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- Brain tissue plasticity: protein synthesis rates o...
- VEGF, FGF-2 and TGFβ expression in the normal and ...
- The Anatomical Society core anatomy syllabus for p...
- Femoral Artery Bypass Graft Pseudoaneurysm Rupture...
- Preliminary use of the PANESS for detecting subtle...
- Intraosseous basivertebral nerve ablation for the ...
- Effects of a sodium fluoride- and phytate-containi...
- Correction to: Cone beam computed tomography and u...
- Objectively Differentiating Movement Patterns betw...
- Issue Information
- Erratum
- Issue Information
- Nitrate Removal from Groundwater by Heterotrophic/...
- Outcomes of the use of Ligamentotaxor® for proxima...
- Nicotinamide N-methyltransferase: potential involv...
- Fracture Resistance of Titanium-Based Lithium Disi...
- Clinical and Novel Biomarkers in the Management of...
- Options for Adjuvant Therapy for Uterine Leiomyosa...
- Second Malignancies after Hematopoietic Stem Cell ...
- Novel Therapies for Older Adults With Acute Lympho...
- Postoperative chemoradiotherapy in patients with h...
- Prevalence of adverse pathological features in 1 t...
- Quality of life during the first year after partia...
- Thyroidectomy in patients who have undergone gastr...
- Role of adjuvant chemoradiotherapy in T4N0 stage I...
- Genetic profiling of cell-free DNA from cerebrospi...
- Final Validation of the ProMisE Molecular Classifi...
- Epigenetic modifiers as new immunomodulatory thera...
- Tumor necrosis and >20 mitoses per 50 high-power f...
- Why does a high-fat diet increase cancer risk?
- High-fat diet and colorectal cancer: myths and facts
- The immediate and short-term effects of bilateral ...
- The impact of anaemia, transfusion dependency, com...
- Editorial Board
- Contents
- Light-emitting Diode Transilluminator for the Iden...
- Gender-specific independent and combined dose–resp...
- Occurrence of nocturia is not mediated by nocturna...
- An Enhanced Recovery after Surgery Pathway for Mic...
- Incisional Negative Pressure Wound Therapy for Pre...
- Successful Hand Replantation in a Case of Total Av...
- Single-Stage Breast Reconstruction Using an All-In...
- Dimensional Error in Rapid Prototyping with Open S...
- Immediate Breast Reconstruction among Patients wit...
- Use of Viable Cryopreserved Placental Membrane as ...
- The Pedicled LICAP Flap Combined with a Free Abdom...
- Adjuvant Therapy for Revision Rhinoplasty of Contr...
- Complications following Nipple-Sparing Mastectomy ...
- V-shaped Internal Nasal Vestibular Flap for Recons...
- Latissimus Dorsi and Immediate Fat Transfer (LIFT)...
- Superficial Inferior Epigastric Artery Flap Salvag...
- Clinical Significance of Venous Anomalies in Syndr...
- Earfold Implantable Clip System for Correction of ...
- Virtual Surgical Planning: The Pearls and Pitfalls
- Reexploring the Anatomy of the Distal Humerus for ...
- ASBA Diplomates Treat Hall of Fame NFL Players at ...
- Prefrontal direct current stimulation in hoarding ...
- Transcranial direct current stimulation unveils co...
- FDA Approves Test of New Drug to Protect Hearing
- Nekrotisierende zervikale Lymphadenopathie mit unk...
- Hörsturz mit Surditas, Schwindel und Tinnitus - ei...
- Endoscopic Endonasal Approach to a Suprasellar Cra...
- Macrophage Density Predicts Facial Nerve Outcome a...
- Prognostic significance of HPV status in the re-ir...
- Forehead reduction and orbital contouring in facia...
- Use of ultrasound-activated resorbable sheets and ...
- Association of sleep habits with behavior problems...
- Gender-specific independent and combined dose–resp...
- Prevalence and characteristics of sleep-disordered...
- Trazodone for the treatment of insomnia: a meta-an...
- Occurrence of nocturia is not mediated by nocturna...
- Characteristics of napping in community-dwelling i...
- Experiences with a modified preauricular mini INCI...
- Survival in patients with submandibular gland carc...
- A questionnaire to assess olfactory rehabilitation...
- The gray scale value of ear tissues undergoing vol...
- Effects of AUT00063, a Kv3.1 channel modulator, on...
- Is flucloxacillin monotherapy sufficient for the t...
- Clinical relevance of oncologic prognostic factors...
- Neutrophil-to-lymphocyte ratio decreases in obstru...
- The Impact of Fellowship in Dietetics on Clinical ...
- Food protein-induced enterocolitis syndrome: a rev...
- High density of M2-macrophages in acral lentiginou...
- IgG4-related sclerosing oesophagitis in a 9-year-o...
- Total extraperitoneal robot assisted laparoscopic ...
- Computational Models of Laryngeal Aerodynamics: Po...
- Long-term outcomes of craniofacial implants for th...
- Diffusion pseudonormalization and clinical outcome...
- Practical issues for the management of hyponatremi...
- Neutrophil-to-lymphocyte ratio decreases in obstru...
- Flavagline analog FL3 induces cell cycle arrest in...
- The human right to communicate: A survey of availa...
- Just Sentences: Human rights to enable participati...
- Urban Neighborhood and Residential Factors Associa...
- Adaptive optical microscopy for neurobiology
- Epileptiform and periodic EEG activities induced b...
- Multisession anodal transcranial direct current st...
- Can clinical neurophysiology assist in patient sel...
- Observations on muscle activity in REM sleep behav...
- Differential changes in the spinal segmental locom...
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Τετάρτη 7 Φεβρουαρίου 2018
Brain tissue plasticity: protein synthesis rates of the human brain
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GZHhzt
VEGF, FGF-2 and TGFβ expression in the normal and regenerating epidermis of geckos: implications for epidermal homeostasis and wound healing in reptiles
Abstract
The skin is a bilayered organ that serves as a key barrier between an organism and its environment. In addition to protecting against microbial invasion, physical trauma and environmental damage, skin participates in maintaining homeostasis. Skin is also capable of spontaneous self-repair following injury. These functions are mediated by numerous pleiotrophic growth factors, including members of the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and transforming growth factor β (TGFβ) families. Although growth factor expression has been well documented in mammals, particularly during wound healing, for groups such as reptiles less is known. Here, we investigate the spatio-temporal pattern of expression of multiple growth factors in normal skin and following a full-thickness cutaneous injury in the representative lizard Eublepharis macularius, the leopard gecko. Unlike mammals, leopard geckos can heal cutaneous wounds without scarring. We demonstrate that before, during and after injury, keratinocytes of the epidermis express a diverse panel of growth factor ligands and receptors, including: VEGF, VEGFR1, VEGFR2, and phosphorylated VEGFR2; FGF-2 and FGFR1; and phosphorylated SMAD2, TGFβ1, and activin βA. Unexpectedly, only the tyrosine kinase receptors VEGFR1 and FGFR1 were dynamically expressed, and only during the earliest phases of re-epithelization; otherwise all the proteins of interest were constitutively present. We propose that the ubiquitous pattern of growth factor expression by keratinocytes is associated with various roles during tissue homeostasis, including protection against ultraviolet photodamage and coordinated body-wide skin shedding.
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The Anatomical Society core anatomy syllabus for pharmacists: outcomes to create a foundation for practice
Abstract
The Anatomical Society has developed a series of learning outcomes that 'experts' within the field would recommend as core knowledge outputs for a Master's Degree Programme in Pharmacy (MPharm) within the UK. Using the Anatomical Society core gross anatomy syllabus for medical anatomy as a foundation, a modified Delphi technique was used to develop outcomes specific to pharmacy graduates. A Delphi panel consisting of medical practitioners, pharmacists and anatomists (n = 39) was created and involved 'experts' representing 20 UK Higher Education Institutions. The output from this study was 49 pharmacy-specific learning outcomes that are applicable to all pharmacy programmes. The new MPharm anatomy syllabus offers a basic anatomical framework upon which pharmacy educators can build the necessary clinical practice and knowledge. These learning outcomes could be used to develop anatomy teaching within an integrated curriculum as per requirements of the General Pharmaceutical Council (GPhC).
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Femoral Artery Bypass Graft Pseudoaneurysm Rupture in a Transfemoral Amputee: A Case Report
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2shYr7R
Preliminary use of the PANESS for detecting subtle motor signs in adolescents with sport-related concussion: a brief report
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Intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: a prospective randomized double-blind sham-controlled multi-center study
Abstract
Purpose
To evaluate the safety and efficacy of radiofrequency (RF) ablation of the basivertebral nerve (BVN) for the treatment of chronic low back pain (CLBP) in a Food and Drug Administration approved Investigational Device Exemption trial. The BVN has been shown to innervate endplate nociceptors which are thought to be a source of CLBP.
Methods
A total of 225 patients diagnosed with CLBP were randomized to either a sham (78 patients) or treatment (147 patients) intervention. The mean age within the study was 47 years (range 25–69) and the mean baseline ODI was 42. All patients had Type I or Type II Modic changes of the treated vertebral bodies. Patients were evaluated preoperatively, and at 2 weeks, 6 weeks and 3, 6 and 12 months postoperatively. The primary endpoint was the comparative change in ODI from baseline to 3 months.
Results
At 3 months, the average ODI in the treatment arm decreased 20.5 points, as compared to a 15.2 point decrease in the sham arm (p = 0.019, per-protocol population). A responder analysis based on ODI decrease ≥ 10 points showed that 75.6% of patients in the treatment arm as compared to 55.3% in the sham control arm exhibited a clinically meaningful improvement at 3 months.
Conclusion
Patients treated with RF ablation of the BVN for CLBP exhibited significantly greater improvement in ODI at 3 months and a higher responder rate than sham treated controls. BVN ablation represents a potential minimally invasive treatment for the relief of chronic low back pain.
Graphical abstract
These slides can be retrieved under Electronic Supplementary Material.
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Effects of a sodium fluoride- and phytate-containing dentifrice on remineralisation of enamel erosive lesions—an in situ randomised clinical study
Abstract
Objective
The objective of this work was to evaluate effects of a dentifrice containing sodium fluoride (1150 ppm F) and the organic polyphosphate phytate (0.85% w/w of the hexa-sodium salt) on in situ remineralisation of early enamel erosive lesions and resistance to subsequent demineralisation.
Materials and methods
Subjects (n = 62) wore palatal appliances holding eight bovine enamel specimens with pre-formed erosive lesions. They brushed their natural teeth with the phytate test dentifrice (TD); a positive control dentifrice (PC, 1150 ppm fluoride as NaF); a reference dentifrice (RD, disodium pyrophosphate + 1100 ppm fluoride as NaF) or a negative control dentifrice (NC, fluoride-free) in a randomised, double-blind, crossover design. Specimens were removed at 2, 4 and 8 h post-brushing and exposed to an ex vivo acid challenge. Surface microhardness (Knoop) was measured at each stage. The primary efficacy variable was relative erosion resistance (RER); other variables included the surface microhardness recovery (SMHR), acid resistance ratio (ARR) and enamel fluoride uptake (EFU).
Results
After 4 h, the results for RER, ARR and EFU were in the order PC > TD = RD > NC with PC > TD = RD = NC for SMHR. Results at 2 and 8 h were generally consistent with the 4 h data. Mineralisation progressed over time. Dentifrices were generally well-tolerated.
Conclusions
In this in situ model, addition of phytate or pyrophosphate to a fluoride dentifrice inhibited the remineralising effect of fluoride. Both formulations still delivered fluoride to the enamel and inhibited demineralisation, albeit to a lesser extent than a polyphosphate-free dentifrice.
Clinical relevance
Addition of phytate or pyrophosphate to a fluoride dentifrice may reduce its net anti-erosive properties.
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Correction to: Cone beam computed tomography and ultrasonography imaging of benign intraosseous jaw lesion: a prospective radiopathological study
Abstract
In the original version of this article, '123 lytic intraosseous jaw lesions diagnosed in 112 patients' was incorrectly presented as '123 lytic intraosseous jaw lesions diagnosed in 121 patients' and 'an average age of 31.7 ± 15.4 (range, 6–72)' was incorrectly presented as 'average age of 15.4 ± 31.7 (range, 6–72)'.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FSH3IX
Objectively Differentiating Movement Patterns between Elite and Novice Athletes
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Nitrate Removal from Groundwater by Heterotrophic/Autotrophic Denitrification Using Easily Degradable Organics and Nano-Zero Valent Iron as Co-Electron Donors
Abstract
Heterotrophic/autotrophic denitrification (HAD) is an effective approach to remove nitrate from contaminated groundwater. To improve its performance, easily degradable organics (methanol, ethanol, oxalic acid, and sodium acetate) and nano-zero valent iron (nZVI) were selected as co-electron donors for HAD, and their effectiveness in enhancing HAD to remove nitrate from simulated groundwater was evaluated. It was found that the removal efficiency of HAD to nitrate was significantly affected by the species of easily degradable organics as their different biological availability. Among the tested organics, ethanol-supported HAD system exhibited a better removal efficiency, and after 10 days reaction, it could achieve a high nitrate removal rate to 85.6% with an initial concentration of 90.94 mg/l, and at the end of the test (27 days), nitrate was almost completely removed in the interaction of heterotrophic denitrification (HD) and autotrophic denitrification (AD), and there was no nitrite and ammonium accumulation (< 0.1 and 1.0 mg/l). Moreover, the initial C/N ratios (0.2, 0.5, 1.0, 2.0, and 4.0) of simulated groundwater had a significant influence on nitrate removal by HAD. Increasing the C/N from 0.2 to 2.0 could markedly enhance nitrate removal efficiency, but continuously increased to 4.0 the removal rate just decreased; nevertheless, the accumulation of nitrite and ammonium were closely related to both the C/N ratios and species of organics. The synergistic effect between HD and AD process plays a vital role in the mixotrophic environment. Therefore, this research provides an effective method for nitrate removal from contaminated water with low organic carbon.
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Outcomes of the use of Ligamentotaxor® for proximal interphalangeal fractures of the hand: North Bristol hand centre experience
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BJZfGA
Nicotinamide N-methyltransferase: potential involvement in cutaneous malignant melanoma
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Fracture Resistance of Titanium-Based Lithium Disilicate and Zirconia Implant Restorations
Abstract
Purpose
To evaluate the fracture resistance of a newer lithium disilicate abutment material.
Materials and Methods
A premolar-shaped implant crown was designed using CAD/CAM software, and four groups of implant and crown combinations were milled: (1) lithium-disilicate hybrid-abutment crown; (2) "screwmentable" lithium-disilicate hybrid abutment/lithium-disilicate crown with screw channel; (3) lithium-disilicate hybrid abutment/lithium-disilicate crown; and (4) zirconia hybrid abutment/lithium-disilicate crown (control). The specimens were cemented to a titanium-base implant system, subjected to thermocycling and cyclic loading, and fractured in a material testing device.
Results
The lithium-disilicate hybrid-abutment crown had significantly greater fracture load than all the other groups, which were not significantly different from each other.
Conclusions
Based on fracture load, the new lithium-disilicate hybrid-abutment material may serve as a viable alternative to the use of zirconia as a hybrid-abutment material.
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Clinical and Novel Biomarkers in the Management of Prostate Cancer
Opinion statement
Clinical outcomes in prostate cancer after initial screening and treatment for organ-confined disease and in advanced stage after drug intervention can be heterogeneous. Serum prostate-specific antigen which has a modest value as a screening biomarker while widely used in practice in all subsequent stages has limitations for prognostication or prediction of drug efficacy. Recent advances in genomic sciences and the identification of the mutational landscape of organ-confined and advanced-stage disease have contributed to the development of molecular biomarker profiling in addition to serum prostate-specific antigen. Genomic biomarkers are in development for application to screening for lethal disease subtypes, monitoring of disease recurrence after initial treatments, prognostication, as well as for prediction of drug efficacy. The application of translational molecular profiling in prostate cancer has the potential to enhance clinical management and outcomes in the future. Molecular biomarkers in development in organ-confined disease include both DNA- and RNA-based candidate and pathway-based biomarkers. In advanced-stage disease, molecular biomarker profiling has emerged for identifying therapeutic targets, prediction of drug efficacy, and for prognostication of survival that includes germline single nucleotide profiling and somatic aberrations including copy number variation and mutations and RNA-based profiling. This review summarizes the current state of clinical biomarkers used in practice, their limitations, and novel molecular biomarkers being developed for several clinical endpoints in early- and late-stage cancer.
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Options for Adjuvant Therapy for Uterine Leiomyosarcoma
Opinion statement
Uterine leiomyosarcoma (uLMS) is a rare disease; in the data from the SEER database, 3165 cases of uLMS were diagnosed between January 2000 and December 2012. While a majority of patients (60%) are diagnosed with early stage disease, recurrence rates are high. Five-year disease-specific survival is 76% for patients with FIGO stage I and 60% for patients with FIGO stage II disease. Adjuvant treatments, including radiation therapy, chemotherapy, and combined modality approaches, have been explored with the goal of demonstrating improved survival. However, heterogeneous patient populations, small sample sizes, and lack of no-treatment control arms have limited the interpretation and reliability of the results from these studies. A randomized trial of adjuvant pelvic radiation compared to no additional treatment showed that adjuvant radiation did not improve recurrence or survival outcomes for early-stage uterine LMS. To date, no prospective, randomized trial has been completed comparing adjuvant chemotherapy to observation. A recent well-designed retrospective study showed that women treated with adjuvant gemcitabine-docetaxel had no improvement in progression-free or overall survival compared to women who received no additional treatment. Thus, current data support our recommendation against adjuvant radiation or chemotherapy treatment for patients with non-morcellated, completely resected, and uterine-confined leiomyosarcoma. We recommend that these patients be observed with periodic surveillance imaging and physical examinations.
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Second Malignancies after Hematopoietic Stem Cell Transplantation
Opinion statement
Second malignancies are a rare but well-defined late complication after autologous and allogeneic hematopoietic stem-cell transplantation (SCT). Solid malignancies occur in up to 15% of patients 15 years after SCT with myeloablative conditioning, with no plateau in the incidence rates. They are responsible for 5–10% of late deaths after SCT. The incidence is increased with advanced age at SCT. The major risk factors are the use of total body irradiation, which is associated with adenocarcinomas and with chronic graft-versus-host disease which is associated with squamous cell cancers. There is less data on the incidence of second malignancies after reduced-intensity conditioning, but it may not be lower. The types of solid tumors reported in excess include melanoma and other skin cancers; cancers of the oral cavity and head and neck, brain, liver, uterine cervix, thyroid, breast, lung; and possibly gastrointestinal cancers. Therapy-related myeloid neoplasms (t-MN) are more common after autologous SCT and may be related mostly to pre-transplant therapies. Post-transplant lymphoproliferative disease is donor-cell-derived lymphoma that is more common after allogeneic SCT with T-cell depletion or intensive immune-suppression state. Second malignancies are most often treated similarly to the standard therapy for similar malignancies. Lifelong cancer screening and prevention interventions are required for all transplantation survivors.
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Novel Therapies for Older Adults With Acute Lymphoblastic Leukemia
Abstract
Purpose of Review
Older adults with acute lymphoblastic leukemia (ALL) have worse survival compared to their younger counterparts. Here, we review the reasons for the poorer outcomes of older patients with ALL and also summarize the current and future therapeutic approaches to ALL in the elderly population.
Recent Findings
The poor outcomes of older adults with ALL are driven largely by lack of tolerance to standard-dose chemotherapy, which leads to unacceptably high rates of myelosuppression-related deaths. Recent studies have shown promising results with the use of low-intensity or chemotherapy-free regimens in older patients with ALL, which are able to retain efficacy without excess toxicity.
Summary
Novel antibody constructs such as inotuzumab ozogamicin and blinatumomab as well as potent later-generation tyrosine kinase inhibitors such as ponatinib hold significant promise in the management of ALL in the older adult. Innovative combination strategies may further improve the outcomes of these patients.
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Postoperative chemoradiotherapy in patients with head and neck cancer aged 70 or older with positive margins or extranodal extension and the influence of nodal classification
Abstract
Background
Postoperative concomitant chemoradiotherapy (CRT) improves outcomes for younger adults with head and neck squamous cell carcinoma (HNSCC) and positive margins or extranodal extension (ENE), but its benefit for older adults is not well established.
Methods
Patients from the National Cancer Data Base (NCDB) with HNSCC undergoing curative-intent resection, neck dissection, and postoperative radiation with positive margins or ENE were identified.
Results
This analysis included 1199 patients aged ≥ 70 years with median follow-up of 42.6 months. Postoperative concurrent CRT was associated with improved overall survival (OS; hazard ratio [HR] 0.752; 95% confidence interval [CI] 0.638-0.886) compared to radiation alone in multivariable analysis. Three-year OS was 52.4% with CRT versus 43.4% with radiation (P = .012) in propensity-score matched cohorts. The survival impact of CRT varied by N classification (P = .002 for interaction), with benefit seen only in those with N2 to N3 disease.
Conclusion
Postoperative concurrent CRT may benefit older patients with HNSCC with positive margins or ENE, particularly those with higher nodal burden.
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Prevalence of adverse pathological features in 1 to 4 cm low-risk differentiated thyroid carcinoma
Abstract
Background
The American Thyroid Association (ATA) recommends thyroid lobectomy for 1 to 4 cm tumors without adverse features. We studied the prevalence of adverse pathological features in patients eligible for unilateral lobectomy.
Methods
We conducted a retrospective study of patients who underwent total thyroidectomy. Patients with differentiated thyroid cancer (DTC) with tumors measuring 1 to 4 cm with no known preoperative adverse features were included in this study. Patients with nodal and distant metastasis, tumors <1 cm to > 4 cm, age < 17 years old, and gross extrathyroidal extension were excluded. Patients with bilateral nodularity on imaging were excluded from the final analysis on adverse features.
Results
There were 59.1% of patients undergoing thyroidectomy with tumors measuring 1 to 4 cm and no preoperatively known adverse features who were eligible for lobectomy under current ATA guidelines who would have needed a completion thyroidectomy after pathological analysis of the index tumor.
Conclusion
Two thirds of the patients may require a completion thyroidectomy if unilateral lobectomy is done in tumors measuring 1 to 4 cm based on adverse pathological features.
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Quality of life during the first year after partial laryngectomy: Longitudinal study
Abstract
Background
This prospective study was conducted to assess changes in quality of life (QOL) of patients who undergo a partial laryngectomy.
Methods
The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires Core and Head and Neck (EORTC-QLQ-C30, QLQ-H&N35) were used preprocedure (n = 218), 1 week (n = 159), 3 months (n = 122), and 1 year after partial laryngectomy (n = 88). Changes over time were analyzed with the Wilcoxon signed rank test and the Holm-Bonferroni method, and interpreted regarding clinical relevance.
Results
Most subscales worsened 1 week postprocedure, but many recovered to baseline level after 1 year. Dyspnea and cognitive functioning deteriorated over time, with worst scores recorded after 1 year. Financial difficulties and fatigue increased after surgery and maintained that level throughout the follow-up period; sticky saliva remained worse than at baseline, despite some improvements over time.
Conclusion
The discovered limitations of QOL should be observed more closely during follow-up treatment, and patients should be informed about these potential effects before partial laryngectomy.
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Thyroidectomy in patients who have undergone gastric bypass surgery
Abstract
Background
Morbid obesity is a chronic condition that may be challenging to treat. Gastric bypass surgery is used to treat morbid obesity and its complications. Hypocalcemia, a known complication after thyroidectomy, is usually transient and treatable. There is a growing body of literature indicating that patients with previous gastric bypass surgery are at an increased risk for recalcitrant, symptomatic hypocalcemia after thyroidectomy. The management of hypocalcemia in patients with prior gastric bypass surgery may be exceedingly difficult.
Methods
Relevant articles published between 2008 and January 2017 were reviewed by topic. The review of literature was conducted using a systematic search of database resources, such as PubMed and EMBASE.
Results
Prior gastric bypass surgery may be an independent risk factor for developing profound hypocalcemia after thyroid surgery.
Conclusion
Refractory hypocalcemia in patients who have undergone gastric bypass surgery is underreported. Careful consideration should be given to performing staged thyroidectomy and, in some cases, reversal of the bariatric surgery.
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Role of adjuvant chemoradiotherapy in T4N0 stage IV head and neck cancer: A National Cancer Database analysis
Abstract
Background
The purpose of this study was to evaluate the role of postoperative adjuvant radiotherapy (surgery + adjuvant RT) versus adjuvant chemoradiotherapy (surgery + adjuvant CRT) in patients with T4N0M0, stage IV head and neck squamous cell carcinoma (HNSCC).
Methods
Between 1998 and 2011, 3518 and 885 patients were treated with surgery + adjuvant RT and surgery + adjuvant CRT, respectively. Three-year overall survival (OS) rates were determined and crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were computed.
Results
Median follow-up was 41.8 months with 2193 reported deaths. The 3-year OS was 67.5% for surgery + adjuvant RT and 70.5% for surgery + adjuvant CRT (P = .013). For negative margins, the corresponding 3-year OS was 70.1% and 74.9% (P = .005). For positive margins, the corresponding 3-year OS was 56.0% and 60.6% (P = .079). On multivariate analysis, the beneficial effect for adjuvant CRT over adjuvant RT was not significant (HR 0.90; CI 0.79-1.03; P = .124).
Conclusion
In this cohort of patients with T4N0 HNSCC treated with surgery, there was no observed survival benefit of adjuvant CRT over adjuvant RT on multivariate analysis.
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Genetic profiling of cell-free DNA from cerebrospinal fluid: opening the barrier to leptomeningeal metastasis in EGFR-mutant NSCLC
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Final Validation of the ProMisE Molecular Classifier for Endometrial Carcinoma in a Large Population-based Case Series.
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Epigenetic modifiers as new immunomodulatory therapies in solid tumours
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Tumor necrosis and >20 mitoses per 50 high-power fields can distinguish ‘very high-risk’ and ‘highest-risk’ within ‘high-risk’ gastric gastrointestinal stromal tumor
Future Oncology, Ahead of Print.
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Why does a high-fat diet increase cancer risk?
Future Oncology, Ahead of Print.
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High-fat diet and colorectal cancer: myths and facts
Future Oncology, Ahead of Print.
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The immediate and short-term effects of bilateral intrahippocampal depth electrodes on verbal memory
Summary
In contrast to previous studies, Ljung et al. provide evidence of permanent cognitive consequences of bilateral intrahippocampal depth electrodes for verbal memory in patients who were not operated or operated in the right temporal lobe. Stimulated by this, we provide historical confirmatory and supplementary evidence of the detrimental effect of bilateral depth electrodes implanted along the longitudinal axis of the hippocampus on verbal learning and especially on delayed verbal memory and recognition performance. This is demonstrated in 31 patients with memory assessments before implantation, after explantation, and 3 months later after left/right temporal lobe surgery. After surgery, significant recovery from postimplantation impairment is found in right temporal patients. Left temporal resection patients stay on the level seen after implantation and do not recover. Surgery, however, has its own effects in addition to the implantation. Intracranial electrodes for electroencephalographic monitoring or electrical stimulation are commonly and increasingly used for diagnosis or treatment in pharmacoresistant epilepsies. Thus, the monitoring of invasive stereotactic approaches is recommended to find safe procedures for the patients. In response to the findings, we restricted indications and used different implantation schemes, different trajectories, and targets to minimize the risk of additional damage.
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The impact of anaemia, transfusion dependency, comorbidities and polypharmacy in elderly patients with low-risk myelodysplastic syndromes
Abstract
Myelodysplastic syndromes (MDS) are heterogeneous clonal disorders ranging from indolent conditions with a near-normal life expectancy to forms approaching acute myeloid leukaemia. Comorbid conditions have rarely been systematically studied among patients with MDS. Older age per se has a negative impact on survival of MDS patients, in particular of those with lower risk. However, age indirectly affects also the survival of higher-risk patients by limiting their eligibility to intensive treatments. In addition, ageing is associated with an increasingly high risk of developing comorbidity, and a high prevalence of comorbid diseases has indeed been reported in MDS patients. The impact of multi-morbidities/comorbidities and polypharmacy in patients with low-risk MDS patients is a poorly explored topic. We focused on medications, multi-morbidities and comorbidities of 155 low-risk MDS patients followed in the haematological outpatients clinics or in medical/oncology wards of our University Hospital. One or more comorbidities were present at diagnosis in 24 younger patients with MDS syndromes (31%), whereas 56 older patients with MDS (75%) presented 1 or more comorbidities (P < 0.001).The most frequent comorbidity was cardiac comorbidity 18% in younger patients and 25% in older patients. With no statistical significance between older and younger patients, congestive heart failure was the most frequent observed disease. Our study has shown a statistical correlation between transfusion dependency and polypathology (P = 0.0014). These data were also confirmed in a subanalysis of the younger group of patients. Our study has shown that comorbidity is very common among patients with MDS, potentially affecting the clinical course and outcome of MDS patients.
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Light-emitting Diode Transilluminator for the Identification of Recipient Veins in Finger Reconstruction
Gender-specific independent and combined dose–response association of napping and night sleep duration with type 2 diabetes mellitus in Chinese rural adults: the RuralDiab study
Source:Sleep Medicine
Author(s): Ruihua Liu, Yuqian Li, Zhenxing Mao, Xiaotian Liu, Haiqing Zhang, Kaili Yang, Honglei Zhang, Runqi Tu, Xinling Qian, Jingjing Jiang, Ronghai Bie, Chongjian Wang
ObjectiveThe aim of this study was to explore the independent and combined dose–response association of napping and night sleep duration with type 2 diabetes mellitus (T2DM) among different genders in Chinese rural population.MethodsA total of 19,257 participants were enrolled in the Rural Diabetes, Obesity and Lifestyle (RuralDiab) study for this research. Napping and night sleep duration were assessed using the Pittsburgh Sleep Quality Index (PSQI). Restricted cubic splines and logistic regression were used to estimate the relationship between napping and night sleep duration with T2DM.ResultsA linear dose–response relationship between napping duration and T2DM as well as a U-shaped relationship between night sleep duration and T2DM were found. Compared with those who reported no napping, participants who had a napping duration of ≥ 91 min were associated with a 19% increase in prevalence of T2DM. Adjusted odds ratios (ORs) (95% confidence intervals (CIs)) for T2DM were 1.48 (1.03, 2.14) and 1.50 (1.22, 1.85) for shorter (≤5 h) and longer (>9 h) night sleep duration compared with the referential group. Additionally, the combination of longer napping duration (≥91 min) and night sleep duration (>9 h) increased 104% (95% CI: 45%, 128%) prevalence for T2DM. These associations were not found in males but were evident in females.ConclusionsLonger napping duration and extreme night sleep duration increased the prevalence of T2DM. Meanwhile, longer napping and night sleep duration might be jointly associated with a higher prevalence of T2DM.
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Occurrence of nocturia is not mediated by nocturnal hypoxia length and severity in patients with sleep-disordered breathing
Source:Sleep Medicine
Author(s): P. Finamore, S. Scarlata, A. Laudisio, F. Galdi, M.E. Pipita, I. Chiarella, R. Giua, L. Cortese, C. Rivera, R. Antonelli Incalzi
BackgroundNocturia is highly prevalent in subjects with respiratory sleep disturbances (ie obstructive sleep apnea). The aim of our study is to evaluate whether nocturia is associated with intermittent desaturations or hypoxia length and severity in people undergoing polysomnography.MethodsWe recruited 275 consecutive subjects attending the outpatient clinic for respiratory diseases at Campus Bio-Medico Teaching Hospital. Nocturia was defined as a self-reported voiding frequency ≥ two per night. The groups with and without nocturia were compared with parametric and non-parametric tests, as appropriated. Multivariable logistic regression analysis was used to assess the association of nocturia with patients' characteristics, including oxygen desaturation index (ODI), respiratory efforts (RE) and oxygen saturation below 90% (TST90).ResultsSixty-six (24%) subjects reported nocturia, the median ODI was 15 (8-31), the median RE was 22 (12-38) and the median TST90 was 4.7 (0.3-20.6). ODI and RE were significantly higher in subjects with nocturia as compared with controls. In the multivariable model, ODI was associated with an increased probability of nocturia (OR=1.03; 95% CI=1.01-.1.06), and the higher the ODI score, the higher the probability to have nocturia (P for trend =.038). No significant association was found between TST90 and the occurrence of nocturia.ConclusionsIntermittent desaturations and not hypoxia length and severity, expressed by TST90, are associated with the occurrence of nocturia in subjects complaining sleep disturbances.
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An Enhanced Recovery after Surgery Pathway for Microvascular Breast Reconstruction Is Safe and Effective
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Incisional Negative Pressure Wound Therapy for Prevention of Wound Healing Complications Following Reduction Mammaplasty
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Successful Hand Replantation in a Case of Total Avulsion without Vein Graft
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Single-Stage Breast Reconstruction Using an All-In-One Adjustable Expander/Implant
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Dimensional Error in Rapid Prototyping with Open Source Software and Low-cost 3D-printer
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Immediate Breast Reconstruction among Patients with Medicare and Private Insurance: A Matched Cohort Analysis
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Use of Viable Cryopreserved Placental Membrane as an Adjunct to Facial Keloid Resection
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The Pedicled LICAP Flap Combined with a Free Abdominal Flap In Autologous Breast Reconstructions
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Adjuvant Therapy for Revision Rhinoplasty of Contracted Nose Using Polydeoxyribonucleotide and Invasive Bipolar Radiofrequency
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Complications following Nipple-Sparing Mastectomy and Immediate Acellular Dermal Matrix Implant-based Breast Reconstruction—A Systematic Review and Meta-analysis
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V-shaped Internal Nasal Vestibular Flap for Reconstruction of Iatrogenic Columellar Defect
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Latissimus Dorsi and Immediate Fat Transfer (LIFT) for Complete Autologous Breast Reconstruction
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Superficial Inferior Epigastric Artery Flap Salvage Technique Using Deep Inferior Epigastric Artery Graft
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Clinical Significance of Venous Anomalies in Syndromic Craniosynostosis
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Earfold Implantable Clip System for Correction of Prominent Ears: Analysis of Safety in 403 Patients
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Virtual Surgical Planning: The Pearls and Pitfalls
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Reexploring the Anatomy of the Distal Humerus for its Role in Providing Vascularized Bone
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ASBA Diplomates Treat Hall of Fame NFL Players at Super Bowl Screening Provided by Pro Player Health Alliance and Project Rose
Gary Baxter, Andre Collins, Earl Campbell, Dr. Rosario, David Gergen, Dr. Wilson and Dr. Roberts
In the days leading up to February 4th, 2018, most of the country was preparing for what is referred to as "The Big Game". The city of Minneapolis was covered with posters that said "Welcome to The Bold North", likely referring to the below freezing temperatures that Minnesota is famous for in the winter. Visitors and locals alike stayed warm indoors, but the men who paved the way for the "Big Game" as we know it today were forging a different path that didn't lead to a field or stadium, but to an office located in the Medical Arts Building – Downtown Minneapolis that saw the likes Mike Singletary, Carl Eller, Earl Campbell and Mike Haynes.
The freezing cold winds of the Bold North didn't stop former NFL players from attending the NFLPA sponsored sleep apnea screening provided by Project Rose and Pro Player Health Alliance (PPHA) on February 1-2, 2018. When David Gergen, CEO OF PPHA, inquired space for the event, Dr. Mark Wilson, DDS was honored to provide his dental/medical office. Dr. Wilson is known as one of the top periodontists in the country and has been trained in sleep for over ten years. Upon arrival, the retired professional athletes were directed to sign official consent forms that allowed their data to be used for research. After completing screener forms that determine if they are at high risk for sleep apnea, Dr. Inell Rosario, MD reviewed the findings and, when medically indicated, ordered home sleep tests (HST) for them. Project Rose, led by NFL great Gary Baxter, provided HST's for the players that weekend. Results were immediately uploaded and reviewed the next day and treatment options were provided.
Dr. Mark Wilson, DDS and Dr. Greg Ross, who are sleep dentists and Diplomates of the American Sleep and Breathing Academy (ASBA), were able to take digital scans of the players' teeth to have Gergen's Sleep Appliance Lab begin fabricating instantly. David Gergen only refers ASBA Diplomates to treat the former NFL players.
Sleep dentists working in collaboration with an ENT who is board-certified in sleep, [Dr. Rosario] ensured a quick, efficient and effective service for the players that impressed participants of the event. Former NFL Linebacker Rick Graf said, "I was so happy to hear about this happening this week. I knew I needed to be tested. I snore, but I knew there was something wrong with my breathing at night too. I'm hoping this oral appliance will change my life. My former teammate, Andre Collins, made this program a reality and I'll be forever thankful to him."
To become a Diplomate of the ASBA, click here.
To register for the ASBA Annual Conference and see the likes of NFL greats mentioned in this article and previous articles, click here.
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Prefrontal direct current stimulation in hoarding disorder: A case report
Source:Brain Stimulation
Author(s): Mirjam Handrack, Ulrich Voderholzer, Caroline Schwartz, Alkomiet Hasan, Frank Padberg, Ulrich Palm
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Transcranial direct current stimulation unveils covert consciousness
Source:Brain Stimulation
Author(s): Aurore Thibaut, Camille Chatelle, Audrey Vanhaudenhuyse, Géraldine Martens, Helena Cassol, Charlotte Martial, Manon Carrière, Alice Barra, Steven Laureys, Olivia Gosseries
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FDA Approves Test of New Drug to Protect Hearing
The first clinical trial of a new drug designed to protect humans' hearing will involve a compound developed at the University of Washington (UW).
The U.S. Food and Drug Administration has approved ORC-13661 as an investigational drug to protect people from the hearing-damaging side effects of aminoglycosides, a class of antibiotics used to combat serious infections. The FDA approval clears the way for a Phase I trial of volunteers to confirm whether the drug, which demonstrated significant protective ability in animal models, is safe for humans.
ORC-13661 represents more than a decade of work by two UW scientists: Edwin Rubel, a professor of hearing sciences in the departments of otolaryngology-head and neck surgery and physiology & biophysics, and David Raible, a professor of biological structure in the School of Medicine.
"Our collaboration started in 2001; it was a novel idea and we got funded," Rubel said. "The goal was to discover how the receptor cells in the inner ear die. Why do some people start to lose their hearing at age 40 and others have good hearing at age 80?"
Their study of zebrafish was pivotal to understanding the mechanisms that affect hearing in humans. Fish have external hair cells akin to the receptor-cell structures in humans' cochleas, which turn sound waves into electrical impulses for the brain to interpret.
"With the hair cells on the outside of their bodies, we could observe them very readily for genetic and molecular studies," Rubel said.
Human receptor cells can be damaged as a secondary effect of antibiotics called aminoglycosides, which doctors employ against severe infections in cases of cystic fibrosis, immune suppression, and premature newborns, among other conditions. These powerul antibiotics – for example, gentamicin and streptomycin – can kill the receptor cells in the cochlea and balance organs, causing permanent hearing loss and unsteadiness for patients.
Over 16 years, Rubel and Raible confirmed that the fishes' hair cells are similar genetically and in other ways to hearing receptor cells in humans and other mammals.
In concert with Julian Simon, a medicinal chemist based at the Fred Hutchinson Cancer Research Center, and others, they tested the ability of more than 10,000 molecules to protect the zebrafishes' hair cells from the toxic effects of these antibiotics.
"We did a phenotypic screen," said Raible. "It's a different approach from many drug screens that target a specific receptor or protein known to be important, and then design a molecule to fit the active site of the protein. Instead, we screened libraries of chemicals to find ones that stopped zebrafish hair cells from dying, and used the one that worked best. But we can't say we know exactly why it works."
Their breakthrough results, published last month, involved a change that amplified the effectiveness of a promising compound from earlier studies. The drug demonstrated outstanding safety and 100-percent protection of hair cells in zebrafish and rats in vivo. This spurred the FDA's action.
In 2013 Raible and Rubel co-founded a company, Oricula Therapeutics, which exclusively licenses patents for ORC-13661 held by the University of Washington and Fred Hutch. Oricula made the application to the FDA and will pursue funding for the Phase I trial of the drug's safety in humans, Rubel said. If that were to succeed, the next step would be testing the drug's effectiveness among patients who must take aminoglycosides to stave off life-threatening infections.
Both scientists reflected on the infusion of $34,000 that got them going back in 2001. The money came from the UW's Royalty Research Fund, a mechanism in which UW's royalty and licensing fee income is selectively reinvested in promising new research.
"It's such a cool thing that the university uses royalties to seed new ideas that might one day reinfuse the fund," Raible said. "The people who came up with the fund should know that it does make a difference in these ventures."
This news original appeared in the UW Medicine Newsroom.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FYavNH
Nekrotisierende zervikale Lymphadenopathie mit unklaren Hautläsionen
Laryngo-Rhino-Otol
DOI: 10.1055/s-0044-101433
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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Hörsturz mit Surditas, Schwindel und Tinnitus - eine 12-jährige Odyssee
Laryngo-Rhino-Otol
DOI: 10.1055/s-0044-100517
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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Endoscopic Endonasal Approach to a Suprasellar Craniopharyngioma
J Neurol Surg B
DOI: 10.1055/s-0038-1623526
We present the case of a 57-year-old male who presented with progressive right side vision loss whose workup revealed a large suprasellar lesion with invasion of the third ventricle. The pituitary stalk was not visible.Hormonal panel showed no hormonal deficits. The initial diagnosis was of a type II transinfundibular craniopharyngioma (as classified by Kassam et al).An endoscopic endonasal transplanum transtuberculum approach was done using a standard binostril four-hand technique, with the patient positioned supine with the head turned to the right side and tilted to the left, fixed in a three-pin head clamp, under imaging guidance. The tumor was carefully dissected away from the optic apparatus while preserving the vessels, mainly the superior hypophyseal artery. The stalk was identified around the tumor and preserved. The third ventricle was entered and inspected at the end of the procedure and a near-total resection (a small residual in the right hypothalamus) with decompression of the optic apparatus was achieved. Reconstruction was done in a multilayered fashion, using collagen matrix and a nasoseptal flap. Patient had an uneventful postoperative stay and was discharged on POD 4, neurologically stable with no hormonal deficits. Pathology confirmed an adamantinomatous craniopharyngioma. Due to a small growth of the residual, patient underwent fractionated stereotactic radiation (50.4Gy in 28 sessions). He presented with panhypopituitarism 2 years after radiation therapy. At 3-month follow-up, his vision was back to normal and 6-year postoperative magnetic resonance imaging showed no signs of recurrence.The link to the video can be found at: https://youtu.be/chG7XIz7a_A.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | open access Full text
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Macrophage Density Predicts Facial Nerve Outcome and Tumor Growth after Subtotal Resection of Vestibular Schwannoma
J Neurol Surg B
DOI: 10.1055/s-0038-1627474
Introduction Vestibular schwannoma (VS) behavior following subtotal resection (STR) is highly variable. Overall progression rates have been reported as high as 44%, and optimal treatment is controversial. Correspondingly, identification of a reliable clinical or pathologic marker associated with progression after STR would help guide decision-making. Methods A prospectively maintained institutional VS registry from 1999 to 2014 was retrospectively reviewed for sporadic VS patients who underwent primary STR without preceding stereotactic radiosurgery (SRS) by a single neurosurgery-neurotology team. Primary endpoints included tumor progression and postoperative facial nerve function. Pathologic specimens were stained for Ki67, CD68, S100, and SOX10 and were quantitated by digital imaging analysis. Macrophage density was defined as the ratio of CD68+ macrophages to S100+ macrophages and Schwannian tumor cells. Clinical outcomes were correlated with pathologic markers. Results Forty-six patients met the study inclusion criteria. Thirteen (28%) progressed during a mean 57 months of follow-up (range 15–149). Favorable postoperative facial nerve function (House–Brackmann I–II) was achieved in 37 (80%). CD68+ cells were present at significantly higher concentrations in tumors that progressed (p = 0.03). Higher macrophage density was significantly associated with both tumor progression (p = 0.02) and unfavorable facial nerve function (p = 0.02). Ki67 percent positivity was not significantly associated with either primary endpoint (p = 0.83; p = 0.58). Conclusions Macrophage density may provide an important marker for individuals at the highest risk for progression of VS after STR, potentially prompting closer surveillance or consideration for upfront SRS following STR. This finding supports preceding conclusions that an intratumoral macrophage-predominant inflammatory response may be a marker for tumor growth and a potential therapeutic target.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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Prognostic significance of HPV status in the re-irradiation of recurrent and second primary cancers of the head and neck
To evaluate the prognostic significance of human papillomavirus (HPV) status among patients treated by salvage radiation therapy for local-regional recurrences and second primary cancers of the head and neck arising in a previously irradiated field.
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Forehead reduction and orbital contouring in facial feminisation surgery for transgender females
Forehead reduction and orbital contouring form a considerable component of the procedures available to feminise the face in transgender females. In this paper I shall discuss the history and development of techniques to reduce bossing of the forehead and contour the orbits, and describe their classification, assessment, surgical approach, and complications.
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Use of ultrasound-activated resorbable sheets and pins in the management of fractures of the condylar neck of the mandible: a case series
The need to treat fractures of the mandibular condyle remains controversial, but when the decision to operate has been made, then multiple forms of fixation are advocated. Traditionally, metal plates and screws have been used, but this is thought to have several disadvantages, particularly in the growing skeleton. Resorbable fixation for maxillofacial fractures has not gained widespread acceptance because of technical difficulties with the materials and concern about inflammatory reactions during their resorption.
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Association of sleep habits with behavior problems and resilience of 6- to 7-year-old children: results from the A-CHILD study
Childhood sleep habits are associated with mental health development; however, little is known about the impact of irregular bedtimes on the mental health of early school-aged children. The aims of this study were to examine the effect of weekday sleep habits (varying bedtimes depending on the night of the week and later than 22:00 h. bedtime) on behavior problems, prosocial behavior, and resilience of children aged 6–7 years.
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Gender-specific independent and combined dose–response association of napping and night sleep duration with type 2 diabetes mellitus in Chinese rural adults: the RuralDiab study
The aim of this study was to explore the independent and combined dose–response association of napping and night sleep duration with type 2 diabetes mellitus (T2DM) among different genders in Chinese rural population.
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Prevalence and characteristics of sleep-disordered breathing in familial dysautonomia
Familial dysautonomia (FD) is an autosomal recessive disorder characterized by impaired development of sensory and afferent autonomic nerves. Untreated sleep-disordered breathing (SDB) has been reported to increase the risk of sudden unexpected death in FD. We aimed to describe the prevalence and characteristics of SDB in FD.
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Trazodone for the treatment of insomnia: a meta-analysis of randomized placebo-controlled trials
To assess the efficacy and tolerability of trazodone compared with placebo in patients with insomnia.
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Occurrence of nocturia is not mediated by nocturnal hypoxia length and severity in patients with sleep-disordered breathing
Nocturia is highly prevalent in subjects with respiratory sleep disturbances (ie obstructive sleep apnea). The aim of our study is to evaluate whether nocturia is associated with intermittent desaturations or hypoxia length and severity in people undergoing polysomnography.
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Characteristics of napping in community-dwelling insomnia patients
We aimed to determine napping characteristics of community-dwelling patients with insomnia disorder (ID) compared to characteristics of normal controls (NC), and to examine the effect of napping on nocturnal sleep.
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Experiences with a modified preauricular mini INCISION with subdermally dissection in condylar and subcondylar fractures of the mandible
Condylar and subcondylar fractures (CSFs) are among the most common mandible fractures. If reduction of these fractures is not carried out correctly, serious complications can result, including infection, damage to temporomandibular joint (TMJ) function, malocclusion, nonunion, malunion, and ankylosis of the TMJ.
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Survival in patients with submandibular gland carcinoma — Results of a multi-institutional retrospective study
Clinical studies demonstrating the prognostic factors in submandibular gland carcinoma are limited because the tumor is relatively rare. The aim of this study was to identify clinical outcomes and prognostic factors in submandibular gland carcinoma.
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A questionnaire to assess olfactory rehabilitation for laryngectomized patients (Provox voice prosthesis users) in Japan
We used a questionnaire to investigate olfactory function and the present state of olfactory rehabilitation for laryngectomized patients in Japan.
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The gray scale value of ear tissues undergoing volume-rendering high-resolution cone-beam computed tomography
When the thresholds for VR reconstruction from multi-slice CT images are changed, problems develop when assessing pathologies in the absence of standardized thresholds. The advantages of CBCT include lower radiation exposure compared with other techniques and better visualization of small ear structures. However, a disadvantage is that the scanner provides unstandardized gray scale values, thus not CT numbers (Hounsfield units, HU).
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Effects of AUT00063, a Kv3.1 channel modulator, on noise-induced hyperactivity in the dorsal cochlear nucleus
Source:Hearing Research
Author(s): Lyall Glait, Weiwen Fan, Gina Stillitano, Sharon Sandridge, Nadia Pilati, Charles Large, Giuseppe Alvaro, James A. Kaltenbach
The purpose of this study was to test whether a Kv3 potassium channel modulator, AUT00063, has therapeutic potential for reversing noise-induced increases in spontaneous neural activity, a state that is widely believed to underlie noise-induced tinnitus. Recordings were conducted in noise exposed and control hamsters from dorsal cochlear nucleus (DCN) fusiform cells before and following intraperitoneal administration of AUT00063 (30 mg/kg). Fusiform cell spontaneous activity was increased in sound-exposed animals, approximating levels that were nearly 50% above those of controls. Administration of AUT00063 resulted in a powerful suppression of this hyperactivity. The first signs of this suppression began 13 min after AUT00063 administration, but activity continued to decline gradually until reaching a floor level which was approximately 60% of pre-drug baseline by 25 min after drug treatment. A similar suppressive effect of AUT00063 was observed in control animals, with onset of suppression first apparent at 13 min post-treatment, but continuing to decline toward a plateau that was 54% of pre-drug baseline and was reached 28 min after drug treatment. In contrast, no suppression of spontaneous activity was observed in animals given similar injections of vehicle (control) solution. The suppressive effect of AUT00063 was achieved without significantly altering heart rate and with minimal effects on response thresholds, supporting the interpretation that the reductions of hyperactivity were not a secondary consequence of a more general physiological suppression of the brain or auditory system. These findings suggest that Kv3 channel modulation may be an effective approach to suppressing spontaneous activity in the auditory system and may provide a future avenue for treatment of tinnitus resulting from exposure to intense sound.
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