OtoRhinoLaryngology News

Σάββατο 4 Νοεμβρίου 2017

Reinforced staplers for distal pancreatectomy

Abstract

Purpose

The safety and efficacy of reinforced staplers during distal pancreatectomy (DP) remain controversial because of the small sample size. This multicenter single-arm prospective study aims to evaluate the safety and efficacy of reinforced staplers with bioabsorbable material during DP.

Methods

Between October 2014 and August 2015, 121 patients scheduled for DP were enrolled in this study at 11 institutions in Japan. The primary endpoint was the incidence of clinically relevant pancreatic fistula. Protocol treatment was defined as "distal pancreatectomy using reinforced staplers."

Results

Per-protocol analysis of 105 patients was performed; 16 of the patients were excluded based on discontinuation of protocol treatment criteria. Clinically relevant pancreatic fistula occurred in 13 (12.4%) of 105 patients. The overall morbidity rate was 29.5% (31 of 105 patients) and severe complication (Clavien classification IIIa or more) was 10.5% (11/105). Mortality rate was 0%, although reoperations were performed on two patients (1.9%). Multivariate logistic regression analysis of independent risk factors for clinically relevant pancreatic fistula after DP using reinforced stapler closure was operative time more than 240 min (P = 0.047, odds ratio 5.79), registration numbers less than 10 (P = 0.046, odds ratio 13.01), and staple line hemorrhage (P = 0.003, odds ratio 16.34).

Conclusion

This study confirms the safety of reinforced staplers for pancreatic stump closure during DP. However, the efficacy of reinforced staplers for decreasing clinically relevant pancreatic fistula could not be drawn from this study.

Trial registration

This prospective study was registered with ClinicalTrials.gov (NCT02270554) and UMIN Clinical Trial Registry (UMIN000015384).

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Perfusion-based human cadaveric specimen as a simulation training model in repairing cerebrospinal fluid leaks during endoscopic endonasal skull base surgery.

Perfusion-based human cadaveric specimen as a simulation training model in repairing cerebrospinal fluid leaks during endoscopic endonasal skull base surgery.

J Neurosurg. 2017 Nov 03;:1-5

Authors: Christian EA, Bakhsheshian J, Strickland BA, Fredrickson VL, Buchanan IA, Pham MH, Cervantes A, Minneti M, Wrobel BB, Giannotta S, Zada G

Abstract
OBJECTIVE Competency in endoscopic endonasal approaches (EEAs) to repair high-flow cerebrospinal fluid (CSF) leaks is an essential component of the neurosurgical training process. The objective of this study was to demonstrate the feasibility of a simulation model for EEA repair of anterior skull base CSF leaks. METHODS Human cadaveric specimens were utilized with a perfusion system to simulate a high-flow CSF leak. Neurological surgery residents (postgraduate year 3 or greater) performed a standard EEA to repair a CSF leak using a combination of fat, fascia lata, and pedicled nasoseptal flaps. A standardized 5-point Likert questionnaire was used to assess the knowledge gained, techniques learned, degree of safety, benefit of CSF perfusion during repair, and pre- and posttraining confidence scores. RESULTS Intrathecal perfusion of fluorescein-infused saline into the ventricular/subarachnoid space was successful in 9 of 9 cases. The addition of CSF reconstitution offered the residents visual feedback for confirmation of intraoperative CSF leak repair. Residents gained new knowledge and a realistic simulation experience by rehearsing the psychomotor skills and techniques required to repair a CSF leak with fat and fascial grafts, as well as to prepare and rotate vascularized nasoseptal flaps. All trainees reported feeling safer with the procedure in a clinical setting and higher average posttraining confidence scores (pretraining 2.22 ± 0.83, posttraining 4.22 ± 0.44, p < 0.001). CONCLUSIONS Perfusion-based human cadaveric models can be utilized as a simulation training model for repairing CSF leaks during EEA.

PMID: 29099299 [PubMed - as supplied by publisher]

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Cranioplasty Using a Mixture of Biologic and Nonbiologic Agents.

Cranioplasty Using a Mixture of Biologic and Nonbiologic Agents.

JAMA Facial Plast Surg. 2017 Nov 02;:

Authors: Arnaoutakis D, Bahrami A, Cohn JE, Smith JE

Abstract
Importance: A surgeon faces challenges with cranioplasty techniques to achieve a successful result with relatively few complications.
Objective: To describe a unique technique for incorporating both biologic autologous bone and nonbiologic allograft materials for defect coverage in cranioplasty with favorable outcomes and low occurrence of complications.
Design, Setting, and Participants: A retrospective medical records review of all 26 patients who underwent primary cranioplasty procedure with a modified technique between January 2011 and December 2015 at a high-volume head and neck oncologic reconstructive practice was conducted; data analysis was also performed during that period. After several years of experience with traditional cranioplasty maneuvers, the modified technique has evolved to incorporate both autologous bone grafts and alloplastic materials in the formation of a shapeable on-lay material. Data were collected on demographics, need for cranioplasty, materials used, outcomes, and risk factors.
Main Outcomes and Measures: Rates of infection, hematoma, flap loss or resorption, cerebrospinal fluid leak, hardware exposure or malfunction, and repeated reconstruction.
Results: Of the 26 patients, 21 (81%) were men; mean (SD) age was 65.8 (14.3) years. Eight (31%) patients had a history of diabetes, 4 (15%) patients were receiving immunosuppressive drugs, and 5 (19%) patients were active smokers at the time of surgery. Neoplasia was the most common cause of the calvarial defect seen, responsible for 20 of 28 (71%) operative defects and necessitated procedures. All but 1 patient achieved successful mineralization following primary cranioplasty with the modified technique; this success was verified based on physical examination and follow-up imaging. Complications were rare and involved only 3 patients who developed postoperative infection; 1 (4%) of these patients lost the integrity of the cranioplasty. Thus, the rate of infection was 11% and loss rate was 4%. Preoperative and postoperative radiotherapy appeared to have no bearing on graft survival.
Conclusions and Relevance: The results using a unique technique for incorporating both biologic autologous bone and nonbiologic allograft materials for defect coverage in cranioplasty are favorable, with satisfactory aesthetic outcomes and limited postoperative complications.
Level of Evidence: 4.

PMID: 29098278 [PubMed - as supplied by publisher]

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Intracranial melanotic schwannomas: a rare variant with unusual adherent features.

Intracranial melanotic schwannomas: a rare variant with unusual adherent features.

J Neurooncol. 2017 Nov 02;:

Authors: Mahato D, Vivas-Buitrago T, Gassie K, Jentoft M, Tavanaiepour D, Quiñones-Hinojosa A

Abstract
Intracranial melanotic schwannomas (IMSch) are extremely rare nerve sheath tumors with features of Schwann cells that produce melanin. After a thorough review of the available literature since 1967, we report not only the 20th case of IMSch but a comprehensive modern-era analysis of radiographic and histological key-points to be considered when diagnosing and treating patients with this rare known entity. This is the case of a 43 years-old woman who presented with severe headaches 9 years ago (2008). At that time, MRI of the brain showed a 1.5 × 1.4 cm lesion at the level of the left cerebellar peduncle without any evidence of edema, mass effect or hydrocephalus. Given that the patient was neurologically intact, a conservative management with serial MRIs was recommended. Patient stopped following up due to the absence of symptoms. Over the course of the past year, patient noted mild left sided hearing loss and facial weakness, as well as some balance instability that progressed over the last 3 months. Given the presentation and progression of these signs and symptoms, a new MRI was performed in which considerable growth of the lesion was identified, measuring 2.5 × 2.8 × 2.6 cm with mass effect on the pons and the inferior fourth ventricle. She underwent a far lateral approach without a C1 hemilaminectomy for the resection of this lesion. Final pathology was consistent with a non-psammomatous melanotic schwannoma (NPMS) with areas of necrosis. Besides this case, only two other cases of IMSch with findings of necrosis have been reported in the literature, all of them reporting a subtotal resection. Evaluation of all previously reported cases of IMSch shows a male prevalence with a 1.6:1 male to female ratio. IMSch is radiographically T2 hypointense and can be differentiated from Schwannomas that are classically T2 hyperintense. In this case, only a subtotal resection was feasible due to the tumor's overwhelming inherent attachment to vital structures such as cranial nerves (CN), brainstem, and vasculature. While MSch is considered histologically benign, several factors including localization, surrounding structures, the rate of growth, tumor volume resection and histological necrosis should be considered in determining prognosis and further adjuvant treatment planning.

PMID: 29098570 [PubMed - as supplied by publisher]

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Intracranial melanotic schwannomas: a rare variant with unusual adherent features.

Intracranial melanotic schwannomas: a rare variant with unusual adherent features.

J Neurooncol. 2017 Nov 02;:

Authors: Mahato D, Vivas-Buitrago T, Gassie K, Jentoft M, Tavanaiepour D, Quiñones-Hinojosa A

PMID: 29098570 [PubMed - as supplied by publisher]

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A Novel Imaging Method for the Cartilaginous Eustachian Tube Lumen: Computerized Tomography During the Forced Response Test.

A Novel Imaging Method for the Cartilaginous Eustachian Tube Lumen: Computerized Tomography During the Forced Response Test.

Ann Otol Rhinol Laryngol. 2017 Nov 01;:3489417740363

Authors: Alper CM, Rath TJ, Teixeira MS, Swarts JD

Abstract
OBJECTIVES: In vivo imaging of the open cartilaginous Eustachian tube (ET) lumen by computed tomography (CT) scan during ET function (ETF) testing to establish new methodology.
METHODS: Five adults underwent unilateral ETF testing of an ear with a nonintact tympanic membrane using the forced response test (FRT) to measure the opening pressure (PO), steady state pressure (PS), and flow conductance (CS). Then at baseline and during the PS phase of the FRT, a temporal-bone CT scan with continuous 0.625 mm thickness was obtained. Multiplanar oblique reformats along the axis of the ET were created, and point value and region of interest (ROI) Hounsfield unit measurements were recorded from the location of the ET lumen.
RESULTS: At the FRT flow rate of 11 ml/min, the average PO, PS, and CS were 370.5 daPa, 119.6 daPa, and 0.16 ml/min/daPa, respectively. For flow rates of 23 and 46 ml/min, these values were 236.2, 204.2, 0.12 and 385.5, 321.1, 0.18, respectively. Although areas with lower attenuation were suggestive of air density, a distinct air-filled cartilaginous ET lumen could not be confirmed.
CONCLUSIONS: While the current imaging parameters failed to resolve the air-soft tissue interface throughout the open cartilaginous ET, further advances in imaging may obviate this limitation.

PMID: 29099232 [PubMed - as supplied by publisher]

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Radiological tumor thickness as a risk factor for local recurrence in early glottic cancer treated with laser cordectomy.

Radiological tumor thickness as a risk factor for local recurrence in early glottic cancer treated with laser cordectomy.

Eur Arch Otorhinolaryngol. 2017 Nov 02;:

Authors: Son HJ, Lee YS, Ku JY, Roh JL, Choi SH, Nam SY, Kim SY

Abstract
OBJECTIVES: Despite the excellent prognosis of early glottic cancer (T1-T2), the significance of preoperatively measured tumor thickness has not been elucidated. We evaluated the role of tumor thickness measured using computed tomography (CT) as a predictive factor for recurrence of early glottic cancer after transoral laser microsurgery (TLM).
METHODS: The medical records of 134 patients who were diagnosed with early glottic squamous cell carcinoma and underwent TLM were reviewed. Age, sex, clinical stage, preoperative biopsy, anterior commissure involvement, CT findings, recurrence, and overall survival were evaluated.
RESULTS: Seventy-three patients (54 T1a, 2 T1b, and 17 T2) were enrolled. Tumor thickness on pathology increased proportionally with increased tumor thickness on CT. The recurrence-free survival (RFS) and overall survival rates were 82.2 and 91.2%, respectively. Upon univariate analysis, RFS was affected by the type of cordectomy, tumor differentiation, margin involvement, anterior commissure involvement, impaired vocal fold mobility, and tumor thickness (> 4 mm) on CT scan (all p < 0.01). Among the relevant covariates, an involved or close resection margin [hazard ratio (HR) 19.2; 95% confidence interval (CI) 3.5-105.6; p < 0.01], impaired vocal cord mobility (HR 8.5; 95% CI 1.45-49.2; p = 0.02), and pathological tumor thickness (> 4 mm) (HR 6.0; p = 0.02) were predictive of RFS.
CONCLUSION: Tumor thickness may be another predictive factor for recurrence in early glottic cancer. Before TLM, reviewing the extent of tumor thickness will help to improve local control in cases of early glottic cancer.

PMID: 29098372 [PubMed - as supplied by publisher]

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[Techniques and progress in the imaging of the ear].

[Techniques and progress in the imaging of the ear].

Presse Med. 2017 Oct 30;:

Authors: Garin A, Benoudiba F, Ducreux D

Abstract
Ear and temporal bone imaging is essential for the diagnostic and preoperative management of middle ear lesions. The scanner is the exam of choice to analyze the walls and the contents of the middle ear. MRI is used to characterize the opacities of the middle ear and to evaluate possible neurological complications. Modern imaging techniques allow intraoperative guidance in otological surgery. Hearing implants are not always a contraindication to MRI but require precautions according to the type of implant.

PMID: 29097036 [PubMed - as supplied by publisher]

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[Good practices with tinnitus in adult].

[Good practices with tinnitus in adult].

Presse Med. 2017 Oct 30;:

Authors: Le Pajolec C, Ohresser M, Nevoux J

Abstract
The interrogation is essential to trace the genesis of the tinnitus and to appreciate its repercussion. Clinical examination should look for a local, vascular or cervical cause. The ENT consultation with audiogram and tinnitus evaluation is essential to know the characteristics of the tinnitus and to consider the treatment. If tinnitus is accompanied by a decrease in hearing, then wearing hearing aids can correct deafness and decrease the tinnitus. The psychological impact of tinnitus must always be taken into account and the use of a multidisciplinary team is an interesting solution. Medical treatments are not very effective; on the other hand psychotherapies (CBT, TRT and sophrology) bring a real improvement. The doctor's speech must always be supportive and provide therapeutic hope.

PMID: 29097035 [PubMed - as supplied by publisher]

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[Medical devices correcting the deafness: Hearing aids and auditory implants].

[Medical devices correcting the deafness: Hearing aids and auditory implants].

Presse Med. 2017 Oct 30;:

Authors: Nevoux J, Coez A, Truy É

Abstract
The management of deafness has become a major public health issue as their lack of detection has a deleterious effect in children and increases the risk factors for aggravation of other pathologies in adults. The detection of deafness remains a real challenge: in the newborn, systematic screening at birth is a good strategy, in adults, much remains to be done. The functional rehabilitation of deafness is based on the use of hearing aids by aerial or bone conduction or of auditory implants. There are three types of auditory implants available: bone anchored hearing implants, middle ear implants and cochlear implants. Many actors, in particular social organizations, can intervene in the financial management of these medical devices.

PMID: 29097034 [PubMed - as supplied by publisher]

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[The tumors of the ear].

[The tumors of the ear].

Presse Med. 2017 Oct 30;:

Authors: Dubernard X, Kleiber JC, Brenet E, Louges MA, Veleine Y, Labrousse M, Makeieff M, Bazin A, Chays A

Abstract
Any cutaneous lesion of the outer ear must be managed jointly by a dermatologist and an ENT, regardless of the age of the patient. The presence of a malignant cutaneous carcinoma (Squamous cell carcinoma or melanoma) of the pavilion requires a minimum extension assessment by a cervical ultrasound, CT-scan and MRI will be prescribed according to the degree of infiltration and the presence of clinics signs (lymphadenopathy, facial paralysis, cognitive impairment). A polyp of the external auditory meatus must be systematically biopsied in consultation and, if necessary, in the operating room with fresh anatomopathological analysis. Any "otitis externa", which does not progress favorably under local treatment, must lead to eliminate a tumoral pathology of the external acoustic meatus or of the middle ear. Any suspicion of cholesteatoma should lead to an ENT consultation to confirm the diagnosis and consider its treatment to limit the auditory dysfunction. Any unilateral neurosensorial hearing loss or unilateral vestibular involvement with normal otoscopy should lead to eliminate a inner ear tumor by an MRI of the inner ear and the ponto-cerebellar angle in millimeter sections.

PMID: 29097033 [PubMed - as supplied by publisher]

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[The infections of the ear].

[The infections of the ear].

Presse Med. 2017 Oct 30;:

Authors: Nowak C, Tanaka L, Bobin S, Nevoux J

Abstract
In front of external otitis in spite of a well-conducted treatment, especially in immunodeficient patient, it is always necessary to look for an osteomyelitis of the skull base that requires an urgent parenteral antibiotic treatment of several weeks. Acute otitis media (AOM) is the most common bacterial infection of the child. In children under 2 years with purulent AOM, antibiotic therapy with amoxicilline is systematic for a period of 8-10 days. After 2 years of age and with mild symptoms of AOM, symptomatic treatment may be justified as first-line treatment. Chronic otitis media is frequent after an episode of AOM and becomes chronic only after 3 months of evolution. Grommets reduce the frequency of AOM episodes. All AOM complicated with meningitis requires monitoring by audiogram and MRI of the ear.

PMID: 29097032 [PubMed - as supplied by publisher]

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Information for Readers

Publication date: November 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 5

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Global issues in allergy and immunology: Parasitic infections and allergy

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Publication date: November 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 5
Author(s): Alvaro A. Cruz, Philip J. Cooper, Camila A. Figueiredo, Neuza M. Alcantara-Neves, Laura C. Rodrigues, Mauricio L. Barreto
Allergic diseases are on the increase globally in parallel with a decrease in parasitic infection. The inverse association between parasitic infections and allergy at an ecological level suggests a causal association. Studies in human subjects have generated a large knowledge base on the complexity of the interrelationship between parasitic infection and allergy. There is evidence for causal links, but the data from animal models are the most compelling: despite the strong type 2 immune responses they induce, helminth infections can suppress allergy through regulatory pathways. Conversely, many helminths can cause allergic-type inflammation, including symptoms of "classical" allergic disease. From an evolutionary perspective, subjects with an effective immune response against helminths can be more susceptible to allergy. This narrative review aims to inform readers of the most relevant up-to-date evidence on the relationship between parasites and allergy. Experiments in animal models have demonstrated the potential benefits of helminth infection or administration of helminth-derived molecules on chronic inflammatory diseases, but thus far, clinical trials in human subjects have not demonstrated unequivocal clinical benefits. Nevertheless, there is sufficiently strong evidence to support continued investigation of the potential benefits of helminth-derived therapies for the prevention or treatment of allergic and other inflammatory diseases.

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Global issues in allergy and immunology: Parasitic infections and allergy

Publication date: November 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 5

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Chronic rhinosinusitis in Asia

Publication date: November 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 5
Author(s): Yuan Zhang, Elien Gevaert, Hongfei Lou, Xiangdong Wang, Luo Zhang, Claus Bachert, Nan Zhang
Chronic rhinosinusitis (CRS), although possibly overdiagnosed, is associated with a high burden of disease and is often difficult to treat in those truly affected. Recent research has demonstrated that inflammatory signatures of CRS vary around the world, with less eosinophilic and more neutrophilic inflammation found in Asia compared with Europe and North America. Although in the Western world about 80% of nasal polyps carry a type 2 signature, this might be between 20% and 60% in China and Korea or Thailand, respectively. These differences are associated with a lower asthma comorbidity and risk of disease recurrence after surgery in the Asian population. As a hallmark of severe type 2 inflammation, eosinophils attacking Staphylococcus aureus at the epithelial barrier have been described recently; they also can be found in a subgroup of Asian patients with nasal polyps. Furthermore, the percentage of type 2 signature disease in patients with CRS is dramatically increasing ("eosinophilic shift") in several Asian countries over the last 20 years. Establishing an accurate diagnosis along with considering the current and shifting patterns of inflammation seen in Asia will enable more effective selection of appropriate pharmacotherapy, surgical therapy, and eventually biotherapy. Determining the causes and pathophysiology for this eosinophilic shift will require additional research.

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Cover 1

Publication date: November 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 5

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Interleukin-1/inhibitory kappa B kinase epsilon-induced glycolysis augment epithelial effector function and promote allergic airways disease

Publication date: Available online 3 November 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Xi Qian, Reem Aboushousha, Cheryl van de Wetering, Shi B. Chia, Eyal Amiel, Robert W. Schneider, Jos LJ. van der Velden, Karolyn G. Lahue, Daisy A. Hoagland, Dylan T. Casey, Nirav Daphtary, Jennifer L. Ather, Matthew J. Randall, Minara Aliyeva, Kendall E. Black, David G. Chapman, Lennart K.A. Lundblad, David H. McMillan, Anne E. Dixon, Vikas Anathy, Charles G. Irvin, Matthew E. Poynter, Emiel. F.M. Wouters, Pamela M. Vacek, Monique Henket, Florence Schleich, Renaud Louis, Albert van der Vliet, Yvonne M.W. Janssen-Heininger
BackgroundEmerging studies suggest that enhanced glycolysis accompanies inflammatory responses. Virtually nothing is known about the relevance of glycolysis in allergic asthma.ObjectivesHere we sought to determine if glycolysis is altered in allergic asthma and to address its importance in the pathogenesis of allergic asthma.MethodsWe examined alterations in glycolysis in sputum samples from asthmatics and primary human nasal cells, and used murine models of allergic asthma as well as primary mouse tracheal epithelial cells to evaluate the relevance of glycolysis.ResultsIn a murine model of allergic asthma, glycolysis was induced in the lungs in an IL-1-dependent manner. Furthermore, administration of IL-1β into airways stimulated lactate production and expression of glycolytic enzymes, with notable expression of lactate dehydrogenase A occurring in the airway epithelium. Indeed, exposure of mouse tracheal epithelial cells to IL-1β or IL-1α resulted in increased glycolytic flux, glucose usage, expression of glycolysis genes, and lactate production. Enhanced glycolysis was required for IL-1β- or IL-1α-mediated pro-inflammatory responses and the stimulatory effects of IL-1β on HDM-induced release of TSLP, and GM-CSF from tracheal epithelial cells. Inhibitor of κB kinase ε was downstream of house dust mite (HDM) or IL-1β, and was required for HDM-induced glycolysis and the pathogenesis of allergic airways disease. SiRNA-ablation of lactate dehydrogenase A attenuated HDM-induced increases in lactate and attenuated HDM-induced disease. Primary nasal epithelial cells from asthmatics intrinsically produced more lactate as compared to cells from healthy subjects. Lactate content was significantly higher in sputum supernatants from asthmatics, notably those patients with >61% neutrophils. A positively correlation was observed between sputum lactate and IL-1β, and lactate content negatively correlated with lung function.ConclusionsCollectively, these findings demonstrate that IL-1β/IKKε signaling plays an important role in HDM-induced glycolysis and the pathogenesis of allergic airways disease.

Graphical abstract

Teaser

IL-1 and IKKε play important roles in HDM-induced glycolysis and the pathogenesis of allergic airways disease, and lactate is a potential biomarker for increased glycolysis and IL-1-associated pro-inflammatory signals in airways of asthmatics.

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The Editors' Choice

Publication date: November 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 5
Author(s): Cezmi A. Akdis, Zuhair K. Ballas

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News Beyond Our Pages

Publication date: November 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 5
Author(s): Marc E. Rothenberg, Jean Bousquet

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Publication date: November 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 5

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CME Activities Calendar

Publication date: November 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 5

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Brief Overview of This Month's JACI

Publication date: November 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 5

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Editorial Board

Publication date: November 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 5

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News & Notes

Publication date: November 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 5

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Letter to the Editor concerning “Ribosomal PCR assay of excised intervertebral discs from patients undergoing single-level primary lumbar microdiscectomy.’’ by Alamin TF, Munoz M, Zagel A, et al.: Eur Spine J 2017

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Lumbar total disc replacement: predictors for long-term outcome

Abstract

Purpose

We aimed to identify patient characteristics associated with favourable long-term outcomes after lumbar total disc replacement (TDR).

Methods

We analysed a cohort of 82 patients with degenerative disc and chronic low back pain (LBP) who were treated with TDR and originally participated in a randomised trial comparing TDR and multidisciplinary rehabilitation. Potential predictors were measured at baseline, and the outcomes assessed 8 years after they received allocated treatment. Outcome measures were dichotomised according to whether the participants achieved a clinically important functional improvement (15 points or more on the Oswestry Disability Index, ODI) (primary outcome) and whether they were employed at 8-year follow-up (secondary outcome). Associations between potential predictors and outcomes were modelled using logistic regression. For the secondary outcome, the results were also organised in a prediction matrix and expressed as probabilities.

Results

For 71 patients treated with TDR according to protocol, the follow-up time was 8 years. For a subgroup of 11 patients randomised to rehabilitation who crossed over and received TDR, the median postoperative follow-up time was 72 (range 41–88) months. Of all assessed baseline variables, only presence of Modic changes (type 1 and/or 2) was statistically significantly associated with an improvement of ≥ 15 ODI points. The probability of employment at 8-year follow-up was 1% for patients with ≥ 1 year of sick leave, comorbidity, ODI ≥ 50 and ≤ 9 years of education prior to treatment, and 87% for patients with < 1 year of sick leave, no comorbidity, ODI < 50 and higher education.

Conclusions

Patients with Modic changes prior to the TDR surgery were more likely to report a clinically important functional improvement at long-term follow-up. Comorbidity, low level of education, long-term sick leave and high ODI score at baseline were associated with unemployment at long-term follow-up.

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Monoamines in Glioblastoma: complex biology with therapeutic potential

Abstract

Glioblastoma (GBM) is characterized by extremely poor prognoses, despite the use of gross surgical resection, alkylating chemotherapeutic agents, and radiotherapy. Evidence increasingly highlights the role of the tumor microenvironment in enabling this aggressive phenotype. Despite this interest, the role of neurotransmitters, brain-specific messengers underlying synaptic transmission, remains murky. These signaling molecules influence a complex network of molecular pathways and cellular behaviors in many CNS-resident cells including neural stem cells and progenitor cells, neurons, and glia cells. Critically, available data convincingly demonstrate that neurotransmitters can influence proliferation, quiescence, and differentiation status of these cells. This ability to affect progenitors and glia—GBM-initiating cells—and their availability in the CNS, strongly support the notion that neurotransmitters participate in the onset and progression of GBM. This review will focus on dopamine and serotonin, as studies indicate they contribute to gliomagenesis. Particular attention will be paid to how these neurotransmitters and their receptors can be utilized as novel therapeutic targets. Overall, this review will analyze the complex biology governing the interaction of GBM with neurotransmitter signaling and highlight how this interplay shapes the aggressive nature of GBM.

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Memantine prevents acute radiation-induced toxicities at hippocampal excitatory synapses

Abstract

Background

Memantine has shown clinical utility in preventing radiation-induced cognitive impairment, but the mechanisms underlying its protective effects remain unknown. We hypothesized that abnormal glutamate signaling causes radiation-induced abnormalities in neuronal structure and that memantine prevents synaptic toxicity.

Methods

Hippocampal cultures expressing eGFP were irradiated or sham-treated and their dendritic spine morphology assessed at acute (minutes) and later (days) times using high-resolution confocal microscopy. Excitatory synapses, defined by co-localization of the pre- and post-synaptic markers vGLUT1 and PSD-95, were also analyzed. Neurons were pretreated with vehicle, the NMDA-type glutamate receptor antagonist memantine, or the glutamate scavenger glutamate pyruvate transaminase (GPT) to assess glutamate signaling. For animal studies, Thy-1-YFP mice were treated with whole brain radiotherapy or sham with or without memantine.

Results

Unlike previously reported long-term losses of dendritic spines, we found that the acute response to radiation is an initial increase in spines and excitatory synapses followed by a decrease in spine/synapse density with altered spine dynamics. Memantine pre-administration prevented this radiation-induced synaptic remodeling.

Conclusions

These results demonstrate that radiation causes rapid, dynamic, changes in synaptic structural plasticity, implicate abnormal glutamate signaling in cognitive dysfunction following brain irradiation, and describe a protective mechanism of memantine.

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Targeting different domains of gap junction protein to control malignant glioma

Abstract

A rational treatment strategy for glioma, the most common primary central nervous system tumor, should focus on early invasive growth and resistance to current therapeutics. Connexin 43 (Cx43), a gap junction protein, plays important roles not only in the development of the central nervous system and but also in the progression of glioma. The different structural domains of Cx43, including extracellular loops, transmembrane domains, and an intracellular carboxyl terminal, have distinct functions in the invasion and proliferation of gliomas. Targeting these domains of Cx43, which is expressed in distinct patterns in the heterogeneous glioma cell population, can inhibit tumor cell invasion and new tumor formation. Thus, this review summarizes the structural characteristics of Cx43, the effects of regulating different Cx43 domains on the biological characteristics of glioma cells, intervention strategies targeting different domains of Cx43, and future research directions.

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Risk factors for asthma after infant bronchiolitis

Abstract

Background

Five studies carried out after bronchiolitis at less than 24 months of age, with a follow up of more than 10 years, reported that atopic dermatitis, family asthma, early-life exposure to tobacco smoke and rhinovirus aetiology were early-life risk factors for later asthma. This study evaluated the long-term outcome at 11-13 years of age of children who were hospitalised for bronchiolitis in early infancy.

Methods

We previously prospectively followed 166 children hospitalised for bronchiolitis at less than six months of age until 5-7 years of age. The current study included a structured questionnaire, parental interviews, clinical examinations and bronchodilation test of 138 of those children at 11-13 years of age.

Results

Respiratory syncytial virus caused 66% of the bronchiolitis cases and nearly half of the patients were exposed to tobacco smoke in early life. Doctor-diagnosed asthma was present in 13% of the former bronchiolitis patients at 11-13 years of age. Maternal asthma was the only independently significant risk factor in early life (adjusted OR 3.45, 95% CI 1.07-11.74), as was allergic rhinitis at 5-7 years of age (adjusted OR 4.06, 95% CI 1.35-12.25).

Conclusions

After bronchiolitis at less than six months of age, the risk of doctor-diagnosed asthma at 11-13 years was about twice that of the general Finnish population. Maternal asthma was the only independently significant early-life risk factor for current asthma at 11-13 years of age.

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Co-targeting PI3K, mTOR, and IGF1R with small molecule inhibitors for treating undifferentiated pleomorphic sarcoma

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Does length of intubation before tracheostomy affect intensive care unit length of stay?

Does length of intubation before tracheostomy affect intensive care unit length of stay?

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Sep 27;:

Authors: Young SR, Bouloux GF, Perez SD, Abramowicz S

Abstract
OBJECTIVE: The purpose of this study was to determine if length of intubation before tracheotomy (LIT) affects length of stay in the intensive care unit (ICU).
STUDY DESIGN: This was a retrospective case series of patients who had open tracheotomies at Grady Memorial Hospital by the Oral and Maxillofacial Surgery (OMS) service. Medical records were reviewed to document patient demographic characteristics, etiology for ventilator dependence, and complications. The primary predictor variable was LIT and primary outcome variable was length of stay in ICU after tracheotomy. Statistical analysis was performed (significance P < .05).
RESULTS: There were 115 patients (mean age 54 years) included in the study. The majority received tracheotomies because of prolonged mechanical ventilation secondary to a medical comorbidity. Intraoperative complications were cardiac arrest and difficulty accessing trachea. Postoperative complications were bleeding. Postoperatively, most patients were discharged from the ICU or weaned off mechanical ventilation within 5 days. The correlation between LIT and ICU stay was not statistically significant, but the trend was positive.
CONCLUSIONS: The results of this study indicate that patients undergoing an earlier tracheotomy were more likely to have an earlier discharge from the ICU.

PMID: 29097138 [PubMed - as supplied by publisher]

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Chemodenervation of the Larynx.

Chemodenervation of the Larynx.

Toxins (Basel). 2017 Nov 02;9(11):

Authors: Kaye R, Blitzer A

Abstract
Botulinum neurotoxin (BoNT) has existed for thousands of years; however, it was not medically utilized until investigations into its therapeutic use began in sincerity during the late 1970s and 1980s. This, coupled with the reclassification of spasmodic dysphonia as a focal dystonia, led to the use of chemodenervation for this disorder, which has since become a refined technique. Indeed, due to its safety and efficacy, BoNT has been investigated in multiple neurolaryngology disorders, including spasmodic dysphonia, vocal tremor, and muscle tension dysphonia. BoNT has been shown to be a useful and safe adjunct in the treatment for these disorders and may reduce or eliminate oral pharmacotherapy and/or prevent the need for a surgical intervention. We present the historical background, development, proposed mechanisms of action, uses, and techniques for administering BoNT for laryngeal disorders, with a particular focus on spasmodic dysphonia.

PMID: 29099066 [PubMed - in process]

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A Method to Administer Agents to the Larynx in an Awake Large Animal.

A Method to Administer Agents to the Larynx in an Awake Large Animal.

J Speech Lang Hear Res. 2017 Nov 02;:1-6

Authors: Durkes A, Sivasankar MP

Abstract
Purpose: This research note describes an adapted experimental methodology to administer an exogenous agent to the larynx and upper airway of awake animals. The exogenous agent could be a perturbation. In the current study, the agent was isotonic saline. Isotonic saline was selected because it is safe, of similar composition to extracellular fluid, and used in voice studies. The described approach allowed large animals such as pigs to be comfortably restrained without chemical sedation or anesthesia for extended periods while receiving the agent.
Method: Six Sinclair pigs were successfully trained with positive reinforcement to voluntarily enter and then be restrained in a Panepinto Sling. Once restrained, the pigs accepted a nose cone that delivered nebulized isotonic saline. This procedure was repeated 3 times per day for 20 days. At the end of the study, the larynx and airway tissues were excised and examined using histology and transmission electron microscopy.
Results: Pathology related to the procedure (i.e., nebulized inhaled isotonic saline or stress) was not identified in any examined tissues.
Conclusions: This methodology allowed for repeated application of exogenous agents to awake, unstressed animals. This method can be used repeatedly in the laboratory to test various therapeutics for safety, toxicity, and dosage. Future studies will specifically manipulate the type of agent to further our understanding of laryngeal pathobiology.

PMID: 29098280 [PubMed - as supplied by publisher]

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Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction.

Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction.

J Appl Physiol (1985). 2017 Nov 02;:jap.00691.2017

Authors: Walsted ES, Faisal A, Jolley CJ, Swanton LL, Pavitt MJ, Luo YM, Backer V, Polkey MI, Hull JH

Abstract
Rationale: Exercise induced laryngeal obstruction (EILO), a phenomenon in which the larynx closes inappropriately during physical activity, is a prevalent cause of exertional dyspnea in young individuals. The physiological ventilatory impact of EILO and its relationship to dyspnea are poorly understood. Objectives: To evaluate exercise related changes in laryngeal aperture on ventilation, pulmonary mechanics and respiratory neural drive. Methods: We prospectively evaluated 12 subjects (six with EILO and six healthy age- and gender-matched controls). Subjects underwent baseline spirometry and a symptom-limited incremental exercise test with simultaneous and synchronized recording of endoscopic video, gastric-, esophageal- and transdiaphragmatic pressures, diaphragm electromyography and respiratory airflow. Results: The EILO and control groups had similar peak work rates and minute ventilation (V̇E) (work rate: 227±35 vs. 237±35W; V̇E: 103±20 vs. 98±23 L/min; p>0.05). At submaximal work rates (140-240W) subjects with EILO demonstrated increased work of breathing (p<0.05) and respiratory neural drive (p<0.05), developing in close temporal association with onset of endoscopic evidence of laryngeal closure (p<0.05). Unexpectedly, a ventilatory increase (p<0.05), driven by augmented tidal volume (p<0.05), was seen in subjects with EILO, before the onset of laryngeal closure; there were however no differences in dyspnea intensity between groups. Conclusion: Using simultaneous measurements of respiratory mechanics and diaphragm electromyography with endoscopic video we demonstrate, for the first time, increased work of breathing and respiratory neural drive in association with the development of EILO. Future detailed investigations are now needed to understand the role of upper airway closure in causing exertional dyspnea and exercise limitation.

PMID: 29097629 [PubMed - as supplied by publisher]

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Detection of voice changes due to aspiration via acoustic voice analysis.

Detection of voice changes due to aspiration via acoustic voice analysis.

Auris Nasus Larynx. 2017 Oct 30;:

Authors: Kang YA, Kim J, Jee SJ, Jo CW, Koo BS

Abstract
OBJECTIVE: Aspiration can occur during swallowing. The present study investigated the feasibility of identifying aspiration risk (AR) via acoustic voice parameters.
MATERIALS AND METHODS: In total, 165 patients scheduled for a videofluoroscopic swallowing study (VFSS) were included. The patients were divided into two groups (AR and non-AR) based on their VFSS results. The AR group, which had ingested materials on or below the vocal folds, included 59 patients (42 males and 17 females). The non-AR group, which showed normal swallowing, included 106 patients (49 males and 57 females). The major cause of swallowing disorders was a stroke. A sustained vowel/a/for at least 3s was recorded before and after swallowing. Eight acoustic voice parameters were measured using PRAAT, including fundamental frequency, standard deviation of F0, jitter, relative average perturbation (RAP), shimmer, amplitude perturbation quotient (APQ), harmonic-to-noise ratio (HNR), and noise-to-harmonic ratio (NHR). Changes in each acoustic voice parameter before and after the VFSS were compared between the two groups with a repeated-measures mixed analysis of variance.
RESULTS: Only RAP showed a statistically significant interaction between group (non-AR and AR) and time (pre- and post-swallowing; p=0.030). RAP decreased after swallowing in the AR group; however, it increased in the non-AR group. Jitter and NHR increased in the non-AR group but decreased in the AR group after swallowing, but the difference was not statistically significant.
CONCLUSIONS: Our results suggest that the accumulation of pasty food in the vocal folds may modify vocal fold vibration and change voice quality in patients with penetration/aspiration. Several acoustic voice parameters, especially jitter, RAP, and NHR, were affected by AR. Thus, acoustic voice analysis may be helpful in making a diagnosis of AR as a supplementary tool for standard swallowing study including VFSS or fiberoptic examination.

PMID: 29097046 [PubMed - as supplied by publisher]

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Evaluation of an Automated Swallow-Detection Algorithm Using Visual Biofeedback in Healthy Adults and Head and Neck Cancer Survivors.

Evaluation of an Automated Swallow-Detection Algorithm Using Visual Biofeedback in Healthy Adults and Head and Neck Cancer Survivors.

Dysphagia. 2017 Nov 02;:

Authors: Constantinescu G, Kuffel K, Aalto D, Hodgetts W, Rieger J

Abstract
Mobile health (mHealth) technologies may offer an opportunity to address longstanding clinical challenges, such as access and adherence to swallowing therapy. Mobili-T(®) is an mHealth device that uses surface electromyography (sEMG) to provide biofeedback on submental muscles activity during exercise. An automated swallow-detection algorithm was developed for Mobili-T(®). This study evaluated the performance of the swallow-detection algorithm. Ten healthy participants and 10 head and neck cancer (HNC) patients were fitted with the device. Signal was acquired during regular, effortful, and Mendelsohn maneuver saliva swallows, as well as lip presses, tongue, and head movements. Signals of interest were tagged during data acquisition and used to evaluate algorithm performance. Sensitivity and positive predictive values (PPV) were calculated for each participant. Saliva swallows were compared between HNC and controls in the four sEMG-based parameters used in the algorithm: duration, peak amplitude ratio, median frequency, and 15th percentile of the power spectrum density. In healthy participants, sensitivity and PPV were 92.3 and 83.9%, respectively. In HNC patients, sensitivity was 92.7% and PPV was 72.2%. In saliva swallows, HNC patients had longer event durations (U = 1925.5, p < 0.001), lower median frequency (U = 2674.0, p < 0.001), and lower 15th percentile of the power spectrum density [t(176.9) = 2.07, p < 0.001] than healthy participants. The automated swallow-detection algorithm performed well with healthy participants and retained a high sensitivity, but had lowered PPV with HNC patients. With respect to Mobili-T(®), the algorithm will next be evaluated using the mHealth system.

PMID: 29098398 [PubMed - as supplied by publisher]

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Flow and Grit by Design: Exploring Gamification in Facilitating Adherence to Swallowing Therapy.

Flow and Grit by Design: Exploring Gamification in Facilitating Adherence to Swallowing Therapy.

Am J Speech Lang Pathol. 2017 Nov 02;:1-8

Authors: Constantinescu G, Rieger J, Mummery K, Hodgetts W

Abstract
Purpose: Delivery of swallowing therapy is faced with challenges regarding access to in-clinic services and adherence to prescribed home programs. Mobile health (mHealth) technologies are being developed at a rapid pace to address these difficulties. Whereas some benefits to using these modern tools for therapy are obvious (e.g., electronic reminders), other advantages are not as well understood. One example is the potential for mHealth devices and apps to enhance adherence to treatment regimens.
Method: This article introduces a number of psychological concepts that relate to adherence and that can be leveraged by mHealth. Elements that contribute to flow (optimal experience) during an activity and those that reinforce grit (perseverance to achieve a long-term goal) can be used to engage patients in their own rehabilitation.
Results: The experience of flow can be targeted by presenting the rehabilitation exercise as an optimally challenging game, one that offers a match between challenge and ability. Grit can be supported by reinforcing routine and by varying the therapy experience using different games.
Conclusions: A combination of hardware and software design approaches have the potential to transform uninteresting and repetitive activities, such as those that make up swallowing therapy regimens, into engaging ones. The field of gamification, however, is still developing, and gamified mHealth apps will need to withstand scientific testing of their claims and demonstrate effectiveness in all phases of outcome research.

PMID: 29098271 [PubMed - as supplied by publisher]

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Electrical stimulation of hyoid muscles in post-stroke dysphagia.

Electrical stimulation of hyoid muscles in post-stroke dysphagia.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017 Nov 02;:

Authors: Konecny P, Elfmark M

Abstract
AIMS: The purpose of this study was to evaluate swallowing changes in post-stroke patients with dysphagia after four weeks of suprahyoid muscles electrical stimulation.
METHODS: This was a prospective randomized study of early stage stroke patients with dysphagia. Electrical stimulation of suprahyoid muscles was given to a group of 54 patients (26 men, average age 70 years) for 20 minutes a day, 5 days a week. Standard orofacial rehabilitation without electrical stimulation was carried out on a control group of 54 patients (31 men, average age 69 years). Swallowing was evaluated at the beginning of the study and at the end, by videofluoroscopy - measuring the time for oral and pharyngeal phases.
RESULTS: The difference in duration of oral transit time (OTT) after the therapy between the study group (average: 0.55 ± 0.01) and the control group (average: 0.29 ± 0.03) was statistically significant (P=0.01). Difference in duration of the pharyngeal transit time (PTT) after the therapy between the study group (average: 0.37 ± 0.02) and control group (average: 0.15 ± 0.02) was also statistically significant (P=0.009).
CONCLUSION: Electrical stimulation of suprahyoid muscles significantly reduced the duration of the oral and pharyngeal phases: in the post-stroke patients with dysphagia used in this study. The result is improved swallowing. This is a recently recommended approach and your study confirms its efficacy.

PMID: 29097820 [PubMed - as supplied by publisher]

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Detection of voice changes due to aspiration via acoustic voice analysis.

Detection of voice changes due to aspiration via acoustic voice analysis.

Auris Nasus Larynx. 2017 Oct 30;:

Authors: Kang YA, Kim J, Jee SJ, Jo CW, Koo BS

PMID: 29097046 [PubMed - as supplied by publisher]

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Evaluation of an Automated Swallow-Detection Algorithm Using Visual Biofeedback in Healthy Adults and Head and Neck Cancer Survivors.

Evaluation of an Automated Swallow-Detection Algorithm Using Visual Biofeedback in Healthy Adults and Head and Neck Cancer Survivors.

Dysphagia. 2017 Nov 02;:

Authors: Constantinescu G, Kuffel K, Aalto D, Hodgetts W, Rieger J

PMID: 29098398 [PubMed - as supplied by publisher]

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Flow and Grit by Design: Exploring Gamification in Facilitating Adherence to Swallowing Therapy.

Flow and Grit by Design: Exploring Gamification in Facilitating Adherence to Swallowing Therapy.

Am J Speech Lang Pathol. 2017 Nov 02;:1-8

Authors: Constantinescu G, Rieger J, Mummery K, Hodgetts W

PMID: 29098271 [PubMed - as supplied by publisher]

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Electrical stimulation of hyoid muscles in post-stroke dysphagia.

Electrical stimulation of hyoid muscles in post-stroke dysphagia.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017 Nov 02;:

Authors: Konecny P, Elfmark M

PMID: 29097820 [PubMed - as supplied by publisher]

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Detection of voice changes due to aspiration via acoustic voice analysis.

Detection of voice changes due to aspiration via acoustic voice analysis.

Auris Nasus Larynx. 2017 Oct 30;:

Authors: Kang YA, Kim J, Jee SJ, Jo CW, Koo BS

PMID: 29097046 [PubMed - as supplied by publisher]

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Comparing state-wide and single-center data to predict high-frequency emergency department utilization among patients with asthma exacerbation

Abstract

Background

Previous studies examining high-frequency ED utilization have primarily used single-center data, potentially leading to ascertainment bias if patients visit multiple centers. The goals of this study were (1) to create a predictive model to prospectively identify patients at risk of high-frequency ED utilization for asthma, and (2) to examine how that model differed using state-wide versus single-center data.

Methods

To track ED visits within a state, we analyzed 2011-2013 data from the New York State Healthcare Cost and Utilization Project (HCUP) State Emergency Department Databases (SEDD). The first year of data (2011) was used to determine prior utilization; 2012 was used to identify index ED visits for asthma and for demographics; and 2013 was used for outcome ascertainment. High-frequency utilization was defined as 4+ ED visits for asthma within one year after the index visit. We performed analyses separately for children (age <21 years) and adults, and constructed two models: one included all state-wide (multi-center) visits, and the other was restricted to index hospital (single-center) visits. Multivariable logistic regression models were developed from potential predictors selected a priori. The final model was chosen by evaluating model performance using AIC scores, 10-fold cross validation, and ROC curves.

Results

Among children, high-frequency ED utilization for asthma was observed in 2,417/94,258 (2.56%) using all state-wide visits, compared to 1,853/94,258 (1.97%) for index hospital visits only. Among adults, the corresponding results were 7,779/159,874 (4.87%) and 5,053/159,874 (3.16%), respectively. In the multi-center visit model, the area under the curve (AUC) from 10-fold cross validation for children was 0.70 (95% CI: 0.69-0.72), compared to 0.71 (95% CI: 0.69-0.72) in the single-center visit model. The corresponding AUC results for adults were 0.76 (95% CI: 0.76-0.77) and 0.76 (0.75-0.77), respectively.

Conclusion

Data available at the index ED visit can predict subsequent high-frequency utilization for asthma with AUC ranging from 0.70-0.76. Model accuracy was similar regardless of whether outcome ascertainment included all state-wide visits (multi-center) or was limited to the index hospital (single-center).

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Early Recurrence of First Unprovoked Seizures in Children

Abstract

Objectives

The risk of early seizure recurrences after first unprovoked seizures in children is largely unknown. We aimed to determine the rate of seizure recurrence within 14 days of first, unprovoked seizures in children and identify associated risk factors. Secondarily, we aimed to determine the risk of recurrence at 48 hours and 4 months.

Methods

We conducted a secondary analysis of a multicenter cohort study of children 29 days-18 years with first, unprovoked seizures. Emergency department (ED) clinicians completed standardized histories and physical examinations. The primary outcome, recurrent seizure at 14 days, and the secondary outcomes, recurrence at 48 hours and 4 months, were assessed by telephone follow-up and medical record review. For each recurrence time point, we excluded those patients for whom no seizure had recurred but chronic antiepileptic drugs (AEDs) had been initiated.

Results

475 patients were enrolled in the parent study. Of evaluable patients for this secondary analysis, 26/392 (6.6%, 95% CI: 4.4-9.6%) had recurrences within 48 hours of the incident seizures, 58/366 (15.8%; 12.3-20.0%) had recurrences within 14 days, and 107/340 (31.5%; 26.6-36.7%) had recurrences within 4 months. On logistic regression analysis, age younger than 3 years was independently associated with a higher risk of 14-day recurrence (adjusted OR 2.1, 95% CI 1.2, 3.7; p=0.01). Having had more than 1 seizure within the 24 hours prior to ED presentation was independently associated with a higher risk of seizure recurrence at 48 hours (adjusted OR 4.3, 95% CI 1.9, 9.8; p<0.001).

Conclusions

Risk of seizure recurrence 14 days after first unprovoked seizures in children is substantial, with younger children at higher risk. Prompt completion of an EEG and evaluation by a neurologist is appropriate for these children.

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Port positioning and docking for single-stage totally robotic dissection for rectal cancer surgery with the Si and Xi Da Vinci Surgical System

Abstract

We have previously reported our technique of single-docking totally robotic dissection for rectal cancer surgery using the Da Vinci^® Si Surgical System in 2009. However, we have since optimised our port placement for the Si system and have developed a novel configuration of port placement and docking for the Da Vinci^® Xi Surgical System. We have performed over 700 cases using this technique with the Si system and have used our Xi technique since 2016 for totally robotic dissection for rectal cancer. We have kept the configuration of port placements for both the Xi and Si system as similar as possible, with the priorities to avoid arm collisions as well as to provide a workable port configuration of two left-handed instruments and one right-handed instrument. To date, there have had no major complications or arm collisions related to this technique of docking, port positioning and instrument placement.

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SIRT3 deacetylates and promotes degradation of P53 in PTEN-defective non-small cell lung cancer

Abstract

Purpose

In non-small cell lung cancer (NSCLC), success of targeted therapy has promoted researches explicitly orientated based on genetic background. Although PTEN deficiency is common in NSCLC, carcinogenesis about such genetic type has not been fully explored. Here, we have found that classical tumor suppressor P53 could be modulated by deacetylase sirtuin-3 (SIRT3) depending on the PTEN condition in NSCLC, which may be a novel breakpoint for handling PTEN deficiency NSCLC.

Methods

First, we examined SIRT3 and P53 expression files in PTEN-deficient NSCLC clinical samples and investigated their correlation. Second, we built SIRT3 high or low expression models in different PTEN conditions by plasmid overexpression or si-RNA interference in NSCLC cell lines and explored the effect of SIRT3 upon P53. Furthermore, we investigated the influence of SIRT3 upon the ubiquitin–proteasome dependent degradation pathway of P53 in PTEN-deficient NSCLC cell lines. Finally, we probed into the deacetylation modification of P53 via SIRT3.

Results

We found that SIRT3 expression was strongly positive and P53 expression was almost negative in PTEN-deficient NSCLC clinical samples. Further, we demonstrated that SIRT3 promoted degradation of P53 in PTEN-deficient NSCLC cell lines via the ubiquitin–proteasome pathway. Finally, we demonstrated that SIRT3 could deacetylate P53 at lysines 320 and 382, which may account for the observed degradation of P53 in PTEN-deficient tumor cells.

Conclusions

We have identified a novel mechanism by which P53 was inactivated via SIRT3 in PTEN-deficient cells. This may shed light on the mechanisms underlying the malignancy of PTEN-deficient NSCLC.

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DNA hypermethylation enhanced telomerase reverse transcriptase expression in human-induced pluripotent stem cells

Abstract

During reprogramming into human induced pluripotent stem cells (iPSCs), several stem cell marker genes are induced, such as OCT-4, NANOG, SALL4, and TERT. OCT-4, NANOG, and SALL4 gene expression can be regulated by DNA methylation. Their promoters become hypomethylated in iPSCs during reprogramming, leading to their induced expression. However, epigenetic regulation of the TERT gene remains unclear. In this study, we focused on epigenetic regulation of the human TERT gene and identified a differentially methylated region (DMR) at a distal region in the TERT promoter between human iPSCs and their parental somatic cells. Interestingly, the TERT-DMR was highly methylated in iPSCs, but low-level methylation was observed in their parental somatic cells. Region-specific, methylated-promoter assays showed that the methylated TERT-DMR up-regulated the promoter activity in iPSCs. In addition, Lamin B1 accumulated at the TERT-DMR in iPSCs, but not in their parent somatic cells. These results suggested that the TERT transcription was enhanced by DNA methylation at the TERT-DMR via binding to nuclear lamina during reprogramming. Our findings shed light on a new functional aspect of DNA methylation in gene expression.

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Lipid Peroxidation and Immune Biomarkers Are Associated with Major Depression and Its Phenotypes, Including Treatment-Resistant Depression and Melancholia

Abstract

To examine immune-inflammatory and oxidative (I&O) biomarkers in major depression (MDD) and its related phenotypes, we recruited 114 well-phenotyped depressed patients and 50 healthy controls and measured serum levels of interleukin (IL)-1α, soluble IL-1 receptor antagonist (sIL-1RA), soluble IL-2 receptor (sIL-2R), soluble IL-6 receptor (sIL-6R), soluble tumor necrosis factor receptor 60 and 80 kDa (sTNF-R1/R2), and thiobarbituric acid reactive substances (TBARS). Obtained results indicate that MDD is characterized by increased sIL-1RA, sTNF-R1, and TBARS concentrations. Melancholic depression is associated with increased sIL-6R but lowered IL-1α levels. A current episode of depression is accompanied by significantly increased sIL-6R compared to the remitted state. Treatment-resistant depression (TRD) is accompanied by increased sIL-6R and TBARS but lowered sTNF-R2 levels compared to non-TRD patients. These immune markers are not significantly correlated with Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Scale (MADRS), number episodes, or age at onset. Our findings show that increased sIL-1RA, sTNF-R1, and TBARS levels may be trait markers of depression, while increased sIL-6R levels may be a state marker of melancholia and an acute phase of depression. MDD is accompanied by increased lipid peroxidation and simultaneous activation of immune pathways, and the compensatory anti-inflammatory reflex system (CIRS). TRD is characterized by highly increased oxidative stress and probably increased TNFα and IL-6 trans-signalling. Novel treatments for major depression should target oxidative stress pathways, while new treatments for TRD should primary target lipid peroxidation and also activated immune-inflammatory pathways.

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Cytomorphologic features of metastatic endometrioid carcinoma by fine needle aspiration

Abstract

Background

Although metastatic disease is commonly seen in high grade carcinomas of gynecologic origin, it also occurs in low to intermediate grade endometrioid carcinomas (LGEMCAs), and may even be the primary presentation of disease. Tissue confirmation is necessary to guide therapy, but performing biopsies might not always be feasible or practical. In such instances, fine needle aspiration (FNA) is a safe and efficient alternative. No comprehensive series describing the cytomorphologic features of metastatic LGEMCA on FNA samples has been published. This study describes clinical and cytomorphologic features of metastatic LGEMCA diagnosed by FNA.

Methods

The pathology archives at 2 academic institutions were searched for patients with endometrial or ovarian endometrioid carcinoma, with concurrent or subsequent sampling of metastatic sites by FNA.

Results

Twelve cases were identified; all slides were reviewed and cytomorphologic features recorded. Four cases were obtained from metastatic sites as primary presentation of disease, and 8 cases were obtained from metastatic sites in patients with known history of LGEMCA. Metastatic LGEMCAs generate cellular specimens composed of cohesive clusters of cells with areas of gland formation. Consistent cytomorphologic features included nuclear overlapping, low to intermediate nuclear to cytoplasmic ratios, round to elongated nuclear shape, finely vacuolated cytoplasm, mild to moderate nuclear membrane irregularities, squamous metaplasia, and inconspicuous nucleoli. Variability was seen with regards to the presence of necrosis (50% of cases) and mitosis (25% of cases).

Conclusion

The presence of these features on FNA samples should raise concern for an underlying gynecologic malignancy.

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Letter to the editor: A rare case of microfilaria in ascitic fluid

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Drug-associated hyperpigmentation of the oral mucosa: report of 4 cases.

Publication date: Available online 3 November 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Konstantinos I. Tosios, Eleni-Marina Kalogirou, Alexandra Sklavounou
ObjectiveTo describe four patients with oral mucosa hyperpigmentation associated with four drug classes and review the literature.Study DesignTwo patients under imatinib and hydroxychloroquine treatment exhibited diffuse palatal hyperpigmentation, while two patients medicated with minocycline and golimumab showed multifocal pigmented macules. In all cases biopsies were performed.ResultsMicroscopically, in all cases there was no increase in the number of melanocytes in the epithelium and pigment granules were present in the lamina propria. The pigment granules in minocycline- and golimumab-associated hyperpigmentation were seen in the superficial lamina propria and reacted for silver but not iron, while in imatinib- and hydroxychloroquine-associated hyperpigmentation were found in the reticular lamina propria and reacted both for silver and iron. A review of the literature found 38 cases of oral mucosa hyperpigmentation attributed to minocycline, 23 to imatinib, one to hydroxychloroquine without microscopic documentation, and none to golimumab.ConclusionThe temporal relationship between pigmentation and drug onset, resolution following drug withdrawal and exclusion of other causes support the diagnosis of drug-induced hyperpigmentation. Microscopic examination may be contributory to diagnosis, as there are differences among drugs in the distribution of pigment granules and their histochemical reactions.

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A preliminary immunohistochemical study of signal transducer and activator of transcription (STAT) proteins in primary oral malignant melanoma

Publication date: Available online 3 November 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Nikolaos G. Nikitakis, Ioannis Gkouveris, Erofili Papadopoulou, Argyrios Daskalopoulos, Alexandra Sklavounou
ObjectivePrimary oral malignant melanoma (POMM) is a rare type of malignancy with a very poor prognosis, the molecular pathogenesis of which remains elusive. The aim of this study was to assess the expression status of signal transducers and activators of transcription (STAT) proteins in POMM.Study DesignSix POMMs were included in the study. Total protein levels of STAT1, 3 and 5a, as well as the tyrosine phosphorylated (activated) form of STAT3 (pSTAT3), were assessed immunohistochemically.ResultsImmunohistochemical evaluation of total STAT3 revealed diffuse and strong cytoplasmic and nuclear expression in the majority of tumor cells of all cases, while activated pSTAT3 showed mostly mild nuclear expression in 5-40% of malignant melanocytes in all cases. Evaluation of STAT1 and STAT5a showed mainly mild cytoplasmic expression in the absence of nuclear localization.ConclusionThe demonstration of aberrant STAT3 expression and activation in oral malignant melanocytes supports a possible role of this molecule in POMM. In contrast, STAT5a shows only limited cytoplasmic expression mitigating against its involvement in POMM. Also, STAT1 low levels may have implications for POMM sensitivity to interferon (IFN)-based therapeutic strategies, considering the role of this molecule in cutaneous melanoma immunotherapy.

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Cell cycle-dependent translocation and regulatory mechanism of CacyBP/SIP in gastric cancer cells.

Our previous results showed that calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP) inhibits the proliferation and tumorigenicity of gastric cancer; however, the exact mechanism remains unclear, especially from the aspect of cell cycle. The subcellular localization of CacyBP/SIP, Siah-1, and Skp1 in SGC7901 gastric cancer cells was assessed by immunofluorescence after cell cycle synchronization. Levels of CacyBP/SIP, Siah-1, Skp1, [beta]-catenin, and p-ERK1/2 were analyzed by western blotting. CacyBP/SIP phosphorylation (p-CacyBP/SIP) and the combining capacity of Siah-1 and Skp1 with CacyBP/SIP in nucleoprotein were determined by immunoprecipitation. CacyBP/SIP, Siah-1, and Skp1 were mainly in the cytoplasm in the G1 phase, but translocated to the nucleus during G2. Their expression in total protein was not altered, but elevated in the G2 phase in nucleoprotein. The CacyBP/SIP nucleus translocation of cells transfected with mutant CacyBP/SIP that does not bind S100 (CacyBP-[DELTA]S100) was significantly increased compared with wild-type CacyBP/SIP. In the G2 phase, p-CacyBP/SIP expression and the combining capacity of Siah-1 and Skp1 with CacyBP/SIP were all increased, whereas levels of [beta]-catenin and p-ERK1/2 reduced, compared with the G1 phase. CacyBP/SIP or CacyBP-[DELTA]S100 overexpression was correlated with constitutively low [beta]-catenin expression and affected its level through cell cycle. CacyBP/SIP overexpression led to retarded proliferation, G1 arrest, and [beta]-catenin reduction, which could be abolished by lithium chloride, [beta]-catenin activator, and further enhanced by the Wnt inhibitor XAV-939. In addition, CacyBP-[DELTA]S100 further suppressed cell proliferation and induced G1 arrest compared with CacyBP/SIP. In conclusion, CacyBP/SIP nuclear localization, dependent on S100 protein, suppresses gastric cancer tumorigenesis through [beta]-catenin degradation and the dephosphorylation of ERK1/2 during the G2 phase. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Autophagy and doxorubicin resistance in cancer.

Doxorubicin (DOX), also known as adriamycin, is a DNA topoisomerase II inhibitor and belongs to the family of anthracycline anticancer drugs. DOX is used for the treatment of a wide variety of cancer types. However, resistance among cancer cells has emerged as a major barrier to effective treatment using DOX. Currently, the role of autophagy in cancer resistance to DOX and the mechanisms involved have become one of the areas of intense investigation. More and more preclinical data are being obtained on reversing DOX resistance through modulation of autophagy as one of the promising therapeutic strategies. This review summarizes the recent advances in autophagy-targeting therapies that overcome DOX resistance from in-vitro studies to animal models for exploration of novel delivery systems. In-depth understanding of the mechanisms of autophagy regulation in relation to DOX resistance and development of molecularly targeted autophagy-modulating agents will provide a promising therapeutic strategy for overcoming DOX resistance in cancer treatment. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Temozolomide treatment of a malignant pheochromocytoma and an unresectable MAX-related paraganglioma.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors with a strong genetic background. The mainstay of treatment for PCC/PGLs is surgery. However, for unresectable lesions, no curative treatment is currently available. Temozolomide (TMZ) has been shown to determine radiological and biochemical response in malignant PCC/PGLs. We report two cases of PCC/PGLs treated with TMZ. Case 1 is a 51-year-old man with local and distant recurrence (liver and bone metastases) of right adrenal PCC. Case 2 is a 54-year-old woman with a PCC/PGL syndrome caused by a mutation in MAX gene (c.171+1G>A), operated on for bilateral adrenal PCC and presenting with a large unresectable abdominal PGL. Both patients presented hypertension due to catecholamine hypersecretion. TMZ determined radiological response according to RECIST criteria, reduction of urinary catecholamine levels, and controlled hypertension in both patients. Furthermore, the current study demonstrates, for the first time, that MAX-related PGLs are responsive to TMZ. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Influence of glutamate-evoked pain and sustained elevated muscle activity on blood oxygenation in the human masseter muscle

This study aimed to investigate the effect of glutamate-evoked masseter muscle pain on intramuscular oxygenation during rest and sustained elevated muscle activity (SEMA). Seventeen healthy individuals participated in two sessions in which they were injected with glutamate and saline in random order. Each session was divided into three, 10-min periods. During the first (period 1) and the last (period 3) 10-min periods, participants performed five intercalated 1-min bouts of masseter SEMA with 1-min periods of 'rest'. At onset of the second 10-min period, glutamate (0.5 ml, 1 M; Ajinomoto, Tokyo, Japan) or isotonic saline (0.5 ml; 0.9%) was injected into the masseter muscle and the participants kept the muscle relaxed in a resting position for 10 min (period 2). The hemodynamic characteristics of the masseter muscle were recorded simultaneously during the experiment by a laser blood-oxygenation monitor. The results demonstrated that glutamate injections caused significant levels of self-reported pain in the masseter muscle; however, this nociceptive input did not have robust effects on intramuscular oxygenation during rest or SEMA tasks. Interestingly, these findings suggest an uncoupling between acute nociceptive activity and hemodynamic parameters in both resting and low-level active jaw muscles. Further studies are needed to explore the pathophysiological significance of blood-flow changes for persistent jaw-muscle pain conditions.

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Ocular Motor Dysfunction Due to Brainstem Disorders.

Background: The brainstem contains numerous structures including afferent and efferent fibers that are involved in generation and control of eye movements. Evidence Acquisition: These structures give rise to distinct patterns of abnormal eye movements when damaged. Defining these ocular motor abnormalities allows a topographic diagnosis of a lesion within the brainstem. Results: Although diverse patterns of impaired eye movements may be observed in lesions of the brainstem, medullary lesions primarily cause various patterns of nystagmus and impaired vestibular eye movements without obvious ophthalmoplegia. By contrast, pontine ophthalmoplegia is characterized by abnormal eye movements in the horizontal plane, while midbrain lesions typically show vertical ophthalmoplegia in addition to pupillary and eyelid abnormalities. Conclusions: Recognition of the patterns and characteristics of abnormal eye movements observed in brainstem lesions is important in understanding the roles of each neural structure and circuit in ocular motor control as well as in localizing the offending lesion. (C) 2017 by North American Neuro-Ophthalmology Society

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Symptom: Serous Effusion

No abstract available

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Innovative Hearing Test for Toddlers and Preschoolers

No abstract available

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Hearing Aids of Tomorrow: Cognitive Control Toward Individualized Experience

No abstract available

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Auditory Hair Cell Stereocilia: Balancing Stability to Gain Sensitivity?

No abstract available

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Music Keeps the Hearing Brain Young

No abstract available

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Dementia and Age-Related Hearing Loss – Part II

No abstract available

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The Past, Present, and Future of the American Tinnitus Association

No abstract available

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Can a Machine Learn to Solve our Speech-in-Noise Problem?

No abstract available

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Audiologists’ Role in Managing Patient Suicide Risk

No abstract available

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Highs, Lows of Developing a CI Clinic in an AuD Program

No abstract available

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Manufacturers News

No abstract available

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Παρασκευή 3 Νοεμβρίου 2017

BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions are frequent in epithelioid glioblastomas: A histological and molecular analysis focusing on intratumoral heterogeneity

Abstract

Epithelioid glioblastoma (E-GBM) is a rare aggressive variant of IDH-wildtype glioblastoma newly recognized in the 2016 World Health Organization classification, composed predominantly of monotonous, patternless sheets of round cells with laterally positioned nuclei and plump eosinophilic cytoplasm. Approximately 50% of E-GBM harbor BRAF V600E, which is much less frequently found in other types of glioblastomas. Most E-GBM are recognized as primary/de novo lesions; however, several E-GBM with co- or pre-existing lower-grade lesions have been reported. To better understand associations between E-GBM and the lower-grade lesions, we undertook a histological and molecular analysis of 14 E-GBM, 10 of which exhibited lower-grade glioma-like components (8 E-GBM with co-existing diffuse glioma-like components, 1 E-GBM with a co-existing PXA-like component, and 1 E-GBM with a pre-existing PXA). Molecular results demonstrated that the prevalence of BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions in E-GBM were 13/14 (93%), 10/14 (71%) and 11/14 (79%), respectively, and concurrent BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions were observed in 7/14 (50%) of E-GBM. These alterations were also frequently seen in the lower-grade lesions irrespective of the histology. Genetic analysis including array comparative genomic hybridization performed for 5 E-GBM with co- and pre-existing lower-grade components revealed that all molecular changes found in the lower-grade components were also observed in the E-GBM components, and additional changes were detected in the E-GBM components. In conclusion, E-GBM frequently exhibit BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions, and these alterations tend to coexist in E-GBM. Taken together with the facts that only one PXA preceded E-GBM among these lower-grade lesions, and that co-occurrence of BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions have been reported to be rare in conventional lower-grade diffuse gliomas, the diffuse glioma-like components may be distinct infiltrative components of E-GBM, reflecting intratumoral heterogeneity. This article is protected by copyright. All rights reserved.

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Phase1 study of cisplatin plus pemetrexed with erlotinib and bevacizumab for chemotherapy-naïve advanced non-squamous non-small cell lung cancer with EGFR mutations

Summary

Background Cisplatin and pemetrexed are very effective against advanced non-squamous non-small cell lung cancer (NSCLC) without EGFR mutations. Erlotinib plus bevacizumab are highly effective against advanced NSCLCs with activating EGFR mutations. We performed this phase I 'Quartet Trial' to determine the safety and efficacy of all 4 agents as a first-line treatment for non-squamous NSCLC patients harboring activating EGFR mutations. Patients and Methods Patients received escalating quartet-agent doses every 3 weeks for 4 cycles. We examined the dose-limiting toxicity (DLT) to determine the maximum tolerated dose (MTD) and recommended dose (RD). Results Ten patients (3 men and 7 women) with a median age of 69 years were enrolled. Four and 6 patients had exon 19 and 21 mutations, respectively; 8 received maintenance therapy without unexpected or cumulative toxicities. One of 6 patients experienced grade 3 vagal reflex at 60 mg/m² cisplatin plus 500 mg/m² pemetrexed with 150 mg erlotinib and 15 mg/kg bevacizumab, which was designated the RD. Four patients experienced no DLT with 75 mg/m² cisplatin plus 500 mg/m² pemetrexed with 150 mg erlotinib and 15 mg/kg bevacizumab (designated the MTD); however, 3 underwent dose reduction due to severe toxicities (grade 3 gastrointestinal hemorrhage, skin rash, nausea, and febrile neutropenia) during induction chemotherapy. The most frequent DLT-phase adverse events were nausea, anorexia, and fatigue. The overall response rate was 100%. Furthermore, the progression-free and overall survival rates were 17.9 and 32.0 months, respectively. Conclusions This quartet chemotherapy regimen was tolerable and effective in our patient population (UMIN000012536).

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Sponsoring Organizations and Liaisons

Publication date: November 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 5

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Publication date: November 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 5

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The Essentials

Publication date: November 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 5

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Academy of Prosthodontics centennial: The emergence and development of prosthodontics as a specialty

Publication date: November 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 5
Author(s): Jonathan P. Wiens, Sreenivas Koka, Gerald Graser, Shane N. White, Carlo P. Marinello, Donald A. Curtis

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Editorial Board

Publication date: November 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 5

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Αρχειοθήκη ιστολογίου

Σάββατο 4 Νοεμβρίου 2017

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Παρασκευή 3 Νοεμβρίου 2017

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