Prox1-GFP/Flt1-DsRed transgenic mice: an animal model for simultaneous live imaging of angiogenesis and lymphangiogenesis

Abstract

The roles of angiogenesis in development, health, and disease have been studied extensively; however, the studies related to lymphatic system are limited due to the difficulty in observing colorless lymphatic vessels. But recently, with the improved technique, the relative importance of the lymphatic system is just being revealed. We bred transgenic mice in which lymphatic endothelial cells express GFP (Prox1-GFP) with mice in which vascular endothelial cells express DsRed (Flt1-DsRed) to generate Prox1-GFP/Flt1-DsRed (PGFD) mice. The inherent fluorescence of blood and lymphatic vessels allows for direct visualization of blood and lymphatic vessels in various organs via confocal and two-photon microscopy and the formation, branching, and regression of both vessel types in the same live mouse cornea throughout an experimental time course. PGFD mice were bred with CDh5CreERT2 and VEGFR2lox knockout mice to examine specific knockouts. These studies showed a novel role for vascular endothelial cell VEGFR2 in regulating VEGFC-induced corneal lymphangiogenesis. Conditional deletion of vascular endothelial VEGFR2 abolished VEGFA- and VEGFC-induced corneal lymphangiogenesis. These results demonstrate the potential use of the PGFD mouse as a powerful animal model for studying angiogenesis and lymphangiogenesis.

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Slow Versus Fast Robot-Assisted Locomotor Training After Severe Stroke: A Randomized Controlled Trial.

Background and Purpose: Robot-assisted locomotor training on a bodyweight-supported treadmill is a rehabilitation intervention that compels repetitive practice of gait movements. Standard treadmill speed may elicit rhythmic movements generated primarily by spinal circuits. Slower-than-standard treadmill speed may elicit discrete movements, which are more complex than rhythmic movements and involve cortical areas. Objective: Compare effects of fast (i.e., rhythmic) versus slow (i.e., discrete) robot-assisted locomotor training on a bodyweight-supported treadmill in subjects with chronic, severe gait deficit after stroke. Methods: Subjects (N = 18) were randomized to receive 30 sessions (5 d/wk) of either fast or slow robot-assisted locomotor training on a bodyweight-supported treadmill in an inpatient setting. Functional ambulation category, time up and go, 6-min walk test, 10-m walk test, Berg Balance Scale, and Fugl-Meyer Assessment were administered at baseline and postintervention. Results: The slow group had statistically significant improvement on functional ambulation category (first quartile-third quartile, P = 0.004), 6-min walk test (95% confidence interval [CI] = 1.8 to 49.0, P = 0.040), Berg Balance Scale (95% CI = 7.4 to 14.8, P

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Cauda Equina Syndrome Due to Vigorous Back Massage With Spinal Manipulation in a Patient With Pre-Existing Lumbar Disc Herniation: A Case Report and Literature Review.

Cauda equina syndrome (CES) resulting from acute lumbar disc herniation due to spinal massage is extremely rare. We present a case of CES caused by the acute worsening of a lumbar disc herniation after a vigorous back massage that included spinal manipulation. After vigorous back massage with spinal manipulation performed by a massage therapist, a 38-yr-old male patient experienced CES with severe numbness in both lower limbs, inability to walk due to weakness of bilateral lower limbs, and incontinence of urine and feces. The magnetic resonance imaging and computer tomography scan results showed that the L4-5 disc herniated down into the spinal canal, extensively compressing the ventral dural sac. The patient was successfully treated with an emergency operation including laminectomy, spinal canal decompression, discectomy, interbody fusion, and pedicle screw fixation. The muscle power in both lower limbs of the patient recovered rapidly to support standing only 1 wk later. Moreover, he regained continence of urine and feces. In conclusion, this case brings us novel knowledge that spinal massage or manipulation may worsen pre-existing disc herniation causing CES, and a timely emergency surgery is necessary and effective for treatment of CES-related symptoms. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Wide Awake Trapeziectomy for Thumb Basal Joint Arthritis.

No abstract available

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Issue Information

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Cost-effectiveness analysis of potentially curative and combination treatments for hepatocellular carcinoma with person-level data in a Canadian setting

Abstract

Patients with early-stage hepatocellular carcinoma (HCC) are potential candidates for curative treatments such as radiofrequency ablation (RFA), surgical resection (SR), or liver transplantation (LT), which have demonstrated a significant survival benefit. We aimed to estimate the cost-effectiveness of curative and combination treatment strategies among patients diagnosed with HCC during 2002–2010. This study used Ontario Cancer Registry-linked administrative data to estimate effectiveness and costs (2013 USD) of the treatment strategies from the healthcare payer's perspective. Multiple imputation by logistic regression was used to handle missing data. A net benefit regression approach of baseline important covariates and propensity score adjustment were used to calculate incremental net benefit to generate incremental cost-effectiveness ratio (ICER) and uncertainty measures. Among 2,222 patients diagnosed with HCC, 10.5%, 14.1%, and 10.3% received RFA, SR, and LT monotherapy, respectively; 0.5–3.1% dual treatments; and 0.5% triple treatments. Compared with no treatment (53.2%), transarterial chemoembolization (TACE) + RFA (average $2,465, 95% CI: −$20,000–$36,600/quality-adjusted life years [QALY]) or RFA monotherapy ($15,553, 95% CI: $3,500–$28,500/QALY) appears to be the most cost-effective modality with lowest ICER value. The cost-effectiveness acceptability curve showed that if the relevant threshold was $50,000/QALY, RFA monotherapy and TACE+ RFA would have a cost-effectiveness probability of 100%. Strategies using LT delivered the most additional QALYs and became cost-effective at a threshold of $77,000/QALY. Our findings found that TACE+ RFA dual treatment or RFA monotherapy appears to be the most cost-effective curative treatment for patients with potential early stage of HCC in Ontario. These findings highlight the importance of identifying and measuring differential benefits, costs, and cost-effectiveness of alternative HCC curative treatments in order to evaluate whether they are providing good value for money in the real world.

The aim of this article was to estimate the cost-effectiveness of mutually exclusive potentially curative monotherapies such as radiofrequency ablation (RFA), surgical resection (SR), or liver transplantation (LT) and combination therapies with palliative treatment (transarterial chemoembolization, TACE) among patients diagnosed with hepatocellular carcinoma (HCC) during 2002–2010. Compared with no treatment, TACE plus RFA (average $2,465, 95% CI: −$20,000–$36,600/quality-adjusted life years [QALY]) or RFA monotherapy ($15,553, 95% CI: $3,500–$28,500/QALY) appears to be the most cost-effective modality with lowest incremental cost-effectiveness ratio (ICER) value. Our findings found that TACE plus RFA dual treatment or RFA monotherapy appears to be the most cost-effective curative treatment for patients with potential early stage of HCC in Ontario, which may potentially provide good value for money in the real world within the context of an organized healthcare system.

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The Patterns of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Use in Patients with Atrial Fibrillation in Seven Balkan Countries: a Report from the BALKAN-AF Survey

Abstract

Introduction

Data on management of atrial fibrillation (AF) in the Balkan Region are scarce. To capture the patterns in AF management in contemporary clinical practice in the Balkan countries a prospective survey was conducted between December 2014 and February 2015, and we report results pertinent to the use of non-vitamin K antagonist oral anticoagulants (NOACs).

Methods

A 14-week prospective, multicenter survey of consecutive AF patients seen by cardiologists or internal medicine specialists was conducted in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Montenegro, Romania, and Serbia (a total of about 50 million inhabitants).

Results

Of 2712 enrolled patients, 2663 (98.2%) had complete data relevant to oral anticoagulant (OAC) use (mean age 69.1 ± 10.9 years, female 44.6%). Overall, OAC was used in 1960 patients (73.6%) of whom 338 (17.2%) received NOACs. Malignancy [odds ratio (OR), 95% confidence interval (CI) 2.06, 1.20–3.56], rhythm control (OR 1.64, 1.25–2.16), and treatment by cardiologists were independent predictors of NOAC use (OR 2.32, 1.51–3.54) [all p < 0.01)], whilst heart failure and valvular disease were negatively associated with NOAC use (both p < 0.01). Individual stroke and bleeding risk were not significantly associated with NOAC use on multivariate analysis.

Conclusions

NOACs are increasingly used in AF patients in the Balkan Region, but NOAC use is predominantly guided by factors other than evidence-based decision-making (e.g., drug availability on the market or reimbursement policy). Efforts are needed to establish an evidence-based approach to OAC selection and to facilitate the optimal use of OAC, thus improving the outcomes in AF patients in this large region.

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Health-Related Quality of Life in Individuals with Down Syndrome: Results from a Non-Interventional Longitudinal Multi-National Study

Abstract

Introduction

To date, there is little research on health-related quality of life (HRQoL) in Down syndrome (DS), and existing research is variable with regard to reported HRQoL in DS. There are also no HRQoL measures developed specifically to be used with individuals with Down syndrome.

Methods

A multi-national, longitudinal, 24-week non-interventional study was conducted in adolescents and adults with DS. HRQoL was assessed (n = 90) using the parent-report KIDSCREEN-27 questionnaire.

Results

HRQoL domain scores were found to be similar to those in the KIDSCREEN-27 European normative group data set on the Physical Well-being, Psychological Well-being, Autonomy and Parent Relations domains. Compared with the normative data set, the adolescent participants with DS in the current study were found to have lower scores on the Social Support and Peers domain and higher scores than the normative group on the School Environment domain. The test-retest reliability of the KIDSCREEN-27 was also examined using the intraclass correlation coefficient (ICC) in a subgroup of stable participants. The KIDSCREEN-27 demonstrated poor-to-moderate test-retest reliability; however, test-retest reliability was assessed using a long time interval between assessment time points.

Conclusion

The findings of this study underline that further research is needed to better understand the nature of HRQoL in DS. Further research using a shorter time interval between assessment time points to examine test-retest reliability is also required.

Funding

F. Hoffmann-La Roche Ltd.

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Author's response

The correspondents raise an important point regarding the drug–device interaction and their references support their concern.1 Indeed, there can be a significant interaction between the delivery device and the drug that can affect systemic delivery to the body.2 Our comment was directed at the amount coming out of the metered-dose inhaler to the mouth and that the total fraction is decreased with a spacer. There are many factors, as summarized in our review, that ultimately affect the amount of drug that is systemically absorbed from the lung or the gastrointestinal tract that can modify the amount available systemically in the body.

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Editorial Board

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Uptake of EpiPen and Allerject (Auvi-Q) epinephrine auto-injectors in Manitoba children

Anaphylaxis guidelines1,2 recommend that all individuals at increased risk of anaphylaxis in the community carry epinephrine auto-injectors (EAIs) to facilitate timely injection of epinephrine during anaphylaxis and decrease the risk of hospitalization and death.3,4

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Immunotherapy and systemic reactions

We read with interest the recent retrospective review by Winslow et al.1 The authors reported systemic reaction (SR) rates lower than those previously published.2 Of note, they use "standard build" for what is typically referred to as "conventional build-up". The advantage of reporting SR rates within a single large practice is the assumed consistency and standardization of immunotherapy delivery.

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Food allergen extracts to diagnose food-induced allergic diseases

To review the manufacturing procedures of food allergen extracts and applicable regulatory requirements from government agencies, potential approaches to standardization, and clinical application of these products. The effects of thermal processing on allergenicity of common food allergens are also considered.

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Table of Contents

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Understanding the biology of disease in underserved children with asthma

African American children are disproportionately affected by asthma compared with non-Hispanic white children. Recent data from the Centers for Disease Control and Prevention indicate that asthma prevalence rates (10.3% vs 7.8%) remain higher among non-Hispanic black children than non-Hispanic white children, and non-Hispanic black children are almost 3 times as likely to die of asthma as non-Hispanic white children.1 Studies have also found that African American children have more frequent and burdensome asthma symptoms and use emergency department (ED) care more frequently than white children.

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Instructions for Authors

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Information for Readers

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Smoking is associated with hypermethylation of the APC 1A promoter in colorectal cancer: the ColoCare Study

Abstract

Smoking tobacco is a known risk factor for the development of colorectal cancer, and for mortality associated with the disease. Smoking has been reported to be associated with changes in DNA methylation in blood and in lung tumour tissues, although there has been scant investigation of how epigenetic factors may be implicated in the increased risk of developing colorectal cancer. To identify epigenetic changes associated with smoking behaviours, we performed epigenome-wide analysis of DNA methylation in colorectal tumours from 36 never smokers, 47 former smokers and 13 active smokers, and adjacent mucosa from 49 never smokers, 64 former smokers and 18 active smokers. Our analyses identified 15 CpG sites within the APC 1A promoter that were significantly hypermethylated and 14 CpG loci within the NFATC1 gene body that were significantly hypomethylated (pLIS<1x10^-5) in tumours of active smokers. The APC 1A promoter was hypermethylated in 7 of 36 tumours from never smokers (19%), 12 of 47 tumours from former smokers (26%), and 8 of 13 tumours from active smokers (62%). Promoter hypermethylation was positively associated with duration of smoking (Spearman rank correlation, ρ=0.26, p=0.03) and was confined to tumours, with hypermethylation never being observed in adjacent mucosa. Further analysis of adjacent mucosa revealed significant hypomethylation of four loci associated with the TNXB gene in tissue from active smokers. Our findings provide exploratory evidence for hypermethylation of the key tumour suppressor gene APC being implicated in smoking-associated colorectal carcinogenesis. Further work is required to establish the validity of our observations in independent cohorts.

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Protein Intake in Chronic Kidney Disease

Abstract

Purpose of Review

The purpose of this review is to better understand the protein needs in patients with chronic kidney disease (CKD) not on dialysis. Protein energy wasting is common in patients with chronic kidney disease, and the incidence increases as the kidney function declines. Typically, protein intake in patients with CKD is lower than the daily-recommended allowance for healthy adults, and that poor nutritional status has been associated with increase in morbidity and mortality. It is of interest to note that the current guidelines for protein intake vary in terms of both quantity as well as the quality, thus making it confusing for the practicing nephrologist.

Recent Findings

Recent studies show that very low protein intake when supplemented by keto-analogues of essential amino acid could be helpful in slowing the progression of chronic kidney disease. However, it is important to understand that recommending low protein intake could be harmful in CKD patients especially those with poor nutritional status or during an acute illness.

Summary

In summary, it is important for the physician to understand that patients with chronic kidney disease have very complex nutritional requirements, and that recommendations for protein intake should be based on the individual patient needs.

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Child abuse and fabricated or induced illness in the ENT setting: a systematic review

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The diagnostic accuracy of non‐imaging screening protocols for vestibular schwannoma in patients with asymmetrical hearing loss and/or unilateral audiovestibular dysfunction: a diagnostic review and meta‐analysis

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The increased expression of TCF3 is correlated with poor prognosis in Chinese patients with nasopharyngeal carcinoma

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Maxillary sinus volume: new physiopathological data in fungal ball genesis? A retrospective study

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New olfactometric findings in Parkinson's disease

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Inner ear disorders in 68 pregnant women: a 20‐year experience

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Comparison of radiologically and histologically determined thickness of bone overlying the superior semicircular canal in sixty‐six cadaveric specimens: impact on the diagnosis of Minor's Syndrome

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Local control of 151 head and neck cutaneous squamous cell carcinoma after radiotherapy: a retrospective study on efficacy and prognostic factors

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Laryngological presentations of Ehlers–Danlos syndrome: case series of nine patients from two London tertiary referral centres

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Introduction of an outpatient clinic safety checklist: our experience

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Screening not staging: a retrospective study of the rate of synchronous primary malignancy in 44 T1/T2 laryngeal cancer in a tertiary head and neck unit

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Surgical management of petrous apex cholesterol granulomas by an infralabyrinthine approach: our experience with fourteen cases

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Minimally invasive endo‐orbital approach to sphenoid wing meningiomas improves visual outcomes – our experience with the first seven cases

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Modification of facial artery myomucosal flap: a novel perforator flap for upper aerodigestive tract reconstruction after head and neck cancer ablation

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Consequences and complications of surgery for tumours of the pre‐ versus post‐styloid parapharyngeal spaces in 41 patients

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Pressure monitoring of the Muller manoeuvre: our experience in twenty‐five obstructive sleep apnoea hypopnoea syndrome patients with oropharyngeal obstruction

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Treating paediatric anterior glottic web: single‐centre experience of 20 patients with comparison among techniques

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Ambulant management of acute tonsillitis in adult patients, a study on 330 patients

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Editorial Board

Publication date: September 2017
Source:British Journal of Oral and Maxillofacial Surgery, Volume 55, Issue 7





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Re: Current thinking about the management of dysfunction of the temporomandibular joint: a review

Publication date: Available online 8 August 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): A. Graham




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Re: Segmental mandibulectomies made easier: a simple drill guide

Publication date: September 2017
Source:British Journal of Oral and Maxillofacial Surgery, Volume 55, Issue 7
Author(s): Y.J. Kim, Y.C. Lee, Y.G. Eun, J.W. Lee




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Diathermy of split-thickness skin graft donor site: a new technique

Publication date: September 2017
Source:British Journal of Oral and Maxillofacial Surgery, Volume 55, Issue 7
Author(s): A.M. Holden, A.N. Beech, J.N. Farrier




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Training Groups

Publication date: September 2017
Source:British Journal of Oral and Maxillofacial Surgery, Volume 55, Issue 7





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Evaluating Brain-Computer Interface Performance Using Color in the P300 Checkerboard Speller

A Brain Computer Interface (BCI) is a specific type of human-machine interaction. BCI is a direct link between the human brain and a computer. BCIs can be defined as invasive utilizing techniques requiring implantation such as electrocorticography (ECoG), or non-invasive techniques utilizing techniques requiring surface electrodes such as electroencephalography (EEG [Wolpaw et al. 2003]). A BCI can provide an important communication outlet for those who are "locked-in" by amyotrophic lateral sclerosis (ALS), brain stem stroke, or head trauma.

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Restricted co-localization of glutamate and dopamine in neurons of the adult sea lamprey brain

Abstract

Co-localization of dopamine with other classical neurotransmitters in the same neuron is a common phenomenon in the brain of vertebrates. In mammals, some dopaminergic neurons of the ventral tegmental area and the hypothalamus have a glutamatergic co-phenotype. However, information on the presence of this type of dopaminergic neurons in other vertebrate groups is very scant. Here, we aimed to provide new insights on the evolution of this neuronal co-phenotype by studying the presence of a dual dopaminergic/glutamatergic neuron phenotype in the central nervous system of lampreys. Double immunofluorescence experiments for dopamine and glutamate in adult sea lampreys revealed co-localization of both neurotransmitters in some neurons of the preoptic nucleus, the nucleus of the postoptic commissure, the dorsal hypothalamus and in cerebrospinal fluid-contacting cells of the caudal rhombencephalon and rostral spinal cord. Moreover, co-localization of dopamine and glutamate was found in dopaminergic fibres in a few brain regions including the lateral pallium, striatum, and the preoptic and postoptic areas but not in the brainstem. Our results suggest that the presence of neurons with a dopaminergic/glutamatergic co-phenotype is a primitive character shared by jawless and jawed vertebrates. However, important differences in the distribution of these neurons and fibres were noted among the few vertebrates investigated to date. This study offers an anatomical basis for further work on the role of glutamate in dopaminergic neurons.

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Complementary value of contralateral parenchymal enhancement on DCE-MRI to prognostic models and molecular assays in high-risk ER+HER2- breast cancer

Purpose: To determine whether markers of healthy breast stroma are able to select a subgroup of patients at low risk of death or metastasis from patients considered at high risk according to routine markers of the tumor. <p>Experimental Design: Patients with ER-positive/HER2-negative breast cancer were consecutively included for retrospective analysis. The contralateral parenchyma was segmented automatically on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), whereupon the average of the top-10% late enhancement was calculated. This contralateral parenchymal enhancement (CPE) was analyzed with respect to routine prognostic models and molecular assays (Nottingham Prognostic Index, Dutch clinical chemotherapy-selection guidelines, 70-gene signature, and 21-gene recurrence score). CPE was split in tertiles and tested for overall and distant disease-free survival. CPE was adjusted for patient and tumor characteristics, as well as systemic therapy, using inverse probability weighting (IPW). Subanalyses were performed in patients at high risk according to prognostic models and molecular assays.</p> <p>Results: Four-hundred-and-fifteen patients were included, constituting the same group in which the association between CPE and survival was discovered. Median follow-up was 85 months, 34/415(8%) patients succumbed. After IPW-adjustment for patient and tumor characteristics, patients with high CPE had significantly better overall survival than those with low CPE in groups at high risk according to the Nottingham Prognostic Index (HR(95%CI):0.08(0.00-0.40),P<.001); Dutch clinical guidelines (HR(95%CI):0.22(0.00-0.81),P=.021); and 21-gene recurrence score (HR(95%CI):0.14(0.00-0.84),P=.030). One group showed a trend (70-gene signature:HR(95%CI):0.25(0.00-1.02),P=.054).</p> Conclusions: In patients at high risk based on the tumor, subgroups at relatively low risk were identified using pretreatment enhancement of the stroma on breast DCE-MRI.

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ANTI-CD137 AND PD-1/PD-L1 ANTIBODIES IN ROUTE TOWARDS CLINICAL SYNERGY.

T-cell co-stimulation and co-inhibition can be exploited  by blocking and agonist monoclonal antibodies (mAbs) respectively. Both strategies can be synergistically combined in mouse models. Early clinical results from combinations of anti-PD-1 mAbs in conjunction with agonist anti-CD137 (4-1BB) mAbs show excellent safety and promising efficacy.

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Burden and profile of somatic mutation in duodenal adenomas from patients with familial adenomatous- and MUTYH-associated polyposis

Purpose: Duodenal polyposis and cancer are important causes of morbidity and mortality in familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). This study aimed to comprehensively characterize somatic genetic changes in FAP and MAP duodenal adenomas to better understand duodenal tumorigenesis in these disorders.<br /><br />Experimental Design: Sixty-nine adenomas were biopsied during endoscopy in 16 FAP and 10 MAP patients with duodenal polyposis. Ten FAP and 10 MAP adenomas and matched blood DNA samples were exome sequenced, 42 further adenomas underwent targeted sequencing and 47 were studied by array comparative genomic hybridization. Findings in FAP and MAP duodenal adenomas were compared to each other and to the reported mutational landscape in FAP and MAP colorectal adenomas.<br /><br />Results: MAP duodenal adenomas had significantly more protein-changing somatic mutations (P = 0.018), truncating mutations (P = 0.006) and copy number variants (P = 0.005) than FAP duodenal adenomas, even though MAP patients had lower Spigelman stage duodenal polyposis. Fifteen genes were significantly recurrently mutated. Targeted sequencing of APC, KRAS, PTCHD2 and PLCL1 identified further mutations in each of these genes in additional duodenal adenomas. In contrast to MAP and FAP colorectal adenomas, neither exome nor targeted sequencing identified WTX mutations (P=0.0017).<br /><br />Conclusions: The mutational landscapes in FAP and MAP duodenal adenomas overlapped with, but had significant differences to those reported in colorectal adenomas. The significantly higher burden of somatic mutations in MAP than FAP duodenal adenomas despite lower Spigelman stage disease could increase cancer risk in the context of apparently less severe benign disease.

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MSH2 Loss in Primary Prostate Cancer

Purpose: Inactivation of mismatch repair (MMR) genes may predict sensitivity to immunotherapy in metastatic prostate cancers. We studied primary prostate tumors with MMR defects. Experimental Design: 1133 primary prostatic adenocarcinomas and 43 prostatic small cell carcinomas (NEPC) were screened by MSH2 immunohistochemistry with confirmation by next-generation sequencing (NGS). Microsatellite instability (MSI) was assessed by PCR and NGS (mSINGS). Results: Of primary adenocarcinomas and NEPC, 1.2% (14/1176) had MSH2 loss. Overall, 8% (7/91) of adenocarcinomas with primary Gleason pattern 5 (Gleason score 9-10) had MSH2 loss compared to 0.4% (5/1042) of tumors with any other scores (p<0.05). 5% (2/43) of NEPC had MSH2 loss. MSH2 was generally homogenously lost, suggesting it was an early/clonal event. NGS confirmed MSH2 loss-of-function alterations in all (12/12) samples, with bi-allelic inactivation in 83% (10/12) and hypermutation in 83% (10/12). Overall, 61% (8/13) and 58% (7/12) of patients had definite MSI by PCR and mSINGS, respectively. Three patients (25%) had germline mutations in MSH2. Tumors with MSH2 loss had a higher density of infiltrating CD8+ lymphocytes compared to grade-matched controls without MSH2 loss (390 vs. 76 cells/mm²; p=0.008), and CD8+ density was correlated with mutation burden among cases with MSH2 loss (r=0.72, p=0.005). T-cell receptor sequencing on a subset revealed a trend towards higher clonality in cases versus controls. Conclusion: Loss of MSH2 protein is correlated with MSH2 inactivation, hypermutation and higher tumor-infiltrating lymphocyte density, and appears most common among very high-grade primary tumors, where routine screening may be warranted if validated in additional cohorts.

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Neurotensin receptor 1 antagonist SR48692 improves response to carboplatin by enhancing apoptosis and inhibiting drug efflux in ovarian cancer

Purpose: The high affinity receptor 1 (NTSR1) and its agonist, neurotensin (NTS), is correlated with tumor cell aggressiveness in most solid tumors. As chemo-resistance and tumor aggressiveness are often related; we decided to study the role of the NTSR1 complex within platinum-based chemotherapy responses. In an ovarian model, we studied carboplatin because it is the main standard of care for ovarian cancer (OC).Experimental Design: Experimental tumors and in vitro studied were performed using SKOV3 and A2780 cells treated with carboplatin, with or without a very specific NTSR1 antagonist, SR48692. We measured the effects of these treatments on cell apoptosis and apoptosis related proteins, platinum accumulation in the cell and nucleus, and the expression and localization of platinum transporters. NTS and NTSR1 labelling was measured in patients with ovarian cancer. Results: SR48692 enhanced the response to carboplatin in OC cells and experimental tumors. When SR48692 is combined to carboplatin, we noted a major improvement of platinum induced DNA damage and cell death, as well as a decrease in tumor growth. The relationship of these results to clinic studies was made by the detection of NTS and NTSR1 in 72% and 74% of OC, respectively. Furthermore, in a large series of high grade OC, NTSR1 mRNA was shown to correlate with higher stages and platinum resistance. Conclusions: This study strongly suggests that the addition of NTSR1 inhibitor in combination with platinum salt-based therapy will improve the response to the drug.

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Amiloride, an old diuretic drug, is a potential therapeutic agent for multiple myeloma

Purpose: <br />The search for new drugs that control the continuous relapses of multiple myeloma is still required. Here, we report for the first time the potent anti-myeloma activity of amiloride, an old potassium-sparing diuretic approved for the treatment of hypertension and edema due to heart failure.<br /><br />Experimental Design:  <p>Myeloma cell lines and primary samples were used to evaluate cytotoxicity of amiloride. In vivo studies were carried out in a xenograft mouse model. The mechanisms of action were investigated using RNA-Seq, qRT-PCR, immunoblotting and immunofluorescence assays.</p> Results: <p>Amiloride-induced apoptosis was observed in a broad panel of MM cell lines and in a xenograft mouse model. Moreover, amiloride also had a synergistic effect when combined with dexamethasone, melphalan, lenalidomide and pomalidomide. RNA-Seq experiments showed that amiloride not only significantly altered the level of transcript isoforms and alternative splicing events, but also deregulated the spliceosomal machinery. Additionally, disruption of the splicing machinery in immunofluorescence studies was associated with the inhibition of myeloma cell viability after amiloride exposure. Although amiloride was able to induce apoptosis in myeloma cells lacking p53 expression, activation of p53 signaling was observed in wild-type and mutated TP53 cells after amiloride exposure. On the other hand, we did not find a significant systemic toxicity in mice treated with amiloride. </p> <br />Conclusions: <p>Overall, our results demonstrate the anti-myeloma activity of amiloride and provide a mechanistic rationale for its use as an alternative treatment option for relapsed MM patients, especially those with 17p deletion or TP53 mutations that are resistant to current therapies.

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Differential toxicity in patients with and without DNA repair mutations: Phase I Study of Carboplatin and Talazoparib in advanced solid tumors

<p>Purpose: The PARP inhibitor, talazoparib, may potentiate activity of chemotherapy in cells vulnerable to DNA damage. Experimental Design: This phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of talazoparib and carboplatin. Pharmacokinetic-modeling explored associations between dosing and hematological toxicity. Results: 24 patients with solid tumors were enrolled in 4 cohorts at 0.75mg and 1mg daily talazoparib and weekly carboplatin (AUC 1 and 1.5, Q2W or Q3W). Dose-limiting toxicities included grade 3 fatigue and grade 4 thrombocytopenia; the maximum tolerated dose was not reached. Grade 3/4 toxicities included fatigue (13%), neutropenia (63%), thrombocytopenia (29%), and anemia (38%). Post-cycle 2 dose modifications were required in all patients. One complete and two partial responses occurred in germline BRCA1/2 (gBRCA1/2) patients. Four patients showed stable disease beyond four months, three of which had mutations in DNA repair pathways. Pharmacokinetic-toxicity modeling showed that after 3 cycles of carboplatin AUC 1.5 Q3W and talazoparib 1mg daily, neutrophil counts decreased 78% (CI: 87 to 68%) from baseline in gBRCA carriers and 63% (CI: 72 to 55%) in non-carriers (p<0.001). This modeling suggests an intermittent, pulse dosing schedule of PARP inhibition, differentiated by gBRCA mutation status may improve tolerance of combination therapy. Conclusions: In order to optimize efficacy and minimize toxicity, we feel that the combination of carboplatin and talazoparib is likely best pursued using differentiated dosing schedules for patients with somatic DNA repair mutations vs. gBRCA mutations.

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Replication stress leading to apoptosis within the S-phase contributes to synergism between vorinostat and AZD1775 in HNSCC harboring high risk TP53 mutation

Purpose: The cure rate for patients with advanced head and neck squamous cell carcinoma (HNSCC) remains poor due to resistance to standard therapy primarily consisting of chemoradiation. Since mutation of TP53 in HNSCC occurs in 60-80% of non-HPV associated cases and is in turn associated with resistance to these treatments, more effective therapies are needed. In this study, we evaluated the efficacy of a regimen combining vorinostat and AZD1775 in HNSCC cells with a variety of p53 mutations. <p>Experimental Design: Clonogenic survival assays and an orthotopic mouse model of oral cancer were used to examine the in vitro and in vivo sensitivity of high-risk mutant p53 HNSCC cell lines to vorinostat in combination with AZD1775. Cell cycle, replication stress, homologous recombination (HR), live cell imaging, RNA-sequencing, and apoptosis analyses were performed to dissect molecular mechanisms.</p> <p>Results: We found that vorinostat synergizes with AZD1775 in vitro to inhibit growth of HNSCC cells harboring high-risk mutp53. These drugs interact synergistically to induce DNA damage, replication stress associated with impaired Rad51-mediated homologous recombination through activation of CDK1 and inhibition of Chk1 phosphorylation, culminating in an early apoptotic cell death during the S-phase of the cell cycle. The combination of vorinostat and AZD1775 inhibits tumor growth and angiogenesis in vivo in an orthotopic mouse model of oral cancer and prolongs animal survival.</p> <p>Conclusions: Vorinostat synergizes with AZD1775 in HNSCC cells with mutant p53 in vitro and in vivo. A strategy combining HDAC and WEE1 inhibition deserves further clinical investigation in patients with advanced HNSCC.

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Cyclophilin A Maintains Glioma-Initiating Cell Stemness by Regulating Wnt/{beta}-catenin Signaling

Purpose: Glioma-initiating cells (GICs) are glioma stem-like cells that contribute to glioblastoma (GBM) development, recurrence, and resistance to chemotherapy and radiotherapy. They have recently become the focus of novel treatment strategies. Cyclophilin A (CypA) is a cytosolic protein that belongs to the peptidyl-prolyl isomerase (PPIase) family and the major intracellular target of the immunosuppressive drug cyclosporin A (CsA). In this study, we investigate the functions of CypA and its mechanism of action in GICs' development. Experimental Design: We analyzed differences in CypA expression between primary tumors and neurospheres from the GDS database, both before and after GIC differentiation. A series of experiments was conducted to investigate the role of CypA in GIC stemness, self-renewal, proliferation, radiotherapy resistance, and mechanism. We then designed glutathione S-transferase (GST) pull-down and co-immunoprecipitation assays to detect signaling activity. Results: In this study, we demonstrated that CypA promotes GIC stemness, self-renewal, proliferation, and radiotherapy resistance. Mechanistically, we found that CypA binds β-catenin and is recruited to Wnt target gene promoters. By increasing the interaction between β-catenin and TCF4, CypA enhances transcriptional activity. Conclusions: Our results demonstrate that CypA enhances GIC stemness, self-renewal, and radio-resistance through Wnt/β-catenin signaling. Due to its promotive effects on GICs, CypA is a potential target for future glioma therapy.

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Targeted proteomics identifies proteomic signatures in liquid-biopsies of the endometrium to diagnose endometrial cancer and assist in the prediction of the optimal surgical treatment

Purpose: Endometrial cancer (EC) diagnosis relies on the observation of tumor cells in endometrial biopsies obtained by aspiration i.e., uterine aspirates), but it is associated with 22% undiagnosed patients and up to 50% of incorrectly assigned EC histotype and grade. We aimed to identify biomarker signatures in the fluid fraction of these biopsies to overcome these limitations. Experimental Design: The levels of 52 proteins were measured in the fluid fraction of uterine aspirates from 116 patients by LC-PRM, the latest generation of targeted mass-spectrometry acquisition. A logistic regression model was used to assess the power of protein panels to differentiate between EC and non-EC patients and between EC histological subtypes. The robustness of the panels was assessed by the "leave-one-out" cross-validation procedure performed within the same cohort of patients and an independent cohort of 38 patients. Results: The levels of 28 proteins were significantly higher in EC patients (n=69) compared to controls (n=47). The combination of MMP9 and KPYM exhibited 94% sensitivity and 87% specificity for detecting EC cases. This panel perfectly complemented the standard diagnosis, achieving 100% of correct diagnosis in this dataset. Nine proteins were significantly increased in endometrioid EC (n=49) compared to serous EC (n=20). The combination of CTNB1, XPO2 and CAPG achieved 95% sensitivity and 96% specificity for the discrimination of these subtypes. Conclusions: We developed two uterine aspirate-based signatures to diagnose EC and classify tumors in the most prevalent histological subtypes. This will improve diagnosis and assist in the prediction of the optimal surgical treatment.

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Editorial Board

Publication date: August 2017
Source:Journal of Oral Biosciences, Volume 59, Issue 3





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GSK 3 inhibition drives maturation of NK cells and enhances their antitumor activity

Maturation of human natural killer cells (NK cells) as defined by accumulation of cell surface expression of CD57 is associated with increased cytotoxic character and TNF and IFN-γ production upon target cell recognition. Notably, multiple studies point to a unique role for CD57+ NK cells in cancer immunosurveillance, yet there is scant information about how they mature. In this study, we show that pharmacological inhibition of GSK3 kinase in peripheral blood NK cells expanded ex vivo with IL-15 greatly enhances CD57 upregulation and late-stage maturation. GSK3 inhibition elevated the expression of several transcription factors associated with late-stage NK cell maturation including T-BET, ZEB2 and BLIMP-1 without affecting viability or proliferation. When exposed to human cancer cells, NK cell expanded ex vivo in the presence of a GSK3 inhibitor exhibited significantly higher production of TNF and IFN-γ, elevated natural cytotoxicity, and increased antibody-dependent cellular cytotoxicity (ADCC). In an established mouse xenograft model of ovarian cancer, adoptive transfer of NK cells conditioned in the same way also displayed more robust and durable tumor control. Our findings show how GSK3 kinase inhibition can greatly enhance the mature character of NK cells most desired for effective cancer immunotherapy.

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ATM deficiency generating genomic instability sensitizes pancreatic ductal adenocarcinoma cells to therapy-induced DNA damage

Pancreatic adenocarcinomas (PDAC) harbour recurrent functional mutations of the master DNA damage response kinase ATM which has been shown to accelerate tumorigenesis and epithelial-mesenchymal transition. To study how ATM deficiency affects genome integrity in this setting, we evaluated the molecular and functional effects of conditional Atm deletion in a mouse model of PDAC. ATM deficiency was associated with increased mitotic defects, recurrent genomic rearrangements and deregulated DNA integrity checkpoints, reminiscent of human PDAC. We hypothesized that altered genome integrity might allow synthetic lethality-based options for targeted therapeutic intervention. Supporting this possibility, we found that the PARP inhibitor olaparib or ATR inhibitors reduced the viability of PDAC cells in vitro and in vivo associated with a genotype-selective increase in apoptosis. Overall, our results offered a preclinical mechanistic rationale for the use of PARP and ATR inhibitors to improve treatment of ATM-mutant PDAC.

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Allergic sensitization to laboratory animals is more associated with asthma, rhinitis and skin symptoms than sensitization to common allergens

Summary

Background

Workers exposed to laboratory animals have a high risk of developing laboratory animal allergy (LAA). Atopy seems to be the main risk factor for LAA. We hypothesized that occupational sensitization is a better predictor for the development of asthma, rhinitis and bronchial hyperresponsiveness than common sensitization.

Objective

To investigate the association between occupational sensitization to laboratory animals and clinical outcomes.

Methods

This was a cross-sectional study performed at two universities on students and employees dealing with small rodents. The subjects were allocated in groups: non-sensitized, common sensitization or occupational sensitization, according to the results of the skin prick test (SPT). All subjects answered a questionnaire about animal exposures, symptoms, allergic diseases, and underwent spirometry and bronchial challenge test with mannitol. Multivariate analysis was performed by using Poisson regression to estimate the prevalence ratio (PR).

Results

Data from 453 volunteers were analyzed. Non-sensitized group comprised 237 subjects; common sensitization group, 142 subjects; and occupational sensitization group, 74 subjects. Occupational sensitization was associated with greater risk for all outcomes studied. When the common sensitization group was reference, skin symptoms had PR of 1.36; 95% confidence interval (CI): 1.01-1.85; wheezing had PR of 1.75; CI 95%: 1.21-2.53; rhinitis had PR of 1.25; 95%: 1.11-1.40; nocturnal dyspnea had PR of 2.40; 95% CI: 1.31-4.40; bronchial hyperresponsiveness had PR of 2.47; 95% CI: 1.50-4.09; and confirmed asthma had PR of 2.65; 95% CI: 1.45-4.85. In addition, the overlap of asthma, rhinitis and skin symptoms in a same subject was significantly more prevalent in the occupational sensitization group, 16.2% versus 4.9% in the common sensitization group.

Conclusion and Clinical Relevance

Occupational sensitization is associated with allergic symptoms and respiratory diseases. SPT with occupational allergens along with other parameters may contribute to detection of risk for allergic and respiratory diseases associated with exposure to laboratory animals.

This article is protected by copyright. All rights reserved.

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Association between infection with H. pylori and atopy in young Ethiopian Children: a longitudinal study

Abstract

Background

Epidemiological evidence from developed countries indicates that Helicobacter pylori infection correlates with a reduced risk of atopy and allergic disorders, however limited data are available from low-income countries.

Objective

We examined associations between H. pylori infection in early childhood and atopy and reported allergic disorders at the age of 6.5 years in an Ethiopian birth cohort.

Methods

A total of 856 children (85.1% of the 1006 original singletons in a population-based birth cohort) were followed up at age six and half years. An interviewer-led questionnaire administered to mothers provided information on demographic and lifestyle variables. Questions on allergic disease symptoms were based on the International Study of Asthma and Allergies in Children (ISAAC) core allergy and environmental questionnaire. Serum samples were analysed for total IgE levels and anti-H. pylori cytotoxin associated gene A (CagA) IgG antibody using commercially available ELISA kits. Stool samples were analysed for H. pylori antigen using a rapid immunochromatographic test. The independent effects of H. pylori infection (measured at age 3, 5 and 6.5 years) on prevalence and incidence of atopy and reported allergic disorders (measured at age 6.5 years) were determined using multiple logistic regression.

Results

In cross-sectional analysis, current H. pylori infection at age 6.5 years was inversely, though not significantly, related to prevalence of atopy and 'any allergic condition' at age 6.5 years. However detection of H. pylori infection at any point up to age 6.5 years was associated with a significantly reduced odds of both atopy and 'any allergic condition' (adjusted OR AOR, 95% CI, 0.54; 0.32 to 0.92, p=0.02, and 0.31; 0.10 to 0.94, p=0.04, respectively). In longitudinal analyses, H. pylori infection at age 3 was inversely associated with incidence of atopy (AOR, 95% CI, 0.49; 0.27 to 0.89, p=0.02). Furthermore, among H. pylori infected children, those with a CagA+ strain had a more pronounced reduction in odds of atopy (AOR=0.35 vs. 0.63 for CagA+ vs. CagA-) and this reduction reached borderline significance.

Conclusion

These data are consistent with the hypothesis that early exposure to H. pylori is inversely associated with atopy and allergic conditions. A possible modest protective association against atopy was observed in those infected with a more virulent CagA+ strain of H. pylori.

This article is protected by copyright. All rights reserved.

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Specialist Peri-Operative Allergy Clinic Services in the UK 2016: Results from the Royal College of Anaesthetists Sixth National Audit Project (NAP6)

Abstract

Background

Guidelines for investigation of perioperative drug allergy exist, but the quality of services is unknown. Specialist perioperative anaphylaxis services were surveyed through the Royal College of Anaesthetists 6^th National Audit Project.

Objectives

We compare self-declared UK practice in specialist perioperative allergy services with national recommendations.

Methods

A SurveyMonkey^™ questionnaire was distributed to providers of allergy services in the UK. Responses were assessed for adherence to the best practice recommendations of the British Society for Allergy and Clinical Immunology, the Association of Anaesthetists of Great Britain and Ireland and the National Institute for Health and Care Excellence (NICE) Guidance on Drug Allergy - CG183.

Results

Over 1200 patients were evaluated in 44 centres annually. Variation in workload, waiting times, access, staffing and diagnostic approach was noted. Paediatric centres had the longest routine waiting times (most wait >13 weeks) in contrast to adult centres (most wait <12 weeks). Service leads are allergists/immunologists (91%) or anaesthetists (7%).

Potentially important differences were seen in: testing repertoire [10/44 (23%) lacked BSACI compliant NMBA panels and 17/44 (39%) lacked a NAP6-defined extended panel; many failed to screen all cases for chlorhexidine 19/44 (43%) or latex 21/44 (48%)], staffing [only 26/44 (59%) had specialist nurses and 18/44 (41%) an anaesthetist], and provision of information [18/44 (41%) gave immediate information in clinic, and 5/44 (11%) on support groups].

Most centres were able to provide diagnostic challenges to antibiotics [40/44 (91%]) and local anaesthetics [41/44 (93%)].

Conclusions and Clinical Relevance

Diagnostic testing is not harmonised, with marked variability in the NMBA panels used to identify safe alternatives. Chlorhexidine and latex are not part of routine testing in many centres.

Poor access to services and patient information provision require attention. Harmonisation of diagnostic approach is desirable, particularly with regard to a minimum NMBA panel for identification of safe alternatives.

This article is protected by copyright. All rights reserved.

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Correlation of volumetric growth and histological grade in 50 meningiomas

Abstract

Introduction

Advances in radiological imaging techniques have enabled volumetric measurements of meningiomas to be easily monitored using serial imaging scans. There is limited literature on the relationship between tumour growth rates and the WHO classification of meningiomas despite tumour growth being a major determinant of type and timing of intervention. Volumetric growth has been successfully used to assess growth of low-grade glioma; however, there is limited information on the volumetric growth rate (VGR) of meningiomas. This study aimed to determine the reliability of VGR measurement in patients with meningioma, assess the relationship between VGR and 2016 WHO grading as well as clinical applicability of VGR in monitoring meningioma growth.

Methods

All histologically proven intracranial meningiomas that underwent resection in a single centre between April 2009 and April 2014 were reviewed and classified according to the 2016 edition of the Classification of the Tumours of the CNS. Only patients who had two pre-operative scans that were at least 3 months apart were included in the study. Two authors performed the volumetric measurements using the Slicer 3D software independently and the inter-rater reliability was assessed. Multiple regression analyses of factors affecting the VGR and VDE of meningiomas were performed using the R statistical software with p < 0.05 considered to be statistically significant.

Results

Of 548 patients who underwent resection of their meningiomas, 66 met the inclusion criteria. Sixteen cases met the exclusion criteria (NF2, spinal location, previous surgical or radiation treatment, significant intra-osseous component and poor quality imaging). Forty-two grade I and 8 grade II meningiomas were included in the analysis. The VGR was significantly higher for grade II meningiomas. Using receiver-operator characteristic (ROC) curve analysis, the optimal threshold that distinguishes between grade I and II meningiomas is 3 cm³/year. Higher histological grade, high initial tumour volume, MRI T2-signal hyperintensity and presence of oedema were found to be significant predictors of higher VGR.

Conclusion

Reliable tools now exist to evaluate and monitor volumetric growth of meningiomas. Grade II meningiomas have significantly higher VGR compared with grade I meningiomas and growth of more than 3 cm³/year is strongly suggestive of a higher grade meningioma. A larger, multi-centre prospective study to investigate the applicability of velocity of growth to predict the outcome of patients with meningioma is warranted.

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Application of a newly designed mandibular distraction device for navigation surgery in goats

This animal study is to investigate the accuracy of navigation-guided mandibular distraction osteogenesis with a special designed distraction device by TBNavis-CMFS navigation system.

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Comparative Cost Analysis of Endoscopic versus Microscopic Endonasal Transsphenoidal Surgery for Pituitary Adenomas

J Neurol Surg B
DOI: 10.1055/s-0037-1604484

Objective This study presents a comparative analysis of cost efficacy between the microscopic and endoscopic transsphenoidal approaches, evaluating neurological outcome, extent of resection (EOR), and inpatient hospital costs. Design This study was a retrospective chart review. Setting This study was conducted at a tertiary care center. Participants The study group consisted of 68 patients with transsphenoidal surgeries between January 2007 and January 2014. Main Outcome Measures Two-sample t-tests and Pearson's chi-square test evaluated inpatient costs, quality-adjusted life years (QALYs), volumetric EOR, and neurological outcomes. Results Total inpatient costs per patient was $22,853 in the microscopic group and less ($19,736) in the endoscopic group (p = 0.049). Operating room costs were $5,974 in the microscopic group and lower in the endoscopic group ($5,045; p = 0.038). Operative time was 203.6 minutes in the microscopic group and 166.3 minutes in the endoscopic group (p = 0.032). The QALY score, length of hospital stay, and postoperative outcomes were found to be similar between the two cohorts. Multivariate linear regression modeling suggested that length of stay (p < 0.001) and operative time (p = 0.008) were important factors that influenced total inpatient costs following transsphenoidal surgery. Conclusion This study shows that transsphenoidal surgery is more cost effective with the endoscopic approach than with the microscopic approach and depends on efficiency in the operating room as well as reduction in the length of hospitalization.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Using a Guided Machine Learning Ensemble Model to Predict Discharge Disposition following Meningioma Resection

J Neurol Surg B
DOI: 10.1055/s-0037-1604393

Objective Machine learning (ML) algorithms are powerful tools for predicting patient outcomes. This study pilots a novel approach to algorithm selection and model creation using prediction of discharge disposition following meningioma resection as a proof of concept. Materials and Methods A diversity of ML algorithms were trained on a single-institution database of meningioma patients to predict discharge disposition. Algorithms were ranked by predictive power and top performers were combined to create an ensemble model. The final ensemble was internally validated on never-before-seen data to demonstrate generalizability. The predictive power of the ensemble was compared with a logistic regression. Further analyses were performed to identify how important variables impact the ensemble. Results Our ensemble model predicted disposition significantly better than a logistic regression (area under the curve of 0.78 and 0.71, respectively, p = 0.01). Tumor size, presentation at the emergency department, body mass index, convexity location, and preoperative motor deficit most strongly influence the model, though the independent impact of individual variables is nuanced. Conclusion Using a novel ML technique, we built a guided ML ensemble model that predicts discharge destination following meningioma resection with greater predictive power than a logistic regression, and that provides greater clinical insight than a univariate analysis. These techniques can be extended to predict many other patient outcomes of interest.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Non-invasive prediction of recurrence in bladder cancer by detecting somatic TERT promoter mutations in urine

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Detection of phosphatidylserine-positive exosomes for the diagnosis of early-stage malignancies

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Geriatric assessment is superior to oncologists’ clinical judgement in identifying frailty

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LIM kinase 1 interacts with myosin-9 and alpha-actinin-4 and promotes colorectal cancer progression

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Integrating cytokines and angiogenic factors and tumour bulk with selected clinical criteria improves determination of prognosis in advanced renal cell carcinoma

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HYPE or HOPE: the prognostic value of infiltrating immune cells in cancer

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Harmonisation of biobanking standards in endometrial cancer research

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UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins–TGF-β1–FAP-α

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Kinase-driven metabolic signalling as a predictor of response to carboplatin–paclitaxel adjuvant treatment in advanced ovarian cancers

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KIBRA attains oncogenic activity by repressing RASSF1A

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TOPK modulates tumour-specific radiosensitivity and correlates with recurrence after prostate radiotherapy

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Clinical study of genomic drivers in pancreatic ductal adenocarcinoma

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Modulating cancer cell survival by targeting intracellular cholesterol transport

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Pre-diagnostic statin use, lymph node status and mortality in women with stages I–III breast cancer

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Re: Current thinking about the management of dysfunction of the temporomandibular joint: a review

I was pleased to read this excellent summary,1 as it offers structured guidance for the management of disorders of the temporomandibular joint (TMJ), which are sometimes difficult to treat. I agree that there is a lack of evidence for some recommended treatments and, as a result, an evidence-based approach is difficult.

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The role of time in phonetic spaces: Temporal resolution in Cantonese tone perception

Publication date: November 2017
Source:Journal of Phonetics, Volume 65
Author(s): Kristine M. Yu
The role of temporal resolution in speech perception (e.g. whether tones are parameterized with fundamental frequency sampled every 10ms, or just twice in the syllable) is sometimes overlooked, and the temporal resolution relevant for tonal perception is still an open question. The choice of temporal resolution matters because how we understand the recognition, dispersion, and learning of phonetic categories is entirely predicated on what parameters we use to define the phonetic space that they lie in. Here, we present a tonal perception experiment in Cantonese where we used interrupted speech in trisyllabic stimuli to study the effect of temporal resolution on human tonal identification. We also performed acoustic classification of the stimuli with support vector machines. Our results show that just a few samples per syllable are enough for humans and machines to classify Cantonese tones with reasonable accuracy, without much difference in performance from having the full speech signal available. The confusion patterns and machine classification results suggest that loss of detailed information about the temporal alignment and shape of fundamental frequency contours was a major cause of decreasing accuracy as resolution decreased. Moreover, machine classification experiments show that for accurate identification of rising tones in Cantonese, it is crucial to extend the temporal window for sampling to the following syllable, due to peak delay.



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Role of Plasma D-Dimer Levels in Breast Cancer Patients and Its Correlation with Clinical and Histopathological Stage

Abstract

Breast cancer, the most common female malignancy, represents a heterogeneous group of tumors, which presen both varied behaviors and response to therapy. This study was done with an attempt to evaluate the role of D-dimer in patients of carcinoma breast, in predicting lymph node metastasis in carcinoma patients and to look for relationship of these markers with histopathologic parameters. Clinical data was obtained from clinical examination of patients admitted in the Department of Surgery with history of breast lump and confirmed with fine needle aspiration cytology (FNAC). Clinical staging was done using TNM staging. D-dimer level was measured prior to commencement of treatment, i.e., modified radical mastectomy (MRM) or neoadjuvant chemotherapy and finally 6 months after surgery or completion of 6 cycles of chemotherapy. The characteristics of the study population Out of 60 study cases minimum age of the patient being 30 years and maximum being 74 years. Of all histopathologic variables examined, D-dimer levels directly correlated with extent of lymph node involvement and lymphovascular invasion, D-dimer levels correlated strongest with the number of positive lymph nodes, but not with tumor size, estrogen receptor status, and progesterone receptor status. This study clearly shows that plasma D-Dimer levels are elevated in carcinoma breast patients. Increased D-Dimer levels are an important marker of clinical stage, lymphovascular invasion, lymph node involvement, and tumor metastasis.

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Characteristics of severe asthma with fungal sensitization

Some patients with severe asthma also have fungal sensitization and are considered to have severe asthma with fungal sensitization. However, there is limited information on the clinical features of SAFS.

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Comparative frequency of four different types of pregnancy-associated thyrotoxicosis in a single thyroid centre

Abstract

Background

Pregnancy and delivery markedly influence thyroid function. However, the comparative prevalence of gestational thyrotoxicosis (GT), new onset of Graves' disease during pregnancy (GD during pregnancy), postpartum destructive thyrotoxicosis (PPT), and postpartum Graves' thyrotoxicosis (PPGD) has not yet been determined.

Methods

We prospectively registered and performed a review of 4127 consecutive non treated female patients with thyrotoxicosis, seen between August 2008 and December 2013 in our outpatient clinic of Kuma Hospital. 187 out of the 4127 women had new diagnosis of thyrotoxicosis during pregnancy or in the postpartum period. We investigated the prevalence of new diagnosis of GT, GD during pregnancy, PPT and PPGD and compared the characteristics of these types of thyrotoxicosis. The postpartum period is defined as twelve months after delivery.

Results

Out of 187 pregnant or postpartum women, we identified 30 (16.0%) with GT, 13 (7.0%) with GD during pregnancy, 42 (22.5%) with PPT, and 102 (54.5%) with PPGD. The onset time of thyrotoxicosis during pregnancy, i.e., both GT and GD during pregnancy, was delayed by a couple of weeks when hCG peaked at 10 gestational weeks. Seventy-six percent of patients with PPT developed thyrotoxicosis between delivery and 4 months postpartum; on the other hand, 83.3% of patients with PPGD developed thyrotoxicosis at 6 months postpartum or later.

Conclusions

We named gestational thyrotoxicosis, new onset of Graves' disease during pregnancy, postpartum destructive thyrotoxicosis, and postpartum Graves' thyrotoxicosis as pregnancy-associated thyrotoxicosis. A clinically significant number of women developed Graves' disease in the postpartum period in a single thyroid centre.

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Insomnia, postpartum depression and estradiol in women after delivery

Abstract

After childbirth, women may develop symptoms of depression with the associated sleep disturbances. This study assessed the relationship between insomnia and both depression symptoms and blood estradiol levels in women during the early postpartum period. 84 patients were assessed 24–48 h after labor. The main assessment methods were the following psychometric scales: Beck Depression Inventory (BDI), Edinburgh Postnatal Depression Scale (EPDS) and Athens Insomnia Scale (AIS). Serum estradiol levels were measured using ELISA assay. Women who developed postpartum insomnia significantly more often reported insomnia during pregnancy (P = 0.001), were more likely to have suffered from depression in the past (P = 0.007) and had significantly higher BDI (P = 0.002) and EPDS (P = 0.048) scores. Our study demonstrated no significant association between Restless Legs Syndrome (RLS) during pregnancy and postpartum insomnia. The groups of women with and without postpartum RLS showed no significant differences in the incidence of postpartum insomnia. No significant differences in estradiol levels were observed in women with and without postpartum insomnia. The study showed the following factors to play a major role in development of postpartum insomnia: an increase in Beck Depression Inventory score, a history of depression and a history of insomnia during pregnancy.

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Allergens displayed on Virus-Like Particles are highly immunogenic but fail to activate human mast cells

Abstract

The goal of allergen-specific immunotherapy is the induction of protective immune responses in the absence of anaphylactic reactions. We have previously shown that Fel d 1, the major cat allergen, displayed in a repetitive fashion on virus-like particles (VLPs) may fulfill these criteria. Specifically, Fel d 1 on VLPs induced strongly increased IgG responses compared to the free allergen in mice while anaphylactic reactions were essentially abolished. Here we extend these findings to human mast cells and offer a mechanistic explanation for the reduced anaphylactic activity. By performing allergen binding studies and cellular activation assays, we demonstrate that the inability of Fel d 1 displayed on VLPs to activate mast cells is based on a biophysical as well as a biochemical mechanism. Firstly, Fel d 1 on VLPs showed a strongly impaired ability to bind to surface-bound IgE as assessed by Surface Plasmon Resonance (SPR) as well as flow cytometry. Secondly, despite residual binding, repetitively displayed allergen on VLPs failed to cause mast cell activation.

These findings indicate that repetitively displaying allergens on VLPs increases their immunogenicity while reducing their potential to cause anaphylactic reactions by essentially eliminating IgE-mediated activation of mast cells.

This article is protected by copyright. All rights reserved.

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Metabolic Tumor Volume of Primary Tumor Predicts Survival Better than T Classification in the Larynx Preservation Approach

Abstract

We aimed to determine whether pretreatment metabolic tumor volume of the primary tumor (T-MTV) or T classification would be a better predictor of laryngectomy-free survival (LFS) and overall survival (OS) after chemoradiotherapy in patients with locally advanced laryngeal or hypopharyngeal cancer requiring total laryngectomy. We analyzed 85 patients using a Cox proportional hazards model and evaluated its usefulness by Akaike's information criterion. A T-MTV cutoff value was determined by time-dependent receiver operating characteristic curve analysis. Interobserver reliability for measuring T-MTV was estimated by the intraclass correlation coefficient (ICC). After adjustment for covariables, T-MTV, irrespective of whether a continuous or dichotomized variable, and T classification remained independent predictors of LFS and OS. Large T-MTV (>28.7 ml) was associated with inferior LFS [hazard ratio (HR), 4.16; 95% confidence interval (CI), 1.97–8.70; P = 0.0003] and inferior OS (HR, 3.18; 95% CI, 1.47–6.69; P = 0.004) compared with small T-MTV (≤28.7 ml). The T-MTV model outperformed the T classification model in predicting LFS and OS (P = 0.007 and 0.01, respectively). The 3-year LFS and OS rates for patients with small versus large T-MTV were 68% versus 9% (P < 0.0001) and 77% versus 25% (P < 0.0001), respectively, while those for patients with T2-T3 versus T4a were 61% versus 31% (P = 0.003) and 71% versus 48% (P = 0.10), respectively. The ICC was 0.99 (95% lower confidence bound, 0.99). Given the excellent interobserver reliability, T-MTV would serve better than T classification to identify patients who benefit from the larynx preservation approach.

This article is protected by copyright. All rights reserved.

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A combination of anti-CD4 antibody treatment and DLI ameliorates GVHD while preserving GVT effects in murine allo-HSCT

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not only a well-established immunotherapy for hematologic malignancies, but is potentially useful for treating solid tumors refractory to available therapies. However, application of allo-HSCT to solid tumors is limited, despite the beneficial anti-tumor effects, by the risk of graft-versus-host disease (GVHD). CD4⁺ T cells have been implicated in several aspects of GVHD, and suppress anti-tumor CD8⁺ T cell responses. In the present study, we investigated clinically applicable allo-HSCT protocols designed to maximize anti-tumor effects while reducing the risk of GVHD. We used a mouse model of allo-HSCT with subcutaneous tumors. We found that myeloablative conditioning was associated with better inhibition of tumor growth but with severe acute GVHD. Early administration of anti-CD4 mAb substantially ameliorated GVHD, while preserving anti-tumor effects, leading to improved survival in myeloablative allo-HSCT. Late administration of anti-CD4 mAb also ameliorated GVHD to some extent. Donor lymphocyte infusion (DLI) in GVHD mice treated with anti-CD4 mAb further suppressed tumor growth without exacerbating GVHD. Collectively, our results suggest that myeloablative allo-HSCT followed by anti-CD4 mAb treatment and DLI may be a potent and safe immunotherapy for patients with cancers refractory to available therapies.

This article is protected by copyright. All rights reserved.

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Disgraced Florida Oncologist Sentenced to 6 Years in Prison

A Florida oncologist who treated her patients with unapproved drugs purchased from overseas has now been sentenced to 70 months in prison.
Medscape Medical News

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Doctors Say Info From Pharma Reps Is Stale

A physician survey suggests that as doctors get more information online, drug reps are falling behind in their sales pitches.
Medscape Medical News

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PET/CT in Esophageal Carcinoma: Applications and Limitations

Squamous cell carcinoma (SqCC) and adenocarcinoma represent approximately 98 % of esophageal malignant tumors. During the last 30 years, the incidence of adenocarcinoma has increased in Western countries (including the USA) where adenocarcinoma currently represents more than 60% of esophageal malignancies, although, worldwide, SqCC continues to be the predominant histologic type. Integrated positron emission tomography (PET)/CT with 2-[fluorine18] fluro-2-deoxy-D-glucose (FDG) is used in many institutions routinely as a tool in the initial staging and then repeated after therapy for the assessment of response to neoadjuvant therapy and detection of recurrent disease in patients with esophageal carcinoma.

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Intra and Extra-Thoracic Muscle Flaps and Chest Wall Reconstruction following Resection of Thoracic Tumors

Improvements in surgical technique over the last decade enable surgeons to perform extensive resection and reconstruction in patients presenting with tumors involving the soft tissue and/or bony structures of the chest wall. The type of surgical resection and its size, depend on the type of tumor resected and its location. In addition to providing a better aesthetic result, the reconstruction restores support and functionality of the thoracic cage. The approach to chest wall repair includes primary closure or reconstruction by using transposition flaps, free flaps, prosthetic material, or a mixture of a flap and prosthetic material.

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Evaluation of the Neo-umbilicus Cutaneous Sensitivity Following Abdominoplasty

Abstract

Background

Abdominal cutaneous sensitivity loss after abdominoplasty is an undesirable outcome. However, little is known in the literature about sensitivity changes of the neo-umbilicus after abdominoplasty. The aim of this study was to evaluate post-abdominoplasty cutaneous sensitivity of the neo-umbilicus using clinical, quantitative, and reproducible methods.

Methods

Patients who underwent abdominoplasty were included, whereas the control group consisted of healthy volunteers with similar demographic characteristics but who did not undergo abdominoplasty. The umbilicus was divided into five zones, and superficial tactile sensitivity and spatial orientation were assessed subjectively (score 1–4) and objectively (Semmes–Weinstein monofilament examination).

Results

Twenty patients (45 ± 12 years) operated on consecutively between April 2012 and May 2016 and 14 healthy volunteers in the control group (39 ± 9 years) could be included. Although there were statistically significant differences (p = 0.0005) in the average cutaneous pressure thresholds between the control group (0.4 g/mm², range 0.07–2 g/mm²) and the study group (0.4 g/mm², range 0.07–4 g/mm²), patient satisfaction after a mean follow-up of 33 ± 16 months (range 10–62 months) was acceptable (mean satisfaction score 1.8 ± 0.7). Furthermore, spatial perceptions were precise in all patients and similar to the control group.

Conclusion

Our long-term results indicate that spontaneous reinnervation of the neo-umbilicus after abdominoplasty together with accurate spatial orientation can occur.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

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Madelung’s Disease: Is Insobriety the Chief Cause?

Abstract

Background

Madelung's disease (MD) is a rare disease of unknown etiology that is characterized by massive fatty deposits distributed in a symmetrical pattern mainly in the head, neck, and upper trunk. Here, we sought to explore the pathogeny and treatment of MD.

Methods

We enrolled ten patients who underwent surgical operations and one patient who refused an operation at our hospital between January 2009 and December 2016. We collected their medical histories and the preoperative and postoperative serological indices. The serum chemistry clinical outcomes were compared between the preoperative and postoperative states.

Results

The mean alcohol intake of the eleven patients exceeded 450 g daily. Ten patients underwent open excisions, and the other patient refused an operation. No significant differences were observed between the preoperative and postoperative serum chemistry results. No recurrence has yet been observed in any of the ten operated patients.

Conclusions

All of the patients in our study had associated alcoholism. Thus, insobriety might be one of the causes of MD. We believe that open operations may be an effective treatment based on the outcomes of the surgeries.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

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ICG-fluorescence imaging for detection of peritoneal metastases and residual tumoral scars in locally advanced ovarian cancer: A pilot study

Background and Objectives

No intraoperative imaging techniques exist for detecting tumor nodules or tumor scar tissues in patients treated with upfront or interval cytoreductive surgery (CS) after neoadjuvant chemotherapy (NAC). The aims of this study were to evaluate the role of indocyanine green (ICG) fluorescence imaging (FI) for the detection of peritoneal metastases (PM) and evaluate whether it can be used to detect remnant tumor cells in scar tissue.

Methods

Patients with PM from ovarian cancer admitted for CS were included. ICG, at 0.25 mg per kg of patient weight, was injected intraoperatively after explorative laparotomy before CS.

Results

A total of 108 peritoneal lesions, including 25 scars, were imaged in 20 patients. Seventy-three were malignant (67.6%) and 35 benign (32.4%). The mean Tumor to Background Ratio (ex vivo) was 1.8 (SD 1.3) in malignant and 1.0 (SD 0.79) in benign nodules (P = 0.007). Of 25 post-NAC scars, the mean Tumor to Background Ratio (TBR) (in vivo) was 2.06 (SD 1.15) in malignant and 1.21 (SD 0.50) in benign nodules (P = 0.26). The positive predictive value of ICG-FI to detect tumor cells in scars was 57.1%.

Conclusions

ICG-FI is accurate to demonstrate PM in ovarian cancer but unable to discriminate between benign and malignant post-NAC.

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Impact of lympho-vascular space invasion on tumor characteristics and survival outcome of women with low-grade serous ovarian carcinoma

Background and Objectives

To examine association of lympho-vascular space invasion (LVSI) with clinico-pathological factors and to evaluate survival of women with low-grade serous ovarian carcinoma containing areas of LVSI.

Methods

This is a multicenter retrospective study examining consecutive cases of surgically treated stage I-IV low-grade serous ovarian carcinoma (n = 178). Archived histopathology slides for the ovarian tumors were reviewed, and LVSI was scored as present or absent. LVSI status was correlated to clinico-pathological findings and survival outcome.

Results

LVSI was seen in 79 cases (44.4%, 95% confidence interval [CI] 37.1-51.7). LVSI was associated with increased risk of omental metastasis (87.0% vs 64.9%, odds ratio [OR] 3.62, P = 0.001), high pelvic lymph node ratio (median 12.9% vs 0%, P = 0.012), and malignant ascites (49.3% vs 32.6%, OR 2.01, P = 0.035). On multivariable analysis, controlling for age, stage, and cytoreductive status, presence of LVSI in the ovarian tumor remained an independent predictor for decreased progression-free survival (5-year rates 21.0% vs 35.7%, adjusted-hazard ratio 1.57, 95%CI 1.06-2.34, P = 0.026). LVSI was significantly associated with increased risk of recurrence in lymph nodes (OR 2.62, 95%CI 1.08-6.35, P = 0.047).

Conclusion

LVSI in the ovarian tumor is associated with adverse clinico-pathological characteristics and decreased progression-free survival in women with low-grade serous ovarian carcinoma.

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The utilization of round window membrane surface tension in facilitating slim electrodes insertion during cochlear implantation

Abstract

This is a prospective randomized study aimed to evaluate the round window membrane (RWM) surface tension in facilitating slim electrodes insertion during cochlear implantation. A total number of (118) children were included in this study (118 implantations). Mean age was 36.72 months (range from 18 to 60 months). This study was conducted from January 2015 to September 2016 at a cochlear implant centre in a tertiary referral hospital. Slit incision in the anterosuperior quadrant of the RWM was done in 70 cases, While RWM cruciate incision was done in 48 cases. Of the 48 patients who underwent RWM cruciate incision, 13 cases had no problem, while in 35 cases, we faced difficult insertion. When slit incision of the RWM was done (70 cases), 68 cases showed smooth insertion, meanwhile, we faced increased operative time due to flopping of the electrode in 2 cases only. Moreover, residual low-frequency hearing preservation was more achieved when slit incision of the RWM was done. Tensile strength of the round window membrane after slit incision of the RWM offers support to slim electrodes during introduction, decreasing incidence of kinking and floppiness, hence shortening the maneuver time and minimizing the number of trials. This facilitates easy smooth slim electrodes introduction, decreasing intracochlear trauma. Moreover, slit incision of the RWM may offer better residual hearing preservations than cruciate incision of the RWM during slim electrodes introduction.

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Evidence-based medicine in plastic surgery

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Effects of transcutaneous electrical stimulation on vocal folds adduction

Abstract

According to most previous studies, inducing movements in internal laryngeal muscles by transcutaneous electrical stimulation (TES) was impossible. However, the movements have been reported after using needle electrodes inserted into the internal superior laryngeal nerve (ISLN). Herein, we aimed to apply an innovative TES protocol to cause movements in vocal folds. A short duration and high frequency electrical current was applied by two surface electrodes just above the entrance of ISLN to larynx. The subjects were 32 normal participants (mean age = 23.87; SD = 3.43). During TES application, the vocal folds' movements were examined by flexible videonasolaryngoscopy. Statistical paired t test was used to analyze the differences of vocal folds opening angle, in degrees, during rest and TES periods. Furthermore, the movements were judged by seven experienced speech pathologists via a 9-point rate scale from −1 (any abduction) to 8 (complete adduction). The mean vocal folds adduction increased by 35.68° (t = 9.35, p > 0.001) due to TES application. The mean qualitative scores assigned by raters to each subject were between 6 and 7 points, which indicate an acceptable adduction in vocal folds through TES. Unlike previous studies, the applied TES protocol in this research induced significant vocal fold movements. This might be attributed to our different stimulation parameters, which were designed to penetrate deeply and stimulate ISLN specifically. It is worth noting that we introduced a novel TES protocol, which should be confirmed and then examined as a complementary therapy for neurologic voice disorders in future studies.

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‘Conservative’ approach to periocular necrotising fasciitis with paranasal sinus involvement

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Letter to the editor on “The therapeutic effect of thymoquinone on acoustic trauma-induced hearing loss in rats”

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Erratum to: Exercise induced laryngeal obstruction: a review of diagnosis and management

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Reply to the letter to the editor concerning: “The therapeutic effect of thymoquinone on acoustic trauma-induced hearing loss in rats”

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Safety of flexible endoscopic biopsy of the pharynx and larynx under topical anesthesia

Abstract

Recent advancements in transnasal endoscopy enable a shift in diagnostic workup of lesions in the pharynx and larynx, from an examination with biopsy under general anesthesia to an office-based examination with flexible endoscopic biopsy under topical anesthesia. Procedural complications were evaluated to assess the safety of office-based flexible endoscopic biopsy in patients with benign and malignant laryngopharyngeal lesions. Patients who underwent flexible endoscopic biopsy from 2012 to 2016 were evaluated retrospectively. Complications were classified using the Clavien–Dindo classification of surgical complications. A total of 201 flexible endoscopic biopsies were performed in 187 patients. Two Clavien–Dindo grade I (laryngospasm and anterior epistaxis), one grade II (laryngeal bleeding), and one grade IIIb (laryngeal edema) complication were observed. The first complication was self-limiting and the other three required an intervention. All patients fully recovered without sequelae. Flexible endoscopic biopsy appears to be a safe office-based procedure for the diagnosis of benign and malignant laryngopharyngeal lesions.

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Response to letter to the editor: “is drug induced sedation endoscopy surgical decision making process objective and systematic?”

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The clinical outcomes of using a new cross-linked hyaluronan gel in endoscopic frontal sinus surgery

Abstract

In endoscopic sinus surgery (ESS) synechiae formation and ostial stenosis are frequently encountered. This is not uncommon after frontal recess and ostium interventions due to the narrow recess and difficult anatomy of the region. The goal of this study is to evaluate the efficacy of the new cross-linked hyaluronan gel—PureRegen^® Gel Sinus—on wound healing and synechiae prevention in endoscopic frontal sinus surgery. The study consists of two groups of patients who underwent ESS, including frontal sinus surgery. In the study group of 37 patients, PureRegen^® Gel Sinus was applied to both the frontal recess and ostium at the end of the procedure. The control group consisted of 28 patients. In this group, nasal dressing material was not applied at the end of surgery—neither to the frontal recess nor to the ostium. Postoperatively, epithelization was found to be significantly better at 2 and 4 weeks in the study group when compared with the findings in patients where no postoperative dressing was applied. In the eighth week, there was no significant difference found between the two groups in terms of epithelization. Synechiae formation was significantly lower in the PureRegen^® Gel Sinus group than the control group at all 2, 4 and 8 weeks postoperative evaluations. The effects of PureRegen^® Gel Sinus on wound healing, especially in reepithelization, have shown to occur earlier in the postoperative period. Rapid reepithelization and control of infection related granulation tissue formation with antibiotics in the early postoperative period may explain the low stenosis rate in frontal sinus ostia in PureRegen^® Gel Sinus applied patients.

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Comparing the outcome of tympanoplasties using bovine pericardium underlay xenografts versus butterfly inlay autografts

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Butterfly cartilage tympanoplasty: an alternative new technique instead of conventional surgery method

Abstract

Butterfly graft inlay tympanoplasty is a well-established technique for the repair of small- and medium-sized perforations. There are some difficulties with application of conventional butterfly technique and it affects our success rate of graft healing. With some modifications of graft preparation we can make better success rates. The aim of this study was to present the new renovation of conventional method, describe about what kind of changes we made and its technical facilities about the procedure. The study design is a prospective case series. This study was carried out on 18 patients who underwent inlay butterfly cartilage tympanoplasty with the new technique for anterior and inferior perforations at an otolaryngology department of a tertiary medical center between November 2015 and August 2016. Patients were followed with otoscopy and audiometry, and graft healing's success. Anatomic closure at 6th month after tympanoplasty was found in all 18 patients. There was no incidence of cartilage graft rejection or displacement. Preoperative mean PTA was 27.7 dB, which improved 6 months after surgery to 10.5 dB (the average value of hearing thresholds at 0.5, 1, 2 and 4 kHz). Butterfly cartilage tympanoplasty technique is safe and efficient in terms of both anatomical closure of the defect and improvement in hearing. We believe with this new technique, we facilitate this procedure in addition to the improvement of patients' comfort and decrease the morbidity of the procedure.

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The utilization of round window membrane surface tension in facilitating slim electrodes insertion during cochlear implantation

Abstract

This is a prospective randomized study aimed to evaluate the round window membrane (RWM) surface tension in facilitating slim electrodes insertion during cochlear implantation. A total number of (118) children were included in this study (118 implantations). Mean age was 36.72 months (range from 18 to 60 months). This study was conducted from January 2015 to September 2016 at a cochlear implant centre in a tertiary referral hospital. Slit incision in the anterosuperior quadrant of the RWM was done in 70 cases, While RWM cruciate incision was done in 48 cases. Of the 48 patients who underwent RWM cruciate incision, 13 cases had no problem, while in 35 cases, we faced difficult insertion. When slit incision of the RWM was done (70 cases), 68 cases showed smooth insertion, meanwhile, we faced increased operative time due to flopping of the electrode in 2 cases only. Moreover, residual low-frequency hearing preservation was more achieved when slit incision of the RWM was done. Tensile strength of the round window membrane after slit incision of the RWM offers support to slim electrodes during introduction, decreasing incidence of kinking and floppiness, hence shortening the maneuver time and minimizing the number of trials. This facilitates easy smooth slim electrodes introduction, decreasing intracochlear trauma. Moreover, slit incision of the RWM may offer better residual hearing preservations than cruciate incision of the RWM during slim electrodes introduction.

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Evidence-based medicine in plastic surgery

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2fqYlVx

Effects of transcutaneous electrical stimulation on vocal folds adduction

Abstract

According to most previous studies, inducing movements in internal laryngeal muscles by transcutaneous electrical stimulation (TES) was impossible. However, the movements have been reported after using needle electrodes inserted into the internal superior laryngeal nerve (ISLN). Herein, we aimed to apply an innovative TES protocol to cause movements in vocal folds. A short duration and high frequency electrical current was applied by two surface electrodes just above the entrance of ISLN to larynx. The subjects were 32 normal participants (mean age = 23.87; SD = 3.43). During TES application, the vocal folds' movements were examined by flexible videonasolaryngoscopy. Statistical paired t test was used to analyze the differences of vocal folds opening angle, in degrees, during rest and TES periods. Furthermore, the movements were judged by seven experienced speech pathologists via a 9-point rate scale from −1 (any abduction) to 8 (complete adduction). The mean vocal folds adduction increased by 35.68° (t = 9.35, p > 0.001) due to TES application. The mean qualitative scores assigned by raters to each subject were between 6 and 7 points, which indicate an acceptable adduction in vocal folds through TES. Unlike previous studies, the applied TES protocol in this research induced significant vocal fold movements. This might be attributed to our different stimulation parameters, which were designed to penetrate deeply and stimulate ISLN specifically. It is worth noting that we introduced a novel TES protocol, which should be confirmed and then examined as a complementary therapy for neurologic voice disorders in future studies.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hIcej5

‘Conservative’ approach to periocular necrotising fasciitis with paranasal sinus involvement

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2fr2UPH

Letter to the editor on “The therapeutic effect of thymoquinone on acoustic trauma-induced hearing loss in rats”

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hH0mxv

Erratum to: Exercise induced laryngeal obstruction: a review of diagnosis and management

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2fr0yjT

Reply to the letter to the editor concerning: “The therapeutic effect of thymoquinone on acoustic trauma-induced hearing loss in rats”

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hIcrCR

Safety of flexible endoscopic biopsy of the pharynx and larynx under topical anesthesia

Abstract

Recent advancements in transnasal endoscopy enable a shift in diagnostic workup of lesions in the pharynx and larynx, from an examination with biopsy under general anesthesia to an office-based examination with flexible endoscopic biopsy under topical anesthesia. Procedural complications were evaluated to assess the safety of office-based flexible endoscopic biopsy in patients with benign and malignant laryngopharyngeal lesions. Patients who underwent flexible endoscopic biopsy from 2012 to 2016 were evaluated retrospectively. Complications were classified using the Clavien–Dindo classification of surgical complications. A total of 201 flexible endoscopic biopsies were performed in 187 patients. Two Clavien–Dindo grade I (laryngospasm and anterior epistaxis), one grade II (laryngeal bleeding), and one grade IIIb (laryngeal edema) complication were observed. The first complication was self-limiting and the other three required an intervention. All patients fully recovered without sequelae. Flexible endoscopic biopsy appears to be a safe office-based procedure for the diagnosis of benign and malignant laryngopharyngeal lesions.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2frbUob

Response to letter to the editor: “is drug induced sedation endoscopy surgical decision making process objective and systematic?”

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hI46Py

The clinical outcomes of using a new cross-linked hyaluronan gel in endoscopic frontal sinus surgery

Abstract

In endoscopic sinus surgery (ESS) synechiae formation and ostial stenosis are frequently encountered. This is not uncommon after frontal recess and ostium interventions due to the narrow recess and difficult anatomy of the region. The goal of this study is to evaluate the efficacy of the new cross-linked hyaluronan gel—PureRegen^® Gel Sinus—on wound healing and synechiae prevention in endoscopic frontal sinus surgery. The study consists of two groups of patients who underwent ESS, including frontal sinus surgery. In the study group of 37 patients, PureRegen^® Gel Sinus was applied to both the frontal recess and ostium at the end of the procedure. The control group consisted of 28 patients. In this group, nasal dressing material was not applied at the end of surgery—neither to the frontal recess nor to the ostium. Postoperatively, epithelization was found to be significantly better at 2 and 4 weeks in the study group when compared with the findings in patients where no postoperative dressing was applied. In the eighth week, there was no significant difference found between the two groups in terms of epithelization. Synechiae formation was significantly lower in the PureRegen^® Gel Sinus group than the control group at all 2, 4 and 8 weeks postoperative evaluations. The effects of PureRegen^® Gel Sinus on wound healing, especially in reepithelization, have shown to occur earlier in the postoperative period. Rapid reepithelization and control of infection related granulation tissue formation with antibiotics in the early postoperative period may explain the low stenosis rate in frontal sinus ostia in PureRegen^® Gel Sinus applied patients.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2fqY84H

Comparing the outcome of tympanoplasties using bovine pericardium underlay xenografts versus butterfly inlay autografts

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hHbP0b

Butterfly cartilage tympanoplasty: an alternative new technique instead of conventional surgery method

Abstract

Butterfly graft inlay tympanoplasty is a well-established technique for the repair of small- and medium-sized perforations. There are some difficulties with application of conventional butterfly technique and it affects our success rate of graft healing. With some modifications of graft preparation we can make better success rates. The aim of this study was to present the new renovation of conventional method, describe about what kind of changes we made and its technical facilities about the procedure. The study design is a prospective case series. This study was carried out on 18 patients who underwent inlay butterfly cartilage tympanoplasty with the new technique for anterior and inferior perforations at an otolaryngology department of a tertiary medical center between November 2015 and August 2016. Patients were followed with otoscopy and audiometry, and graft healing's success. Anatomic closure at 6th month after tympanoplasty was found in all 18 patients. There was no incidence of cartilage graft rejection or displacement. Preoperative mean PTA was 27.7 dB, which improved 6 months after surgery to 10.5 dB (the average value of hearing thresholds at 0.5, 1, 2 and 4 kHz). Butterfly cartilage tympanoplasty technique is safe and efficient in terms of both anatomical closure of the defect and improvement in hearing. We believe with this new technique, we facilitate this procedure in addition to the improvement of patients' comfort and decrease the morbidity of the procedure.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2fqdsyo