Pharyngocutaneous fistula (PCF) is a problematic complication following total laryngectomy. Disagreement remains regarding predisposing factors. This study examines perioperative factors predicting PCF followi...
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Τρίτη 22 Αυγούστου 2017
Peri-operative factors predisposing to pharyngocutaneous fistula after total laryngectomy: analysis of a large multi-institutional patient cohort
Nocebo Effect in Meniere's Disease: a Meta-analysis of Placebo-controlled Randomized Controlled Trials.
Objective: To estimate the frequency and strength of nocebo effects in trials for Meniere disease (MD). Data Sources: A literature search was conducted in PUBMED. The search terms we used were " Meniere or Meniere's," "treatment," and "placebo." Limitations included article type to be Clinical Trial or Randomized Controlled Trial, text availability to be Full text, Species to be Humans and Language to be English. Study Selection: We included placebo-controlled pharmaceutical RCTs that referred specifically to MD and recruited at least 10 adults in each arm. We excluded those studies with JADAD score
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Tourette syndrome: a disorder of the social decision-making network
Abstract
Tourette syndrome is a common neurodevelopmental disorder defined by characteristic involuntary movements, tics, with both motor and phonic components. Tourette syndrome is usually conceptualized as a basal ganglia disorder, with an emphasis on striatal dysfunction. While considerable evidence is consistent with these concepts, imaging data suggest diffuse functional and structural abnormalities in Tourette syndrome brain. Tourette syndrome exhibits features that are difficult to explain solely based on basal ganglia circuit dysfunctions. These features include the natural history of tic expression, with typical onset of tics around ages 5 to 7 years and exacerbation during the peri-pubertal years, marked sex disparity with higher male prevalence, and the characteristic distribution of tics. The latter are usually repetitive, somewhat stereotyped involuntary eye, facial and head movements, and phonations. A major functional role of eye, face, and head movements is social signalling. Prior work in social neuroscience identified a phylogenetically conserved network of sexually dimorphic subcortical nuclei, the Social Behaviour Network, mediating many social behaviours. Social behaviour network function is modulated developmentally by gonadal steroids and social behaviour network outputs are stereotyped sex and species specific behaviours. In 2011 O'Connell and Hofmann proposed that the social behaviour network interdigitates with the basal ganglia to form a greater network, the social decision-making network. The social decision-making network may have two functionally complementary limbs: the basal ganglia component responsible for evaluation of socially relevant stimuli and actions with the social behaviour network component responsible for the performance of social acts. Social decision-making network dysfunction can explain major features of the neurobiology of Tourette syndrome. Tourette syndrome may be a disorder of social communication resulting from developmental abnormalities at several levels of the social decision-making network. The social decision-making network dysfunction hypothesis suggests new avenues for research in Tourette syndrome and new potential therapeutic targets.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2xbyFAy
The Evolving Role of Tumor Treating Fields in Managing Glioblastoma: Guide for Oncologists.
Glioblastoma (GBM) is a devastating brain tumor with poor prognosis despite advances in surgery, radiation, and chemotherapy. Survival of patients with glioblastoma remains poor, with only 1 in 4 patients alive at 2 years, and a 5-year survival rate of about 5%. Recurrence is nearly universal and, after recurrence, prognosis is poor with very short progression-free survival and overall survival (OS). Various salvage chemotherapy strategies have been applied with limited success. Tumor Treating Fields (TTFields) are a novel treatment modality approved for treatment of either newly diagnosed or recurrent GBM. TTFields therapy involves a medical device and transducer arrays to provide targeted delivery of low intensity, intermediate frequency, alternating electric fields to produce antimitotic effects selective for rapidly dividing tumor cells with limited toxicity. In the phase 3 EF-14 trial, TTFields plus temozolomide provided significantly longer progression-free survival and OS compared with temozolomide alone in patients with newly diagnosed GBM after initial chemoradiotherapy. The addition of TTFields to standard therapy improved median OS from 15.6 to 20.5 months (P=0.04). In the phase 3 EF-11 trial, for recurrent GBM, TTFields provided comparable efficacy as investigator's choice systemic therapy, with improved patient-reported quality of life and a lower incidence of serious adverse events. Primary toxicity associated with TTFields is skin irritation generally managed with array relocation and topical treatments including antibiotics and steroids. TTFields therapy has demonstrated proven efficacy in management of GBM, including improvement in OS for patients with newly diagnosed GBM, and is under current investigation in other brain and extracranial tumors. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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Constructing a patient-specific computer model of the upper airway in sleep apnea patients
Objective
The use of computer simulation to develop a high-fidelity model has been proposed as a novel and cost-effective alternative to help guide therapeutic intervention in sleep apnea surgery. We describe a computer model based on patient-specific anatomy of obstructive sleep apnea (OSA) subjects wherein the percentage and sites of upper airway collapse are compared to findings on drug-induced sleep endoscopy (DISE).
Study Design
Basic science computer model generation.
Methods
Three-dimensional finite element techniques were undertaken for model development in a pilot study of four OSA patients. Magnetic resonance imaging was used to capture patient anatomy and software employed to outline critical anatomical structures. A finite-element mesh was applied to the volume enclosed by each structure. Linear and hyperelastic soft-tissue properties for various subsites (tonsils, uvula, soft palate, and tongue base) were derived using an inverse finite-element technique from surgical specimens. Each model underwent computer simulation to determine the degree of displacement on various structures within the upper airway, and these findings were compared to DISE exams performed on the four study patients.
Results
Computer simulation predictions for percentage of airway collapse and site of maximal collapse show agreement with observed results seen on endoscopic visualization.
Conclusion
Modeling the upper airway in OSA patients is feasible and holds promise in aiding patient-specific surgical treatment.
Level of Evidence
NA. Laryngoscope, 2017
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Efficacy and rebound rates in propranolol-treated subglottic hemangioma: A literature review
Objective
Propranolol has recently become the treatment of choice for management of subglottic and airway hemangiomas. This literature review aimed to determine the success rate of propranolol for managing these lesions as well as the rate of rebound growth following propranolol treatment cessation.
Study Design
Literature search involving MEDLINE and Scopus to identify English-language articles.
Methods
Studies were identified using hemangioma, subglottic or airway, and propranolol for search terms. Studies were eligible for inclusion if they reported the treatment used, individual deidentified patient data, and contained patients without medical or surgical treatment prior to propranolol therapy
Results
Initial review included 107 abstracts. Twenty-four articles including case reports and case series met inclusion criteria and were included in the qualitative analysis. Forty-nine patients were included. Twenty-eight (57%) were treated with propranolol alone, and 20 (41%) were treated with a combination of propranolol and a corticosteroid. Thirty-seven (76%) of patients were treated with a dose of 2 mg/kg/d of propranolol. The initial treatment was successful in 43 (88%) of patients. Rebound growth occurred in four (9%) patients. Overall, six (12%) patients underwent surgical resection.
Conclusions
Propranolol is efficacious for treating subglottic hemangiomas. Rebound growth does occur in a small subset of patients during the propranolol wean. Close observation for children during weaning of propranolol therapy for subglottic hemangioma is essential. Adjunctive management strategies need to be used in patients with rebound growth. Laryngoscope, 2017
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Pharmacokinetic variability of valproate in women of childbearing age
Summary
The purpose was to investigate pharmacokinetic variability of valproic acid (VPA) in women of childbearing age by therapeutic drug monitoring (TDM) data to elucidate the variable relationship between dose and serum concentrations with the ultimate aim of facilitating safer use of VPA. Anonymized retrospective data from the TDM database (2006–2015) at the National Center for Epilepsy in Norway were used. Trough total concentrations of VPA at assumed steady state in women aged 14–46 years were analyzed. Data from 643 nonpregnant women of childbearing age (mean age = 27 years) were included. Mean dose and serum concentration of VPA were 968 (standard deviation [SD] = 453) mg/day and 411 (SD = 138) μmol/L, respectively, and 59% used polytherapy. The pharmacokinetic variability in serum concentration/dose (C/D) ratios between women was extensive. For doses <700 mg/day (n = 202; 32%; 150–625 mg/day), mean serum concentration was 336 μmol/L and variability in C/D ratio was 10-fold. The variability decreased with increasing dose to eightfold (≥700 to <1,500 mg/day, n = 358) and fourfold (≥1,500 mg/day, n = 96). This study demonstrates the extensive pharmacokinetic variability of VPA among women of childbearing age, which is most pronounced at low doses. In future studies, serum concentrations of VPA, rather than dosage, should be used as a guide for exposure of VPA and possible risks of teratogenicity to evaluate safety aspects of VPA in women.
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Ischemic Preconditioning Blunts Muscle Damage Responses Induced by Eccentric Exercise.
Purpose: Ischemic preconditioning (IPC) is known to reduce muscle damage induced by ischemia and reperfusion-injury (I/R-Injury) during surgery. Due to similarities between the pathophysiological formation of I/R-injury and eccentric exercise-induced muscle damage (EIMD), as characterized by an intracellular accumulation of Ca2+, an increased production of reactive oxygen species and increased pro-inflammatory signaling, the purpose of the present study was to investigate whether IPC performed prior to eccentric exercise may also protect against EIMD. Methods: Nineteen healthy men were matched to an eccentric only (ECC) (n=9) or eccentric proceeded by IPC group (IPC+ECC) (n=10). The exercise protocol consisted of bilateral biceps curls (3x10 repetitions at 80% of the concentric 1RM). In IPC+ECC, IPC was applied bilaterally at the upper arms by a tourniquet (200 mmHg) immediately prior to the exercise (3x5 minutes of occlusion, separated by 5 minutes of reperfusion). Creatine Kinase (CK), arm circumference, subjective pain (VAS score) and radial displacement (Tensiomyography, Dm) were assessed before IPC, pre-exercise, post-exercise, 20 minutes-, 2 hours-, 24 hours-, 48 hours- and 72 hours post-exercise. Results: CK differed from baseline only in ECC at 48h (p
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The Impact of Waiting List Bmi Changes on the Short-Term Outcomes of Lung Transplantation.
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Cytoreductive nephrectomy for metastatic renal cell carcinoma: inequities in access exist despite improved survival
Abstract
The use of cytoreductive nephrectomy (CRN) in the targeted therapy era is still debated. We aimed to determine factors associated with reduced use of CRN and determine the effect of CRN on overall survival in patients with metastatic renal cell carcinoma (RCC). All advanced RCC diagnosed between 2001 and 2009 in New South Wales, Australia, were identified from the Central Cancer Registry. Records of treatment and death were electronically linked. Follow-up was to the end of 2011. Multivariable logistic regression analysis was used to determine factors associated with the receipt of CRN. Cox proportional hazards model was used to determine factors associated with survival. A total of 1062 patients were identified with metastatic RCC of whom 289 (27%) received CRN. There was no difference in the use of CRN over the time period of the study. Females (OR 0.68 (95% CI: 0.48–0.96)), unmarried individuals (OR 0.68 (95% CI: 0.48–0.96)), treatment in a nonteaching hospital (OR 0.26 (95% CI: 0.18–0.36)) and individuals without private insurance (OR 0.29 (95% CI: 0.20–0.41)) all had reduced likelihood of receiving CRN. On multivariable analysis, not receiving CRN resulted in a 90% increase in death (HR 1.90 (95% CI: 1.61–2.25)). In addition, increasing age (P < 0.001), increasing Charlson comorbidity status (P = 0.002) and female gender also had a significant independent association with death. Despite a strong association with improved survival, individuals who are elderly, female, have treatment in a nonteaching facility or have no private insurance have a reduced likelihood of receiving CRN.
Cytoreductive nephrectomy is commonly used in conjunction with systemic therapy to treat advanced renal cell carcinoma. Despite a strong association with improved survival, individuals who are elderly, female, have treatment in a nonteaching facility or do not have private insurance have a reduced likelihood of receiving this surgery.
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The Ideal Buttock Size
What is the 'ideal' female buttock shape? A survey of plastic surgeons and the general public provides some insight.
Plastic and Reconstructive Surgery
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The colorectal cancer immune microenvironment and approach to immunotherapies
Future Oncology, Ahead of Print.
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Should we be combining local tumor therapies with immunotherapies as standard?
Future Oncology, Ahead of Print.
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Docetaxel or abiraterone in addition to androgen deprivation therapy in metastatic castration-sensitive prostate cancer
Future Oncology, Ahead of Print.
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How and when adjuvant treatment should be intensified in stage III colorectal cancers?
Future Oncology, Ahead of Print.
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Do Children and Adolescents with Inflammatory Bowel Disease Complete Clinical Disease Indices Similar to Physicians?.
Objective: The degree to which children and adolescents with inflammatory bowel disease (IBD) complete clinical disease activity indices in accordance with their physician is indefinite. Therefore, we investigated the agreement between patient- and physician-based clinical indices in children and adolescents with a previous diagnosis of IBD. Methods: In this cross-sectional study, IBD patients (8-18 years) were included prospectively. Patients completed a patient-based short Pediatric Crohn's Disease Activity Index (shPCDAI) for Crohn's disease or the Pediatric Ulcerative Colitis Activity Index (PUCAI) for ulcerative or indeterminate colitis. Physicians completed the original physician-based shPCDAI or PUCAI. Agreement was calculated with linear weighted kappa. Results: In total, 154 pairs of clinical indices were collected: 89 pairs of shPCDAI's (median age at assessment 15.6 years, 61% male) and 55 pairs of PUCAI's (median age at assessment 14.0 years, 44% male). The shPCDAI disease activity category only fairly agreed between patient- and physician-based indices (kappa: 0.40 [95%CI 0.24-0.55], p
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Characterizing the Age and Stimulus Frequency Interaction for Ocular Vestibular-Evoked Myogenic Potentials.
Objectives: The normal process of aging is mostly associated with global decline in almost all sensory aspects of the human body. While aging affects the 500-Hz tone burst-evoked ocular vestibular-evoked myogenic potentials (oVEMPs) by reducing the amplitudes and prolonging the latencies, its interaction with oVEMP responses at other frequencies has not been studied. Therefore, the present study aimed at investigating the impact of advancing age on the frequency tuning of oVEMP. Design: Using a cross-sectional research design, oVEMPs were recorded for tone burst frequencies of 250, 500, 750, 1000, 1500, and 2000 Hz from 270 healthy individuals divided into six age groups (10-20, 20-30, 30-40, 40-50, 50-60, and >60 years). Results: The results revealed significantly lower response rates and amplitudes in age groups above 50 years of age than all the other groups at nearly all the frequencies (p =1000 Hz in most of the individuals above 60 years of age (p =1000 Hz in older adults, especially above 60 years of age. Conclusions: The results of the study showed significantly higher prevalence of frequency tuning at 1000 Hz in older adults above 60 years of age. Because the shift in frequency tuning to >=1000 Hz is frequently used for identification of Meniere's disease, it is suggested that age-related correction be used for the diagnosis of Meniere's disease when using frequency tuning of oVEMP. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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The colorectal cancer immune microenvironment and approach to immunotherapies
Future Oncology, Ahead of Print.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2xaZIfv
Should we be combining local tumor therapies with immunotherapies as standard?
Future Oncology, Ahead of Print.
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Docetaxel or abiraterone in addition to androgen deprivation therapy in metastatic castration-sensitive prostate cancer
Future Oncology, Ahead of Print.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vWYHsS
How and when adjuvant treatment should be intensified in stage III colorectal cancers?
Future Oncology, Ahead of Print.
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Technical tip for direct closure of donor site of anterolateral thigh rectangular flaps wider than 9 cm used for pharyngo-esophageal reconstruction
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Ciliated muconodular papillary tumors of the lung with KRAS/BRAF/AKT1 mutation
Ciliated muconodular papillary tumors (CMPTs) are newly recognized rare peripheral lung nodules that are histologically characterized by ciliated columnar, goblet, and basal cells. Although recent studies have...
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Comparison of the efficacy and feasibility of laser enucleation of bladder tumor versus transurethral resection of bladder tumor: a meta-analysis
Abstract
The transurethral resection of bladder tumor (TURBT) remains the most widely used method in the surgical treatment of the non-muscle invasive bladder tumor (NMIBT). Despite its popularity, the laser technique has been widely used in urology as an alternative, via the application of transurethral laser enucleation of bladder tumor. The aim of the present study was to compare the efficacy and feasibility between transurethral laser enucleation and transurethral resection of bladder tumor. A systematic search of the following databases was conducted: PubMed, Wed of Science, Cochrane Library, EMBASE, Google scholar, and Medline. The search included studies up to the 1st of January 2017. The outcomes of interest that were used in order to assess the two techniques included operation time, catheterization time, hospitalization time, obturator nerve reflex, bladder perforation, bladder irritation, 24-month-recurrence rate, and the postoperative adjuvant intravesical chemotherapy. A total of 13 trials with 2012 participants were included, of which 975 and 1037 underwent transurethral laser enucleation and transurethral resection of bladder tumor, respectively. No significant difference was noted in the operation time between the two groups, although significant differences were reported for the variables catheterization time, hospitalization time, obturator nerve reflex, bladder perforation, bladder irritation, and 24-month-recurrence rate. In the mitomycin and epirubicin subgroups, no significant differences were observed in the laser enucleation and TURBT methods with regard to the 24-month-recurrence rate. The laser enucleation was superior to TURBT with regard to the parameters obturator nerve reflex, bladder perforation, catheterization time, hospitalization time, and 24-month-recurrence rate. Moreover, laser enucleation can offer a more accurate result of the tumor's pathological stage and grade.
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Comprehensive catwalk gait analysis in a chronic model of multiple sclerosis subjected to treadmill exercise training
Multiple sclerosis (MS) is a demyelinating disease with a wide range of symptoms including walking impairment and neuropathic pain mainly represented by mechanical allodynia. Noteworthy, exercise preconditioni...
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The Gulf War era multiple sclerosis cohort: 3. Early clinical features
Objectives
To present clinical features at diagnosis for a large nationwide incident cohort of multiple sclerosis (MS) among those serving in the US military during the Gulf War era (GWE).
Materials & Methods
Medical records and databases from the Department of Veterans Affairs (VA) for cases of MS with onset in or after 1990, active duty between 1990 and 2007 and service connection by the VA, were reviewed for diagnosis and demographic variables. Neurological involvement was summarized by the Kurtzke Disability Status Scale (DSS) and the Multiple Sclerosis Severity Score (MSSS).
Results
Among 1919 cases of clinically definite MS, 94% had a relapsing-remitting course and 6% were primary progressive at diagnosis. More males of all races and blacks of both sexes were progressive. At diagnosis, functional system involvement was pyramidal 69%, cerebellar 58%, sensory 55%, brainstem 45%, bowel/bladder 23%, cerebral 23%, visual 18%, and other 5%. Mean DSS scores were: white males, females 2.9, 2.7; black males, females 3.3, 2.8; and other-race males, females 3.2, 2.6. Mean and median MSSS were marginally greater in black males and other males compared to the other sex-race groups.
Conclusions
In this incident cohort, males and blacks had significantly higher proportions of primary progressive MS. DSS at diagnosis was significantly more severe in blacks and significantly less so in whites and in women vs men, but MSSS was only marginally greater in black males and other-race males. This morbidity assessment early in the course of MS provides population-based data for diagnosis, management, and prognosis.
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Cognitive complaint in early Parkinson's disease: A pilot study
Background
Subjective cognitive complaint (SCC) is a criterion recommended by the Movement Disorder Society (MDS) task force for the diagnosis of mild cognitive impairment (MCI). Until now there were few specific tools for detecting SCC in PD. We sought to develop a new tool to assess SCC specifically dedicated for PD.
Materials and Methods
We set a group of experts in movements disorders and neurocognition to develop an easy-to-use tool based on a visual analogue scale (VAS) for five cognitive domains: memory, executive functions, spatial orientation, attention, and language. We use it to assess SCC twice (at a one-month interval) in PD patients with disease duration of less than 5 years. Comprehensibility of the VAS was assessed. Controls were assessed with the same VAS. Patients with PD also underwent neuropsychological testing.
Results
VAS was easily understandable by the 70 patients with PD. We found significant SCC for the patients with PD vs controls in three cognitive domains: executive functions (1.7 ± 1.9 vs 0.8 ± 1.1; P < .001), language (2.3 ± 2.5 vs 1.0 ± 1.3, P < .001), and attention (2.1 ± 2.2 vs 1.2 ± 1.2; P < .01). Reproducibility between the two evaluations of patients with PD was good. There was no relationship between SCC and the results of neuropsychological testing.
Conclusions
SCC seems to appear early in PD, in three cognitive domains (executive functions, language, and attention), and VAS might be a good way to detect SCC in PD, but need to be validated.
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Differential Response Pattern of Oropharyngeal Pressure by Bolus and Dry Swallows
Abstract
The aim of this study was to determine if bolus and dry swallow showed similar pressure changes in the oropharynx using our newly developed device. A unique character of it includes that baropressure can be measured with the sensor being placed in the balloon and can assess the swallowing mechanics in terms of pressure changes in the oropharynx with less influences of direct contacts of boluses and oropharyngeal structures during swallow indirectly. Fifteen healthy subjects swallowed saliva (dry), 15 ml of water, 45 ml of water, and 15 ml of two different types of food in terms of viscosity (potage soup-type and mayonnaise-type foods). Suprahyoid muscle activity was recorded simultaneously. Three parameters, area under the curve (AUC), peak amplitude, and duration of pressure, were analyzed from each swallow. Almost all of the bolus swallowing events had biphasic baropressure responses consisting of an early phase and late phase (99%), whereas 90% of the saliva swallowing events had a single phase. AUC, peak, and duration displayed greater effects during the late phase than during the early phase. Baropressure of the early phase, but not of the late phase, significantly increased with increasing volume; however, small but significant viscosity effects on pressure were seen during both phases. Peak pressure of the late phase was preceded by maximum muscle activity, whereas that of the early phase was seen when muscle activity displayed a peak response. These findings indicated that our device with the ability to measure baropressure has the potential to provide additional parameter to assess the swallow physiology, and biphasic baropressure responses in the early and late phases could reflect functional aspects of the swallowing reflexes.
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Predictive Value of the New Zealand Secretion Scale (NZSS) for Pneumonia
Abstract
Accumulated pharyngo-laryngeal secretions have been associated with aspiration and pneumonia. While traditional secretion scales evaluate location and amount, the eight-point New Zealand Secretion Scale (NZSS) uniquely encompasses a responsiveness subcomponent. This prospective observational study investigated the predictive value of NZSS for aspiration and pneumonia. Consecutive inpatients (N:180) referred for flexible endoscopic evaluation of swallowing (FEES) were recruited (neurological 49%, critical care 31%, structural 15%, other 5% etiologies). Mean age was 63 years (range 18–95 years, S.D. 18). A standardized protocol was completed on 264 FEES (180 first FEES, 84 repeat FEES). Penetration-aspiration scale (PAS) (ICC = .89) and NZSS (ICC = .91) were independently scored by two raters. Aspiration of food and/or fluids occurred in 36% of FEES; 24% silently. Median NZSS was 3 (range 0–7); with silent aspiration of secretions in 33% of FEES. There was a significant correlation between NZSS and PAS (R = .37, p < .001). Incidence of pneumonia during admission was 46% and was significantly associated with PAS (p < .001), NZSS (p < .001), age (p < .001), and tracheostomy (p < .001). Of those who developed pneumonia, 33% had both high PAS (>5) and high NZSS (>4). Eleven percent of those who developed pneumonia had an elevated NZSS (>4) in the absence of aspiration (PAS < 6). This large study reports the significant relationship between accumulated secretions, airway responsiveness, and pneumonia. This comprehensive scale is a useful tool when carrying out endoscopic evaluation and has the potential to predict pneumonia in patients irrespective of their aspiration status.
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Cross-Cultural Adaptation and Validation of the SWAL-QoL Questionnaire in Greek
Abstract
The purpose of this study was to translate and adapt the 44-item SWAL-QoL into Greek and examine its internal consistency, test–retest reliability, external construct validity, and discriminant validity in order to provide a validated dysphagia-specific QoL instrument in the Greek language. The instrument was translated into Greek using the back translation to ensure linguistic validity and was culturally adapted resulting in the SWAL-QoL-GR. Two groups of participants were included: a patient group of 86 adults (48 males; age range: 18–87 years) diagnosed with oropharyngeal dysphagia, and an age-matched healthy control group (39 adults; 19 males; age range: 18–84 years). The Greek 30-item version of the WHOQOL-BREF was used for assessment of construct validity. Overall, the questionnaire achieved good to excellent psychometric values. Internal consistency of all 10 subscales and the physical symptoms scale of the SWAL-QoL-GR assessed by Cronbach's α was good to excellent (0.811 < α < 0.940). Test–retest validity was found to be good to excellent as well. In addition, moderate to strong correlations were found between seven of the ten subscales of the SWAL-QoL-GR with limited items of the WHOQΟL-BREF (0.401 < ρ < 0.65), supporting good construct validity of the SWAL-QoL-GR. The SWAL-QoL-GR also correctly differentiated between patients with dysphagia and age-matched healthy controls (p < 0.001) on all 11 scales, further indicating excellent discriminant validity. Finally, no significant differences were found between the two sexes. This cultural adaptation and validation allows the use of this tool in Greece, further enhancing our clinical and scientific efforts to increase the evidence-based practice resources for dysphagia rehabilitation in Greece.
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Changes in Swallowing-Related Quality of Life After Endoscopic Treatment for Zenker’s Diverticulum Using the SWAL-QOL Questionnaire
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Differential Response Pattern of Oropharyngeal Pressure by Bolus and Dry Swallows
Abstract
The aim of this study was to determine if bolus and dry swallow showed similar pressure changes in the oropharynx using our newly developed device. A unique character of it includes that baropressure can be measured with the sensor being placed in the balloon and can assess the swallowing mechanics in terms of pressure changes in the oropharynx with less influences of direct contacts of boluses and oropharyngeal structures during swallow indirectly. Fifteen healthy subjects swallowed saliva (dry), 15 ml of water, 45 ml of water, and 15 ml of two different types of food in terms of viscosity (potage soup-type and mayonnaise-type foods). Suprahyoid muscle activity was recorded simultaneously. Three parameters, area under the curve (AUC), peak amplitude, and duration of pressure, were analyzed from each swallow. Almost all of the bolus swallowing events had biphasic baropressure responses consisting of an early phase and late phase (99%), whereas 90% of the saliva swallowing events had a single phase. AUC, peak, and duration displayed greater effects during the late phase than during the early phase. Baropressure of the early phase, but not of the late phase, significantly increased with increasing volume; however, small but significant viscosity effects on pressure were seen during both phases. Peak pressure of the late phase was preceded by maximum muscle activity, whereas that of the early phase was seen when muscle activity displayed a peak response. These findings indicated that our device with the ability to measure baropressure has the potential to provide additional parameter to assess the swallow physiology, and biphasic baropressure responses in the early and late phases could reflect functional aspects of the swallowing reflexes.
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Predictive Value of the New Zealand Secretion Scale (NZSS) for Pneumonia
Abstract
Accumulated pharyngo-laryngeal secretions have been associated with aspiration and pneumonia. While traditional secretion scales evaluate location and amount, the eight-point New Zealand Secretion Scale (NZSS) uniquely encompasses a responsiveness subcomponent. This prospective observational study investigated the predictive value of NZSS for aspiration and pneumonia. Consecutive inpatients (N:180) referred for flexible endoscopic evaluation of swallowing (FEES) were recruited (neurological 49%, critical care 31%, structural 15%, other 5% etiologies). Mean age was 63 years (range 18–95 years, S.D. 18). A standardized protocol was completed on 264 FEES (180 first FEES, 84 repeat FEES). Penetration-aspiration scale (PAS) (ICC = .89) and NZSS (ICC = .91) were independently scored by two raters. Aspiration of food and/or fluids occurred in 36% of FEES; 24% silently. Median NZSS was 3 (range 0–7); with silent aspiration of secretions in 33% of FEES. There was a significant correlation between NZSS and PAS (R = .37, p < .001). Incidence of pneumonia during admission was 46% and was significantly associated with PAS (p < .001), NZSS (p < .001), age (p < .001), and tracheostomy (p < .001). Of those who developed pneumonia, 33% had both high PAS (>5) and high NZSS (>4). Eleven percent of those who developed pneumonia had an elevated NZSS (>4) in the absence of aspiration (PAS < 6). This large study reports the significant relationship between accumulated secretions, airway responsiveness, and pneumonia. This comprehensive scale is a useful tool when carrying out endoscopic evaluation and has the potential to predict pneumonia in patients irrespective of their aspiration status.
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Cross-Cultural Adaptation and Validation of the SWAL-QoL Questionnaire in Greek
Abstract
The purpose of this study was to translate and adapt the 44-item SWAL-QoL into Greek and examine its internal consistency, test–retest reliability, external construct validity, and discriminant validity in order to provide a validated dysphagia-specific QoL instrument in the Greek language. The instrument was translated into Greek using the back translation to ensure linguistic validity and was culturally adapted resulting in the SWAL-QoL-GR. Two groups of participants were included: a patient group of 86 adults (48 males; age range: 18–87 years) diagnosed with oropharyngeal dysphagia, and an age-matched healthy control group (39 adults; 19 males; age range: 18–84 years). The Greek 30-item version of the WHOQOL-BREF was used for assessment of construct validity. Overall, the questionnaire achieved good to excellent psychometric values. Internal consistency of all 10 subscales and the physical symptoms scale of the SWAL-QoL-GR assessed by Cronbach's α was good to excellent (0.811 < α < 0.940). Test–retest validity was found to be good to excellent as well. In addition, moderate to strong correlations were found between seven of the ten subscales of the SWAL-QoL-GR with limited items of the WHOQΟL-BREF (0.401 < ρ < 0.65), supporting good construct validity of the SWAL-QoL-GR. The SWAL-QoL-GR also correctly differentiated between patients with dysphagia and age-matched healthy controls (p < 0.001) on all 11 scales, further indicating excellent discriminant validity. Finally, no significant differences were found between the two sexes. This cultural adaptation and validation allows the use of this tool in Greece, further enhancing our clinical and scientific efforts to increase the evidence-based practice resources for dysphagia rehabilitation in Greece.
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Changes in Swallowing-Related Quality of Life After Endoscopic Treatment for Zenker’s Diverticulum Using the SWAL-QOL Questionnaire
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Long noncoding RNA ZEB1-AS1 epigenetically regulates the expressions of ZEB1 and downstream molecules in prostate cancer
Abstract
Background
Emerging studies show that long noncoding RNAs (lncRNAs) play important roles in carcinogenesis and cancer progression. The lncRNA ZEB1 antisense 1 (ZEB1-AS1) derives from the promoter region of ZEB1 and we still know little about its expressions, roles and mechanisms.
Methods
RACE was used to obtain the sequence of ZEB1-AS1. RNA interference was used to decrease ZEB1-AS1 expression. Adenovirus expression vector was used to increase ZEB1-AS1 expression. CHIP and RIP were used to detect the epigenetic mechanisms by which ZEB1-AS1 regulated ZEB1. CCK8 assay, wound healing assay and transwell assay were used to measure proliferation and migration of prostate cancer cells.
Results
In this study, in prostate cancer cells, we found that RNAi-mediated downregulation of ZEB1-AS1 induced significant ZEB1 inhibition while artificial overexpression of ZEB1-AS1 rescued ZEB1 expression, which means that ZEB1-AS1 promotes ZEB1 expression. Also, ZEB1-AS1 indirectly inhibited miR200c, the well-known target of ZEB1, and upregulated miR200c's target BMI1. Mechanistically, ZEB1-AS1 bound and recruited histone methyltransferase MLL1 to the promoter region of ZEB1, induced H3K4me3 modification therein, and activated ZEB1 transcription. Biologically, ZEB1-AS1 promoted proliferation and migration of prostate cancer cells.
Conclusions
Collectively, ZEB1-AS1 functions as an oncogene in prostate cancer via epigenetically activating ZEB1 and indirectly regulating downstream molecules of ZEB1.
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Pioneering Review Compares State-Level Hearing Aid Coverage
Researchers at the University of South Florida conducted the first-ever comprehensive review of state Medicaid hearing aid coverage for older adults. The study was published in the August edition of Health Affairs entitled "Medicaid Hearing Aid Coverage for Older Adult Beneficiaries: A State-by-State Comparison."
While more than 26 million older adults in the United States have hearing loss, only about 25 percent of those with moderate to severe hearing loss use hearing aids, and the percentage may be even lower in those with mild to moderate hearing loss. The study's lead author, Michelle Arnold, AuD, highlighted the significance of the issue: "Lack of hearing aid uptake is a public health concern, as untreated age-related hearing loss, with its concomitant reductions in speech understanding is associated with increased risks of social isolation, falls, hospitalizations and cognitive decline and with a disease burden of up to four disability-adjusted life years."
The researchers found that 22 states do not provide Medicaid hearing aid coverage at all since coverage is not federally mandated. Of the states that do provide coverage, the extent varies widely.
The study used six criteria to rank the states' Medicaid coverage policies, including eligibility of assessment and treatment, two hearing aids, batteries, supplies, follow-up rehabilitation, and repairs or replacement.
The researchers conclude the study by urging that "federal policy makers should consider making hearing health care, including the coverage of hearing aids, mandated under Medicaid."
Published: 8/22/2017 3:59:00 PM
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Early Intervention Improves Vocabulary of Hearing- Impaired Children
A recent study conducted at the Institute of Cognitive Science (ICS) at the University of Colorado found that infants born with hearing loss who are identified and treated according to the Early Hearing Detection and Intervention (EHDI) guidelines have markedly better vocabulary outcomes than those who are not. This is the first multi-state study to examine the effectiveness of all three stages of EHDI on vocabulary outcomes.
The study analyzed 448 children (between the ages of 8 to 39 months) with hearing loss participating in the National Early Childhood Assessment Project in 12 states. Fifty-eight percent of the study participants were found to meet the EHDI 1-3-6 guidelines.
The EHDI 1-3-6 guidelines include a hearing loss screening within one month of age, a diagnosis of hearing loss by a specialist within three months of age, and an intervention by six months.
Of the participants who were treated within six months, their Vocabulary Quotients (VQs) had a mean of 82, while 64 percent of those who did not meet EHDI guidelines but had no additional disabilities had a score less than 75 (100 is the norm).
According to Christine Yoshinaga-Itano, PhD, audiologist and researcher at ICS, children who do not receive early intervention in accordance with the EHDI timeframe are considered to have what amounts to an "environmentally induced and preventable secondary disability" and observed to function like children with cognitive delay.
The researchers concluded that future systemic improvement of vocabulary learning will need to focus on "preventing widening delays with chronological age, assisting mothers with lower levels of education, and incorporating adults who are deaf/hard of hearing in the intervention process."
Published: 8/22/2017 8:28:00 AM
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Deletion of 11q in neuroblastomas drives sensitivity to PARP inhibition
Purpose: Despite advances in multimodal therapy, neuroblastomas with hemizygous deletion in chromosome 11q (20-30%) undergo consecutive recurrences with poor outcome. We hypothesized that patients with 11q loss may share a druggable molecular target(s) that can be exploited for a precision medicine strategy to improve treatment outcome. Experimental Design: SNP arrays were combined with next generation sequencing (NGS) to precisely define the deleted region in 17 primary 11q-loss neuroblastomas and identify allelic variants in genes relevant for neuroblastoma aetiology. We assessed PARP inhibitor olaparib in combination with other chemotherapy medications using both in vitro and in vivo models. Results: We detected that ATM haploinsufficiency and ATM allelic variants are common genetic hallmarks of 11q-loss neuroblastomas. Based on the distinct DNA repair pathways triggered by ATM and PARP, we postulated that 11q-loss may define a subgroup of neuroblastomas with higher sensitivity to PARP inhibitors. Noteworthy, concomitant treatment with olaparib and DNA alkylating agent temozolomide potently inhibited growth of cell lines harboring 11q-loss. This drug synergism was less potent when temozolomide was exchanged for cisplatin or irinotecan. Intact 11q cells concomitantly treated with ATM inhibitor displayed growth arrest and enhanced apoptosis, revealing a role for ATM in the mechanism that mediates sensitivity to temozolomide-olaparib. Interestingly, functional TP53 is required for efficacy of this treatment. In an in vivo model, co-administration of temozolomide-olaparib resulted in sustained xenograft regression. Conclusions: Our findings reveal a potent synergism between temozolomide and olaparib in treatment of neuroblastomas with 11q loss and provide a rationale for further clinical investigation.
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Frequent Genetic Aberrations in the CDK4 Pathway in Acral Melanoma indicate the potential for CDK4/6 Inhibitors in Targeted Therapy
Purpose: Effective therapies for the majority of metastatic acral melanoma (AM) patients has not been established. Thus, we investigated genetic aberrations of CDK4 pathway in AM and evaluate the efficacy of CDK4/6 inhibitors in targeted therapy of AM. Experimental Design: A total of 514 primary AM samples were examined for the copy number variations (CNVs) of CDK4 pathway-related genes, including Cdk4, Ccnd1 and P16INK4a, by QuantiGenePlex DNA Assay. The sensitivity of established AM cell lines and patient-derived xenograft (PDX) containing typical CDK4 aberrations to CDK4/6 inhibitors was evaluated. Results: Among the 514 samples, 203 cases, 137 cases and 310 cases respectively showed Cdk4 gain (39.5%), Ccnd1 gain (26.7%) and p16INK4a loss (60.3%). The overall frequency of AMs that contain at least one aberration in Cdk4, Ccnd1 and P16INK4a was 82.7%. The median overall survival time for AM patients with concurrent Cdk4 gain with P16INK4a loss was significantly shorter than that for patients without such aberrations P = .005). The pan-CDK inhibitor AT7519 and selective CDK4/6 inhibitor PD0332991 could inhibit the cell viability of AM cells and the tumor growth of PDX with Cdk4 gain plus Ccnd1 gain, Cdk4 gain plus P16INK4a loss and Ccnd1 gain plus P16INK4a loss. Conclusions: Genetic aberration of CDK4 pathway is a frequent event in AM. AM cell lines and PDX containing CDK4 pathway aberrations are sensitive to CDK4/6 inhibitors. Our study provides evidence for the testing of CDK4/6 inhibitors in AM patients.
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Local allergic rhinitis is an independent rhinitis phenotype: The results of a 10-years follow-up study
Abstract
Background
The knowledge about the natural history of local allergic rhinitis (LAR) is limited. One unmeet question is to demonstrate whether LAR should be considered the first step in the development of allergic rhinitis (AR) or an independent phenotype. The aim of this study was to prospectively evaluate the natural history of a population with LAR, the potential conversion to AR with systemic atopy, and the development of asthma during 10 years.
Methods
This is the second phase of a 10 year follow-up study of a cohort of 176 patients with LAR of recent onset and 115 age- and sex-matched healthy controls prospectively evaluated from 2005 to 2016. Clinical-demographic questionnaire, spirometry, skin prick-test, and specific-IgE were evaluated yearly. Nasal allergen provocation tests (NAPT) with D. pteronyssinus, Alternaria alternata, Olea europaea, and grass pollen were performed at baseline, and after 5 and 10 years.
Results
After 10 years LAR patients experienced a significant and clinically relevant worsening of the rhinitis, with increase of emergency assistance, development of asthma, loss of allergen tolerance, and impairment of the quality of life. This worsening became significant after 5 years and progressed throughout 10 years.
A similar rate of development of AR with systemic atopy was detected in patients and controls (9.7% vs 7.8%, Log-rank p=0.623). In 5 patients conversion to systemic atopy occurred >10 years (3%).
Conclusions
LAR is a well-differentiated clinical entity with a low rate of development of systemic atopy, a natural evolution towards worsening and a risk factor for suffering asthma.
This article is protected by copyright. All rights reserved.
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Motor impairment and compensation in a hemiparkinsonian rat model: correlation between dopamine depletion severity, cerebral metabolism and gait patterns
Abstract
Background
In Parkinson's disease (PD), cerebral dopamine depletion is associated with PD subtype-specific metabolic patterns of hypo- and hypermetabolism. It has been hypothesised that hypometabolism reflects impairment, while hypermetabolism may indicate compensatory activity. In order to associate metabolic patterns with pathophysiological and compensatory mechanisms, we combined resting state [18F]FDG-PET (to demonstrate brain metabolism in awake animals), [18F]FDOPA-PET (dopamine depletion severity) and gait analysis in a unilateral 6-hydroxydopamine rat model.
Results
We found unilateral nigro-striatal dopaminergic loss to decrease swing speed of the contralesional forelimb and stride length of all paws in association with depletion severity. Depletion severity was found to correlate with compensatory changes such as increased stance time of the other three paws and diagonal weight shift to the ipsilesional hind paw. [18F]FDG-PET revealed ipsilesional hypo- and contralesional hypermetabolism; metabolic deactivation of the ipsilesional network needed for sensorimotor integration (hippocampus/retrosplenial cortex/lateral posterior thalamus) was solely associated with bradykinesia, but hypometabolism of the ipsilesional rostral forelimb area was related to both pathological and compensatory gait changes. Mixed effects were also found for hypermetabolism of the contralesional midbrain locomotor region, while contralesional striatal hyperactivation was linked to motor impairments rather than compensation.
Conclusions
Our results indicate that ipsilesional hypo- and contralesional hypermetabolism contribute to both motor impairment and compensation. This is the first time when energy metabolism, dopamine depletion and gait analysis were combined in a hemiparkinsonian model. By experimentally increasing or decreasing compensational brain activity, its potential and limits can be further investigated.
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Combined targeting of Arf1 and Ras potentiates anticancer activity for prostate cancer therapeutics
Abstract
Background
Although major improvements have been made in surgical management, chemotherapeutic, and radiotherapeutic of prostate cancer, many prostate cancers remain refractory to treatment with standard agents. Therefore, the identification of new molecular targets in cancer progression and development of novel therapeutic strategies to target them are very necessary for achieving better survival for patients with prostate cancer. Activation of small GTPases such as Ras and Arf1 is a critical component of the signaling pathways for most of the receptors shown to be upregulated in advanced prostate cancer.
Methods
The drug effects on cell proliferation were measured by CellTiter 96® AQueous One Solution Cell Proliferation Assay. The drug effects on cell migration and invasion were determined by Radius™ 24-well and Matrigel-coated Boyden chambers. The drug effects on apoptosis were assessed by FITC Annexin V Apoptosis Detection Kit with 7-AAD and Western blot with antibodies against cleaved PARP and Caspase 3. A NOD/SCID mouse model generated by subcutaneous injection was used to assess the in vivo drug efficacy in tumor growth. ERK activation and tumor cell proliferation in xenografts were examined by immunohistochemistry.
Results
We show that Exo2, a small-molecule inhibitor that reduces Arf1 activation, effectively suppresses prostate cancer cell proliferation by blocking ERK1/2 activation. Exo2 also has other effects, inhibiting migration and invasion of PCa cells and inducing apoptosis. The Ras inhibitor salirasib augments Exo2-induced cytotoxicity in prostate cancer cells partially by enhancing the suppression of ERK1/2 phosphorylation. In a xenograft mouse model of prostate cancer, Exo2 reduces prostate tumor burden and inhibits ERK1/2 activation at a dose of 20 mg/kg. Synergistic treatment of salirasib and Exo2 exhibits a superior inhibitory effect on prostate tumor growth compared with either drug alone, which may be attributed to the more efficient inhibition of ERK1/2 phosphorylation.
Conclusion
This study suggests that simultaneous blockade of Arf1 and Ras activation in prostate cancer cells is a potential targeted therapeutic strategy for preventing prostate cancer development.
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Characterization of in vivo resistance to osimertinib and JNJ-61186372, an EGFR/Met bi-specific antibody, reveals unique and consensus mechanisms of resistance
Approximately 10% of non-small cell lung cancer (NSCLC) patients in the U.S. and 40% of NSCLC patients in Asia have activating EGFR mutations and are eligible to receive targeted anti-EGFR therapy. Despite an extension of life expectancy associated with this treatment, resistance to EGFR tyrosine kinase inhibitors and anti-EGFR antibodies is almost inevitable. To identify additional signaling routes that can be co-targeted to overcome resistance, we quantified tumor-specific molecular changes that govern resistant cancer cell growth and survival. Mass spectrometry-based quantitative proteomics was used to profile in vivo signaling changes in 41 therapy resistant tumors from four xenograft NSCLC models. We identified unique and tumor-specific tyrosine phosphorylation rewiring in tumors resistant to treatment with the irreversible third generation EGFR-inhibitor, osimertinib, or the novel dual-targeting EGFR/Met antibody, JNJ-61186372. Tumor-specific increases in tyrosine-phosphorylated peptides from EGFR family members, Shc1 and Gab1 or Src family kinase substrates were observed, underscoring a differential ability of tumors to uniquely escape EGFR inhibition. Although most resistant tumors within each treatment group displayed a marked inhibition of EGFR as well as Src family kinase (SFK) signaling, the combination of EGFR inhibition (osimertinib) and SFK inhibition (saracatinib or dasatinib) led to further decrease in cell growth in vitro. This result suggests that residual SFK signaling mediates therapeutic resistance and that elimination of this signal through combination therapy may delay onset of resistance. Overall, analysis of individual resistant tumors captured unique in vivo signaling rewiring that would have been masked by analysis of in vitro cell population averages.
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Targeting TAO kinases using a new inhibitor compound delays mitosis and induces mitotic cell death in centrosome amplified breast cancer cells.
Thousand-and-one amino acid kinases (TAOKs) 1 and 2 are activated catalytically during mitosis and can contribute to mitotic cell rounding and spindle positioning. Here, we characterize a compound that inhibits TAOK1 and TAOK2 activity with IC50 values of 11-15 nM, is ATP-competitive and targets these kinases selectively. TAOK inhibition or depletion in centrosome amplified SKBR3 or BT549 breast cancer cell models increases the mitotic population, the percentages of mitotic cells displaying amplified centrosomes and multipolar spindles, induces cell death and inhibits cell growth. In contrast, non-tumorigenic and dividing bipolar MCF-10A breast cells appear less dependent on TAOK activity and can complete mitosis and proliferate in the presence of the TAOK inhibitor. We demonstrate that TAOK1 and TAOK2 localize to the cytoplasm and centrosomes respectively during mitosis. Live cell imaging shows that the TAOK inhibitor prolongs the duration of mitosis in SKBR3 cells, increases mitotic cell death and reduces the percentages of cells exiting mitosis, whereas MCF-10A cells continue to divide and proliferate. Over 80% of breast cancer tissues display supernumerary centrosomes and tumor cells frequently cluster extra centrosomes to avoid multipolar mitoses and associated cell death. Consequently, drugs that stimulate centrosome declustering and induce multipolarity are likely to target dividing centrosome amplified cancer cells preferentially, whilst sparing normal bipolar cells. Our results demonstrate that TAOK inhibition can enhance centrosome declustering and mitotic catastrophe in cancer cells and these proteins may therefore offer novel therapeutic targets suitable for drug inhibition and the potential treatment of breast cancers, where supernumerary centrosomes occur.
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HPMA-Copolymer Nanocarrier Targets Tumor-Associated Macrophages in Primary and Metastatic Breast Cancer
Polymeric nanocarriers such as N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers deliver drugs to solid tumors and avoid the systemic toxicity of conventional chemotherapy. Because HPMA copolymers can target sites of inflammation and accumulate within innate immune cells, we hypothesized that HPMA copolymers could target tumor-associated macrophages (TAMs) in both primary and metastatic tumor microenvironments. We verified this hypothesis, first in preliminary experiments with isolated bone marrow macrophage cultures in vitro, and subsequently in a spontaneously metastatic murine breast cancer model generated from a well-established, cytogenetically characterized 4T1 breast cancer cell line. Using our standardized experimental conditions, we detected primary orthotopic tumor growth at 7 days and metastatic tumors at 28 days after orthotopic transplantation of 4T1 cells into the mammary fat pad. We investigated the uptake of HPMA copolymer conjugated with Alexa Fluor 647 and folic acid (P-Alexa647-FA) and HPMA copolymer conjugated with IRDye 800CW (P-IRDye), following their retroorbital injection into the primary and metastatic tumor-bearing mice. A significant uptake of P-IRDye was observed at all primary and metastatic tumor sites in these mice, and the P-Alexa647-FA signal was found specifically within CD11b+TAMs co-stained with pan macrophage marker CD68. These findings demonstrate, for the first time, a novel capacity of a P-Alexa647-FA conjugate to colocalize to CD11b+CD68+ TAMs in both primary and metastatic breast tumors. This underscores the potential of this HPMA nanocarrier to deliver functional therapeutics that specifically target tumor-promoting macrophage activation and/or polarization during tumor development.
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Arginine Deprivation Therapy: Putative Strategy to Eradicate Glioblastoma Cells by Radiosensitization
Tumor cells - even if non-auxotrophic - are often highly sensitive to arginine deficiency. We hypothesized that arginine deprivation therapy (ADT) if combined with irradiation could be a new treatment strategy for glioblastoma (GBM) patients since systemic ADT is independent of local penetration and diffusion limitations. A proof-of-principle in vitro study was performed with ADT been mimicked by application of recombinant human arginase or arginine-free diets. <p>ADT inhibited 2-D growth and cell cycle progression, and reduced growth recovery after completion of treatment in four different GBM cell line models. Cells were less susceptible to ADT alone in the presence of citrulline and in a 3-D environment. Migration and 3-D invasion were not unfavourably affected. However, ADT caused a significant radiosensitization which was more pronounced in a GBM cell model with p53 loss of function as compared to its p53- wildtype counterpart. The synergistic effect was independent of basic and induced argininosuccinate synthase (ASS) or argininosuccinate lyase (ASL) protein expression and not abrogated by the presence of citrulline. The radiosensitizing potential was maintained or even more distinguishable in a 3-D environment as verified in p53-knockdown and p53-wildtype U87-MG cells via a 60-day spheroid control probability assay. While the underlying mechanism is still ambiguous, the observation of ADT-induced radiosensitization is of great clinical interest, in particular for patients with GBM showing high radioresistance and/or p53 loss of function.
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Intermediate-term outcome after PSMA-PET guided high-dose radiotherapy of recurrent high-risk prostate cancer patients
Abstract
Background
By the use of PSMA positron emission tomography (PET) detection of prostate cancer lesions with a high sensitivity and specificity combined with a favorable lesion to background contrast is feasible. Therefore, PSMA-PET is increasingly used for planning of radiotherapy treatment; however, any data on intermediate-term outcome is missing so far.
Methods
Patients with high-risk or very high risk prostate cancer, referred for salvage radiotherapy (SRT, n = 22) between 2013 and 2015, underwent PSMA-PET prior to therapy. Irradiation was planned on PET data with boost to macroscopic tumors/metastases. Treatment related toxicity was measured using Common Terminology Criteria for Adverse Events (CTCAE, v4.0).
Result
Findings in PSMA-PET led to treatment modifications in 77% of SRT patients compared to available CT information. One patient did not receive irradiation due to disseminated disease, the other patients received increased boost doses to macroscopic disease and/or inclusion of additional target volumes. Toxicity was low as only 2 patients reported toxicities > grade 1. With a Median follow-up time of 29 in patients that were not lost to follow-up, prolonged PSA responses below baseline were observed in the majority of patients (14 of 20). In hormone-naïve SRT patients (n = 11), radiotherapy led to prolonged PSA decrease in 8/11 patients, however with 3 of these 8 patients receiving repeated PSMA based irradiation of novel lesions during follow-up.
Conclusion
PSMA-PET guided planning of radiotherapy led to change of treatment in the majority of patients. Treatment related toxicity was well tolerated and promising results regarding intermediate-term PSA decrease were observed.
Trial registration
No trial registration was performed due to retrospective evaluation.
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Preoperative intensity-modulated radiotherapy with a simultaneous integrated boost combined with Capecitabine in locally advanced rectal cancer: short-term results of a multicentric study
Preoperative radiotherapy (RT) in combination with fluoropyrimidine-based chemotherapy (CT) is the standard of care in patients with locally advanced, T3-T4 N0–2, rectal cancer (LARC). Given the correlation be...
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Thoracolithiasis – CT findings of intrapleural loose bodies
Thoracoliths are rare benign intrapleural loose bodies, often containing calcification, that are mobile in the pleural cavity. The presence of these intrapleural nodules is referred to as thoracolithiasis. The exact etiology of thoracoliths is unknown, but they presumably result from a prior episode of mediastinal (epipericardial) fat necrosis. Thoracoliths are usually asymptomatic and incidentally encountered on CT.However, they sometimes pose diagnostic challenges, as a thoracolith may be located within a pleural fissure, and is then indistinguishable from a pulmonary nodule.
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Human pluripotent stem cell-derived TSC2-haploinsufficient smooth muscle cells recapitulate features of Lymphangioleiomyomatosis
Lymphangioleiomyomatosis (LAM) is a progressive destructive neoplasm of the lung associated with inactivating mutations in the TSC1 or TSC2 tumor suppressor genes. Cell or animal models that accurately reflect the pathology of LAM have been challenging to develop. Here we generated a robust human cell model of LAM by reprogramming TSC2 mutation-bearing fibroblasts from a patient with both Tuberous Sclerosis Complex (TSC) and LAM (TSC-LAM) into induced pluripotent stem cells (iPSCs), followed by selection of cells that resemble those found in LAM tumors by unbiased in vivo differentiation. We established expandable cell lines under smooth muscle cell (SMC) growth conditions that retained a patient-specific genomic TSC2+/- mutation and recapitulated the molecular and functional characteristics of pulmonary LAM cells. These include multiple indicators of hyperactive mTORC1 signaling, presence of specific neural crest and SMC markers, expression of VEGF-D and female sex hormone receptors, reduced autophagy, and metabolic reprogramming. Intriguingly, the LAM-like features of these cells suggest that haploinsufficiency at the TSC2 locus contributed to LAM pathology, and demonstrated that iPSC reprogramming and SMC lineage differentiation of somatic patient cells with germline mutations was a viable approach to generate LAM-like cells. The patient-derived SMC lines we have developed thus represent a novel cellular model of LAM which can advance our understanding of disease pathogenesis and develop therapeutic strategies against LAM.
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Stent migration into the abdominal cavity after EUS-guided hepaticogastrostomy
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Esophageal Cryoablation Using Retrograde Per-Gastrostomy Ventilation in A Patient with Pharyngoesophageal Stenosis
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GIE: At the Focal Point Direct Visualization of IgG4-related Cholangiopathy
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Acute suppurative cholangitis due to an impacted pancreatic stone: a rare adverse event in the setting of chronic calcified pancreatitis
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The correlation between periodontal health status and suspectibility to infections associated with craniomaxillofacial osteosynthesis plates
none.
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Utility of Tc-99m MDP bone SPECT in evaluation of osseous involvement in craniofacial malignancies
To assess the role of technetium-99m methoxy diphosphonate (Tc-99m MDP) single photon emission tomography (SPECT) imaging for the detection of osseous invasion in craniofacial malignancies.
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Clinical study of splint therapeutic efficacy for the relief of temporomandibular joint discomfort
This study aimed to evaluate the relationship between displacement of the mandibular condyle/disc due to occlusal splint insertion with splint therapy and changes in discomfort of the temporomandibular joint (TMJ), and to clarify the relationships between the outcomes over time of temporomandibular discomfort and TMJ magnetic resonance imaging (MRI) findings at the initiation of splint therapy.
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New Kids in the Neighborhood: Biosimilars
Mineral Intake and Status of Cow's Milk Allergic Infants Consuming an Amino Acid-based Formula
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Alas, Who and What Can We Trust? Patients, Parents, Surrogate Markers, or the Specific Carbohydrate Diet
Dietary Inadequacies in HIV-infected and Uninfected School-aged Children in Johannesburg, South Africa
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No Need for Routine Endoscopy in Children With Celiac Disease on a Gluten-free Diet
A Child With Ichthyosis and Liver Failure
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Zero, One, or Two Endoscopies to Diagnose and Monitor Pediatric Celiac Disease? The Jury Is Still Out
Early and Late Factors Impacting Patient and Graft Outcome in Pediatric Liver Transplantation: Summary of an ESPGHAN Monothematic Conference
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Detection of Sepsis in Preterm Infants by Fecal Volatile Organic Compounds Analysis: A Proof of Principle Study
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Feed-induced Dystonias in Children With Severe Central Nervous System Disorders
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Esomeprazole FDA Approval in Children With GERD: Exposure-Matching and Exposure-Response
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Endoscopic Closure of Gastric Leak Following Sleeve Gastrectomy in a Pediatric Patient
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Low-impedance Baseline Values Predict Severe Esophagitis
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Omega-3 fatty acid levels in red blood cell membranes and physical decline over 3 years: longitudinal data from the MAPT study
Abstract
Studies have shown that omega-3 polyunsaturated fatty acids (PUFAs) are associated with brain, cardiovascular, and immune function, as well as physical performance and bone health in older adults. So far, few studies have investigated the associations between PUFA status and performance-based tests of physical function. The objective of this study was to investigate the associations between the omega-3 PUFA levels (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)) in red blood cell (RBC) membranes and physical performance, in a sample of community-dwelling older adults. This is a longitudinal observational study using data from the Multidomain Alzheimer's Disease Trial (MAPT), a randomized, placebo-controlled trial. Four hundred participants from MAPT placebo group with available PUFA data were included. Omega-3 PUFA levels in RBC membranes were measured at baseline, and their percentage of total RBC membrane fatty acid content was calculated. We dichotomized the standardized omega-3 PUFA levels in RBC membranes as low (lowest quartile) vs. high (three upper quartiles). Gait speed (in m/s) and short physical performance battery (SPPB) score (range from 0 to 12, higher is better) were used to assess physical performance at baseline and after 6, 12, 24, and 36 months. Participants were 75.2 (± 4.3) years old and 68% were female. Bivariate analyses found that the characteristic of the participants in the lowest quartile of omega-3 PUFA levels (Q1) and those in the three upper quartiles (Q2–Q4) was not different at baseline; only those in Q1 were slightly older. In an unadjusted model, the difference in gait speed after 3 years of follow-up was significant (− 0.09 ± 0.03 m/s; p = 0.008) between participants in Q1 and those in Q2–Q4. In a model adjusted for age, gender, educational level, cognitive function, depressive status, body mass index, physical activity, grip strength, and their time interaction, this difference remained clinically relevant (− 0.07 ± 0.04 m/s; p = 0.075). No difference between the two groups was found for the SPPB score development over 3 years. Older adults with subjective memory complaints and in the lower quartile of omega-3 have a faster decline on gait speed compared to people in the three upper quartiles. Other longitudinal studies are needed to explore this association and to examine mechanisms.
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Convex Bone Deformity after Closed Reduction of Nasal Bone Fracture
Nasal fractures are the most common type of facial fracture treated by plastic surgeons. Here, we clarify the postoperative deformities that frequently remain after closed reduction of fresh nasal bone fracture by three-dimensional computed tomography (3D-CT).
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Clinical Outcomes for Minimally Invasive Primary and Secondary Orbital Reconstruction using an Advanced Synergistic Combination of Navigation and Endoscopy
Sequelae of inadequate orbital reconstruction include enophthalmos, hypoglobus, and diplopia. Accuracy of orbital reconstruction is largely subjective and especially difficult to achieve due to anatomic distortion in secondary or late reconstruction and in extensive injury. We combined computer navigation and endoscopy to perform accurate, aesthetic, and safe minimal-access primary and secondary orbital reconstruction.
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Sentinel lymph node biopsy for thin melanomas under the American Joint Committee on Cancer 8th edition cancer staging system
The American Joint Committee on Cancer (AJCC) will implement the 8th edition of their cancer staging system on the 1st January 2018, with changes to the way in which thin melanomas are classified. Our understanding of these criteria contrasts with previous correspondence in this journal.1 Tumours with a Breslow thickness <0.8mm will be classified as T1a if they do not exhibit ulceration, and as T1b if they do exhibit ulceration. All tumours measuring 0.8-1.0mm thick will be reclassified as T1b regardless of ulceration.
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Preventing the Complications of Tissue Expansion Using Fat Grafting Under Expanded Skin
We read with great interest the brief clinical report entitled "Preventing the complications of tissue expansion using fat grafting under expanded skin" by Jiang et al.1 The authors demonstrate for the first time a technique improving the texture of expanded skin and preventing expansion failure by lipofilling into the ischemic region of the expanded flap. We would like to congratulate the authors for their primary work to make the skin expansion can be smoothly completed. Improving expansion efficiency and decreasing complications of expansion are always the subjects that we have thought a great deal about and worked intensively on.
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Motor Nerve to the Masseter: A Pediatric Anatomic Study and the “3:1 Rule”
The motor nerve to the masseter (masseteric nerve) provides a robust local neural source for facial reanimation and nerve transfer. Its intraoperative identification is well-described in adults. The purpose of this study was to determine the location of the motor nerve to the masseter in the pediatric population using surgical landmarks.
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Non-living microvascular training models: Face validity of liquid latex and the challenge of structural vs. “physiological” patency assessment
Microvascular anastomosis training increasingly uses assessment tools to objectively evaluate the surgeons' performance and to track progression in this challenging learning curve. The first steps in microvascular skills acquisition are accomplished via a variety of training models in a safe simulation training environment1, with an increasing use of non-living biological models over living animal models, in line with the ethical considerations of replacement, reduction and refinement.
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Gender Perception After Raising Vowel Fundamental and Formant Frequencies: Considerations for Oral Resonance Research
Voice feminization therapy for male-to-female transgender women typically targets increasing fundamental frequency (F0). Increasing vowel formant frequencies (FFs) has also been proposed. To better understand formant conditions that shift listeners' perception of gender from male to "not-male," individual and combined vowel FFs were incrementally raised, whereas F0 was held constant at a gender-ambiguous level.
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Peri-operative factors predisposing to pharyngocutaneous fistula after total laryngectomy: analysis of a large multi-institutional patient cohort
Abstract
Background
Pharyngocutaneous fistula (PCF) is a problematic complication following total laryngectomy. Disagreement remains regarding predisposing factors. This study examines perioperative factors predicting PCF following total laryngectomy using a large multicenter data registry.
Methods
Retrospective cohort analysis was performed using patients undergoing total laryngectomy in the ACS-NSQIP database for 2006–2014. Sub-analysis was performed based on reconstruction type. Outcome of interest was PCF development within 30 days.
Results
Multivariate analysis of 971 patients was performed. Three variables showed statistical significance in predicting PCF: wound classification of 3 and 4 vs. 1–2 (OR 6.42 P < 0.0004 and OR 8.87, P < 0.0042), pre-operative transfusion of > 4 units of packed red blood cells (OR 6.28, P = 0.043), and free flap versus no flap reconstruction (OR 2.81, P = 0.008).
Conclusions
This study identifies important risk factors for development of PCF following total laryngectomy in a large, multi-institutional cohort of patients, thereby identifying a subset of patients at increased risk.
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Development of a Universal Nutritional Screening Platform for Plastic Surgery Patients
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Temporomandibular joint reconstruction after condylar fracture complication related to osteosynthesis material
Total condylar resorption and the failure of bone synthesis material as postoperative complications of condyle fracture are seldom reported in the literature. When these occur, they may severely limit temporomandibular joint (TMJ) function. In such cases, a reconstruction of the joint is indicated, which can be achieved by means of an alloplastic prosthesis. This article reports a rare case of impaction of osteosynthesis material in the region of the base of the skull associated with a mandibular condyle fracture treated with rigid internal fixation, which resulted in complications.
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Novel Multidisciplinary Management of a Retropharyngeal Hematoma With Pulmonary Stenting
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Is voice therapy effective for the treatment of dysphonic patients with benign vocal fold lesions?
To update our knowledge regarding the effectiveness of voice therapy for the treatment of vocal disturbance associated with benign vocal fold lesions, including vocal polyps, nodules and cysts, and for determining the utility of voice therapy in treating organic voice disorders, while highlighting problems for the future development of this clinical field.
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Risk factors for the occurrence of epistaxis: Prospective study
Analyse and compare the characteristics of patients with epistaxis admitted to the otolaryngology emergency department with those provided by a control group. Establish a model to identify epistaxis predictive factors.
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A case of ectopic salivary gland of the larynx
A 46-year-old man presented with sore throat. Laryngoscopic findings revealed a smooth yellow mass occupying the anterior portion of the false vocal fold on the left side. The authors performed biopsy under general anesthesia. The histopathological diagnosis was ectopic salivary gland. Because salivary glands are usually not found under the false vocal fold mucosa, ectopic salivary gland of the larynx was diagnosed.It is necessary to consider the possibility of ectopic salivary gland for mass lesions if swelling of the provisional vocal cord is found.
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Whole-genome sequencing revealed novel prognostic biomarkers and promising targets for therapy of ovarian clear cell carcinoma
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Knowledge or noise? Making sense of General Practitioners’ and Consultant use of 2-week-wait referrals for suspected cancer
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Long-term outcomes of patients with 10 or more colorectal liver metastases
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Leukocyte telomere length and renal cell carcinoma survival in two studies
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Hamburg-Glasgow classification: preoperative staging by combination of disseminated tumour load and systemic inflammation in oesophageal carcinoma
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Correlation between circulating mutant DNA and metabolic tumour burden in advanced non-small cell lung cancer patients
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The cost-effectiveness of screening for ovarian cancer: results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)
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Height, selected genetic markers and prostate cancer risk: results from the PRACTICAL consortium
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Lurbinectedin reduces tumour-associated macrophages and the inflammatory tumour microenvironment in preclinical models
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The role of miRNAs in human papilloma virus (HPV)-associated cancers: bridging between HPV-related head and neck cancer and cervical cancer
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HMGA1 expression levels are elevated in pancreatic intraepithelial neoplasia cells in the Ptf1a-Cre; LSL-KrasG12D transgenic mouse model of pancreatic cancer
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Platelet releasate promotes breast cancer growth and angiogenesis via VEGF–integrin cooperative signalling
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Nuclear expression of Gli-1 is predictive of pathologic complete response to chemoradiation in trimodality treated oesophageal cancer patients
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A comparative study of germline BRCA1 and BRCA2 mutation screening methods in use in 20 European clinical diagnostic laboratories
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TCTP as a therapeutic target in melanoma treatment
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Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma
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A combined biomarker panel shows improved sensitivity for the early detection of ovarian cancer allowing the identification of the most aggressive type II tumours
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Re: Re: Mandibular Wing Osteotomy: technical modification
We thank Dr Brusco for his interest in our recent paper and for his valuable comments on the use of 3-dimensional printed cutting guides for use with the chin wing technique of osteotomy. His concerns are well-founded, but while we also wish to gain the best aesthetic result, we think that the introduction of new techniques to minimise the risk of permanent damage to the inferior alveolar nerve should not be avoided, particularly at a tertiary centre that trains residents as one of its main purposes.
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Re: Mandibular wing osteotomy: technical modification
My compliments to Coopman et al on their recent paper.1 I am familiar with the "chin wing" and its technical issues because I worked with Albino Triaca in the Klinik Pyramide in Zürich while it was being developed, and I wish to raise a point that is crucial for the success of the operation.
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If trainers regularly validate trainees’ eLogbook records, they will spot a trainee who is not keeping theirs up-to-date
The months of June and July are the season of the Annual Review of Competence Progression. During the last few weeks we have both participated in two different processes of review, during which a trainee in Oral and Maxillofacial Surgery had entered NO procedures into the eLogbook during the previous six months.
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Customised instrument to retract alveolar subperiosteal flap during the placement of dental implants: new technique
Retraction of subperiosteal flaps on the buccolingual aspect of the alveolar ridge is important for the proper insertion of dental implants. The width and height of alveolar bone should be felt clearly to prevent misdirection of the implant or penetration of bony walls.1 Recently the Thudichum nasal speculum was described for retraction during the procedure,1 and here we describe a self-retaining instrument that we designed to retract the alveolar subperiosteal flap.
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A Call for Federal Regulation of Obstructive Sleep Apnea in Transportation Workers
In a continuing quest to achieve regulatory consistency for diagnosing and treating obstructive sleep apnea in transportation workers, several sleep dentists took their concerns to Capitol Hill.
Drs. Elliott Alpher, Neal Seltzer and Michael Baylin met with a legislative aide for Senator Chris Van Hollen. (D – MD). Dr. Alpher and Dr. Baylin are Maryland residents. The three expressed concerns over the recent federal decision to halt work on a rule that would have regulated the diagnosis and treatment of obstructive sleep apnea in truck drivers and railway workers. Two weeks ago, the Federal Motor Carrier Safety Administration (FMCSA) and the Federal Railway Administration (FRA) discontinued the plan to establish a federal regulation. Instead the two agencies said that companies could develop their own standards.
The goal of the meeting with Senator Van Hollen's legislative aide for health issues was to ask the Senator to seek renewal of the formal regulatory rule-making. In addition, the doctors requested that a dental sleep medical practitioner be appointed to the FMCSA Medical Review Board, which establishes medical standards for transportation workers and sets training policy for certified medical examiners.
During the 45-minute session, the doctors explained that transportation workers endure long hours and irregular sleep patterns making them at higher risk of suffering from obstructive sleep disorders. They added that an estimated 18 million people suffer but are undiagnosed or treated.
"The health and well-being of truck drivers is critical to everyone on the highway," said Dr. Neal Seltzer of Long Island Smile.
"The lack of sleep and obstructive breathing are epidemics that will affect at least the next few generations," said Dr. Elliott Alpher.
"This lack affects your entire health and well-being," said Dr. Michael Baylin.
In a separate action, several senators called for Trump Administration to explain why it cancelled the rule-making. In a letter to the Department of Transportation on Monday, August 21, several senators asked for an explanation and all the documents that were used to cancel the rule-making process. The senators called on the Administration to reverse its decision.
"We strongly believe that DOT should immediately reconsider the decision to help avoid future fatigue-related tragedies."
The letter details several deadly railway crashes that were linked to undiagnosed sleep disorders. These included a 2013 Metro-North train derailment in New York and a New Jersey Transit crash last year. The letter is signed by Sens. Cory Booker (N.J.), Chuck Schumer (N.Y.), Bob Menendez (N.J.) and Kirsten Gillibrand (N.Y.).
For several years, The American Sleep and Breathing Academy has advocated for science-based diagnostic and treatment guidelines for the commercial trucking industry. In 2016, ASBA members submitted more than 1,000 pages of expert comments to a proposed federal rulemaking that would have established incomplete, confusing and inconsistent regulations for the diagnosis and treatment of obstructive sleep apnea.
Establishing consistent, science-based guidelines for the diagnosis and treatment of obstructive sleep apnea will improve the health of the workers and make the roads safer.
Current FMSCA Medical Review Board guidelines base a diagnosis upon three criteria, while the ASBA standard includes 14 scientific and medical points, including intraoral exams and measurements and allows for a home sleep study.
Further, the FMCSA guidelines require the driver to stop working, go to a sleep lab and return to work only conditionally until there is a diagnosis and treatment. This is costly, time-consuming and by the estimates of one trucking association, can cost the driver $5,000 to $7,000 each time.
FMCSA guidelines dictate that the continuous airway device, CPAP, is the preferred method of treatment. Patients are required to wear the CPAP for only four hours during their sleep periods. Dental sleep appliances are allowed only after the failure of CPAP therapy to improve the patient's breathing.
Pilot Sleep Program Needs Dental Sleep Expertise
In addition to the obstructive sleep apnea rule-making, the trio asked that a dental sleep medicine practitioner be allowed to help establish the proper protocol and data analysis methods for a proposed FMCSA pilot program called "Split Berth." It will examine whether allowing drivers to divide their current 14-hour work schedule and 10-hour consecutive sleep requirements into periods they manage would be beneficial. Currently the pilot program is under consideration.
While the split berth idea is favored by truck drivers, Drs. Alpher, Baylin and Seltzer expressed concerns that the pilot program is being established without the expertise of dental sleep medicine specialists.
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Chest radiographic features of human metapneumovirus infection in pediatric patients
Abstract
Background
Human metapneumovirus (HMPV) was identified in 2001 and is a common cause of acute respiratory illness in young children. The radiologic characteristics of laboratory-confirmed HMPV acute respiratory illness in young children have not been systematically assessed.
Objective
We systematically evaluated the radiographic characteristics of acute respiratory illness associated with HMPV in a prospective cohort of pediatric patients.
Materials and methods
We included chest radiographs from children <5 years old with acute respiratory illness who were enrolled in the prospective New Vaccine Surveillance Network (NVSN) study from 2003 to 2009 and were diagnosed with HMPV by reverse transcription-polymerase chain reaction (RT-PCR). Of 215 HMPV-positive subjects enrolled at our tertiary care children's hospital, 68 had chest radiographs obtained by the treating clinician that were available for review. Two fellowship-trained pediatric radiologists, independently and then in consensus, retrospectively evaluated these chest radiographs for their radiographic features.
Results
Parahilar opacities were the most commonly observed abnormality, occurring in 87% of children with HMPV. Hyperinflation also occurred frequently (69%). Atelectasis (40%) and consolidation (18%) appeared less frequently. Pleural effusion and pneumothorax were not seen on any radiographs.
Conclusion
The clinical presentations of HMPV include bronchiolitis, croup and pneumonia. Dominant chest radiographic abnormalities include parahilar opacities and hyperinflation, with occasional consolidation. Recognition of the imaging patterns seen with common viral illnesses like respiratory syncytial virus (RSV) and HMPV might facilitate diagnosis and limit unnecessary antibiotic treatment.
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