Cochlear implantation using the underwater technique: long-term results

Abstract

Introduction

The opening of the round window and the insertion of the electrode array into the scala tympani during cochlear implant surgery can lead to a pressure shock of the delicate inner ear structures. By filling the tympanic cavity with Ringer Solution during these surgical steps (underwater technique), the hydrostatic pressure of the fluid acts as a smooth pressure stabilizer, avoiding a pressure shock of the inner ear structures. The aim of this retrospective study was to present long-term results of this new method of cochlear implantation in underwater technique.

Methods

Altogether, 47 implantations in 43 patients with residual hearing at the frequencies 250, 500 and 1000 Hz in the unaided preoperative pure tone audiometry were included. A cochlear implantation via round window with a conventional full-length electrode was performed in underwater technique. Changes of residual hearing 7 weeks and 24 months after surgery were analyzed.

Results

Overall postimplant hearing preservation 7 weeks after implantation was achieved in 22 ears (47%). Subsequent follow-up was performed on average 24 months after surgery (range 12 months–4.2 years) in all patients. At this late postoperative evaluation, preservation of hearing was recorded in 18 ears (38%). Neither the follow-up time nor the type of electrode had a significant impact on the postoperative hearing loss.

Conclusion

The underwater technique is an atraumatic cochlear implantation technique with hearing preservation rates comparable to results in literature and a very small hearing preservation decline rate over time even when using full-length CI electrodes.

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Stapes Surgery Teaching Tool: A Simple, Stable and Successful Technique

Abstract

Stapes surgery is a highly skilled surgery among otological procedures and needs a good dexterity. To improve the skills one may need to do procedures using temporal bone dissections. We describe a procedure that is simple, inexpensive and improves the skills and can be done using easily available materials like disposable syringe, stapler pin and a forceps.

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Risk of depression among patients with acne in the U.K.: a population-based cohort study

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Comparative safety and efficacy of topical mometasone furoate with other topical corticosteroids

Abstract

Derivatives of hydrocortisone, such as mometasone furoate, a (2′) furoate-17 ester with chlorine substitutions at positions 9 and 21, have been designed to improve efficacy and reduce the incidence of adverse effects. An extensive literature search of MEDLINE, Embase and other databases was conducted to review the safety and efficacy of various formulations of topical mometasone furoate. Mometasone furoate exhibits high potency with greater anti-inflammatory activity and a longer duration of action than betamethasone. In clinical trials, mometasone furoate shows comparable or significantly better efficacy, depending on the comparator, in all indications studied in both adults and children. It is well tolerated with only transient, mild to moderate local adverse effects. It is characterised by low systemic availability due to its high lipophilicity, low percutaneous absorption and rapid hepatic biotransformation, and consequently has no significant effect on the hypothalamic-pituitary-adrenal axis. The molecular biotransformation of mometasone furoate in the skin results in a lower affinity with dermal cells than epidermal cells, which contributes to its low atrophogenicity. Sensitisation to mometasone furoate is low. Overall, mometasone furoate is a highly efficacious potent corticosteroid with a low risk of both local and systemic adverse effects.

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Infant case of tinea faciei caused by Microsporum canis

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Necrobiosis lipoidica with mucin deposition in a patient with autoimmune thyroiditis

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Decrease in eosinophils infiltrating into the skin of patients with dipeptidyl peptidase-4 inhibitor-related bullous pemphigoid

Abstract

Bullous pemphigoid (BP) is an acquired autoimmune blistering disease in which autoantibodies against epitopes in the basement membrane zone of the skin such as BP180 or BP230 are produced. Dipeptidyl peptidase (DPP)-4 inhibitors have become commonly used to treat diabetes. As DPP-4 inhibitors are more commonly prescribed for diabetes, BP related to DPP-4 inhibitors has been reported and has attracted attention. Therefore, we retrospectively investigated patients who were diagnosed with BP in order to examine characteristics of DPP-4 inhibitor-related BP (nine patients; median age, 85 years) in comparison with non-DPP-4 inhibitor-related BP (21; median age, 85 years). There was no significant difference in Bullous Pemphigoid Disease Area Index between DPP-4 inhibitor-related BP patients and non-DPP-4 inhibitor-related BP patients, except for erosions/blisters score in mucosa. Laboratory tests revealed no significant differences between DPP-4 inhibitor-related BP patients and non-DPP-4 inhibitor-related BP patients in total white blood cell count, eosinophil count, neutrophil count and the titer of anti-BP180 antibody. The number of eosinophils infiltrating into the skin was significantly lower in patients with DPP4 inhibitor-related BP than in patients with non-DPP4 inhibitor-related BP. Our results showed that DPP-4 inhibitor-related BP has some distinct pathological characteristics from BP not associated with DPP-4 inhibitor.

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Randomized investigator-blinded comparative study of moisturizer containing 4-t-butylcyclohexanol and licochalcone A versus 0.02% triamcinolone acetonide cream in facial dermatitis

Summary

Background

Facial dermatitis can result from various conditions, some of which are of a chronic and relapsing nature. The use of topical corticosteroid therapy may lead to additional adverse effects.

Objective

To compare the efficacy of moisturizer containing 4-t-butylcyclohexanol, which acts as a sensitivity regulator, and licochalcone A, an anti-inflammatory agent from the licorice plant Glycyrrhiza inflata, with that of 0.02% triamcinolone acetonide (TA) for the treatment of facial dermatitis.

Methods

This was a randomized, prospective, investigator-blinded study. Eighty participants with mild to moderate facial dermatitis were randomly treated with either the test facial moisturizer or 0.02% TA twice daily for the first 2 weeks. For the subsequent 2 weeks, all patients used only the test moisturizer. Clinical assessment by investigators, bioengineering measurements, patients' subjective evaluation, and clinical photography were performed at baseline, week 2, and week 4.

Results

Both treatments showed a statistically significant improvement with regard to physician clinical assessment, skin hydration, transepidermal water loss, and patient-assessed visual analog scale after 2 and 4 weeks of treatment compared with baseline. The test facial moisturizer produced better skin hydration than TCS. The improvement in TEWL after 4 weeks of using the test moisturizer was comparable with 2-week treatment with 0.02% TA cream. However, subjective evaluation by patients indicated that TA more rapidly improved sensation sensitivity.

Conclusion

The test facial moisturizer was slower than 0.02% TA in improving facial dermatitis, but showed greater benefit in erythema control and skin hydration.

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Upper Lid Thick Skin Blepharoplasty

Facial plast Surg 2018; 34: 043-049
DOI: 10.1055/s-0037-1615824

While many of the basic tenants of upper lid blepharoplasty remain constant regardless of skin type, the thick-skinned eyelid patient requires special consideration. The brow may be naturally lower in the thick-skinned patient. These patients are more prone to having the brow pulled downward while attempting to remove redundant skin. There may also be more fat in the medial and central compartments. There may be fat in a lateral compartment overlying the lacrimal gland. Patient's expectations for a deep lid sulcus and complete excision of redundant skin may not be possible. They are more prone to an observable scar, a small dog ear at the lateral wound edge, and prolonged postoperative lid edema. Patients with lifelong upper lid fullness must get some input from significant others because their upper face aesthetic will change. In these patients, the eyelid surgery is not a rejuvenation, but a creation.
[...]

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Integrated Management of the Thick-Skinned Rhinoplasty Patient

Facial plast Surg 2018; 34: 003-008
DOI: 10.1055/s-0037-1617445

Patients with thick skin are a challenge in facial plastic surgery. Rhinoplasty is still the most frequently performed facial plastic procedure worldwide and it becomes very difficult to obtain optimal consistent results in these patients. A systematic presurgical skin evaluation is performed dividing skin into type I–III depending on the elasticity, oiliness, presence of skin alterations, size of skin pores, and laxity. Depending on the skin type, presurgical, surgical, and postsurgical management of the epidermis and dermis is defined. Preconditioning and treating thick skin can improve postsurgical results and reduce postsurgical unwanted results.
[...]

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Indications and Use of Isotretinoin in Facial Plastic Surgery

Facial plast Surg 2018; 34: 075-081
DOI: 10.1055/s-0037-1617446

Isotretinoin is a first generation retinoid with pleiotropic effects on keratinocyte differentiation, proliferation, and activity of sebaceous glands. For years, there has been intense debate on whether the use of isotretinoin combined with cosmetic or surgical procedures is safe and potentially more efficient than either therapy alone. Due to delays in wound healing and keloid formation, conservative recommendations were not to combine isotretinoin with any plastic surgery or local treatment at 6 to 12 months after discontinuation of the drug. However, there is increasing evidence that a combination approach is not only safe, but may also provide excellent cosmetic outcomes in acne scars, sebaceous gland hyperplasia, and thick-skinned patients undergoing facial plastic surgery. In particular, low-dose regimens of isotretinoin may offer advantages over standard dosage treatments because of better tolerability and safety in long-term use adjunct with surgical interventions. In this article, the authors aim to summarize the current evidence on the use of isotretinoin in facial plastic surgery and to share their experience from selected patients.
[...]

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Use of 5-Fluorouracil for Management of the Thick-Skinned Nose

Facial plast Surg 2018; 34: 009-013
DOI: 10.1055/s-0037-1617420

Patients with a thick nasal skin and soft tissue envelope can have unpredictable results and irregular scarring after rhinoplasty surgery. These patients typically have sebaceous tissue over the nasal tip and are particularly susceptible to soft tissue polly beak formation and excess scar tissue in the radix, tip, and septum. Targeted injections of 5-fluorouracil alone or mixed with low concentrations of steroid can be useful to prevent and treat excess postoperative scar tissue deposition. Ideally, four to six injections are performed every 1 to 4 weeks beginning 1 week postoperatively. The injections are most beneficial when performed within the first 3 months after surgery. Even a single injection may improve outcomes with minimal side effects.
[...]

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Surgical Approach to the Thick Nasolabial Folds, Jowls and Heavy Neck—How to Approach and Suspend the Facial Ligaments

Facial plast Surg 2018; 34: 059-065
DOI: 10.1055/s-0037-1615283

Patients with thick skin typically present with a redundant, baggy, lax skin envelope together with prominent nasolabial folds, jowls, and a heavy neck. Durable and natural-appearing rejuvenation is not possible unless the deformities are addressed adequately and harmoniously in these patients. Traditional superficial musculoaponeurotic system techniques do not include surgical release of the zygomatic cutaneous ligaments and repositioning of descendent malar fat pad, and may lead to an unbalanced, unnatural appearance and the lateral sweep phenomenon. Additional attempts to improve unopposed nasolabial folds such as fat grafting to malar region are more likely to result with a "stuffed" look, far from a natural and rejuvenated appearance, and must therefore be avoided. The facelift techniques including true release of the anchoring ligaments of the midface and allowing adequate repositioning of saggy tissues are ideal for these patients to obtain harmonious, natural result. Despite the extensive dissections, maximal release, and maximal lateral pull, additional maneuvers, e.g., platysmaplasty, subplatysmal fat removal, or partial resection of submandibular glands may be required for satisfying result in patients with heavy neck. In this article, the authors outline the relevant anatomy of the facial retaining ligaments and their implications to surgical management of patients with heavy skin are discussed.
[...]

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Reducing Periorbital Edema and Ecchymosis after Rhinoplasty: Literature Review and Personal Approach

Facial plast Surg 2018; 34: 014-021
DOI: 10.1055/s-0037-1617444

Postoperative periorbital edema and ecchymosis are most bothersome to rhinoplasty patients. The degree of swelling and bruising is influenced by several factors, and numerous prophylactic and therapeutic measures have been described in the literature. This article reviews the current literature and concludes with the author's suggestions on how to best minimize postoperative periorbital edema and ecchymosis.
[...]

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Managing the Thick Skin in Facial Plastic Surgery

Facial plast Surg 2018; 34: 001-002
DOI: 10.1055/s-0037-1617447

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Surgical Management of the Thick-Skinned Nose

Facial plast Surg 2018; 34: 022-028
DOI: 10.1055/s-0037-1617421

When executed properly, open structure rhinoplasty can dramatically improve the consistency, durability, and quality of the cosmetic surgical outcome. Moreover, in expert hands, dramatic transformations in skeletal architecture can be accomplished with minimal risk and unparalleled control, all while preserving nasal airway function. While skeletal enhancements have become increasingly more controlled and precise, the outer skin-soft tissue envelope (SSTE) often presents a formidable obstacle to a satisfactory cosmetic result. In noses with unusually thick skin, excessive skin volume and characteristically hostile healing responses frequently combine to obscure or sometimes even negate cosmetic skeletal modifications and taint the surgical outcome. For this challenging patient subgroup, care must be taken to optimize the SSTE using a graduated treatment strategy directed at minimizing skin thickness and controlling unfavorable healing responses. When appropriate efforts are implemented to manage thick nasal skin, cosmetic outcomes are often substantially improved, sometimes even negating the ill-effects of thick skin altogether.
[...]

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Managing the Lower Eyelid Complex in the Thick-Skinned Patient

Facial plast Surg 2018; 34: 050-058
DOI: 10.1055/s-0037-1617419

Thick skin presents a unique set of challenges within the realm of facial plastic surgery, and addressing the lower lid complex is no exception. There are several procedures for addressing the lower lids, the first and foremost being lower lid blepharoplasty. However, the remaining procedures combined with surgical techniques have exclusive implications in thick skin. Understanding the anatomy and various techniques that can be applied to thick skin can help achieve aesthetically more pleasing results in comparison to those of thin skin. As will be discussed in this article, patients with skin color of Fitzpatrick's grade III or higher have several characteristics associated with their skin, including thicker dermis as well as different patterns of aging, which have implications for addressing the lower lid complex. The senior author has extensive experience performing lower lid procedures and seeks to impart how best to understand and adapt for these differences to allow for the best aesthetic result.
[...]

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Surgical Tips for the Management of the Wide Nasal Base

Facial plast Surg 2018; 34: 029-035
DOI: 10.1055/s-0037-1621714

Alar base reduction (ABR) was first described by Weir in 1892, but continues to be a controversial topic in rhinoplasty in terms of optimal techniques. The authors describe the techniques for ABR including internal, external and combined ABR, flare excisions, and alar hooding reductions. The techniques described have resulted in consistent outcomes with acceptable scarring and high patient satisfaction.
[...]

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Cool Atmospheric Plasma (J-Plasma) and New Options for Facial Contouring and Skin Rejuvenation of the Heavy Face and Neck

Facial plast Surg 2018; 34: 066-074
DOI: 10.1055/s-0037-1621713

Treating patients with heavy or thick features comes with challenges not present in those patients lacking these physical characteristics. The authors report our experience with cool atmospheric plasma for facial contouring and skin rejuvenation of the heavy face and neck including rhinophyma. Cool atmospheric plasma is generated by running helium gas over radiofrequency energy. The resulting plasma is a fourth state of matter and has enhanced clinical effects for ablation and thinning of skin and soft tissues as well of contouring and tightening of deeper soft tissues and fascia. Cool helium plasma has been a very effective tool for skin rejuvenation and skin tightening as well as using it as a tool for nonexcisional microinvasive face and neck rejuvenation. Future research may indicate that it can help treat primary or recurrent superficial cutaneous malignancies.
[...]

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Management of the Heavy Brows: Long-Term Surgical Options

Facial plast Surg 2018; 34: 036-042
DOI: 10.1055/s-0037-1617422

One of the first signs of aging belongs to the upper third of the face. With the aging process, mestizo facial features become more prominent. The thicker skin-soft tissue envelope (S-STE) has a tendency to sag more, hooding of the eyelids tends to be more pronounced, and there is a tendency for eyebrows to droop, specifically the tail of the brows, because of the loss of support. A "tired" or "sad" look implies that the complex eyebrow-upper eyelid is showing one or more of these signs. Different surgical as well as non-surgical techniques have been described to treat this area, every one of them aiming at making the patient look rested and natural. The objective of this study is to describe a technique for endoscopic brow lifting, consisting on minimal incisions, a biplanar dissection, and a different fixation technique designed for helping reshape the brow. This particular surgical technique has shown the advantage of being minimally invasive and effective. Careful analysis of the patient should be made to decide both the technique and the changes desired by the patient and the surgeon. The authors believe the technique described is another option for approaching and fixating the heavy eyebrows in mestizo patients.
[...]

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Straticyte demonstrates prognostic value over oral epithelial dysplasia grade for oral potentially malignant lesion assessment

Publication date: February 2018
Source:Oral Oncology, Volume 77
Author(s): Jason T.K. Hwang, Ying R. Gu, Benjamin J. Dickson, Mi Shen, Ranju Ralhan, Paul G. Walfish, David Mock, Kenneth P.H. Pritzker




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Editorial Board/Aims & Scope

Publication date: February 2018
Source:Oral Oncology, Volume 77





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Topical therapy for refractory rhinosinusitis caused by methicillin-resistant Staphylococcus aureus: First report in a prospective series

The incidence of refractory chronic rhinosinusitis (CRS) associated with methicillin-resistant Staphylococcus aureus (MRSA) is rising and remains a therapeutic challenge. The goal of this study is to demonstrate the efficacy of a non-invasive topical therapy against MRSA in these patients.

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Factors affecting the outcome of adenoidectomy in children treated for chronic otitis media with effusion

The aim of this cohort was to determine potential risk factors, concerning the effectiveness of adenoidectomy in the treatment of chronic otitis media with effusion in children.

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Author's response to ‘fractional exhaled nitric oxide: signaling lung function changes in obstructive lung diseases.’

We would like to express our appreciation to the authors of the correspondence in response to our article. Fractional exhaled nitric oxide (FeNO) is known as a noninvasive biomarker reflecting allergic airway inflammation in asthma. Some reports have suggested relationships between FeNO and both bronchial hyperresponsiveness and airway obstruction. In our study, we concluded that elevated mean FeNO levels may indicate annual declines of forced expiratory volume in one second (FEV1) in asthmatic subjects.

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Tribute to albert sheffer MD and sheldon spector MD

A lot will be spoken and written about Albert Sheffer MD and Sheldon Spector MD, and they will be honored for their accomplishments and character. The Joint Task Force on Practice Parameters would like to insure that they are honored as well for the roles that they played in the development of guidelines for the field of allergy and immunology, since their outstanding careers can be linked to their commitment in this regard.

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Skiing and Snowboarding: Safety On The Slopes

With the winter Olympics starting this week, not to mention cold temperatures and occasional snow here at home, you might be considering a trip to a local ski resort.  Skiing and snowboarding appeal to all ages and sizes. And it's a great activity for winter weekends.  It can also be a good workout and provide some practice for kids learning coordination and body control.  Here are a few tips to help keep you and your family safe, while having fun on the slopes.

• Proper clothing is important: Look for clothing that is water and wind-resistant. Hats are important because most heat loss occurs through the head.  Layers are a great way to deal with changing temperatures.  You will get warm with skiing and want to have layers to shed.
• Wear a helmet! Like riding a bike or scooter, you have to wear a helmet.  High speeds, trees, other skiers, all put your child at risk for a possible head injury.  Wearing a helmet will reduce this risk.
• Apply sunscreen before hitting the slopes: Sun reflects off of the snow and can lead to sunburn easier than you think.
• Proper equipment is key: You wouldn't go out on the soccer field with shoes that are too big. The same goes for skiing.  Have proper boots, bindings, and skis fitted by a professional.  Improper equipment can lead to something as simple as blisters or as serious as a broken bone.
• Take a lesson: Like other sports, proper technique is important to avoid injury.  At least for the first time on the mountain, it's great if your child takes a skiing or snowboard lesson from a qualified instructor.  They can spend the morning learning and the rest of the day skiing safely with the family.
• Stick to slopes of your ability: Watch signs closely to indicate the difficulty of the slope. If you or your child gets in over his or her head, move to the side, take of your skis/snowboard and slide down the hill.  Many ski resorts have runs with trees.  BEWARE!  These runs also have rocks and can be hazardous.  Make sure the ability level is there to complete these runs.
• Drink lots of water: The cold weather can make dehydration deceiving. Drink plenty of water when taking breaks in the lodge.

Following these suggestions can help keep you and your child safe on the slopes.  Skiing in pairs is super important, especially when you kids are first starting out.  In case of a fall, it is important to have someone there to help.  If the fall is serious, contact ski patrol for help.

The post Skiing and Snowboarding: Safety On The Slopes appeared first on ChildrensMD.

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Mouse Study Adds to Evidence Linking Gut Bacteria and Obesity

A new Johns Hopkins study of mice with the rodent equivalent of metabolic syndrome has added to evidence that the intestinal microbiome — a "garden" of bacterial, viral and fungal genes — plays a substantial role in the development of obesity and insulin resistance in mammals, including humans.

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Evaluation of Dynamic CT Scans and Analyzing Its Efficacy Accuracy in Staging of Laryngeal CA: A Prospective Analysis of 30 Patients and Review of Literature

Abstract

Laryngeal and hypopharyngeal cancer is the most common cancer in the head and neck. It is the most commonly reported human malignancy, with more than 100,000 cases reported annually worldwide. Thus, exact staging of the tumor is of utmost importance in the decision making of the management of these patients. CT can directly evaluate penetration of tumor into the laryngeal soft tissues and cartilages; whereas laryngoscopy and contrast laryngography can only infer deepseated abnormalities from changes in surface contour of the laryngeal cavity. The main aims of our study were: (1) To assess whether dynamic CT scans increase the diagnostic efficacy for laryngeal and hypopharyngeal cancers and its extent in surrounding structures. (2) To assess the importance of phonation CT scans in evaluation and diagnosis of vocal cord paralysis/fixity and involvement of subglottic region and pre epiglottic space.

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Evaluation of Dynamic CT Scans and Analyzing Its Efficacy Accuracy in Staging of Laryngeal CA: A Prospective Analysis of 30 Patients and Review of Literature

Abstract

Laryngeal and hypopharyngeal cancer is the most common cancer in the head and neck. It is the most commonly reported human malignancy, with more than 100,000 cases reported annually worldwide. Thus, exact staging of the tumor is of utmost importance in the decision making of the management of these patients. CT can directly evaluate penetration of tumor into the laryngeal soft tissues and cartilages; whereas laryngoscopy and contrast laryngography can only infer deepseated abnormalities from changes in surface contour of the laryngeal cavity. The main aims of our study were: (1) To assess whether dynamic CT scans increase the diagnostic efficacy for laryngeal and hypopharyngeal cancers and its extent in surrounding structures. (2) To assess the importance of phonation CT scans in evaluation and diagnosis of vocal cord paralysis/fixity and involvement of subglottic region and pre epiglottic space.

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Salvage skull base reconstruction in the endoscopic era: Vastus lateralis free tissue transfer

Abstract

Background

When locoregional flaps fail to reconstruct the skull base, the microvascular surgeon faces several reconstructive challenges. We present our technique and results of salvage anterior skull base reconstruction utilizing the vastus lateralis free tissue transfer (VLFTT).

Methods

Four patients with anterior skull base defects after previous locoregional flap failure underwent free tissue transfer reconstruction with VLFTT.

Results

The success rate of free tissue transfer was 100%. Complete separation of the intracranial and sinonasal cavities was achieved in all patients; thus, resolving the cerebrospinal fluid (CSF) leakage in all patients. The VLFTT was inset through a minimally invasive approach utilizing an anterior maxillotomy via a gingivobuccal incision, an endoscopic medial maxillectomy, and endoscopic inset in all patients. No vein grafts were needed.

Conclusion

This technique permits endoscopic endonasal inset and placement of reliable, well vascularized free tissue that may be utilized for complex, secondary reconstruction of the skull base.

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Brief Summary Report from the 14th Biennial Meeting of the International Xenotransplantation Association

The fourteenth meeting of the International Xenotransplantation Association (IXA) 2017, was held at University of Maryland, Baltimore, between September 19th and 23rd, 2017. This monograph summarizes reported progress in the field. Address for correspondence: Richard N. Pierson III, MD, Austen Professor of Cardiac Surgery, Massachusetts General Hospital, Cox 6-662, Cardiac Surgery, 55 Fruit Street, Boston, MA 02114 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Protecting Donor Livers During Normothermic Machine Perfusion With Stem Cell EVs

No abstract available

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Extended Pancreas Donor Program – The EXPAND Study A prospective multicenter trial testing the use of pancreas donors over age 50

AbstractBackgroundPancreas transplantation is the only curative treatment option for patients with juvenile diabetes. Organ shortage and restrictive allocation criteria are the main reasons for increasing waitlists leading to severe morbidity and mortality. We designed a study to increase the donor pool with extended donor criteria (EDC) organs (donor age 50-60 years or BMI 30-34kg/m2).MethodsUtilization of EDC organs required the implementation of a new allocation system within Eurotransplant. The study was a prospective, multicenter, two-armed trial. The primary endpoint was pancreas function after 3 months. Rejection episodes, kidney function and waitlist time were secondary endpoints. Patients receiving an EDC organ were study-group patients; recipients of standard organs were control-group patients. Follow-up was 1 year.Results79 patients were included in 12 German centers; 18 received EDC organs and 61 received standard organs. Recipient demographics were similar. Mean EDC donor age was 51.4 ± 5 years versus 31.7 ± 12 in the control group. Insulin-free graft survival was 83.3% for EDC and 67.2% for standard organs (p=0.245) after 3 months. 1-year pancreas survival was 83.3% and 83.5% in the EDC versus standard group. 1-year kidney allograft survival was approximately 94% in both groups. Rejection episodes and morbidity were similar.ConclusionEXPAND shows in a prospective trial that selected EDC organs of donors aged >50 years can be used with outcomes similar to standard-criteria organs, therefore showing potential to reduce organ shortage and waiting times. This study substantiates the full implementation of EDC organs in a pancreas allocation system. Background Pancreas transplantation is the only curative treatment option for patients with juvenile diabetes. Organ shortage and restrictive allocation criteria are the main reasons for increasing waitlists leading to severe morbidity and mortality. We designed a study to increase the donor pool with extended donor criteria (EDC) organs (donor age 50-60 years or BMI 30-34kg/m2). Methods Utilization of EDC organs required the implementation of a new allocation system within Eurotransplant. The study was a prospective, multicenter, two-armed trial. The primary endpoint was pancreas function after 3 months. Rejection episodes, kidney function and waitlist time were secondary endpoints. Patients receiving an EDC organ were study-group patients; recipients of standard organs were control-group patients. Follow-up was 1 year. Results 79 patients were included in 12 German centers; 18 received EDC organs and 61 received standard organs. Recipient demographics were similar. Mean EDC donor age was 51.4 ± 5 years versus 31.7 ± 12 in the control group. Insulin-free graft survival was 83.3% for EDC and 67.2% for standard organs (p=0.245) after 3 months. 1-year pancreas survival was 83.3% and 83.5% in the EDC versus standard group. 1-year kidney allograft survival was approximately 94% in both groups. Rejection episodes and morbidity were similar. Conclusion EXPAND shows in a prospective trial that selected EDC organs of donors aged >50 years can be used with outcomes similar to standard-criteria organs, therefore showing potential to reduce organ shortage and waiting times. This study substantiates the full implementation of EDC organs in a pancreas allocation system. Corresponding author: Dr. Andrea Proneth, University Hospital Freiburg, Department of Surgery, Hugstetter Str. 55, 79106 Freiburg, Germany, e-mail: andrea.proneth@uniklinik-freiburg.de Trial registration: Trial registered at http://ift.tt/PmpYKN NCT01384006 Competing interests: A.P.'s 1, 16 institution (University Hospital Regensburg) received a research grant from Astellas and Novartis to support the conduct of the trial. H.J.S has received lecture honoraria and reimbursement of travel expenses from Novartis, Astellas, Pfizer and Roche, and also receives research support from Pfizer and Novartis. S.A.F. has received lecture honoraria, reimbursement of travel expenses and receives research support from Novartis, Astellas, BMS and Roche. FR received travel grants and speaker's bureau from Novartis, Roche, Biotest and Astellas. All other authors declare that they have no competing interests. The study was sponsored by the University Hospital Regensburg and was supported by research grants from Astellas and Novartis. Authors' contributions: A.P.1, 16 and S.A.F initiated, designed and coordinated the study. A.P.1, 16 collected an interpreted data for analysis, managed medical monitoring and wrote the first manuscript draft. E.K.G. and R.V. were involved in designing the study and critical data interpretation and analysis. A.A.S was involved in launching and designing the study, as well as data collection and inclusion of study patients. R.V., P.S.3, A. W., H.A., S.M., S.N., M.H., M.A.S., B.B., P.S.11,15, T.B., W.O.B., A.P.13, F.R. and H.J.S. were involved in data collection and inclusion of study patients, local ethics approval and critical intellectual discussion of the manuscript. All authors reviewed and approved the manuscript. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Airway inflammation after epicutaneous sensitization of mice requires protease activity of low-dose allergen inhalation

Publication date: Available online 6 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Izumi Nishioka, Toshiro Takai, Natsuko Maruyama, Seiji Kamijo, Punyada Suchiva, Mayu Suzuki, Shinya Kunimine, Hirono Ochi, Sakiko Shimura, Katsuko Sudo, Hideoki Ogawa, Ko Okumura, Shigaku Ikeda




http://ift.tt/2nOhNfx

Epidermal lipid composition, barrier integrity and eczematous inflammation are associated with skin microbiome configuration

Publication date: Available online 5 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Hansjörg Baurecht, Malte C. Rühlemann, Elke Rodríguez, Frederieke Thielking, Inken Harder, Anna-Sophie Erkens, Dora Stölzl, Eva Ellinghaus, Melanie Hotze, Wolfgang Lieb, Sheng Wang, Femke-Anouska Heinsen, Andre Franke, Stephan Weidinger
BackgroundGenomic approaches have revealed characteristic site-specificities of skin bacterial community structures. In addition, in children with atopic dermatitis (AD), characteristic shifts were described at creases and in particular during flares, which have been postulated to mirror the disturbed skin barrier function and/or cutaneous inflammation.ObjectiveWe sought to comprehensively analyse microbial configurations in AD across body sites, and to explore the impact of distinct abnormalities of epidermal barrier function.MethodsThe skin microbiome was determined by bacterial 16S rRNA sequencing at 4 nonlesional body sites as well as acute and chronic lesions of 10 AD patients and 10 healthy controls matched for age, sex and FLG mutation status. Nonlesional sampling sites were characterized for skin physiology parameters including chromatography-based lipid profiling.ResultsEpidermal lipid composition, in particular levels of long-chain unsaturated free fatty acids, strongly correlated with bacterial composition, in particular Propionibacteria and Corynebacteria abundance. AD displayed a distinct community structure with increased abundance and altered composition of staphylococcal species across body sites with the strongest loss of diversity and increase of S. aureus seen on chronic lesions, and a progressive shift from nonlesional skin to acute and chronic lesions. FLG deficient skin showed a distinct microbiome composition partly resembling the AD-related pattern.ConclusionEpidermal barrier integrity and function impact the skin microbiome composition. AD shows an altered microbial configuration across diverse body sites, which however is most pronounced at sites of predilection and atopic dermatitis. Eczematous affection appears to be a more important determinant than body site.



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Characterization of drug-neutralizing antibodies in patients with Fabry disease during infusion

Publication date: Available online 5 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Malte Lenders, Boris Schmitz, Stefan Martin Brand, Dirk Foell, Eva Brand
In patients with Fabry disease, neutralizing anti-drug antibodies were identified as IgG4 isotypes. The determination of antibody titers during infusions indicated that high dosages of enzyme overcome anti-drug antibody titers, necessitating individually tailored dose adjustment.



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SCCA2 is a reliable biomarker for evaluating pediatric atopic dermatitis

Publication date: Available online 5 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Mizuho Nagao, Shinichiro Inagaki, Toshiki Kawano, Yoshinori Azuma, Noriko Nomura, Yasuhiko Noguchi, Shoichiro Ohta, Atsushi Kawaguchi, Hiroshi Odajima, Yukihiro Ohya, Takao Fujisawa, Kenji Izuhara




http://ift.tt/2E6iADH

Reprograming Immunity to Food Allergens

Publication date: Available online 5 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Ashley L. St. John, Gladys W.X. Ang, Abhay P.S. Rathore, Soman N. Abraham
A novel immune-modulatory therapy utilizing targeted delivery of cytokines to draining lymph nodes effectively reprograms Th2 allergic responses towards a Th1 and tolerogenic profile, resulting in protection from peanut antigen-induced anaphylaxis.



http://ift.tt/2nOyG9R

Autonomous role of Wiskott-Aldrich Syndrome platelet deficiency in inducing autoimmunity and inflammation

Publication date: Available online 6 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Lucia Sereni, Maria Carmina Castiello, Francesco Marangoni, Achille Anselmo, Dario di Silvestre, Sara Motta, Elena Draghici, Stefano Mantero, Adrian J. Thrasher, Silvia Giliani, Alessandro Aiuti, Pierluigi Mauri, Luigi D. Notarangelo, Marita Bosticardo, Anna Villa
BackgroundWiskott-Aldrich Syndrome (WAS) is an X-linked immunodeficiency characterized by eczema, infections and susceptibility to develop autoimmunity and malignancies. Thrombocytopenia is a constant finding, but its pathogenesis remains elusive.ObjectiveTo dissect the basis of WAS platelet (PLT) defect we used a novel conditional mouse model (CoWas) lacking WASp only in the megakaryocytic lineage in presence of a normal immunological environment and in parallel we analysed samples obtained from WAS patients.MethodsPhenotypical and functional characterization of megakaryocytes and platelets in mutant CoWas mice and WAS patients with and without autoantibodies were performed. Platelet antigen expression was examined through protein expression profile and cluster proteomic interaction network. Platelet immunogenicity was tested by ELISA assays and B and PLTs co-culture.ResultsCoWas displayed increased MK numbers and normal thrombopoiesis in vitro but WASp-deficient PLTs had short lifespan and high expression of activation markers. Proteomic analysis identified signatures compatible with defects in cytoskeletal reorganization and metabolism, yet surprisingly increased antigen-processing capabilities. In addition, WASp-deficient PLTs expressed high levels of surface and soluble CD40L and were capable of inducing B-cell activation in vitro. WASp-deficient PLTs were highly immunostimulatory in mice and triggered the generation of antibodies specific for WASp-deficient PLTs even in the context of a normal immune system. WAS patients also showed PLT hyperactivation and elevated plasma soluble CD40L levels correlating with the presence of auto-antibodies.ConclusionOverall, these findings suggest that intrinsic defects in WASp-deficient PLTs decrease their lifespan and dysregulate immune responses, corroborating the role of PLTs as modulators of inflammation and immunity.

Graphical abstract

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Vaccine-associated hypersensitivity

Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2
Author(s): Michael M. McNeil, Frank DeStefano
Information for Category 1 CME CreditCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions.Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted.Date of Original Release: February 2018. Credit may be obtained for these courses until January 31, 2019.Copyright Statement: Copyright © 2018-2019. All rights reserved.Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Michael M. McNeil, MD, MPH, and Frank DeStefano, MD, MPH (authors); Zuhair K. Ballas, MD (editor)Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: The authors declare that they have no relevant conflicts of interest. Z. K. Ballas (editor) disclosed no relevant financial relationships.Activity Objectives:1. To be able to discuss the differences in underlying mechanisms and presentation of immediate and delayed vaccine reactions.2. To be aware of the most recent vaccine guidelines regarding patients with egg allergy and influenza vaccination.3. To understand the limited data supporting other components of vaccines that might be implicated as possible causes of anaphylaxis.4. To be able to discuss the rate and clinical risk factors for vaccine-triggered anaphylaxis.Recognition of Commercial Support: This CME activity has not received external commercial support.List of CME Exam Authors: Daniel Har, MD, Shyam Joshi, MD, Mariam Wahidi, MD, Shazia Lutfeali, MD, and David A. Khan, MD.Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: The exam authors disclosed no relevant financial relationships.Vaccine-associated hypersensitivity reactions are not infrequent; however, serious acute-onset, presumably IgE-mediated or IgG and complement-mediated anaphylactic or serious delayed-onset T cell–mediated systemic reactions are considered extremely rare. Hypersensitivity can occur because of either the active vaccine component (antigen) or one of the other components. Postvaccination acute-onset hypersensitivity reactions include self-limited localized adverse events and, rarely, systemic reactions ranging from urticaria/angioedema to full-blown anaphylaxis with multisystem involvement. Risk of anaphylaxis after all vaccines is estimated to be 1.31 (95% CI, 0.90-1.84) per million vaccine doses, respectively. Serious hypersensitivity reactions after influenza vaccines are particularly important because of the large number of persons vaccinated annually. Influenza vaccines are unique in requiring annual changes in the vaccines' antigenic composition to match the predicted circulating influenza strains. Recently, novel influenza vaccine types were introduced in the United States (recombinant vaccines, some with higher antigen content and a new adjuvanted vaccine). Providers should be aware of changing recommendations on the basis of recent published evidence for persons with a history of egg allergy to receive annual influenza vaccination. Further research is needed to elucidate the pathophysiology and risk factors for reported vaccine-associated adverse events. Further research is also needed to determine whether repeated annual inactivated influenza vaccination, the number of vaccine antigens administered at the same time, and the current timing of routine infant vaccinations are optimal for overall population well-being.



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Vaccine-associated hypersensitivity

Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2





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Novel therapies for alopecia areata: The era of rational drug development

Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2
Author(s): Etienne C.E. Wang, Zhenpeng Dai, Angela M. Christiano
Treatments for alopecia areata (AA) have evolved over the decades from broad and nonspecific therapies to those that are now more targeted and rationally selected. This was achieved by means of close cooperation and communication between clinicians and basic scientists, which resulted in the elucidation and understanding of the unique pathophysiology of AA. In this review we discuss this evolution and how novel therapies for AA have changed over the decades, what we have in our current arsenal of drugs for this potentially devastating disease, and what the future holds.



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The Editors' Choice

Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2
Author(s): Zuhair K. Ballas




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News Beyond Our Pages

Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2
Author(s): Marc E. Rothenberg, Jean Bousquet




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The keratin 16 null phenotype is modestly impacted by genetic strain background in mice

Abstract

The type I intermediate filament keratin 16 (K16) is constitutively expressed in ectoderm-derived appendages and is inducibly expressed in the epidermis upon barrier-compromising challenges. Dominantly-acting missense alleles in KRT16 are causative for pachyonychia congenita (PC), a genodermatosis involving debilitating palmoplantar keratoderma (PPK), nail dystrophy, oral lesions and, frequently, alterations in glands and hair. C57Bl/6;Krt16^-/- mice develop oral lesions early after birth and PC-like PPK lesions as young adults. These PPK lesions have a marked dysregulation of skin barrier related genes and innate immunity effectors (e.g., danger-associated molecular patterns), and are preceded by oxidative stress secondary to hypoactive Nrf2 signaling. These molecular features are present in PPK lesions of PC patients. Here we report that all components of the C57Bl/6;Krt16^-/- mouse phenotype occur as well in the FVB strain background, albeit less severely so, a significant observation in light of variations in the clinical presentation of individuals harboring disease-causing mutations in the KRT16 gene.

This article is protected by copyright. All rights reserved.

http://ift.tt/2ELL8zs

UVB and NGF-induced cutaneous sensitization in humans selectively augment cowhage and histamine-induced pain and mechanical hyperknesis

Abstract

Exaggerated itch responses to pruritic chemical provocations and mechanical stimuli are evident in patients with chronic itch, e.g., in atopic dermatitis. Currently used human models of itch do not account for such itch sensitization features and the mechanisms underlying clinical itch sensitization are unknown. This study utilized two established human models of cutaneous nociceptive sensitization to explore how pre-established inflammatory hyperalgesia (ultraviolet-B-irradiation; 'UVB') and non-inflammatory neurotrophic pain sensitization (nerve growth factor; 'NGF') alter sensitivity to chemical and mechanically-evoked itch. Twenty healthy volunteers participated in the UVB-experiment. Six volar forearm areas (2cm diameter) were UVB-irradiated with ≥2 x minimal erythemal dose and two non-irradiated areas were used as controls. Sixteen healthy volunteers participated in the NGF-experiment and had 2μg intradermally injected (4x50μL in 2cm diameter areas) into both volar forearms. Isotonic saline was applied as control. Pain sensitivity measurements (mechanical and heat pain thresholds) were conducted to validate the models. Subsequently, itch was evoked using histamine and cowhage spicules in the sensitized skin areas and itch/pain was rated using visual analogue scales. Mechanical hyperknesis (increased itch to punctuate stimuli) was probed with von Frey filaments before/after each itch provocation. Both UVB- and NGF-models induced robust primary mechanical hyperalgesia (p<0.01) and hyperknesis (p<0.05). Neither of the models augmented itch in response to chemical itch provocations but significant increases specifically for pain ratings were observed for both histamine and cowhage (p<0.05). This suggests that these models are of limited value as proxies for the itch sensitization to pruritogens observed in inflammatory dermatoses.

This article is protected by copyright. All rights reserved.

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Laparoscopic low anterior resection for rectal cancer with rectal prolapse: a case report

Rectal cancer with rectal prolapse is rare, described by only a few case reports. Recently, laparoscopic surgery has become standard procedure for either rectal cancer or rectal prolapse. However, the use of l...

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Central Serous Chorioretinopathy Associated with Desmopressin Nasal Spray: Causality or Unfortunate Association

Purpose: To describe the possible association between central serous chorioretinopathy (CSCR) and desmopressin use. Methods: The case histories of 2 middle-aged men with CSCR using desmopressin nasal spray were studied. Results: The diagnosis of CSCR was made on the basis of clinical features and ancillary testing (fluorescein angiography and optical coherence tomography). Both patients were using desmopressin nasal spray for polyuria when they developed the first ocular symptoms. Both of them also had an independent risk factor for developing CSCR. Conclusion: We suggest that desmopressin-induced hypercortisolism might implicate the development of CSCR in some patients. A larger study on patients using desmopressin nasal spray would be beneficial to confirm the possible association between this form of therapy and the development of CSCR.
Case Rep Ophthalmol 2018;9:120–125

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Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study

Caniglia, EC; Cain, LE; Sabin, CA; Robins, JM; Logan, R; Abgrall, S; Mugavero, MJ; ... Hernan, MA; + view all Caniglia, EC; Cain, LE; Sabin, CA; Robins, JM; Logan, R; Abgrall, S; Mugavero, MJ; Hernandez-Diaz, S; Meyer, L; Seng, R; Drozd, DR; Seage, GR; Bonnet, F; Dabis, F; Moore, RD; Reiss, P; van Sighem, A; Mathews, WC; del Amo, J; Moreno, S; Deeks, SG; Muga, R; Boswell, SL; Ferrer, E; Eron, JJ; Napravnik, S; Jose, S; Phillips, A; Justice, AC; Tate, JP; Gill, J; Pacheco, A; Veloso, VG; Bucher, HC; Egger, M; Furrer, H; Porter, K; Touloumi, G; Crane, H; Miro, JM; Sterne, JA; Costagliola, D; Saag, M; Hernan, MA; - view fewer (2017) Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study. The Lancet HIV , 4 (6) e251-e259. 10.1016/S2352-3018(17)30043-7 . Green open access

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Training cortical signals by means of a BMI-EEG system, its evolution and intervention. A case report

Monge-Pereira, E; Casatorres Perez-Higueras, I; Fernandez-Gonzalez, P; Ibanez-Pereda, J; Ignacio Serrano, J; Molina-Rueda, F; (2017) Training cortical signals by means of a BMI-EEG system, its evolution and intervention. A case report. Revista De Neurología , 64 (8) pp. 362-366.

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The Camden & Islington Research Database: Using electronic mental health records for research

Werbeloff, N; Osborn, DPJ; Patel, R; Taylor, M; Stewart, R; Broadbent, M; Hayes, JF; (2018) The Camden & Islington Research Database: Using electronic mental health records for research. PLoS One , 13 (1) , Article e0190703. 10.1371/journal.pone.0190703 . Green open access

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Preventing the spread of multidrug-resistant tuberculosis and protecting contacts of infectious cases

Fox, GJ; Schaaf, HS; Mandalakas, A; Chiappini, E; Zumla, A; Marais, BJ; (2017) Preventing the spread of multidrug-resistant tuberculosis and protecting contacts of infectious cases. Clinical Microbiology and Infection , 23 (3) pp. 147-153. 10.1016/j.cmi.2016.08.024 . Green open access

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Room-Temperature Plasma-Assisted Inkjet Printing of Highly Conductive Silver on Paper

Knapp, CE; Chemin, JB; Douglas, SP; Abessolo Ondo, D; Guillot, J; Choquet, P; Boscher, ND; (2018) Room-Temperature Plasma-Assisted Inkjet Printing of Highly Conductive Silver on Paper. Advanced Materials Technologies 10.1002/admt.201700326 .

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Failure to initiate HIV treatment in patients with high CD4 counts: evidence from demographic surveillance in rural South Africa

Bor, J; Chiu, C; Ahmed, S; Katz, I; Fox, MP; Rosen, S; Yapa, M; ... Bärnighausen, T; + view all Bor, J; Chiu, C; Ahmed, S; Katz, I; Fox, MP; Rosen, S; Yapa, M; Tanser, F; Pillay, D; Bärnighausen, T; - view fewer (2018) Failure to initiate HIV treatment in patients with high CD4 counts: evidence from demographic surveillance in rural South Africa. Tropical Medicine and International Health , 23 (2) 10.1111/tmi.13013 .

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Revisiting the genetics of APOE

Carmona, S; Kun-Rodrigues, C; Brás, J; Guerreiro, R; (2017) Revisiting the genetics of APOE. Sinapse , 17 (2) pp. 27-36. Green open access

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Youth, waste and work in Mathare: whose business and whose politics?

Thieme, T; (2010) Youth, waste and work in Mathare: whose business and whose politics? Environment and Urbanization , 22 (2) pp. 333-352. 10.1177/0956247810379946 .

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A scalable method to quantify the relationship between urban form and socio-economic indexes

Venerandi, A; Quattrone, G; Capra, L; (2018) A scalable method to quantify the relationship between urban form and socio-economic indexes. EPJ Data Science 10.1140/epjds/s13688-018-0132-1 . Green open access

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Can we measure inflation expectations using commodity futures prices?

Coffman, DD; Saleuddin, R; (2018) Can we measure inflation expectations using commodity futures prices? Structural Change and Economic Dynamics 10.1016/j.strueco.2018.01.002 . (In press).

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Effect of population viral load on prospective HIV incidence in a hyperendemic rural African community

Tanser, F; Vandormael, A; Cuadros, D; Phillips, AN; de Oliveira, T; Tomita, A; Barnighausen, T; Tanser, F; Vandormael, A; Cuadros, D; Phillips, AN; de Oliveira, T; Tomita, A; Barnighausen, T; Pillay, D; - view fewer (2017) Effect of population viral load on prospective HIV incidence in a hyperendemic rural African community. Science Translational Medicine , 9 (420) , Article eaam8012. 10.1126/scitranslmed.aam8012 .

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TMS of primary motor cortex with a biphasic pulse activates two independent sets of excitable neurones

Sommer, M; Ciocca, M; Chieffo, R; Hammond, P; Neef, A; Paulus, W; Rothwell, JC; Sommer, M; Ciocca, M; Chieffo, R; Hammond, P; Neef, A; Paulus, W; Rothwell, JC; Hannah, R; - view fewer (2018) TMS of primary motor cortex with a biphasic pulse activates two independent sets of excitable neurones. Brain Stimulation 10.1016/j.brs.2018.01.001 . (In press). Green open access

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Voluntary motor commands reveal awareness and control of involuntary movement

De Havas, J; Ghosh, A; Gomi, H; Haggard, P; (2016) Voluntary motor commands reveal awareness and control of involuntary movement. Cognition , 155 pp. 155-167. 10.1016/j.cognition.2016.06.012 . Green open access

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Smartphone app as a museum guide. Testing the Open Art application with blind, deaf, and sighted users

Jankowska, A; Szarkowska, A; Krejtz, K; Fidyka, A; Kowalski, J; Wichrowski, M; (2017) Smartphone app as a museum guide. Testing the Open Art application with blind, deaf, and sighted users. Rivista internazionale di tecnica della traduzione 10.13137/2421-6763/17354 . (In press).

http://ift.tt/2E6BVjM

A first-in-human study of the novel HIV-fusion inhibitor C34-PEG(4)-Chol

Quinn, K; Traboni, C; Penchala, SD; Bouliotis, G; Doyle, N; Libri, V; Khoo, S; ... Winston, A; + view all Quinn, K; Traboni, C; Penchala, SD; Bouliotis, G; Doyle, N; Libri, V; Khoo, S; Ashby, D; Weber, J; Nicosia, A; Cortese, R; Pessi, A; Winston, A; - view fewer (2017) A first-in-human study of the novel HIV-fusion inhibitor C34-PEG(4)-Chol. Scientific Reports , 7 , Article 9447. 10.1038/s41598-017-09230-0 . Green open access

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Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study

Guerreiro, R; Ross, OA; Kun-Rodrigues, C; Hernandez, DG; Orme, T; Eicher, JD; Shepherd, CE; ... Bras, J; + view all Guerreiro, R; Ross, OA; Kun-Rodrigues, C; Hernandez, DG; Orme, T; Eicher, JD; Shepherd, CE; Parkkinen, L; Darwent, L; Heckman, MG; Scholz, SW; Troncoso, JC; Pletnikova, O; Ansorge, O; Clarimon, J; Lleo, A; Morenas-Rodriguez, E; Clark, L; Honig, LS; Marder, K; Lemstra, A; Rogaeva, E; St George-Hyslop, P; Londos, E; Zetterberg, H; Barber, I; Braae, A; Brown, K; Morgan, K; Troakes, C; Al-Sarraj, S; Lashley, T; Holton, J; Compta, Y; Van Deerlin, V; Serrano, GE; Beach, TG; Lesage, S; Galasko, D; Masliah, E; Santana, I; Pastor, P; Diez-Fairen, M; Aguilar, M; Tienari, PJ; Myllykangas, L; Oinas, M; Revesz, T; Lees, A; Boeve, BF; Petersen, RC; Ferman, TJ; Escott-Price, V; Graff-Radford, N; Cairns, NJ; Morris, JC; Pickering-Brown, S; Mann, D; Halliday, GM; Hardy, J; Trojanowski, JQ; Dickson, DW; Singleton, A; Stone, DJ; Bras, J; - view fewer (2018) Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. The Lancet Neurology , 17 (1) pp. 64-74. 10.1016/S1474-4422(17)30400-3 .

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Universal test and treat and the HIV epidemic in rural South Africa: a phase 4, open-label, community cluster randomised trial

Iwuji, CC; Orne-Gliemann, J; Larmarange, J; Balestre, E; Thiebaut, R; Tanser, F; Okesola, N; ... ANRS 12249 TasP Study Group, ; + view all Iwuji, CC; Orne-Gliemann, J; Larmarange, J; Balestre, E; Thiebaut, R; Tanser, F; Okesola, N; Makowa, T; Dreyer, J; Herbst, K; McGrath, N; Bärnighausen, T; Boyer, S; De Oliveira, T; Rekacewicz, C; Bazin, B; Newell, M-L; Pillay, D; Dabis, F; ANRS 12249 TasP Study Group, ; - view fewer (2017) Universal test and treat and the HIV epidemic in rural South Africa: a phase 4, open-label, community cluster randomised trial. Lancet HIV 10.1016/S2352-3018(17)30205-9 . (In press).

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Agreed Definitions and a Shared Vision for New Standards in Stroke Recovery Research: The Stroke Recovery and Rehabilitation Roundtable Taskforce

Bernhardt, J; Hayward, KS; Kwakkel, G; Ward, NS; Wolf, SL; Borschmann, K; Krakauer, JW; ... Cramer, SC; + view all Bernhardt, J; Hayward, KS; Kwakkel, G; Ward, NS; Wolf, SL; Borschmann, K; Krakauer, JW; Boyd, LA; Carmichael, ST; Corbett, D; Cramer, SC; - view fewer (2017) Agreed Definitions and a Shared Vision for New Standards in Stroke Recovery Research: The Stroke Recovery and Rehabilitation Roundtable Taskforce. Neurorehabilitation and Neural Repair , 31 (9) pp. 793-799. 10.1177/1545968317732668 . Green open access

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Selective distortion of body image by asynchronous visuotactile stimulation.

Perez-Marcos, D; Martini, M; Fuentes, CT; Bellido Rivas, AI; Haggard, P; Sanchez-Vives, MV; (2018) Selective distortion of body image by asynchronous visuotactile stimulation. Body Image , 24 pp. 55-61. 10.1016/j.bodyim.2017.11.002 .

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War and Social Attitudes

Child, TB; Nikolova, E; (2018) War and Social Attitudes. Conflict Management and Peace Science (In press). Green open access

http://ift.tt/2E7VKXZ

PROGRESS Trial - Prophylactic Gabapentin for Relief of Symptoms and Improved Swallowing

Conditions:   Oropharyngeal Cancer;   HPV-Related Squamous Cell Carcinoma
Intervention:   Drug: Gabapentin
Sponsor:   University of Chicago
Recruiting

http://ift.tt/2nHxFkV

A Retrospective Clinical Study of Apatinib in Combination With Radiotherapy / Chemotherapy Second-line and Above in the Treatment of Recurrent / Metastatic Head and Neck Squamous Cell Carcinoma

Condition:   Head and Neck Squamous Cell Carcinoma
Intervention:   Drug: Apatinib plus chemoradiation
Sponsors:   Henan Cancer Hospital;   Jiangsu HengRui Medicine Co., Ltd.
Recruiting

http://ift.tt/2BZ0FbY

Lingual tonsillectomy with palatal surgery for the treatment of obstructive sleep apnea in adults: a systematic review and meta-analysis

Abstract

Objective

To conduct a systematic review and meta-analysis to evaluate effects of lingual tonsillectomy with palatal surgery as a combined procedure for the treatment of obstructive sleep apnea (OSA) in adults.

Search methods

Data source: a comprehensive search of MEDLINE, Scopus, Ovid, Web of Science, and the Cochrane Library was performed through November 2017. Manual searches and subject matter expert input were also obtained. This review includes studies assessing efficacy of lingual tonsillectomy with palatal surgery as a combined procedure for the treatment of OSA in adults, who had multilevel obstruction including lingual tonsil hypertrophy, in which apnea/hypopnea index (AHI) or respiratory disturbance index (RDI) were reported.

Results

A total of four studies (107 patients) met our inclusion criteria. Pooled random effects analysis demonstrated a statistically significant improvement of polysomnographic respiratory events postoperatively, with average AHI reduction of 18.51 events per hour, [95% confidence interval (CI) (− 31.72, − 5.31); P = 0.006] and increase in minimal arterial oxygen saturation of 5.26 [95% CI (0.10, 10.42); P = 0.05]. The result also showed that the procedures significantly improved sleepiness resulting in an average Epworth Sleepiness Scale (ESS) reduction of 5.44 [95% CI (− 8.69, − 2.18); P = 0.001].

Conclusion

A combination of lingual tonsillectomy with palatal surgery may offer benefits in a selected group of OSA adults, in terms of apnea/hypopnea index, minimal arterial oxygen saturation and Epworth Sleepiness Scale. Data were based on meta-analysis of all case series with 2–6 months' follow-up.

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A systematic review and meta-analysis of genotypic methods for detecting antibiotic resistance in Helicobacter pylori

Abstract

Background

Antibiotic susceptibility testing is essential for tailored treatments to cure Helicobacter pylori (H. pylori) infection. However, phenotypic methods have some limitations.

Objectives

To evaluate the feasibility of genotypic detection methods compared with phenotypic detection methods using samples taken from H. pylori-infected patients.

Methods

Literature searches were conducted in the following databases (from January 2000 to November 2016): PubMed, Embase, the Cochrane Library, and Web of Science. A meta-analysis and systematic review was performed for studies that compared genotypic methods with phenotypic methods for the detection of H. pylori antibiotic susceptibility.

Results

This meta-analysis showed that the pooled sensitivity, specificity, and diagnostic odds ratio (DOR) for the A2142G/C and/or A2143G combination for the detection of clarithromycin resistance in the strain samples were 0.97 (95% CI: 0.94-0.99), 1.00 (95% CI: 0.99-1.00), and 13 742 (95% CI: 1708-110 554), respectively. The pooled sensitivity, specificity, and DOR for the A2142G/C and/or A2143G combination for the detection of clarithromycin resistance in biopsy samples were 0.96 (95% CI: 0.90-0.99), 0.96 (95% CI: 0.91-0.99), and 722 (95% CI: 117-4443), respectively. The summarized sensitivity, specificity, and DOR value for the ability of the genotypic methods to detect quinolone resistance in biopsy specimens were 0.97 (95% CI: 0.87-0.99), 0.99 (95% CI: 0.92-1.00), and 6042 (95% CI: 486-75 143), respectively.

Conclusion

The genotypic detection methods were reliable for the diagnosis of clarithromycin and quinolone resistance in the strain and biopsy specimens. The A2142G/C and/or A2143G combination had the best sensitivity and specificity for the detection of clarithromycin resistance.

http://ift.tt/2E7aO8B

A Study of Clinicopathological Profile of Salivary Gland Swellings

Abstract

Salivary gland diseases usually present as a swelling of the affected gland. These lesions are commonly encountered in day to day practice. A salivary gland swelling can present in a variety of locations, depending on the salivary gland affected. The purpose of the study is to know the incidence of salivary gland swellings and the usefulness of FNAC in evaluating these swellings. The present study is a time bound prospective study of fifty consecutive cases of salivary gland swellings admitted in our hospital during the period November 2014–August 2016. Most of the patients underwent pre-operative work up with FNAC and patients indicated for surgery underwent surgery and HPE. Salivary gland swelling occurred more commonly in 3rd decade of life and equal number of cases were seen in both genders. Most of the patients presented with salivary gland swelling (98%). 21 (42%) were non neoplastic, 29 (58%) were neoplastic swellings, 18 (36%) were benign of which pleomorphic adenoma was the most common and 11 (22%) were malignant of which adenoid cystic carcinoma was the most common. Parotid gland was the most common gland involved. Fine needle aspiration cytology was highly sensitive for benign tumours and highly specific for malignant tumours. FNAC should be first choice of investigation in evaluating the salivary gland pathologies. Early diagnosis and subsequent appropriate management carries good prognosis.

http://ift.tt/2BGr2YH

Differential binding affinity of mutated peptides for MHC class I is a predictor of survival in advanced lung cancer and melanoma

Ghorani, E; Rosenthal, R; McGranahan, N; Reading, JL; Lynch, M; Peggs, KS; Swanton, C; Ghorani, E; Rosenthal, R; McGranahan, N; Reading, JL; Lynch, M; Peggs, KS; Swanton, C; Quezada, SA; - view fewer (2018) Differential binding affinity of mutated peptides for MHC class I is a predictor of survival in advanced lung cancer and melanoma. Annals of Oncology , 29 (1) pp. 271-279. 10.1093/annonc/mdx687 . Green open access

http://ift.tt/2BeqwAb

Isolation of Human Photoreceptor Precursors via a Cell Surface Marker Panel from Stem Cell-derived Retinal Organoids and Fetal Retinae

Lakowski, J; Welby, E; Budinger, D; Di Marco, F; Di Foggia, V; Bainbridge, JWB; Wallace, K; ... Sowden, JC; + view all Lakowski, J; Welby, E; Budinger, D; Di Marco, F; Di Foggia, V; Bainbridge, JWB; Wallace, K; Gamm, DM; Ali, RR; Sowden, JC; - view fewer (2018) Isolation of Human Photoreceptor Precursors via a Cell Surface Marker Panel from Stem Cell-derived Retinal Organoids and Fetal Retinae. Stem Cells 10.1002/stem.2775 . (In press). Green open access

http://ift.tt/2BHorxl

Para Teachers in India: Status and Impact

Kingdon, GG; Sipahimalani-Rao, V; (2010) Para Teachers in India: Status and Impact. Economic and Political Weekly , 40 (12) pp. 59-67.

http://ift.tt/2Be0DAr

Latent tuberculous screening of recent migrants attending language classes: a cohort study and cost analysis

Usdin, M; Dedicoat, M; Gajraj, R; Harrison, P; Kaur, H; Duffield, K; Walker, C-L; ... Zenner, D; + view all Usdin, M; Dedicoat, M; Gajraj, R; Harrison, P; Kaur, H; Duffield, K; Walker, C-L; Akram, Y; Aiyedun, V; Mohamed, H; Zenner, D; - view fewer (2017) Latent tuberculous screening of recent migrants attending language classes: a cohort study and cost analysis. The International Journal of Tuberculosis and Lung Disease , 21 (2) pp. 175-180. 10.5588/ijtld.16.0398 .

http://ift.tt/2BHJbVI

Non-invasive brain stimulation to promote motor and functional recovery following spinal cord injury

Gunduz, A; Rothwell, J; Vidal, J; Kumru, H; (2017) Non-invasive brain stimulation to promote motor and functional recovery following spinal cord injury. Neural Regeneration Research , 12 (12) pp. 1933-1938. 10.4103/1673-5374.221143 . Green open access

http://ift.tt/2BcFfLK

Operando Spectroscopic Studies of Cu–SSZ-13 for NH3–SCR deNOx Investigates the Role of NH3 in Observed Cu(II) Reduction at High NO Conversions

Greenaway, AG; Lezcano-Gonzalez, I; Agote-Aran, M; Gibson, EK; Odarchenko, Y; Beale, AM; (2018) Operando Spectroscopic Studies of Cu–SSZ-13 for NH3–SCR deNOx Investigates the Role of NH3 in Observed Cu(II) Reduction at High NO Conversions. Topics in Catalysis 10.1007/s11244-018-0888-3 . (In press). Green open access

http://ift.tt/2BIZbqD

Chapter 13 : Crisis-Affected Populations and Tuberculosis

Zenner, D; (2017) Chapter 13 : Crisis-Affected Populations and Tuberculosis. In: Schlossberg, D, (ed.) Tuberculosis and Nontuberculous Mycobacterial Infections. (pp. 229-236). ASM Press: Washington D.C, USA.

http://ift.tt/2BehcMj

Privacy, self-disclosure and real-name policy social media: The past and the future of their identity recognition techniques and the implications of a potential mainstream use of biometric technologies

Routsis, V; (2014) Privacy, self-disclosure and real-name policy social media: The past and the future of their identity recognition techniques and the implications of a potential mainstream use of biometric technologies. Presented at: Defining the Sensor Society, University of Queensland, Australia.

http://ift.tt/2BK6oGQ

Flow Data

Duke-Williams, O; Routsis, V; (2014) Flow Data. Presented at: Census Research User Conference 2014, Royal Statistical Society, London, United Kingdom. Green open access

http://ift.tt/2BdH7E7

Reservoir pressure separation at brachial, carotid and radial arteries: A quantitative comparison and evaluation

Ebner, M; Parker, K; Vercauteren, T; Ourselin, S; Wassertheurer, S; Hughes, AD; Hametner, B; (2017) Reservoir pressure separation at brachial, carotid and radial arteries: A quantitative comparison and evaluation. Presented at: UNSPECIFIED.

http://ift.tt/2BK6oqk

Magnetoencephalographic Correlates of Perceptual State During Auditory Bistability

Sanders, RD; Winston, JS; Barnes, GR; Rees, G; (2018) Magnetoencephalographic Correlates of Perceptual State During Auditory Bistability. Scientific Reports , 8 , Article 976. 10.1038/s41598-018-19287-0 . Green open access

http://ift.tt/2BdH775

The impact of migration on tuberculosis epidemiology and control in high-income countries: a review

Pareek, M; Greenaway, C; Noori, T; Munoz, J; Zenner, D; (2016) The impact of migration on tuberculosis epidemiology and control in high-income countries: a review. BMC Medicine , 14 , Article 48. 10.1186/s12916-016-0595-5 . Green open access

http://ift.tt/2BH9NGp

Calculating reservoir pressure with or without flow information: Similarity and algorithmic sensitivity at radial artery

Ebner, M; Parker, K; Vercauteren, T; Ourselin, S; Wassertheurer, S; Hughes, AD; Hametner, B; (2017) Calculating reservoir pressure with or without flow information: Similarity and algorithmic sensitivity at radial artery. Presented at: Artery17, Pisa, Italy.

http://ift.tt/2Bar4XE

Outcomes following Serial Intragastric Balloon Therapy for Obesity and Nonalcoholic Fatty Liver Disease in a Single Centre

Vi, N; Li, J; Gan, J; Cordero, P; Ray, S; Solis-Cuevas, A; Khatib, M; Vi, N; Li, J; Gan, J; Cordero, P; Ray, S; Solis-Cuevas, A; Khatib, M; Oben, JA; - view fewer (2017) Outcomes following Serial Intragastric Balloon Therapy for Obesity and Nonalcoholic Fatty Liver Disease in a Single Centre. Canadian Journal of Gastroenterology and Hepatology , 2017 , Article 4697194. 10.1155/2017/4697194 . Green open access

http://ift.tt/2BHoj0P

Fairness and Accountability Design Needs for Algorithmic Support in High-Stakes Public Sector Decision-Making

Veale, M; Van Kleek, M; Binns, R; (2018) Fairness and Accountability Design Needs for Algorithmic Support in High-Stakes Public Sector Decision-Making. In: (Proceedings) CHI'18: ACM Conference on Human Factors in Computing Systems. ACM (In press). Green open access

http://ift.tt/2Beh8w3

Parallel changes in serum proteins and diffusion tensor imaging in methamphetamine-associated psychosis

Breen, MS; Uhlmann, A; Ozcan, S; Chan, M; Pinto, D; Bahn, S; Stein, DJ; (2017) Parallel changes in serum proteins and diffusion tensor imaging in methamphetamine-associated psychosis. Scientific Reports , 7 , Article 43777. 10.1038/srep43777 . Green open access

http://ift.tt/2BFSl5a

Motivation to reduce alcohol consumption and subsequent attempts at reduction and changes in consumption in increasing and higher-risk drinkers in England: a prospective population survey

de Vocht, F; Brown, J; Beard, E; West, R; Michie, S; Campbell, R; Hickman, M; (2018) Motivation to reduce alcohol consumption and subsequent attempts at reduction and changes in consumption in increasing and higher-risk drinkers in England: a prospective population survey. Addiction 10.1111/add.14132 . (In press). Green open access

http://ift.tt/2Ba2YMJ

Energy-Efficient Heterogeneous Cellular Networks with Spectrum Underlay and Overlay Access

Tang, J; So, DKC; Alsusa, EA; Hamdi, KA; Shojaeifard, A; Wong, KK; (2017) Energy-Efficient Heterogeneous Cellular Networks with Spectrum Underlay and Overlay Access. IEEE Transactions on Vehicular Technology 10.1109/TVT.2017.2773506 . (In press). Green open access

http://ift.tt/2BIgaJG

Just-In-Time Kernel Regression for Expectation Propagation

Jitkrittum, W; Gretton, A; Heess, N; Eslami, A; Lakshminarayanan, B; Sejdinovic, D; Szabo, Z; (2015) Just-In-Time Kernel Regression for Expectation Propagation. In: Proceeding of Large-Scale Kernel Learning: Challenges and New Opportunities workshop. : Lille, France. (In press).

http://ift.tt/2Bc8dvb

Petri Automata

Brunet, P; Pous, D; (2017) Petri Automata. Logical Methods in Computer Science , 13 (3) , Article 33. 10.23638/LMCS-13(3:33)2017 . Green open access

http://ift.tt/2BJ6Sxa

Asthma in inner city children: recent insights United States

Purpose of review Children living in US inner cities experience disparate burdens of asthma, especially in severity, impairment, exacerbations, and morbidity. Investigations seeking to better understand the factors and mechanisms underlying asthma prevalence, severity, and exacerbation in children living in these communities can lead to interventions that can narrow asthma disparities and potentially benefit all children with asthma. This update will focus on recent (i.e. late 2016–2017) advances in the understanding of asthma in US inner city children. Recent findings Studies published in the past year expand understanding of asthma prevalence, severity, exacerbation, and the outcomes of guidelines-based management of these at-risk children, including: asthma phenotypes in US inner city children that are severe and difficult-to-control; key environmental determinants and mechanisms underlying asthma severity and exacerbations (e.g. allergy-mediated exacerbation susceptibility to rhinovirus); the importance of schools as a place for provocative exposures (e.g. mouse allergen, nitrogen dioxide) as well as a place where asthma care and outcomes can be improved; and the development and validation of clinically useful indices for gauging asthma severity and predicting exacerbations. Summary These recent studies provide a trove of actionable findings that can improve asthma care and outcomes for these at-risk children. Correspondence to Andrew H. Liu, MD, Children's Hospital Colorado and University of Colorado School of Medicine, 13123 East 16th Avenue, Box B395, Aurora, CO 80045, USA. Tel: +1 720 777 2127; e-mail: Andrew.liu@childrenscolorado.org Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Asthma exacerbation prediction: recent insights

Purpose of review Asthma attacks are frequent in children with asthma and can lead to significant adverse outcomes including time off school, hospital admission and death. Identifying children at risk of an asthma attack affords the opportunity to prevent attacks and improve outcomes. Recent findings Clinical features, patient behaviours and characteristics, physiological factors, environmental data and biomarkers are all associated with asthma attacks and can be used in asthma exacerbation prediction models. Recent studies have better characterized children at risk of an attack: history of a severe exacerbation in the previous 12 months, poor adherence and current poor control are important features which should alert healthcare professionals to the need for remedial action. There is increasing interest in the use of biomarkers. A number of novel biomarkers, including patterns of volatile organic compounds in exhaled breath, show promise. Biomarkers are likely to be of greatest utility if measured frequently and combined with other measures. To date, most prediction models are based on epidemiological data and population-based risk. The use of digital technology affords the opportunity to collect large amounts of real-time data, including clinical and physiological measurements and combine these with environmental data to develop personal risk scores. These developments need to be matched by changes in clinical guidelines away from a focus on current asthma control and stepwise escalation in drug therapy towards inclusion of personal risk scores and tailored management strategies including nonpharmacological approaches. Summary There have been significant steps towards personalized prediction models of asthma attacks. The utility of such models needs to be tested in the ability not only to predict attacks but also to reduce them. Correspondence to Dr Louise Fleming, MB ChB, MD, Clinical Senior Lecturer, Paediatric Respiratory Consultant, Department of Respiratory Paediatrics, Royal Brompton Hospital, Sydney Street, London SW3 6NP. Tel: +02073528121; e-mail: l.fleming@rbht.nhs.uk Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Precision medicine in the treatment of primary immunodeficiency diseases

Purpose of the review Since the 1990s with the advances in molecular biology, a number of genetic defects have been described. The International Union of Immunological Sciences has recently updated the classification of genetic defects associated with primary immune deficiencies that now number 354. With the ever-expanding list of new monogenic disorders and a better understanding of the immunobiology and function of these defective genes, new therapies have emerged particularly aimed at the autoimmune and inflammatory conditions that plague these patients. Recent findings Immune deficiencies associated with gain-of-function (GOF) mutations are a potential category for targeted therapies to control the GOF activities of the mutated gene. In addition to the increased susceptibility to infections these patients have autoimmune and inflammatory diseases that are difficult to control with conventional therapies. The dysregulated immune functions of the activated phospholipase-3-kinase δ syndrome, cytotoxic T lymphocyte-associated antigen-4 haploinsufficiency, lipopolysaccharide-responsive beige-like anchor deficiency, the GOF mutations of signal transducer and activator of transcription 1 and 3 immune deficiencies will be reviewed. The targeted therapies for each of these immune deficiencies using small molecule kinase inhibitors and fusion protein biologic modifiers will be described. Summary In this review, we explore the recent advances in precision medicine treatment of several primary immunodeficiency syndromes in which immune dysregulation is a key feature. Understanding the immunobiology associated with these GOF mutations has led to the use of biologic therapies to better control the associated autoimmune and inflammatory manifestations. Correspondence to Mark Ballow, MD, Morsani College of Medicine, Tampa; Division of Allergy and Immunology, Department of Pediatrics, Children's Research Institute (4th floor), 140 7th Ave South, St Petersburg, Florida 33701-4899, USA. E-mail: mballow@health.usf.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Role of IL-13Rα2 in modulating IL-13 induced MUC5AC and ciliary changes in healthy and CRSwNP mucosa

Abstract

Background

The IL-13 receptor α2 (IL-13Rα2) is a receptor for IL-13 which has conflicting roles in mediating IL-13 responses in the lower airway; with little known about its impact on upper airway diseases. We sought to investigate the expression of IL-13 receptors, IL-13Rα1 and IL-13Rα2, in chronically inflamed nasal epithelium, and explore IL-13 induced signaling pathways in an in vitro model of human nasal epithelial cells (hNECs).

Methods

The protein and mRNA expression levels of IL-13 and its receptors in nasal biopsies of patients with nasal polyps (NP) and healthy controls were evaluated. We investigated goblet cell stimulation with mucus hypersecretion induced by IL-13 (10 ng/mL, 72 hours) treatment in hNECs using a pseudo-stratified epithelium in air-liquid interface (ALI) culture.

Results

There were significant increases in IL-13, IL-13Rα1 and IL-13Rα2 mRNA and protein levels in NP epithelium with healthy controls as baseline. MUC5AC mRNA positively correlated with IL-13Rα2 (r=0.5886, p=0.002) but not with IL-13Rα1 in primary hNECs. IL-13 treatment resulted in a significant increase in mRNA and protein levels of IL-13Rα2 only in hNECs.. IL-13 treatment induced an activation of extracellular signal-regulated kinases (ERK)1/2 and an upregulation of C-JUN; where the IL-13 induced effects on hNECs could be attenuated by ERK1/2 inhibitor (50 μMol/L) or dexamethasone (10^-4-10^-7 Mol/L) treatment.

Conclusions

IL-13Rα2 has a potential role in IL-13 induced MUC5AC and ciliary changes through ERK1/2 signal pathway in the nasal epithelium. IL-13Rα2 may contribute to airway inflammation and aberrant remodeling which are the main pathological features of CRSwNP.

This article is protected by copyright. All rights reserved.

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Patient preference study for different characteristics of systemic psoriasis treatments (Protimisis)

Abstract

"The Protimisis" study was a multicenter, cross-sectional study investigating the relative importance and economic value that patients assign to different characteristics of systemic psoriasis treatments. Treatment preferences were investigated with the DCE methodology and patients had to decide over the most important aspects of different psoriasis treatments. A questionnaire regarding demographic data/medical history and the DLQI and EQ-5D-3L questionnaires were also completed.

A total of 310 patients were included. Out of those, 37.4% reported using oral medications for psoriasis as their most recent treatment, while the remaining patients reported treatment with injections once per week (14.8%), injections twice per week (7.4%), injections once every three months (29.4%) and intravenous injections every two months (8.4%) as their most recent treatment. Mean DLQI score was 6.6 (SD 6.5), and in the EQ-5D-3L index, 71.0% of patients reported having problems with anxiety or depression.

DCE analysis showed a clear preference for treatments with longer dosing intervals, rapid onset of action, lasting clinical response, low risk of SAEs and lower cost. The risk of SAEs was the most important treatment characteristic (54% of patients). Older patients showed less concern for safety matters than younger patients. The highest willingness-to-pay was recorded for treatments with longer dosing intervals and for safer treatment options.

http://ift.tt/2BaoalI

Bacillus Calmette-Guerin, polysaccharide nucleic acid in the treatment of cutaneous and oral lichen planus

Abstract

The aim of this study was to evaluate the safety and efficacy of Bacillus Calmette-Guerin, polysaccharide nucleic acid (BCG-PSN) therapy in the treatment of oral and cutaneous LP. Twenty-four LP patients were included in this study and classified randomly into; Oral LP group (OLP), 11 patients and Cutaneous LP group (CLP), 13 patients. All patients received intradermal injections of BCG-PSN, twice weekly for three weeks. Patients with complete response were followed up for 3 months. The assessment in OLP was based on the reduction in the treated area, (Reticulation/Erythema/Ulceration) REU scoring system and numerical rating scale (NRS). CLP evaluated by the response to treatment as (complete, partial and no response) and visual analogue scale (VAS). There were highly significant differences in the diminution of lesion areas (p < .006), NRS scores (p < .001), REU score (p < .011), and VAS (p < .001) after treatment. The majority of patients achieved complete response after 3-week management. The BCG-PNS is safe and effective in the treatment of oral and cutaneous LP.

http://ift.tt/2BH7L9f

The concept of type 2 segmental mosaicism, expanding from dermatology to general medicine

Abstract

In autosomal dominant skin disorders, the well-known type 1 segmental mosaicism reflects heterozygosity for a postzygotic new mutation. By contrast, type 2 segmental mosaicism originates in a heterozygous embryo from an early postzygotic mutational event giving rise to loss of the corresponding wild-type allele, which results in a pronounced segmental involvement being superimposed on the ordinary, non-segmental phenotype. Today, this concept has been proven by molecular analysis in many cutaneous traits. The purpose of this review was to seek publications of cases suggesting an extracutaneous manifestation of type 2 segmental mosaicism. Case reports documenting a pronounced extracutaneous segmental involvement were collected from the literature available in PubMed and from personal communications to the author. Pertinent cases are compared to the description of cutaneous segmental mosaicism of type 1 or type 2 as reported in a given trait. In total, reports suggesting extracutaneous type 2 segmental mosaicism were found in 14 different autosomal dominant skin disorders. In this way, clinical evidence is accumulated that extracutaneous type 2 segmental mosaicism does likewise occur in many autosomal dominant skin disorders. So far, however, molecular proof of this particular form of mosaicism is lacking. The present review may stimulate readers to inform colleagues of other specialties on this new concept, in order to initiate further research in this particular field of knowledge that has important implications for diagnosis, treatment and genetic counseling.

This article is protected by copyright. All rights reserved.

http://ift.tt/2BcKqv6

A Study of Clinicopathological Profile of Salivary Gland Swellings

Abstract

Salivary gland diseases usually present as a swelling of the affected gland. These lesions are commonly encountered in day to day practice. A salivary gland swelling can present in a variety of locations, depending on the salivary gland affected. The purpose of the study is to know the incidence of salivary gland swellings and the usefulness of FNAC in evaluating these swellings. The present study is a time bound prospective study of fifty consecutive cases of salivary gland swellings admitted in our hospital during the period November 2014–August 2016. Most of the patients underwent pre-operative work up with FNAC and patients indicated for surgery underwent surgery and HPE. Salivary gland swelling occurred more commonly in 3rd decade of life and equal number of cases were seen in both genders. Most of the patients presented with salivary gland swelling (98%). 21 (42%) were non neoplastic, 29 (58%) were neoplastic swellings, 18 (36%) were benign of which pleomorphic adenoma was the most common and 11 (22%) were malignant of which adenoid cystic carcinoma was the most common. Parotid gland was the most common gland involved. Fine needle aspiration cytology was highly sensitive for benign tumours and highly specific for malignant tumours. FNAC should be first choice of investigation in evaluating the salivary gland pathologies. Early diagnosis and subsequent appropriate management carries good prognosis.

http://ift.tt/2BGr2YH

Editorial Board

Publication date: January 2018
Source:Autoimmunity Reviews, Volume 17, Issue 1





http://ift.tt/2C0RUy4

Aspirin does not prevent growth of vestibular schwannomas: A case-control study

Objectives/Hypothesis

To determine if aspirin intake is associated with reduced growth of vestibular schwannomas (VS). To determine the prevalence of contraindications to regular aspirin in patients with VS.

Study Design

Retrospective, observational case-control study.

Methods

The study utilized a postal questionnaire and telephone interviews to determine aspirin exposure. Propensity score matching was used to control for age, sex, and tumor size. Cases were defined as patients with VS proven to have grown on serial magnetic resonance imaging (MRI). Controls were defined as patient with VS stable on serial MRI. Prevalence of regular aspirin use was compared in patients with growing VS versus stable VS. Absolute and relative contraindications to aspirin intake were recorded.

Results

Six hundred fifty-three patients with VS were contacted, and responses were received by 67% (220 cases and 217 controls). The mean tumor size was 11.3 mm (9.0 mm and 13.3 mm in controls and cases, respectively). Aspirin exposure was more common in stable VS than growing VS (22.1% vs. 17.3%). However, following matching to control for covariates, aspirin was not found to be associated with VS stability (P = .475). Multiple logistic regression (analysis of variance) found tumor size to be the only factor strongly associated with tumor growth (P < .0001). Ninety-two percent of patients were able to take aspirin, with the majority being at low risk of complications from regular use.

Conclusions

This study aimed to examine the relationship between aspirin intake and VS stability. In contrast to previous reports, after controlling for covariates, the findings do not demonstrate an association. Only tumor size at diagnosis appears predictive of risk of VS growth.

Level of Evidence

3b. Laryngoscope, 2018

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Efficacy and safety of continuous every 2-week dosing of ixekizumab over 52 weeks in patients with moderate-to-severe plaque psoriasis in a randomized phase 3 trial (IXORA-P)

Abstract

Introduction

Ixekizumab is an interleukin-17A antagonist approved for treatment of moderate-to-severe plaque psoriasis with recommended 160-mg starting dose, then 80 mg every 2 weeks (Q2W) through Week 12, and every 4 weeks (Q4W) thereafter. This study evaluated continuous every 2-week dosing (Q2W) over 52 weeks.

Methods

In this Phase 3, multicentre, double-blinded, parallel-group trial, three ixekizumab dosing regimens were assessed for efficacy and safety at Week 52 in patients with moderate-to-severe plaque psoriasis randomized at a 2:1:1 ratio to continuous Q2W (N=611), continuous Q4W (N=310), or dose adjustment per protocol (Q4W/Q2W, N=306), each with a 160-mg starting dose. Dose adjustment was determined by predefined criteria to which investigators were blinded; 72 (23.5%) patients in the Q4W/Q2W group adjusted dose. Efficacy outcomes were evaluated using logistic regression.

Results

Co-primary endpoints were met at Week 52; Psoriasis Area and Severity Index 75 responses for Q2W and Q4W dose groups were 85.9% and 79.0%, respectively (p=0.006), and static Patient Global Assessment 0/1 responses for Q2W and Q4W dose groups were 78.6% and 70.6%, respectively (p=0.005). Treatment-emergent and serious adverse events were comparable across dose groups.

Conclusions

Ixekizumab Q2W had higher efficacy at Week 52 compared to Q4W, with no increase in safety events.

This article is protected by copyright. All rights reserved.

http://ift.tt/2E644Ye

Complement activation in hidradenitis suppurativa: a new pathway of pathogenesis?

Abstract

Objective

Despite the heavy purulence observed in hidradenitis suppurativa (HS), kinetics of complement anaphylatoxins acting to prime chemotaxis of neutrophils has never been studied. Complement activation was explored in HS.

Methods

Circulating concentrations of complement factor C5a as well as of membrane attack complex C5b-9 were determined in the plasma of 54 treatment naïve patients and of 14 healthy controls as well as in the pus of seven patients. Results were correlated with Hurley stage and iHS4 score of severity. Peripheral blood mononuclear cells (PBMCs) were isolated form seven Hurley III stage patients and seven healthy volunteers and stimulated in the presence of 25% of plasma for the production of tumor necrosis factor-alpha (TNFα).

Results

Circulating C5a and C5b-9 were significantly greater in patient than in control plasma; however concentrations in pus were very low. Circulating C5a levels exceeding 28 ng/ml were associated with specificity greater than 90% with occurrence of HS. Circulating C5a and C5b-9 were greater among the more severe patients. PBMCs of patients produced great TNFα concentrations only when growth medium was enriched with patient plasma; this was reversed with the addition of the C5a blocker IFX-1.

Conclusions

Systemic complement activation occurs in HS and may be used as a surrogate biomarker of HS. C5a stimulates over-production of TNFα and may be a future therapeutic target.

This article is protected by copyright. All rights reserved.

http://ift.tt/2EILu9Q