Unprecedented response to combination BRAF and MEK inhibitors in adult anaplastic ganglioglioma

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Analyzing the interactions of mRNAs, miRNAs, lncRNAs and circRNAs to predict competing endogenous RNA networks in glioblastoma

Abstract

Cross-talk between competitive endogenous RNAs (ceRNAs) may play a critical role in revealing potential mechanisms of tumor development and physiology. Glioblastoma is the most common type of malignant primary brain tumor, and the mechanisms of tumor genesis and development in glioblastoma are unclear. Here, to investigate the role of non-coding RNAs and the ceRNA network in glioblastoma, we performed paired-end RNA sequencing and microarray analyses to obtain the expression profiles of mRNAs, lncRNAs, circRNAs and miRNAs. We identified that the expression of 501 lncRNAs, 1999 mRNAs, 2038 circRNAs and 143 miRNAs were often altered between glioblastoma and matched normal brain tissue. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed on these differentially expressed mRNAs and miRNA-mediated target genes of lncRNAs and circRNAs. Furthermore, we used a multi-step computational framework and several bioinformatics methods to construct a ceRNA network combining mRNAs, miRNAs, lncRNAs and circRNA, based on co-expression analysis between the differentially expressed RNAs. We identified that plenty of lncRNAs, CircRNAs and their downstream target genes in the ceRNA network are related to glutamatergic synapse, suggesting that glutamate metabolism is involved in glioma biological functions. Our results will accelerate the understanding of tumorigenesis, cancer progression and even therapeutic targeting in glioblastoma.

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A comparison of semi-automated volumetric vs linear measurement of small vestibular schwannomas

Abstract

Objective

Accurate and precise measurement of vestibular schwannoma (VS) size is key to clinical management decisions. Linear measurements are used in routine clinical practice but are prone to measurement error. This study aims to compare a semi-automated volume segmentation tool against standard linear method for measuring small VS. This study also examines whether oblique tumour orientation can contribute to linear measurement error.

Study design

Experimental comparison of observer agreement using two measurement techniques.

Setting

Tertiary skull base unit.

Participants

Twenty-four patients with unilateral sporadic small (< 15 mm maximum intracranial dimension) VS imaged with 1 mm-thickness T1-weighted Gadolinium enhanced MRI.

Main outcome measures

(1) Intra and inter-observer intraclass correlation coefficients (ICC), repeatability coefficients (RC), and relative smallest detectable difference (%SDD). (2) Mean change in maximum linear dimension following reformatting to correct for oblique orientation of VS.

Results

Intra-observer ICC was higher for semi-automated volumetric when compared with linear measurements, 0.998 (95% CI 0.994–0.999) vs 0.936 (95% CI 0.856–0.972), p < 0.0001. Inter-observer ICC was also higher for volumetric vs linear measurements, 0.989 (95% CI 0.975–0.995) vs 0.946 (95% CI 0.880–0.976), p = 0.0045. The intra-observer %SDD was similar for volumetric and linear measurements, 9.9% vs 11.8%. However, the inter-observer %SDD was greater for volumetric than linear measurements, 20.1% vs 10.6%. Following oblique reformatting to correct tumour angulation, the mean increase in size was 1.14 mm (p = 0.04).

Conclusion

Semi-automated volumetric measurements are more repeatable than linear measurements when measuring small VS and should be considered for use in clinical practice. Oblique orientation of VS may contribute to linear measurement error.

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The Importance of Television Closed Captioning and Captioned Telephone Service for People with Hearing Loss

How closed captioning and captioned telephone service can help people with hearing loss have a better understanding of speech on the television and telephone.

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Is sugammadex alone sufficient to cause anaphylaxis?

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The long-term effect of erythropoiesis stimulating agents given to preterm infants: a proton magnetic resonance spectroscopy study on neurometabolites in early childhood

Abstract

Background

Erythropoiesis stimulating agents (ESAs) are neuroprotective in cell and animal models of preterm birth. Prematurity has been shown to alter neurometabolite levels in children in studies using proton magnetic resonance spectroscopy (1H-MRS).

Objective

We hypothesized that ESA treatment in premature infants would tend to normalize neurometabolites by 4–6 years of age.

Materials and methods

Children in a longitudinal study of neurodevelopment underwent MRI and 1H-MRS at approximately 4 years and 6 years of age. Prematurely born children (500–1,250 g birth weight) received ESAs (erythropoietin or darbepoetin) or placebo during their neonatal hospitalization, and these groups were compared to healthy term controls. 1H-MRS spectra were obtained from the anterior cingulate (gray matter) and frontal lobe white matter, assessing combined N-acetylaspartate and N-acetylaspartylglutamate (tNAA), myo-inositol, choline compounds (Cho), combined creatine and phosphocreatine, and combined glutamate and glutamine.

Results

No significant (P≤0.5) group differences were observed for any metabolite level. Significant age-related increases in white-matter tNAA and Cho were observed, as well as a trend for increased gray-matter tNAA.

Conclusion

Neither prematurity nor neonatal ESA treatment was associated with differences in brain metabolite levels in the children of this study at a significance level of 0.05. These findings suggest that earlier differences that might have existed had normalized by 4–6 years of age or were too small to be statistically significant in the current sample.

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Cognitive dysfunction after generalized tonic-clonic status epilepticus in adults

Objectives

Generalized tonic-clonic status epilepticus (GTC-SE) is considered a risk for cognitive impairment. Research with standardized tools is scarce and non-conclusive. We systematically assessed short-term and long-term cognitive function after GTC-SE.

Materials and methods

Thirty-three patients were tested after the clinical post-ictal phase of GTC-SE (timepoint 1) and again after 1 year (timepoint 2). Twenty controls were examined with the same tests. Tests from Cambridge Neuropsychological Test Automated Battery were used. Motor screening test (MOT) assessed motor speed, delayed matching to sample (DMS) and paired associates learning (PAL) assessed memory, and Stockings of Cambridge (SOC) assessed executive function. Estimated premorbid IQ and radiologically visible brain lesions were controlled for in adjusted results. Outcome measures were z-scores, the number of standard deviations a score deviates from the mean of a norm population.

Results

At timepoint 1, unadjusted patient results were significantly below both norm and control group performances on all subtests. Patient mean was 1.9 z-scores below controls (P < .001) on PAL total errors. Results remained significant for PAL and DMS after adjustments. Patient results improved at timepoint 2, but memory tests remained lower than norms and for controls. An executive dysfunction emerged on the most complex SOC stage (z-score difference −0.83; P = .008, adjusted difference −0.94; P = .02).

Conclusions

Memory and learning impairment in the early phase after SE and late developing executive dysfunction remained significant after adjusting for estimated premorbid IQ and pre-SE brain lesions. Results suggest that GTC-SE poses a risk for cognitive impairment.

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Pustular psoriasis and related pustular skin diseases

Summary

Patients with pustular psoriasis or related pustular diseases may have genetic abnormalities impairing the function of key players of the innate skin immune system. Recently, identification of these abnormalities has changed the paradigm of several of these diseases. These include generalized pustular psoriasis, palmoplantar pustular psoriasis and acrodermatitis continua of Hallopeau, and also drug-induced acute exanthematous generalized pustular eruption. Identified mutations in IL36RN, CARD14 and AP1S3 in different groups of patients lead to enhanced inflammatory cascade in several cellular subtypes including keratinocytes, and to the recruitment and activation of neutrophils and macrophages. These insights have unveiled pathophysiological features that shift the existing paradigms and emphasize the autoinflammatory nature of skin pustular disorders. They also highlight the crucial role of the innate immune system across entities belonging to the psoriasis disease spectrum, allowing identification of new appealing therapeutic targets.

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Sarcoidosis with muscular involvement demonstrated on gallium-67 scintigraphy

LETTER

Hippokratia 2016, 20(4):319

Meristoudis G¹, Tryfon S², Notopoulos A^1
1Nuclear Medicine Department, Hippokration Hospital
²Pulmonary Department, Papanikolaou Hospital, Thessaloniki, Greece

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Effects of radial extracorporeal shock wave therapy on hand spasticity in poststroke patient

CASE REPORT

Hippokratia 2016, 20(4):309-312

Gjerakaroska Savevska C, Nikolikj Dimitrova E, Gocevska M
Institute for Physical and Rehabilitation Medicine, Medical Faculty, "Ss Ciryl and Methodius" University, Skopje, F.Y.R. of Macedonia

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The Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire: cultural adaptation and validation of the Greek version

RESEARCH ARTICLE

Hippokratia 2016, 20(4):264-267

Tailachidis P^1,2, Tsimtsiou_­­ Z³, Galanis P^2,4, Theodorou M², Kouvelas D¹, Athanasakis K^2,5
12^nd Department of Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
²Faculty of Economics and Management, Open University of Cyprus, Nicosia, Cyprus
³Department of Hygiene, Faculty of Medicine, Aristotle University of Thessaloniki Thessaloniki, Greece
⁴Center for Health Services Management and Evaluation, Department of Nursing, University of Athens, Athens, Greece
⁵Department of Health Economics, National School of Public Health, Athens, Greece

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Anesthesia management of a patient with a femoral neck fracture and hereditary hemorrhagic telangiectasia

CASE REPORT

Hippokratia 2016, 20(4):303-305

Tsoleridis T, Galanou L, Tsoleridis S
Department of Anesthesiology and Pain Treatment, General Hospital of Rhodes, Rhodes, Greece

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The relationship between neutrophil/lymphocyte and platelet/lymphocyte ratios with oxidative stress in active Crohn’s disease patients

RESEARCH ARTICLE

Hippokratia 2016, 20(4):268-273

Eraldemir FC¹, Musul M², Duman AE³, Oztas B⁴, Baydemir C⁵, Hulagu S^3
1Department of Biochemistry, Medical School, University of Kocaeli, Kocaeli
²Laboratory of Biochemistry, Bucak State Hospital, Burdur
³Department of Gastroenterology, Medical School, University of Kocaeli, Kocaeli
⁴Department of Biochemistry, Sisli Hamidiye Etfal Research and Training Hospital, Istanbul
⁵Department of Biostatistic, Medical School, University of Kocaeli, Kocaeli, Turkey

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MicroRNA expression in patients with squamous cell carcinoma of the tongue

LETTER

Hippokratia 2016, 20(4):317

Paraskevopoulos K¹, Touplikioti P², Antoniades K^1
1Department of Oral and Maxillofacial Surgery, 'G.Papanikolaou' General Hospital
²Department of Cytopathology, Theageneio Anticancer Hospital, Thessaloniki, Greece

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Epidemiology and outcome of elderly admitted to the ward for sepsis

RESEARCH ARTICLE

Hippokratia 2016, 20(4):274-278

Pyrpasopoulou A^1,2, Pateinakis P¹, Varouktsi A¹, Georgianou E¹, Zografou I¹, Roilides E^2,3, Karagiannis A^1
12nd Propedeutic Department of Internal Medicine
²Infectious Diseases Unit
³3rd Pediatric Department, Hippokration Hospital, Thessaloniki, Greece

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The adipokines in the pathogenesis and treatment of nonalcoholic fatty liver disease

REVIEW ARTICLE

Hippokratia 2016, 20(4):259-263

Boutari C¹, Tziomalos K², Athyros VG^1
1Second Propedeutic Department of Internal Medicine, Hippokration Hospital
²First Propedeutic Department of Internal Medicine, AHEPA Hospital Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Home intravenous antibiotic therapy in children with cystic fibrosis: clinical outcome, quality of life and economic benefit

RSEARCH ARTICLE

Hippokratia 2016, 20(4):279-283

Chrysochoou EA, Hatziagorou E, Kirvassilis F, Tsanakas J
3rd Pediatric Department, Pediatric Pulmonology and Cystic Fibrosis Unit, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece

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Multifocal splenic abscesses in immunocompetent adult due to cat-scratch disease

CASE REPORT

Hippokratia 2016, 20(4):306-308

Gkamprela E¹, Papadimitropoulos V¹, Papadopoulos N², Deutsch M^1
1Second Department of Internal Medicine, "Hippokration" General Hospital of Athens, National and Kapodistrian University of Athens
²First Department of Internal Medicine, 417 Army Share Fund Hospital of Athens, Athens, Greece

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Prevalence and social determinants of smoking in the adult Greek Cypriot population

RESEARCH ARTICLE

Hippokratia 2016, 20(4):284-291

Nicolaou SA¹, Heraclides A², Markides KS³, Charalambous A^2
1Department of Life and Health Sciences
²Medical School, Center of Primary Care and Population Health, University of Nicosia, Nicosia, Cyprus
³Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, USA

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Anal canal gastrointestinal stromal tumors - report of a rare case and review of the literature

CASE REPORT

Hippokratia 2016, 20(4):313-316

Paramythiotis D¹, Bangeas P¹, Karakatsanis A¹, Karayannopoulou G², Michalopoulos A^1
11st Propedeutic Surgical Department, A.H.E.P.A. University Hospital
²Pathology Department, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Ultrastructural evaluation of intramuscular applied botulinum toxin type A in striated muscles of rats

RESEARCH ARTICLE

Hippokratia 2016, 20(4):292-298

Kocaelli H¹, Yaltirik M¹, Ayhan M¹,  Aktar F², Atalay B¹,  Yalcin S^1
1Department of Oral and Maxillofacial Surgery, Faculty of Dentistry
²Department of Histology and Embryology, Faculty of Medicine, Istanbul University, Istanbul, Turkey

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Giant hypopharyngeal fibrovascular polyp

LETTER

Hippokratia 2016, 20(4): 318

Radovanovic Z¹, Stankovic M^2
1Institute for Radiology
²Clinic for Otolaryngology, Clinical Center Nis, Serbia

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Endonasal endoscopic repair of cerebrospinal fluid leaks versus craniotomy: comparison of the outcomes

CASE SERIES

Hippokratia 2016, 20(4):299-302

Christoforidou A¹, Tsitsopoulos PP², Selviaridis P³, Vital V¹, Constantinidis J^1
11st Department of Otorhinolaryngology Head and Neck Surgery, AHEPA Hospital
²2nd Department of Neurosurgery, Ippokratio General Hospital
³1st Department of Neurosurgery, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Rectovaginal tear after sexual intercourse in a young woman-a case report

LETTER

Hippokratia 2016, 20(4):320

Daniilidis A¹, Panteleris N¹, Symeonidis N^2
12nd Department of Obstetrics and Gynecology
²2nd Propedeutical Department of Surgery, Hippokratio General Hospital, Aristotle University of Thessaloniki, Greece

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A phase 1, dose-escalation study of PF-06664178, an anti-Trop-2/Aur0101 antibody-drug conjugate in patients with advanced or metastatic solid tumors

Summary

Purpose and Methods Trop-2 is a glycoprotein over-expressed in many solid tumors but at low levels in normal human tissue, providing a potential therapeutic target. We conducted a phase 1 dose-finding study of PF-06664178, an antibody-drug conjugate that targets Trop-2 for the selective delivery of the cytotoxic payload Aur0101. The primary objective was to determine the maximum tolerated dose and recommended phase 2 dose. Secondary objectives included further characterization of the safety profile, pharmacokinetics and antitumor activity. Eligible patients were enrolled and received multiple escalating doses of PF-06664178 in an open-label and unblinded manner based on a modified continual reassessment method. Results Thirty-one patients with advanced or metastatic solid tumors were treated with escalating doses of PF-06664178 given intravenously every 21 days. Doses explored ranged from 0.15 mg/kg to 4.8 mg/kg. Seven patients experienced at least one dose limiting toxicity (DLT), either neutropenia or rash. Doses of 3.60 mg/kg, 4.2 mg/kg and 4.8 mg/kg were considered intolerable due to DLTs in skin rash, mucosa and neutropenia. Best overall response was stable disease in 11 patients (37.9%). None of the patients had a partial or complete response. Systemic exposure of PF-06664178 increased in a dose-related manner. Serum concentrations of free Aur0101 were substantially lower than those of PF-06664178 and total antibody. No correlation of Trop-2 expression and objective response was observed, although Trop-2 overexpression was not required for study entry. The intermediate dose of 2.4 mg/kg appeared to be the highest tolerated dose, but this was not fully explored as the study was terminated early due to excess toxicity. Conclusion PF-06664178 showed toxicity at high dose levels with modest antitumor activity. Neutropenia, skin rash and mucosal inflammation were dose limiting toxicities. Findings from this study may potentially aid in future antibody drug conjugate design and trials.

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Impact of Gastric Acid Induced Surface Changes on Mechanical Behavior and Optical Characteristics of Dental Ceramics

Abstract

Purpose

To test the impact of exposure to artificial gastric acid combined with toothbrush abrasion on the properties of dental ceramics. Earlier research has indicated that immersion in artificial gastric acid has caused increased surface roughness of dental ceramics; however, the combined effects of acid immersion and toothbrush abrasion and the impact of increased surface roughness on mechanical strength and optical properties have not been studied.

Materials and Methods

Three commercially available ceramics were chosen for this study: feldspathic porcelain, lithium disilicate glass-ceramic, and monolithic zirconium oxide. The specimens (10 × 1 mm discs) were cut, thermally treated as required, and polished. Each material was divided into four groups (n = 8 per group): control (no exposure), acid only, brush only, acid + brush. The specimens were immersed in artificial gastric acid (50 ml of 0.2% [w/v] sodium chloride in 0.7% [v/v] hydrochloric acid mixed with 0.16 g of pepsin powder, pH = 2) for 2 minutes and rinsed with deionized water for 2 minutes. The procedure was repeated 6 times/day × 9 days, and specimens were stored in deionized water at 37°C. Toothbrush abrasion was performed using an ISO/ADA design brushing machine for 100 cycles/day × 9 days. The acid + brush group received both treatments. Specimens were examined under SEM and an optical microscope for morphological changes. Color and translucency were measured using spectrophotometer CIELAB coordinates (L*, a*, b*). Surface gloss was measured using a gloss meter. Surface roughness was measured using a stylus profilometer. Biaxial flexural strength was measured using a mechanical testing machine. The data were analyzed by one-way ANOVA followed by Tukey's HSD post hoc test (p < 0.05).

Results

Statistically significant changes were found for color, gloss, and surface roughness for porcelain and e.max specimens. No statistically significant changes were found for any properties of zirconia specimens.

Conclusions

The acid treatment affected the surface roughness, color, and gloss of porcelain and e.max ceramics. The changes in translucency and mechanical strength for all materials were not statistically significant. Zirconia ceramic showed resistance to all treatments.

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Assessing the onset of allergic rhinitis by nasal cytology and immunoglobulin E antibody levels in children

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Headaches and facial pain in rhinology

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Role of group 2 innate lymphocytes in aspirin-exacerbated respiratory disease pathogenesis

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Open access: Is there a predator at the door?

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Naive and effector B-cell subtypes are increased in chronic rhinosinusitis with polyps

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Optimal cutoff values of allergen-specific immunoglobulin E to house dust mites and animal dander based on skin-prick test results: Analysis in 16,209 patients with allergic rhinitis

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Oral allergy syndrome

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Endoscopically assisted Crawford tube placement results in shorter general anesthesia times in pediatric patients

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How often is sinus surgery performed for chronic rhinosinusitis with versus without nasal polyps?

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Management of odontogenic cysts by endonasal endoscopic techniques: A systematic review and case series

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Comparison between endoscopic and external dacryocystorhinostomy by using the Lacrimal Symptom Questionnaire: A pilot study

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Extent of surgery in endoscopic transsphenoidal skull base approaches and the effects on sinonasal morbidity

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Use of intraoperative negative margins reduces inverted papilloma recurrence

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Using the nasoseptal flap for reconstruction after endoscopic debridement of radionecrosis in nasopharyngeal carcinoma

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Esthetic nasolabial angle according to the degree of upper lip protrusion in an Asian population

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Transnasal endoscopic resection of pediatric orbital cyst: “How I do it”

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Superior turbinate eosinophilia correlates with olfactory deficit in chronic rhinosinusitis patients.

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Outpatient erbium:YAG (2940 nm) laser treatment for snoring: a prospective study on 40 patients

Abstract

Snoring is a sleep phenomenon due to the partial upper airway obstruction during sleep which causes vibration of the tissues of the rhino-oro-hypopharynx and less frequently the larynx. This study evaluated the use and effectiveness of the erbium:YAG 2940-nm laser as an adjunctive in providing treatment for patients suffering from chronic snoring-related sleep disorders. A prospective study of 40 consecutive patients with snoring and sleep disorders was performed, assessing data before and after three Er:YAG laser treatment sessions. During laser treatment, the pain was almost absent. There were no side effects, except a very mild sore throat in 1 out of 40 patients. The patient's evaluation of satisfaction of the results obtained after the treatments showed that 85% of cases were very satisfied, 5 patients (12.5%) reported being fairly satisfied with the treatment and only 1 subject (2.5%) was not satisfied. Mallampati, Friedman Tongue Position, and degree of O (oropharynx) at nose oropharynx hypopharynx and larynx classification were significantly decreased after the laser sessions. The decrease of Epworth Sleepiness Scale and Visual Analogue Scale for loudness of snoring, waking up during sleep because of snoring, dry mouth on waking, and choking was all statistically significant. The incidence of dreaming during the night also raised significantly; 30/40 (75%) of cases perceived less tightness in their throat and better breathing after treatment. These results were stable at 20 months follow-up (14–24 q) in 72% of cases. Nonsurgical and non-invasive Er:YAG laser treatment demonstrated to be a valid procedure in reducing the loudness of snoring.

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High final energy of gallium arsenide laser increases MyoD gene expression during the intermediate phase of muscle regeneration after cryoinjury in rats

Abstract

The aim of this study was to determine the effects of gallium arsenide (GaAs) laser on IGF-I, MyoD, MAFbx, and TNF-α gene expression during the intermediate phase of muscle regeneration after cryoinjury 21 Wistar rats were divided into three groups (n = 7 per group): untreated with no injury (control group), cryoinjury without GaAs (injured group), and cryoinjury with GaAs (GaAs-injured group). The cryoinjury was induced in the central region of the tibialis anterior muscle (TA). The region injured was irradiated once a day during 14 days using GaAs laser (904 nm; spot size 0.035 cm², output power 50 mW; energy density 69 J cm⁻²; exposure time 4 s per point; final energy 4.8 J). Twenty-four hours after the last application, the right and left TA muscles were collected for histological (collagen content) and molecular (gene expression of IGF-I, MyoD, MAFbx, and TNF-α) analyses, respectively. Data were analyzed using one-way ANOVA at P < 0.05. There were no significant (P > 0.05) differences in collagen density and IGF-I gene expression in all experimental groups. There were similar (P < 0.05) decreases in MAFbx and TNF-α gene expression in the injured and GaAs-injured groups, compared to control group. The MyoD gene expression increased (P = 0.008) in the GaAs-injured group, but not in the injured group (P = 0.338), compared to control group. GaAs laser therapy had a positive effect on MyoD gene expression, but not IGF-I, MAFbx, and TNF-α, during intermediary phases (14 days post-injury) of muscle repair.

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Effect of Cyclodextrin-Enhanced Dissolution on Mass Removal and Mass-Flux Reduction Relationships for Non-uniformly Organic Liquid Distribution in Heterogeneous Porous Media

Abstract

A series of 2-D tank experiments were conducted to investigate the impact of non-uniform organic-liquid distribution, type of porous media, and methyl-beta-cyclodextrin (MCD) flooding on the relationship between source zone mass removal and mass-flux reduction for heterogeneous porous media. Trichloroethene was used as the model organic liquid, and MCD was used as enhanced flushing reagent. The results were also compared to those of water-flood control experiments. The results showed that the representative heterogeneous system exhibited specific non-ideal multi-step mass-flux reduction/mass removal behavior depended upon different porous media configurations. This non-ideal behavior was observed for both the water-flood and MCD flooding experiments. For all cases, early stage of trichloroethene mass removal was controlled by greater relative hydraulically accessibility of the dense non-aqueous-phase liquid (DNAPL) source distributed within the porous media matrix compared to later stage removal which was controlled by poorly hydraulically accessible mass associated with higher saturated or pooled DNAPL source zones. The results of this study significantly revealed the impact of non-uniform organic liquid distribution, flow-field heterogeneity, type of porous media, and the concentration of MCD on mass removal and mass-flux reduction behavior.

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Concealed complete response in melanoma patients under therapy with immune checkpoint inhibitors: two case reports

Abstract

Background

The assessment of tumor size by RECIST using CT scans and MRIs is considered to be standard of care for staging cancer patients. Despite radiologic evidence of widespread disease, we document for the first time that patients were completely free of viable tumor.

Case presentation

Two patients with metastatic melanoma were treated with immune checkpoint inhibitors (ipilimumab/ nivolumab) and progressive metastases were detected on CT-scans performed shortly before histologic examinations. In both patients histologic assessment revealed a complete response with necrotic and scarred lesions free of tumor. One of the patients had started immunotherapy 20 months before with an initial partial response.

Conclusions

This phenomenon of a concealed complete response can lead to overtreatment or unnecessary change in treatment. Thus, it is essential to raise awareness for it. Correct identification of responders to immune checkpoint inhibitor therapy is crucial to spare patients immune-mediated side effects and unnecessary as well as expensive treatment. Regression of metastases without decline in size, in these cases manifesting as complete responses, are probably more common than expected and identified to date. Until such responses can be readily identified by new imaging techniques, we recommend liberal biopsies for histologic assessment of progressive metastases in patients during and/or after immune checkpoint inhibitor therapy.

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A Potential Cure for Genetic Deafness

​Researchers from the Howard Hughes Medical Institute have successfully prevented genetic hearing loss in mice through the genome editing technology CRISPR-Cas9 in a recent study. (Nature 2017. doi: 10.1038/nature25164. [Epub ahead of print].) They injected a single treatment of a genome editing cocktail, which acted as molecular scissors and disrupted the mutation in the gene Tmc1, into the inner ears of infant mice with that mutation. The hair cells in treated ears resembled those in healthy animals after eight weeks, and treated ears could hear sounds about 15 dB lower than untreated ears. 

                                                       

Scientists can gauge mouse hearing by measuring how much noise (dB SPL) it takes to trigger an auditory brainstem response (ABR). Sounds starting at roughly 30 decibels can spark brain activity in normal mice (green/bottom line). Mice with the Tmc1 mutation lose their ability to hear and eventually become deaf. But injecting their inner ears with a genome editing agent made them more sensitive to sound (blue/middle line) than ears without an injection (red/top line). Credit: X. Gao, et al./Nature 2017 (http://bit.ly/2CZXbdR). ​

A single spelling error in Tmc1causes the loss of the inner ear's hair cells over time, and just one copy of a mutated Tmc1 gene causes progressive hearing loss leading to profound deafness in both humans and mice. Scientists at Howard Hughes snipped both strands of the DNA double helix with Cas9 to disable the gene. The challenge of the study lied in directing Cas9 to only the bad copy of Tmc1 and not the good one because the two copies differ by just one DNA letter. Researchers in this study packaged Cas9 and the guiding RNA into a greasy bundle that slips inside cells but doesn't stick around, allowing Cas9 to hit the bad gene copy and fade away before it could harm the good one. 

       

In the genome editing technology known as CRISPR-Cas9, RNA (blue) guides the protein Cas9 (large bumpy structure) to a target site in DNA (red). Cas9 unwinds the DNA double helix and acts as molecular scissors, snipping both strands of DNA. This animation is a preview of an interactive web feature that HHMI BioInteractive will debut in March of 2018. Credit: Howard Hughes Medical Institute (http://bit.ly/2CZXbdR).

​David Liu, PhD, a professor of chemistry and chemical biology at Harvard University and an investigator in the study, said the work is among the first to apply a genome editing approach to deafness in animals, and the positive change they observed in the mice could make a major difference in the quality of life for patients with hearing loss. "We hope that the work will one day inform the development of a cure for certain forms of genetic deafness in people," he said. 

Published: 1/14/2018 2:13:00 PM

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Frontmatter

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: i-iv

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Growth and growth hormone: recent papers on efficacy and adverse effects of growth hormone and World Health Organisation growth standards

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 1-3

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Allergic and non-allergic skin reactions associated with growth hormone therapy: elucidation of causative agents

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 5-11

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Adherence to growth hormone therapy in children and its potential barriers

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 13-20

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Short-term adverse effects of testosterone used for priming in prepubertal boys before growth hormone stimulation test

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 21-24

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Growth response to growth hormone treatment in patients with SHOX deficiency can be predicted by the Cologne prediction model

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 25-31

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WHO 2006 Child Growth Standards overestimate short stature and underestimate overweight in Japanese children

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 33-38

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Identifying depressive symptoms among diabetes type and the impact on hemoglobin A1c

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 39-44

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Insulin resistance and lung function in obese asthmatic pre-pubertal children

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 45-51

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Obesity is associated with vitamin D deficiency in Danish children and adolescents

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 53-61

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Daily sitting time associated with the risk of metabolic syndrome in Korean adolescents

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 63-69

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Molecular basis and clinical presentation of classic galactosemia in a Croatian population

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 71-75

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Clinical outcome in a series of pediatric patients with congenital generalized lipodystrophies treated with dietary therapy

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 77-83

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Spondyloepiphyseal or spondylometaphyseal dysplasia in ancient Greek art

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 85-86

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Sirolimus therapy for congenital hyperinsulinism in an infant with a novel homozygous KCNJ11 mutation

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 87-89

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Veganism as a cause of iodine deficient hypothyroidism

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 91-94

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A case of Riley Ruvalcaba syndrome with a novel PTEN mutation accompanied by diffuse testicular microlithiasis and precocious puberty

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 95-99

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Addison’s disease presenting with perimyocarditis

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 1
Pages: 101-105

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Submental artery island flap with simultaneous level I neck dissection.

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Submental artery island flap with simultaneous level I neck dissection.

Head Neck. 2018 Jan 13;:

Authors: Eskander A, Strigenz D, Seim N, Ozer E

Abstract
BACKGROUND: The purpose of this study was to illustrate the submental island flap elevation technique with simultaneous level I neck dissection followed by the inset and reconstruction of an oropharyngeal defect.
METHODS: A 63-year-old patient with a T2N1M0 human papillomavirus-positive squamous cell carcinoma of the tonsil was treated with concurrent chemoradiotherapy (cisplatin + 66 Gy). A local recurrence 2.5 years after treatment was treated surgically and reconstructed with a submental island flap.
RESULTS: There were no complications and oral diet was initiated at 2 weeks and the gastrostomy tube was removed 1 month postoperatively. A video demonstration of the submental island flap elevation is included with a focus on how levels 1A and 1B can be dissected safely and this can be viewed online on Head & Neck's home page at http://ift.tt/13H5MtY.
CONCLUSION: The submental island flap can be performed safely with a level I neck dissection for head and neck reconstruction.

PMID: 29331076 [PubMed - as supplied by publisher]

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Attenuation of noise-induced hyperactivity in the dorsal cochlear nucleus by pre-treatment with MK-801.

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Attenuation of noise-induced hyperactivity in the dorsal cochlear nucleus by pre-treatment with MK-801.

Brain Res. 2018 Jan 09;:

Authors: Criddle MW, Godfrey DA, Kaltenbach JA

Abstract
It has previously been hypothesized that hyperactivity of central auditory neurons following exposure to intense noise is a consequence of synaptic alterations. Recent studies suggest the involvement of NMDA receptors in the induction of this hyperactive state. NMDA receptors can mediate long term changes in the excitability of neurons through their involvement in excitotoxic injury and long term potentiation and depression. In this study, we examined the effect of administering an NMDA receptor blocker on the induction of hyperactivity in the dorsal cochlear nucleus (DCN) following intense sound exposure. Our prediction was that if hyperactivity induced by intense sound exposure is dependent on NMDA receptors, then blocking these receptors by administering an NMDA receptor antagonist just before animals are exposed to intense sound should reduce the degree of hyperactivity that subsequently emerges. We compared the levels of hyperactivity that develop in the DCN after intense sound exposure to activity recorded in control animals that were not sound exposed. One group of animals to be sound exposed received intraperitoneal injection of MK-801 twenty minutes preceding the sound exposure, while the other group received injection of saline. Recordings performed in the DCN 26-28 days post-exposure revealed increased response thresholds and widespread increases in spontaneous activity in the saline-treated animals that had been sound exposed, consistent with earlier studies. The animals treated with MK-801 preceding sound exposure showed similarly elevated thresholds but an attenuation of hyperactivity in the DCN; the attenuation was most robust in the high frequency half of the DCN, but lower levels of hyperactivity were also found in the low frequency half. These findings suggest that NMDA receptors are an important component of the hyperactivity-inducing mechanism following intense sound exposure. They further suggest that blockade of NMDA receptors may offer a useful therapeutic approach to preventing induction of noise-induced hyperactivity-related hearing disorders, such as tinnitus and hyperacusis.

PMID: 29329983 [PubMed - as supplied by publisher]

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Genotype-phenotype correlations in individuals with pathogenic RERE variants.

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Genotype-phenotype correlations in individuals with pathogenic RERE variants.

Hum Mutat. 2018 Jan 13;:

Authors: Jordan VK, Fregeau B, Ge X, Giordano J, Wapner RJ, Balci TB, Carter MT, Bernat JA, Moccia AN, Srivastava A, Martin DM, Bielas SL, Pappas J, Svoboda MD, Rio M, Boddaert N, Cantagrel V, Lewis AM, Scaglia F, Undiagnosed Diseases Network, Kohler JN, Bernstein JA, Dries AM, Rosenfeld JA, DeFilippo C, Thorson W, Yang Y, Sherr EH, Bi W, Scott DA

Abstract
Heterozygous variants in the arginine-glutamic acid dipeptide repeats gene (RERE) have been shown to cause neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH). Here we report nine individuals with NEDBEH who carry partial deletions or deleterious sequence variants in RERE. These variants were found to be de novo in all cases in which parental samples were available. An analysis of data from individuals with NEDBEH suggests that point mutations affecting the Atrophin-1 domain of RERE are associated with an increased risk of structural eye defects, congenital heart defects, renal anomalies and sensorineural hearing loss when compared to loss-of-function variants that are likely to lead to haploinsufficiency. A high percentage of RERE pathogenic variants affect a histidine-rich region in the Atrophin-1 domain. We have also identified a recurrent two-amino-acid duplication in this region that is associated with the development of a CHARGE syndrome-like phenotype. We conclude that mutations affecting RERE result in a spectrum of clinical phenotypes. Genotype-phenotype correlations exist and can be used to guide medical decision making. Consideration should also be given to screening for RERE variants in individuals who fulfill diagnostic criteria for CHARGE syndrome but do not carry pathogenic variants in CHD7. This article is protected by copyright. All rights reserved.

PMID: 29330883 [PubMed - as supplied by publisher]

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Outcome of Preterm Infants With Postnatal Cytomegalovirus Infection.

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Outcome of Preterm Infants With Postnatal Cytomegalovirus Infection.

Pediatrics. 2018 Jan 12;:

Authors: Gunkel J, de Vries LS, Jongmans M, Koopman-Esseboom C, van Haastert IC, Eijsermans MCJ, van Stam C, van Zanten BGA, Wolfs TFW, Nijman J

Abstract
OBJECTIVES: To assess whether preterm infants with postnatal cytomegalovirus infection develop neurologic sequelae in early childhood.
METHODS: Infants <32 weeks' gestation were prospectively screened for cytomegalovirus (CMV) at term-equivalent age. Neurodevelopment was compared between CMV-positive and CMV-negative infants by using the Griffiths Mental Development Scales (GMDS) at 16 months' corrected age (CA); the Bayley Scales of Infant and Toddler Development, Third Edition or the GMDS at 24 to 30 months' CA; and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition and Movement Assessment Battery for Children, Second Edition at 6 years of age. At 6 years old, hearing was assessed in CMV-positive children.
RESULTS: Neurodevelopment was assessed in 356 infants at 16 months' CA, of whom 49 (14%) were infected and 307 (86%) were noninfected. Infected infants performed significantly better on the GMDS locomotor scale. There were no differences at 24 to 30 months' CA on the Bayley Scales of Infant and Toddler Development, Third Edition or GMDS. At 6 years of age, infected children scored lower on the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, but mean scores were within normal range, reaching significance only in verbal IQ (96 [SD 17] vs 103 [SD 15] points; P = .046). Multiple regression indicated no impact of CMV status but significant influence of maternal education and ethnicity on verbal IQ. No significant differences in motor development were found and none of the infected children developed sensorineural hearing loss.
CONCLUSIONS: In this cohort study, postnatal cytomegalovirus infection in preterm children did not have an adverse effect on neurodevelopment within the first 6 years of life.

PMID: 29330315 [PubMed - as supplied by publisher]

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Assessment of vestibular-evoked myogenic potentials and video head impulse test in type 2 diabetes mellitus patients with or without polyneuropathy.

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Assessment of vestibular-evoked myogenic potentials and video head impulse test in type 2 diabetes mellitus patients with or without polyneuropathy.

Eur Arch Otorhinolaryngol. 2018 Jan 13;:

Authors: Kalkan M, Bayram A, Gökay F, Cura HS, Mutlu C

Abstract
This study aimed to compare cervical vestibular-evoked myogenic potentials (cVEMP), ocular vestibular-evoked myogenic potentials (oVEMP) and video head impulse test (vHIT) results between patients with type 2 diabetes mellitus (DM) or diabetic polyneuropathy (DPN) and healthy controls to determine vestibular end-organ pathologies. The participants in the present study consisted of three groups: the type 2 DM group (n = 33 patients), the DPN group (n = 33 patients), and the age- and sex-matched control group (n = 35). Cervical VEMP, oVEMP and vHIT were performed for each participant in the study and test results were compared between the groups. Peak-to-peak amplitudes of cVEMP (p13-n21) and oVEMP (n10-p15) were significantly lower in the DM and DPN groups than the control group. The values of vHIT were not statistically different between the groups. To our knowledge, the present study is the first report investigating oVEMP and cVEMP responses combined with vHIT findings in patients with DM and DPN. Vestibular end-organ pathologies can be determined via clinical vestibular diagnostic tools in spite of prominent vestibular symptoms in patients with type 2 DM as well as patients with DPN.

PMID: 29330601 [PubMed - as supplied by publisher]

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The impact of acoustic neuroma on long-term quality-of-life outcomes in the United Kingdom.

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The impact of acoustic neuroma on long-term quality-of-life outcomes in the United Kingdom.

Eur Arch Otorhinolaryngol. 2018 Jan 12;:

Authors: Lodder WL, van der Laan BFAM, Lesser TH, Leong SC

Abstract
OBJECTIVE: To quantify the impact of acoustic neuroma on the quality-of-life (QOL) patients in the United Kingdom.
STUDY DESIGN: Online questionnaire survey.
PATIENTS: Members of the British Acoustic Neuroma Association received PANQOL questionnaires.
RESULTS: Of the 880 BANA members contacted, 397 (45.1%) responded, although only 359 had complete datasets for analysis. Composite QOL scores were as follows: for microsurgery 58 (SD 35), for radiotherapy 56 (SD18), for combination of surgery and radiotherapy 49 (SD 14), and for the observation group 54 (SD 20). No statistical significance with ANOVA (p = 0.532). Mean (SD) composite QOL scores were as follows: for follow-up < 6 52 (SD 18), for follow-up 6-10 55 (SD 20) and follow-up > 10 years 65 (SD 45). Overall, these values were significantly different compared by ANOVA (p < 0.001). Patients with facial paralysis showed no statistical significant differences between the different treatment groups.
CONCLUSIONS: Short- (< 6 years) and long-term (> 10 years) QOL outcomes show no significant differences between the different treatment groups.

PMID: 29330600 [PubMed - as supplied by publisher]

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Infraorbital foramen localization in orbitozygomatic fractures: a CT study with intraoperative finding.

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Infraorbital foramen localization in orbitozygomatic fractures: a CT study with intraoperative finding.

Eur Arch Otorhinolaryngol. 2018 Jan 12;:

Authors: El-Anwar MW, Sweed AH

Abstract
OBJECTIVE: The aim of this study was to assess the infraorbital foramen (IOF) using CT in patients with Zygomaticomaxillary complex (ZMC) fractures (midface fracture).
PATIENTS AND METHODS: This prospective study was carried out on 49 patients had ZMC fractures (98 sides) and 27 patients (54 sides) with craniomaxillofacial fractures rather than fractured ZMC as a control. Using CT, position of IOF was documented on 3D view in relation to inferior orbital rim, tooth root relation and finally with a novel imaginary line passing between anterior nasal spine and whitnall tubercle.
RESULTS: Position of IOF had fixed anatomical landmark: just lateral to a line drawn between the anterior nasal spine to whitnall tubercle (clinically between nasal tip-lateral canthal ligament) and lateral to vertical plane to root of maxillary canine also with variable distance from inferior orbital rim ranged from 4.56 to 18.03 mm with a mean of 7.9 ± 2.447 mm.
CONCLUSION: Even though ZMC fractures disturb the anatomical location of the ZMC bones, there are still preserved reliable fixed landmarks maxillofacial surgeons can depend on to identify and preserve ION.

PMID: 29330599 [PubMed - as supplied by publisher]

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Satisfaction in rhinoplasty: the possible impact of anxiety and functional outcome.

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Satisfaction in rhinoplasty: the possible impact of anxiety and functional outcome.

Eur Arch Otorhinolaryngol. 2018 Jan 12;:

Authors: Koybasi S, Bicer YO, Seyhan S, Kesgin S

Abstract
BACKGROUND: Rhinoplasty is a complex but commonly applied surgical procedure. Patient satisfaction is the least discussed but one of the most important determinants of surgical success.
OBJECTIVES: Evaluation of the patient satisfaction together with surgeon satisfaction were the main goals of this study. The roles of anxiety, gender, age and follow-up period were also studied.
PATIENTS AND METHODS: 53 eligible patients operated by the first two authors within the previous 2 years were enrolled in the study. The medical records were reviewed for demographic data as well as the details of the surgical procedure. Functional and esthetic satisfactions of the patients were evaluated by VAS and ROE respectively. Surgeon satisfaction was evaluated by VAS in crosswise manner. Anxiety was measured by STAI_s and STAI_t scales.
RESULTS: The analysis concerning esthetic results as well as functional results did not reveal any significant difference between the two surgeons (p = 0.132, p = 0.43 respectively). ROE scores were significantly different among patients with "good" and "very good" functional results. The difference between surgeon satisfaction and patient satisfaction was found to be insignificant (p = 0.273). Correlation analysis yielded a positive correlation between STAI_I and STAI_II (Pearson r = 0.335, p = 0.014) but not between STAI scores and ROE scores. Moreover, there was no relation between anxiety scores and the functional results. Likely, gender as well as age, follow-up, and surgical technique were not found to have any effect on patient satisfaction either.
CONCLUSION: Patient satisfaction is preferential in rhinoplasty. In our patient series, patient satisfaction was shown to be correlated with functional outcome but not with surgeon satisfaction. Anxiety was not found to have a significant impact on results of rhinoplasty. Our results should be interpreted cautiously keeping in mind that our patients' primary drive for rhinoplasty was functional.

PMID: 29330598 [PubMed - as supplied by publisher]

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Inpatient treatment of patients with idiopathic sudden sensorineural hearing loss: a population-based healthcare research study.

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Inpatient treatment of patients with idiopathic sudden sensorineural hearing loss: a population-based healthcare research study.

Eur Arch Otorhinolaryngol. 2018 Jan 12;:

Authors: Heuschkel A, Geißler K, Boeger D, Buentzel J, Esser D, Hoffmann K, Jecker P, Mueller A, Radtke G, Guntinas-Lichius O

Abstract
PURPOSE: The aim was to determine inpatient treatment rates of idiopathic sudden sensorineural hearing loss (ISSNHL) with focus on diagnostics, treatment, and outcome.
METHODS: A retrospective population-based study in the federal state Thuringia in 2011 and 2012 was performed on all 490 inpatients (51% females, median age: 60 years) treated for ISSNHL (Median duration: 7 days). The association between analyzed parameters and the probability of recovery was tested using univariable and multivariable statistics.
RESULTS: The inpatient treatment rate for ISSNHL was 11.23 per 100,000. 172 patients (35%) had an outpatient treatment prior to inpatient treatment. For pure-tone audiometry of the three most affected frequencies (3PTAmax), the initial median hearing loss was 66.67 dB, the median absolute hearing gain ΔPTAabs was 10.0 dB, and the median relative hearing gain in relation with the contralateral side ΔPTArel contral was 30.86%. 51% of the patients reached a ΔPTAabs of ≥ 10 dB. About 2 of 5 patients recovered to a ΔPTArel contral ≥ 50% or reached ≤ 10 dB of contralateral ear. The multivariate analysis revealed that an ISSNHL on the left side [Hazard ratio (HR) = 1.6.88; confidence interval (CI) = 1.161-2.454], no down-sloping audiogram type (HR = 2.016; CI = 1.391-2.921), and no prior outpatient prednisolone treatment (HR = 2.374; CI = 1.505-3.745) were independent factors associated with better recovery (ΔPTAabs ≥ 10 dB).
CONCLUSION: Inpatient treatment of ISSNHL is variable in daily practice. The population-based recovery rate was worse than reported in clinical trials. More standardization and clearer criteria for outpatient, inpatient, and salvage therapy are needed.

PMID: 29330597 [PubMed - as supplied by publisher]

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Assessment of vestibular-evoked myogenic potentials and video head impulse test in type 2 diabetes mellitus patients with or without polyneuropathy.

Related Articles

Assessment of vestibular-evoked myogenic potentials and video head impulse test in type 2 diabetes mellitus patients with or without polyneuropathy.

Eur Arch Otorhinolaryngol. 2018 Jan 13;:

Authors: Kalkan M, Bayram A, Gökay F, Cura HS, Mutlu C

Abstract
This study aimed to compare cervical vestibular-evoked myogenic potentials (cVEMP), ocular vestibular-evoked myogenic potentials (oVEMP) and video head impulse test (vHIT) results between patients with type 2 diabetes mellitus (DM) or diabetic polyneuropathy (DPN) and healthy controls to determine vestibular end-organ pathologies. The participants in the present study consisted of three groups: the type 2 DM group (n = 33 patients), the DPN group (n = 33 patients), and the age- and sex-matched control group (n = 35). Cervical VEMP, oVEMP and vHIT were performed for each participant in the study and test results were compared between the groups. Peak-to-peak amplitudes of cVEMP (p13-n21) and oVEMP (n10-p15) were significantly lower in the DM and DPN groups than the control group. The values of vHIT were not statistically different between the groups. To our knowledge, the present study is the first report investigating oVEMP and cVEMP responses combined with vHIT findings in patients with DM and DPN. Vestibular end-organ pathologies can be determined via clinical vestibular diagnostic tools in spite of prominent vestibular symptoms in patients with type 2 DM as well as patients with DPN.

PMID: 29330601 [PubMed - as supplied by publisher]

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The impact of acoustic neuroma on long-term quality-of-life outcomes in the United Kingdom.

Related Articles

The impact of acoustic neuroma on long-term quality-of-life outcomes in the United Kingdom.

Eur Arch Otorhinolaryngol. 2018 Jan 12;:

Authors: Lodder WL, van der Laan BFAM, Lesser TH, Leong SC

Abstract
OBJECTIVE: To quantify the impact of acoustic neuroma on the quality-of-life (QOL) patients in the United Kingdom.
STUDY DESIGN: Online questionnaire survey.
PATIENTS: Members of the British Acoustic Neuroma Association received PANQOL questionnaires.
RESULTS: Of the 880 BANA members contacted, 397 (45.1%) responded, although only 359 had complete datasets for analysis. Composite QOL scores were as follows: for microsurgery 58 (SD 35), for radiotherapy 56 (SD18), for combination of surgery and radiotherapy 49 (SD 14), and for the observation group 54 (SD 20). No statistical significance with ANOVA (p = 0.532). Mean (SD) composite QOL scores were as follows: for follow-up < 6 52 (SD 18), for follow-up 6-10 55 (SD 20) and follow-up > 10 years 65 (SD 45). Overall, these values were significantly different compared by ANOVA (p < 0.001). Patients with facial paralysis showed no statistical significant differences between the different treatment groups.
CONCLUSIONS: Short- (< 6 years) and long-term (> 10 years) QOL outcomes show no significant differences between the different treatment groups.

PMID: 29330600 [PubMed - as supplied by publisher]

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Association of Homocysteine with Aysmptomatic Intracranial and Extracranial Arterial Stenosis in Hypertension Patients.

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Association of Homocysteine with Aysmptomatic Intracranial and Extracranial Arterial Stenosis in Hypertension Patients.

Sci Rep. 2018 Jan 12;8(1):595

Authors: Wang Y, Zhang J, Qian Y, Tang X, Ling H, Chen K, Li Y, Gao P, Zhu D

Abstract
Elevated plasma homocysteine (Hcy) is suggested as an independent risk factor for stroke. We aimed to investigate the association of Hcy concentration with intracranial atherosclerosis (ICAS) and extracranial AS (ECAS) in hypertensive patients without stroke in Chinese population and to explore modified effect of methylenetetrahydrofolate reductase (MTHFR) C677T on their relationship. The stenosis of intracranial and extracranial arteries were evaluated in a total of 929 subjects through computerized tomographic angiography (CTA) from aortic arch to the skull base. Hcy concentration showed significantly association with both ICAS (OR: 1.105; 95% CI: 1.057-1.155) and ECAS (OR: 1.096; 95% CI: 1.047-1.146) for 1 µmol/L increment in Hcy. Meanwhile, hyperhomocysteinemia (≥15 µmol/L) was also displayed association with ICAS (OR: 1.587; 95% CI: 1.029-2.446) and ECAS (OR: 2.164; 95% CI: 1.392-3.364) after fully adjustment. Furthermore, in the subgroup analysis, such association remained significant only in the subjects that were younger, with normal renal function and with MTHFR 677 C allele. Our study showed the significant association of Hcy with ECAS and ICAS in asymptomatic hypertension patients. Hcy played a universal effect on the cervico-cerebral atherosclerosis. Such association was modified by the MTHFR C677T genotype.

PMID: 29330520 [PubMed - in process]

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Frontoethmoidal Schwannoma with Exertional Cerebrospinal Fluid Rhinorrhea: a Case Report and Review of the Literature.

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Frontoethmoidal Schwannoma with Exertional Cerebrospinal Fluid Rhinorrhea: a Case Report and Review of the Literature.

World Neurosurg. 2018 Jan 09;:

Authors: Yoneoka Y, Akiyama K, Seki Y, Hasegawa G, Kakita A

Abstract
BACKGROUND: Frontoethmoidal schwannomas are rare. No case manifesting exertional cerebrospinal fluid (CSF) rhinorrhea has ever been reported to the best of our knowledge.
CASE DESCRIPTION: In this report, we describe an extremely rare case of frontoethmoidal schwannoma extending through the olfactory groove (OG) with exertional CSF rhinorrhea as the initial symptom. A 50-year-old woman was presented to our clinic for frequent nasal discharge on exertion. A postcontrast computed tomographic scan demonstrated heterogeneously enhanced tumor from the anterior cranial fossa to the anterior ethmoid sinus. A gadolinium-enhanced T1-weighted magnetic resonance image revealed a well-defined heterogeneously enhanced tumor situated in the midline anterior cranial fossa and the anterior ethmoid sinus. After the resection, the defect of the right anterior skull base was reconstructed with a fascia graft and adipose tissue taken from the abdomen as well as a pedicle periosteum flap. A histological examination revealed the tumor as schwannoma. Her rhinorrhea completely resolved. She regained sense of smell and taste one month after the operation.
CONCLUSION: According to previous reports, para/peri-OG schwannomas can be divided into four types: subfrontal; nasoethomoidal; frontoethomoidal; and ethomofrontal. Among them, a frontoethomoidal schwannoma can manifest exertional CSF rhinorrhea as an initial symptom.

PMID: 29330076 [PubMed - as supplied by publisher]

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Otolaryngology/head and neck region manifestations of Brucella

Objectives/Hypothesis

Patients with Brucella infection present with nonspecific symptoms originating from different organs. In this study, we investigated the manifestations involving principally the otolaryngology/head and neck region.

Study Design

Retrospective cohort chart review.

Methods

A retrospective analysis of patients diagnosed with brucellosis in a tertiary medical center. Medical records of 55 patients treated for positive Brucella blood cultures between 2007 and 2016 were analyzed. Clinical manifestations localized to the otolaryngology/head and neck region were evaluated.

Results

Most patients (78%) in our study group lived in rural areas. There was an almost equal gender distribution and a wide age range (2–77 years). Nonspecific symptoms, including fever (71%), fatigue (31%), weight loss (20%), and night sweats (32.7%) were the most common. Of the specific organ systems affected by Brucella, the osteoarthritic system was most commonly infected (45.5%). Three patients (5.5%) presented with predominantly localized otolaryngology/head and neck region symptoms, consisting of necrotic lymphadenopathy or a thyroid abscess. All patients underwent drainage procedures, and the diagnosis was confirmed by positive blood and pus cultures. Complete resolution was achieved with prolonged antibiotic treatment.

Conclusions

Brucella infection should be suspected in patients with nonspecific constitutional symptoms associated with neck lymphadenopathy or thyroid abscess, especially in those living in rural areas. A high index of suspicion is mandatory for proper diagnosis and treatment. Formal drainage and prolonged antibiotic treatments are required. We strongly recommend simple drainage and not excision as the mainstay of surgical treatment.

Level of Evidence

4. Laryngoscope, 2018

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Oblique thyroarytenoid muscle in humans: An independent muscle or an accessory belly?

Objectives/Hypothesis

This study aimed to determine the prevalence and morphological variations of the oblique thyroarytenoid (TA) muscle in humans.

Study Design

Cadaveric anatomic dissections.

Methods

One hundred hemilarynges from 50 formalin-embalmed cadavers were dissected to investigate the morphology of muscle fibers of the TA muscle.

Results

Thirty-six (36%) hemilarynges were found to have a distinct oblique belly superficial to the TA muscle. In 28 cases, the belly had a relatively constant origin and an insertion that extended straight onto the TA muscle from the anterosuperior area of the internal surface of the thyroid lamina to the base of the muscular process of the arytenoid cartilage. Eight cases were located in a similar area but with some differences in the origin or insertion features.

Conclusions

We proposed that the oblique TA muscle has a high prevalence and probably acts to close and relax the vocal cords. It remains to be determined whether the oblique TA muscle is an independent muscle or an accessory belly of the main TA muscle.

Level of Evidence

NA Laryngoscope, 2018

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Gongylonema pulchrum infection in the human oral cavity: A case report and literature review.

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Gongylonema pulchrum infection in the human oral cavity: A case report and literature review.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Dec 08;:

Authors: Xiaodan L, Zhensheng W, Ying H, Hongwei L, Jianqiu J, Peiru Z, Sha S, Zhimin Y

Abstract
Gongylonema infection is a zoonotic disease occurring throughout the world and is mainly caused by consumption of contaminated water and raw food. Adult Gongylonema worms can exist as parasites in the human body for up to 10 years and cause symptoms of local irritation in the oral cavity, esophagus, and pharynx. Herein, we report a rare case in which live Gongylonema pulchrum was detected and extracted from the oral cavity of a woman. The pathogen was confirmed as G. pulchrum on the basis of microscopic examination and morphologic analysis. The patient's symptoms resolved immediately after surgical removal of the parasite, and the patient has been advised not to drink water that has not been boiled and to avoid consuming unwashed raw vegetables.

PMID: 29329982 [PubMed - as supplied by publisher]

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Cancers, Vol. 10, Pages 20: Alcohol-Derived Acetaldehyde Exposure in the Oral Cavity

Cancers, Vol. 10, Pages 20: Alcohol-Derived Acetaldehyde Exposure in the Oral Cavity

Cancers doi: 10.3390/cancers10010020

Authors: Alessia Stornetta Valeria Guidolin Silvia Balbo

Alcohol is classified by the International Agency for Research on Cancer (IARC) as a human carcinogen and its consumption has been associated to an increased risk of liver, breast, colorectum, and upper aerodigestive tract (UADT) cancers. Its mechanisms of carcinogenicity remain unclear and various hypotheses have been formulated depending on the target organ considered. In the case of UADT cancers, alcohol's major metabolite acetaldehyde seems to play a crucial role. Acetaldehyde reacts with DNA inducing modifications, which, if not repaired, can result in mutations and lead to cancer development. Despite alcohol being mainly metabolized in the liver, several studies performed in humans found higher levels of acetaldehyde in saliva compared to those found in blood immediately after alcohol consumption. These results suggest that alcohol-derived acetaldehyde exposure may occur in the oral cavity independently from liver metabolism. This hypothesis is supported by our recent results showing the presence of acetaldehyde-related DNA modifications in oral cells of monkeys and humans exposed to alcohol, overall suggesting that the alcohol metabolism in the oral cavity is an independent cancer risk factor. This review article will focus on illustrating the factors modulating alcohol-derived acetaldehyde exposure and effects in the oral cavity.

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