Background New direct antiviral agents (DAA) for HCV treatment result in sustained viral response (SVR) in most patients. However, predicting the point of no-return is still an unmet need for those with advanced liver disease. Aim to assess if baseline liver volume is a predictor of post-SVR liver function. Methods Cirrhotic patients assessed for liver transplantation (LT) and consecutively treated with DAA between September 2014 and 2015 who achieved an SVR were included. Pretreatment liver (LV) and spleen (SV) volumes adjusted by Body Surface Area (BSA) were calculated from CT/MR images. Liver function was assessed by Child-Turcotte-Pugh (CTP) and MELD scores and a multivariate mixed regression model was used to identify baseline factors associated with improvement of liver function overtime. Results We included 42 patients with a median age of 58.6 years (Q1-Q3: 52.7 - 68.8); MELD, 14 (11-17); CTP, 9 (8-10); LV, 1400.9 mL (1183.2-1601.4); SV, 782.9 mL (490.6-1118.8). MELD scores at baseline and at last control were 14 (11-17) and 10 (8-12), respectively (p
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Δευτέρα 30 Οκτωβρίου 2017
Brain Integrity Changes underlying Cognitive and Functional Recovery Postliver Transplant Continue to Evolve Over 1 Year
Abstract: Background There is evidence of brain recovery on brain MRI early postliver transplant(LT) but the longer-term impact is unclear. Aim of this study was to determine the change in brain MRI parameters, cognition and health-related quality of life (HRQOL) between 6 and 12 months post-LT. Methods Listed cirrhotics underwent cognitive, HRQOL and brain MRI pre, 6 months (post-LT1) and 1-year (post-LT2) post-LT. Assessment of MRI changes between visits was performed for ammonia-associated metabolite changes using spectroscopy (MRS), white matter changes using Tract-based Spatial Statistics (TBSS) analysis on Diffusion Tensor Imaging (DTI) data and grey matter changes using Voxel-based morphometry (VBM) analysis on 3D high resolution T1-weighted images. Results Forty-five patients were included of which, twenty-three were tested at all visits. Cognitive and HRQOL scores improved between all visits compared to pre-LT values. This trend continued on MRS with reduced glutamine+glutamate(Glx) and higher myoinositol(mI), Choline(Cho) between pre-LT/post-LT1 but lower degrees of improvement between post-LT1/post-LT2. On DTI, mean-diffusivity(MD), linear-diffusivity(LD) and mode of anisotropy(MO) continued to increase in the posterior internal capsule at both post-LT visits. On VBM, a continued increase was seen in basal ganglia grey matter between both post-LT visits was seen. Conclusions HRQOL and cognition continue to improve compared to pre-LT values up to 1 year post-LT, although the rate of improvement slows down after 6 months. Grey matter increase is steady over time at 1 year although changes in ammonia-related metabolites and white matter integrity improve at a slower pace at 1 year post-LT. Corresponding Author: Jasmohan S Bajaj, MD, MS, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, 1201 Broad Rock Boulevard, Richmond, VA, 23221, USA, Phone: (804) 675-5802, Fax: (804) 675 5816. Email: jasmohan.bajaj@vcuhealth.org Author contributions: JSB, VA, JS, FGM, JBW were involved in research design, performance of the research and data analysis, MBW, HSG, DMH, MF, EAG, AF, RKS, RTS, PP, AJS, MSS, SM, VL were involved in performance of the research, LRT was involved in data analysis, All authors participated in the writing of the paper. Funding: Partly supported by NIH RO1DK089713 and VA Merit Review 1I0CX001076 to JSB Disclosure: The authors declare no conflicts of interest Presentation: Portions of this study were presented as an oral presentation at the EASL conference in Amsterdam 2017. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
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Process of tight junction recovery in the injured vocal fold epithelium: Morphological and paracellular permeability analysis
Objectives/Hypothesis
The vocal fold epithelium that includes tight junction (TJ)-based barrier function protects underlying connective tissues from external insults. TJs play an important role to control paracellular permeability of not only solutes but also ions, and preserve the vocal fold homeostasis. However, the distribution of TJs and paracellular diffusion barrier across the entire vocal fold epithelium are still unknown. The aim of this study was to identify the distribution of TJs in the vocal fold epithelium and to characterize the recovery process of TJ-based paracellular diffusion barrier in a rat model of vocal fold injury.
Study Design
Animal experiments with controls.
Methods
Normal and vocal fold–injured rats were used. Larynges were harvested for immunohistochemical examination of TJ proteins. For functional analysis, a tracer permeability assay was performed using EZ-Link Sulfo-NHS-LC-Biotin.
Results
TJ proteins occludin and zonula occludens 1 signals were localized to the junctional regions of the most luminal cell layers of the vocal fold epithelium. The injured region had been recovered with epithelium at 5 days postinjury, but the paracellular diffusion barrier assays revealed that biotinylation reagents diffused into the lamina propria at 5 days postinjury, and were blocked at the epithelium at 14 and 28 days postinjury.
Conclusions
It was strongly suggested that TJs in the vocal fold epithelium exist at the junctional regions of the first layer of stratified squamous epithelium. TJ-based paracellular diffusion barrier following vocal fold injury is recovered by 14 days postinjury, and this period corresponds with the time course of structural changes in the regenerating epithelium layer.
Level of Evidence
NA Laryngoscope, 2017
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MRSA chronic bacterial laryngitis: A growing problem
Objectives
Chronic bacterial infection of the larynx is characterized by long-standing hoarseness and exudative laryngitis. Prolonged antibiotic therapy is required to clear the infection, and methicillin-resistant staphylococcus aureus (MRSA) may be the responsible pathogen. The objective of this study was to describe the presentation, comorbidities, treatment response, and underlying etiology— including the incidence of MRSA—in our patient population with chronic bacterial laryngitis.
Methods
A review of patients with a diagnosis of chronic bacterial laryngitis from 2012 to 2016 was performed. Diagnosis of chronic bacterial laryngitis was based on clinical history and findings on flexible laryngoscopy. In selected cases, the diagnosis of bacterial laryngitis was confirmed by operative biopsy. Information regarding clinical presentation and course was collected.
Results
Twenty-eight patients were included in the study. Twenty-three were treated empirically with Amoxicillin-clavulonic acid for a minimum of 21 days. Twelve of the 23 (52%) had recurrence or nonresolution of infection. Seven of the 12 nonresponders (58%) were found to have MRSA by laryngeal tissue culture. Five patients were treated initially with Sulfamethoxazole and trimethoprim, and all resolved the infection without the need for further treatment. There was a nonstatistically significant increase in smoking and reflux in the MRSA population compared to the non-MRSA group.
Conclusion
MRSA infection was documented in 30% of patients overall with chronic bacterial laryngitis. Based on the results of the study, a treatment algorithm for management of this unusual patient population is suggested.
Level of Evidence
4. Laryngoscope, 2017
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Selective recurrent laryngeal nerve stimulation using a penetrating electrode array in the feline model
Objectives/Hypothesis
Laryngeal muscles (LMs) are controlled by the recurrent laryngeal nerve (RLN), injury of which can result in vocal fold (VF) paralysis (VFP). We aimed to introduce a bioelectric approach to selective stimulation of LMs and graded muscle contraction responses.
Study Design
Acute experiments in cats.
Methods
The study included six anesthetized cats. In four cats, a multichannel penetrating microelectrode array (MEA) was placed into an uninjured RLN. For RLN injury experiments, one cat received a standardized hemostat-crush injury, and one cat received a transection-reapproximation injury 4 months prior to testing. In each experiment, three LMs (thyroarytenoid, posterior cricoarytenoid, and cricothyroid muscles) were monitored with an electromyographic (EMG) nerve integrity monitoring system. Electrical current pulses were delivered to each stimulating channel individually. Elicited EMG voltage outputs were recorded for each muscle. Direct videolaryngoscopy was performed for visualization of VF movement.
Results
Stimulation through individual channels led to selective activation of restricted nerve populations, resulting in selective contraction of individual LMs. Increasing current levels resulted in rising EMG voltage responses. Typically, activation of individual muscles was successfully achieved via single placement of the MEA by selection of appropriate stimulation channels. VF abduction was predominantly observed on videolaryngoscopy. Nerve histology confirmed injury in cases of RLN crush and transection experiments.
Conclusions
We demonstrated the ability of a penetrating MEA to selectively stimulate restricted fiber populations within the feline RLN and selectively elicit contractions of discrete LMs in both acute and injury-model experiments, suggesting a potential role for intraneural MEA implantation in VFP management.
Level of Evidence
NA Laryngoscope, 2017
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Upper airway stimulation therapy and prior airway surgery for obstructive sleep apnea
Objective
To determine if patients with prior airway surgery for obstructive sleep apnea (OSA) had increased benefit following implantation with hypoglossal nerve stimulator.
Study Design
Retrospective chart review at a single institution tertiary academic care center.
Methods
Following implantation with hypoglossal nerve stimulator device, the outcomes of patients who underwent prior airway surgery for OSA were compared with those who did not. Primary outcome measures included apnea-hypopnea index (AHI) and nadir oxyhemoglobin saturation (NOS) as measured by polysomnography. Secondary outcome measures included Epworth Sleepiness Scale.
Results
Forty-seven patients underwent implantation with hypoglossal nerve stimulator. Of these, 30 patients had undergone prior airway surgery for OSA, whereas 16 did not. Mean preoperative AHI and NOS were 39.3 ± 2.8 and 78% ± 1.8% for all patients, 39.4 ± 3.7 and 79% ± 14% for patients with prior airway surgery, and 39.1 ± 4.0 and 77% ± 2.6% for patients without prior surgery. Mean postoperative AHI and NOS were 3.9 ± 1.2 and 91% ± 0.4% for all patients, 4.2 ± 1.7 and 91% ± 0.5% for patients with prior surgery, and 3.4 ± 1.5 and 93% ± 0.6% for patients without prior surgery (P = 0.756 and 0.053, respectively).
Conclusion
Overall, patients had significant improvement following implantation with hypoglossal nerve stimulator. Prior airway surgery had no statistically significant effect on postoperative AHI or NOS.
Level of Evidence
4. Laryngoscope, 2017
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Oropharyngeal squamous cell carcinoma incidence and mortality trends in the United States, 1973–2013
Objective
To analyze oropharyngeal squamous cell carcinoma incidence and mortality trends in the United States for the years 1973 through 2013.
Study Design
Cross-sectional study using a large population-based cancer database.
Methods
Data on incidence and mortality rates were extracted from the Surveillance, Epidemiology, and End Results (SEER) 9 Database. Annual percentage change in rates was calculated using Joinpoint regression analysis (National Cancer Institute, Bethesda, MD).
Results
Incidence rates increased (annual percent change [APC]; 1.52, 95% confidence interval [CI] 0.17 to 2.88) from 1973 to 1983, remained stable (APC −0.52, 95% CI −1.30 to 0.26) from 1983 to 1997, and increased (APC 1.32, 95% CI 0.83 to 1.81) from 1997 to 2013. Overall, incidence rates increased for males (APC 0.73, 95% CI 0.22 to 1.25) but not females (APC −0.77, 95% CI −0.68 to 0.82). Incidence rates increased in the white population (APC 0.79, 95% CI 0.33 to 1.25) but decreased in the black population (APC −0.72, 95% CI −1.41 to −0.02). The incidence rates increased for tongue-base tumors (APC 1.17, 95% CI 0.42 to 1.92) and tonsil tumors (APC 0.47, 95% CI 1.10 to 4.96) but decreased for other sites. Incidence-based mortality decreased (APC −0.78, 95% CI −1.13 to −0.42) from 1993 to 2013.
Conclusion
Oropharyngeal squamous cell carcinoma incidence rates increased in a nonlinear fashion from 1973 to 2013, whereas mortality rates declined. This, along with variation in trends by demographic and tumor factors, suggest that human papilloma virus is the main driver of the recent rise in incidence.
Level of Evidence
2b. Laryngoscope, 2017
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A matched comparison of human papillomavirus–induced squamous cancer of unknown primary with early oropharynx cancer
Objectives/Hypothesis
Patients with human papillomavirus (HPV)–induced cancer of unknown primary (CUP) are generally excluded from clinical trials, despite surgical series reporting detection rates of occult oropharynx primaries of >80%. We performed a matched-pair analysis to compare outcomes between T0N1-3M0 HPV+ CUP and T1-2N1-3M0 HPV+ oropharynx known primary (OPX).
Study Design
Retrospective cohort study at a single institution.
Methods
Patients with early T stage, node positive HPV+ OPX or CUP treated with curative intent between 1998 and 2016 were identified. For a subgroup of CUP patients with an unknown HPV status, we imputed HPV status and included patients with a >80% probability of being HPV+. Cohorts were matched based on patient demographics using a nearest neighbor propensity technique. After matching, patients were grouped according to either a favorable or unfavorable risk stratification designations per current NRG Oncology clinical trial enrollment criteria. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier analysis.
Results
Of 298 patients with T1-2N1-3 OPX, 48 were matched to 48 HPV+ CUP patients (32 with confirmed and 16 imputed HPV status). Median follow-up for CUP (34.1 months) and OPX (27.8 months) patients were similar (P = .23).There were no significant differences between the CUP and OPX groups for 3-year DFS (89% vs. 85%, P = .44), and 3-year OS (91% vs. 91%, P = .11), respectively.
Conclusions
Patients with T0N+M0 HPV-induced CUP have similar survival outcomes to matched patients with T1-2N+M0 HPV+ OPX. These patients can reasonably be included in clinical trials investigating the role of treatment deintensification and risk stratified similar to patients with early-stage known primary OPX cancer.
Level of Evidence
4. Laryngoscope, 2017
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Feasibility of preservation of chorda tympani nerve during noninflammatory ear surgery: A systematic review
Objective
The objective of our systematic review is to investigate the postoperative gustatory function of the chorda tympani nerve following noninflammatory ear surgery for which the chorda tympani is at risk for iatrogenic injury (stretching, handling, or sacrificing).
Data Sources
PubMed and EMBASE.
Review Methods
A PubMed and EMBASE databases search was conducted on November 15, 2016. Study inclusion criteria included: 1) ear surgery performed for noninflammatory ear diseases, and 2) gustatory function of the chorda tympani reported as an outcome. The quality of eligible studies was assessed using the risk of bias assessment tool for nonrandomized studies. Study characteristics and outcome data of the included studies were extracted.
Results
In total 1,094 articles were retrieved. Fourteen studies encompassing 1,062 operated ears were included after quality assessment. Stapedectomy was the most frequent surgical procedure performed in 398 ears. The follow-up time varied between 6 weeks and 99 months. Patients with a preserved chorda tympani were less symptomatic (24% was symptomatic) compared to patients with a stretched (53% was symptomatic) or sacrificed chorda tympani (47% was symptomatic). The recovery rate varied from 61% to 79%. The results of the electrogustometry and strip test showed a discrepancy with the subjective complaints of the patients.
Conclusion
Patients with a stretched chorda tympani were slightly more symptomatic compared to patients with a sacrificed chorda tympani. Therefore, in cases for which the chorda tympani greatly hinders a proper view of the surgical field, sacrificing the nerve could be considered to maximize surgical performance and have a satisfactory postoperative result. Laryngoscope, 2017
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Utility of intraoperative imaging in cochlear implantation: A systematic review
Background
Many institutions routinely perform intraoperative imaging during cochlear implant (CI) surgery to determine accurate electrode placement. Different modalities exist; however, there remains some controversy regarding the usefulness of intraoperative imaging.
Objective
Systematically review the utility of intraoperative imaging in CI surgery and implications for management.
Methods
PubMed, EMBASE, Medline, CINAHL, and Cochrane library were searched from inception to April 2017. Studies analyzing the use of intraoperative imaging during CI surgery were included. Outcome measures included unsatisfactory placement and change in management. Two independent evaluators reviewed each abstract and article.
Results
Two hundred and sixty-seven articles were identified. Of those, 17 met inclusion criteria. There were no randomized controlled trials. Intraoperative X-rays were performed in 917 CIs in eight studies. Placement was unsatisfactory on radiograph in 19 implants (3.5%), and management was changed in 18 of 19 (94.7%). Intraoperative computed tomography (CT) was performed in 69 CIs in seven studies. Placement was unsatisfactory on CT in two implants (3.0%), and management was changed in both (100%). Intraoperative real-time fluoroscopy was performed in 20 CIs in two studies to help guide correct placement. Twenty-two of these patients had abnormal cochleas. Fifteen out of 17 studies concluded that intraoperative imaging is useful, especially with challenging anatomy or when the surgeon questions placement.
Conclusion
Intraoperative imaging detects unsatisfactory placement of electrodes during CI surgery at a low, but not negligible, rate. The current literature is not conclusive regarding the utility of routine imaging, but it appears to be most useful with abnormal cochlear anatomy or when the surgeon questions placement.
Level of Evidence
NA. Laryngoscope, 2017
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CXCL13 expression is prognostic and predictive for postoperative adjuvant chemotherapy benefit in patients with gastric cancer
Abstract
Background
Chemokine (C-X-C motif) ligand 13 (CXCL13/BLC/BCA-1) is a cytokine from C-X-C chemokine family, which is selectively chemotactic for B cells. Previous research has demonstrated that high CXCL13 expression is correlated to poor prognosis in various cancers. However, the association between CXCL13 expression and gastric cancer is still unclear.
Methods
Intratumoral CXCL13 expression was evaluated by immunohistochemistry using a semi-quantitative method (modified H-score) in a testing set of 214 and a validation set of 227 randomly selected gastric cancer patients resected in 2008 in one institution. The median value was used as the cut-off point. We performed correlative analysis of CXCL-13 expression with clinicopathological variables, Kaplan–Meier analysis for association with overall survival (OS), and multivariate modeling.
Results
High CXCL13 expression was associated with larger tumor diameter and shorter OS. By multivariate analysis, CXCL13 expression was associated with OS independently from clinicopathological factors. Within the T2–4 stage patients group, low CXCL13 expression was associated with longer survival, especially in the subgroup of patients (57.6%) who received adjuvant chemotherapy.
Conclusions
Intratumoral CXCL13 expression appears as an independent prognostic marker for patients after gastric cancer resection. In addition, CXCL13 expression may serve as a predictive biomarker of response to postoperative adjuvant chemotherapy in these patients.
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Unnecessary preoperative biliary drainage: impact on perioperative outcomes of resectable periampullary tumors
Abstract
Objective
Routine preoperative endoscopic biliary drainage (PEBD) is not recommended for malignant periampullary tumors (MPT) with uncomplicated obstructive cholestasis, yet many patients still receive routine PEBD. Herein were assessed perioperative outcomes of routine PEBD in resectable MPT with uncomplicated biliary obstruction.
Methods
From 2008 to 2014, we identified three groups among patients undergoing surgery for resectable MPT: "unnecessary-PEBD" (despite recommendations), "necessary-PEBD" (following recommendations), and "upfront-surgery groups." The first two groups were compared on referral patterns, drainage procedure, and post-PEBD complications; "Unnecessary-PEBD" and "upfront-surgery" groups were compared on perioperative outcomes.
Results
A total 140 patients underwent surgery for resectable MPT; 38 had cholestasis with clear PEBD indication ("necessary-PEBD"). A further 66 presented uncomplicated obstructive cholestasis with total bilirubin < 300 μmol/l, of whom 26 had unnecessary PEBD and 40 underwent upfront surgery. In total, 40.1% of PEBD were unnecessary and 64.1% were performed before surgical consultation. Time-to-surgery was significantly increased in the "unnecessary-PEBD" group by a mean ± SD 35.3 ± 5.5 days as compared to "upfront-surgery" group (95%CI [24.4–46.2]; p < 0.001). The "unnecessary-PEBD" group had a post-PEBD complication rate of 34.6%, and 7.7% were unresectable due to severe fibrosis following PEBD-induced acute pancreatitis. Perioperative severe complication rate was higher in the "unnecessary-PEBD" (73.1%) than in the "upfront-surgery" group (37.5%, p = 0.005), as was Clavien-Dindo grade > II post-operative complication rate (65.4 and 37.5%; p = 0.03).
Conclusion
Routine preoperative biliary drainage is associated with an increased morbidity and persists despite recommendations against its systematic use. Early multidisciplinary team discussions with pancreatic surgeons should be implemented with an aim to reduce unnecessary stenting and improve patient outcomes.
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Clinical Results and Technical Complications of Posterior Implant-Supported Modified Monolithic Zirconia Single Crowns and Short-Span Fixed Dental Prostheses: A 2-Year Pilot Study
Abstract
Purpose
The purpose of this clinical trial was to investigate the clinical outcomes of implant-supported modified monolithic zirconia single crowns (SCs) and short-span fixed dental prostheses (FDPs) after a follow-up of 2 years.
Materials and Methods
Twenty-seven patients in need of implant-supported SCs or 3-unit FDPs in the posterior maxilla or mandible were consecutively selected for this study. A total of 56 modified monolithic zirconia prostheses including 44 SCs (8 screw-retained, 36 cement-retained) and twelve 3-unit FDPs (5 screw-retained, 7 cement-retained) were included in this study. All patients were followed at 6 months, 12 months, 18 months, and 2 years after placement of the modified monolithic zirconia prostheses. During the follow-up period, all prostheses were evaluated with clinical and radiographic examinations. The following technical parameters were assessed: framework fracture, fracture of veneering porcelain, screw loosening, loss of retention because of prosthesis de-cementation and opposing tooth fracture.
Results
No implant was lost during the follow-up period, yielding a 2-year implant survival of 100%. One FDP failed because of framework fracture. The overall prosthesis survival rate was 98.2% after 2 years of clinical service. During the study, 5 complication events were observed in 3 SCs and one FDP, including one fracture of veneering porcelain and 2 screw loosenings in 3 SCs, and loss of retention and opposing tooth fracture in the same FDP. Therefore, the complication-free rate of prostheses was 91.1%.
Conclusion
According to the results of this study, the modified monolithic zirconia design used in this study resulted in a favorable short-term outcome for posterior implant-supported SCs and 3-unit FDPs.
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Analysis of Shade Matching in Natural Dentitions Using Intraoral Digital Spectrophotometer in LED and Filtered LED Light Sources
Abstract
Purpose
To evaluate the shade matching capabilities in natural dentitions using Vita Toothguide 3D-Master and an intraoral digital spectrophotometer (Vita Easyshade Advance 4.0) in various light sources.
Materials and Methods
Participants between 20 and 40 years old with natural, unrestored right maxillary central incisors, no history of bleaching, orthodontic treatment, or malocclusion and no rotations were included. According to their shades, subjects were randomly selected and grouped into A1, A2, and A3. A total of 100 participants (50 male and 50 female) in each group were chosen for this study. Shade selection was made between 10 am and 2 pm for all light sources. The same examiner selected the shade of natural teeth with Vita Toothguide 3D-Master under natural light within 2 minutes. Once the Vita Toothguide 3D-Masterwas matched with the maxillary right central incisor, the L*, a*, and b* values, chroma, and hue were recorded with Vita Easyshade Advance 4.0 by placing it on the shade tab under the same light source. The values were statistically analyzed using one-way ANOVA and Tukey's HSD post hoc test with SPSS v22.0 software.
Results
The mean ∆E*ab values for shades A1, A2, and A3 for groups 1, 2, and 3 were statistically significantly different from each other (p < 0.001).
Conclusion
The intraoral digital spectrophotometer showed statistically significant differences in shade matching compared to Vita Toothguide 3D-Master. Incandescent light showed more accurate shade matching than the filtered LED, LED, and daylight.
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Tooth Color as a Predictor of Oral Health-Related Quality of Life in Young Adults
Abstract
Purpose
Smiling plays an important role in social interaction. The purpose of this research was to explore the extent to which objective parameters of color of one's own teeth affected the social and emotional dimensions of young adults' lives.
Materials and Methods
The sample included 134 subjects—students of the University of Rijeka, Croatia (65% female) aged 19 to 28 years (median 21). All subjects had six intact maxillary anterior teeth without restorations or severe malocclusions and healthy gingiva with no signs of inflammation. Tooth color was assessed intraorally using a spectrophotometer. Lightness, chroma, and translucency of the right maxillary central incisors (the reference teeth) were calculated and used for analysis. Subjects reported dimensions of their oral health-related quality of life (OHRQoL) using the Oral Health Impact Profile (OHIP), Orofacial Esthetic Scale (OES), and the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ). Linear relationships between elements of tooth color and OHRQoL were explored using Pearson correlations. Multiple linear regression, while controlling for the influence of age and gender, was also calculated. ANOVA with a Tukey post hoc test was employed to test whether nonlinear relationships existed between OHRQoL and categories of color elements.
Results
Dental self-confidence, esthetic concerns, orofacial appearance, social impact and psychological impact were not related to lightness, chroma, or translucency of the subjects' teeth. Neither linear nor nonlinear relationships were detected between those aspects. Satisfaction with smile esthetics was only related to translucency where subjects with moderate translucency were least likely to be satisfied (p = 0.033). Women tended to report greater psychosocial impacts than men (p < 0.05), regardless of their tooth color.
Conclusion
According to the results of this study objective, measurable, quantitative parameters of tooth color did not accurately predict psychosocial dimensions of OHRQoL in dentate young adults.
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A Prospective International Multicentre Cohort Study of Intraoperative Heart Rate and Systolic Blood Pressure and Myocardial Injury After Noncardiac Surgery: Results of the VISION Study
BACKGROUND: The association between intraoperative cardiovascular changes and perioperative myocardial injury has chiefly focused on hypotension during noncardiac surgery. However, the relative influence of blood pressure and heart rate (HR) remains unclear. We investigated both individual and codependent relationships among intraoperative HR, systolic blood pressure (SBP), and myocardial injury after noncardiac surgery (MINS). METHODS: Secondary analysis of the Vascular Events in Noncardiac Surgery Cohort Evaluation (VISION) study, a prospective international cohort study of noncardiac surgical patients. Multivariable logistic regression analysis tested for associations between intraoperative HR and/or SBP and MINS, defined by an elevated serum troponin T adjudicated as due to an ischemic etiology, within 30 days after surgery. Predefined thresholds for intraoperative HR and SBP were: maximum HR >100 beats or minimum HR 160 mm Hg or minimum SBP 100 bpm was associated with MINS (odds ratio [OR], 1.27 [1.07–1.50]; P 160 mm Hg was associated with MINS (OR, 1.16 [1.01–1.34]; P = .04) and myocardial infarction (OR, 1.34 [1.09–1.64]; P = .01) but, paradoxically, reduced mortality (OR, 0.76 [0.58–0.99]; P = .04). Minimum HR 100 bpm was more strongly associated with MINS (OR, 1.42 [1.15–1.76]; P
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Impact of Anesthetic Regimen on Remote Ischemic Preconditioning in the Rat Heart In Vivo
Remote ischemic preconditioning (RIPC) seems to be a promising cardioprotective strategy with contradictive clinical data suggesting the anesthetic regimen influencing the favorable impact of RIPC. This study aimed to investigate whether cardio protection by RIPC is abolished by anesthetic regimens. Male Wistar rats were randomized to 6 groups. Anesthesia was either maintained by pentobarbital (Pento) alone or a combination of sevoflurane (Sevo) and remifentanil or propofol (Prop) and remifentanil in combination with and without RIPC. RIPC reduced infarct size in Pento- and Sevo-anesthetized rats (Pento-RIPC: 30% ± 9% versus Pento-control [Con]: 65% ± 6%, P
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Healthcare Simulation Education: Evidence, Theory and Practice, 1st ed.
The Local, Global Perspective
A Left Ventricle to Left Atrial Appendage Fistula After Mitral Valve Replacement
Pressure Waveform Analysis
Monitoring cardiac output is of special interest for detecting early hemodynamic impairment and for guiding its treatment. Among the techniques that are available to monitor cardiac output, pressure waveform analysis estimates cardiac output from the shape of the arterial pressure curve. It is based on the general principle that the amplitude of the systolic part of the arterial curve is proportional to cardiac output and arterial compliance. Such an estimation of cardiac output has the advantage of being continuous and in real time. With "calibrated" devices, the initial estimation of cardiac output by pressure waveform analysis is calibrated by measurements of cardiac output made by transpulmonary thermal or lithium dilution. Later, at each time transpulmonary dilution is performed, the estimation by pressure waveform analysis, which may drift over time, is calibrated again. By contrast, uncalibrated devices do not use any independent measurement of cardiac output. Unlike calibrated devices, they can be plugged to any arterial catheter. Nevertheless, uncalibrated devices are not reliable in cases of significant short-term changes in arterial resistance, as for instance in patients undergoing liver surgery or those with vasodilatory shock receiving vasopressors. Perioperative hemodynamic monitoring is recommended for high-risk surgical patients since it reduces the number of complications in these patients. The pressure waveform analysis monitoring, especially with uncalibrated devices, is suitable for this purpose. In the intensive care setting, hemodynamic monitoring is recommended for patients with acute circulatory failure, who do not respond to initial therapy. Since these patients often experience large changes in arterial resistance, either spontaneously or due to vasoactive drugs, calibrated devices are more suitable in this context. Not only are they more reliable than uncalibrated devices but also they provide a comprehensive hemodynamic assessment through measurements of a variety of transpulmonary thermodilution-related variables. In this review, we summarize the characteristics of the monitoring devices using the pressure waveform analysis and discuss the appropriate use of different devices in the perioperative and intensive care unit settings. Accepted for publication August 30, 2017. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Jean-Louis Teboul, MD, PhD, Service de réanimation médicale, Hôpitaux universitaires Paris-Sud, Hôpital de Bicêtre, 78 rue du Général Leclerc, Le Kremlin-Bicêtre F-94270, France. Address e-mail to jean-louis.teboul@aphp.fr. © 2017 International Anesthesia Research Society
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Anaesthesia for the Elderly Patient, 2nd ed.
The Effect of Adding Subarachnoid Epinephrine to Hyperbaric Bupivacaine and Morphine for Repeat Cesarean Delivery: A Double-Blind Prospective Randomized Control Trial
BACKGROUND: Spinal anesthesia has become the most common type of anesthetic for cesarean delivery. The major limitation to spinal anesthesia is that the duration of the anesthetic may not be adequate in the event of a prolonged surgery. Some practitioners add epinephrine to hyperbaric bupivacaine to increase the duration, although its effect has not been fully studied. We therefore aimed to evaluate whether adding epinephrine to the spinal medication prolongs the duration of action of the resultant block in women presenting for repeat cesarean delivery. METHODS: Sixty-eight patients were randomized to receive no epinephrine (NE group), epinephrine 100 µg (low-dose [LD] group), or epinephrine 200 µg (high-dose [HD] group) with a standardized spinal mixture (1.5 mL 0.75% hyperbaric bupivacaine with 0.25 mg morphine). Sixty-five patients were included for primary analysis. Our primary outcome was time to intraoperative activation of the epidural catheter or postoperative regression of sensory blockade to T-10 dermatome level as measured by pinprick sensation; motor recovery was a secondary outcome, and graded via a Modified Bromage scale. RESULTS: Block onset time, vital sign changes, and the incidence of hypotension; nausea, and vomiting were similar among groups. Median difference in time to T-10 regression was greatest in the HD group compared to the NE group (median difference [min] [95% confidence interval]: 40 [15–60]; P = .007), followed by the HD group to the LD group (30 [15–45]; P = .007). Comparisons of LD to NE were not significant, but trended to an increase in T-10 regression time (10 [−15 to 30]; P = .76). Median difference in time to knee extension (Bromage 3) was also greatest in the HD group when compared to both the LD and NE group (median difference [min] [95% confidence interval]: 30 [0–60]; P = .034, 60 [0–93]; P = .007). Median difference time to knee extension (min) between the LD and NE group was also significant (37.5 [15–60]; P = .001]. Pain scores during the procedure were higher in the NE group (median [interquartile range] HD: 0 [0–0], LD: 0 [0–0], NE: 0 [0–3]; P = .02) during uterine closure and were otherwise not significantly different from the other groups. CONCLUSIONS: In this single center, prospective, double-blind, randomized control trial, the addition of epinephrine 200 µg to hyperbaric bupivacaine and preservative-free morphine for repeat cesarean delivery prolonged the duration of the sensory blockade. Motor blockade was similarly prolonged and block quality may have been enhanced. Accepted for publication August 30, 2017. Funding: Funding for this study was procured though the Icahn School of Medicine at Mount Sinai. Clinical Trial # (ClinicalTrials.gov): NCT02369510. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Daniel Katz, MD, Department of Anesthesiology, Pain, and Perioperative Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Pl, KCC 8th Floor Box 1010, New York, NY 10029. Address e-mail to Daniel.Katz@MountSinai.org. © 2017 International Anesthesia Research Society
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Use of 3D Transesophageal Echocardiography and the Clock-Face Model to Localize and Facilitate Closure of a Mitral Paravalvular Defect
Synthetic regulatory RNAs selectively suppress the progression of bladder cancer
The traditional treatment for cancer is lack of specificity and efficacy. Modular synthetic regulatory RNAs, such as inhibitive RNA (iRNA) and active RNA (aRNA), may overcome these limitations. Here, we synthe...
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Prognostic Significance of Macroscopic Appearance in Clear Cell Renal Cell Carcinoma and Its Metastasis-Predicting Model
Prognostic significance of macroscopic appearance of clear cell renal cell carcinoma (ccRCC) has not yet been studied. This study aimed to define the prognostic significance of macroscopic appearance and to propose a prognostic model for post-operative metastasis in ccRCC. A total of 1,025 patients with ccRCC were analyzed for the development dataset. A separate cohort of 399 such patients was used as an external validation dataset. Macroscopic appearances were initially divided into four groups, but were later divided into two groups: a simple nodular group (700 cases, 68.3%) and an irregular outline group (325 cases, 32.7%). During the 66.1-month mean follow-up period, 98 patients (9.6%) developed metastasis. Univariate analysis revealed that metastasis was associated with older age, radical nephrectomy, larger tumor size, higher tumor grade and stage, and the irregular outline group. On multivariate analysis, age, tumor size, and macroscopic appearance remained as independent prognostic factors. These factors were used to build a prognostic model, which divided into three risk groups. The probabilities of 5-year metastasis-free survival in the low-, intermediate-, and high-risk groups were 98%, 83%, and 53%, respectively. The results showed prognostic significance of macroscopic appearance in ccRCC and propose a prognostic model to guide post-operative management of patients with ccRCC.
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Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids
Abstract
Background
Cancer cells that enter the metastatic cascade require traits that allow them to survive within the circulation and colonize distant organ sites. As disseminating cancer cells adapt to their changing microenvironments, they also modify their metabolism and metabolite production.
Methods
A mouse xenograft model of spontaneous tumor metastasis was used to determine the metabolic rewiring that occurs between primary cancers and their metastases. An "autonomous" mass spectrometry-based untargeted metabolomic workflow with integrative metabolic pathway analysis revealed a number of differentially regulated metabolites in primary mammary fat pad (MFP) tumors compared to microdissected paired lung metastases. The study was further extended to analyze metabolites in paired normal tissues which determined the potential influence of metabolites from the microenvironment.
Results
Metabolomic analysis revealed that multiple metabolites were increased in metastases, including cholesterol sulfate and phospholipids (phosphatidylglycerols and phosphatidylethanolamine). Metabolite analysis of normal lung tissue in the mouse model also revealed increased levels of these metabolites compared to tissues from normal MFP and primary MFP tumors, indicating potential extracellular uptake by cancer cells in lung metastases. These results indicate a potential functional importance of cholesterol sulfate and phospholipids in propagating metastasis. In addition, metabolites involved in DNA/RNA synthesis and the TCA cycle were decreased in lung metastases compared to primary MFP tumors.
Conclusions
Using an integrated metabolomic workflow, this study identified a link between cholesterol sulfate and phospholipids, metabolic characteristics of the metastatic niche, and the capacity of tumor cells to colonize distant sites.
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The pathogenesis of cutaneous squamous cell carcinoma in organ transplant recipients
Summary
The pathogenesis of keratinocyte carcinoma following organ transplantation is multifactorial, and recent evidence suggests a complex and often synergistic interplay between the carcinogenic effects of ultraviolet radiation, compromised immune surveillance, direct pro- and anticarcinogenic effects of drugs, oncogenic viruses (in particular, beta-genus human papillomaviruses) and host genetic susceptibility factors. We present an overview of those factors for which there is currently the most convincing evidence and highlight important gaps in our knowledge. In particular, a clear understanding of the interdependence and relative contributions of these co-factors is currently lacking, yet has important implications for rational development of clinically relevant biomarkers and targeted strategies for treatment and prevention of post-transplant keratinocyte cancers.
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Research gaps in the management and prevention of cutaneous squamous cell carcinoma in organ transplant recipients
Summary
Although tremendous progress has been made in recent years in skin cancer care for organ transplant recipients, significant gaps remain in data-driven clinical guidelines, particularly for the treatment and prevention of cutaneous squamous cell carcinoma (cSCC), the most common malignancy among this population. In this review, we aim to summarize current knowledge around the management of cSCC and highlight the most significant gaps in knowledge that continue to pose challenges in the delivery of skin cancer care for organ transplant recipients. We suggest future directions for research that will bridge existing gaps and establish evidence-driven guidelines for primary prevention, screening and treatment of cSCC in this high-risk patient population.
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A New Age of Communication Powered by Purposeful Innovation
This course covers Phonak's latest product introductions as well as software and programming details to promote successful patient hearing instrument fittings.
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Language Outcomes in Children Who Are Deaf and Hard of Hearing: The Role of Language Ability Before Hearing Aid Intervention
Purpose
Early auditory experiences are fundamental in infant language acquisition. Research consistently demonstrates the benefits of early intervention (i.e., hearing aids) to language outcomes in children who are deaf and hard of hearing. The nature of these benefits and their relation with prefitting development are, however, not well understood. Method
This study examined Ontario Infant Hearing Program birth cohorts to explore predictors of performance on the Preschool Language Scale–Fourth Edition at the time of (N = 47) and after (N = 19) initial hearing aid intervention. Results
Regression analyses revealed that, before the hearing aid fitting, severity of hearing loss negatively predicted 19% and 10% of the variance in auditory comprehension and expressive communication, respectively. After hearing aid fitting, children's standard scores on language measures remained stable, but they made significant improvement in their progress values, which represent individual skills acquired on the test, rather than standing relative to same-age peers. Magnitude of change in progress values was predicted by a negative interaction of prefitting language ability and severity of hearing loss for the Auditory Comprehension scale. Conclusions
These findings highlight the importance of considering a child's prefitting language ability in interpreting eventual language outcomes. Possible mechanisms of hearing aid benefit are discussed. Supplemental Materials
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Associations Between the 2D:4D Proxy Biomarker for Prenatal Hormone Exposures and Symptoms of Developmental Language Disorder
Purpose
Relative lengths of the index (2D) and ring (4D) fingers in humans represent a retrospective biomarker of prenatal hormonal exposures. For this reason, the 2D:4D digit ratio can be used to investigate potential hormonal contributions to the etiology of neurodevelopmental disorders. This study tested potential group differences in 2D:4D digit ratios in a sample of boys with and without developmental language disorder (DLD) and examined the strength of associations between 2D:4D digit ratio and a battery of verbal and nonverbal measures. Method
A group of 29 boys affected by DLD and a group of 76 boys with typical language abilities participated (age range = 5;6–11;0 years). Scanned images were used to measure finger lengths. Language measures included the core language subtests from the Clinical Evaluation of Language Fundamentals–Fourth Edition (Semel, Wiig, & Secord, 2003), a nonword repetition task, a sentence recall task, and the Test of Early Grammatical Impairment (Rice & Wexler, 2001). Results
Significant group differences indicated lower 2D:4D digit ratios in the group with DLD. Modest associations were found between 2D:4D digit ratios and some Clinical Evaluation of Language Fundamentals–Fourth Edition subtests. Conclusions
Prenatal hormone exposures may play a role in the etiology of some language symptoms.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_JSLHR-L-17-0143/2661523/Associations-Between-the-2D4D-Proxy-Biomarker-for
Predicting Intelligibility Gains in Individuals With Dysarthria From Baseline Speech Features
Purpose
Across the treatment literature, behavioral speech modifications have produced variable intelligibility changes in speakers with dysarthria. This study is the first of two articles exploring whether measurements of baseline speech features can predict speakers' responses to these modifications. Methods
Fifty speakers (7 older individuals and 43 speakers with dysarthria) read a standard passage in habitual, loud, and slow speaking modes. Eighteen listeners rated how easy the speech samples were to understand. Baseline acoustic measurements of articulation, prosody, and voice quality were collected with perceptual measures of severity. Results
Cues to speak louder and reduce rate did not confer intelligibility benefits to every speaker. The degree to which cues to speak louder improved intelligibility could be predicted by speakers' baseline articulation rates and overall dysarthria severity. Improvements in the slow condition could be predicted by speakers' baseline severity and temporal variability. Speakers with a breathier voice quality tended to perform better in the loud condition than in the slow condition. Conclusions
Assessments of baseline speech features can be used to predict appropriate treatment strategies for speakers with dysarthria. Further development of these assessments could provide the basis for more individualized treatment programs.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2016_JSLHR-S-16-0218/2661025/Predicting-Intelligibility-Gains-in-Individuals
Predicting Intelligibility Gains in Dysarthria Through Automated Speech Feature Analysis
Purpose
Behavioral speech modifications have variable effects on the intelligibility of speakers with dysarthria. In the companion article, a significant relationship was found between measures of speakers' baseline speech and their intelligibility gains following cues to speak louder and reduce rate (Fletcher, McAuliffe, Lansford, Sinex, & Liss, 2017). This study reexamines these features and assesses whether automated acoustic assessments can also be used to predict intelligibility gains. Method
Fifty speakers (7 older individuals and 43 with dysarthria) read a passage in habitual, loud, and slow speaking modes. Automated measurements of long-term average spectra, envelope modulation spectra, and Mel-frequency cepstral coefficients were extracted from short segments of participants' baseline speech. Intelligibility gains were statistically modeled, and the predictive power of the baseline speech measures was assessed using cross-validation. Results
Statistical models could predict the intelligibility gains of speakers they had not been trained on. The automated acoustic features were better able to predict speakers' improvement in the loud condition than the manual measures reported in the companion article. Conclusions
These acoustic analyses present a promising tool for rapidly assessing treatment options. Automated measures of baseline speech patterns may enable more selective inclusion criteria and stronger group outcomes within treatment studies.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_JSLHR-S-16-0453/2661026/Predicting-Intelligibility-Gains-in-Dysarthria
Odontogenic sinusitis: developments in diagnosis, microbiology, and treatment.
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Delayed complications from expanded endonasal surgery for intracranial tumors.
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Review and update on postoperative opioid use after nasal and sinus surgery.
Purpose of review: We examine the current literature on pain management after sinus and nasal surgery. The goal after surgery is to provide effective pain management without having too many 'leftovers', as leftover medications are an important source of opioids that are fueling the current prescription narcotic epidemic in the United States. There are more than 250 000 sinus operations and 260 000 septoplasties performed annually, and surgeons commonly prescribe a narcotic pain medication for postoperative pain management. Recent findings: The literature suggests that an evidence-based approach may lead surgeons to prescribe significantly less narcotic pain medication for these procedures without affecting pain management. Summary: An evidence-based approach to pain management can result in unchanged pain control and a significant positive impact on the narcotic abuse epidemic. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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Value of T1-weighted Magnetic Resonance Imaging in Cholesteatoma Detection.
Objective: To reveal the usefulness of T1-weighted (T1W) imaging on diagnostic magnetic resonance (MR) imaging for cholesteatoma. Study Design: A retrospective case review. Setting: Tertiary referral center. Patients: Fifty-three patients (57 ears) suspected to have cholesteatomas and treated (6-82 yr of age). Intervention: Preoperative MR imaging, including non-echo planar (non-EP) diffusion-weighted (DW) and T1W imaging. Main Outcome Measures: Primary outcome measures included the comparison between the diagnostic accuracy for the detection of cholesteatomas using non-EP DW imaging alone (criterion 1) and non-EP DW imaging along with T1W imaging (criterion 2). Diagnostic accuracy was evaluated in each case by comparing MR imaging with surgical findings. Secondary outcome measures included the comparison of the rates of cases showing a high T1W signal between cholesteatomas and noncholesteatomas which showed a high non-EP DW signal. Results: The sensitivity, specificity, and accuracy according to criterion 1 were 93.5, 63.6, and 87.7% and those according to criterion 2 were 89.1, 100, and 91.2%, respectively. Of 43 cholesteatoma cases indicating a high non-EP DW signal, only 2 cases showed a high T1W signal (5%). On the other hand, all four noncholesteatoma cases indicating high non-EP DW signal showed a high T1W signal (100%), and these rates were significantly different (p
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Usefulness of Electrical Auditory Brainstem Responses to Assess the Functionality of the Cochlear Nerve Using an Intracochlear Test Electrode.
Objective: To use an intracochlear test electrode to assess the integrity and the functionality of the auditory nerve in cochlear implant (CI) recipients and to compare electrical auditory brainstem responses (eABR) via the test electrode with the eABR responses with the CI. Setting: Otolaryngology department, tertiary referral hospital. Patients: Ten subjects (age at implantation 55 yr, range, 19-72) were subsequently implanted with a MED-EL CONCERTO CI on the side without any useful residual hearing. Interventions: Following identification of the round window (RW), the test electrode was inserted in the cochlea previous to cochlear implantation. Main Outcome Measures: To assess the quality of an eABR waveform, scoring criteria from Walton et al. (2008) were chosen. The waveforms in each session were classified by detecting waves III and V by the algorithm and visual assessment of the waveform. Speech performance was evaluated with monosyllables, disyllables, and sentence recognition tests. Results: It was possible to evoke electrical stimulation responses along with both the test electrode and the CI in all subjects. No significant differences in latencies or amplitudes after stimulation were found between the test electrode and the CI. All subjects obtained useful hearing with their CI and use their implants daily. Conclusions: The intracochlear test electrode may be suitable to test the integrity of the auditory nerve by recording eABR signals. This allows for further research on the status of the auditory nerve after tumor removal and correlation with auditory performance. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company
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The Etiological Relationship Between Migraine and Sudden Hearing Loss.
Objectives: To investigate the relationship between sudden sensorineural hearing loss (SSNHL) and migraine, assess the prevalence of migraine in patients with idiopathic SSNHL, and determine a possible common vascular etiopathogenesis for migraine and SSNHL. Study Design: Prospective cohort study. Setting: Tertiary referral center. Patients: This study initially assessed 178 SSNHL cases obtained from the Head and Neck Surgery Clinic patient database at a tertiary hospital in Turkey between January 2011 and March 2016. Ultimately, a total of 61 idiopathic SSNHL patients participated in the present study. Interventions: Diagnostic. Main Outcome Measures: Cases with inflammation in the middle or inner ear; a retro cochlear tumor; autoimmune, infectious, functional, metabolic, neoplastic, traumatic, toxic, or vascular causes; Meniere's disease; otosclerosis; multiple sclerosis; and/or cerebrovascular diseases were excluded. Results: Of the 61 idiopathic SSHNL patients, 34 were women (55.74%); and 24 (39.34%) had migraine, according to the criteria of the International Headache Society (IHS). The mean age of the migraine patients (Group 1) was 43.83 +/- 13.16 years, and that of those without migraine (Group 2) was 51.05 +/- 16.49 years. The groups did not significantly differ in terms of age, sex, or SSNHL recovery rates according to the Siegel criteria (p > 0.05). Ten of the migraine patients experienced visual aura, and the recovery rates of this group were higher. Additionally, the rate of total hearing loss was lower in Group 1 (n = 3, 12.5%) than in Group 2 (n = 10, 27%). Conclusion: SSNHL patients had a higher prevalence of migraine. Although those with migraine had higher recovery rates, the differences were not statistically significant. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company
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Therapeutic Mastoidectomy Does Not Increase Postoperative Complications in the Management of the Chronic Ear.
Objective: Tympanoplasty with or without concurrent therapeutic mastoidectomy is a controversial topic in the management of chronic ear disease. We sought to describe whether there is a significant difference in postoperative complications. Study Design: Retrospective cohort study. Setting: American College of Surgeons National Surgical Quality Improvement Program public files. Patients: Current procedural terminology codes were used to identify patients with chronic ear disease undergoing tympanoplasty +/- concurrent mastoidectomy in the 2011 to 14 American College of Surgeons National Surgical Quality Improvement Program files. Intervention: Therapeutic. Main Outcome Measures: Variables were compared with [chi]2, Fischer's exact, and Mann-Whitney U tests, as appropriate to analyze postoperative complications between tympanoplasty with or without concurrent mastoidectomy. To account for confounding factors, presence of a complication was analyzed in binary logistic regression. Analysis considered sex, hypertension, obesity, advanced age, diabetes, smoking status, American Society of Anesthesiologists Physical status, procedure. Results: There were 4,087 patients identified meeting criteria (tympanoplasty = 2,798, tympanomastoidectomy = 1,289). There was no statistical difference in postoperative complications (tympanoplasty n = 49 [1. 8%], tympanomastoidectomy n = 33 [2. 6%]; p = 0. 087) or return to the operating room (tympanoplasty = 4 [0. 1%], tympanomastoidectomy = 6 [0. 5%]; p = 0. 082). Binary logistic regression demonstrated smoking as a predictor of a postoperative complication (OR: 1. 758, 95% CI: 1. 084-2. 851; p = 0. 022), while concurrent mastoidectomy did not significantly increase the risk of complication (OR: 1. 440, 95% CI: 0. 915-2. 268; p = 0. 115). There was a significant difference in mean operative time between tympanoplasty and tympanomastoidectomy: 85.7 versus 154.23 min, p
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Intracochlear Measurements of Interaural Time and Level Differences Conveyed by Bilateral Bone Conduction Systems.
Hypothesis: Intracochlear pressures (PIC) and stapes velocity (Vstap) elicited by bilaterally placed bone-anchored hearing devices (BAHD) will be systematically modulated by imposed interaural time (ITD) and level differences (ILD), demonstrating the potential for users of bilateral BAHD to access these binaural cues. Background: BAHD are traditionally implanted unilaterally under the assumption that transcranial cross-talk limits interaural differences. Recent studies have demonstrated improvements in binaural and spatial performance with bilateral BAHD; however, objective measures of binaural cues from bilateral BAHDs are lacking. Methods: Bone-conduction transducers were coupled to both mastoids of cadaveric specimens via implanted titanium abutments. PIC and Vstap were measured using intracochlear pressure probes and laser Doppler vibrometry, respectively, during stimulation with pure-tone stimuli of varied frequency (250-4000 Hz) under ipsilateral, contralateral, and bilateral ITD (-1 to 1 ms) and ILD (-20 to 20 dB) conditions. Results: Bilateral stimulation produced constructive and destructive interference patterns that varied dramatically with ITD and stimulus frequency. Variation of ITD led to large variation of PIC and Vstap, with opposing effects in ipsilateral and contralateral ears expected to lead to "ITD to ILD conversion." Variation of ILD produced more straightforward (monotonic) variations of PIC and Vstap, with ipsilateral-favoring ILD producing higher PIC and Vstap than contralateral-favoring. Conclusion: Variation of ITDs and ILDs conveyed by BAHDs systematically modulated cochlear inputs. While transcranial cross-talk leads to complex interactions that depend on cue type and stimulus frequency, binaural disparities potentiate binaural benefit, providing a basis for improved sound localization and speech-in-noise perception. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company
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CD31 Expression Determines Redox Status and Chemoresistance in Human Angiosarcomas
Purpose: Angiosarcomas (AS) are soft tissue sarcomas with endothelial differentiation and vasoformative capacity. Most AS show strong constitutive expression of the endothelial adhesion receptor CD31/PECAM-1 pointing to an important role of this molecule. However, the biological function of CD31 in AS is unknown. Experimental Design: The expression levels of CD31 in AS cells and its effects on cell viability, colony formation and chemoresistance was evaluated in human AS clinical samples and in cell lines through isolation of CD31high and CD31low cell subsets. The redox-regulatory CD31 function linked to YAP signaling was determined using a CD31 blocking antibody and siRNA approach and was further validated in CD31-knockout endothelial cells. Results: We found that most AS contain a small CD31low cell population. CD31low cells had lost part of their endothelial properties, were more tumorigenic and chemoresistant than CD31high cells due to more efficient reactive oxygen species (ROS) detoxification. Active downregulation of CD31 resulted in loss of endothelial tube formation, nuclear accumulation of YAP, and YAP-dependent induction of antioxidative enzymes. Addition of pazopanib, a known enhancer of proteasomal YAP degradation re-sensitized CD31low cells for doxorubicin resulting in growth suppression and induction of apoptosis. Conclusions: Human AS contain a small aggressive CD31low population that have lost part of their endothelial differentiation programs and are more resistant against oxidative stress and DNA damage due to intensified YAP signaling. Our finding that the addition of YAP inhibitors can re-sensitize CD31low cells towards doxorubicin may aid in the rational development of novel combination therapies to treat AS.
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Clinical and Immunological Biomarkers for Histologic Regression of High Grade Cervical Dysplasia and Clearance of HPV16 and HPV18 after Immunotherapy
Purpose: As previously reported, treatment of high grade cervical dysplasia with VGX-3100 resulted in complete histopathologic regression (CR) concomitant with elimination of HPV16/18 infection in 40.0% of VGX-3100-treated patients compared to only 14.3% in placebo recipients in a randomized PhaseIIb study. Here, we identify clinical and immunological characteristics that either predicted or correlated with therapeutic benefit from VGX-3100 to identify parameters that might guide clinical decision-making for this disease. Experimental Design: We analyzed samples taken from cervical swabs, whole blood and tissue biopsies/resections to determine correlates and predictors of treatment success. Results. At study entry, the presence of pre-existing immunosuppressive factors such as FoxP3 and PD-L1 in cervical lesions showed no association with treatment outcome. The combination of HPV typing and cervical cytology following dosing was predictive for both histologic regression and elimination of detectable virus at the efficacy assessment twenty two weeks later (negative predictive value 94%). Patients treated with VGX-3100 who had lesion regression had a statistically significant >2-fold increase in CD137+perforin+CD8+ Tcells specific for the HPV genotype causing disease. Increases in cervical mucosal CD137+ and CD103+ infiltrates were observed only in treated patients. Perforin+ cell infiltrates were significantly increased >2-fold in cervical tissue only in treated patients who had histologic CR. Conclusion. Quantitative measures associated with an effector immune response to VGX-3100 antigens were associated with lesion regression. Consequently, these analyses indicate that certain immunologic responses associate with successful resolution of HPV-induced pre-malignancy, with particular emphasis on the upregulation of perforin in the immunotherapy induced immune response.
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A Randomized, Double-blind, Placebo-controlled Phase 2 Study of Ontuxizumab (MORAb-004) in Patients with Chemorefractory Metastatic Colorectal Cancer
Purpose: The purpose of this study was to evaluate the safety and efficacy of ontuxizumab (MORAb-004), a monoclonal antibody that interferes with endosialin (tumor endothelial marker-1 [TEM-1]) function, in patients with chemorefractory metastatic colorectal cancer and to identify a responsive patient population based on biomarkers. Design: This was a randomized, double-blind, placebo-controlled, Phase 2 study. Patients were randomly assigned in a 2:1 ratio to receive weekly intravenous ontuxizumab (8 mg/kg) or placebo plus best supportive care (BSC) until progression or unacceptable toxicity. Tissue and blood biomarkers were evaluated for their ability to identify a patient population that was responsive to ontuxizumab. Results: A total of 126 patients were enrolled. No significant difference between the ontuxizumab and placebo groups was evident for the primary endpoint of progression-free survival (PFS), with a median PFS of 8.1 weeks in each group (hazard ratio of 1.13; 95% confidence interval: 0.76, 1.67; P=0.53). There were no significant differences between groups for overall survival (OS) or overall response rate (ORR). The most common treatment-emergent adverse events (TEAEs) in the ontuxizumab group (vs the placebo group, respectively) were fatigue (53.7% vs 47.5%), nausea (39.0% vs 35.0%), decreased appetite (34.1% vs 27.5%), and constipation (28.0% vs 32.5%). The most common Grade 3/4 TEAE in the ontuxizumab group vs placebo was back pain (11.0% vs 0%). No single biomarker clearly identified patients responsive to ontuxizumab. Conclusion: No benefit with ontuxizumab monotherapy compared with placebo for clinical response parameters of PFS, OS, or ORR was demonstrated. Ontuxizumab was well tolerated.
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Global metabolic profiling identifies a pivotal role of proline and hydroxyproline metabolism in supporting hypoxic response in hepatocellular carcinoma.
Purpose: Metabolic reprogramming is frequently identified in hepatocellular carcinoma, which is the most common type of liver malignancy. The reprogrammed cellular metabolisms promote tumor cell survival, proliferation, angiogenesis and metastasis. However, the mechanisms of this process remain unclear in hepatocellular carcinoma. Experimental Design: Theglobal non-targeted metabolic studyin 69 paired hepatic carcinomas and adjacent tissue specimens were performed using capillary electrophoresis-time of flight mass spectrometry (CE-TOF/MS)-based approach. Key findings were validated by targeted metabolomic approach. Biological studies were also performed to investigate the role of proline biosynthesis in HCC pathogenesis. Results: Proline metabolism wasmarkedly changed in HCC tumor tissue, characterized withaccelerated consumption of proline and accumulation of hydroxyproline, which significantly correlated with α-fetoproteinlevels and poor prognosisin HCC.In addition, we found that hydroxyproline promoted hypoxia- and HIF-dependent phenotype in HCC. Moreover, we demonstrated that hypoxia activated proline biosynthesis via upregulation of ALDH18A, subsequently leading to accumulation of hydroxyproline via attenuated PRODH2 activity. More importantly, we showed that glutamine, proline and hydroxyproline metabolic axis supported HCC cell survival through modulating HIF1α stability in response to hypoxia. Finally, Inhibition of proline biosynthesis significantly enhanced cytotoxicity of sorafenib in vitro and in vivo. Conclusions: Our results demonstrate that hypoxic microenvironment activates proline metabolism, resulting in accumulation of hydroxyproline that promotes HCC tumor progression and sorafenib resistance through modulating HIF1α. These findings provide the proof of concept for targeting proline metabolism as a potential therapeutic strategy for hepatocellular carcinoma.
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Hypoxia-inducible PIM kinase expression promotes resistance to anti-angiogenic agents
Purpose: Patients develop resistance to anti-angiogenic drugs, secondary to changes in the tumor microenvironment, including hypoxia. PIM kinases are pro-survival kinases and their expression increases in hypoxia. The goal of this study was to determine whether targeting hypoxia-induced PIM kinase expression is effective in combination with VEGF-targeting agents. The rationale for this therapeutic approach is based on the fact that anti-angiogenic drugs can make tumors hypoxic, and thus more sensitive to PIM inhibitors. Experimental Design: Xenograft and orthotopic models of prostate and colon cancer were used to assess the effect of PIM activation on the efficacy of VEGF-targeting agents. Immunohistochemistry and in vivo imaging were used to analyze angiogenesis, apoptosis, proliferation, and metastasis. Biochemical studies were performed to characterize the novel signaling pathway linking PIM and HIF-1. Results: PIM was upregulated following treatment with anti-VEGF therapies, and PIM1 overexpression reduced the ability of these drugs to disrupt vasculature and block tumor growth. PIM inhibitors reduced HIF-1 activity, opposing the shift to a pro-angiogenic gene signature associated with hypoxia. Combined inhibition of PIM and VEGF produced a synergistic anti-tumor response characterized by decreased proliferation, reduced tumor vasculature, and decreased metastasis. Conclusions: This study describes PIM kinase expression as a novel mechanism of resistance to anti-angiogenic agents. Our data provide justification for combining PIM and VEGF inhibitors to treat solid tumors. The unique ability of PIM inhibitors to concomitantly target HIF-1 and selectively kill hypoxic tumor cells addresses two major components of tumor progression and therapeutic resistance.
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Inhibition of REDD1 sensitizes bladder urothelial carcinoma to paclitaxel by inhibiting autophagy
Purpose: Regulated in development and DNA damage response-1 (REDD1) is a stress related protein and is involved in the progression of cancer. The role and regulatory mechanism of REDD1 in bladder urothelial carcinoma (BUC), however, is yet unidentified. Experimental Design: The expression of REDD1 in BUC was detected by western blot and immunohistochemistry. The correlation between REDD1 expression and clinical features in BUC patients were assessed. The effects of REDD1 on cellular proliferation, apoptosis, autophagy, and paclitaxel sensitivity were determined both in vitro and in vivo. Then the targeted-regulating mechanism of REDD1 by microRNAs was explored. Results: Here the significant increase of REDD1 expression is detected in BUC tissue, and REDD1 is firstly reported as an independent prognostic factor in BUC patients. Silencing REDD1 expression in T24 and EJ cells decreased cell proliferation, increased apoptosis, and decreased autophagy, whereas the ectopic expression of REDD1 in RT4 and BIU87 cells had the opposite effect. Additionally, the REDD1-mediated proliferation, apoptosis, and autophagy are found to be negatively regulated by miR-22 in vitro, which intensify the paclitaxel sensitivity via inhibition of the well-acknowledged REDD1-EEF2K-autophagy axis. AKT/mTOR signaling initially activated or inhibited in response to silencing or enhancing REDD1 expression and then recovered rapidly. Lastly, the inhibited REDD1 expression by either RNAi or miR-22 sensitizes BUC tumor cells to paclitaxel in a subcutaneous transplant sarcoma model in vivo. Conclusion: REDD1 is confirmed as an oncogene in BUC, and antagonizing REDD1 could be a potential therapeutic strategy to sensitize BUC cells to paclitaxel.
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Targeting CDH17 in cancer: when blocking the ligand beats blocking the receptor?
Cadherin-17 (CDH17) has been implicated as pro-tumorigenic for many years but mechanisms have been unclear. A Spanish team have generated antibodies to an RGD-motif in CDH17 that inhibits integrin α2β1 binding to CDH17 and thereby inhibits integrin activation, tumorigenesis and metastasis. These reagents may have therapeutic potential.
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The effects of an 8-week stabilization exercise program on lumbar multifidus muscle thickness and activation as measured with ultrasound imaging in patients with low back pain: An exploratory study
Lumbar statilization exercise programs (LSEP) produce positive effects on clinical outcomes, but the underlying mechanisms remain fairly unexplored. Psychological and neuromuscular mechanisms can be involved such as a better activation of the lumbar multifidus which represents one possibility.
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Mandarin (Simplified) Chinese Version of the Voice Activity and Participation Profile: Adaptation and Validation
The purpose of this study was to evaluate the reliability and validity of the Mandarin (simplified) Chinese version of Voice Activity and Participation Profile (MC-VAPP) in mainland China.
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Idiopathic Supraglottic Stenosis Refractory to Multiple Interventions Improved With Serial Office-based Steroid Injections
The objective of this study was to describe a patient with idiopathic supraglottic stenosis who experienced persistent disease despite multiple office-based and operative interventions, whose disease is now better controlled with scheduled serial office-based steroid injections.
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Prevalence and Risk Factors of Self-reported Voice Problems Among Yakshagana Artists
Yakshagana /jakʃaga:na/ is a form of folk theater of India. It is a blend of music, acting, dance, costume, dialogue, and stage techniques with an exclusive style and form. Even though Yakshagana artists (singers and actors) are professional voice users, no reports are available in the literature regarding the prevalence of voice problems (VPs) in these performers.
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Value of T1-weighted Magnetic Resonance Imaging in Cholesteatoma Detection.
Objective: To reveal the usefulness of T1-weighted (T1W) imaging on diagnostic magnetic resonance (MR) imaging for cholesteatoma. Study Design: A retrospective case review. Setting: Tertiary referral center. Patients: Fifty-three patients (57 ears) suspected to have cholesteatomas and treated (6-82 yr of age). Intervention: Preoperative MR imaging, including non-echo planar (non-EP) diffusion-weighted (DW) and T1W imaging. Main Outcome Measures: Primary outcome measures included the comparison between the diagnostic accuracy for the detection of cholesteatomas using non-EP DW imaging alone (criterion 1) and non-EP DW imaging along with T1W imaging (criterion 2). Diagnostic accuracy was evaluated in each case by comparing MR imaging with surgical findings. Secondary outcome measures included the comparison of the rates of cases showing a high T1W signal between cholesteatomas and noncholesteatomas which showed a high non-EP DW signal. Results: The sensitivity, specificity, and accuracy according to criterion 1 were 93.5, 63.6, and 87.7% and those according to criterion 2 were 89.1, 100, and 91.2%, respectively. Of 43 cholesteatoma cases indicating a high non-EP DW signal, only 2 cases showed a high T1W signal (5%). On the other hand, all four noncholesteatoma cases indicating high non-EP DW signal showed a high T1W signal (100%), and these rates were significantly different (p
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Usefulness of Electrical Auditory Brainstem Responses to Assess the Functionality of the Cochlear Nerve Using an Intracochlear Test Electrode.
Objective: To use an intracochlear test electrode to assess the integrity and the functionality of the auditory nerve in cochlear implant (CI) recipients and to compare electrical auditory brainstem responses (eABR) via the test electrode with the eABR responses with the CI. Setting: Otolaryngology department, tertiary referral hospital. Patients: Ten subjects (age at implantation 55 yr, range, 19-72) were subsequently implanted with a MED-EL CONCERTO CI on the side without any useful residual hearing. Interventions: Following identification of the round window (RW), the test electrode was inserted in the cochlea previous to cochlear implantation. Main Outcome Measures: To assess the quality of an eABR waveform, scoring criteria from Walton et al. (2008) were chosen. The waveforms in each session were classified by detecting waves III and V by the algorithm and visual assessment of the waveform. Speech performance was evaluated with monosyllables, disyllables, and sentence recognition tests. Results: It was possible to evoke electrical stimulation responses along with both the test electrode and the CI in all subjects. No significant differences in latencies or amplitudes after stimulation were found between the test electrode and the CI. All subjects obtained useful hearing with their CI and use their implants daily. Conclusions: The intracochlear test electrode may be suitable to test the integrity of the auditory nerve by recording eABR signals. This allows for further research on the status of the auditory nerve after tumor removal and correlation with auditory performance. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company
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from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2xC3vlY
The Etiological Relationship Between Migraine and Sudden Hearing Loss.
Objectives: To investigate the relationship between sudden sensorineural hearing loss (SSNHL) and migraine, assess the prevalence of migraine in patients with idiopathic SSNHL, and determine a possible common vascular etiopathogenesis for migraine and SSNHL. Study Design: Prospective cohort study. Setting: Tertiary referral center. Patients: This study initially assessed 178 SSNHL cases obtained from the Head and Neck Surgery Clinic patient database at a tertiary hospital in Turkey between January 2011 and March 2016. Ultimately, a total of 61 idiopathic SSNHL patients participated in the present study. Interventions: Diagnostic. Main Outcome Measures: Cases with inflammation in the middle or inner ear; a retro cochlear tumor; autoimmune, infectious, functional, metabolic, neoplastic, traumatic, toxic, or vascular causes; Meniere's disease; otosclerosis; multiple sclerosis; and/or cerebrovascular diseases were excluded. Results: Of the 61 idiopathic SSHNL patients, 34 were women (55.74%); and 24 (39.34%) had migraine, according to the criteria of the International Headache Society (IHS). The mean age of the migraine patients (Group 1) was 43.83 +/- 13.16 years, and that of those without migraine (Group 2) was 51.05 +/- 16.49 years. The groups did not significantly differ in terms of age, sex, or SSNHL recovery rates according to the Siegel criteria (p > 0.05). Ten of the migraine patients experienced visual aura, and the recovery rates of this group were higher. Additionally, the rate of total hearing loss was lower in Group 1 (n = 3, 12.5%) than in Group 2 (n = 10, 27%). Conclusion: SSNHL patients had a higher prevalence of migraine. Although those with migraine had higher recovery rates, the differences were not statistically significant. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company
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from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A1x5CU
Therapeutic Mastoidectomy Does Not Increase Postoperative Complications in the Management of the Chronic Ear.
Objective: Tympanoplasty with or without concurrent therapeutic mastoidectomy is a controversial topic in the management of chronic ear disease. We sought to describe whether there is a significant difference in postoperative complications. Study Design: Retrospective cohort study. Setting: American College of Surgeons National Surgical Quality Improvement Program public files. Patients: Current procedural terminology codes were used to identify patients with chronic ear disease undergoing tympanoplasty +/- concurrent mastoidectomy in the 2011 to 14 American College of Surgeons National Surgical Quality Improvement Program files. Intervention: Therapeutic. Main Outcome Measures: Variables were compared with [chi]2, Fischer's exact, and Mann-Whitney U tests, as appropriate to analyze postoperative complications between tympanoplasty with or without concurrent mastoidectomy. To account for confounding factors, presence of a complication was analyzed in binary logistic regression. Analysis considered sex, hypertension, obesity, advanced age, diabetes, smoking status, American Society of Anesthesiologists Physical status, procedure. Results: There were 4,087 patients identified meeting criteria (tympanoplasty = 2,798, tympanomastoidectomy = 1,289). There was no statistical difference in postoperative complications (tympanoplasty n = 49 [1. 8%], tympanomastoidectomy n = 33 [2. 6%]; p = 0. 087) or return to the operating room (tympanoplasty = 4 [0. 1%], tympanomastoidectomy = 6 [0. 5%]; p = 0. 082). Binary logistic regression demonstrated smoking as a predictor of a postoperative complication (OR: 1. 758, 95% CI: 1. 084-2. 851; p = 0. 022), while concurrent mastoidectomy did not significantly increase the risk of complication (OR: 1. 440, 95% CI: 0. 915-2. 268; p = 0. 115). There was a significant difference in mean operative time between tympanoplasty and tympanomastoidectomy: 85.7 versus 154.23 min, p
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Intracochlear Measurements of Interaural Time and Level Differences Conveyed by Bilateral Bone Conduction Systems.
Hypothesis: Intracochlear pressures (PIC) and stapes velocity (Vstap) elicited by bilaterally placed bone-anchored hearing devices (BAHD) will be systematically modulated by imposed interaural time (ITD) and level differences (ILD), demonstrating the potential for users of bilateral BAHD to access these binaural cues. Background: BAHD are traditionally implanted unilaterally under the assumption that transcranial cross-talk limits interaural differences. Recent studies have demonstrated improvements in binaural and spatial performance with bilateral BAHD; however, objective measures of binaural cues from bilateral BAHDs are lacking. Methods: Bone-conduction transducers were coupled to both mastoids of cadaveric specimens via implanted titanium abutments. PIC and Vstap were measured using intracochlear pressure probes and laser Doppler vibrometry, respectively, during stimulation with pure-tone stimuli of varied frequency (250-4000 Hz) under ipsilateral, contralateral, and bilateral ITD (-1 to 1 ms) and ILD (-20 to 20 dB) conditions. Results: Bilateral stimulation produced constructive and destructive interference patterns that varied dramatically with ITD and stimulus frequency. Variation of ITD led to large variation of PIC and Vstap, with opposing effects in ipsilateral and contralateral ears expected to lead to "ITD to ILD conversion." Variation of ILD produced more straightforward (monotonic) variations of PIC and Vstap, with ipsilateral-favoring ILD producing higher PIC and Vstap than contralateral-favoring. Conclusion: Variation of ITDs and ILDs conveyed by BAHDs systematically modulated cochlear inputs. While transcranial cross-talk leads to complex interactions that depend on cue type and stimulus frequency, binaural disparities potentiate binaural benefit, providing a basis for improved sound localization and speech-in-noise perception. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company
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from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A2iXZZ
Detection of voice changes due to aspiration via acoustic voice analysis
Aspiration can occur during swallowing. The present study investigated the feasibility of identifying aspiration risk (AR) via acoustic voice parameters.
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Modified lateral orbital wall decompression in Graves’ orbitopathy using computer-assisted planning
Graves' orbitopathy, a condition seen in the autoimmune syndrome Graves' disease, affects the fatty tissue and muscles inside the orbit. Graves' orbitopathy is associated with increasing exophthalmos and sometimes leads to compressive dysthyroid optic neuropathy, resulting in progressive vision loss. Dysthyroid compressive optic neuropathy, functional problems, and cosmetic problems are the main indications for surgical decompression of the orbit, especially if conservative treatment has not led to a reduction in symptoms.
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Does incorporating collagen and chondroitin sulfate matrix in implant surfaces enhance osseointegration? A systematic review and meta-analysis
Implant surface modification has been used to improve osseointegration. However, evidence regarding improved new bone formation (NBF) and osseointegration with the use of collagen–chondroitin sulfate (CS) matrix coated implants remains unclear. The aim of this study was to assess the efficacy of collagen–CS matrix coating on the osseointegration of implants. The focused question was "Does the incorporation of collagen–CS matrix in implant surfaces influence osseointegration?" To answer the question, indexed databases were searched up to July 2017 using various combinations of the key words "collagen", "chondroitin sulfate", "osseointegration", and "implants".
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Effect of Peroral Administration of Chromium on Insulin Signaling Pathway in Skeletal Muscle Tissue of Holstein Calves
Abstract
The objective of this study was to investigate the effects of peroral administration of chromium-enriched yeast on glucose tolerance in Holstein calves, assessed by insulin signaling pathway molecule determination and intravenous glucose tolerance test (IVGTT). Twenty-four Holstein calves, aged 1 month, were chosen for the study and divided into two groups: the PoCr group (n = 12) that perorally received 0.04 mg of Cr/kg of body mass daily, for 70 days, and the NCr group (n = 12) that received no chromium supplementation. Skeletal tissue samples from each calf were obtained on day 0 and day 70 of the experiment. Chromium supplementation increased protein content of the insulin β-subunit receptor, phosphorylation of insulin receptor substrate 1 at Tyrosine 632, phosphorylation of Akt at Serine 473, glucose transporter-4, and AMP-activated protein kinase in skeletal muscle tissue, while phosphorylation of insulin receptor substrate 1 at Serine 307 was not affected by chromium treatment. Results obtained during IVGTT, which was conducted on days 0, 30, 50, and 70, suggested an increased insulin sensitivity and, consequently, a better utilization of glucose in the PoCr group. Lower basal concentrations of glucose and insulin in the PoCr group on days 30 and 70 were also obtained. Our results indicate that chromium supplementation improves glucose utilization in calves by enhancing insulin intracellular signaling in the skeletal muscle tissue.
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Tracing Tellurium and Its Nanostructures in Biology
Abstract
Tellurium (Te) is a semimetal rare element in nature. Together with oxygen, sulfur (S), and selenium (Se), Te is considered a member of chalcogen group. Over recent decades, Te applications continued to emerge in different fields including metallurgy, glass industry, electronics, and applied chemical industries. Along these lines, Te has recently attracted research attention in various fields. Though Te exists in biologic organisms such as microbes, yeast, and human body, its importance and role and some of its potential implications have long been ignored. Some promising applications of Te using its inorganic and organic derivatives including novel Te nanostructures are being introduced. Before discovery and straightforward availability of antibiotics, Te had considered and had been used as an antibacterial element. Antilishmaniasis, antiinflammatory, antiatherosclerotic, and immuno-modulating properties of Te have been described for many years, while the innovative applications of Te have started to emerge along with nanotechnological advances over the recent years. Te quantum dots (QDs) and related nanostructures have proposed novel applications in the biological detection systems such as biosensors. In addition, Te nanostructures are used in labeling, imaging, and targeted drug delivery systems and are tested for antibacterial or antifungal properties. In addition, Te nanoparticles show novel lipid-lowering, antioxidant, and free radical scavenging properties. This review presents an overview on the novel forms of Te, their potential applications, as well as related toxicity profiles.
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Protective Effect of Selenium on Aflatoxin B1-Induced Testicular Toxicity in Mice
Abstract
Aflatoxins have been considered as one of the major risk factors of male infertility, and aflatoxin B1 (AFB1) is the most highly toxic and prevalent member of the aflatoxins family. Selenium (Se), an essential nutritional trace mineral for normal testicular development and male fertility, has received extensive intensive on protective effects of male reproductive system due to its potential antioxidant and activating testosterone synthesis. To investigate the protective effect of Se on AFB1-induced testicular toxicity, the mice were orally administered with AFB1 (0.75 mg/kg) and Se (0.2 mg/kg or 0.4 mg/kg) for 45 days. We found that that Se elevated testes index, sperm functional parameters (concentration, malformation, and motility), and the level of serum testosterone in AFB1-exposed mice. Moreover, our results showed that Se attenuated the AFB1-induced oxidative stress and the reduction of testicular testosterone synthesis enzyme protein expression such as steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage (P450scc), and 17β-hydroxysteroid dehydrogenase (17β-HSD) in AFB1-exposed mice. These results demonstrated that Se conferred protection against AFB1-induced testicular toxicity and can be attributed to its antioxidant and increased testosterone level by stimulating protein expression of StAR and testosterone synthetic enzymes.
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Effects of Ag Nanoparticles on Growth and Fat Body Proteins in Silkworms ( Bombyx mori )
Abstract
Ag nanoparticles (AgNPs), a widely used non-antibiotic, antibacterial material, have shown toxic and other potentially harmful effects in mammals. However, the deleterious effects of AgNPs on insects are still unknown. Here, we studied the effects of AgNPs on the model invertebrate organism Bombyx mori. After feeding silkworm larvae different concentrations of AgNPs, we evaluated the changes of B. mori body weights, survival rates, and proteomic differences. The results showed that low concentrations (<400 mg/L) of AgNPs promoted the growth and cocoon weights of B. mori. Although high concentrations (≥800 mg/L) of AgNPs also improved B. mori growth, they resulted in silkworm death. An analysis of fat body proteomic differences revealed 13 significant differences in fat body protein spots, nine of which exhibited significantly downregulated expression, while four showed significantly upregulated expression. Reverse transcription–polymerase chain reaction results showed that at an AgNP concentration of 1600 mg/L, the expression levels of seven proteins were similar to the transcription levels of their corresponding genes. Our results suggest that AgNPs lowered the resistance to oxidative stress, affected cell apoptosis, and induced cell necrosis by regulating related protein metabolism and metabolic pathways in B. mori.
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Ameliorated Effects of (−)-Epigallocatechin Gallate Against Toxicity Induced by Vanadium in the Kidneys of Wistar Rats
Abstract
The aim of the study was to assess the protective effect of (−)-epigallocatechin gallate (EGCG), a flavonoid abundant in green tea, against ammonium metavanadate (AMV)-induced oxidative stress in male Wistar rats. Four groups of animals have been used, a control group and three test groups. In the first test group, AMV was intra-peritoneally (i.p) injected daily (5 mg/kg body weight for five consecutive days). The second test group of animals was also injected daily with EGCG (5 mg/kg body weight) during the same period. However, the third test group was i.p. injected with both AMV and EGCG (5 mg/kg body weight for five consecutive days). When given alone, AMV induced an oxidative stress evidenced by an increase of lipid peroxidation levels (expressed as TBARS concentration) in kidney. In these animals, activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were significantly decreased, suggesting significant reduction of the antioxidant defense system at the cell level. Kidney histological sections, showed glomerular hypertrophy and tubular dilatation. In AMV-treated animals receiving EGCG, the oxidative stress was much less pronounced and activities of antioxidant enzymes were kept close to control values. Histopathological changes were less prominent. Our results confirm that green tea and other sources of flavonoids might confer a strong protection against ammonium metavanadate-induced oxidative stress.
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