Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
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.
Animal experiments with controls.
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.
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.
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.
NA Laryngoscope, 2017
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.
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.
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.
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.
4. Laryngoscope, 2017
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.
Acute experiments in cats.
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.
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.
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.
NA Laryngoscope, 2017
To determine if patients with prior airway surgery for obstructive sleep apnea (OSA) had increased benefit following implantation with hypoglossal nerve stimulator.
Retrospective chart review at a single institution tertiary academic care center.
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.
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).
Overall, patients had significant improvement following implantation with hypoglossal nerve stimulator. Prior airway surgery had no statistically significant effect on postoperative AHI or NOS.
4. Laryngoscope, 2017
To analyze oropharyngeal squamous cell carcinoma incidence and mortality trends in the United States for the years 1973 through 2013.
Cross-sectional study using a large population-based cancer database.
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).
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.
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.
2b. Laryngoscope, 2017
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).
Retrospective cohort study at a single institution.
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.
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.
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.
4. Laryngoscope, 2017
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).
PubMed and EMBASE.
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.
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.
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
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.
Systematically review the utility of intraoperative imaging in CI surgery and implications for management.
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.
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.
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.
NA. Laryngoscope, 2017
Oxybenzone (Benzophenone-3) is an emerging human and environmental contaminant used in sunscreens and personal care products to help minimize the damaging effects of ultraviolet radiation. The Center for Disease Control fourth national report on human exposure to environmental chemicals demonstrated that approximately 97% of the people tested have oxybenzone present in their urine, and independent scientists have reported various concentrations in waterways and fish worldwide. Oxybenzone can also react with chlorine, producing hazardous by-products that can concentrate in swimming pools and wastewater treatment plants. Moreover, adverse reactions could very well be increased by the closed loop of ingesting fish contaminated with oxybenzone and/or washing the ingredient off our bodies and having it return in drinking water as treatment plants do not effectively remove the chemical as part of their processing protocols. In humans, oxybenzone has been reported to produce contact and photocontact allergy reactions, implemented as a possible endocrine disruptor and has been linked to Hirschsprung's disease. Environmentally, oxybenzone has been shown to produce a variety of toxic reactions in coral and fish ranging from reef bleaching to mortality. Lastly, with the rise in skin cancer rates and the availability of more effective sunscreen actives such as micronized zinc oxide and titanium dioxide, serious doubts about the relative prevention benefit of personal care products containing oxybenzone must be raised and compared with the potential negative health and environmental effects caused by the accumulation of this and other chemicals in the ecosystem.
The National Institute for Health and Care Excellence (NICE), as part of the institute's single technology appraisal (STA) process, invited the manufacturer of pomalidomide (POM; Imnovid®, Celgene) to submit evidence regarding the clinical and cost effectiveness of the drug in combination with dexamethasone (POM + LoDEX) for the treatment of relapsed and refractory multiple myeloma (RRMM) after at least two regimens including lenalidomide (LEN) and bortezomib (BOR). Kleijnen Systematic Reviews Ltd (KSR) and Erasmus University Rotterdam were commissioned as the Evidence Review Group (ERG) for this submission. The ERG reviewed the evidence submitted by the manufacturer, validated the manufacturer's decision analytic model, and conducted exploratory analyses in order to assess the robustness and validity of the presented clinical and cost-effectiveness results. This paper describes the company submission, the ERG assessment, and NICE's subsequent decisions. The company conducted a systematic review to identify studies comparing POM with comparators outlined in the NICE scope: panobinostat with bortezomib and dexamethasone (PANO + BOR + DEX), bendamustine with thalidomide and dexamethasone (BTD) and conventional chemotherapy (CC). The main clinical effectiveness evidence was obtained from MM-003, a randomized controlled trial (RCT) comparing POM + LoDEX with high-dose dexamethasone (HiDEX; used as a proxy for CC). Additional data from other studies were also used as nonrandomized observational data sources for the indirect treatment comparison of POM + LoDEX with BTD and PANO + BOR + DEX. Covariate or treatment switching adjustment methods were used for each comparison. The model developed in Microsoft® Excel 2010 using a semi-Markov partitioned survival structure, submitted in the original submission to NICE for TA338, was adapted for the present assessment of the cost effectiveness of POM + LoDEX. Updated evidence from the clinical-effectiveness part was used for the survival modelling of progression-free survival and overall survival. For POM + LoDEX, the patient access scheme (PAS) discount was applied to the POM price. Three separate comparisons were conducted for each comparator, each comparison using a different dataset and adjustment methods. The ERG identified and corrected some errors, and the corrected incremental cost-effectiveness ratios (ICERs) for POM + LoDEX versus each comparator were presented: approximately £45,000 per quality-adjusted life-year (QALY) gained versus BTD, savings of approximately £143,000 per QALY lost versus PANO + BOR + DEX, and approximately £49,000 per QALY gained versus CC. The ERG also conducted full incremental analyses, which revealed that CC, POM + LoDEX and PANO + BOR + DEX were on the cost-effectiveness frontier. The committee's decision on the technology under analysis deemed that POM + LoDEX should be recommended as an option for treating multiple myeloma in adults at third or subsequent relapse of treatments including both LEN and BOR, contingent on the company providing POM with the discount agreed in the PAS.
Oxybenzone (Benzophenone-3) is an emerging human and environmental contaminant used in sunscreens and personal care products to help minimize the damaging effects of ultraviolet radiation. The Center for Disease Control fourth national report on human exposure to environmental chemicals demonstrated that approximately 97% of the people tested have oxybenzone present in their urine, and independent scientists have reported various concentrations in waterways and fish worldwide. Oxybenzone can also react with chlorine, producing hazardous by-products that can concentrate in swimming pools and wastewater treatment plants. Moreover, adverse reactions could very well be increased by the closed loop of ingesting fish contaminated with oxybenzone and/or washing the ingredient off our bodies and having it return in drinking water as treatment plants do not effectively remove the chemical as part of their processing protocols. In humans, oxybenzone has been reported to produce contact and photocontact allergy reactions, implemented as a possible endocrine disruptor and has been linked to Hirschsprung's disease. Environmentally, oxybenzone has been shown to produce a variety of toxic reactions in coral and fish ranging from reef bleaching to mortality. Lastly, with the rise in skin cancer rates and the availability of more effective sunscreen actives such as micronized zinc oxide and titanium dioxide, serious doubts about the relative prevention benefit of personal care products containing oxybenzone must be raised and compared with the potential negative health and environmental effects caused by the accumulation of this and other chemicals in the ecosystem.
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.
Animal experiments with controls.
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.
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.
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.
NA Laryngoscope, 2017
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.
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.
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.
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.
4. Laryngoscope, 2017
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.
Acute experiments in cats.
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.
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.
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.
NA Laryngoscope, 2017
To determine if patients with prior airway surgery for obstructive sleep apnea (OSA) had increased benefit following implantation with hypoglossal nerve stimulator.
Retrospective chart review at a single institution tertiary academic care center.
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.
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).
Overall, patients had significant improvement following implantation with hypoglossal nerve stimulator. Prior airway surgery had no statistically significant effect on postoperative AHI or NOS.
4. Laryngoscope, 2017
To analyze oropharyngeal squamous cell carcinoma incidence and mortality trends in the United States for the years 1973 through 2013.
Cross-sectional study using a large population-based cancer database.
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).
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.
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.
2b. Laryngoscope, 2017
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).
Retrospective cohort study at a single institution.
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.
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.
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.
4. Laryngoscope, 2017
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).
PubMed and EMBASE.
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.
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.
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
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.
Systematically review the utility of intraoperative imaging in CI surgery and implications for management.
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.
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.
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.
NA. Laryngoscope, 2017
The association between single nucleotide polymorphisms (SNPs) of the collagen gene and intracranial aneurysm (IA) pathogenesis remains controversial. Thus, in this study, a meta-analysis was performed to evaluate the association between collagen gene SNPs and the incidence of IA. A systematic search of major online databases up to March 2017 was performed. Five genetic models (allelic, dominant, recessive, heterozygous, and homozygous models) were used to analyze the associations. A total of 14 trials with 13,709 patients were included. Four collagen genes, COL1A2 (21 SNPs), COL3A1 (7 SNPs), COL4A1 (6 SNPs), and COL4A2 (1 SNP), were analyzed. We observed that rs42524 in the COL1A2 gene was associated with a significant increase in the risk of IA in Japanese patients (allelic model: OR, 1.94; 95% CI, 1.03–3.64; p = 0.04); the rs1800255 polymorphism in the COL3A1 gene was significantly correlated with Chinese IA patients (allelic model: OR, 1.50; 95% CI, 1.30–1.73; p < 0.001); and rs2621215 was significantly correlated with IA for the heterozygous model (OR, 1.58; 95% CI, 1.15–2.17; p = 0.005) and the dominant model (OR, 1.49; 95% CI, 1.09–2.02; p = 0.012). Furthermore, in the COL4A1 gene, there was a significant relationship between the rs3783107 polymorphism and a Dutch IA population (allelic model: OR, 1.23; 95% CI, 1.06–1.42; p = 0.006), and the prevalence ratio of mutation carriers in the Dutch population was significantly higher than that in the Japanese population (ROR, 1.31; 95% CI, 1.07–1.63; p = 0.008). The rs1800255 polymorphism in COL3A1 is robustly correlated with IA in the Chinese population. Three COL1A2 SNPs—rs42524, rs1800238, and rs2621215—should be studied further.
Copper-catalyzed chelation assisted ortho-nitration of aryls with benzazoles as efficient directing group has been achieved. The reaction is general and efficient for electronically differentiated aryls and pharmacophorically important directing groups i.e., benzoxazoles, benzthiazoles and benzimidazoles. This class of nitro-products have significance as fluorogenic and potential nitroreductase substrates for the detection of clinically important microorganisms. The nitration reaction proceeds with inexpensive copper catalyst and mild, cheap and environmentally friendly nitro source, Fe(NO3)3.9H2O. This operationally simple and functional group tolerant protocol highlights the high regioselectivity for the nitration of 2-aryl benzazoles without the exclusion of air or moisture.
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.
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.
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%.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
A series of heteroleptic platinum(II) complexes of the general formula [PtX(iPrEug)(NHC)] (2-7) bearing the organometallic π/σ chelator iPrEug (isopropyl eugenoxyacetate), varying halido and NHCs ligands derived from imidazole, benzimidazole and triazole have been prepared and fully characterized by elemental analyses, ESI mass spectrometry, IR and NMR spectroscopies. Complexes 3 and 5-7 were also characterized by single-crystal X-ray diffraction. The air-stable complexes are rare examples of platinum(II) compounds containing three different types of carbon donors, i.e. aryl, carbene and olefin. Unsymmetrical NHCs lead to rotameric pairs of 4 and 5 exhibiting different NMR spectroscopic features. Spectroscopic studies also revealed that the introduction of a NHC leads to a weakening of the metal-olefin bond and strengthening of the metal-aryl bond. Backbone and thus electronic variations among the NHCs on the other hand show little influence on the bonding of the iPrEug chelator.
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.
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.
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.
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.
This course covers Phonak's latest product introductions as well as software and programming details to promote successful patient hearing instrument fittings.
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/2gXqXHp
via IFTTT
Cartilage elasticity changes with cartilage degeneration. Hence, cartilage elasticity detection might be an alternative to traditional imaging methods for the early diagnosis of osteoarthritis. Based on the wa...
from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/2ygBBAg
via IFTTT
