Upfront surgery versus definitive chemoradiotherapy in patients with human Papillomavirus-associated oropharyngeal squamous cell cancer

Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Jacqueline R. Kelly, Henry S. Park, Yi An, Wendell G. Yarbrough, Joseph N. Contessa, Roy Decker, Saral Mehra, Benjamin L. Judson, Barbara Burtness, Zain Husain
ObjectivesCurrently, human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV-A OPC) is managed with either primary surgery or definitive chemoradiotherapy (CRT), despite the lack of supporting randomized prospective data. We therefore assessed the outcomes of each treatment strategy using the National Cancer Database (NCDB).MethodsThe NCDB was used to identify patients diagnosed with cT1 N2a-2b or cT2 N1-2b HPV-A OPC from 2010 to 2013 who underwent treatment with primary surgery or CRT. Demographic and clinicopathologic predictors of treatment were analyzed by the chi-square test and logistic regression. Overall survival (OS) was evaluated using multivariable Cox proportional hazard regression, Kaplan-Meier, log-rank test, and propensity score-matched analysis.ResultsWe identified 3063 patients; 1576 (51.5%) received CRT and 1487 (48.5%) underwent primary surgery. Median follow up was 32 months. 972 (65.4%) surgical patients received adjuvant CRT. On multivariable Cox regression, 3-year OS was comparable between surgery and CRT (hazard ratio [HR] 1.08, 95% confidence interval [CI] 0.83–1.41, P = 0.58). Inferior OS was significantly associated with increasing clinical T and N stage, older age, and non-private insurance. Propensity score-matching yielded a 2526 patient cohort and redemonstrated similar OS (HR, 1.09; 95% CI 0.81–1.47; P = 0.55). Comparable outcomes persisted in a subset analysis of patients with margin-negative resection, with 3-year OS 90.8% in CRT patients vs. 93.6% in surgery patients (log-rank P = 0.27).ConclusionsUpfront surgery and CRT yielded comparable 3-year OS outcomes in this cohort. In this national sample, 65.4% of surgical patients received trimodal therapy with adjuvant CRT, highlighting the need for improved patient selection for primary surgery.



http://ift.tt/2oUsluK

Chemoradiotherapy using retrograde superselective intra-arterial infusion for tongue cancer: Analysis of therapeutic results in 118 cases

Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Kenji Mitsudo, Yuichiro Hayashi, Shuhei Minamiyama, Nobuhide Ohashi, Masaki Iida, Toshinori Iwai, Senri Oguri, Toshiyuki Koizumi, Mitomu Kioi, Makoto Hirota, Izumi Koike, Masaharu Hata, Iwai Tohnai
ObjectivesTo evaluate the therapeutic results and rate of organ preservation in patients with squamous cell carcinoma of the tongue treated with retrograde superselective intra-arterial chemoradiotherapy.Materials and methodsBetween June 2006 and June 2015, 118 patients with tongue cancer were treated with intra-arterial chemoradiotherapy. Treatment consisted of radiotherapy (total 50–70 Gy) and daily concurrent intra-arterial chemotherapy (docetaxel, total 50–70 mg/m²; cisplatin, total 125–175 mg/m²) for 5–7 weeks. Locoregional control and overall survival rates were calculated by the Kaplan-Meier method. Cox's proportional hazards model was used for both univariate and multivariate analyses.ResultsThe median follow-up for all patients was 38.5 months (range, 3–129 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 113 (95.8%) of 118 cases. Three-year locoregional control and overall survival rates were 80.3% and 81.5%, respectively. Grade 3 or 4 toxicities included neutropenia in 16.1% and mucositis in 87.3%. Grade 3 toxicities included anemia in 12.7%, thrombocytopenia in 3.4%, nausea/vomiting in 3.4%, dermatitis in 45.7%, dysphagia in 74.6%, and fever in 2.5% of patients. Late toxicity consisting of grade 3 osteoradionecrosis of the jaw occurred in 4.2% of patients. On univariate analysis, T stage and overall stage were significantly associated with locoregional control, and N stage and overall stage were significantly associated with overall survival. On multivariate analysis, the only significant predictor of overall survival was overall stage classification.ConclusionRetrograde superselective intra-arterial chemoradiotherapy for tongue cancer provided good overall survival and locoregional control.



http://ift.tt/2HjtEdv

An internally validated prognostic model for success in revision stapes surgery for otosclerosis

Objectives/Hypothesis

To develop a prediction model that can accurately predict the chance of success following revision stapes surgery in patients with recurrent or persistent otosclerosis at 2- to 6-months follow-up and to validate this model internally.

Study Design

A retrospective cohort study of prospectively gathered data in a tertiary referral center.

Methods

The associations of 11 prognostic factors with treatment success were tested in 705 cases using multivariable logistic regression analysis with backward selection. Success was defined as a mean air-bone gap closure to 10 dB or less. The most relevant predictors were used to derive a clinical prediction rule to determine the probability of success. Internal validation by means of bootstrapping was performed. Model performance indices, including the Hosmer-Lemeshow test, the area under the receiver operating characteristics curve (AUC), and the explained variance were calculated.

Results

Success was achieved in 57.7% of cases at 2- to 6-months follow-up. Certain previous surgical techniques, primary causes of failure leading up to revision stapes surgery, and positions of the prosthesis placed during revision surgery were associated with higher success percentages. The clinical prediction rule performed moderately well in the original dataset (Hosmer-Lemeshow P = .78; AUC = 0.73; explained variance = 22%), which slightly decreased following internal validation by means of bootstrapping (AUC = 0.69; explained variance = 13%).

Conclusions

Our study established the importance of previous surgical technique, primary cause of failure, and type of the prosthesis placed during the revision surgery in predicting the probability of success following stapes surgery at 2- to 6-months follow-up.

Level of Evidence

2b. Laryngoscope, 2018

http://ift.tt/2G8znU5

Complex Association Patterns for Inflammatory Mediators in Induced Sputum from Subjects with Asthma

Abstract

Background

The release of various inflammatory mediators into the bronchial lumen is thought to reflect both the type and degree of airway inflammation, eosinophilic Th2, and Th9, or neutrophilic Th1, and Th17, in patients with asthma.

Aims

We investigated whether cytokines and chemokines differed in sputum from subjects with more severe compared with milder asthma, and if unbiased factor analysis of cytokine and chemokine groupings indicates specific inflammatory pathways.

Methods

Cell-free supernatants from induced sputum were obtained from subjects with a broad range of asthma severity (n=158) and assessed using Milliplex^® Cytokines/Chemokine kits I, II, and III, measuring 75 individual proteins. Each cytokine, chemokine, or growth factor concentration was examined for differences between asthma severity groups, for association with leukocyte counts, and by factor analysis.

Results

Severe asthma subjects had 9 increased and 4 decreased proteins compared to mild asthma subjects and fewer differences compared to moderate asthma. Twenty-six mediators were significantly associated with an increasing single leukocyte type: 16 with neutrophils (3 interleukins [IL], 3 CC-chemokines, 4 CXC-chemokines, 4 growth factors, TNF-α, and CX3CL1/Fractalkine); 5 with lymphocytes (IL-7, IL-16, IL-23, IFN-α2 and CCL4/MIP1β); IL-15 and CCL15/MIP1δ with macrophages; IL-5 with eosinophils; and IL-4 and TNFSF10/TRAIL with airway epithelial cells. Factor analysis grouped 43 cytokines, chemokines and growth factors which had no missing data onto the first 10 factors, containing mixes of Th1, Th2, Th9 and Th17 inflammatory and anti-inflammatory proteins.

Conclusions

Sputum cytokines, chemokines and growth factors were increased in severe asthma, primarily with increased neutrophils. Factor analysis identified complex inflammatory protein interactions, suggesting airway inflammation in asthma is characterized by overlapping immune pathways. Thus, focus on a single specific inflammatory mediator or pathway may limit understanding the complexity of inflammation underlying airway changes in asthma and selection of appropriate therapy.

This article is protected by copyright. All rights reserved.

http://ift.tt/2oVyzdZ

Systemic nocardiosis in a lepromatous leprosy patient with type 2 reaction

http://ift.tt/2FvuovP

The histologic detection of Helicobacter pylori in seropositive subjects is affected by pathology and secretory ability of the stomach

Abstract

Background

Helicobacter pylori is unevenly distributed in hypochlorhydric environments. The study aim was to elucidate the risk factors for a negative Giemsa staining finding in seropositive subjects by measuring the secretory ability of the stomach.

Methods

Subjects aged over 18 years were included consecutively after endoscopic biopsy at gastric lesions with color or structural changes. Blood was sampled for the serum pepsinogen (PG) assay and H. pylori serology test. After excluding the subjects with past H. pylori eradication, the risk factors for a negative Giemsa staining finding in seropositive subjects were analyzed.

Results

Among 872 included subjects, a discrepancy between the serum anti-H. pylori IgG and Giemsa staining findings was found in 158 (18.1%) subjects, including 145 Giemsa-negative, seropositive subjects. Gastric adenocarcinoma/adenoma (OR = 11.090, 95% CI = 3.490-35.236) and low serum PG II level (OR = 0.931, 95% CI = 0.899-0.963) were the independent risk factors for a negative Giemsa staining finding in seropositive subjects. The cutoff value of serum PG II level was 7.45 ng/mL (area under curve [AUC] = 0.904, 95% CI = 0.881-0.927). Follow-up studies of Giemsa staining at different sites of the stomach revealed that 75% of the Giemsa-negative seropositive subjects with adenocarcinoma are positive, whereas none of those with low serum PG II level of <7.45 ng/mL revealed positive findings.

Conclusions

The risk of a negative Giemsa staining finding in seropositive subjects is increased in gastric adenocarcinoma/adenoma specimens and in subjects with a diminished gastric secretory ability with low serum PG II level of <7.45 ng/mL. A false-negative Giemsa staining finding is common in subjects with adenocarcinoma, and therefore, additional biopsies at different sites should be performed in these subjects.

http://ift.tt/2HjHr40

Beneficial effect of Burdock complex on asymptomatic Helicobacter pylori-infected subjects: A randomized, double-blind placebo-controlled clinical trial

Abstract

Background

Burdock complex (BC) constitutes of burdock (Arctium lappa), angelica (Angelica sinensis), gromwell (Lithospermum erythrorhizon), and sesame (Sesamum indicum) oil, which are commonly used in traditional Chinese medicine (TCM) for treating various disorders. This study intended to examine the anti-H. pylori activity of BC on AGS cell model as well as in asymptomatic H. pylori-infected subjects.

Materials and Methods

AGS cell incubated with H. pylori and treated with BC to evaluate the minimum inhibition concentration (MIC), cell viability (MTT) anti-adhesion activity, and inflammatory markers. In case of clinical trial, H. pylori-positive subjects (urea breath test [UBT] >10%, n = 36) were enrolled and requested to intake BC (n = 19) or placebo (n = 17) for 8 weeks. Antioxidant capacity, total phenol, UBT, inflammatory markers were analyzed at the initial, 4th, 8th, and 10th weeks. Moreover, the endoscopic examination was carried out on baseline and 10th week.

Results

In vitro studies showed that BC treatment significantly inhibited (P < .05) the inflammatory markers and adhesion of H. pylori to AGS cell. However, H. pylori-infected subject ingested with BC for 8 weeks significantly decreased (P < .05) the UBT value, inflammatory markers with improved antioxidant activity, and phenolic levels as compared to placebo. Also, consumption of BC considerably healed the ulcer wound.

Conclusion

Overall, the BC could attenuate H. pylori infection by inhibiting H. pylori adhesion and subsequent inflammatory response on the gastric epithelial cell (AGS) as well as clinically ameliorated UBT, antioxidant capacity, and alleviated inflammation to display its anti-H. pylori activity.

http://ift.tt/2FAwKwG

Counterfeit esthetic devices and patient safety in dermatology

Summary

This study addresses the dilemma concerned with meeting patients who may have encountered counterfeit esthetic devices in the marketplace. Over the past several years, we have witnessed a rise in counterfeit injectables and medical devices in our field. Often times, the procedures are marketed to patients at significantly reduced prices compared to competitors. Patients may be unaware that counterfeit devices exist and may unknowingly have procedures completed using untested and uncertified devices. It is important for clinicians to recognize when their patients may be encountering counterfeit devices, know what to do in this situation, and offer the best recommendations.

http://ift.tt/2oVeqVn

Association between bilateral segmental vitiligo and lichen striatus: an expression of mosaicism?

http://ift.tt/2FrNFy4

45th Annual Meeting of the Arbeitsgemeinschaft Dermatologische Forschung (ADF) Zurich, Switzerland, March 7-10, 2018

http://ift.tt/2oYRHa4

Clinical Snippets

http://ift.tt/2FB0EB4

Beyond the physico-chemical barrier: Glycerol and xylitol markedly yet differentially alter gene expression profiles and modify signalling pathways in human epidermal keratinocytes

Abstract

Polyols (e.g. glycerol, xylitol) are implicated as moisturizers of the skin and other epithelial tissues. However, we lack information about their exact cellular mechanisms and their effects on the gene expression profiles. Therefore, in this study, we aimed at investigating the effects of glycerol and xylitol on human epidermal keratinocytes. The polyols (identical osmolarities; xylitol: 0.0045%-0.45%; glycerol: 0.0027%-0.27%) did not alter cellular viability or intracellular calcium concentration. However, they exerted differential effects on the expression of certain genes and signalling pathways. Indeed, both polyols up-regulated the expression of filaggrin, loricrin, involucrin and occludin; yet, xylitol exerted somewhat more profound effects. Moreover, while both polyols stimulated the MAPK pathway, only xylitol induced the activation-dependent translocation of protein kinase Cδ, a key promoter of epidermal differentiation. Finally, in various keratinocyte inflammation models, both polyols (albeit with different efficacies) exerted anti-inflammatory effects. Taken together, these data strongly suggest that glycerol and xylitol differentially modulate expressions of multiple genes and activities of signalling pathways in epidermal keratinocytes. Thus, our findings invite clinical trials to explore the applicability and the impact of a combined glycerol-xylitol therapy in the management of various skin conditions.

http://ift.tt/2oYRy6w

Issue Information

http://ift.tt/2FCZ0ic

A case of CD8+ and CD56+ cytotoxic variant of poikilodermatous mycosis fungoides: Dermoscopic features of reticular pigmentation and vascular structures

http://ift.tt/2oXBrHe

A novel IKBKG mutation in a patient with incontinentia pigmenti and features of hepatic ciliopathy

Abstract

We describe a new mutation in exon 4 of IKBKG, encoding nuclear factor-kappa B in a patient with incontinentia pigmenti. The patient had a severe cholestatic liver disease with features of a ciliopathy and underwent liver transplantation. We cannot establish a link between incontinentia pigmenti, a very rare disease, and hepatic ciliopathy, but we suggest that hepatic evaluation should be considered in patients with incontinentia pigmenti.

http://ift.tt/2tvTVTW

Valoración de la reacción emocional provocada por la prueba vestibular calórica mediante monitorización de variables fisiológicas

Publication date: Available online 8 March 2018
Source:Acta Otorrinolaringológica Española
Author(s): Rafael Barona-de-Guzmán, Claudio Krstulovic-Roa, Elena Donderis-Malea, Luz Barona-Lleó
Introducción y objetivosLa valoración emocional que provoca el vértigo se realiza mediante la historia clínica y diversos cuestionarios subjetivos. El objetivo del presente trabajo es valorar la respuesta emocional de forma objetiva, en sujetos normales, durante la crisis de vértigo inducida.Material y métodoSe realizó la prueba vestibular calórica con agua fría en 30 sujetos sanos. Durante los 60s previos a la estimulación y los 60s posteriores a la misma se monitorizaron las siguientes variables fisiológicas: Conductabilidad cutánea, Volumen de pulso periférico, Temperatura corporal, Contracción muscular, Frecuencia cardiaca y Frecuencia respiratoria. Se valoró la velocidad angular máxima de la fase lenta del nistagmo provocado en cada estimulación.ResultadosDurante las crisis de vértigo, la conductabilidad cutánea presentó un aumento estadísticamente significativo con relación al periodo previo a las mismas, mientras que el volumen de pulso periférico presentó una disminución estadísticamente significativa. No hubo relación entre la velocidad angular de la fase lenta del nistagmo provocado y los cambios de la conductabilidad y el volumen de pulso periférico. La disminución provocada en el volumen de pulso periférico fue significativamente mayor en la segunda crisis de vértigo.ConclusionesLa conductabilidad cutánea y el volumen de pulso periférico cambiaron de forma significativa durante las crisis de vértigo. No Hubo relación entre la intensidad de la crisis vertiginosa provocada y los cambios producidos en estas variables. El estrés generado por la estimulación calórica es mayor en la segunda crisis, cuando el sujeto tiene experiencia del vértigo que provoca la estimulación.Introduction and objectivesThe emotional evaluation of the causes of vertigo is made using the clinical records and several subjective questionnaires. The aim of the present study is to evaluate the emotional response objectively, in normal subjects, during an induced vertigo crisis.Material and methodA caloric vestibular test with cold water was performed on 30 healthy subjects. The following physiological parameters were monitored during the 60seconds prior to and the 60seconds after the stimulation: Skin Conductivity, Peripheral Pulse Volume, Body Temperature, Muscle Contraction, Heart Rate, and Respiratory Rate. The maximum angular speed of the nystagmus slow phase at each stimulation was assessed.ResultsSkin conductance presented a statistically significant increase during the vertigo crisis in relation to the prior period while the peripheral pulse volume presented a statistically significant decrease. There was no relationship between the slow phase of the provoked nystagmus angular speed and skin conductance and peripheral pulse volume changes. The decrease in peripheral pulse volume was significantly higher in the second vertigo crisis.ConclusionsSkin conductance and peripheral pulse volume changed significantly during a vertigo crisis. There was no relation between the provoked vertiginous crisis intensity and the changes produced in those variables. The stress generated by the caloric stimulation is higher in the second crisis, when the subject has experience of the vertigo caused by the stimulation.



http://ift.tt/2p0SRlu

Home particle repositioning maneuver to prevent the recurrence of posterior canal BPPV

To check the value of home particle repositioning maneuver in the prevention of the recurrence of posterior canal benign paroxysmal positional vertigo (pc-BPPV).

http://ift.tt/2Dbf6u8

Home particle repositioning maneuver to prevent the recurrence of posterior canal BPPV

Publication date: Available online 8 March 2018
Source:Auris Nasus Larynx
Author(s): Elshahat Ibrahem Ismail, Ashraf Elsayed Morgan, Mohamed Moustafa Abdeltawwab
ObjectiveTo check the value of home particle repositioning maneuver in the prevention of the recurrence of posterior canal benign paroxysmal positional vertigo (pc-BPPV).MethodsIn this study, patients diagnosed as unilateral posterior canal BPPV were selected following an accurate evaluation using video goggle VNG system. All patients were managed by particle repositioning maneuver (PRM). Patients were instructed to do home PRM once weekly for five years. Then, they were divided into two groups (according to choice of patient to do PRM). The first group (control group) consisted of 144 patients who did not do home PRM; whereas the second group (study group) included 165 patients who performed home PRM. All patients (control & study groups) were followed up every four months for five years.ResultsThe study found out that the recurrence rate of pc-BPPV in control group was 33 patients in the first year (27.2%), 11 patients in second year (9%), 5 patients in third year (4%), 3 patients in fourth year (2.5%) and 3 patients in fifth year (2.5%). The recurrence of pc-BPPV in the treated side (study group) of patients was reported as 5 patients in the first year (3.5%), 3 patients in the second year (2%), 2 patients in the third year (1.4%), 2 patients in the fourth year (1.4%), and 1 patient in the fifth year (0.7%). There was statistically significant difference between the control and the study groups regarding the recurrence rates in the first year follow up which was the highest in first four months.ConclusionHome particle repositioning maneuver has the capacity to prevent the recurrence of pc-BPPV. It proved to be more successful and functional in minimizing the recurrence of the disease in the study than in the control group. Hence, home particle repositioning maneuver is highly recommended for one year at least in pc-BPPV.



http://ift.tt/2oTxvaC

Adjusted calculation model of heparin management during cardiopulmonary bypass in obese patients: A randomised controlled trial

BACKGROUND Anticoagulation during cardiopulmonary bypass (CPB) is usually adapted to total body weight (TBW). This may be inaccurate in obese patients and lead to heparin overdose with a risk of bleeding. OBJECTIVES To validate the efficacy and safety of an adjusted calculation model of heparin dosing based on ideal body weight (IBW) rather than TBW in obese CPB patients, with an expected target mean plasma heparin concentration of 4.5 IU ml−1 after onset of CPB in the experimental group. DESIGN Prospective, randomised controlled study. SETTING University hospital. PATIENTS Sixty obese patients (BMI ≥ 30 kg m−2) scheduled for CPB were included from January to June 2016. INTERVENTIONS Patients received a bolus dose of unfractionated heparin of either 300 IU kg−1 of TBW or 340 IU kg−1 of IBW before onset of CPB. Additional adjusted boluses were injected to maintain an activated clotting time (ACT) of at least 400 s. MAIN OUTCOME MEASURES Plasma heparin concentration and ACT were measured at different time points. Total heparin doses and transfusion requirements were recorded. RESULTS The target heparin concentration of 4.5 IU ml−1 was reached in the IBW group at the onset of CPB and maintained at all time points during CPB. Heparin concentrations were significantly higher in the TBW group after the bolus (6.52 ± 0.97 vs. 4.54 ± 1.13 IU ml−1, P 

http://ift.tt/2HhVhno

Spinal anaesthesia with chloroprocaine 1% versus total intravenous anaesthesia for outpatient knee arthroscopy: A randomised controlled trial

BACKGROUND Both general and spinal anaesthesia with short-acting local anaesthetics are suitable and reliable for knee arthroscopy as an ambulatory procedure. Chloroprocaine (CP) 1% seems to be the ideal spinal local anaesthetic for this indication. OBJECTIVE The aim of this study was to compare spinal anaesthesia using CP 1% with general for outpatient knee arthroscopy with regard to procedure times, occurrence of pain, patient satisfaction and recovery, and also costs. DESIGN A randomised controlled single-centre trial. SETTING University Medical Centre Mannheim, Department of Anaesthesiology and Surgical Intensive Care Medicine, Mannheim, Germany. April 2014 to August 2015. PATIENTS A total of 50 patients (women/men, 18 to 80 years old, ASA I to III) undergoing outpatient knee arthroscopy were included. A contra-indication to an allocated anaesthetic technique or an allergy to medication required in the protocol led to exclusion. INTERVENTIONS Either general anaesthesia with sufentanil, propofol and a laryngeal mask for airway-management or spinal with 40-mg CP 1% were used. We noted procedure times, patient satisfaction/recovery and conducted a 7-day follow-up. MAIN OUTOMES Primary outcome was duration of stay in the day-surgery centre. Secondary outcomes were first occurrence of pain, patient satisfaction, quality of recovery and adverse effects. In addition, we analysed treatment costs. RESULTS Spinal had faster recovery than general anaesthesia with patients reaching discharge criteria significantly earlier [117 min (66 to 167) versus 142 min (82 to 228), P = 0.0047]. Pain occurred significantly earlier in the general anaesthesia group (P = 0.0072). Costs were less with spinal anaesthesia (cost ratio spinal: general 0.57). Patients felt significantly more uncomfortable after general anaesthesia (P = 0.0096). CONCLUSION Spinal anaesthesia with 40-mg CP 1% leads to a significantly earlier discharge and is cheaper compared with general. TRIAL REGISTRATION German Clinical Trials Register, www.drks.de, identifier: DRKS00005989. Correspondence to Prof. Dr. med. Marc D. Schmittner, Head, Department of Anaesthesiology, Intensive Care and Pain Medicine, BG Klinikum Unfallkrankenhaus Berlin gGmbH, Warener Str. 7, 12683 Berlin, Germany Tel: +49 (0) 30 56 81 3100; fax: +49 (0) 30 56 81 3103; e-mail: marc.schmittner@ukb.de © 2018 European Society of Anaesthesiology

http://ift.tt/2FyuExn

Cancer immunotherapy in patients with brain metastases

Abstract

The exclusion of "real-world" patients from registration clinical trials of cancer immunotherapy represents a significant emerging issue. For instance, a large fraction of cancer patients develops brain metastases during the course of the disease, but results from large prospective clinical trials investigating this considerable proportion of the cancer patient population are currently lacking. To provide a useful tool for the clinician in a "real-world" setting, we have reviewed the available literature regarding the safety and efficacy of immune check-point inhibitors in patients with cancer metastatic to the brain. Overall, these data provide encouraging evidence that these therapeutic agents can induce intracranial objective responses, particularly in patients with asymptomatic and previously untreated brain metastases. Larger prospective studies are needed to confirm these initial results.

http://ift.tt/2DcPA7F

Advances in the Approach to the Patient with Food Allergy

Publication date: Available online 8 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Amy M. Scurlock, Stacie M. Jones
Advances in food allergy diagnosis, management, prevention and therapeutic interventions have been significant over the past two decades. Evidence based national and international guidelines have streamlined food allergy diagnosis and management, while paradigm shifting work in primary prevention of peanut allergy has resulted in significant modifications in the approach to early food introduction in infants and toddlers. Innovative investigation of food allergy epidemiology, systems biology, impact, and management has provided important insights. While active therapeutic approaches to food allergy presently remain experimental, progress toward licensed therapies has been substantial. Mechanistic understanding of the immunologic processes underlying food allergy and immunotherapy will inform the future design of therapeutic approaches targeting the food allergic response. Global strategies to mitigate the substantial medical, economic, and psychosocial burden of food allergy in affected individuals and families will require engagement of stakeholders across multiple sectors in research, healthcare, public health, government, educational institutions and industry. However, the relationship between the well-informed allergy care provider and the patient and family remains fundamental for optimizing the care of the patient with food allergy.



http://ift.tt/2I9BTu2

Refractory Airway Type-2 Inflammation in a Large Subgroup of Asthmatics treated with Inhaled Corticosteroids

Publication date: Available online 7 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Michael C. Peters, Sheena Kerr, Eleanor M. Dunican, Prescott G. Woodruff, Merritt L. Fajt, Bruce D. Levy, Elliot Israel, Brenda R. Phillips, David T. Mauger, Suzy A. Comhair, Serpil C. Erzurum, Mats W. Johansson, Nizar N. Jarjour, Andrea M. Coverstone, Mario Castro, Annette T. Hastie, Eugene R. Bleecker, Sally E. Wenzel, John V. Fahy
BackgroundAirway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients on high dose inhaled corticosteroids (ICS) is uncertain.ObjectiveTo determine if airway type 2 inflammation persists in patients treated with ICS and to evaluate the clinical features of patients with steroid resistant airway type-2 inflammation.MethodsWe used qPCR to generate a composite metric of type-2 cytokine gene expression (type 2 Gene Mean, "T2GM") in induced sputum cells from healthy controls, severe asthma patients on ICS (n=174), and non-severe asthma patients on ICS (n=85). We explored relationships between asthma outcomes and the T2GM, and the utility of non-invasive biomarkers of the airway T2GM.ResultsThe sputum cell T2GM in asthma subjects was significantly increased in asthma subjects and remained high following treatment with intramuscular triamcinolone. We used the median value for the T2GM as a cutoff to classify "steroid-treated type 2-low" (stT2-low) and "steroid-resistant type 2-high" (srT2-high) subgroups. Compared to patients with stT2-low asthma, those with srT2-high asthma were older age and had more severe asthma. Blood eosinophil cell counts predicted srT2-high asthma when BMI was < 40, but not when it was ≥40, whereas, blood IgE strongly predicted srT2-high asthma when age was < 34 years but not when it was ≥34.ConclusionDespite ICS therapy many asthmatics have persistent airway type 2 inflammation, (srT2-high asthma) and these patients are older and have more severe disease. Body weight and age modify the performance of blood-based biomarkers of airway type-2 inflammation.



http://ift.tt/2oW0ZDU

Non-PTLD Malignancy post HSCT in patients with Primary Immunodeficiency: UK experience

Publication date: Available online 7 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Mohamed Najib Mohamed Unni, Reem Elfeky, Kanchan Rao, Zohreh Nademi, Robert Chiesa, Persis Amrolia, Roderick Skinner, Olga Slater, Austen Worth, Terence Flood, Mario Abinun, Sophie Hambleton, Waseem Qasim, Hubert B. Gaspar, Andrew J. Cant, Andrew R. Gennery, Paul Veys, Mary A. Slatter
Secondary malignancy post haematopoietic stem cell transplantation (HSCT) for malignant disorders is well recognized. There are very few published reports on malignancy post HSCT for Primary Immunodeficiency (PID). We report 12 cases of 944 patients, who developed non-PTLD malignancy post-HSCT for PID.



http://ift.tt/2IcC1sB

A RAB27A 5’UTR structural variant associated with late-onset hemophagocytic lymphohistiocytosis and normal pigmentation

Publication date: Available online 6 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Bianca Tesi, Jelena Rascon, Samuel C.C. Chiang, Birute Burnyte, Alexandra Löfstedt, Anders Fasth, Miriam Heizmann, Sandra Juozapaite, Rosita Kiudeliene, Egle Kvedaraite, Valdone Miseviciene, Audrone Muleviciene, Martha-Lena Müller, Magnus Nordenskjöld, Reda Matuzeviciene, Ruta Samaitiene, Carsten Speckmann, Sigita Stankeviciene, Vytautas Zekas, Matthias Voss, Stephan Ehl, Nerija Vaiciene-Magistris, Jan-Inge Henter, Marie Meeths, Yenan T. Bryceson




http://ift.tt/2oZ9NJm

Managing Asthma in Pregnancy (MAP) trial: FeNO levels and childhood asthma

Publication date: Available online 8 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Matthew Morten, Adam Collison, Vanessa E. Murphy, Daniel Barker, Christopher Oldmeadow, John Attia, Joseph Meredith, Heather Powell, Paul D. Robinson, Peter D. Sly, Peter G. Gibson, Joerg Mattes
BackgroundThe single-centre double-blind, randomised controlled Managing Asthma in Pregnancy (MAP) trial in Newcastle, Australia, compared a treatment algorithm using the fraction of exhaled nitric oxide (FeNO) in combination with asthma symptoms (FeNO group) against a treatment algorithm using clinical symptoms only (clinical group) in pregnant asthmatic women (ANZ Clinical Trials Registry, number 12607000561482). The primary outcome was a 50% reduction in asthma exacerbations during pregnancy in the FeNO group. However, the effect of FeNO-guided management on the development of asthma in the offspring is unknown.ObjectiveWe sought to investigate the effect of FeNO-guided asthma management during pregnancy on asthma incidence in childhood.Methods179 mothers consented to participate in the Growing Into Asthma (GIA) double-blind follow-up study with the primary aim to determine the effect of FeNO-guided asthma management on childhood asthma incidence.Results140 children (78%) were followed up at 4 to 6 years of age. FeNO-guided as compared to symptoms only based approach significantly reduced doctor diagnosed asthma (25·9% versus 43·2%; odds ratio [OR] 0.46, 95% confidence interval [CI] 0.22 to 0.96, p=0.04). Furthermore frequent wheeze (OR 0.27; CI 0.09 to 0.87, p=0.03), use of short-acting beta agonists (OR 0.49; CI 0.25 to 0.97; p=0.04), and emergency department visits for asthma (OR 0.17, CI 0.04 to 0.76; p=0.02) in the past 12 months were less common in children born to mothers from the FeNO group. Doctor diagnosed asthma was associated with common risk alleles for early-onset asthma at gene locus 17q21 (p=0·01 for rs8069176; p=0·03 for rs8076131), and higher airways resistance (p=0·02) and FeNO levels (p=0·03). A causal mediation analysis suggested natural indirect effects of FeNO-guided asthma management on childhood asthma through "any use" and "time to first change in dose" of inhaled corticosteroids during the MAP trial (OR 0.83; CI 0.59 to 0.99 and OR 0.90, CI 0.70 to 1.03, respectively).ConclusionFeNO-guided asthma management during pregnancy prevented doctor diagnosed asthma in the offspring at preschool age, in part mediated through changes in use and dosing of inhaled corticosteroids during the MAP trial.



http://ift.tt/2IfcxuW

Transcriptomic analysis of FUCA1 knockdown in keratinocytes reveals new insights in the pathogenesis of fucosidosis skin lesions

Abstract

Fucosidosis is a rare lysosomal storage disease which has been classified into two subtypes, depending on the severity of clinical signs and symptoms. Fucosidosis patients' skin abnormalities include angiokeratoma corporis diffusum, widespread telangiectasia, thick skin, hyperhidrosis and hypohidrosis, acrocyanosis and distal transverse nail bands. It has been described that >50% of fucosidosis patients have angiokeratoma. At molecular level, fucosidosis is caused by lysosomal alpha-L-fucosidase (FUCA1) gene mutations. Obtaining samples for functional studies has been challenging due to the inherent difficulty in finding affected individuals. The effect of FUCA1 dysfunction on gene expression is unknown.

The aim of the present study was to analyse, in keratinocytes, the transcriptomic effect of FUCA1 knock-down for a better understanding of skin lesions' pathogenesis affecting fucosidosis patients. FUCA1 knock-down (siRNA) was performed in human HaCaT immortalised keratinocytes. Affymetrix arrays and qPCR were used for analysing gene expression. Bioinformatics was used for functional clustering of modified genes.

387 genes showed differential expression between FUCA1 silenced and non-silenced cells (222 up-regulated and 165 down-regulated). Upregulated genes belonged to two major groups: keratinocyte differentiation/epidermal development (n=17) and immune response (n= 61). Several transcription factors were upregulated in FUCA1-siRNA transfected cells. This effect might partly have been produced by abnormal transcription factor expression, i.e. FOXN1. We thus propose that fucosidosis-related skin lesions (e.g. angiokeratoma) and those of other diseases (e.g. psoriasis) might be caused by dysfunctions in common aetiological overlapping molecular cascades.

This article is protected by copyright. All rights reserved.

http://ift.tt/2G7YR4i

3D skin models for 3R research: the potential of 3D reconstructed skin models to study skin barrier function

Abstract

The skin barrier is an important shield regulating the outside-in as well as inside-out penetration of water, nutrients, ions and environmental stimuli. We can distinguish four different barrier compartments, the physical, chemical, immunological and microbial skin barrier. Well-functioning of those is needed to protect our body from the environment. To better understand the function and the contribution of barrier dysfunction in skin diseases, 3D skin or epidermal models are a valuable tool for in vitro studies. In this review we summarize the development and application of different skin models in skin barrier research. During the last years enormous effort was made on optimizing these models to better mimic the in vivo composition of the skin, by fine-tuning cell culture media, culture conditions and including additional cells and tissue components. Thereby in vitro barrier formation and function has been improved significantly. Moreover, in this review we point towards changes and chances for in vitro 3D skin models to be used for skin barrier research in the nearby future.

This article is protected by copyright. All rights reserved.

http://ift.tt/2DbgjBu

An Uncommon Cutaneous Lesion

A male smoker in his 60s presented with a right supraclavicular cutaneous mass that had persisted for 2 years; a biopsy of a pulmonary nodule showed a well-differentiated adenocarcinoma with lepidic pattern, and further workup revealed an intestinal tumor as the primary source. What is your diagnosis?

http://ift.tt/2HiA3pm

Errors in Questionnaire Scoring Algorithm

In the Original Investigation titled "Development and Initial Validation of a Consumer Questionnaire to Predict the Presence of Ear Disease," published online on August 3, 2017, and in the October 2017 issue of JAMA Otolaryngology–Head & Neck Surgery, there were errors in the analysis code for 3 of the questionnaire items (questions 16, 18, and 19). For these 3 questions, the 4-item rating scales were dichotomized incorrectly. Using the corrected algorithm resulted in changed sensitivity and specificity, odds ratios, and 95% CIs, as detailed herein. The corrections are also explained in a Letter to the Editor. In the abstract Results, descriptions of the sensitivity and specificity have been corrected to 90% (95% CI, 84%-94%) and 72% (95% CI, 59%-82%), respectively, for the training sample and 76% (95% CI, 61%-87%) and 80% (95% CI, 51%-95%) for the test sample, respectively. In the Statistical Analysis paragraph of the Methods section, rating scale items should have been dichotomized as 0 for "never" and "occasionally" and as 1 for "sometimes" and "always" rather than scored on a scale of 0 to 4. In the Results section, the odds ratio and 95% CI for the association between CEDRA score and presence of disease changed. In addition, the probability, sensitivity, and specificity values changed. In the third paragraph of the Discussion, all percentages have changed. Figure 2 has been replaced with a graph incorporating a corrected receiver operating characteristic curve, and the figure caption has been updated. This article was corrected online.

http://ift.tt/2FDFfqG

Opsoclonus-Myoclonus Syndrome—Reply

In Reply We thank Drs Kim and Budhram for their valuable suggestion. Owing to the 600-word limit in the Observation section, much of the information associated with this patient had to be omitted in the article. Herein we fill in some of the gaps. We agree that magnetic resonance imaging is the first priority for excluding a paraneoplastic or parainfectious origin when treating a patient with opsoclonus. Small cell carcinoma of the lung, breast cancer, and ovarian cancer are most prevelent in adults with opsoclonus, whereas neuroblastoma accounts for more than 50% prevalence in children. Of course, such work-up had been done in this patient, yet the results were negative. Occasionally, other neoplasms (ie, non-Hodgkin's lymphoma, malignant lymphoma) have also been related to opsoclonus. In addition, many parainfectious origins were proposed, namely, streptococcus, varicella-zoster virus, Epstein-Barr virus, human immunodeficiency virus (HIV), and lyme disease, for example.

http://ift.tt/2HiA24M

Opioid Prescription Patterns Among Patients With Head and Neck Cancer

This cross-sectional analysis quantifies the use of opioid analgesics among patients with head and neck cancer and compares this with use among patients with lung or colon cancer.

http://ift.tt/2FDbiqT

Brain-Derived Neurotrophic Factor Therapy and Cochlear Implantation

This Viewpoint cites several examples of how brain-derived neurotrophic factor therapy affects outcomes of cochlear implantation.

http://ift.tt/2Hh5ekW

Opsoclonus-Myoclonus Syndrome—Additional Clinical Considerations

To the Editor We read with interest the report by Hsu et al describing a 39-year-old woman with opsoclonus-myoclonus syndrome (OMS). Although an intriguing case, several aspects of the treatment should be addressed for others who may encounter this condition.

http://ift.tt/2FEvGrI

Patient-Reported Dysphagia After Thyroidectomy

This patient open-interview study attempts to characterize the effect of swallowing-related symptoms after thyroidectomy on patient quality of life and related outcomes.

http://ift.tt/2Hh5aSe

Errors in Items and Algorithm in Questionnaire for Validation Study

To the Editor We write to report a scoring algorithm error that was included in our article, "Development and Initial Validation of a Consumer Questionnaire to Predict the Presence of Ear Disease," published online on August 3, 2017, and in the October 2017 issue of JAMA Otolaryngology–Head & Neck Surgery. In this study, we examined the validity of the Consumer Ear Disease Risk Assessment (CEDRA), a questionnaire for the self-assessment of risk of ear diseases associated with hearing loss. The error was discovered by a member of our research team who was preparing a digital version of the questionnaire used in our study. The error occurred in the analysis code for 3 of the 28 questionnaire items included in the scoring (questions 16, 18, and 19). For these 3 questions, the 4-item rating scales were dichotomized incorrectly. After correcting the algorithm for these questions, we found slightly different results, without any differences in statistical significance of these results. The overall results and conclusions remain unchanged.

http://ift.tt/2FzlwIO

Otolaryngology Resident Education and the Core Competencies

This systematic review summarizes the quantity and nature of otolaryngology residency training literature and evaluates whether this literature aligns with the 6 core competencies identified by the Accreditation Council for Graduate Medical Education.

http://ift.tt/2Hh5a4G

Survival and Time to Radiation After Surgery in Head and Neck Cancer

Using data from the National Cancer Database, this cohort study examines the association of delayed time to radiotherapy with survival outcomes in patients with head and neck squamous cell carcinoma.

http://ift.tt/2oSBq7k

Postoperative cesarean pain: real but is it preventable?

Purpose of review Cesarean section is the most common surgical procedure performed in the world. Postoperative pain management remains a challenge, particularly in a context of enhanced recovery after surgery. Several barriers related to the specific condition of 'postpartum recovery' may prevent application of effective analgesia in this population. The present review focuses on novel approaches of cesarean section postoperative pain assessment, beyond pain-rating intensity, including objective patient-centered recovery parameters. Predictive tools currently available to target patients at high risk of acute and chronic pain are also examined. Recent findings Postoperative pain after cesarean section is more severe than reported in the majority of randomized control trials. Pain seriously interferes with early and also late functional recovery, although Enhanced Recovery after Surgery (ERAS) programmes are being promoted. Pain-rating scores can differ from scores of physical comfort and physical independence, which are priorities for postpartum patients. Further, the value of subjective pain intensity rating to adapt analgesic prescription is misleading and may promote opioid over-prescription. Available tools to predict at-risk patients for severe pain after cesarean section are not easy to use in daily clinical practice and have, at best, moderate predictive value. Summary Patient and healthcare provider education on reported pain and well tolerated analgesic use is the key to improve postpartum pain management after cesarean section. Correspondence to Patricia Lavand'homme, MD, PhD, Department of Anesthesiology, Cliniques Universitaires St Luc - University Catholic of Louvain, Av Hippocrate 10, B-1200 Brussels, Belgium. Tel: +32 2 764 18 21; fax: +32 2 764 36 99; e-mail: patricia.lavandhomme@uclouvain.be Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2FzkIng

Can This Topical Cream Prevent Nonmelanoma Skin Cancer?

A study tested whether prophylactic application of topical fluorouracil can prevent nonmelanoma skin cancer.
Medscape Dermatology

http://ift.tt/2FDF6DJ

Parotid adenoid cystic carcinoma: Retrospective single institute analysis

Publication date: Available online 7 March 2018
Source:American Journal of Otolaryngology
Author(s): Mohamed Nazmy ElBeltagi




http://ift.tt/2oTBoMy

Nasal polyposis pathophysiology: Endotype and phenotype open issues

Publication date: Available online 7 March 2018
Source:American Journal of Otolaryngology
Author(s): Giuseppe Brescia, Claudia Zanotti, Daniela Parrino, Umberto Barion, Gino Marioni
PurposeEndotyping chronic rhinosinusitis with nasal polyps (CRSwNP) poses a challenge for rhinologists nowadays. Phenotyping CRSwNP proved inappropriate as an approach to their classification because of their common clinical features. Endotyping, being based on the pathogenic mechanism, provides a precise picture more appropriate for use in clinical practice. Patients' treatment and follow-up can thus be tailored to cope with the degree of aggressiveness of a specific CRSwNP endotype.The aim of this study was to analyze the available information about the main currently accepted endotypes of CRSwNP; furthermore, we reported and commented evidence regarding some clinical conditions associated with nasal polyposis which could be related with new endotypes.Materials and methodsPubmed and Scopus electronic database were searched. The main available studies about CRSwNP endotyping published predominantly in the last 5 years were critically analyzed.ResultsThe pathophysiological features of some asthma-related CRSwNP (allergic fungal rhinosinusitis, aspirin-exacerbated respiratory disease) are quite well understood, including them among known endotypes of CRSwNP. On the other hand, because of their known pathophysiological mechanisms, some well-known diseases associated with aggressive forms of CRSwNP, such as eosinophilic granulomatosis with polyangiitis, primary ciliary dyskinesia and cystic fibrosis, should be investigated as potentially related with CRSwNP endotypes.ConclusionsCRSwNP comprises several inflammatory endotypes defined by different pathogenic mechanisms. These endotypes correlate with the disease's clinical manifestations and behavior. A thorough understanding of CRSwNP endotypes will enable targeted medical therapies and tailored follow-up protocols.



http://ift.tt/2tqEyMB

The association between otogenic lateral sinus thrombosis and thrombophilia – A long-term follow-up

Publication date: Available online 7 March 2018
Source:American Journal of Otolaryngology
Author(s): Schneider Shay, Kapelushnik Joseph, Kraus Mordechai, El-Saied Sabri, Levi Itai, Kaplan Daniel Michael
PurposeOtogenic lateral sinus thrombosis (OLST) is an intracranial, potentially life-threatening complication of acute and chronic otitis media. Since congenital thrombophilic disorders are risk factors for cerebral venous thrombosis, OLST may be related to thrombophilia. The aim of our study was twofold: to evaluate whether patients who suffered from OLST in childhood also have thrombophilia, and whether these patients experienced thromboembolic episodes in future years.Study designRetrospective case series.MethodsThe medical charts of all children hospitalized for OLST at Soroka University Medical Center of Israel, a tertiary referral hospital, from January 1983 to September 2014 were reviewed. The patients were invited for a follow-up visit and comprehensive medical history was taken along with a physical examination and laboratory work-up for thrombophilia.Main findingsSeven patients were included in the study. Of these, 3 (43%) had results suggesting thrombophilic disorders manifested by elevated levels of factor IX and decreased levels of protein S activity (n = 1), decreased levels of proteins C and S activity (n = 1), and elevated levels of antibodies to cardiolipin (n = 1). No patients experienced clear thrombophilic events; however, 2 patients (29%) with later proven thrombophilia suffered neurologic sequelae, possibly suggesting thrombophilic events.ConclusionsPediatric OLST secondary to acute otitis media and mastoiditis may reflect an underlying thrombophilia. Laboratory work-up for thrombophilia should be performed, and anticoagulant treatment may be warranted in managing these patients.



http://ift.tt/2oUOo4N

Analysis of non-posterior canal benign paroxysmal positional vertigo in patients treated using the particle repositioning chair: A large, single-institution series

Publication date: Available online 7 March 2018
Source:American Journal of Otolaryngology
Author(s): Alexander L. Luryi, David Wright, Juliana Lawrence, Seilesh Babu, Michael LaRouere, Dennis I. Bojrab, Eric W. Sargent, John Zappia, Christopher A. Schutt
PurposeBenign paroxysmal positional vertigo (BPPV) involving the horizontal and superior semicircular canals is difficult to study due to variability in diagnosis. We aim to compare disease, treatment, and outcome characteristics between patients with BPPV of non-posterior semicircular canals (NP-BPPV) and BPPV involving the posterior canal only (P-BPPV) using the particle repositioning chair as a diagnostic and therapeutic tool.MethodsRetrospective review of patients diagnosed with and treated for BPPV at a high volume otology institution using the particle repositioning chair.ResultsA total of 610 patients with BPPV were identified, 19.0% of whom had NP-BPPV. Patients with NP-BPPV were more likely to have bilateral BPPV (52.6% vs. 27.6%, p < 0.0005) and Meniere's disease (12.1% vs. 5.9%, p = 0.02) and were more likely to have caloric weakness (40.3% vs. 24.3%, p = 0.01). Patients with NP-BPPV required more treatments for BPPV (average 3.4 vs. 2.4, p = 0.01) but did not have a significantly different rate of resolution, rate of recurrence, or time to resolution or recurrence than patients with posterior canal BPPV.ConclusionsComparison of NP-BPPV and P-BPPV is presented with reliable diagnosis by the particle repositioning chair. NP-BPPV affects 19% of patients with BPPV, and these patients are more likely to have bilateral BPPV and to require more treatment visits but have similar outcomes to those with P-BPPV. NP-BPPV is common and should be part of the differential diagnosis for patients presenting with positional vertigo.



http://ift.tt/2tqEmwR

Progressive functional improvement in hemiglossectomy defects reconstructed with radial forearm free flap at 6-months

Publication date: Available online 7 March 2018
Source:American Journal of Otolaryngology
Author(s): Khoi Anh Nguyen, Truong Xuan Bui, Hue Van Nguyen, Richard O. Wein
ObjectiveThe purposes of the study was to evaluate for the functional improvement of outcomes of patients undergoing surgical management for tongue cancer at varying periods after surgery.DesignCase series with intervention.ParticipantsThirty consecutive patients, from 2011 to 2015, with carcinoma of the tongue undergoing surgical resection and reconstruction with a radial forearm free flap.Main measuresThe Speech Intelligibility Test (SIT) is used for objective evaluation of speech function. The 7-point ordinal scale Functional Oral Intake Score (FOIS) was used to estimate the swallowing function.ResultsThe patients included were 25 men and 5 women with a mean age of 50.4 years (range – 27–65). All tumors were squamous cell carcinomas and all patients underwent a hemiglossectomy. There were two complete flap failures, with a resultant flap success rate of 93.3%. The initial mean speech intelligibility scores at 1-month increased from 72.3 ± 0.2 to 77.7 ± 8.9 at 6-months after surgery (p = 0.05). Similarly, the mean score of swallowing function improved from 6.1 at 1-month to 6.8 at 6-months after surgery (p = 0.05).ConclusionReconstruction of hemiglossectomy defects with a radial forearm free flap offers functional benefits in speech and deglutition that demonstrate progressive improvement when 1- and 6-month post-surgical assessments are compared.



http://ift.tt/2oTSfyU

Identification of specifically reduced Th2 cell subsets in allergic rhinitis patients after sublingual immunotherapy

Abstract

Background

Although Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis (AR), the factors that induce and sustain the pathogenesis of AR remain unclear. The recent development of sublingual immunotherapy (SLIT) is expected to allow changes to the underlying pathogenesis of AR. However, which Th2 cell subsets are important in house dust mite-induced AR (HDM-AR), the influence of SLIT on the pathogenic Th2 cells, and the association of Th2 cell subsets with SLIT efficacy have not been clarified.

Methods

The cytokine production and frequency of HDM-reactive T cell subsets in peripheral blood mononuclear cells (PBMCs) were evaluated using flow cytometry in 89 HDM-AR patients (placebo (n=43) and HDM 300 IR (n=46)) who participated in a placebo-controlled study of SLIT with HDM tablets. All patients provided samples both before treatment as a baseline and at the end of the 52-week study. The PBMCs were stained with CellTrace^™ Violet (CTV) before culture with HDM extract, and HDM-reactive T cells were detected as the proliferated cells with diminished CTV.

Results

HDM-reactive IL-5⁺IL-13⁺CD27⁻CD161⁺CD4⁺ cells and ST2⁺CD45RO⁺CD4⁺ cells were observed in the peripheral blood from each patient with HDM-AR; these cells significantly decreased after SLIT in the group treated with active tablets. HDM-reactive ST2⁺CD45RO⁺CD4⁺ cells were significantly lower in active-responders.

Conclusion

Allergen-reactive ST2⁺CD45RO⁺CD4⁺ cells or those combined with IL-5⁺IL-13⁺CD27⁻CD161⁺CD4⁺ cells may be useful as markers indicating the successful treatment of SLIT. These cells may play a crucial role in the pathogenesis of AR as pathogenic memory Th2 cells.

This article is protected by copyright. All rights reserved.

http://ift.tt/2tt2aQS

Chronic urticaria can be caused by cancer and resolves with its cure

Abstract

We present 26 cases (ours and 25 from an extended literature review) in which chronic spontaneous urticaria (CSU) seems to be caused by a malignancy (mostly carcinoma or hematologic malignancy): the CSU precedes the neoplasia diagnosis by some months (2-8mo in 80%) and resolved days after chemotherapy/ surgical resection of the malignancy. In three patients, the urticaria flare-up alerted the treating physician of neoplasia recurrence. There could be publication bias, but the narrow time-span between cancer remission and urticaria resolution and especially the recurrence of urticaria that led to detection of cancer relapse in some of our cases are arguments in favor of a causal relationship. Physicians treating CSU should be aware of this. As in all CSU, complete blood count, C reactive protein and erythrocyte sedimentation rate should form part of the initial work-up. As age-indicated screening, over 45 years, a mastography/prostate antigen test should be taken and in recalcitrant, treatment-resistant CSU i.a. a thyroid gland ultrasound could be considered to rule out the most frequently associated malignancies.

This article is protected by copyright. All rights reserved.

http://ift.tt/2oUCSGq

Incidence of cephalosporin-induced anaphylaxis and clinical efficacy of screening intradermal tests with cephalosporins: a large multicenter retrospective cohort study

Abstract

Background

Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests.

Methods

In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into four groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins.

Results

We identified 76 cases of cephalosporin-induced anaphylaxis with 1,123,345 exposures to intravenous cephalosporins (6.8 per 100,000 exposures) and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100,000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100,000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone and cefuroxime; 9.3 per 100,000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox and cefotiam. The clinical effectiveness of routine screening IDT was not significant (p = 0.06).

Conclusions

The incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Although screening IDT showed no clinical efficacy in general, it may be useful for certain cephalosporins.

This article is protected by copyright. All rights reserved.

http://ift.tt/2tnI7mA

Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease

Franzmeier, N; Düzel, E; Jessen, F; Buerger, K; Levin, J; Duering, M; Dichgans, M; ... Ewers, M; + view all Franzmeier, N; Düzel, E; Jessen, F; Buerger, K; Levin, J; Duering, M; Dichgans, M; Haass, C; Suárez-Calvet, M; Fagan, AM; Paumier, K; Benzinger, T; Masters, CL; Morris, JC; Perneczky, R; Janowitz, D; Catak, C; Wolfsgruber, S; Wagner, M; Teipel, S; Kilimann, I; Ramirez, A; Rossor, M; Jucker, M; Chhatwal, J; Spottke, A; Boecker, H; Brosseron, F; Falkai, P; Fliessbach, K; Heneka, MT; Laske, C; Nestor, P; Peters, O; Fuentes, M; Menne, F; Priller, J; Spruth, EJ; Franke, C; Schneider, A; Kofler, B; Westerteicher, C; Speck, O; Wiltfang, J; Bartels, C; Araque Caballero, MÁ; Metzger, C; Bittner, D; Weiner, M; Lee, J-H; Salloway, S; Danek, A; Goate, A; Schofield, PR; Bateman, RJ; Ewers, M; - view fewer (2018) Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease. Brain 10.1093/brain/awy008 . (In press). Green open access

http://ift.tt/2FmXWj0

Exploring the potential for cross disciplinary working with archives and records management

Bunn, J; (2015) Exploring the potential for cross disciplinary working with archives and records management. In: Inkpen, Kori and Woo, Woontack, (eds.) Proceedings of the 33rd Annual ACM Conference Extended Abstracts on Human Factors in Computing Systems - CHI EA '15. (pp. pp. 2169-2174). ACM: New York, USA. Green open access

http://ift.tt/2FqhtLu

Lacunar Infarcts, but Not Perivascular Spaces, Are Predictors of Cognitive Decline in Cerebral Small-Vessel Disease

Benjamin, P; Trippier, S; Lawrence, AJ; Lambert, C; Zeestraten, E; Williams, OA; Patel, B; ... Markus, HS; + view all Benjamin, P; Trippier, S; Lawrence, AJ; Lambert, C; Zeestraten, E; Williams, OA; Patel, B; Morris, RG; Barrick, TR; MacKinnon, AD; Markus, HS; - view fewer (2018) Lacunar Infarcts, but Not Perivascular Spaces, Are Predictors of Cognitive Decline in Cerebral Small-Vessel Disease. Stroke , 49 (3) pp. 586-593. 10.1161/STROKEAHA.117.017526 . Green open access

http://ift.tt/2Fmq9Xp

The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management

Tranebjærg, L; Strenzke, N; Lindholm, S; Rendtorff, ND; Poulsen, H; Khandelia, H; Kopec, W; ... Bitner-Glindzicz, M; + view all Tranebjærg, L; Strenzke, N; Lindholm, S; Rendtorff, ND; Poulsen, H; Khandelia, H; Kopec, W; Lyngbye, TJB; Hamel, C; Delettre, C; Bocquet, B; Bille, M; Owen, HH; Bek, T; Jensen, H; Østergaard, K; Möller, C; Luxon, L; Carr, L; Wilson, L; Rajput, K; Sirimanna, T; Harrop-Griffiths, K; Rahman, S; Vona, B; Doll, J; Haaf, T; Bartsch, O; Rosewich, H; Moser, T; Bitner-Glindzicz, M; - view fewer (2018) The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management. Human Genetics , 137 (2) pp. 111-127. 10.1007/s00439-017-1862-z .

http://ift.tt/2Db0Wcr

Teaching principles of network and agent-based models to architecture students

Al-Sayed, K; Griffiths, S; Karimi, K; (2015) Teaching principles of network and agent-based models to architecture students. In: Karimi, K and Vaughan, L and Sailer, K and Bolton, T, (eds.) Proceedings of the 10th Space Syntax Symposium (SSS10). Space Syntax Laboratory, The Bartlett School of Architecture, University College London: London, United Kingdom. Green open access

http://ift.tt/2FoKXNK

[18F]FSPG-PET reveals increased cystine/glutamate antiporter (xc-) activity in a mouse model of multiple sclerosis.

Hoehne, A; James, ML; Alam, IS; Ronald, JA; Schneider, B; D'Souza, A; Witney, TH; ... Gambhir, SS; + view all Hoehne, A; James, ML; Alam, IS; Ronald, JA; Schneider, B; D'Souza, A; Witney, TH; Andrews, LE; Cropper, HC; Behera, D; Gowrishankar, G; Ding, Z; Wyss-Coray, T; Chin, FT; Biswal, S; Gambhir, SS; - view fewer (2018) [18F]FSPG-PET reveals increased cystine/glutamate antiporter (xc-) activity in a mouse model of multiple sclerosis. Journal of Neuroinflammation , 15 , Article 55. 10.1186/s12974-018-1080-1 . Green open access

http://ift.tt/2Dci3KP

C-11-PE2I and F-18-Dopa PET for Assessing Progression Rate in Parkinson's: A Longitudinal Study

Li, W; Lao-Kaim, NP; Roussakis, AA; Martin-Bastida, A; Valle-Guzman, N; Paul, G; Loane, C; ... Piccini, P; + view all Li, W; Lao-Kaim, NP; Roussakis, AA; Martin-Bastida, A; Valle-Guzman, N; Paul, G; Loane, C; Widner, H; Politis, M; Foltynie, T; Barker, RA; Piccini, P; - view fewer (2017) C-11-PE2I and F-18-Dopa PET for Assessing Progression Rate in Parkinson's: A Longitudinal Study. Movement Disorders , 33 (1) pp. 117-127. 10.1002/mds.27183 .

http://ift.tt/2FkMuo1

Lighting quality: Possibility of luminance distribution as its determinant

Mansfield, KP; Oi, N; (2015) Lighting quality: Possibility of luminance distribution as its determinant. In: Proceedings of the 28th Session of the CIE. (pp. pp. 1111-1120). CIE: Manchester, United Kingdom.

http://ift.tt/2FovdGF

A comparative analysis of surface and bulk contributions to second-harmonic generation in centrosymmetric nanoparticles

Timbrell, D; You, JW; Kivshar, YS; Panoiu, NC; (2018) A comparative analysis of surface and bulk contributions to second-harmonic generation in centrosymmetric nanoparticles. Scientific Reports , 8 , Article 3586. 10.1038/s41598-018-21850-8 . Green open access

http://ift.tt/2FkMhBf

Parton distributions and lattice QCD calculations: A community white paper

Lin, HW; Nocera, ER; Olness, F; Orginos, K; Rojo, J; Accardi, A; Alexandrou, C; ... Zanotti, J; + view all Lin, HW; Nocera, ER; Olness, F; Orginos, K; Rojo, J; Accardi, A; Alexandrou, C; Bacchetta, A; Bozzi, G; Chen, JW; Collins, S; Cooper-Sarkar, A; Constantinou, M; Del Debbio, L; Engelhardt, M; Green, J; Gupta, R; Harland-Lang, LA; Ishikawa, T; Kusina, A; Liu, KF; Liuti, S; Monahan, C; Nadolsky, P; Qiu, JW; Schienbein, I; Schierholz, G; Thorne, RS; Vogelsang, W; Wittig, H; Yuan, CP; Zanotti, J; - view fewer (2018) Parton distributions and lattice QCD calculations: A community white paper. Progress in Particle and Nuclear Physics 10.1016/j.ppnp.2018.01.007 . (In press).

http://ift.tt/2DbOoBz

Efficiency of pseudospectrum methods for estimation of the cosmic microwave background B-mode power spectrum

Ferte, A; Grain, J; Tristram, M; Stompor, R; (2013) Efficiency of pseudospectrum methods for estimation of the cosmic microwave background B-mode power spectrum. Physical Review D , 88 (2) , Article 023524. 10.1103/PhysRevD.88.023524 . Green open access

http://ift.tt/2FnCiLT

A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets

Hobor, F; Dallmann, A; Ball, NJ; Cicchini, C; Battistelli, C; Ogrodowicz, RW; Christodoulou, E; ... Ramos, A; + view all Hobor, F; Dallmann, A; Ball, NJ; Cicchini, C; Battistelli, C; Ogrodowicz, RW; Christodoulou, E; Martin, SR; Castello, A; Tripodi, M; Taylor, IA; Ramos, A; - view fewer (2018) A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets. Nature Communications , 9 , Article 831. 10.1038/s41467-018-03182-3 . Green open access

http://ift.tt/2DaqTsR

Characteristics and mortality risk of children with life-threatening influenza infection admitted to paediatric intensive care in England 2003–2015

Hardelid, P; Kapetanstrataki, M; Norman, L; Fleming, SJ; Lister, P; Gilbert, R; Parslow, RC; (2018) Characteristics and mortality risk of children with life-threatening influenza infection admitted to paediatric intensive care in England 2003–2015. Respiratory Medicine , 137 pp. 23-29. 10.1016/j.rmed.2018.02.012 .

http://ift.tt/2FnCafn

Numerical studies of shear-thinning droplet formation in a microfluidic T-junction using two-phase level-SET method

Wonga, V-L; Loizou, K; Lau, P-L; Graham, RS; Hewakandamby, BN; (2017) Numerical studies of shear-thinning droplet formation in a microfluidic T-junction using two-phase level-SET method. Chemical Engineering Science , 174 pp. 157-173. 10.1016/j.ces.2017.08.027 .

http://ift.tt/2DbQTUl

Landscape and Consumer Culture in the Design Work of Humphry Repton and Gordon Cullen: A Methodological Framework

Engler, M.; (2018) Landscape and Consumer Culture in the Design Work of Humphry Repton and Gordon Cullen: A Methodological Framework. Architecture_MPS , 13 (2) pp. 1-24. 10.14324/111.444.amps.2018v13i2.001 . Green open access

http://ift.tt/2Fk7kE4

A novel physiological role for ARF1 in the formation of bidirectional tubules from the Golgi

Bottanelli, F; Kilian, N; Ernst, AM; Rivera-Molina, F; Schroeder, LK; Kromann, EB; Lessard, MD; ... Rothman, JE; + view all Bottanelli, F; Kilian, N; Ernst, AM; Rivera-Molina, F; Schroeder, LK; Kromann, EB; Lessard, MD; Erdmann, RS; Schepartz, A; Baddeley, D; Bewersdorf, J; Toomre, D; Rothman, JE; - view fewer (2017) A novel physiological role for ARF1 in the formation of bidirectional tubules from the Golgi. Molecular Biology of the Cell , 28 (12) pp. 1676-1687. 10.1091/mbc.E16-12-0863 . Green open access

http://ift.tt/2FqzpG1

An Investigation of the Role of Radiative and Nonradiative Recombination Processes in InAs/GaAs 1−x Sb x Quantum Dot Solar Cells

Cheng, Y; Meleco, AJ; Roeth, AJ; Whiteside, VR; Debnath, MC; Mishima, TD; Santos, MB; ... Sellers, IR; + view all Cheng, Y; Meleco, AJ; Roeth, AJ; Whiteside, VR; Debnath, MC; Mishima, TD; Santos, MB; Hatch, S; Liu, H; Sellers, IR; - view fewer (2018) An Investigation of the Role of Radiative and Nonradiative Recombination Processes in InAs/GaAs 1−x Sb x Quantum Dot Solar Cells. IEEE Journal of Photovoltaics , 8 (2) pp. 487-492. 10.1109/JPHOTOV.2017.2779325 . Green open access

http://ift.tt/2FlKQTb

Relative orientation of collagen molecules within a fibril: a homology model for homo sapiens type I collagen.

Collier, TA; Nash, A; Birch, HL; de Leeuw, NH; (2018) Relative orientation of collagen molecules within a fibril: a homology model for homo sapiens type I collagen. J Biomol Struct Dyn 10.1080/07391102.2018.1433553 . (In press). Green open access

http://ift.tt/2Daezsz

Accretion of a symmetry-breaking scalar field by a Schwarzschild black hole

Traykova, D; Braden, J; Peiris, HV; (2018) Accretion of a symmetry-breaking scalar field by a Schwarzschild black hole. Philosophical Transactions of the Royal Society A: Mathematical, Physical & Engineering Sciences , 376 (2114) , Article 20170122. 10.1098/rsta.2017.0122 . Green open access

http://ift.tt/2FiAZ0q

A high-coverage draft genome of the mycalesine butterfly Bicyclus anynana

Nowell, RW; Elsworth, B; Oostra, V; Zwaan, BJ; Wheat, CW; Saastamoinen, M; Saccheri, IJ; ... Blaxter, M; + view all Nowell, RW; Elsworth, B; Oostra, V; Zwaan, BJ; Wheat, CW; Saastamoinen, M; Saccheri, IJ; Van't Hof, AE; Wasik, BR; Connahs, H; Aslam, ML; Kumar, S; Challis, RJ; Monteiro, A; Brakefield, PM; Blaxter, M; - view fewer (2017) A high-coverage draft genome of the mycalesine butterfly Bicyclus anynana. GigaScience , 6 (7) pp. 1-7. 10.1093/gigascience/gix035 . Green open access

http://ift.tt/2DaNu8g

The role of sciatic nerve block to complement femoral nerve block in total knee arthroplasty: a meta-analysis of randomized controlled trials

Abstract

Introduction

Femoral nerve block (FNB) appears to have higher postoperative analgesic benefits compared with the patient-controlled analgesia (PCA) in total knee arthroplasty (TKA). However, the role of sciatic nerve block (SNB) as a complement to FNB remains controversial. We performed a meta-analysis assessing the benefits of the SNB as a complement to FNB, as well as comparing the efficacy of single-injection versus continuous SNB in TKA.

Methods

Our group conducted a systematic literature search in PubMed, EMBASE and Google Scholar. We retrieved randomized trials comparing either SNB versus placebo or continuous versus single-injection SNB. The intervention group was the use of SNB as a complement to FNB, while the control group was FNB alone. Pain score at rest and movement (at 4, 12, 24, 48 and 72 h), patient-controlled intravenous opioid consumption, length of hospital stay, and incidence of nausea were extracted from each study. Random-effects model was used for meta-analysis and standardized mean difference (SMD) was used as the effect size.

Results

Ten articles comprising 514 patients were included to compare the effects of SNB combined with FNB versus FNB alone. Interventional group was found to significantly reduce pain score at for 4 h (SMD = − 0.94, 95% CI − 1.42 to − 0.47, P < 0.001, I² = 76.5%) compared with the control group. Pain score at rest was significantly reduced at movement for 12 h (SMD = − 0.29, 95% CI − 0.54 to − 0.04, P = 0.02, I² = 0%). Opioid consumption was significantly reduced at 24 (SMD = − 0.60, 95% CI − 1.01 to − 0.17, P = 0.01, I² = 69.1%) and 48 h (SMD = − 1.04, 95% CI − 1.46 to − 0.61, P < 0.001, I² = 43.4%) after TKA using SNB as a complement to FNB. Three articles were additionally meta-analyzed to compare the efficacy of single-injection (n = 79) versus continuous SNB (n = 79), being the latter one significantly associated with less pain score at 24 (SMD = -0.77, 95% CI − 1.10 to − 0.45, P < 0.001, I² = 0%) and 48 h (SMD = − 0.69, 95% CI − 1.01 to − 0.36, P < 0.001, I² = 0%), but not at 12 h (SMD = − 0.34, 95% CI − 0.73 to − 0.06, P = 0.10, I² = 0%).

Conclusions

This meta-analysis provides evidence-based supports to the benefits of SNB as a complement to FNB in TKA. The combination sciatic–femoral nerve block appears to be the optimal choice for patients in high risk of postoperative opioids consumption or acute pain after TKA.

http://ift.tt/2oZdPRV

Preoperative Lund-Mackay computed tomography score is associated with preoperative symptom severity and predicts quality-of-life outcome trajectories after sinus surgery

Background

Disagreement exists about the relationship between Lund-Mackay CT scores (LMCTS) and quality-of-life outcome (QoL) measures. We investigated whether preoperative LMCTS are associated with preoperative QoL, and whether LMCTS is predictive of postoperative QoL outcomes in chronic rhinosinusitis (CRS) patients.

Methods

Adult patients with medically recalcitrant CRS (n = 665) were enrolled in a prospective, observational cohort study. Preoperative LMCTS and pre- and postoperative self-reported QoL outcomes (22-item Sino-Nasal Outcomes Test [SNOT-22]) were collected and evaluated over 12 months. Five hundred sixty-eight patients met the inclusion criteria. Longitudinal linear mixed-effects modeling was used to investigate the effect of LMCTS on QoL after functional endoscopic sinus surgery (FESS).

Results

Preoperative LMCTS were significantly associated with preoperative SNOT-22 scores (p < 0.01) and postoperative SNOT-22 scores (p < 0.001), driven by Extranasal and Rhinologic subdomains of the QoL questionaire. Patients in the lowest preoperative LMCTS quartile had the lowest mean change in SNOT-22 scores at 12 months (16.8 points; 95% confidence interval [CI], 12.2-21.3). Patients in the second and third lowest preoperative LMCTS quartiles had mean changes at 12 months of 21.1 points (95% CI, 16.7-25.4) and 23.1 points (95% CI, 18.3-27.9). Patients in the highest preoperative LMCTS quartile had the greatest improvement in SNOT-22 scores after FESS (29.9 points; 95% CI, 24.9-34.8). The difference in QoL change at 12 months between the highest and lowest preoperative LMCTS quartiles was 13.1 points (95% CI, 6.0-20.2; p < 0.001).

Conclusion

Our study demonstrates that preoperative LMCTS correlate with preoperative extranasal and rhinologic symptom severity and that the LMCTS is an indicator of postsurgical QoL outcomes for medically recalcitrant chronic rhinosinusitis patients in a large tertiary otolaryngology setting.

http://ift.tt/2FsdYEo

The effect of medical treatments on the bacterial microbiome in patients with chronic rhinosinusitis: a pilot study

Background

Antibiotics and corticosteroids are prescribed to patients with chronic rhinosinusitis (CRS) to reduce bacterial burden and mucosal inflammation. Unfortunately, clinical improvement is often short-lived and symptoms frequently recur following cessation of treatment. The impact of these systemic therapies on bacterial communities is not well understood. Improved knowledge of how medical therapies influence the intranasal ecosystem may allow for more effective prescribing and the development of more targeted treatments.

Methods

Twenty patients with CRS were randomized to receive either doxycycline 100 mg twice daily or prednisone 30 mg once daily for 7 days. A further 6 patients with CRS were recruited as untreated controls. Swabs were taken immediately before and after the study period. Symptom scores (22-item Sino-Nasal Outcome Test [SNOT-22]) were recorded. Bacterial communities were characterized using 16S ribosomal RNA (rRNA) gene-targeted amplicon sequencing. Bacterial abundance was estimated using quantitative polymerase chain reaction (PCR) of 16S rRNA gene copies.

Results

Bacterial profiles were dominated by members of the genera Corynebacterium and Staphylococcus. Patients treated with either doxycycline or prednisone had variable and unpredictable changes in communities. The average relative abundance of Propionibacterium increased after treatment in the doxycycline treatment group, and Corynebacterium reduced in the prednisone group. Significant differences in clinical scores, bacterial community richness, diversity, and bacterial abundance were not seen after treatment.

Conclusion

The short-term response of bacterial communities to antibiotic or corticosteroid therapy is unpredictable. This study suggests that the use of systemic therapy in patients with stable CRS should be rationalized to minimize antibiotic-associated morbidity and bacterial dysbiosis.

http://ift.tt/2FjY1nC

Case 7-2018: A 25-Year-Old Man with New-Onset Seizures

Presentation of Case. Dr. Ethan I. Meltzer (Neurology): A 25-year-old man was admitted to this hospital because of new-onset seizures. The patient had been in his usual state of health until 2 days before admission, when episodes of twitching of the head and neck occurred. The first episode…

http://ift.tt/2Fod4IV

Inhibition of methionine gamma lyase deaminase and the growth of Porphyromonas gingivalis: A therapeutic target for halitosis/periodontitis

Publication date: June 2018
Source:Archives of Oral Biology, Volume 90
Author(s): U. Kandalam, N. Ledra, H. Laubach, K.V. Venkatachalam
Background and objectivesPathogenic infections caused by Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia can result in the production of volatile sulfur compounds (VSC's) and other toxic compounds from methionine catabolism that can lead to halitosis and periodontitis. Our aim is to block the activity of methionine gammalyase-deaminase (Mgld) of methionine catabolism to prevent halitosis/periodontitis.DesignsCloned, expressed, Mgld protein was tested for purity by SDS-PAGE and western blotting. Mgld activity was tested by UV–vis spectroscopy and DTNB assay. Effects of Mgld inhibitor propargylglycine (PGLY) was tested on P. gingivalis growth by turbidity measurements. The effects of PGLY on oral epithelial and periodontal ligament cells in culture at different concentrations and time were tested for cell viability by MTT and Live-Dead assays. Amino acid comparisons of Mgld from different oral pathogens were done using standard bioinformatics program.ResultsPropargylglycine (PGLY) inhibited purified Mgld activity completely. In vivo, PGLY is a potent inhibitor on the growth of the P. gingivalis over 24 h, grown at 25 °C and 37 °C. Correspondingly in vivo Mgld activity was also affected by PGLY. Amino acid comparisons of oral pathogens showed 100% identity on the key residues of Mgld catalysis. Mammalian oral cell lines with PGLY, showed no difference in cell death over untreated controls assessed by MTT and Live-Dead assays.ConclusionsPGLY arrest's VSC's production by P. gingivalis. Since initial Mgld activity is inhibited subsequent enzymatic and nonenzymatic products formed will be prevented. PGLY showed no toxicity towards cultured mammalian oral cells. Thus, PGLY can serve as a mouthwash ingredient to prevent halitosis/periodontitis.



http://ift.tt/2FrQVtx

Thrombectomy for late occlusion of high flow extracranial-intracranial saphenous vein bypass graft after 27 years of patency

High flow extracranial–intracranial (EC-IC) bypass with a saphenous vein graft (SVG) has been used for more than 40 years in patients with giant aneurysms of the posterior circulation refractory to medical management, and has demonstrated high long term patency rates. We report the case of a patient treated with external carotid artery (ECA)–posterior cerebral artery SVG bypass in 1989 who presented 27 years later with paresthesias and confusion, and was found to have partial occlusion of her SVG bypass graft and a basilar occlusion. She was treated with mechanical thrombectomy of the basilar occlusion via the partially thrombosed graft, the first report of such a procedure through a high flow posterior circulation EC-IC SVG, resulting in improvement of the patient's neurologic examination. At 27 years, this is the longest reported delay in thrombosis of a high flow SVG bypass graft, highlighting the long term patency of these grafts and the feasibility of thrombectomy through occluded bypass grafts.

http://ift.tt/2FDaYs2

Caregiver and expecting caregiver support for early peanut introduction guidelines

Publication date: Available online 7 March 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Matthew Greenhawt, Edmond S. Chan, David M. Fleischer, Allison Hicks, Rachel Wilson, Marcus Shaker, Carina Venter, David Stukus
BackgroundRecent guidelines recommend early peanut introduction (EPI) beginning around 4-6 months in infants with either severe eczema and/or egg allergy, and around 6 months for all other infants. Caregiver preferences for such practices are unkown.MethodsWe explored preferences for EPI and in-office allergy risk assessment (IRA) through a nationally-representative survey of expecting (n=1000) and new caregivers of infants < 1 year (n=1000).ResultsAmong a primarily female (99.7%), married (80.3%), and white (74.4%) sample, 29% had no/vague awareness of the new guidelines, 61% had no/minimal concern for their child developing food allergy, but 54% felt timing of introduction has moderate/strong importance for developing food allergy. Only 31% expressed willingness for EPI before/around 6 months of life, with 40% reporting willingness to introduce peanut after 11 months of life, similar to tree nuts and seafood. However, 60% reported willingness to introduce egg before 8 months. 51% and 56.8% were unwilling to allow IRA methods such as skin testing and oral challenge before 11 months of life, respectively. Odds of willingness to both delay peanut introduction and undergo challenge after 6 months of life were lower among expecting caregivers (OR 0.79, CI 0.65-0.96; OR 0.67, CI 0.54-0.82, respectively).ConclusionsAmong new and expecting caregivers, there is poor current willingness and questionable support for early allergenic solid food recommendations, including IRA before introduction. Willingness was better among expecting versus current caregivers. These trends underscore a need for broader formal implementation planning to facilitate early allergen introduction and maximize its preventive benefits



http://ift.tt/2G6Ff06

Brief electrical stimulation and synkinesis after facial nerve crush injury: a randomized prospective animal study

Recent studies have examined the effects of brief electrical stimulation (BES) on nerve regeneration, with some suggesting that BES accelerates facial nerve recovery. However, the facial nerve outcome measurem...

http://ift.tt/2tozpVg

Pachydermoperiostosis in a patient with chronic hepatitis B virus infection referred as acromegaly: a case report

Primary hypertrophic osteoarthropathy also known as pachydermoperiostosis is a rare genetic disorder that has often been confused with acromegaly because of similar clinical features. Vascular endothelial grow...

http://ift.tt/2FqGer8

Identification of Cha o 3 homolog Cry j 4 from Cryptomeria japonica (Japanese cedar) pollen: Limitation of the present Japanese cedar–specific ASIT

Publication date: Available online 7 March 2018
Source:Allergology International
Author(s): Toshihiro Osada, Yuki Tanaka, Akira Yamada, Eiji Sasaki, Teruhiro Utsugi
BackgroundAbout one-third of the Japanese population suffers from Japanese cedar pollinosis, which is frequently accompanied by Japanese cypress pollinosis. Recently, a novel major Japanese cypress pollen allergen, Cha o 3, was discovered. However, whether a Cha o 3 homolog is present in Japanese cedar pollen remains to be determined.MethodsWestern blot analysis was performed using Cha o 3–specific antiserum. In addition, cloning of the gene encoding Cry j 4 was conducted using total cDNA from the male flower of Japanese cedar trees. Allergen potency and cross-reactivity were investigated using a T-cell proliferation assay, basophil activation test, and ImmunoCAP inhibition assay.ResultsA low amount of Cha o 3 homolog protein was detected in Japanese cedar pollen extract. The deduced amino acid sequence of Cry j 4 showed 84% identity to that of Cha o 3. Cross-reactivity between Cry j 4 and Cha o 3 was observed at the T cell and IgE levels.ConclusionsCry j 4 was discovered as a counterpart allergen of Cha o 3 in Japanese cedar pollen, with a relationship similar to that between Cry j 1–Cha o 1 and Cry j 2–Cha o 2. Our findings also suggest that allergen-specific immunotherapy (ASIT) using Japanese cedar pollen extract does not induce adequate immune tolerance to Cha o 3 due to the low amount of Cry j 4 in Japanese cedar pollen. Therefore, ASIT using Cha o 3 or cypress pollen extract coupled with Japanese cedar pollen extract is required in order to optimally control allergy symptoms during Japanese cypress pollen season.



http://ift.tt/2GahhkZ

A report of rare adverse tissue reaction to Ethilon® Nylon Suture

Abstract

This report describes a rare severe tissue reaction, as demonstrated in clinical photographs, to nylon sutures and illustrates how simple immediate removal of sutures isolates the irritant stimulus and results in rapid resolution, without the risk, cost and inconvenience of antibiotic treatment.

http://ift.tt/2Fyu3LZ

A rare case of giant extra-ovarian mucinous cystadenoma arising from sigmoid mesocolon

Abstract

An 80-year-old female presented with one month history of acutely worsening abdominal distention and pain, without features of bowel obstruction. A giant intra-abdominal simple cyst, separate from the ovaries, was seen on imaging. Initial haematological and biochemical investigations, including tumour markers, were normal. At laparotomy, the cystic tumour was discovered to arise from the sigmoid mesocolon and was resected en bloc. Histopathology revealed the tumour to be a benign extra-ovarian mucinous cystadenoma, which is a neoplasm of ovarian origin that can arise from extra-ovarian sites, including the mesentery. Extra-ovarian mucinous cystadenoma arising specifically from the mesentery are very rare intra-abdominal neoplasms with malignant potential despite its benign appearance on investigations. This case aims to raise awareness of this condition and to highlight its diagnostic approach and surgical management.

http://ift.tt/2FrfdDU

Genetically modified haloes: towards controlled experiments in ΛCDM galaxy formation

Roth, N; Pontzen, A; Peiris, HV; (2016) Genetically modified haloes: towards controlled experiments in ΛCDM galaxy formation. Monthly Notices of the Royal Astronomical Society , 455 (1) pp. 974-986. 10.1093/mnras/stv2375 . Green open access

http://ift.tt/2G6o52G

Antimicrobial and efflux inhibiting activity of natural products from Swazi medicinal plants

Sibandze, GF; (2018) Antimicrobial and efflux inhibiting activity of natural products from Swazi medicinal plants. Doctoral thesis (Ph.D), UCL (University College London).

http://ift.tt/2Frjnf1

Decentralised manufacturing of cell and gene therapy products: Learning from other healthcare sectors

Harrison, RP; Ruck, S; Rafiq, QA; Medcalf, N; (2018) Decentralised manufacturing of cell and gene therapy products: Learning from other healthcare sectors. Biotechnology Advances , 36 (2) pp. 345-357. 10.1016/j.biotechadv.2017.12.013 . Green open access

http://ift.tt/2G3ZRWQ

Glaucoma Care

Sharma, A; (2018) Glaucoma Care. Doctoral thesis (Ph.D), UCL (University College London). Green open access

http://ift.tt/2FrjmYv

Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease: a randomised blinded evaluation

Blomstedt, P; Stenmark Persson, R; Hariz, G-M; Linder, J; Fredricks, A; Häggström, B; Philipsson, J; ... Hariz, M; + view all Blomstedt, P; Stenmark Persson, R; Hariz, G-M; Linder, J; Fredricks, A; Häggström, B; Philipsson, J; Forsgren, L; Hariz, M; - view fewer (2018) Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease: a randomised blinded evaluation. Journal of Neurology, Neurosurgery and Psychiatry 10.1136/jnnp-2017-317219 . (In press). Green open access

http://ift.tt/2G7QPrO

Development of Easily Accessible Electricity Consumption Model Using Open Data and GA-SVR

Wang, S; (2018) Development of Easily Accessible Electricity Consumption Model Using Open Data and GA-SVR. Energies , 11 (2) , Article 373. 10.3390/en11020373 . Green open access

http://ift.tt/2DaiOnC

Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease

Lambert, C; Benjamin, P; Zeestraten, E; Lawrence, AJ; Barrick, TR; Markus, HS; (2016) Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease. Brain , 139 (4) pp. 1136-1151. 10.1093/brain/aww009 . Green open access

http://ift.tt/2G5yKuF

Developmental transcriptomics of the brittle star Amphiura filiformis reveals gene regulatory network rewiring in echinoderm larval skeleton evolution

Dylus, DV; Czarkwiani, A; Blowes, LM; Elphick, MR; Oliveri, P; (2018) Developmental transcriptomics of the brittle star Amphiura filiformis reveals gene regulatory network rewiring in echinoderm larval skeleton evolution. Genome Biology , 19 , Article 26. 10.1186/s13059-018-1402-8 . Green open access

http://ift.tt/2FqD5HQ

Ectopic GRHL2 Expression Due to Non-coding Mutations Promotes Cell State Transition and Causes Posterior Polymorphous Corneal Dystrophy 4

Liskova, P; Dudakova, L; Evans, CJ; Rojas Lopez, KE; Pontikos, N; Athanasiou, D; Jama, H; ... Hardcastle, AJ; + view all Liskova, P; Dudakova, L; Evans, CJ; Rojas Lopez, KE; Pontikos, N; Athanasiou, D; Jama, H; Sach, J; Skalicka, P; Stranecky, V; Kmoch, S; Thaung, C; Filipec, M; Cheetham, ME; Davidson, AE; Tuft, SJ; Hardcastle, AJ; - view fewer (2018) Ectopic GRHL2 Expression Due to Non-coding Mutations Promotes Cell State Transition and Causes Posterior Polymorphous Corneal Dystrophy 4. American Journal of Human Genetics , 102 (3) pp. 447-459. 10.1016/j.ajhg.2018.02.002 . Green open access

http://ift.tt/2G6gamd

Other disorders often associated with psychological trauma

Luyten, P; Van Assche, L; Kadriu, F; Krans, J; Claes, L; Fonagy, P; (2017) Other disorders often associated with psychological trauma. In: Dalenberg, C and Gold, S and Cook, J, (eds.) APA handbook of trauma psychology. American Psychological Association: Washington, DC, Unites States.

http://ift.tt/2D9RbeD

Elements of the complete blood count associated with cardiovascular disease incidence: Findings from the EPIC-NL cohort study

Lassale, C; Curtis, A; Abete, I; van der Schouw, YT; Verschuren, WMM; Lu, Y; Bueno-de-Mesquita, HBA; (2018) Elements of the complete blood count associated with cardiovascular disease incidence: Findings from the EPIC-NL cohort study. Scientific Reports , 8 , Article 3290. 10.1038/s41598-018-21661-x . Green open access

http://ift.tt/2G7QwgE

The control of Gaussian quantum states

Shackerley-Bennett, Uther; (2018) The control of Gaussian quantum states. Doctoral thesis (Ph.D), UCL (University College London). Green open access

http://ift.tt/2D9tGCx

Contribution of perinatal conditions to cerebral palsy in Uganda

Hassell, J; Tann, C; Idro, R; Robertson, NJ; (2018) Contribution of perinatal conditions to cerebral palsy in Uganda. [Editorial comment]. The Lancet Global Health , 6 (3) E248-E249. 10.1016/S2214-109X(18)30041-X . Green open access

http://ift.tt/2G6ozWM

Design and Performance Analysis of Urban Traffic Control Systems

Sha, Rui; (2018) Design and Performance Analysis of Urban Traffic Control Systems. Doctoral thesis (Ph.D), UCL (University College London).

http://ift.tt/2FqD3jc

Assessing patient-reported quality of life outcomes in vulva cancer patients

Froeding, L; Greimel, E; Lanceley, A; Oberguggenberger, A; Schmalz, C; Radisic, V; Nordin, A; ... Jensen, P; + view all Froeding, L; Greimel, E; Lanceley, A; Oberguggenberger, A; Schmalz, C; Radisic, V; Nordin, A; Galalaei, R; Kuljanic, K; Vistad, I; Schnack, T; Jensen, P; - view fewer (2018) Assessing patient-reported quality of life outcomes in vulva cancer patients. International Journal of Gynecological Cancer 10.1097/IGC.0000000000001211 . (In press).

http://ift.tt/2G5Yrvd

Exploring the lived experience of fibromyalgia using creative data collection methods

Brown, N; (2018) Exploring the lived experience of fibromyalgia using creative data collection methods. Cogent Social Sciences 10.1080/23311886.2018.1447759 . (In press). Green open access

http://ift.tt/2Fre0wm

Progression of MRI markers in cerebral small vessel disease: Sample size considerations for clinical trials

Benjamin, P; Zeestraten, E; Lambert, C; Ster, IC; Williams, OA; Lawrence, AJ; Patel, B; ... Markus, HS; + view all Benjamin, P; Zeestraten, E; Lambert, C; Ster, IC; Williams, OA; Lawrence, AJ; Patel, B; MacKinnon, AD; Barrick, TR; Markus, HS; - view fewer (2016) Progression of MRI markers in cerebral small vessel disease: Sample size considerations for clinical trials. Journal of Cerebral Blood Flow & Metabolism , 36 (1) pp. 228-240. 10.1038/jcbfm.2015.113 . Green open access

http://ift.tt/2G9qTMM

Investigation of cell cycle status in patients with acute myeloid leukaemia

Sellar, RS; (2018) Investigation of cell cycle status in patients with acute myeloid leukaemia. Doctoral thesis (Ph.D), UCL (University College London). Green open access

http://ift.tt/2Fn0cCT

Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry

Martinez-Ramirez, D; Jimenez-Shahed, J; Leckman, JF; Porta, M; Servello, D; Meng, F-G; Kuhn, J; ... Okun, MS; + view all Martinez-Ramirez, D; Jimenez-Shahed, J; Leckman, JF; Porta, M; Servello, D; Meng, F-G; Kuhn, J; Huys, D; Baldermann, JC; Foltynie, T; Hariz, MI; Joyce, EM; Zrinzo, L; Kefalopoulou, Z; Silburn, P; Coyne, T; Mogilner, AY; Pourfar, MH; Khandhar, SM; Auyeung, M; Ostrem, JL; Visser-Vandewalle, V; Welter, M-L; Mallet, L; Karachi, C; Houeto, JL; Klassen, BT; Ackermans, L; Kaido, T; Temel, Y; Gross, RE; Walker, HC; Lozano, AM; Walter, BL; Mari, Z; Anderson, WS; Changizi, BK; Moro, E; Zauber, SE; Schrock, LE; Zhang, J-G; Hu, W; Rizer, K; Monari, EH; Foote, KD; Malaty, IA; Deeb, W; Gunduz, A; Okun, MS; - view fewer (2018) Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry. JAMA Neurology 10.1001/jamaneurol.2017.4317 . (In press).

http://ift.tt/2G3Sz5v

Defining thalamic nuclei and topographic connectivity gradients in vivo

Lambert, C; Simon, H; Colman, J; Barrick, TR; (2017) Defining thalamic nuclei and topographic connectivity gradients in vivo. Neuroimage , 158 pp. 466-479. 10.1016/j.neuroimage.2016.08.028 . Green open access

http://ift.tt/2FrdWN8

Prevalence of hidradenitis suppurativa in Brazil: a population survey

http://ift.tt/2HhHPjw

In This Issue

http://ift.tt/2HduE2M

Schlafen-8 is essential for lymphatic endothelial cell activation in experimental autoimmune encephalomyelitis

Abstract

Schlafen-8 (Slfn8) is a member of the Schlafen family of proteins, which harbor helicase domains and are induced by LPS and interferons. It has been reported that the Schlafen family are involved in various cellular functions, including proliferation, differentiation and regulation of virus replication. Slfn8 has been implicated in T-cell differentiation in the thymus. However, the roles of Slfn8 in the immune system remains unclear. In this study, we generated Slfn8 knockout mice (Slfn8^−/−) and investigated the immunological role of Slfn8 using the T-cell-mediated autoimmune model experimental autoimmune encephalomyelitis (EAE). We found that the clinical score was reduced in Slfn8^−/− mice. IL-6 and IL-17A cytokine production, which are associated with EAE onset and progression, were decreased in the lymph nodes of Slfn8^−/− mice. Immune cell populations in Slfn8^−/− mice, including macrophages, neutrophils, T cells and B cells, did not reveal significant differences compared with wild-type mice. In vitro activation of Slfn8^−/− T cells in response to TCR stimulation also did not reveal significant differences. To confirm the involvement of non-hematopoietic cells, we isolated CD45⁻ CD31⁺ endothelial cells and CD45⁻CD31⁻ gp38⁺ fibroblastic reticular cells by FACS sorting. We showed that the levels of IL-6 and Slfn8 mRNA in CD45⁻ CD31⁺ endothelial cells were increased after EAE induction. In contrast, the level of IL-6 mRNA after EAE induction was markedly decreased in CD31⁺ endothelial cells from Slfn8^−/− mice. These results indicate that Slfn8 may play a role in EAE by regulating inflammation in endothelial cells.

http://ift.tt/2FD8PwM

Mechanisms controlling nucleic acid-sensing Toll-like receptors

Abstract

Nucleic acid (NA)-sensing Toll-like receptors (TLRs) respond to DNA/RNA derived from pathogens and dead cells. Structural studies have revealed a variety of molecular mechanisms by which TLRs sense NAs. Double-stranded RNA and single-stranded DNA directly bind to TLR3 and TLR9, respectively, whereas TLR7 and TLR8 bind to nucleosides and oligoribonucleotides derived from RNAs. Activation of ligand-bound TLRs is influenced by the functional status of TLRs. Proteolytic cleavage of NA-sensing TLRs enables ligand-dependent TLR dimerization. Trafficking of ligand-activated TLRs in endosomal and lysosomal compartments is requisite for production of type I interferons. Activation of NA-sensing TLRs is required for the control of viruses such as herpes simplex virus and endogenous retroviruses. On the other hand, excessive activation of NA-sensing TLRs drives disease progression in a variety of inflammatory diseases including systemic lupus erythematosus, heart failure, arthritis and non-alcoholic steatohepatitis. NA-sensing TLRs are targets for therapeutic intervention in these diseases. We here focus on our recent progresses in our understanding of NA-sensing TLRs.

http://ift.tt/2Hh4Gvu