survey.

Endoscope holders in Cranial Neurosurgery: Part 2 - An international survey.

World Neurosurg. 2018 Jan 02;:

Authors: Paraskevopoulos D, Constantini S, Bal J, Roth J

Abstract
BACKGROUND: Following a prior systematic review of currently available endoscope holders (EH), we aspired to detect trends, task-specific preferences and pitfalls of EH in various cranial neuroendoscopic procedures.
METHODS: A questionnaire was disseminated to members of the International Federation of Neuroendoscopy (IFNE). The questionnaire evaluated indications and pitfalls of EH in different applications, in particular, differentiating between intraventricular and skull base endoscopy, as well as sub-categories of these two main fields. Furthermore, interest or involvement in research projects on EH was investigated.
RESULTS: Fifty two surgeons responded, with a broad geographic distribution. Most (54%) do not routinely use EH. Others utilize holders mainly for intraventricular rather than skull base procedures. Most surgeons (96%) regularly work with a co-surgeon. Reported weaknesses of EH included crude movements, downward drift, loss of depth perception, lack of flexibility, iatrogenic injury, cost and bulky construct. There is still a lack of consensus on surgical indications. Tumor resections in intraventricular and skull base regions (not small sellar tumors) seem to stand out as good, widely accepted indications.
CONCLUSION: Although EH have a role in cranial neuroendoscopy, their use seems limited and their technical features are regarded as suboptimal by most neuroendoscopists. Weaknesses and implications were detected in all application categories (skull base and intraventricular), but may vary slightly. Potentially, separate systems with distinct features may be required for skull base versus intraventricular surgery. There is a need for further evolution of EH, which could lead to a future paradigm shift in their use.

PMID: 29305118 [PubMed - as supplied by publisher]

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Cranial Tumor Surgical Outcomes at a High-Volume Academic Referral Center.

Cranial Tumor Surgical Outcomes at a High-Volume Academic Referral Center.

Mayo Clin Proc. 2018 Jan;93(1):16-24

Authors: Brown DA, Himes BT, Major BT, Mundell BF, Kumar R, Kall B, Meyer FB, Link MJ, Pollock BE, Atkinson JD, Van Gompel JJ, Marsh WR, Lanzino G, Bydon M, Parney IF

Abstract
OBJECTIVE: To determine adverse event rates for adult cranial neuro-oncologic surgeries performed at a high-volume quaternary academic center and assess the impact of resident participation on perioperative complication rates.
PATIENTS AND METHODS: All adult patients undergoing neurosurgical intervention for an intracranial neoplastic lesion between January 1, 2009, and December 31, 2013, were included. Cases were categorized as biopsy, extra-axial/skull base, intra-axial, or transsphenoidal. Complications were categorized as neurologic, medical, wound, mortality, or none and compared for patients managed by a chief resident vs a consultant neurosurgeon.
RESULTS: A total of 6277 neurosurgical procedures for intracranial neoplasms were performed. After excluding radiosurgical procedures and pediatric patients, 4151 adult patients who underwent 4423 procedures were available for analysis. Complications were infrequent, with overall rates of 9.8% (435 of 4423 procedures), 1.7% (73 of 4423), and 1.4% (63 of 4423) for neurologic, medical, and wound complications, respectively. The rate of perioperative mortality was 0.3% (14 of 4423 procedures). Case performance and management by a chief resident did not negatively impact outcome.
CONCLUSION: In our large-volume brain tumor practice, rates of complications were low, and management of cases by chief residents in a semiautonomous manner did not negatively impact surgical outcomes.

PMID: 29304919 [PubMed - in process]

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Effect of transcranial direct current stimulation on short-term and long-term treatment of chronic tinnitus

Publication date: Available online 6 January 2018
Source:American Journal of Otolaryngology
Author(s): Hamidreza Abtahi, Ahmadreza Okhovvat, Somaiie Heidari, Azar Gharagazarloo, Motahare Mirdamadi, Mohammad Hossein Nilforoush, Hossein Ghazavi
ObjectiveThis study was conducted to investigate the effectiveness of anodal and cathodal methods in reducing the intensity of tinnitus and to compare them with the control.MethodologyThis randomized double-blind clinical trial with case and control groups was conducted in Al-Zahra Hospital in Isfahan between 2015 and 2016. In this trial, 51 patients with tinnitus, for at least one year, were selected among those outpatients visiting the throat, nose and ear clinic within this period. Inclusion criteria were patients on electrical stimulation prohibition, with Ménière's disease, otosclerosis, chronic headache, and pulsatile tinnitus. Patients were randomly divided in three equal-sized groups: anodal stimulation group, cathodal stimulation group, and control group. The subjects received 20-min current stimulation (2 mA). Five subjects were selected from those with a significant difference between the stimulated states (anodal or cathodal) and/or control. They received weekly transcranial electrical stimulation for two months, and their long-term recovery from tinnitus was investigated. Data analysis was done with SPSS20.ResultsFindings showed no significant between-groups difference in mean scores of tinnitus before the intervention (p = .68); whereas, this difference was significant immediately after the intervention (p = .02) and 1 h after it (p = .03). The mean score of tinnitus in the anodal stimulation group was significantly lower than the control; whereas, no significant difference was observed between the anodal and cathodal stimulation groups, and between the cathodal and control groups (p < .05). Findings also showed that the mean scores of tinnitus in two cathodal stimulation groups (p = .24) and control group (p = .62) were not significantly different at three different points of time; whereas, this score was significantly different in the anodal group at these time points (p = .01).ConclusionIn conclusion, anodal stimulation was more effective than the cathodal and control stimulation in reducing the intensity of tinnitus in the short term.



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