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

Onset of action of the fixed combination intranasal azelastine-fluticasone propionate in an allergen exposure chamber

Publication date: Available online 7 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Jean Bousquet, Eli Meltzer, Peter Couroux, Arkady Koltun, Ferdinand Kopietz, Ullrich Munzel, Hans Christian Kuhl, Duc Tung Nguyen, Anne Marie Salapatek, David Price
BackgroundA fixed-dose combination of intranasal azelastine hydrochloride–fluticasone propionate (MP-AzeFlu) is the most effective treatment of allergic rhinitis (AR), but its onset of action requires further investigation.ObjectivesThis study compared onset of action of MP-AzeFlu with the free combination of oral loratadine and intranasal fluticasone propionate (LORA/INFP).MethodsIn this single-center randomized, placebo-controlled, double-blind, double-dummy, three-period crossover trial, AR symptoms were induced in asymptomatic patients by ragweed pollen challenge in an allergen environmental exposure chamber. Patients received single-dose MP-AzeFlu, LORA/INFP, or placebo and were monitored for 4 hours. The primary outcome was onset of action measured by total nasal symptom score (TNSS). Secondary measures were total ocular symptom score (TOSS), total score of the seven nasal and ocular symptoms (T7SS), and the global visual analogue scale (VAS).ResultsThe full analysis set included 82 patients; 78 completed all treatments. TNSS was significantly reduced versus placebo from 5 minutes for MP-AzeFlu and 150 minutes for LORA/INFP onward (both P<0.05) until the end of assessment (0 to 4 hours). MP-AzeFlu reduced TNSS to a greater extent at each time point from 5 to 90 minutes (P<0.05) and over the entire assessment interval (P≤0.005) versus LORA/INFP or placebo. No statistically significant difference between LORA/INFP and placebo was observed over the assessment interval (P=0.182). MP-AzeFlu onset of action assessed by TOSS, T7SS, and VAS was 10 minutes, 2 hours earlier than with LORA/INFP.ConclusionMP-AzeFlu had a more rapid onset of action (5 minutes) and was more effective than LORA/INFP.Registration of the trialClinicalTrials.gov Identifier: NCT03004131; Key words: allergic rhinitis, azelastine, environmental exposure chamber, fluticasone propionate, loratadine, onset of action

Smell loss is associated with severe and uncontrolled disease in children and adolescents with persistent allergic rhinitis

Publication date: Available online 6 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Franklin Mariño-Sanchez, Meritxell Valls-Mateus, Oliver Haag, Isam Alobid, Jean Bousquet, Joaquim Mullol

A favorable response to omalizumab in a patient with cheilitis granulomatosa

Publication date: Available online 6 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Eustachio Nettis, Elisabetta Di Leo, Maria Bisaccia, Carolina Marasco, Caterina Foti, Angelo Vacca

Increased Dose and Duration of Statin Use is Associated with Decreased Asthma-Related Emergency Department Visits and Hospitalizations

Publication date: Available online 6 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Jiu-Yao Wang, Tsung-Chieh Yao, Yu-Ting Tsai, Ann Chen Wu, Hui-Ju Tsai
BackgroundStatins have pleiotropic anti-inflammatory and immunomodulatory effects, yet the effect of statin use on asthma-related emergency department (ED) visits and hospitalizations has remained unclear, especially in Asian populations.ObjectiveWe sought to examine the effect of statin therapy on asthma-related ED visits and/or hospitalizations.MethodsA cohort study was conducted using data from Taiwan's National Health Insurance Research Database from 2001 to 2013. A total of 117,595 adult patients with asthma were included. The outcomes were defined as asthma-related ED visits and/or hospitalizations. Multiple Cox proportional hazards models were applied to determine the effect of statin use on asthma-related ED visits and/or hospitalizations.ResultsThere were 3,417 asthma-related ED visits and/or hospitalizations among 117,595 subjects with asthma. Statin users were significantly less likely to experience asthma-related ED visits and/or hospitalizations (adjusted hazard ratio: 0.81; 95% confidence interval: 0.74-0.89) compared with nonstatin users. The risks of asthma-related ED visits and/or hospitalizations were decreased among those with a higher cumulative defined daily dose (DDD), greater average DDD, and longer cumulative-day users than the counterparts.ConclusionsOur study suggests that statin use is associated with the decreased risk of asthma-related ED visits and/or hospitalizations in patients with asthma. A dose-response effect of statin use is also observed in this study. Therefore, future randomized clinical trials would be warranted to further evaluate the association.

Immune modulation in a patient with Morquio syndrome treated with enzyme replacement therapy

Publication date: Available online 6 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Angela Sun, Walaa Alshuaibi, Daniel Petroni, Suzanne Skoda-Smith, Michael J. Goldberg, Susan Hale

Efficacy and safety of five-day challenge for the evaluation of non-severe amoxicillin allergy in children

Publication date: Available online 7 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Roxane Labrosse, Louis Paradis, Jonathan Lacombe, Kathryn Samaan, François Graham, Jean Paradis, Philipps Bégin, Anne Des Roches
BackgroundPenicillin allergy is the most frequent drug allergy, among which aminopenicillins are reputed for causing delayed rashes in children, particularly in the context of viral infections. Despite a negative allergy evaluation, a significant proportion of individuals continue to avoid penicillin antibiotics for fear of an allergic reaction.ObjectivesThis study sought to evaluate the safety and efficacy of a five-day challenge to amoxicillin and the proportion of subsequent use of amoxicillin.MethodsPediatric patients with a history of a reaction to amoxicillin were prospectively recruited in the study. All patients were challenged, and those with negative immediate challenges underwent an ambulatory five-day challenge of amoxicillin to rule out nonimmediate reactions. Patients were called 2 years after their initial allergy evaluation to assess subsequent amoxicillin use and tolerance.ResultsOne hundred thirty children with a history of amoxicillin allergy underwent a graded drug provocation test (DPT) to amoxicillin. Three patients had a positive immediate challenge, three had a positive nonimmediate challenge, and two were equivocal. Of the 122 patients with a negative challenge, 114 (93.4%) were reached 2 years after their initial allergy evaluation: 75 had used antibiotics since, of which only 1 (1.3%) had refused to reuse amoxicillin because of fear of an allergic reaction. Finally, five-day DPT resulted in a 24.1% decrease in future penicillin avoidance compared to classical single-dose graded DPT performed over one day in a historical cohort (p<0.0001).ConclusionFive-day challenge is a safe and effective way to rule out nonimmediate amoxicillin allergy, and it ensures a better compliance with future penicillin use.

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.

Infant case of tinea faciei caused by Microsporum canis

Necrobiosis lipoidica with mucin deposition in a patient with autoimmune thyroiditis

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.

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.

Numerical simulation of the intra-annual evolution of beryllium-7 ( 7 Ве) in the surface layer of the Black Sea

Abstract

A numerical model simulating the distribution of ⁷Ве in the Black Sea was developed and applied to study the spatial and temporal variations in the content of ⁷Be in the surface waters. Variations in the distribution of ⁷Ве were analyzed for the period from January to December of 2012. The average seasonal content of ⁷Ве in the surface layer ranges from 2.2 to 6.2 Bq m⁻³. The maximum concentration is typical for the eastern part of the sea in winter to spring, and the minimum concentration is typical for the central and western parts of the sea in summer. The seasonally averaged activity of ⁷Ве on suspended matter ranges from 440 to 1560 Bq kg⁻¹. The highest values are observed in the sea in winter to spring, and the lowest values are typically observed in the central and western parts of the sea in summer. It was revealed that the adsorption of ⁷Ве on suspended matter is most significant for the evolution of the content of this radionuclide in shelf waters.

Identification of functional groups of Opuntia ficus-indica involved in coagulation process after its active part extraction

Abstract

Opuntia ficus-indica that belongs to the Cactaceae family and is a member of Opuntia kind has received increasing research interest for wastewater treatment by flocculation. The objectives of this study were (i) to provide more information regarding the active constituents of Opuntia spp. and (ii) to improve the extracting and using conditions of the flocculant molecules for water treatment. A classic approach by jar test experiments was used with raw and extracted material by solubilization and precipitation. The surface properties of solid material were characterized by FTIR, SEM, zeta potential measurement, and surface titration. The splitting based on the solubility of the material with pH and the titration of functional groups completed the method. The optimal pH value for a coagulation–flocculation process using cactus solid material (CSM) was 10.0 and a processing rate of 35 mg L⁻¹. The alkaline pH of flocculation suggests an adsorption mechanism with bridging effect between particles by water-soluble extracted molecules. To validate this mechanism, an extraction water was carried out at pH = 10 (optimum of flocculation) and the solution was acidified (pH = 7) to allow precipitation of so considered active flocculant molecules. The strong flocculant property of this extract was verified, and titration of this solution showed at least one specific pKa of 9.0 ± 0.6. This pKa corresponds to phenol groups, which could be assigned to lignin and tannin.

Microwave-assisted extraction and dyeing of chemical and bio-mordanted cotton fabric using harmal seeds as a source of natural dye

Abstract

The revival of cultural heritage in a form of natural colorants for textile dyeing is gaining popularity due to their soothing nature and bright shades. The present study was conducted to explore the coloring potential of harmala (Peganum harmala) seeds and to improve color strength of dye using microwave radiations followed by a mordanting process. The results showed that harmala plant seeds could be an excellent source of natural dyes for cotton dyeing if the irradiated acidified methanolic extract (RE, 4 min) is used to dye un-irradiated fabric (NRC) at 85 °C for 45 min using a dye bath of pH 9.0 having salt concentration of 7 g/100 mL. Alum (1%) as pre-mordants and iron (7%) as post-mordants have improved the color strength in chemical mordanting more than other mordants employed. The bio-mordants employed reveal that 10% of acacia as pre-bio-mordants and 7% of acacia as post-bio-mordants are effective amounts to obtain high color strength. Suggested ISO standards for colorfastness illustrate that bio-mordanting has given more excellent rating as compared to chemical mordants. It is concluded that harmala seeds have a great potential to act as a source of natural colorant for cotton dyeing under the influence of microwave radiation.

Levels and distribution of cobalt and nickel in the aquatic macrophytes found in Skadar Lake, Montenegro

Abstract

Macrophytes react to changes in the quality of the environment in which they live (water/sediment), and they are good bioindicators of surface water conditions. In the present study, the content of the metals cobalt (Co) and nickel (Ni) was determined in the sediment, the water, and different organs of macrophytes from six localities around Lake Skadar, across four different seasons of year. The aquatic macrophytes that have been used as bioindicator species in this study are Phragmites australis (an emerged species), Ceratophyllum demersum (a submerged species), and Lemna minor (a floating species). The aim of this study was to determine the distribution of metals in macrophyte tissues and also to discover the degree of bioaccumulation of the investigated metals, depending both on the location and on the season. The content of Co and Ni in the examined parts of the macrophytes was in the range of 0.04–8.78 and 0.30–28.5 ppm, respectively. The greatest content of the investigated metal in the organs of P. australis and C. demersum was recorded at the beginning of and during the growing season. Greater concentrations of metals in the tissue of L. minor were observed at the end of the growing season.

Using laboratory-generated biosolids to evaluate the microbial ecotoxicity of triclosan in a simulated land application scenario

Abstract

Land application accounts for approximately 50% of wastewater solids disposal in the USA. Yet, little is known regarding the ecological impacts of many non-regulated chemicals found in biosolids. In most previous studies aimed at assessing ecological impacts, a model biosolid is generated by spiking high concentrations of the target chemical into a soil or biosolid. This approach does not account for the interaction of the chemical of interest with the solids throughout the biosolids production process (a.k.a., aging) which may impact the bioavailability and, thus, ultimate toxicity of the chemical. In the present study, using a lab-scale wastewater and digestion treatment system, we generated biosolids which contained aged triclosan and compared ecological impacts to that of spiked biosolids. Ecotoxicity was assessed based on functional and community structure changes to soil denitrifiers, microorganisms critical to nitrogen cycling. A decrease in denitrifier abundance and diversity was observed in the aged biosolids at concentrations of 17.9 ± 1.93 μg/kg while decreases in activity were observed at 26.9 ± 4.6 μg/kg. In the spiked biosolids treatment, lower denitrifier abundance, diversity, and activity were observed at triclosan (TCS) concentrations of 68.6 ± 26.9 μg/kg. This difference suggests a need to better understand TCS bioavailability dynamics.

Complications After Vulvar and Perineal Reconstruction With a Lotus Petal Flap

Background Lotus petal flaps are often used to reconstruct defects in the vulvoperineal area. Wound complications occur more often after surgery in the vulvoperineal area than in other areas of the body. Postoperative complications have a great impact on patients' well-being, length of hospital stay, care needed, and return to participation in daily life. Therefore, it is important to determine which patients are more prone to develop complications. Methods All lotus petal flap reconstructions in our center between January 2004 and August 2014 were retrospectively reviewed. Complications were categorized by the Clavien-Dindo classification. Results Ninety-three patients with 137 flaps were reviewed. The complication rates did not differ significantly between the reconstruction areas. In 30.1% of subjects, no complications were reported. A total of 51.7% of the subjects experienced Clavien-Dindo grade I or II complications, which required no or minor intervention. In 18.3% of subjects, intervention was required under general anesthesia (Clavien-Dindo grade IIIb complications), usually for debridement (64.7%). Donor site morbidity occurred in 14.0% of the subjects. The age group younger than 60 years showed a significantly higher rate of complications compared with the group older than 60 years (P = 0.015; odds ratio, 0.235; 95% confidence interval, 0.073–0.754). Conclusions This is the largest study to date on the complications of the lotus petal flap reconstruction. Complication rates did not differ between vulvar, perineal, and vulvoperineal reconstruction. Young patients seem to have a higher risk of developing complications.

Fingertip Replantation Without and With Palmar Venous Anastomosis: Analysis of the Survival Rates and Vein Distribution

No abstract available

Insurance Appeals for Pediatric Reconstructive Surgery: A Micro Cost Analysis and How-to Guide

Background When insurance coverage for pediatric reconstructive procedures is denied, a stressful and time-consuming appeals process ensues. This article discusses the results of a micro cost analysis performed to better understand the time and monetary burden that the insurance process places on our clinic and families. We also advise plastic surgeons on how to appeal insurance denials for necessary reconstructive procedures. Methods Our micro cost analysis focused on patients with congenital breast anomalies who were denied insurance coverage during the preservice insurance authorization process. We surveyed staff and family members to determine the steps involved in the insurance process and how long each person spent on each step. We combined this with average compensation data to calculate cost. Results For the 5 patients included in our analysis, the insurance process took an average of 7.4 hours of institutional time and cost $521.43 per patient. All patients were denied coverage during prior authorization and required a peer-to-peer, and all denials occurred because surgery was deemed cosmetic or not medically necessary. Conclusions This analysis estimated the time and monetary cost of the insurance process in our department. Access to care was limited by prior authorization and the opinion of medical directors that these procedures are unnecessary or cosmetic. We encourage plastic surgeons to continue to perform patient-centered outcomes research in their practice to build on literature that proves the functional and psychosocial benefits of reconstructive procedures.

Botulinum Toxin Therapy: Is Syringe Type Related to Cost-Effectiveness?

Introduction Clostridium botulinum toxin is effective through cleaving presynaptic proteins at the neuromuscular junction, which prevents the release of acetylcholine and inhibits muscle contraction. Several serotypes of botulinum toxin (BT) exist; however, only 2 types have been approved by the US Food and Drug Administration for commercial and medical use, A and B. Both types of BT must be administered intramuscularly with a syringe, but the type of syringe is the injector's preference. Which syringe type is most efficient in minimizing product waste and most cost-effective for the patient and provider? Methods We performed a single-center, open-label, analytical study using BT therapy and 2 types of syringes for analytics of cost-effectiveness. OnabotulinumtoxinA was the neuromodulator used in this report. Vials (100 U) of BT A were each reconstituted with 2.5 mL of 0.9% sodium chloride, for a final concentration of 4 U/0.1 mL. High-dead-space syringes are compared with low-dead-space syringes: 1-mL tuberculin (TB) luer slip syringe with detachable 25-gauge needle and 1-mL ultrafine insulin syringe with an attached 31-gauge needle, respectively. After each syringe was evacuated, the TB syringe was noted to contain 0.05 mL of the remaining product in the hub. Results Providers are discarding approximately 2 U of BT per TB syringe product injection. If the physician uses 30 syringes per day, 3 days a week, for 1 year, it equals to a lost revenue of approximately $155,500 per year. To individualize the cost-effective analysis, average quantity of syringes used per patient and overall patient volume must be considered, with corresponding adjustment of cost and units discarded. Discussion The American Society of Plastic Surgeons reported that the use of neuromodulators has increased by approximately 797% from 2000 to 2016. During that period, the price of neuromodulators has also increased by approximately 85%. Considering these statistics, the type of syringe used for BT neuromodular injection is a thought-provoking concept but surrounded by a paucity of data. Overall, our data suggest that the use of ultrafine insulin syringes for injection of BT reduces product waste and is cost-effective for the patient and the provider.

Course Review: Plastic Surgery for Surgical Trainees

Early in their careers, trainees contemplating a career in plastic surgery may have limited specialty experience. Courses can provide valuable insight into specialty training and help develop necessary basic skills. However, this is not without a significant financial burden. Plastic Surgery for Surgical Trainees is a 1-day course that only costs £50 GBP (US $65). Accredited by the Royal College of Surgeons, this course held in Bristol, United Kingdom, offers an inexpensive practical introduction toward plastic surgical techniques for trainees interested in plastic surgery and those in other surgical specialties. In this review, we provide an evaluation of the course.

The Surgical Management of Nerve Gaps: Present and Future

Peripheral nerve injuries can result in significant morbidity, including motor and/or sensory loss, which can affect significantly the life of the patient. Nowadays, the gold standard for the treatment of nerve section is end-to-end neurorrhaphy. Unfortunately, in some cases, there is segmental loss of the nerve trunk. Nerve mobilization allows primary repair of the sectioned nerve by end-to-end neurorrhaphy if the gap is less than 1 cm. When the nerve gap exceeds 1 cm, autologous nerve grafting is the gold standard of treatment. To overcome the limited availability and the donor site morbidity, other techniques have been used: vascularized nerve grafts, cellular and acellular allografts, nerve conduits, nerve transfers, and end-to-side neurorrhaphy. The purpose of this review is to present an overview of the literature on the applications of these techniques in peripheral nerve repair. Furthermore, preoperative evaluation, timing of repair, and future perspectives are also discussed.

Characterizing Breast Deformities After Massive Weight Loss: Utilizing the Pittsburgh Rating Scale to Examine Factors Affecting Severity Score and Surgical Decision Making in a Retrospective Series

Background and Objectives Massive weight loss (MWL) can result in variable contour deformities of the breasts. The Pittsburgh Rating Scale (PRS) was designed to describe the multitude of deformities after MWL and recommends operations to consider for surgical improvement. We present the first comprehensive description of breast deformities in a large sample of MWL patients, examine factors affecting the severity of deformities, and report the correlation between PRS score and surgical decision making. Methods A retrospective review of all MWL patients presenting for breast surgery at our institution's Life After Weight Loss program from 2004 to 2015 was performed. Information including demographics, body mass indices (BMIs), method of weight loss, and type of surgical intervention was collected. Preoperative breast photographs were blinded and scored according to the PRS. Results A total of 204 MWL patients were identified; 26% (53) scored 1, 34% (69) scored 2, and 40% (82) scored 3 on the PRS. Greater deformities were seen after weight loss from bariatric surgery versus diet and exercise alone (P = 0.031), in mastopexy versus augmentation/mastopexy (P = 0.001), and in breast reduction versus augmentation/mastopexy patients (P > 0.0001). Patients who underwent reduction mammaplasty had the greatest maximum BMI compared with other procedures (P = 0.016). The PRS scores were positively correlated to maximum BMI (P

Mixed Versus Pure Variants of Desmoplastic Melanoma: The Cleveland Clinic Experience

Background Desmoplastic melanoma (DM) is a subvariant of spindle cell melanoma, accounting for less than 4% of all cutaneous melanomas. It occurs later in life and is associated with chronic sun exposure. Desmoplastic melanoma prognosis is considered more favorable than other variants, with lower rates of metastasis and higher survival. Recently, DM has been further subclassified into pure and mixed, calling into question surgical management and patient outcomes as well as viability of current nationwide databases without this distinction. Methods We identified all patients with a histopathologic diagnosis of DM from the Cleveland Clinic electronic melanoma database (n = 58) from 1997 to 2013. Clinical and histopathologic data were collected. Comparison in clinical variables was performed between patients who had pure (n = 15) and mixed (n = 43) variants of DM. Results There were no differences in age, sex, location of lesion, Breslow depth, ulceration, or regression. Patients with mixed DM were more likely to have lymphovascular invasion (P = 0.03) compared with pure DM. There was no difference in performance of sentinel lymph node biopsy (P = 0.25) or sentinel lymph node positivity (P = 0.31) between the 2 groups. Recurrence was present in 13.3% of pure and 30.2% of mixed patients. Overall, Kaplan-Meier 3-year survival was 75% for pure and 80% for mixed DM (P = 0.53). Conclusions Pure and mixed DMs seem to have similar clinical characteristics and outcomes. This indicates that analysis of national datasets without this subclassification remains viable.

Surgeon-Controlled Comparison of Direct-to-Implant and 2-Stage Tissue Expander–Implant Immediate Breast Reconstruction Outcomes

Background Current literature comparing outcomes of immediate breast reconstruction using direct-to-implant (DTI) single-stage and 2-stage tissue expanders (TEs) is conflicting. This study compared overall outcomes and determined predictive patient factors associated with higher complication rates. Methods After institutional review board approval, a retrospective cohort study of consecutive patients who underwent immediate breast reconstruction from 2010 to 2014 at a single hospital was performed. Demographic data and complications were recorded and compared using univariate analysis. Infection was defined as any patient receiving antibiotics beyond the expected postoperative course or restarting antibiotics for a suspected infection. Results Seventy-nine breasts (50 patients) underwent immediate breast reconstruction using tissue expansion, and 117 breasts (69 patients) underwent immediate breast reconstruction using the DTI technique. Overall complications, infection rate, and rate of aesthetic revisions were higher in the TE group compared with the DTI group. There was no difference in rates of seroma, hematoma, and mastectomy skin flap necrosis between the 2 groups. Infectious complications were significantly higher in patients with body mass index of greater than 30 who underwent TE-based reconstruction than those who underwent DTI-based reconstruction. Conclusions Single-stage DTI immediate breast reconstruction has less overall complications than 2-stage TE-based immediate reconstruction. Direct-to-implant immediate breast reconstruction may provide favorable outcomes in patients with body mass index of greater than 30.

Three-Dimensional Ultrasound Versus Computerized Tomography in Fat Graft Volumetric Analysis

Studies evaluating fat grafting in mice have frequently used micro–computed tomography (micro-CT) as an accurate radiographic tool to measure longitudinal volume retention without killing the animal. Over the past decade, however, microultrasonography has emerged as an equally powerful preclinical imaging tool. Given their respective strengths in 3-dimensional reconstruction, there is no study to our knowledge that directly compares micro-CT with microultrasound in volumetric analysis. In this study, we compared the performance of micro-CT with microultrasound in the evaluation of adipose tissue graft volume in a murine model. Fifteen immunodeficient mice were given 200 μL of adipose tissue grafts. In vivo volumetric analysis of the grafts by micro-CT and microultrasound was conducted at discrete time points up to postoperative day 105. Three mice were killed at multiple time points, and explanted grafts were reimaged by CT and ultrasound, as mentioned previously. Analysis revealed that in vivo graft volumes measured by micro-CT do not differ significantly from those of microultrasound. Furthermore, both micro-CT and microultrasound were capable of accurately measuring fat grafts as in vivo volumes closely correlated with explanted volumes. Finally, ultrasound was found to yield improved soft tissue contrast compared with micro-CT. Therefore, either modality may be used, depending on experimental needs.

Comparative Outcomes of Inferior Pedicle and Superomedial Pedicle Technique With Wise Pattern Reduction in Gigantomastic Patients

Introduction Although multiple pedicle and skin excision techniques exist for gigantomastic breast reduction, no consensus exists as to which method is most effective in providing an aesthetically pleasing breast, especially in the long-term period. This study aimed to compare the aesthetic and surgical outcomes between inferior pedicle and superomedial pedicle reductions, which both use Wise pattern skin excision in gigantomastic patients. Methods A prospective study was planned, and the number of patients was determined before the beginning of the study. Fifty inferior pedicle breast reductions (25 patients) were matched to 50 superomedial pedicle breast reductions (25 patients) after a 1-year postoperative period. Matching was done based on age, body mass index, size of reduction, minor and major postoperative complications, symptomatic relief, long-term measurements of the nipple-areola complex position, and inferior pole length elongation at 1 year postoperatively. Results There was no significant difference in complications between the inferior and superomedial pedicle groups. The mean resection weight was 1320 (right) and 1355 g (left) in the inferior pedicle group and 1380 (right) and 1310 g (left) in the superomedial pedicle group (P

Meeting Review: 8th Annual Egyptian International Conference of Hand and Microsurgery

No abstract available

Liposomal Bupivacaine May Benefit Select Reduction Mammaplasty Patients

Background Postoperative pain control can be challenging in reduction mammaplasty patients. This study compares perioperative liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, Inc, San Diego, Calif) with standard local anesthetics to determine if liposomal bupivacaine decreases opioid and antiemetic use, impacting length of stay and complication rates, thus improving patient outcomes. Methods A retrospective review of 170 reduction mammaplasty patients was performed. Patients were divided into groups based on local anesthetic used (bupivacaine only and liposomal bupivacaine) and into subgroups based on obesity classification. Length of hospital stay; pain scores immediately postoperatively, at discharge, and at follow-up; and postoperative analgesics and antiemetics were compared. Further analysis was performed after weight stratification within pre- and postmenopausal categories. Results Liposomal bupivacaine resulted in less pain than bupivacaine immediately postoperatively and at discharge in obesity class I (P = 0.021 and P = 0.018). In obesity class II, antiemetic use was lower in the liposomal bupivacaine group (P = 0.012). Length of stay was persistently lower with liposomal bupivacaine for premenopausal women, and this difference was significant in obesity class I (P = 0.038). In premenopausal women, discharge pain scores were lower in the overweight liposomal bupivacaine group (P = 0.034) and analgesic use was lower in obesity class III (P = 0.004). Conclusions Liposomal bupivacaine decreases postoperative pain, opioid, and antiemetic use in select patients. Liposomal bupivacaine might not be equally efficacious in pain reduction in obese or postmenopausal women given the theoretical increased absorption by adipose tissue. In addition, liposomal bupivacaine may have a dose-dependent effect, and weight-based dosing should be investigated.

Components Separation for Abdominal Wall Reconstruction in the Recalcitrant, High-Comorbidity Patient: A Review of 311 Single-Surgeon Cases

Purpose Components separation of the abdominal musculature remains a mainstay for closure of complicated midline and paramedian abdominal wall defects. The authors critically analyzed their experience with this technique to identify prognosticators affecting long-term clinical outcomes. Methods A retrospective review was performed of patients undergoing components separation by a single senior surgeon (J.M.R.) between 2000 and 2010. Numerous perioperative patient characteristics were collected and analyzed to determine their effects on long-term clinical outcomes. Multivariable logistic regression was used to predict hernia recurrence and other adverse clinical outcomes. Results A total of 311 patients were identified (male, 51.1%). Mean age was 53.1 ± 14.0 years, preoperative body mass index was 33.1 ± 8.2 kg/m2, and defect width was 11.4 ± 7.5 cm. Patients who had prior hernia repair were 97.4%, with 38.3% having prior mesh placement. Average follow-up was 2.9 ± 2.4 years. Overall hernia recurrence rate was 18.3%. Postoperative complications included seroma (9.3%), superficial wound infection (9.0%), skin dehiscence (4.82%), hematoma (3.2%), deep vein thrombos or pulmonary emolbus (3.2%), and skin flap ischemia (1.0%). Respiratory comorbidity (odds ratio, [OR], 2.02; P

Graphical Calculation of Estimated Energy Expenditure in Burn Patients

Background Historically, estimated energy expenditure (EEE) has been related to the percent of body surface area burned. Subsequent evaluations of these estimates have indicated that the earlier formulas may overestimate the amount of caloric support necessary for burn-injured patients. Ireton-Jones et al derived 2 equations for determining the EEE required to support burn patients, 1 for ventilator-dependent patients and 1 for spontaneously breathing patients. Evidence has proved their reliability, but they remain challenging to apply in a clinical setting given the difficult and cumbersome mathematics involved. This study aims to introduce a graphical calculation of EEE in burn patients that can be easily used in the clinical setting. Methods The multivariant linear regression analysis from Ireton-Jones et al yielded equations that were rearranged into the form of a simple linear equation of the type y = mx + b. By choosing an energy expenditure and the age of the subject, the weight was calculated. The endpoints were then calculated, and a graph was mapped by means of Adobe FrameMaker. Results A graphical representation of Ireton-Jones et al's equations was obtained by plotting the weight (kg) on the y axis, the age (years) on the x axis, and a series of parallel lines representing the EEE in burn patients. The EEE has been displayed graphically on a grid to allow rapid determination of the EEE needed for a given patient of a designated weight and age. Two graphs were plotted: 1 for ventilator-dependent patients and 1 for spontaneously breathing patients. Correction factors for sex, the presence of additional trauma, and obesity are indicated on the graphical calculators. Conclusions We propose a graphical tool to calculate caloric requirements in a fast, easy, and portable manner.

The Distally Based Peroneus Brevis Flap: The 5-Step Technique

The peroneus brevis flap was first described as proximally based by Mathes et al (Surg Clin North Am. 1974;54:1337–1354) and later by Jackson and Scheker (Injury. 1982;13:324–330). A distally based version of this flap by Mathes and Nahai (Reconstructive Surgery: Principles, Anatomy and Technique. 1997:1437e46) was subsequently described in 1997. The first case series of distally based flaps was published by Eren et al (Plast Reconstr Surg. 2001;107:1443–1448). In our experience, the distally based flap is a useful muscle flap to reconstruct small defects in the lateral distal third of the leg. Initial interest and confidence in the use of this flap in our unit were hindered by lack of direct experience and descriptive detail in the literature. We have now developed a systematic approach to harvest the distally pedicled peroneus brevis muscle flap in 5 reproducible, safe steps. This has allowed the flap to become adopted as a standard technique of limb reconstruction in our unit with no cases of flap loss.

Retrospective Review of Free Anterolateral Thigh Flaps for Limb Salvage in Severely Injured High-Voltage Electrical Burn Patients

Background High-voltage electrical injuries usually cause extensive and devastating damages to the extremities. Timely and effective coverage of the wounds to maximally preserve the viable tissue is important for salvage and the ultimate functional outcome of the involved extremities. In this study, free anterolateral thigh flaps with a single-perforator pedicle were conducted to maximize tissue salvage and decrease late skeletal and neuromuscular complications of the involved extremities injured by high-voltage electricity. Methods From June 2012 to December 2015, 12 patients with high-voltage electrical injuries on the extremities were recruited. After primary or secondary debridement, free anterolateral thigh flaps with a single-perforator pedicle were used for limb salvage. Patients' clinical records, including etiology, sex, age, perforator type, defect location, duration before admission, defect and flap size, timing of reconstruction, and complications, were extracted and analyzed. Results All patients were followed up ranging from 10 to 25 months, with an average follow-up of 15.9 months. Free anterolateral thigh flap with a single-perforator pedicle was performed for 12 consecutive patients with high-voltage electrical injuries. The mean time taken before the transplantation of the flap was 5.25 days, with a range from 2 to 8 days. The average size of the resultant defects after debridement was 187.0 cm2 (84–350 cm2), the average size of the flaps was 265.3 cm2 (119–448 cm2), and the average time of the surgical operation was 314.6 minutes (260–355 minutes). All flaps healed uneventfully without associated complications. No weakness of the donor thigh was observed in all cases. Conclusions Free anterolateral thigh flaps with a single-perforator pedicle were an effective and reliable therapeutic intervention for the management of severe high-voltage electrical injuries on the extremities.

A Cross-Sectional Study of Variations in Reimbursement for Breast Reconstruction: Is A Healthcare Disparity On the Horizon?

Background Despite growing demand for breast reconstruction, financial disincentives to perform breast reconstruction in patients with government-sponsored insurance plans may lead to longer wait times and decreased access to care. We identify the variation in reimbursement for implant and autologous reconstruction as a step toward understanding these financial implications, to develop safeguards to minimize effects on access to care. Methods Billing data were collected over a 10-year period for patients undergoing implant-based (19357) or free-flap (19364) breast reconstruction. Patients were placed into cohorts according to insurance type—Medicare, Medicaid, or private insurance, and these were directly compared. Results A total of 2691 women underwent breast reconstruction between 2003 and 2013; 71.2% had private insurance, 13.3% had Medicaid, and 14.49% had Medicare. For implant-based reconstructions, the average reimbursement of total charges was 16.3% for Medicaid, 28.3% for Medicare, and 67.2% for private insurance. For autologous reconstruction, average reimbursement was 12.37% for Medicaid, 22.9% for Medicare, and 35.35% for private insurance. Hourly reimbursement estimates for Medicaid patients undergoing autologous reconstruction were lowest. The highest hourly reimbursement estimate was for privately insured patients undergoing implant-based reconstruction. Over time, reimbursement for autologous reconstruction has declined significantly for all payor types, whereas implant-based reimbursement disparities are narrowing. Conclusions We found that wide variations in reimbursement for breast reconstruction procedures exist and may preclude some surgeons from offering certain reconstructive options to a subset of patients. Understanding these discrepancies is a key first step in minimizing a potential care delivery disparity for this patient population.

Interposition Tendon Graft and Tension in the Repair of Closed Rupture of the Flexor Digitorum Profundus in Zone III or IV

We report the results of interposition tendon grafts using the ipsilateral palmaris longus tendon in 12 patients with closed flexor digitorum profundus tendon ruptures in zone III or IV of 14 digits between June 2006 and October 2015. Before surgery, 2 patients were diagnosed with closed tendon ruptures that occurred after nonunion of hamate hook fractures. The other 10 patients were diagnosed with spontaneous tendon ruptures of unknown cause. In 2 of the 10 patients with spontaneous tendon rupture, the cause of the rupture was not found. In the other 8 patients, there was rough surface with deficient overlying soft tissue on the radial side of the hamate hook. In all cases, the ruptured flexor digitorum profundus was reconstructed by applying overtension on the tendon graft, causing greater flexion than for the other normal digits. Hamate hook excision was also performed on 10 subjects with abnormalities. Postoperatively, the patients were followed for an average of 22.5 months (range, 12–64 months). At the final follow-up, the mean Disabilities of the Arm, Shoulder, and Hand questionnaire score was 5.7 (range, 3.3–8.3). There were excellent results in all 14 digits according to Strickland and Glogovac criteria. The mean total active motion was 167 degrees (range, 160–180 degrees). There were no surgical complications, including infection, adhesions, or tendon rerupture. There were excellent clinical results with the interposition tendon graft using palmaris longus for closed tendon rupture in zone III or IV of the hand. Applying overtension to the grafted tendon appears to be beneficial.

Determination of Pneumatic Tourniquet Pressure of Lower Limb by Ultrasonic Doppler

Objective The aim of this study was to investigate the clinical effect of tourniquet inflation pressure setting by ultrasonic Doppler on lower limb operation. Methods Ninety-six patients with total knee arthroplasty were selected in this study from January 2015 to December 2015. The patients were randomly divided into the study group and the control group with 48 cases in each group. In the control group, the tourniquet pressure is determined by the doctor's request for the patient's condition, but all the tourniquet pressure values should be 80 KPa or less. In the study group, ultrasonic Doppler was used to monitor the popliteal artery blood flow of surgery limb with the maximum systolic velocity in artery as a reference value. The pressure of pneumatic tourniquet gradually increased until the maximum systolic velocity was reduced to 0. At this time, the popliteal artery blood flow was not present. The 2 groups of patients with lower extremity tourniquet pressure, hemostatic effect of intraoperative tourniquet, and the incidence of adverse reaction using tourniquets were observed and recorded. Results In the study group, the lower extremity tourniquet pressure and the incidence of adverse reaction using tourniquets were all better than that in control group; the difference between 2 groups was significant (P 0.05). Conclusions The method of ultrasonic Doppler setting lower extremity tourniquet pressure during the operation could not only ensure the hemostatic effect, but it could also provide the optimum individual pneumatic tourniquet pressure value for patients. In the meanwhile, it could reduce the incidence of adverse reaction using tourniquets effectively as well as improve the safety of the tourniquet. This method played an important role in the recovery of patients.

An infant with generalized pustular psoriasis and geographic tongue had a heterozygous IL36RN mutation and IgG2 deficiency

Pathogenic gene mutations in IL36RN, which encodes the interleukin 36-receptor antagonist (IL36Ra), were reported as causative genetic defects in several generalized pustular psoriasis (GPP) cases in 2011 [1,2]. Later, we reported that "GPP without psoriasis vulgaris (PV)" patients had homozygous or compound heterozygous mutations in IL36RN, and only a small number of "GPP with PV" patients had IL36RN mutations [3,4]. Mutation of IL36RN has been associated with GPP in both its heterozygous and homozygous states.

Requirement of MHC class I on radioresistant cells for granzyme B expression from CD8+ T cells in murine contact hypersensitivity

Allergic contact dermatitis (ACD) is a common cutaneous disorder that affects around 15–20% of the general population worldwide. Haptens, chemical compounds of molecular weight smaller than 500 Da, are assumed to react with self-peptides or −proteins to serve as pathogenic antigens (Ags) in ACD [1,2]. Ag-presented-CD8+ T cells at the elicitation phase produce interferon (IFN)-γ and cytotoxic granules such as granzyme B and perforin, and provoke inflammation [2–4]. Dermal dendritic cells (dDCs) are considered essential for the presentation of these haptenized-Ag to CD8+ T cells [2,5,6].

Pro-fibrotic Phenotype of Human Skin Fibroblasts Induced by Periostin via Modulating TGF-β Signaling

Excessive accumulation of extracellular matrix (ECM) components is a hallmark of organ fibrosis. It is a final common outcome for several diseases, including fibroproliferative disorders such as systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF), which leads to significant morbidity and mortality [1]. Unfortunately, no effective therapy for organ fibrosis is yet available. Uncontrolled wound healing responses, including acute and chronic inflammation, angiogenesis, activation of resident cells, and abnormal ECM remodeling, are thought to be involved in the pathogenesis of fibrosis.

The recent development of advanced wastewater treatment by ozone and biological aerated filter

Abstract

The combination of ozone and biological aerated filter (O₃/BAF) has been widely studied and applied in polishing different biological secondary effluents. O₃/BAF has the advantages of high pollutants removal rate, low operating cost, and flexible combination types. The principle and combination, effect of ozone dosage and influent suspended solids (SS) on O₃/BAF, applications, current research focuses, and development are discussed. The ozone can break refractory macromolecules into small and biodegradable fragments, increasing the biodegradation. It benefits the operation of BAF. The coupling of ozonation and BAF is efficient in the removal of refractory organic pollutants from different wastewaters. Ozonation can also be used as the post-treatment option after BAF to guarantee the effluent qualities. Normally, the ozone dosage varied from 5 to 125 mg/L with the contact time of 4 to 60 min, while the hydraulic retention time (HRT) of BAF is usually between 2 to 5 h when treating different biological effluents. The effluent COD is normally lower than 50 mg/L. Most of the organic micropollutants (OMPs) in the biological effluent, such as antibiotics, pharmaceuticals, personal care products, steroid hormones, and industrial chemicals, can be efficiently removed by O₃/BAF. More importantly, the O₃/BAF can obviously reduce the toxicity of the wastewater. The residual ozone of about 0.2 mg/L in the ozonation effluent benefits the performance of BAF. The future trends of O₃/BAF are also discussed in the paper.

The occurrence of selected xenobiotics in the Danube river via LC-MS/MS

Abstract

Having in mind that there is a general lack of monitoring plans and precaution measures in the developing countries and that the Danube is the second longest river in Europe, the estimation of the relevant concentration levels of unregulated xenobiotics is a topic of interest both on local and international level. The selected pharmaceuticals, caffeine, and benzotriazole presented in the collected water samples from seven representative locations around the territory of Novi Sad, Serbia, during 1-year period, were analyzed with the use of solid-phase extraction followed by the liquid chromatography coupled with triple quad tandem mass spectrometry. The most frequently detected compounds were caffeine and carbamazepine in the concentrations up to 621 and 22.2 ng/L, respectively, while the maximum concentration of the analyzed pharmaceuticals was obtained for ibuprofen (60.1 ng/L). The presence of benzotriazole along the analyzed section of the river was confirmed in the concentration levels up to 26.7 ng/L. Although sulfamethoxazole and desmethyldiazepam were detected at trace levels (0.22 and 3.41 ng/L, respectively); the presence of these pharmaceuticals in complex mixtures should not be neglected. Due to the frequent detection caffeine, carbamazepine, ibuprofen, and benzotriazole could be proper candidate for hydrophilic anthropogenic markers for quantification of wastewater contamination in surface water in the analyzed Danube section.

Occurrence, source, and ecological risk of antibiotics in Dongting Lake, China

Abstract

The pollution characteristics and ecological risk of 12 classified as sulfonamide, trimethoprim, quinolone, and tetracycline antibiotics in Dongting Lake, China, were studied. The total concentrations of the antibiotics ranged from 1.06 to 135.40 ng L⁻¹ for all sampling sites. The highest average concentration was observed for sulfadiazine, followed by sulfamethoxazole. The detection frequencies (over 60%) of sulfonamides were higher than those of other antibiotics. The direct discharge of the aquaculture, livestock, and poultry wastewater might be the main pollution sources of antibiotics in the Dongting Lake. The pollution levels of antibiotics decreased in the order of East Dongting Lake > South Dongting Lake > West Dongting Lake, which may be related to the distribution and the scale of the aquaculture, livestock, and poultry sources. The seasonal changes of antibiotic concentration were relatively diversified, with the dry season generally having higher concentrations than the wet season. The results of the ecological risk assessment indicated that sulfamethoxazole, ciprofloxacin, and sarafloxacin might pose a significant risk to the aquatic organisms in Dongting Lake, especially in Potou and Nandu. This study enriches the research of emerging pollutants in freshwater lake.

Graphical abstract

In reply to “re: Antibiotic prophylaxis in breast reduction surgery: A systematic review and meta-analysis”

We read with interest the letter written by Drs. Bechar, Skillman and Hardwicke criticizing some points on methodology of our article, published previously in this journal,1 however, we have some points to expose and explain.

Jan C. Schmidt: Das Andere der Natur. Neue Wege der Naturphilosophie

Preventive role of ramelteon and suvorexant for postoperative delirium after pharyngolaryngectomy with esophagectomy

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.

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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.

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Impacts of earthworm activity on the fate of straw carbon in soil: a microcosm experiment

Abstract

Earthworms not only facilitate carbon (C) stabilization, but also accelerate organic matter mineralization by enhancing microbial respiration. However, the fate (mineralization vs stabilization) of newly added C by straw returning in arable lands with earthworm activity is still unclear. In the present 40 days incubation study, we incorporated artificially ¹³C–labeled straw into soil with and without presence of earthworms (Metaphire guillelmi). Flux measurements of CO₂ from soil (mineralization) were taken regularly, while straw-derived C remaining in the soil (stabilization) was measured at the end of the incubation. There was no significant difference of the cumulative CO₂ emission between earthworm presence and absence treatment. However, earthworm presence significantly decreased straw-derived cumulative CO₂-C emission when compared with the treatment without earthworm. Besides, earthworm incubation led to a significantly low light fraction organic carbon (LFOC) content and straw-derived LFOC proportion. Relative to the non-earthworm treatment, straw-derived C content significantly decreased in micro-aggregates (< 0.25 mm), but increased in large macro-aggregates (> 2 mm) in the earthworm treatment. In total, only 3.8% of added straw C was assimilated by earthworm within 40 days, while most of the straw C remained in the soil. Earthworms decreased straw-derived CO₂-C emission from 10.0 to 8.1% when compared with the non-earthworm treatment. In the present short period incubation experiment, compared with the soil without earthworms, the presence of Metaphire guillelmi (1) resulted a higher soil CO₂ emissions, which may mainly evolved from the older SOC, and (2) stabilized more residue-derived C in the soil aggregates. We therefore propose that Metaphire guillelmi may increase soil organic carbon pool turnover rates in the short term after straw returning by replacement of older SOC with newly added straw C.

Use of SkinFibrometer® to measure skin elasticity and its correlation with Cutometer® and DUB® Skinscanner

Abstract

Background

Skin elasticity is an important indicator of skin aging. The aim of this study was to demonstrate that the SkinFibrometer^® is appropriate for measuring skin biomechanical properties, and to correlate it with elasticity parameters measured using the Cutometer^® and with dermis structural properties measured using DUB^® Skinscanner.

Materials and methods

Twenty-one individuals participated in this study. The skin of the cheek, around the eye, and the volar forearm were evaluated. To analyze correlations of elasticity parameters, the induration value against the indenter pressure of SkinFibrometer^® and R, Q parameters of Cutometer^® were compared. Dermal echogenicity using DUB^® Skinscanner was compared with the induration value of SkinFibrometer^®.

Results

The younger age group showed more firm and elastic skin properties compared to the older age group, and the elasticity values of the volar forearm were significantly higher than those of the cheek and around the eye region. Even though the measuring principle is different, both SkinFibrometer^® and Cutometer^® demonstrated the same trends of skin elasticity differences according to age and anatomical regions. There were significant correlations between the induration value of SkinFibrometer^®, representing skin firmness, and R0, Q0 and R2, R5, R7, Q1, Q2 of Cutometer^®, which represent skin firmness and resilience, respectively (P < .01). In addition, dermal echogenicity positively correlated with skin firmness determined by SkinFibrometer^® (P < .01).

Conclusion

We identified correlations between skin elasticity parameters evaluated by two different methods of suction and indentation, and demonstrated that the SkinFibrometer^® is an objective, non-invasive evaluation tool for skin stiffness and elasticity.

A Time-Series Study of the Effect of Air Pollution on Outpatient Visits for Acne Vulgaris in Beijing

Background/Aims: There is increasing evidence that exposure to air pollutants, including particulate matter (PM_2.5, PM₁₀), nitrogen dioxide (NO₂), and sulfur dioxide (SO₂), might aggravate preexisting skin diseases such as eczema and urticaria. Here we investigated if a possible link exists between air pollution and acne vulgaris. We assessed the association between ambient air pollutant concentrations and the number of visits of patients for acne vulgaris to a dermatological outpatient clinic in Beijing, China, from April 1, 2012 to April 30, 2014. Methods: In this time period, 59,325 outpatient visits were recorded because of acne vulgaris. Daily air pollution parameters for PM₁₀, PM_2.5, SO₂, and NO₂ were obtained from the Beijing Municipal Environmental Monitoring Center. Results: Increased concentrations of ambient PM_2.5, PM₁₀, and NO₂ were significantly associated with increased numbers of outpatient visits for acne vulgaris over the 2 years. These effects could be observed for NO₂ in a single-pollutant model and for PM_2.5, PM₁₀, and NO₂ in 2-pollutant models, which are closer to real-life exposure. Of note, these effects were specific because they were not observed for increased SO₂ concentrations, which even showed negative correlations in all test models. Conclusion: This study provides indirect evidence for a link between acne vulgaris and air pollution.
Skin Pharmacol Physiol 2018;31:107-113

Eco-design of cosmetic formulae: methodology and application

Abstract

Objective

This article describes an easy-to-use eco-design methodology developed and applied since 2014 by the L'Oréal Group to improve the sustainable performance of its new products without any compromise on their cosmetic efficacy.

Methods

Cosmetic products, after being used, are often discharged into the sewers and the aquatic compartment. This discharge is considered as dispersive and continuous. A consistent progress in reducing the environmental impact of cosmetic products can be achieved through focusing upon three strategic indicators: biodegradability, grey water footprint adapted for eco-design (GWFE) and a global indicator, complementary to these two endpoints. Biodegradability represents the key process in the removal of organic ingredients from the environment. GWFE is defined herein as the theoretical volume of natural freshwater required to dilute a cosmetic formula after being used by the consumer, down to a concentration without any foreseeable toxic effects upon aquatic species. Finally, the complementary indicator highlights a possible alert on formula ingredients due to an unfavorable environmental profile based on hazard properties: e.g. GHS/CLP (Global Harmonization System/Classification, Labelling and Packaging) H410 classification or potential vPvB (very Persistent and very Bioaccumulative) classification.

Results

The eco-design of a new cosmetic product can be a challenge as the cosmetic properties and quality of this new product should at least match the benchmark reference. As shown in the case studies described herein, new methodologies have been developed to maximize the biodegradability of cosmetic formulae, to minimize their GWFE and to limit the use of ingredients that present an unfavorable environmental profile, while reaching the highest standards in terms of cosmetic efficacy.

Conclusion

By applying these methodologies, highly biodegradable products (≥ 95% based on ingredient composition) have been developed and marketed, with a low GWFE. This new eco-design approach shows that embedding sustainability in developing new cosmetic products can also open up new innovative opportunities.

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An efficient and reusable quaternary ammonium fabric adsorbent prepared by radiation grafting for removal of Cr(VI) from wastewater

Abstract

A novel quaternary ammonium polyethylene nonwoven fabric for removing chromium ions from water was prepared via radiation-induced grafting of glycidyl methacrylate and further modification with N,N′-dimethylethylenediamine. The structural and morphological characteristics of the adsorbent were analyzed using Fourier transform infrared spectroscopy (FTIR), thermogravimetry and differential thermogravimetry (TG/DTG), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). The influences of several principal factors, including pH value, initial Cr(VI) concentration, contact time, and coexisting anions (including SO₄²⁻, CO₃²⁻, NO₃⁻, PO₄³⁻, and Cl⁻), on adsorption performance were investigated via batch tests. The results showed that the optimum removal efficiency was 99.2% at pH 3 and the maximum adsorption quantity for Cr(VI) at 25 °C was 336 mg/g. The adsorption kinetic parameters were better fitted with the pseudo-second-order kinetic model, and the equilibrium data were described very well by the Freundlich isotherm model. Furthermore, the as-synthesized adsorbent exhibited excellent regeneration and recyclability while maintaining high adsorption performance after five adsorption/desorption cycles.

The effect of light and temperature on the dynamic state of Rhodobacter sphaeroides reaction centers proteins determined from changes in tryptophan fluorescence lifetime and P+QA− recombination kinetics

Publication date: March 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 180
Author(s): Peter P. Knox, Vladimir V. Gorokhov, Boris N. Korvatovskiy, Eugene P. Lukashev, Sergey N. Goryachev, Vladimir Z. Paschenko, Andrew B. Rubin
The temperature dependencies of the rate of dark recombination of separated charges between the photoactive bacteriochlorophyll and the primary quinone acceptor (QA) in photosynthetic reaction centers (RCs) of the purple bacteria Rhodobacter sphaeroides (Rb. sphaeroides) were investigated. Measurements were performed in water−glycerol and trehalose environments after freezing to −180 °C in the dark and under actinic light with subsequent heating. Simultaneously, the RC tryptophanyl fluorescence lifetime in the spectral range between 323 and 348 nm was measured under these conditions. A correlation was found between the temperature dependencies of the functional and dynamic parameters of RCs in different solvent mixtures.For the first time, differences in the average fluorescence lifetime of tryptophanyl residues were measured between RCs frozen in the dark and in the actinic light. The obtained results can be explained by the RC transitions between different conformational states and the dynamic processes in the structure of the hydrogen bonds of RCs. We assumed that RCs exist in two main microconformations – "fast" and "slow", which are characterized by different rates of P⁺ and QA⁻ recombination reactions. The "fast" conformation is induced in frozen RCs in the dark, while the "slow" conformation of RC occurs when the RC preparation is frozen under actinic light. An explanation of the temperature dependencies of tryptophan fluorescence lifetimes in RC proteins was made under the assumption that temperature changes affect mainly the electron transfer from the indole ring of the tryptophan molecule to the nearest amide or carboxyl groups.

RE: Vitamin D and Fracture Risk in Early Childhood: A Case-Control Study

RE: “Vitamin D and fracture risk in Early childhood: a case-control study”

Oral Contraceptive Use and Risks of Cancer in the NIH-AARP Diet and Health Study

Abstract

Although use of oral contraceptives (OC) is common, their influence on carcinogenesis is not fully understood. We used Cox proportional hazards models to examine OC use (never/<1 year (reference), 1–4, 5–9, 10+ years) and development of incident cancers across body sites within the same base population: women in the prospective NIH-AARP Diet and Health Study (enrolled 1995–1996, followed until 2011). Adjustment for confounding varied by outcome; all models accounted for age, race, body mass index, and smoking status and included ≥100,000 women. Any OC use conferred a 3% reduction in the risk for any cancer (hazard ratio = 0.97, 95% confidence interval: 0.95, 0.99). Expected risk reductions that strengthened with duration of use were identified for ovarian and endometrial cancers and were suggested for kidney cancer (P-trends < 0.05). We noted reduced risk for non-Hodgkin lymphoma (hazard ratio = 0.79, confidence interval: 0.64, 0.97) with 10+ years of use. We observed a 37% reduced risk for bladder cancer and 46% increased risk for pancreatic cancer among long-term users who were ≤60 at baseline. OC use did not influence risks for most other cancers evaluated. Given the high prevalence of use and changing formulations, future studies are warranted to fully understand the chemopreventive effects of these medications.

Hemoglobin A1c and Cardiovascular Disease Incidence in Type 1 Diabetes: An Application Of Joint Modeling Of Longitudinal And Time-To-Event Data In The Pittsburgh Epidemiology Of Diabetes Complications (EDC) Study

Abstract

Type 1 diabetes (T1D) is associated with increased cardiovascular disease (CVD) risk, but hyperglycemia, measured by HbA1c (%), which characterizes T1D has itself been an inconsistent CVD predictor. However, only baseline HbA1c or a summary measure (e.g., mean over follow-up) is usually analyzed. Joint models allow longitudinal repeated covariates, modeled using random effects, and time-to-event data to be modeled simultaneously. Data are from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, an ongoing, prospective cohort study of childhood-onset T1D followed beginning in 1986–1988 that has repeatedly reported little association between baseline or mean follow-up HbA1c and coronary artery disease incidence. Of 561 participants without CVD at baseline, 263 (42.1%) developed CVD over 25 years. In joint models, each one percent increase in HbA1c trajectory was associated with a 1.3-fold increased CVD risk (95% Confidence Interval (CI): 1.07, 1.45), after adjusting for baseline values of other CVD risk factors, and a 1.13-fold increased risk (95% CI: 0.99, 1.32) after adjusting for updated means of other CVD factors. These findings, which support the need for good glycemic control to prevent CVD in T1D, underscore the importance of utilizing methods incorporating within-subject variation over time when analyzing and interpreting longitudinal cohort study data.

Health and Mortality Risks for Caregivers Vary by Age: A Census-Based Record Linkage Study

Abstract

Due to the focus of studies about caregiving responsibilities on older caregivers, there has been a deficit of research on young caregivers. We aimed to investigate the association between caregiving and health/mortality risk in young caregivers when compared with their non-caregiving peers and older caregivers. A census-based record linkage was implemented linking all residents enumerated in the 2011 Northern Ireland Census with subsequently registered deaths data, until the end of 2015. Among those aged 5–24 years at the 2011 Census, approximately 4.5% (19,621) of the cohort reported that they were caregivers. The presence of a chronic physical (mobility difficulties) and/or mental health condition was measured through the Census; all-cause mortality was assessed by official mortality records. Young caregivers were less likely than their non-caregiving peers to report chronic mobility problems (OR_adj = 0.81 95% CI: 0.84, 0.96), but more likely to report chronic poor mental health (OR_adj = 1.44 95% CI: 1.31, 1.58). They also differ from older caregivers (P < 0.001) and are at significantly higher mortality risk than their peers (HR_adj = 1.54 95% CI: 1.10, 2.14). A dose response relationship between hours devoted to caregiving duties and mortality risk was evident. Young caregivers are at significantly increased risk of poor health outcomes.

The Brazilian Longitudinal Study of Aging (ELSI-BRAZIL): Objectives and Design

Abstract

Brazil is experiencing one of the world's fastest demographic aging worldwide. This demographic transition is occurring in a context of few resources and great social inequalities. The Brazilian Longitudinal Study of Aging (ELSI-Brazil) is a nationally representative study of 9,412 people aged 50 years and over, residing in 70 municipalities across the 5 great Brazilian regions. The study allows investigations of the aging process, its health, psychosocial and economic determinants and societal consequences. The baseline examination (2015–16) included detailed household and individual interviews and physical measurements (blood pressure, anthropometry, grip strength, timed walk and balance tests). Blood tests and samples storage were performed in a sub-sample of study participants. Subsequent waves are planned every 3 years. The study adopts a common conceptual framework of other great-scale longitudinal studies of aging in the world, namely Health and Retirement family, allowing cross-national comparisons. The goal of ELSI-Brazil is not only to build an understanding of aging in a large Western middle-income country in rapid demographic transition, but also to provide scientific data for to support and study policy changes that may affect older adults. This paper describes the methodology of the study and some descriptive results of the baseline survey.

Paraneoplastic plaque-like cutaneous mucinosis in a patient with lung adenocarcinoma

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.

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.

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.

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No BRAF V600E Mutation Identified in 28 Periocular Pyogenic Granuloma

Purpose: BRAF V600E mutations were recently identified in some pyogenic granulomas of skin, particularly lesions arising in patients with port wine stains. In this study, the authors analyzed BRAF gene status in 28 periocular pyogenic granulomas to determine its role in their pathogenesis. Methods: Retrospective review of ophthalmic pathology archives from 2007 to 2016 was used to identify pyogenic granulomas of the conjunctiva, eyelid, and orbit. Three eyelid nevi were also analyzed as positive controls. BRAF V600E status was assessed by pyrosequencing of DNA extracted from excess formalin-fixed, paraffin-embedded surgical material. Results: Microscopic examination of the periocular pyogenic granuloma specimens revealed proliferative vascular lesions, with radiating capillary channels surrounded by variable degrees of acute and chronic inflammation. Sequencing did not identify a BRAF V600E mutation in any of the 28 sporadic pyogenic granulomas, including 13 on the eyelid. In contrast, mutation analyses performed in parallel in melanocytic nevi of the eyelid identified BRAF V600E alterations in all 3 cases. Conclusions: The lack of BRAF V600E mutations in 28 sporadic pyogenic granulomas of the conjunctiva and eyelid suggests that such alterations are not a common driver in the pathogenesis of these periocular vascular lesions. Accepted for publication December 22, 2017. The study was funded in part by an unrestricted grant from Research to Prevent Blindness. The authors have no conflicts of interest to disclose. Address correspondence and reprint requests to Charles G. Eberhart, M.D., Ph.D., 720 Rutland Ave, Ross Bldg 558, Baltimore, MD 21205. E-mail: ceberha@jhmi.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Photochemically Induced Crosslinking of Tarsal Collagen as a Treatment for Eyelid Laxity: Assessing Potentiality in Animal Tissue

Purpose: An experimental study to demonstrate in animal eyelids that the controlled exposure of excised tarsal plate to ultraviolet-A radiation can induce a rigidification effect due to photochemical crosslinking of the constitutive collagen. Methods: Excised strips of sheep tarsus were irradiated with ultraviolet-A rays (wavelength 365 nm) at low and high irradiances, in the presence of riboflavin as a photosensitizer, using radiation sources available for corneal collagen crosslinking procedure. The tensile strength and Young's modulus (stiffness) of irradiated and control samples were measured in a mechanical tester and analyzed statistically. Histologic examination of the specimens was carried out to evaluate the effect of radiation on the meibomian glands and collagen organization. Results: Mechanical evaluation showed that irradiation induced both stiffening and strengthening of the tarsal plate specimens, and this effect was enhanced at the higher levels of irradiance. The changes in mechanical properties can be attributed to a process of photochemically induced crosslinking of tarsal collagen. Histology revealed no changes in the meibomian glands or in the fibrous collagen system of the tarsus. Conclusions: These findings indicate that irradiation of tarsal collagen leading to tissue stiffening could be a safe procedure for treating lax eyelid conditions in human patients. Accepted for publication December 5, 2017. Supported by an unrestricted grant from the Queensland Eye Institute Foundation, South Brisbane, Queensland, Australia. The funders had no role in the concept, design, and conduct of the study; neither in the preparation, review, or approval of manuscript for publication. Australian Provisional Patent Application No. 2017900561 has been filed on February 21, 2017, and assigned to the Queensland Eye Institute Foundation, by the authors Tai M. Smith, Brendan G. Cronin, Shuko Suzuki, and Traian V. Chirila as inventors. Address correspondence and reprint requests to Traian V. Chirila, B.Eng., Ph.D., F.R.A.C.I., F.R.S.C., Queensland Eye Institute, 140 Melbourne Street, South Brisbane, QLD 4101, Australia. E-mail: traian.chirila@qei.org.au. © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Novel FOXC2 Mutation and Distichiasis in a Patient With Lymphedema-Distichiasis Syndrome

A 4 year-old-boy was referred for distichiasis of the upper and lower lids of both eyes that had been present since at least 1 year of age. The patient's family history was notable for distichiasis and lymphedema affecting numerous family members. The patient was found to have a novel heterozygous variant (c.741_742insGG) in the FOXC2 gene. Mutations in the FOXC2 gene are associated with lymphedema-distichiasis syndrome. An important feature of lymphedema-distichiasis syndrome is that distichiasis is typically present prior to the onset of lymphedema. Accepted for publication November 5, 2017. Research to Prevent Blindness unrestricted departmental award (Vanderbilt University Medical Center, Department of Ophthalmology & Visual Sciences). The authors have no conflicts of interest to disclose. Address Correspondence and reprint requests to: Louise A. Mawn, M.D., F.A.C.S., Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, 2311 Pierce Avenue, Nashville, TN 37232. E-mail: louise.a.mawn@vanderbilt.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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.

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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.

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The Role of Sex, Gender, Health Factors, and Job Context in Workplace Accommodation Use Among Men and Women with Arthritis

Abstract

Background

With the aging of populations in many countries, workers are expected to remain employed longer but may struggle with the onset of common, chronic conditions like arthritis. To date, few studies have examined workplace policies and practices that could help accommodate individuals with arthritis, and fewer still have used a sex and gender-based approach to explore similarities and differences between women and men.

Objectives

This study compared the health and work contexts of workers aged ≥50 years to better understand similarities and differences between women and men in accommodation availability, need, use, and unmet needs.

Methods

A cross-sectional survey of men and women with osteoarthritis (OA), inflammatory arthritis (IA), or both OA and IA was administered online or by telephone and assessed demographics (e.g. age, education), health (e.g. pain, fatigue, workplace activity limitations), work context factors (e.g. job sector, full/part-time work, job control), and workplace accommodations (e.g. health benefits, flexible hours, special equipment/adaptations, modified duties). Sex and gender-based analyses examined similarities and differences between men and women and included descriptive statistics, multivariable multinomial analyses, and nested regression analyses.

Results

There was a 58.9% response rate and final sample of 463 participants (women, n = 266; men, n = 197; OA = 59.0%; IA/both IA and OA = 23.7%; unsure = 17.3%). Women and men were significantly different in a number of health (e.g. fatigue, health variability, workplace activity limitations) and work context factors (e.g. job sector, part-time work, job stress). However, in other respects, they were similar (e.g. pain, job involving physical demands, size of organization, shift work, union membership, job control). There were no differences between men and women in the availability or use of workplace accommodations. However, women reported significantly more accommodation needs and had greater unmet needs. Multivariable multinomial analyses found male/female as a binary variable did not explain differences in accommodation need, use, and unmet need. Nested analyses highlighted that differences in health variables explained male/female differences in accommodation need, while work context differences explained male/female differences in whether needs were met.

Conclusions

The findings highlight that women and men draw on a range of existing accommodation policies and practices to help manage their arthritis and that most have their accommodation needs met. Decomposing the context within which men and women with arthritis work suggests that women may face health and work context challenges that differ from men and that are related to greater accommodation needs and unmet need. This highlights potential vulnerabilities in the work of women that need to be addressed.

A TRIGLYCERIDE-RICH LIPOPROTEIN ENVIRONMENT EXACERBATES RENAL INJURY IN THE ACCELERATED NEPHROTOXIC NEPHRITIS MODEL

Summary

Hyperlipidemia accompanies chronic renal disease either as a consequence of the renal dysfunction or as part of generalised metabolic derangements. Under both situations, the lipid profile is characterised by accumulation of triglyceride-rich lipoproteins (TGRLs). This lipid profile is increasingly recognised as a risk factor for cardiovascular complications. Whether it may pose a risk for renal injury as well remains unclear. A hyper-TGRL state was generated in C57BL/6 mice using the poloxamer-407 (P-407) and immune complex-mediated renal injury was triggered using the accelerated nephrotoxic nephritis (ANTN) model. The hyper-TGRL animals were hypersensitive to ANTN demonstrated by greater haematuria and glomerular cellularity. These changes were accompanied by increased glomerular accumulation of CD68⁺ macrophages. The hypersensitive response to ANTN was not seen in low density lipoprotein receptor knock-out mice fed with high fat diet, where triglyceride levels were lower but cholesterol levels comparable to those obtained using P-407. These data indicate that a hyper-TGRL state might be more detrimental to the kidneys than low density lipoprotein driven hypercholesterolemia during immune complex-mediated nephritis. We speculate that the hyper-TGRL environment primes the kidney to exacerbated renal damage following an inflammatory insult with increased accumulation of macrophages that may play a key role in mediating the injurious effects. This article is protected by copyright. All rights reserved.