Αρχειοθήκη ιστολογίου

Τρίτη 29 Αυγούστου 2017

Coblation Versus Conventional Tonsillectomy: A Double Blind Randomized Controlled Trial

Abstract

Post tonsillectomy bleeding and pain are two main problems following traditional tonsillectomy. Coblation therapy (controlled ablation) was first used in tonsillectomy in 2001. A great amount of literature debated around its use with controversial opinions regarding its benefits, efficacy, and cost. This is a prospective double-blind randomized controlled study that compares between coblation tonsillectomy and conventional tonsillectomy as regard operative time, operative blood loss, time needed to return back to the normal activity and diet, and incidence of postoperative hemorrhage whether primary or secondary. The study included 1004 patients with mean age of 10.4 years (range from 4 to 35 years). The first group (coblation tonsillectomy group) included 507 patients, age ranging from 4 to 35 years with mean age 15.1 year. This group included 277 female (54.6%) and 230 male (45.4%). The second group (conventional tonsillectomy group) included 497 patients, age ranging from 4 to 24 years and mean age 14.7 years. This group included 274 female (55.1%) and 223 male (44.9%). Coblation tonsillectomy offers significant advantages over dissection method with less operative time, decreased intraoperative blood loss, early restoration of daily activities and normal diet. However coblation tonsillectomy is associated with a higher incidence of secondary hemorrhage.



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Computer-assisted stereology and automated image analysis for quantification of tumor infiltrating lymphocytes in colon cancer

Precise prognostic and predictive variables allowing improved post-operative treatment stratification are missing in patients treated for stage II colon cancer (CC). Investigation of tumor infiltrating lymphoc...

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How Short is Short, and Why? A Probable Case of Proportionate Dwarfism from Egypt's 3rd Intermediate Period in the Dakhleh Oasis, Egypt

Abstract

This study describes a probable proportionate dwarf from a Third Intermediate Period cemetery at Ain Tirghi in the Dakhleh Oasis, Egypt. The skeleton (Burial 22 or B22) is an adult female estimated to be in her mid to late thirties. Most medical literature defines an adult stature of 2 standard deviations below the population mean as an indicator for clinically short stature, with some bioarchaeologists and clinicians identifying severe short stature at 3 standard deviations below the population mean. B22 satisfies either criteria when compared with the Ain Tirghi adult female population mean for measurements of the radii and femora, as well as the summed measurements of the femora and tibiae. Her limb proportions were normal and this, with a lack of morphological abnormalities, eliminated several possible causes of small stature (e.g. achondroplasia). The differential diagnosis for an individual with short stature and normal proportions indicates that she represents a probable case of pituitary dwarfism, or hypopituitarism. B22 was buried in the same fashion as adjacent burials in a family group burial and showed no differential indication of physiological stress or illness. Contextualized with the Egyptological and archaeological evidence of dwarfism in Egypt, this case study considers the social perceptions of dwarfism in ancient Egypt and suggests that pituitary dwarfs, like disproportionate dwarfs, likely led normal, if not privileged lives. Therefore, according to the social theory of disability, B22 was not necessarily disabled despite her impairment.



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Erratum to: The Future of Periodontal-Systemic Associations: Raising the Standards



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Mucosal Perfusion Preservation by a Novel Shapeable Tissue Expander for Oral Reconstruction.

Background: There are few methods for expanding oral mucosa, and these often cause complications such as tissue necrosis and expander eruption. This study examines mucosal blood perfusion following insertion of a novel shapeable hydrogel tissue expander (HTE). The canine model used subgingival insertion of HTE following tooth extraction and alveolar bone reduction. The primary goal of this study was to gain understanding of epithelial perfusion and reparative responses of gingival mucosa during HTE expansion. Methods: Nine Beagle dogs underwent bilateral premolar maxillary and mandibular tooth extraction. Three to four months later, HTE-contoured inserts were implanted submucosally under the buccal surface of the alveolar ridge. After removal and following a 6- to 7-month period of healing, new HTE implants were inserted at the same sites. The area was assessed weekly for tissue perfusion and volume of expansion. Biopsies for histological analysis were performed at the time of expander removal. Results: Within 2 weeks following the second insertion, blood flow returned to baseline (defined as the values of perfusion measurements at the presurgery assessment) and remained normal until hydrogel full expansion and removal. Volume expansion analysis revealed that the hydrogel doubled in volume. Histological assessment showed no macrophage or inflammatory infiltration of the mucosa. No superficial fibrosis, decreased vascularity, or mucosal change was seen. Conclusion: Maintenance of adequate tissue perfusion is a clinically important aspect of tissue expander performance to reduce risk of device loss or injury to the patient, particularly for areas with a history of previous surgeries. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Double-Pedicled Free Deep Inferior Epigastric Perforator Flap for the Coverage of Thigh Soft-Tissue Defect.

Summary: Soft-tissue defects caused by radiation injury are a challenging task for the reconstructive surgeon, due to the extent of the soft-tissue damage and the associated injuries of the local blood vessels and bone tissue. We present the application of the versatile deep inferior epigastric perforator (DIEP) flap for the coverage of an extended lateral thigh soft-tissue defect after the surgical resection of an undifferentiated pleomorphic high-grade sarcoma, neoadjuvant chemotherapy, and adjuvant chemo- and radiotherapy. A double-pedicled free DIEP flap (756 cm2) was harvested and anastomosed to the transverse branch of the lateral femoral circumflex artery and a lateral branch of the popliteal artery (P1). The flap survived completely without serious complications, and the patient was able to walk with crutches 3 months postoperatively. This is the first case report of a free bipedicled DIEP flap for the coverage of a thigh defect in a male patient. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Authors' Reply: "Organ Transplantation in Australia: Inequities in Access and Outcome for Indigenous Australians".

No abstract available

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Organ Transplantation in Australia: Inequities in Access and Outcome for Indigenous Australians.

No abstract available

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Lung Retransplantation: Practical and Ethical Considerations Raised by the Hannover Protocol.

No abstract available

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Midterm Outcomes of 12 Renal Transplant Recipients Treated With Eculizumab to Prevent Atypical Hemolytic Syndrome Recurrence.

Background: Atypical hemolytic uremic syndrome (aHUS) is an orphan disease with a high rate of recurrence after kidney transplantation. However, reports of successful prevention of posttransplant aHUS recurrence with eculizumab emerged a few years ago. To further delineate its optimal use, we describe the largest series of kidney transplant recipients treated with prophylactic eculizumab. Methods: Twelve renal transplant recipients with aHUS-related end stage renal disease received eculizumab: 10 from day 0 and 2 at the time of recurrence (days 6 and 25). Clinical and histological features, complement assessment and free eculizumab measurements were analyzed. The median follow-up was 24.6 months. Results: 5 patients had failed at least 1 previous renal transplant from aHUS. A genetic mutation was identified in 9 patients, anti-H antibodies were found in 2. No patient demonstrated biological recurrence of thrombotic microangiopathy (TMA) under treatment. Three antibody-mediated rejections (ABMRs) occurred without detectable C5 residual activity. ABMR was associated with subclinical TMA in 2 patients. One patient lost his graft after several complications, including ABMR. One patient experienced post-transplant C3 glomerulonephritis. The last median serum creatinine was 128.2 +/- 40.8 [mu]mol/l. Conclusions: These data confirm that eculizumab is highly effective in preventing posttransplantation aHUS recurrence, yet may not fully block ABMR pathogenesis. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Effect of personality traits on adherence with positive airway pressure therapy in obstructive sleep apnea patients

Abstract

Purpose

Patient adherence with positive airway pressure (PAP) therapy is a significant clinical problem in obstructive sleep apnea treatment. Personality traits may be a factor for non-adherence. The aim of this study is to investigate the relationship between PAP therapy adherence and patient personality traits.

Methods

Patients were screened and recruited during their visit to a sleep clinic. Baseline data were collected from each patient's electronic chart. Behavioral inhibition system/behavioral activation system (BIS/BAS) scales, short measure of five-factor model personality traits (mini-IPIP), positive and negative affect score (PANAS), and appetitive motivation scores (AMS) tests were used to measure personality traits. Data from the PAP device were obtained following a minimum of an initial 30 days, with adherence defined as >4 h/night on 70% of nights. Univariate and multivariate logistic regression and Pearson correlation tests were used to analyze the data.

Results

A total of 400 patients were recruited. Three hundred twenty-one patients had all the data and were included in the study. Behavioral activation system–fun seeking (BAS-FS) and, to a certain extent, negative affect were significantly associated with adherence. Intellect/imagination was marginally significant. Additionally, older age (>65 years), profession, PAP type, side effects, efficiency, apnea–hypopnea index (AHI), and residual AHI showed significant associations with patient adherence with PAP therapy. Multivariate analysis revealed that BAS-FS was still a significant predictor of adherence even after adjusting for other covariates.

Conclusion

BAS-FS, negative affect, and intellect/imagination are significant factors for adherence to PAP therapy in obstructive sleep apnea patients.



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Effect of personality traits on adherence with positive airway pressure therapy in obstructive sleep apnea patients

Abstract

Purpose

Patient adherence with positive airway pressure (PAP) therapy is a significant clinical problem in obstructive sleep apnea treatment. Personality traits may be a factor for non-adherence. The aim of this study is to investigate the relationship between PAP therapy adherence and patient personality traits.

Methods

Patients were screened and recruited during their visit to a sleep clinic. Baseline data were collected from each patient's electronic chart. Behavioral inhibition system/behavioral activation system (BIS/BAS) scales, short measure of five-factor model personality traits (mini-IPIP), positive and negative affect score (PANAS), and appetitive motivation scores (AMS) tests were used to measure personality traits. Data from the PAP device were obtained following a minimum of an initial 30 days, with adherence defined as >4 h/night on 70% of nights. Univariate and multivariate logistic regression and Pearson correlation tests were used to analyze the data.

Results

A total of 400 patients were recruited. Three hundred twenty-one patients had all the data and were included in the study. Behavioral activation system–fun seeking (BAS-FS) and, to a certain extent, negative affect were significantly associated with adherence. Intellect/imagination was marginally significant. Additionally, older age (>65 years), profession, PAP type, side effects, efficiency, apnea–hypopnea index (AHI), and residual AHI showed significant associations with patient adherence with PAP therapy. Multivariate analysis revealed that BAS-FS was still a significant predictor of adherence even after adjusting for other covariates.

Conclusion

BAS-FS, negative affect, and intellect/imagination are significant factors for adherence to PAP therapy in obstructive sleep apnea patients.



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Surface EMG signals in very late-stage of Duchenne muscular dystrophy: a case study

Robotic arm supports aim at improving the quality of life for adults with Duchenne muscular dystrophy (DMD) by augmenting their residual functional abilities. A critical component of robotic arm supports is th...

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Dopaminergic dysfunction in neurodevelopmental disorders: recent advances and synergistic technologies to aid basic research

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): J Elliott Robinson, Viviana Gradinaru
Neurodevelopmental disorders (NDDs) represent a diverse group of syndromes characterized by abnormal development of the central nervous system and whose symptomatology includes cognitive, emotional, sensory, and motor impairments. The identification of causative genetic defects has allowed for creation of transgenic NDD mouse models that have revealed pathophysiological mechanisms of disease phenotypes in a neural circuit- and cell type-specific manner. Mouse models of several syndromes, including Rett syndrome, Fragile X syndrome, Angelman syndrome, Neurofibromatosis type 1, etc., exhibit abnormalities in the structure and function of dopaminergic circuitry, which regulates motivation, motor behavior, sociability, attention, and executive function. Recent advances in technologies for functional circuit mapping, including tissue clearing, viral vector-based tracing methods, and optical readouts of neural activity, have refined our knowledge of dopaminergic circuits in unperturbed states, yet these tools have not been widely applied to NDD research. Here, we will review recent findings exploring dopaminergic function in NDD models and discuss the promise of new tools to probe NDD pathophysiology in these circuits.

Graphical abstract

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Chromatin-remodeling enzymes in control of Schwann cell development, maintenance and plasticity

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Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47
Author(s): Claire Jacob
Gene regulation is essential for cellular differentiation and plasticity. Schwann cells (SCs), the myelinating glia of the peripheral nervous system (PNS), develop from neural crest cells to mature myelinating SCs and can at early developmental stage differentiate into various cell types. After a PNS lesion, SCs can also convert into repair cells that guide and stimulate axonal regrowth, and remyelinate regenerated axons. What controls their development and versatile nature? Several recent studies highlight the key roles of chromatin modifiers in these processes, allowing SCs to regulate their gene expression profile and thereby acquire or change their identity and quickly react to their environment.



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Mechanisms of Müller glial cell morphogenesis

Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47
Author(s): Ryan B MacDonald, Mark Charlton-Perkins, William A Harris
Müller Glia (MG), the radial glia cells of the retina, have spectacular morphologies subserving their enormous functional complexity. As early as 1892, the great neuroanatomist Santiago Ramon y Cajal studied the morphological development of MG, defining several steps in their morphogenesis [1,2]. However, the molecular cues controlling these developmental steps remain poorly understood. As MG have roles to play in every cellular and plexiform layer, this review discusses our current understanding on how MG morphology may be linked to their function, including the developmental mechanisms involved in MG patterning and morphogenesis. Uncovering the mechanisms governing glial morphogenesis, using transcriptomics and imaging, may provide shed new light on the pathophysiology and treatment of human neurological disorders.

Graphical abstract

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Quantifying behavior to solve sensorimotor transformations: advances from worms and flies

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Publication date: October 2017
Source:Current Opinion in Neurobiology, Volume 46
Author(s): Adam J Calhoun, Mala Murthy
The development of new computational tools has recently opened up the study of natural behaviors at a precision that was previously unachievable. These tools permit a highly quantitative analysis of behavioral dynamics at timescales that are well matched to the timescales of neural activity. Here we examine how combining these methods with established techniques for estimating an animal's sensory experience presents exciting new opportunities for dissecting the sensorimotor transformations performed by the nervous system. We focus this review primarily on examples from Caenorhabditis elegans and Drosophila melanogaster—for these model systems, computational approaches to characterize behavior, in combination with unparalleled genetic tools for neural activation, silencing, and recording, have already proven instrumental for illuminating underlying neural mechanisms.



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From the statistics of connectivity to the statistics of spike times in neuronal networks

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Publication date: October 2017
Source:Current Opinion in Neurobiology, Volume 46
Author(s): Gabriel Koch Ocker, Yu Hu, Michael A Buice, Brent Doiron, Krešimir Josić, Robert Rosenbaum, Eric Shea-Brown
An essential step toward understanding neural circuits is linking their structure and their dynamics. In general, this relationship can be almost arbitrarily complex. Recent theoretical work has, however, begun to identify some broad principles underlying collective spiking activity in neural circuits. The first is that local features of network connectivity can be surprisingly effective in predicting global statistics of activity across a network. The second is that, for the important case of large networks with excitatory-inhibitory balance, correlated spiking persists or vanishes depending on the spatial scales of recurrent and feedforward connectivity. We close by showing how these ideas, together with plasticity rules, can help to close the loop between network structure and activity statistics.



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Detection of the Cyanotoxins L-BMAA Uptake and Accumulation in Primary Neurons and Astrocytes

Abstract

We show for the first time that a newly developed polyclonal antibody (pAb) can specifically target the cyanotoxin β-methylamino-L-alanine (BMAA) and can be used to enable direct visualization of BMAA entry and accumulation in primary brain cells. We used this pAb to investigate the effect of acute and chronic accumulation, and toxicity of both BMAA and its natural isomer 2,4-diaminobutyric acid (DAB), separately or in combination, on primary cultures of rat neurons. We further present evidence that co-treatment with BMAA and DAB increased neuronal death, as measured by MAP2 fluorescence level, and appeared to reduce BMAA accumulation. DAB is likely to be acting synergistically with BMAA resulting in higher level of cellular toxicity. We also found that glial cells such as microglia and astrocytes are also able to directly uptake BMAA indicating that additional brain cell types are affected by BMAA-induced toxicity. Therefore, BMAA clearly acts at multiple cellular levels to possibly increase the risk of developing neurodegenerative diseases, including neuro- and gliotoxicity and synergetic exacerbation with other cyanotoxins.



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The use of ofatumumab in the treatment of B-cell malignancies

Future Oncology, Ahead of Print.


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Erratum to: The Future of Periodontal-Systemic Associations: Raising the Standards



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The use of ofatumumab in the treatment of B-cell malignancies

Future Oncology, Ahead of Print.


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MET-GRB2 Signaling-Associated Complexes Correlate with Oncogenic MET Signaling and Sensitivity to MET Kinase Inhibitors

Purpose: Targeting MET in cancer is hampered by lack of diagnostics that accurately reflect high MET signaling and dependence. We hypothesized that assays reflecting MET signaling associated protein complexes could redefine tumors dependent on MET and could add additional precision beyond genomic assessments. Experimental Design: We utilized biochemical approaches, cellular viability studies and proximity ligation assays to assess MET dependence. We examined MET signaling complexes in lung cancer patient specimens (N=406) and patient-derived xenograft models of solid tumors (N=308). We evaluated response to crizotinib in a MET-amplified cohort of patient-derived xenografts models of lung cancer (N=6) and provide a case report of a lung cancer patient harboring a exon14 MET splice variant. Results: We found the interaction of MET with the adaptor protein GRB2 is necessary for oncogenic survival signaling by MET. MET:GRB2 complexes were identified only within MET¬¬-amplified patient-derived xenograft (PDX) models and patient specimens but exhibit substantial variability. Lack of MET:GRB2 complexes was associated with lack of response to MET TKI in cell lines and PDX models. Presence of MET:GRB2 complexes can further sub type tumors with exon14 MET splice variants. Presence of these complexes correlated with response to crizotinib in one patient with exon14 MET lacking MET gene amplification. Conclusions: Proximity assays measuring MET:GRB2 signaling complexes provide novel insights into MET-mediated signaling and could complement current clinical genomics-based assay platforms.



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A panel of novel detection and prognostic methylated DNA markers in primary non-small cell lung cancer and serum DNA

Purpose: To establish a novel panel of cancer-specific methylated genes for cancer detection and prognostic stratification of early stage non-small cell lung cancer (NSCLC). Experimental Design: Identification of differentially methylated regions (DMRs) was performed with bumphunter on "The Cancer Genome Atlas (TCGA)" dataset, and clinical utility was assessed using quantitative methylation-specific PCR assay in multiple sets of primary NSCLC and body fluids that included serum, pleural effusion, and ascites samples. Results: A methylation panel of 6 genes (CDO1, HOXA9, AJAP1, PTGDR, UNCX, and MARCH11) was selected from TCGA dataset. Promoter methylation of the gene panel was detected in 92.2% (83/90) of the training cohort with a specificity of 72.0% (18/25) and in 93.0% (40/43) of an independent cohort of stage IA primary NSCLC. In serum samples from the later 43 stage IA subjects and population-matched 42 control subjects, the gene panel yielded a sensitivity of 72.1% (31/41) and specificity of 71.4% (30/42). Similar diagnostic accuracy was observed in pleural effusion and ascites samples. A prognostic risk category based on the methylation status of CDO1, HOXA9, PTGDR, and AJAP1 refined the risk stratification for outcomes as an independent prognostic factor for an early stage disease. Moreover, the paralogue group for HOXA9, predominantly overexpressed in subjects with HOXA9 methylation, showed poor outcomes. Conclusion: Promoter methylation of a panel of 6 genes has potential for use as a biomarker for early cancer detection and to predict prognosis at the time of diagnosis.



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Prognostic role of Epidermal growth factor receptor variant III (EGFRvIII) positivity in EGFR-amplified primary and recurrent glioblastomas

Purpose: Approximately 40% of all glioblastomas have amplified the epidermal growth factor receptor (EGFR) gene and about half of these tumors express the EGFRvIII variant. The prognostic role of EGFRvIII in EGFR-amplified glioblastoma patients and changes in EGFRvIII expression in recurrent versus primary glioblastomas remain controversial, but such data are highly relevant for EGFRvIII-targeted therapies. Experimental design: EGFR-amplified glioblastomas from 106 patients were assessed for EGFRvIII positivity. Changes in EGFR amplification and EGFRvIII status from primary to recurrent glioblastomas were evaluated in 40 patients with EGFR-amplified tumors and 33 patients with EGFR-non-amplified tumors. EGFR single nucleotide variants (SNVs) were assessed in 27 patients. Data were correlated with outcome and validated in 150 glioblastoma patients from The Cancer Genome Atlas (TCGA) consortium. Results: Sixty of 106 EGFR-amplified glioblastomas were EGFRvIII-positive (56.6%). EGFRvIII positivity was not associated with different progression-free or overall survival. EGFRvIII status was unchanged at recurrence in 35 of 40 patients with EGFR-amplified primary tumors (87.5%). Four patients lost and one patient gained EGFRvIII positivity at recurrence. None of 33 EGFR-non-amplified glioblastomas acquired EGFR amplification or EGFRvIII at recurrence. EGFR SNVs were frequent in EGFR-amplified tumors, but were not linked to survival. Conclusions: EGFRvIII and EGFR SNVs are not prognostic in EGFR-amplified glioblastoma patients. EGFR amplification is retained in recurrent glioblastomas. Most EGFRvIII-positive glioblastomas maintain EGFRvIII positivity at recurrence. However, EGFRvIII expression may change in a subset of patients at recurrence, thus repeated biopsy with reassessment of EGFRvIII status is recommended for recurrent glioblastoma patients to receive EGFRvIII-targeting agents.



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Macrophages facilitate resistance to anti-VEGF therapy by altered VEGFR expression

Purpose:VEGF-targeted therapies have modest efficacy in cancer patients, but acquired resistance is common. The mechanisms underlying such resistance are poorly understood. Experimental Design: To evaluate the potential role of immune cells in the development of resistance to VEGF blockade, we first established a preclinical model of adaptive resistance to anti-VEGF therapy. Additional in vitro and in vivo studies were carried out to characterize the role of macrophages in such resistance. Results: Using murine cancer models of adaptive resistance to anti-VEGF antibody (AVA), we found a previously unrecognized role of macrophages in such resistance. Macrophages were actively recruited to the tumor microenvironment and were responsible for the emergence of AVA resistance. Depletion of macrophages following emergence of resistance halted tumor growth and prolonged survival of tumor-bearing mice. In a macrophage-deficient mouse model, resistance to AVA failed to develop, but could be induced by injection of macrophages. Downregulation of macrophage VEGFR-1 and VEGFR-3 expression accompanied upregulation of alternative angiogenic pathways, facilitating escape from anti-VEGF therapy. Conclusions: These findings provide a new understanding of the mechanisms underlying the modest efficacy of current anti-angiogenesis therapies and identify new opportunities for combination approaches for ovarian and other cancers.



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Low-dose cyclophosphamide induces anti-tumor T-cell responses which associate with survival in metastatic colorectal cancer

Purpose: Anti-cancer T-cell responses can control tumors, but immune-suppressive mechanisms in vivo prevent their function. The role of regulatory T-cells (Tregs) in metastatic colorectal cancer (mCRC) is unclear. We have previously shown depletion of Tregs enhances CRC-specific effector T-cell responses. Low dose cyclophosphamide (CPM) targets Tregs in animal models and some human studies, however the effect of CPM in mCRC is unknown. Experimental Design: Fifty-five mCRC patients were enrolled onto a phase I/II trial and randomized to receive two week-long courses of low-dose (50mg twice-a-day) CPM or not. The absolute number, phenotype and anti-tumor function of peripheral blood-derived lymphocyte subsets were monitored throughout treatment, along with 18-month follow-up. Results: Initially CPM reduced proliferation in all lymphocyte subsets, however, a rapid mobilization of effector T-cells overcame this decrease, leading to increased absolute T-cell numbers. In contrast, a reduction in proportional and absolute Treg, B-cell and NK-cell numbers occurred. The expansion and subsequent activation of effector T-cells was focused on tumor-specific T-cells, producing both granzyme B and IFN-gamma. CPM-treated patients demonstrating the most enhanced IFN-gamma+ tumor-specific T-cell responses exhibited a significant delay in tumor progression (HR=0.29, 95% CI 0.12-0.69, P=0.0047), compared to non-responders and no-treatment controls. Conclusions: CPM-induced Treg-depletion is mirrored by a striking boost to anti-tumor immunity. This study provides the first direct evidence of the benefit of naturally primed T-cells in mCRC patients. Our results also support the concept that non-mutated self-antigens can act as useful targets for immunotherapies.



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Non-Hodgkin and Hodgkin lymphomas select for overexpression of BCLW

Purpose: B-cell lymphomas must acquire resistance to apoptosis during their development. We recently discovered BCLW, an anti-apoptotic BCL2 family member thought only to contribute to spermatogenesis, was overexpressed in diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. To gain insight into the contribution of BCLW to B-cell lymphomas and its potential to confer resistance to BCL2 inhibitors, we investigated the expression of BCLW and the other anti-apoptotic BCL2 family members in six different B-cell lymphomas. Experimental Design: We performed a large-scale gene expression analysis of data sets comprising approximately 2300 lymphoma patient samples, including non-Hodgkin and Hodgkin lymphomas as well as indolent and aggressive lymphomas. Data were validated experimentally with qRT-PCR and immunohistochemistry. Results: We report BCLW is significantly overexpressed in aggressive and indolent lymphomas, including DLBCL, Burkitt, follicular, mantle cell, marginal zone, and Hodgkin lymphomas. Notably, BCLW was preferentially overexpressed over that of BCL2 and negatively correlated with BCL2 in specific lymphomas. Unexpectedly, BCLW was overexpressed as frequently as BCL2 in follicular lymphoma. Evaluation of all five anti-apoptotic BCL2 family members in six types of B-cell lymphoma revealed that BCL2, BCLW, and BCLX were consistently overexpressed, whereas MCL1 and A1 were not. Additionally, individual lymphomas frequently overexpressed more than one anti-apoptotic BCL2 family member. Conclusions: Our comprehensive analysis indicates B-cell lymphomas commonly select for BCLW overexpression in combination with or instead of other anti-apoptotic BCL2 family members. Our results suggest BCLW is likely equally as important in lymphomagenesis as BCL2 and that targeting BCLW in lymphomas should be considered.



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Effects of rifampin, itraconazole and esomeprazole on the pharmacokinetics of alisertib, an investigational aurora a kinase inhibitor in patients with advanced malignancies

Summary

Aim Two studies investigated the effect of gastric acid reducing agents and strong inducers/inhibitors of CYP3A4 on the pharmacokinetics of alisertib, an investigational Aurora A kinase inhibitor, in patients with advanced malignancies. Methods In Study 1, patients received single doses of alisertib (50 mg) in the presence and absence of either esomeprazole (40 mg once daily [QD]) or rifampin (600 mg QD). In Study 2, patients received single doses of alisertib (30 mg) in the presence and absence of itraconazole (200 mg QD). Blood samples for alisertib and 2 major metabolites were collected up to 72 h (Study 1) and 96 h (Study 2) postdose. Area under the curve from time zero extrapolated to infinity (AUC0-inf) and maximum concentrations (Cmax) were calculated and compared using analysis of variance to estimate least squares (LS) mean ratios and 90% confidence intervals (CIs). Results The LS mean ratios (90% CIs) for alisertib AUC0-inf and Cmax in the presence compared to the absence of esomeprazole were 1.28 (1.07, 1.53) and 1.14 (0.97, 1.35), respectively. The LS mean ratios (90% CIs) for alisertib AUC0-inf and Cmax in the presence compared to the absence of rifampin were 0.53 (0.41, 0.70) and 1.03 (0.84, 1.26), respectively. The LS mean ratios (90% CIs) for alisertib AUC0-inf and Cmax in the presence compared to the absence of itraconazole were 1.39 (0.99, 1.95) and 0.98 (0.82, 1.19), respectively. Conclusions The use of gastric acid reducing agents, strong CYP3A inhibitors or strong metabolic enzyme inducers should be avoided in patients receiving alisertib.



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Hemophilic pseudotumor of the mandible in a patient with hemophilia B

Abstract

Introduction

Hemophilic pseudotumor is a rare complication occurring in patients with hemophilia, frequently seen in the femur, tibia, pelvic bones, iliac bones, or rarely in the maxillofacial region.

Case report

A 7-year-old male reported with a spontaneous extra-oral swelling that was managed with pre-operative transfusion of factor IX along with curettage of the lesion. Our report presents only the fourth case in literature wherein this tumor presented in a patient with hemophilia B.

Finding

Hemophilic pseudotumor is a rare entity in the maxillofacial region. High degree of suspicion is required for diagnosis, and close coordination between the medical and surgical teams aids in management.



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"Ear Nose Throat J"[jour]; +20 new citations

20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Ear Nose Throat J"[jour]

These pubmed results were generated on 2017/08/29

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.



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Hemophilic pseudotumor of the mandible in a patient with hemophilia B

Abstract

Introduction

Hemophilic pseudotumor is a rare complication occurring in patients with hemophilia, frequently seen in the femur, tibia, pelvic bones, iliac bones, or rarely in the maxillofacial region.

Case report

A 7-year-old male reported with a spontaneous extra-oral swelling that was managed with pre-operative transfusion of factor IX along with curettage of the lesion. Our report presents only the fourth case in literature wherein this tumor presented in a patient with hemophilia B.

Finding

Hemophilic pseudotumor is a rare entity in the maxillofacial region. High degree of suspicion is required for diagnosis, and close coordination between the medical and surgical teams aids in management.



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Grafting materials for alveolar cleft reconstruction: a systematic review and best-evidence synthesis

The purpose of this study was to compare the efficacy of alveolar bone reconstruction for alveolar cleft patients performed with the traditional iliac graft or alternative/supplementary bone grafting materials. Electronic databases, relevant journals, and reference lists of the included studies were searched to the end of June 2016. A best-evidence synthesis was performed to draw conclusions. A total of 38 studies were included, which provided 25 pieces of evidence: seven of moderate evidence and 18 of insufficient evidence.

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Rate-control with beta-blockers versus calcium-channel blockers in the emergency setting: predictors of medication class choice and associated hospitalization

Abstract

Objectives

Rate-control is an important component of the management of patients with atrial fibrillation (AF). Previous studies of emergency department (ED) rate-control have been limited by relatively small sample sizes. We examined the use of beta-blockers (BB) versus non-dihydropyridine calcium channel blockers (CCB) in ED patients from 24 sites, and the associated hospital admission rates.

Methods

In this pre-planned sub-study, we examined chart data on AF patients who visited one of 24 hospital EDs in Ontario, Canada, between April 2008 and March 2009. We describe the proportion of patients who received either a BB or a CCB, had a heart rate < 110 beats/minute 2 hours later, and any complications. We used hierarchical logistic regression modeling to determine the predictors of BB versus CCB use, and to assess the between-hospital variation in use of BB versus CCB. Solely in patients who had no rhythm control attempts, we examined the difference in the probability of hospital admission after propensity score matching patients by medication class.

Results

Of the 1639 patients who received either a BB (n=429) or a CCB (n=1210), 70.9% of the patients who received a BB had successful rate-control, versus 66.1% for a CCB. Complications were rare (2.4%), and the large majority were hypotension (2.0%). In adjusted analyses, predictors of receiving a BB (compared to a CCB) included already being on a BB, being sent in from a doctor's office, or being seen at a teaching hospital. In contrast, patients with evidence of heart failure, prior use of a CCB, a higher presenting heart rate, a successful pharmacological cardioversion (versus no attempt), or who were seen at the highest AF volume EDs were significantly less likely to receive a BB, compared to a CCB. Systematic between-hospital differences accounted for 8% of the variation in BB versus CCB use. Hospital characteristics accounted for the large majority of that variation: after accounting for patient characteristics the between-hospital variation decreased by a relative 2.8%. By further adjusting for hospital characteristics, it decreased by a relative 74.7%. Among propensity-score matched patients with no rhythm-control attempts, more CCB patients were admitted (51.6%) compared to BB patients (40.0%) (difference of 11.6%; 95% CI, 7.9-16.2).

Conclusions

In this study of 24 EDs, CCBs were used more frequently for rate-control than BBs, and complications were rare and easily managed using both agents. Variation between hospitals in BB versus CCB use was predominantly due to hospital characteristics such as teaching status and AF volumes, rather than different case-mix. Among patients who did not receive attempts at rhythm control, use of a BB for rate control was associated with a lower rate of hospitalization.

This article is protected by copyright. All rights reserved.



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The 2017 Academic Emergency Medicine Consensus Conference: Catalyzing System Change through Healthcare Simulation: Systems, Competency, and Outcomes

Abstract

Over the past decade, emergency medicine took a lead role in healthcare simulation in part due to its demands for successful interprofessional and multidisciplinary collaboration, along with educational needs in a diverse array of cognitive and procedural skills. Simulation-based methodologies have the capacity to support training and research platforms that model micro-, meso- and macro- systems of healthcare. To fully capitalize on the potential of simulation-based research to improve emergency healthcare delivery will require the application of rigorous methods from engineering, social science, and basic science disciplines. The Academic Emergency Medicine (AEM) Consensus Conference, "Catalyzing System Change Through Healthcare Simulation: Systems, Competency, and Outcome" was conceived to foster discussion among experts in emergency medicine, engineering, and social sciences, focusing on key barriers and opportunities in simulation-based research. This executive summary describes the overall rationale for the conference, conference planning, consensus-building approaches, and outlines the focus of the eight breakout sessions. The consensus outcomes from each breakout session are summarized in Proceedings papers published in this issue of Academic Emergency Medicine. Each paper provides an overview of methodological and knowledge gaps in simulation research and identifies future research targets aimed at improving the safety and quality of healthcare.

This article is protected by copyright. All rights reserved.



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Effect of body posture on chewing behaviors in healthy volunteers

Abstract

Mastication is essential to the eating process, and forms an important part of feeding behavior. Many factors related to the food bolus, such as bolus texture and size, are known to influence mastication. The aim of the present study was to determine the effects of body posture on (1) chewing duration prior to the first swallow and (2) patterns of mastication-related EMG activity. We asked 10 healthy adults to chew 8 g of steamed rice with barium sulfate while we recorded masseter, suprahyoid, and infrahyoid muscle activity and simultaneously collected videofluorographic images. Participants chewed in either an upright or reclining position. Chewing duration, which was defined as the time from the start of mastication to the first swallow, was not different between the positions. However, the variability of chewing duration was larger in the upright vs. reclining position, and the chewing duration in the reclining position was distributed around 15 s. Masseter activity gradually decreased in a time dependent manner and was significantly larger at the early vs. late stage of mastication. Suprahyoid activity was significantly larger at the early vs. middle stage of mastication in the upright position only. Finally, masseter activity per second was negatively correlated with changes in chewing duration, i.e., the larger the increase in chewing duration in the reclining position, the more the decrease in masseter activity per second. These results suggest that position-dependent changes in chewing behaviors, as described by chewing duration and EMG activity, may vary among participants.

This article is protected by copyright. All rights reserved.



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Jaw sensorimotor control in healthy adults and effects of aging

Summary

The orofacial sensorimotor system is a unique system significantly distinguished from the spinal sensorimotor system. The jaw muscles are involved in mastication, swallowing and articulatory speech movements and their integration with respiration. These sensorimotor functions are vital for sustaining life and necessitate complex neuromuscular processing to provide for exquisite sensorimotor control of numerous orofacial muscles. The function of the jaw muscles in relation to sensorimotor control of these movements may be subject to aging-related declines. This review will focus on peripheral, brainstem and higher brain centre mechanisms involved in reflex regulation and sensorimotor coordination and control of jaw muscles in healthy adults. It will outline the limited literature bearing on age-related declines in jaw sensorimotor functions and control including reduced biting forces and increased risk of impaired chewing, speaking and swallowing. The mechanisms underlying these alterations include age-related degenerative changes within the peripheral neuromuscular system and in brain regions involved in the generation and control of jaw movements. In light of the vital role of jaw sensorimotor functions in sustaining life, normal aging involves compensatory mechanisms that utilize the neuroplastic capacity of the brain and the recruitment of additional brain regions involved in sensorimotor performance and closely associated functions (e.g., cognition and memory). However, these regions are themselves susceptible to detrimental age-related changes. Thus, better understanding of the peripheral and central mechanisms underlying age-related sensorimotor impairment is crucial for developing improved treatment approaches to prevent or cure impaired jaw sensorimotor functions and to thereby improve health and quality of life.

This article is protected by copyright. All rights reserved.



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Changes in psychological health, subjective food intake ability, and oral health-related quality of life during orthodontic treatment

Abstract

Background

Assessing changes in patient's psychological health and oral health-related quality of life (OHRQoL) over time during orthodontic treatment may help clinicians to treat patients more carefully.

Objectives

To evaluate changes in mental health, self-reported masticatory ability, and OHRQoL during orthodontic treatment in adults.

Methods

This prospective study included 66 adults (30 men, 36 women; mean age, 24.2 ± 5.2 years). Each patient completed the Korean versions of the State-Trait Anxiety Inventory, Zung Self-Rating Depression Scale, Rosenberg self-esteem scale, key subjective food intake ability (KFIA) test for five key foods, and Oral Health Impact Profile-14 (OHIP-14K) at baseline (T0), 12 months after treatment initiation (T1), and debonding (T2).

Results

All variables changed with time. Self-esteem and the total OHIP-14K score significantly decreased and increased, respectively, at T1, with a particular increase in the psychological and social disabilities scores. There were no significant differences in any questionnaire scores before and after treatment. The total OHIP-14K score was positively correlated with trait anxiety and depression, and negatively correlated with self-esteem and KFIA at T0, regardless of the treatment duration. Older patients showed a significant increase in the total OHIP-14K score at T1 and T2. OHRQoL worsened with an increase in the treatment duration.

Conclusions

Our results suggest that OHRQoL temporarily deteriorates, with the development of psychological and social disabilities, during orthodontic treatment. This is related to the baseline age, psychological health, and self-reported masticatory function. However, patients recover once the treatment is complete.

This article is protected by copyright. All rights reserved.



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Masticatory performance-related factors in preschool children: Establishing a method to assess masticatory performance in preschool children using colour-changeable chewing gum

Abstract

Background

A knowledge gap regarding masticatory performance in preschool children exists, which in turn delays intervention for preventive care; therefore, a method to easily assess performance is needed.

Objective

To investigate the feasibility of assessing masticatory performance using colour-changeable chewing gum, and to investigate masticatory performance-related factors in preschool children.

Methods

This cross-sectional survey was conducted in two childcare facilities and our laboratory. First, a one-third quantity of colour-changeable chewing gum was masticated by six adults to assess the nature and progression of colour changes in this quantity. Then, masticatory performance in 370 children 4 to 6 years of age was assessed using the same quantity of colour-changeable chewing gum (60 chew strokes). The maximum bite force, body height, weight, age, and number of healthy teeth were recorded. A t-test was performed to determine whether gum-chewing experience or lack thereof produced a significant difference in masticatory performance. The Spearman's rank correlation coefficient was then determined for masticatory performance assessment values and other factors solely for children with gum-chewing experience.

Results

Measurements from 259 children were obtained. Children with gum-chewing experience demonstrated significantly higher assessment values, and were deemed to have been correctly assessed. A very weak but significant positive correlation was observed only between masticatory performance and the number of healthy teeth.

Conclusions

The masticatory performance of preschool children was easily assessed using colour-changeable chewing gum. The assessment values demonstrated significant correlation with the number of healthy teeth, but not with maximum bite force, body height, weight, or age.

This article is protected by copyright. All rights reserved.



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Depressive Symptoms Account for Differences between Self-reported Versus Polysomnographic Assessment of Sleep Quality in Women with Myofascial TMD

Abstract

Background

Temporomandibular disorder (TMD) patients report poor sleep quality on the Pittsburgh Sleep Quality Index (PSQI). However, polysomnographic (PSG) studies show meager evidence of sleep disturbance on standard physiological measures.

Objective

The present aim was to analyze self-reported sleep quality in TMD as a function of myofascial pain, PSG parameters, and depressive symptomatology.

Methods

PSQI scores from 124 women with myofascial TMD and 46 matched controls were hierarchically regressed onto TMD presence, ratings of pain intensity and pain-related disability, in-lab PSG variables, and depressive symptoms (Symptoms Checklist-90).

Results

Relative to controls, TMD cases had higher PSQI scores, representing poorer subjective sleep, and more depressive symptoms (both P < 0.001). Higher PSQI scores were strongly predicted by more depressive symptoms (P < 0.001, R2 = 26%). Of 19 PSG variables, two had modest contributions to higher PSQI scores: longer REM latency in TMD cases (P = 0.01, R2 = 3%) and more awakenings in all participants (P = 0.03, R2 = 2%). After accounting for these factors, TMD presence and pain ratings were not significantly related to PSQI scores.

Conclusion

These results show that reported poor sleep quality in TMD is better explained by depressive symptoms than by PSG-assessed sleep disturbances or myofascial pain. As TMD cases lacked typical PSG features of clinical depression, the results suggest a negative cognitive bias in TMD and caution against interpreting self-report sleep measures as accurate indicators of PSG sleep disturbance. Future investigations should take account of depressive symptomatology when interpreting reports of poor sleep.

This article is protected by copyright. All rights reserved.



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Hemophilic pseudotumor of the mandible in a patient with hemophilia B

Abstract

Introduction

Hemophilic pseudotumor is a rare complication occurring in patients with hemophilia, frequently seen in the femur, tibia, pelvic bones, iliac bones, or rarely in the maxillofacial region.

Case report

A 7-year-old male reported with a spontaneous extra-oral swelling that was managed with pre-operative transfusion of factor IX along with curettage of the lesion. Our report presents only the fourth case in literature wherein this tumor presented in a patient with hemophilia B.

Finding

Hemophilic pseudotumor is a rare entity in the maxillofacial region. High degree of suspicion is required for diagnosis, and close coordination between the medical and surgical teams aids in management.



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Gender difference and laterality of sleep position

A higher incidence in women (approximately 7:3) and a predominant involvement of the right ear (approximately 7:5) are interesting features of BPPV (benign paroxysmal positional vertigo). It is speculated that these features are related to sleep position. The first aim of this study was to compare the frequency of position shifts during sleep between men and women. The second aim was to elucidate any differences in sleep position between men and women. The third aim was to clarify the laterality of sleep position.

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Is voice therapy effective for the treatment of dysphonic patients with benign vocal fold lesions?

Related Articles

Is voice therapy effective for the treatment of dysphonic patients with benign vocal fold lesions?

Auris Nasus Larynx. 2017 Aug 22;:

Authors: Ogawa M, Inohara H

Abstract
OBJECTIVE: To update our knowledge regarding the effectiveness of voice therapy for the treatment of vocal disturbance associated with benign vocal fold lesions, including vocal polyps, nodules and cysts, and for determining the utility of voice therapy in treating organic voice disorders, while highlighting problems for the future development of this clinical field.
METHODS: We conducted a review of the most recent literature on the therapeutic effects of voice therapy, vocal hygiene education or direct vocal training on vocal quality, the lesion appearance and discomfort felt by patients due to the clinical entity of benign vocal fold mass lesions.
RESULTS: Although voice therapy is principally indicated for the treatment of functional dysphonia without any organic abnormalities in the vocal folds, a number of clinicians have attempted to perform voice therapy even in dysphonic patients with benign mass lesions in the vocal folds. The two major possible reasons for the effectiveness of voice therapy on vocal disturbance associated with benign vocal fold lesions are hypothesized to be the regression of lesions and the correction of excessive/inappropriate muscle contraction of the phonatory organs. According to the current literature, a substantial proportion of vocal polyps certainly tend to shrink after voice therapy, but whether or not the regression results from voice therapy, vocal hygiene education or a natural cure is unclear at present due to the lack of controlled studies comparing two groups with and without interventions. Regarding vocal nodules, no studies have investigated the effectiveness of voice therapy using proper experimental methodology. Vocal cysts are difficult to cure by voice therapy without surgical excision according to previous studies. Evidences remains insufficient to support the use of voice therapy against benign vocal fold lesions.
CONCLUSION: Evidences at present is therefore still insufficient to support the use of voice therapy for the treatment of benign vocal fold lesions.

PMID: 28844607 [PubMed - as supplied by publisher]



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"Ear Nose Throat J"[jour]; +20 new citations

20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Ear Nose Throat J"[jour]

These pubmed results were generated on 2017/08/29

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.



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Effects of Aging on Vocal Fundamental Frequency and Vowel Formants in Men and Women

This study reports data on vocal fundamental frequency (fo) and the first four formant frequencies (F1, F2, F3, F4) for four vowels produced by speakers in three adult age cohorts, in a test of the null hypothesis that there are no age-related changes in these variables. Participants were 43 men and 53 women between the ages of 20 and 92 years.

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Influence of tumor response and treatment schedule on the distribution of tumor recurrence in esophageal cancer patients treated with neoadjuvant chemoradiotherapy

Background and Objectives

The impact of different neoadjuvant chemoradiotherapy (nCRT) schedules and pathologic complete response (pCR) on the distribution of recurrence is unclear in esophageal cancer (EC). We assessed the effect of pCR and nCRT schedule in EC.

Methods

Patients with T1N+/T2-4aN0-3/M0 EC treated in different centers, with either carboplatin/paclitaxel/41.4 Gy (CROSS: n = 134) or Cisplatin/5-fluorouracil/45-50.4 Gy (Cis/5FU: n = 88) followed by surgery were included. The effect of pCR on distribution and site-specific recurrence was determined for the CROSS group. After propensity score matching we compared the impact of both schedules (n = 63 each) on the recurrence pattern.

Results

Overall (P = 0.005) and disease-free survival (P = 0.002) were significantly longer after pCR (n = 24). The pattern of recurrence differed between pCR and non-pCR group (P = 0.001) for locoregional (0 vs 7; 6.4%), distant (5; 20.8% vs 36; 32.7%), and combined local and distant (0 vs 21; 19.1%), respectively. After pCR, less local and distant recurrences were seen (P = 0.008). With equal median time to recurrence, the distribution of metastases only differed for lung metastases (P = 0.029), with 15 (23.8%) in the CROSS group versus 6 (9.5%) following Cis/5FU.

Conclusions

Patients with pCR have less local and distant recurrence. The nCRT regime had a minor influence on the site-specific distribution of recurrence.



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The preoperative globulin-to-albumin ratio, a novel inflammation-based prognostic system, predicts survival after potentially curative liver resection for patients with hepatocellular carcinoma

Background and Objectives

Although the globulin-to-albumin ratio (GAR) is useful for prognostication of patients with various cancers, its relationship with hepatocellular carcinoma (HCC) remains unclear. The study aims to investigate the relationship between GAR and postoperative survival among patients with HCC undergoing potentially curative liver resection (LR).

Methods

We retrospectively reviewed 368 patients with newly diagnosed HCC who underwent initial and potentially curative LR. Univariate and multivariate analyses using the Cox proportional hazard model were performed to detect clinical characteristics that correlated with overall survival (OS). Kaplan-Meier analysis and log-rank test were used to compare OS and disease-free survival (DFS).

Results

The result of multivariate analysis using 25 clinical characteristics selected by univariate analysis revealed that the GAR (≥0.918/<0.918) was significantly associated with OS (hazard ratio [HR], 2.398; 95% confidence interval [CI], 1.012-5.683; P = 0.047), as well as platelet count (<14/≥14, ×104/mm3) and portal vein invasion (presence/absence). Kaplan-Meier analysis and log-rank test demonstrated that the OS and DFS of patients with a high GAR (>0.918) were significantly worse than that of patients with a low GAR (≤0.918).

Conclusions

The GAR is a useful predictor of postoperative survival among patients with HCC undergoing potentially curative LR.



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Detection of hereditary hearing loss gene by DNA microarray

OBJECTIVE: Screening genes in patients suffering clinically sporadic deafness, using DNA microarray, and evaluating the application value of the clinical detection.

PATIENTS AND METHODS: DNA extracted from patients' venous blood was amplified by PCR, and hybridization was carried out in a myriad class clean room. Nine mutation sites of four deaf genes commonly seen in Chinese people were tested.

RESULTS: Among 24 patients, 7 cases with mutations were detected, with a positive rate of 29.17%. These include 4 cases with GJB2 gene mutation (16.67%), of which 1 case with 176 del 16 site heterozygous mutation; 1 with 235 del C site homozygous mutation; 2 with 299 del AT site heterozygous mutation; 1 with SLC26A4 gene IVS7-2A>G site heterozygous mutation (4.17%), 2 with mitochondrion 12SrRNA gene1555A>G site homogeneous mutation (8.33%). No GJB3 gene mutation was detected.

CONCLUSIONS: Gene chip technology of hereditary hearing loss can detect related mutation sites of hearing loss rapidly and with high-throughput, which meets the demands of clinical deaf gene detection.

L'articolo Detection of hereditary hearing loss gene by DNA microarray sembra essere il primo su European Review.



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Corrigendum to “New approach to improve the keratinised peri-implant soft tissues in patients with intraoral osteocutaneous reconstruction using a free flap” [Br J Oral Maxillofac Surg 55 (September (7)) (2017) 732–33]

The author regrets incorrect captions being published for Figs. 2 and 3 in the above referenced paper.

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Randomised controlled clinical trial of augmentation of the alveolar ridge using recombinant human bone morphogenetic protein 2 with hydroxyapatite and bovine-derived xenografts: comparison of changes in volume

The aim of this randomised controlled clinical trial was to assess the early efficacy of bone morphogenetic protein-2 with hydroxyapatite granules (BMP-2/hydroxyapatite) on augmentation of the alveolar ridge, by comparing changes in volume with those associated with the use of an inorganic bovine-derived xenograft (BDX). We studied 20 patients who were divided into two groups using a table of random numbers, and BMP-2/hydroxyapatite and BDX were applied accordingly. Computed tomographic (CT) images and panoramic radiographs were obtained immediately after operation and four months later.

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Sentinel lymph node biopsy for oral squamous cell carcinoma. Where are we now?

Recent data have confirmed that elective surgical management of the cN0 neck improves survival in patients with early (T1-T2) oral squamous cell carcinoma (SCC), and is better than watchful waiting. However, elective neck dissection (END) may not always be necessary. Sentinel node biopsy (SNB), which is a reliable staging test for patients with early disease and a radiologically N0 neck, can detect occult metastases with a sensitivity of 86%–94%. Patients with no sign of metastases on SNB could avoid neck dissection, and individual treatment should reduce both morbidity and cost.

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Systematic three-dimensional analysis of wafer-based maxillary repositioning procedures in orthognathic surgery

Little is known about the three-dimensional (3D) transfer accuracy in maxillary repositioning procedures based on conventionally manufactured dental-mounted wafers. The purpose of the present study was a systematic 3D analysis for wafer-based maxillary positioning in orthognathic surgery.

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Force and deformation stresses in customized and non-customized plates during simulation of advancement genioplasty

The aim of this study was to evaluate the distribution of deformation stresses in customized and non-customized plates during simulated advancement genioplasty, using the finite element method.

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The effects of surgically assisted rapid maxillary expansion (SARME) on the dental show and chin projection

None.

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Issue Information



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British Society for Matrix Biology Spring 2017 Meeting: Matrix Proteoglycans: active participants in cell-extracellular matrix communication



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Histological, morphometric, protein and gene expression analyses of rat retinas with ischaemia–reperfusion injury model treated with sildenafil citrate

Summary

The aim of this study was to better understand the role of apoptosis in a retinal ischaemia–reperfusion injury model and to determine whether sildenafil citrate treatment can prevent retinal cell apoptosis. Thirty-six rats were divided into a control group (= 6) and two experimentally induced ischaemia–reperfusion groups (7 and 21 days; = 15 per group). The induced ischaemia–reperfusion groups were treated with sildenafil for 7 and 21 days (= 10 per group), and 10 animals were treated with a placebo for the same period (= 5 per group). Paracentesis of the anterior chamber was performed with a 30-G needle attached to a saline solution (0.9%) bag positioned at a height of 150 cm above the eye for 60 min. Intraocular pressure was measured by rebound tonometer (TonoVet®). The eyes were analysed by histology and morphometry, and by immunohistochemistry and qRT-PCR for expression of Caspase-7, Caspase-6, Caspase-9, Tnf-r2, Fas-l, Bcl-2 and Bax. Sildenafil-treated animals showed lower levels of histopathological changes (inflammatory, cellular and tissue) than their placebo-treated counterparts at both 7 and 21 days. The retinal ganglion cell layer (RGC) was preserved in the sildenafil groups (SG), with a cell count closer to control than in the placebo groups (PG). Caspase-7 expression was significantly higher in both treated groups at 7 days compared to controls. Gene expression levels in both treatment groups differed from the controls, but in SG Bax and Caspase-6 expression levels were similar to control animals. These results suggest that the main mechanism of retinal cell death in this model is apoptosis, as there is an increase in pro-apoptotic factors and decrease in the anti-apoptotic ones. Also, sildenafil seems to protect the retinal ganglion cell layer from apoptosis. Cell survival was evident in the histological and morphometric analyses, and sildenafil treatment had a protective effect in the apoptosis pathways, with gene expression levels in SG similar to the controls.



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Evolution of gender representation among Canadian OTL-HNS residents: a 27-year analysis

The proportion of females enrolling into medical schools has been growing steadily. However, the representation of female residents among individual specialties has shown considerable variation. The purpose of...

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The estimates of 5-year lung cancer prevalence in adult population in 2012



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IN THIS ISSUE



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Joint Symposium of Korean Cancer Association & UICC-ARO—Cross-boundary cancer studies: cancer and Universal Health Coverage (UHC) in Asia

Abstract
On 16 June 2016, the Korean Cancer Association (KCA) and Union for International Cancer Control-Asia Regional Office (UICC-ARO) organized a joint symposium as part of the official program of the 42nd Annual Meeting of the Korean Cancer Association to discuss the topic 'Cross-boundary Cancer Studies: Cancer and Universal Health Coverage (UHC) in Asia.' Universal Health Coverage is included in the Sustainable Development Goals adopted by the United Nations as part of the 2030 Agenda for Sustainable Development. The objectives of UHC are to ensure that all people can receive high-quality medical services, are protected from public health risks, and are prevented from falling into poverty due to medical costs or loss of income arising from illness. The participants discussed the growing cost of cancer in the Asian region and the challenges that this poses to the establishment and deployment of UHC in the countries of Asia, all of which face budgetary and other systemic constraints in controlling cancer in the region. Representatives from Korea, Japan and Indonesia reported on the status of UHC in their countries and the challenges that are being faced, many of which are common to other countries in Asia. In addition to country-specific presentations about the progress of and challenges facing UHC, there were also presentations from WHO Kobe Centre concerning advancing UHC in non-communicable diseases and prospects for further collaboration and research on UHC. A presentation from the University of Tokyo also highlighted the need to focus on multidisciplinary studies in an age of globalization and digitization.

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Sex differences in lung cancer survival: long-term trends using population-based cancer registry data in Osaka, Japan

Abstract
Objective
Several studies of sex differences in lung cancer survival have been reported. However, large-size population-based studies based on long-term observation are scarce. We investigated long-term trends in sex differences in lung cancer survival using population-based cancer registry data from Osaka, Japan.
Methods
We analyzed 79 330 cases from the Osaka Cancer Registry (OCR) diagnosed between 1975 and 2007. We calculated 5-year relative survival in the six periods (1975–1980, 1981–1986, 1987–1992, 1993–1997, 1998–2002 and 2003–2007). To estimate the trends in sex differences in lung cancer survival throughout the study period, we applied a multivariate excess hazard model to control for confounders.
Results
The proportion of adenocarcinoma (ADC) and 5-year relative relative survival have increased for both sexes. Sex differences in lung cancer survival have widened over the period, especially in ADC and since the late 1990s. The excess hazard ratio of death within 5 years for males was 1.19 (95% CI: 1.16–1.21), adjusting for period at diagnosis, histologic type, stage, age group and treatment.
Conclusion
We reported that females have better prognosis in lung cancer than males and the sex differences in lung cancer survival have become wider in Osaka, Japan. This can be partly explained by the sex differences in the proportions of histologic type and stage. Further studies considering other factors that influence sex differences in lung cancer survival are needed.

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Local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer

Abstract
Background
Radiotherapy is an effective treatment for the postoperative loco-regional recurrence of esophageal cancer; however, the optimal treatment field remains controversial. This study aims to evaluate the outcome of local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer.
Methods
We retrospectively investigated 35 patients treated for a postoperative loco-regional recurrence of esophageal cancer with local field radiotherapy between December 2008 and March 2016. The median irradiation dose was 60 Gy (range: 50–67.5 Gy). Thirty-one (88.6%) patients received concurrent chemotherapy.
Results
The median follow-up period was 18 months (range: 5–94 months). The 2-year overall survival was 55.7%, with a median survival time of 29.9 months. In the univariate analysis, the maximal diameter ≤20 mm (P = 0.0383), solitary lesion (P = 0.0352), and the complete remission after treatment (P = 0.00411) had a significantly better prognosis. A total of 27 of 35 patients (77.1%) had progressive disease (loco-regional failure [n = 9], distant metastasis [n = 7], and both loco-regional failure and distant metastasis [n = 11]). No patients had Grade 3 or greater mucositis.
Conclusion
Local field radiotherapy is a considerable treatment option for postoperative loco-regional recurrence of esophageal cancer.

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Leptomeningeal metastases of lung adenocarcinoma detected by 18 F-FDG PET/CT



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Retrospective analysis of definitive radiotherapy for neck node metastasis from unknown primary tumor: Japanese Radiation Oncology Study Group study

Abstract
Objective
To investigate the optimal treatment method and risk factor of neck node metastasis from unknown primary tumors (NUP) treated by radiotherapy.
Methods
Retrospective case study based on a multi-institutional survey was conducted by the Japanese Radiation Oncology Study Group. Patients pathologically diagnosed as having NUP from 1998 to 2007 were identified. Univariate and multivariate analyses of overall survival (OS), progression free survival (PFS), neck progression free survival (NPFS) and mucosal progression free survival (MPFS) were evaluated.
Results
In total, 130 patients with median age of 65 years were included. Nodal stages N1, N2a, N2b and N2c were observed for 10, 26, 43, 12 and 39 patients, respectively. All the patients received radiotherapy (RT) with neck dissection in 60 and with chemotherapy in 67 cases. The median doses to the metastatic nodes, prophylactic neck and prophylactic mucosal sites were 60.0, 50.4 and 50.4 Gy, respectively. The median follow-up period for surviving patients was 42 months. Among 12 patients, occult primary tumors in the neck region developed after radiotherapy. The 5-year OS, PFS, NPFS and MPFS were 58.1%, 42.4%, 47.3% and 54.9%, respectively. Univariate analysis showed that lower N stage (N1–2b), non-bulky node (<6 cm) and negative extracapsular extension (ECE) status were the factors associated with favorable OS, PFS, NPFS and MPFS. Radical surgery proved to be a favorable factor of OS, NPFS and MPFS. On multivariate analysis, lower N stage and negative ECE status were correlated with improved survival.
Conclusions
Lower nodal stage and negative ECE status showed a favorable impact on survival and disease control in patients with NUP treated by radiotherapy.

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Antitumor activity of iNGR-GRIM-19 in colorectal cancer

Abstract
Background
Gene associated with retinoid-interferon induced mortality-19 (GRIM-19) plays crucial roles in carcinogenesis.
Objective
To explore the antitumor activity of internalizing NGR (iNGR) gene associated with GRIM-19 in colorectal cancer.
Methods
Cells were incubated with fluorescein isothiocyanate-labeled fusion proteins followed by fluorescence microscopic analysis. Cell proliferation was determined by MTT assay. Cell cycle was analyzed by flow cytometric analysis. Cell migration and invasion capacity were evaluated by wound scratch and Transwell assays, respectively. Apoptosis was measured by Annexin V/PI staining and TUNEL assay. Gene expressions were determined by RT-PCR and Western blotting. Nude mice bearing colorectal cancer received vehicle, GRIM-19, or iNGR-GRIM-19 fusion protein injection, and the in vivo antitumor capacity of the fusion proteins was examined.
Results
iNGR-GRIM-19 was specifically taken up by human colorectal cancer Colo205 cells, but not corneal epithelial (HCEpic) cells, whereas GRIM-19 was not internalized by either cell type. Unlike GRIM-19, incubation with iNGR-GRIM-19 dose-dependently inhibited proliferation, induced G1 phase arrest, suppressed cell migration and invasion, and caused apoptosis in Colo205 cells. Additionally, injection of iNGR-GRIM-19 extended the lifespan of colorectal cancer-bearing nude mice and reduced in vivo tumor growth as compared with vehicle or GRIM-19 treatment. iNGR-GRIM-19 was localized only in the tumor mass, without affecting other tissues, such as liver or kidney. iNGR-GRIM-19 injection led to G1 phase arrest and induced cell apoptosis in xenografted colorectal cancer tissues.
Conclusions
iNGR-GRIM-19 has an efficient antitumor activity in vitro and in vivo, and might be a promising agent for the treatment of colorectal cancer.

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Adherence to oral chemotherapy medications among gastroenterological cancer patients visiting an outpatient clinic

Abstract
Objective
The purpose of this study was to investigate medication adherence to oral chemotherapy medications and determinants of medication non-adherence to them among gastroenterological cancer patients.
Methods
A cross-sectional study was conducted on 117 consecutive, consenting, eligible patients visiting an outpatient clinic of university hospital in Japan. Good medication adherence was defined as taking 100% of the prescribed dose. Medication adherence was measured via self-report. We hypothesized that there was a significant relationship between medication non-adherence and the five factors defined by the World Health Organization: patient-related, socioeconomic-related, condition-related, treatment-related, and healthcare-system/provider-related factors. Multiple logistic regression models were used to identify factors associated with oral chemotherapy medication non-adherence.
Results
The proportion of patients showing good medication adherence was 56.4%. The multiple logistic regression analysis revealed that the determinants of medication non-adherence to oral chemotherapy medications included having a history of patient-caused treatment interruptions due to worsening of symptoms (adjusted odds ratio [AOR] = 9.59, 95% confidence interval [CI] = 1.38–66.47), having diarrhea (AOR = 3.25, 95% CI = 1.13–9.34), experiencing pain (AOR = 0.17, 95% CI = 0.05–0.55), taking oral chemotherapy medication every 8 h (AOR = 5.52, 95% CI = 1.71–17.81), and diminished sense of priority for medication (AOR = 1.40, 95% CI = 1.21–1.63).
Conclusions
This study suggests that many patients with gastroenterological cancer were non-adherent to oral chemotherapy medications. It might be necessary to conduct periodic screening and connect patients at a high risk of medication non-adherence to appropriate support.

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A Phase II study of palonosetron, aprepitant, dexamethasone and olanzapine for the prevention of cisplatin-based chemotherapy-induced nausea and vomiting in patients with thoracic malignancy

Abstract
Background
The three-drug combination of a 5-hydroxytryptamine type 3 receptor antagonist, a neurokinin 1 receptor antagonist and dexamethasone is recommended for patients receiving highly emetogenic chemotherapy. However, standard antiemetic therapy is not completely effective in all patients.
Methods
We conducted an open-label, single-center, single-arm Phase II study to evaluate the efficacy of olanzapine in combination with standard antiemetic therapy in preventing chemotherapy-induced nausea and vomiting in patients with thoracic malignancy receiving their first cycle of cisplatin-based chemotherapy. Patients received 5 mg oral olanzapine on Days 1–5 in combination with standard antiemetic therapy. The primary endpoint was complete response (no vomiting and no use of rescue therapy) during the overall Phase (0–120 h post-chemotherapy).
Results
Twenty-three men and seven women were enrolled between May and October 2015. The median age was 64 years (range: 36–75 years). The most common chemotherapy regimen was 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed, which was administered to 14 patients. Complete response rates in acute (0–24 h post-chemotherapy), delayed (24–120 h post-chemotherapy) and overall phases were 100%, 83% and 83% (90% confidence interval: 70–92%; 95% confidence interval: 66–93%), respectively. There were no Grade 3 or Grade 4 adverse events. Although four patients (13%) experienced Grade 1 somnolence, no patients discontinued olanzapine.
Conclusions
The addition of 5 mg oral olanzapine to standard antiemetic therapy demonstrates promising efficacy in preventing cisplatin-based chemotherapy-induced nausea and vomiting and an acceptable safety profile in patients with thoracic malignancy.

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Efficacy of early ureteral ligation on prevention of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma: a prospective single-arm multicenter clinical trial

Abstract
Objective
The rate of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma is high. Seeding upper urinary tract urothelial carcinoma cells onto the damaged bladder wall is considered to be one of the causes of intravesical recurrence after radical nephroureterectomy. We evaluated the utility of early ureteral ligation in preventing the intravesical recurrence.
Methods
This prospective single-arm clinical trial included patients who underwent radical nephroureterectomy for upper urinary tract urothelial carcinoma in the Tohoku Urological Evidence-Based Medicine Study Group between 2012 and 2013. Early ureteral ligation was defined as ligation of the ureter as quickly as possible after expanding the retroperitoneal space. A historical control was extracted from 454 patients who underwent radical nephroureterectomy in the same group, using propensity score-matched analysis. Intravesical recurrence-free survival rates were analyzed using Kaplan–Meier curves. Factors predicting intravesical recurrence were assessed using multivariate analyses.
Results
Seventy-four patients underwent early ureteral ligation. Seventeen (23%) patients had intravesical recurrence with a median follow-up period of 24 months. The 1- and 2-year intravesical recurrence-free survival rates in the early ureteral ligation group were 81% and 76%, and in the control group 75% and 63%, respectively (P = 0.160). In patients with renal pelvic cancer, the 1- and 2-year intravesical recurrence-free survival rates in the early ureteral ligation group were 89% and 86%, but in the control group 74% and 64%, respectively (P = 0.025). However, intravesical recurrence-free survival rates were similar in patients with ureteral cancer. Multivariate analyses of a subset of patients with renal pelvic cancer identified early ureteral ligation as an independent predictor of intravesical recurrence.
Conclusions
Early ureteral ligation decreases the rate of intravesical recurrence after radical nephroureterectomy in patients with renal pelvic cancer. Thus, early ureteral ligation might help in prevention of intravesical recurrence for renal pelvic cancer.

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The effect of predisposing atheroembolic risk factors on renal functional recovery between laparoscopy and open technique in patients with T1-stage renal cell carcinoma who underwent partial nephrectomy: a retrospective comparison study

Abstract
Objective
The present study aimed to determine the effect of an increasing number of predisposing atheroembolic risk factors on the development of chronic kidney disease (CKD) after partial nephrectomy (PN) in patients with T1-stage renal cell carcinoma (RCC).
Methods
The study included 147 patients with T1-stage RCC with a normal contralateral kidney and without preoperative CKD, who underwent open (OPN, N = 83, 56.5%) or laparoscopic PN (LPN, N = 64, 43.5%) between 2003 and 2014. Postoperative CKD was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m2. The predictive factors for CKD between OPN and LPN were statistically assessed among various known clinicopathological factors associated with renal function in PN with a significance of two-sided P value <0.05.
Results
During a median follow-up of 42 months, the recurrence rate was 0.7% (n = 1), and the rate of postoperative CKD was 11.6% (n = 17). Significant differences in CKD-free survival were observed among patients with atheroembolic risks 5–7, 3–4 and 1–2 (P = 0.027). Regarding the predictive factors for the postoperative development of CKD between OPN and LPN, a predisposing atheroembolic risk ≥3 was significant among other clinicopathological factors in multivariate analysis (hazard ratio, 3.007, P = 0.031).
Conclusion
Patients with T1-staged RCC with ≥3 predisposing atheroembolic risk factors have a significantly higher risk of developing CKD after PN. Patients who underwent LPN had a lesser incidence of CKD development than patients who underwent OPN with ≥3 predisposing atheroembolic risk factors.

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Optimism, pessimism and self-efficacy in female cancer patients

Abstract
Objective
The aim of this examination was to study whether psychological resource variables (optimism and self-efficacy) decrease when cancer is present and to test the predictive power of these variables for anxiety, depression and quality of life (QoL).
Methods
The patient sample was comprised of 354 German women suffering from breast cancer or gynecological cancer. Participants filled in the resource assessment tools Life Orientation Test-Revised and the General Self-Efficacy Scale as well as the Hospital Anxiety and Depression Scale, the Patient Health Questionnaire-4 and the QoL instrument EORTC QLQ-C30 at two time points: (t1) during patients' hospital stay and (t2) 3 months later.
Results
The mean scores for optimism (total score: M = 16.2) and self-efficacy (M = 29.8) were even somewhat higher than the corresponding means of the general population. Optimism and self-efficacy were positively correlated with QoL (r between 0.15 and 0.17, P < 0.01) and negatively associated with anxiety and depression (r between −0.17 and −0.36, P < 0.01). However, only optimism was predictive of the t2 anxiety, depression and QoL scores when statistically taking into account the baseline levels of the outcome variables.
Conclusions
Having cancer does not generally reduce optimism and self-efficacy on the level of patients' mean scores. Cancer patients with a high level of habitual optimism will adapt to their disease better than pessimistic patients, even if the baseline levels of the outcome variables have been accounted for.

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Is preoperative spirometry a predictive marker for postoperative complications after colorectal cancer surgery?

Abstract
Background
Spirometry is a basic test that provides much information about pulmonary function; it is performed preoperatively in almost all patients undergoing colorectal cancer (CRC) surgery in our hospital. However, the value of spirometry as a preoperative test for CRC surgery remains unknown. The aim of this study was to determine whether spirometry is useful to predict postoperative complications (PCs) after CRC surgery.
Methods
The medical records of 1236 patients who had preoperative spirometry tests and underwent CRC surgery between 2005 and 2014 were reviewed. Preoperative spirometry results, such as forced vital capacity (FVC), one-second forced expiratory volume (FEV1), %VC (FVC/predicted VC) and FEV1/FVC (%FEV1), were analyzed with regard to PCs, including pneumonia.
Results
PCs were found in 383 (30.9%) patients, including 218 (56%) with surgical site infections, 67 (17%) with bowel obstruction, 62 (16%) with leakage and 20 (5.2%) with pneumonia. Of the spirometry results, %VC was correlated with PC according to logistic regression analysis (odds ratio, OR = 0.99, 95% confidence interval, CI = 0.98–0.99; P = 0.034). Multivariate analysis after adjusting for male sex, age, laparoscopic surgery, tumor location, operation time and blood loss showed that a lower %VC tends to be a risk factor for PC (OR = 0.99, 95% CI = 0.98–1.002; P = 0.159) and %VC was an independent risk factor for postoperative pneumonia in PCs (OR = 0.97, 95% CI = 0.94–0.99; P = 0.049).
Conclusions
In CRC surgery, %VC may be a predictor of postoperative complications, especially pneumonia.

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Severe esophagitis associated with cytomegalovirus during concurrent chemoradiotherapy for esophageal cancer

Abstract
Although radiation esophagitis is one of the most common adverse events that occurs during chemoradiotherapy (CRT) in patients with esophageal cancer, CRT-associated cytomegalovirus (CMV) esophagitis is rare. CMV esophagitis typically occurs in patients with an immunosuppressed status. Here we report a case of CMV esophagitis during CRT initially treated as radiation esophagitis. A 64-year-old man with mid-thoracic esophageal cancer was admitted to our hospital with clinical stage cT4bN1M1 (supraclavicular lymph node metastasis) Stage IV according to the UICC ver. 7 guidelines, and he was administered definitive concurrent CRT. From the 39th day of CRT onwards, he presented with a sustained fever and severe odynophagia that was resistant to antibiotic therapy. An esophagoscopy revealed severe esophagitis with a circumferential ulcer throughout the entire esophagus, and CMV esophagitis was clinically suspected because of positive result of CMV antigenemia. Subsequently, antiviral therapy for CMV provided dramatic relief of his symptoms. Later, CMV DNA was confirmed with a polymerase chain reaction in the biopsy specimen.The symptoms of CMV esophagitis resemble those of radiation esophagitis and can make the diagnosis difficult. Thus, CMV esophagitis associated CRT may be overlooked or masked by radiation esophagitis and can cause a delay in healing. Therefore, CMV esophagitis may be considered when severe intractable esophagitis is observed during CRT.

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Yokukansan for the treatment of preoperative anxiety and postoperative delirium in colorectal cancer patients: a retrospective study

Abstract
Background
Yokukansan (YKS), a Japanese traditional herbal medicine for neurosis and insomnia, is speculated to be useful for perioperative psychiatric symptoms in cancer patients, but there exists little empirical evidence. This study provides preliminary data about the efficacy, feasibility, and side effects of YKS for the treatment of preoperative anxiety and postoperative delirium in cancer patients.
Methods
We retrospectively reviewed the medical records of colorectal cancer patients who took YKS for preoperative anxiety, evaluating the following: (1) patient characteristics, (2) feasibility of taking YKS, (3) changes in preoperative anxiety based on the Clinical Global Impression (CGI) scale and Edmonton Symptom Assessment System-revised (ESAS-r-anxiety), (4) incidence of postoperative delirium and (5) YKS-related side effects.
Results
We reviewed 19 medical records. There was a significant difference between ESAS-r-anxiety scores (P = 0.028) before and after taking YKS, but no difference between CGI scores (P = 0.056). The incidence of postoperative delirium was 5.2% (95% CI = 0.0–14.5). One patient could not complete the course of YKS during the perioperative administration period, but there were no side effects of Grade 2 or worse according to the Common Terminology Criteria for Adverse Events v4.
Conclusions
Cancer patients could safely take YKS before surgery. There was a significant improvement in preoperative anxiety after taking YKS, and the incident rate of postoperative delirium was lower than in previous studies. These results suggest that YKS may be useful for perioperative psychiatric symptoms in cancer patients. Further well-designed studies are needed to substantiate our results.

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Efficacy of radiotherapy for primary tumor in patients with unresectable pancreatic neuroendocrine tumors

Abstract
Background
Detailed information regarding the clinical efficacy of radiotherapy (RT) for primary tumor in patients with unresectable pancreatic neuroendocrine tumors (pNETs) is unknown. We therefore performed a retrospective study to evaluate the efficacy and safety of RT for primary pancreatic tumors in patients with pNETs.
Methods
We investigated 11 patients with pNETs who received RT to the primary site between January 1997 and June 2015. Seven patients had Grade 2 neuroendocrine tumors (NET-G2) and four had neuroendocrine carcinoma (NEC) according to the 2010 WHO histopathological classification.
Results
The tumor response and control rates were 27.2% and 100%, respectively (3: partial response, 8: stable disease). Among patients with NET-G2 tumors, the response rate was 28.5% (2/7 patients) and symptomatic improvement was noted in 33.3% of the patients (1/3 patients). The response rate for patients with NEC were 25% (1/4), one NEC patients with symptoms exhibited symptomatic improvement. The median overall survival and median progression-free survival were 35.9 months and 5.5 months, respectively. Grade 3 diarrhea as an acute toxicity and Grade 3 gastrointestinal hemorrhage as a late toxicity were observed.
Conclusions
RT to the primary cancer site in patients with pNETs was an effective modality for local disease control and the treated patients had good outcomes. If metastatic tumors are under control, RT to the primary site may be beneficial for patients with pNETs.

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Effective chemomobilization with etoposide and cytarabine (EC regimen) in lymphoma patients: a single-center, retrospective, observational study

Abstract
Objective
Autologous stem cell transplantation is an important strategy for patients with relapsed or refractory lymphoma. Although various regimens for peripheral blood stem cell collection have been used, the optimal regimen has not yet been established. We aimed to evaluate the mobilization efficacy and safety of the regimen consisted of etoposide and cytarabine (EC regimen).
Methods
We retrospectively analyzed the clinical data of 46 lymphoma patients who received peripheral blood stem cell mobilization with the EC regimen [etoposide (100 mg/m2/day, days 1–4) and cytarabine (100 mg/m2/day, days 1–4)] at Toyohashi municipal hospital from 2004 to 2013.
Results
The median age of the patients was 55 years. The most common underlying diseases were diffuse large B-cell lymphoma (46%) and follicular lymphoma (26%). Three-quarters of patients were in their second complete or partial remission. The median total number of collected CD34+ cells was 10.6 × 106 kg–1. Forty-two patients (91%) yielded at least 2 × 106 kg–1 CD34+ cells within a median of 2 apheresis days, and 33 patients (72%) achieved it with only one apheresis. Successful mobilization was observed in five of six patients who failed to mobilize previously. Although febrile neutropenia occurred in 22 patients (48%), no fatal infection was observed.
Conclusion
The EC regimen was highly effective in lymphoma patients, including patients who mobilized poorly with other regimens.

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Postmarketing surveillance study of erlotinib plus gemcitabine for pancreatic cancer in Japan: POLARIS final analysis

Abstract
Objective
Erlotinib plus gemcitabine is approved in Japan for the treatment of metastatic pancreatic cancer. The POLARIS surveillance study investigated safety (focusing on interstitial lung disease [ILD]) and efficacy of erlotinib plus gemcitabine in Japanese pancreatic cancer patients.
Methods
Patients receiving erlotinib plus gemcitabine for pancreatic cancer in Japan between July 2011 and August 2012 were enrolled. ILD-like events were independently confirmed by a review committee. Overall survival (OS) and progression-free survival (PFS) were assessed, and risk factors for ILD occurrence were analyzed by multivariate Cox regression analysis.
Results
Safety data were available for 843 patients and efficacy data for 841. Adverse drug reactions were reported in 83.5% of patients, no new safety signals were identified. ILD events were confirmed by the review committee in 52 patients (6.2%), with two fatal cases (0.2%). Median time from initial erlotinib treatment to ILD events was 70.5 days. Of the 52 patients with ILD events, 86.5% improved or fully recovered from ILD (median time 24 days). Multivariate analysis identified previous or concurrent lung disease (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.0–4.5; P = 0.0365) and ≥3 organs with metastases (HR, 4.2; 95% CI, 2.2–8.2; P < 0.0001) as potential ILD risk factors. Accumulated OS rate at 28 weeks was 68.2%, and median PFS was 92 days (95% CI, 86–101).
Conclusions
Erlotinib plus gemcitabine has an acceptable safety and efficacy profile in pancreatic cancer; however, patients should be assessed for previous/concurrent lung disease and metastatic burden, before and during treatment.

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Cardiovascular toxic effects of targeted cancer therapy

Abstract
Over the past decade, there has been a major shift in chemotherapy from non-specific cytotoxic drugs to molecular targeted drug therapies. As more molecular targeted therapies are developed, new types of cardiovascular toxicities induced by targeted therapies are a growing problem. Cardiotoxicity induced by the human epidermal growth factor receptor-2 inhibitor trastuzumab manifests as decreased left ventricular ejection fraction. In contrast to anthracycline treatment, most cardiac events occur during trastuzumab treatment, but are reversed quickly when treatment is interrupted and cardiac intervention is established. Vascular endothelial growth factor pathway inhibitors decrease vascular tone, leading to hypertension. After drug initiation, the early detection and aggressive pharmacological management of hypertension are necessary to avoid severe complications. Cardiovascular safety is an emerging challenge in patients treated with newer generations of BCR-ABL inhibitors. Although rare, dasatinib-induced pulmonary hypertension is potentially fatal. Vascular events including cardiac and cerebral ischemic events and peripheral arterial occlusive disease have emerged as a new type of toxicity in patients treated with ponatinib and nilotinib. Thus, a wide variety of cardiovascular toxicities have been observed in patients treated with targeted drugs and have become a critically important topic of discussion for the practicing oncologist and cardiologists. Awareness of the potential side effects, recognition of signs and symptoms, and the establishment of therapeutic strategies are all crucial to providing quality patient care.

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