Dry skin manifestations in Sjögren syndrome and atopic dermatitis related to aberrant sudomotor function in inflammatory allergic skin diseases

Publication date: Available online 10 August 2018

Source: Allergology International

Author(s): Ichiro Katayama

Abstract

We have reported characteristic cutaneous manifestations of Sjögren syndrome (SS) with special references to autoimmune anhidrosis or hypoidrosis and related mucocutaenous manifestations in addition to annular erythema or cutaneous vasculitis. Although significance of cutaneous manifestations of SS has been gradually recognized in rheumatologists, sudomotor function has not been fully evaluated and recognized in the diagnosis of SS except for dermatologists. SS is a relatively underestimated collagen disease in contrast to SLE, systemic sclerosis, or dermatomyositis, special care should be needed not to make misdiagnosis of SS when we see the patients with common skin disease such as, drug eruption, infections skin disease or xerosis in the daily practice. In contrast to pathomechanisms of dry skin observed in SS, we recently reported that reduced sweating function and dry skin seen in atopic dermatitis (AD) are mediated by histamine or substance P, those are usually restored to normal levels after improvement of the dermatitis by topical corticosteroid ointment with or without oral anti-histamine. Therefore, xerotic skin lesions seen in SS and AD might be attributable to different pathomechanisms with similar dry skin manifestations. We recently reported that SS promotes dry skin when complicated with AD possibly due to acceleration of hypoidrosis. In this review, we would like to summarize our recent understanding of regulatory mechanism of impaired sweating function in allergic inflammatory skin diseases by introducing clinical presentations of AD/SS overlap cases as the model of hypoidrotic inflammatory skin diseases.

https://ift.tt/2KP3O2I

Synergetic effect of hydrochar on the transport of anatase titanium dioxide nanoparticles in the presence of phosphate in saturated quartz sand

Abstract

The rapid development of nanomaterials has led to the unavoidable leakage and release of nanoparticles (NPs) into soil and the underlying groundwater. It is possible for chars and phosphate introduced into soil to improve crop soil properties by improving contact with NPs. In this study, the influences of hydrochar and/or phosphate on the anatase nTiO₂ transport behaviors were investigated under different conditions. The breakthrough curves (BTCs) and retention profiles were obtained by the saturated sand column experiments. The additional analysis of zeta potentials, sedimentation kinetics, Raman mapping, and the two-site kinetic attachment model (TSKAM) was conducted to explore the possible underlying mechanisms. The simultaneous presence of phosphate and hydrochar acted in a synergetic fashion to enhance the transport of nTiO₂ in a sand medium compared to the facilitated effect of single phosphate or hydrochar. The higher levels of hydrochar induce the more nTiO₂ in the high IC solution passing through the saturated sand columns in the co-presence of phosphate. It was attributed to the competitive adsorption of hydrochar with nTiO₂ to the sand site and the phosphate adsorption on nTiO₂ occurred simultaneously through the sand columns. The fitting results of BTCs using TSKAM showed that the value of k₂ for nTiO₂ (the irreversible attachment coefficient at site 2) was smaller than that of k_1d/k₁ (the first-order reversible detachment and attachment coefficient at site 1, respectively), suggesting irreversible retention of anatase nTiO₂ at site 1. The value of k_1d/k₁ could be better used to explain the retention of nTiO₂ with combined phosphate and hydrochar. This study provides insight into the implications of phosphate and/or hydrochar for nTiO₂ transport in crop soil environments.

Graphical abstract

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Rigid dilatation of pediatric laryngotracheal stenosis as an adequate alternative to balloon dilatation

Abstract

Introduction

Endoscopic balloon dilation (EBD) is the mainstay of endoscopic therapy for laryngotracheal stenosis (LTS), although there is no evidence that it achieves better results than traditional rigid laryngeal dilators. Rigid bougie dilators are less expensive and easier to use, and confer the advantage of providing tactile information about the stenosis to the surgeon. We analyzed the outcome of endoscopic rigid bougie dilatation of LTS in a large series of children and compared it to the reported results of EBD in the same setting.

Patients and methods

All cases of pediatric LTS treated by endoscopic rigid dilatation in a tertiary referral center between 2006 and 2015 were retrospectively studied. They were divided into a primary dilatation group (PDG) and a post-reconstruction dilatation group (PRG). The PDG children had no history of reconstructive airway surgery, and dilatation was the major treatment approach. The PRG children underwent dilatations after airway reconstruction surgery as part of routine postoperative management. A successful primary outcome was defined as improvement of dyspnea and achievement of a functional airway without reconstructive laryngotracheal surgery or need for a tracheostomy at final follow-up.

Results

Sixty-two children (68 cases, mean age 5.1 years, range 0.7–17.2) underwent 156 endoscopic rigid dilatations. Successful outcome was achieved in 48 cases (70.6%), 73.0% in the PDG and 67.7% in the PRG. There were no procedure-related adverse events.

Conclusions

Endoscopic rigid dilatation is a relatively inexpensive and efficacious tool in endoscopic management of pediatric LTS. Its success rates are in the same range as those of EBD.

https://ift.tt/2MCxr99

Rocuronium pharmacodynamic models for published five pharmacokinetic models: age and sex are covariates in pharmacodynamic models

Abstract

Purpose

Equilibration rate constant is necessary to calculate effect-site concentration, which is useful to control drug effect. We developed pharmacodynamic models for published five compartmental pharmacokinetic models published by Wierda, Szenohradszky, Cooper, Alvarez-Gomez, and McCoy.

Methods

We used 3848 train-of-four ratios from 15 male and nine female patients (21–76 years; 44–93 kg body weight; 148–181 cm height; and 17.3–29.8 kg/m² body mass index) as pharmacodynamic measures, which were collected at the start of 0.6 mg/kg rocuronium administration until the end of the surgery. Effect compartment was assumed to be connected to central compartment of the pharmacokinetic model with equilibration rate constant (k_e0). Sigmoid E_max model was fitted to describe the relationship between train-of-four ratio and effect-site concentration. Age, sex, and body mass index were assessed as possible covariates of the following model parameters: k_e0, effect-site concentration for half of maximum effect, and the steepness of the effect-site concentration versus effect relationship.

Results

The duration of neuromuscular monitoring was 69 (37–129) [median (range)] min. All pharmacodynamic models included age and three included sex as significant covariates. K_e0 values ranged between 0.0820 and 0.247 depending on the pharmacokinetic model. The time-courses of the effect-site concentration were similar among the pharmacodynamic models for Wierda, Cooper, and Alvarez-Gomez pharmacokinetic models, which were lower than that for the Szenohradszky pharmacokinetic model.

Conclusion

Each pharmacodynamic model with the corresponding pharmacokinetic model can be described the time course of rocuronium effect appropriately. The required effect-site concentration of rocuronium for a pharmacodynamic effect was depending on the applied models.

https://ift.tt/2nvhbfc

A Twenty-two-year Experience with Hymenoptera Venom Immunotherapy in a US Pediatric Tertiary Care Center: 1996-2018

Publication date: Available online 11 August 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Sultan Albuhairi, Kristel El Khoury, Christina Yee, Lynda Schneider, Rima Rachid

https://ift.tt/2P0vDZ6

A Phase 2a Study of Toreforant, a Histamine H4 Receptor Antagonist, in Eosinophilic Asthma

Publication date: Available online 11 August 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Alexa P. Kollmeier, Elliot S. Barnathan, Christopher O'Brien, Bin Chen, Yichuan (Karen) Xia, Bei Zhou, Matthew J. Loza, Philip E. Silkoff, Michelle Ge, Robin L. Thurmond

https://ift.tt/2B2gQdz

Nuclear loss and cytoplasmic expression of androgen receptor in penile carcinomas: role as a driver event and as a prognosis factor

Abstract

Androgen receptor (AR) is a member of the steroid and nuclear family receptor that acts as transcription factor. AR signaling plays pivotal role in the development and progression of prostate cancer. However, the role of AR in penile cancer (PeCa) is poorly explored. Our previous molecular studies unveiled frequent AR mRNA loss in PeCa, which was further predicted as a major driver alteration in this neoplasm. Herein, we assessed the AR protein expression in 59 usual PeCa tissues and 42 surrounding normal tissues (SNT) by immunohistochemistry using a tissue microarray. In a paired analysis, we found a total absence of nuclear AR expression in PeCa while 95.2% of SNT samples presented strong nuclear AR expression (P < 0.001). Interestingly, 17 of 42 PeCa presented weak or moderate cytoplasmic AR staining, contrasting with 5 of 42 SNT (P = 0.008). Increased levels of AR cytoplasmic expression were related with poor prognosis features including advanced clinical staging (P = 0.044), compromised surgical margins (P = 0.005), and pathological inguinal node status (P = 0.047). Furthermore, AR cytoplasmic expression was also related with shorter overall survival (P = 0.032). In conclusion, the frequent loss of nuclear AR protein levels suggests a potential function in PeCa development. Based on this result, the androgen deprivation therapy is not indicated for PeCa patients. In addition, the AR cytoplasmic expression found in a significant number of cases (40.5%) showed prognostic value and pathways activated by the non-genomic AR signaling may represent a promising therapeutic strategy.

https://ift.tt/2B2OEHq

Mercury contamination in the sludge of drinking water treatment plants dumping into a reservoir in Rio de Janeiro, Brazil

Abstract

Although sludge piles from drinking water treatment plants can contain harmful substances, in many countries, their disposal methods are still unregulated. Besides aluminum, which is a major constituent in these residues, many other contaminants—like trace metals—can be present and may result from the quality of the raw materials used for water treatment. The application of these chemicals for the treatment of drinking water can generate toxic sludge and contaminate the produced water. In the present work, mercury contamination in the sludge piles of two drinking water treatment plants located along the margins of the Juturnaíba Reservoir, Southeast Brazil, was evaluated to verify whether contaminants are incorporated during water treatment. In the summer 2012, five cores were collected from the piles, and were analyzed for Eh, granulometry, total carbon, total nitrogen, and total mercury. The results indicated an anoxic environment, reflecting composition of the suspended matter. Carbon and nitrogen presented elevated concentrations, but also seemed to reproduce the characteristics of the suspended matter in the raw water. The concentrations of mercury were extremely variable but presented unexpectedly high values in some of the layers, reaching 18,484 ng g⁻¹. On the other hand, concentrations ten times lower than those observed in the natural system (8 ng g⁻¹) could be observed. It was concluded that the only possible source for the contamination of the sludge was the chemicals used for water treatment.

https://ift.tt/2B1eFqs

Environmental functions of biochar—a special issue for the 3 rd Asia Pacific Biochar Conference (APBC 2016)

https://ift.tt/2vBZNtv

School Absenteeism Associated with Asthma and Allergic Diseases in Korean School-Aged Children

Pediatric Allergy, Immunology, and Pulmonology, Ahead of Print.


https://ift.tt/2MGvfNy

Suicide: A Taboo Topic That We Must Talk About Now

Violence and Gender, Ahead of Print.


https://ift.tt/2MBtgdC

Effectiveness of First‐Line Bevacizumab in Metastatic Colorectal Cancer: The Observational Cohort Study GRETA

AbstractBackground.Scant real‐world data exist on the clinical outcomes associated with the use of bevacizumab‐containing chemotherapy (B+CT) in patients with metastatic colorectal cancer (mCRC). The primary objective of the GRETA cohort study was to compare the overall survival (OS) of patients with mCRC treated with first‐line B+CT versus chemotherapy (CT) alone, in an Italian clinical practice setting.Materials and Methods.Incident patients with mCRC were identified during the period 2010–2012 from five population‐based cancer registries in Italy. Cases were linked to regional health care utilization databases to obtain the entire spectrum of health services provided to each patient. Patients starting a first‐line treatment with B+CT or CT alone within 90 days from the diagnosis were included in the study cohort. A propensity score (PS) method was applied to account for residual confounding.Results.Of 480 patients with mCRC included in the study cohort, 21.0 received first‐line B+CT, and 79.0% received CT. Patients receiving B+CT were younger (p < .001) and underwent surgery more frequently (p = .001). The median OS was 22.5 and 14.6 months for B+CT and CT, respectively (p = .011). The corresponding hazard ratios adjusted by multivariate modeling and PS matched analysis were 0.82 (95% confidence interval [CI], 0.62–1.08) and 0.86 (95% CI, 0.56–1.33), respectively. Similar results were observed after subgrouping by age and surgery.Conclusion.In this Italian real‐world setting of unselected mCRC, the OS of patients treated with B+CT was consistent with previous observational and patient‐registry studies. However, definitive evidence of an improvement in OS cannot be drawn.Implications for Practice.Bevacizumab is a well‐established first‐line treatment for metastatic colorectal cancer. However, there is scarce evidence in the literature about its effectiveness in clinical practice. Evaluating this topic should be of interest for both clinicians and regulatory agencies. In this study, the median overall survival of the bevacizumab cohort was strikingly coherent with that reported in large observational series of unselected patients, thus suggesting a consistent and reproducible effect of the drug in clinical practice. Although consistent results were observed both in the overall population and in age and surgery subgroups, the present study did not offer definitive evidence of an improvement in OS.

https://ift.tt/2KKfvYf

Wide Range of Clinical Outcomes in Patients with Gliomatosis Cerebri Growth Pattern: A Clinical, Radiographic, and Histopathologic Study

AbstractBackground.The 2016 World Health Organization Classification of Central Nervous System Tumors categorizes gliomatosis cerebri growth pattern (GC) as a subgroup of diffuse infiltrating gliomas, defined by extent of brain involvement on magnetic resonance imaging (MRI). Clinical and radiographic features in GC patients are highly heterogeneous; however, prognosis has historically been considered poor.Subjects, Materials, and Methods.We performed a retrospective search for patients at our institution meeting radiographic criteria of primary, type I GC (defined as diffuse tumor infiltration without associated tumor mass and contrast enhancement on MRI) and analyzed their clinical, imaging, and histopathologic features.Results.A total of 34 patients met radiographic criteria of primary, type I GC, and 33 had a confirmed histologic diagnosis of an infiltrating glial neoplasm. Age >47 years at diagnosis was associated with worse overall survival (OS) compared with age ≤47 years (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.01–1.07, p = .003). Patients with grade 2 tumors demonstrated a trend for improved OS compared with those with grade 3 tumors (HR 2.65, 95% CI 0.99–7.08, p = .051). Except for brainstem involvement, extent or location of radiographic involvement did not detectably affect clinical outcome. IDH mutation status identified a subgroup of GC patients with particularly long survival up to 25 years and was associated with longer time to progression (HR 4.81, 95% CI 0.99–23.47, p = .052).Conclusion.Patients with primary, type I GC do not uniformly carry a poor prognosis, even in the presence of widespread radiographic involvement. Consistent with other reports, IDH mutation status may identify patients with improved clinical outcome. Molecular characterization, rather than MRI features, may be most valuable for prognostication and management of GC patients.Implications for Practice.Patients with gliomatosis cerebri growth pattern (GC) constitute a challenge to clinicians, given their wide range of clinical, histologic, and radiographic presentation, heterogeneous outcome patterns, and the lack of consensus on a standardized treatment approach. This study highlights that radiographic extent of disease—albeit category‐defining—does not detectably influence survival and that IDH mutations may impact clinical outcome. Practicing oncologists should be aware that select GC patients may demonstrate exceptionally favorable survival times and prognosticate patients based on molecular markers, rather than imaging features alone.

https://ift.tt/2P0RzmD

Analysis of Risk Factors for Unplanned Reoperation Following Free Flap Surgery of the Head and Neck

The Laryngoscope, EarlyView.


https://ift.tt/2nrEd6p

Smith–Lemli–Opitz syndrome presenting as acute adrenal crisis in a child: a case report

Smith–Lemli–Opitz syndrome is a rare autosomal recessive disorder of cholesterol biosynthesis which is characterized by multiple congenital malformations and global developmental delay. Here we report the case...

https://ift.tt/2OX3vWR

Review of Common Alternative Herbal “Remedies” for Skin Cancer

BACKGROUND Alternative herbal remedies for skin cancer are commonly found on the Internet. Many websites contain inaccurate or false information regarding side effects and efficacy. OBJECTIVE To review the evidence behind several commonly advertised herbal remedies that claim to cure skin cancer: black salve, eggplant, frankincense, cannabis, black raspberry, milk thistle, St. John's wort, and turmeric. METHODS A PubMed search was performed using the common and scientific names of frequently advertised herbal remedies along with the terms "nonmelanoma skin cancer," or "basal cell carcinoma" or "squamous cell carcinoma," or "melanoma." RESULTS Some preclinical studies have shown positive evidence that these substances can induce apoptosis in skin cancer, but clinical studies proving efficacy are either insufficient, nonexistent, or show negative evidence. Botanicals that were excluded are those that do not have published studies of their efficacy as skin cancer treatments. CONCLUSION Online advertising may tempt patients to use botanical agents while citing efficacy found in preclinical studies. However, many agents lack strong clinical evidence of efficacy. Dermatologists must be aware of common herbal alternatives for skin cancer treatment to maintain effective patient communication and education. Address correspondence and reprint requests to: Jeremy T. Kampp, MD, 4225 Roosevelt Way NE, 4th floor, Seattle, WA 98105, or e-mail: jkampp@uw.edu The authors have indicated no significant interest with commercial supporters. © 2018 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2nz8pgh

Phase 3 Study of OnabotulinumtoxinA Distributed Between Frontalis, Glabellar Complex, and Lateral Canthal Areas for Treatment of Upper Facial Lines

BACKGROUND Although commonly practiced, simultaneous onabotulinumtoxinA injections to multiple facial areas have not been investigated in prospective studies. OBJECTIVE Evaluate safety and efficacy of onabotulinumtoxinA for treatment of forehead lines (FHL) distributed between the frontalis (20 U) and glabellar complex (20 U), with or without simultaneous lateral canthal areas (crow's feet lines [CFL], 24 U) treatment. METHODS Subjects with moderate to severe FHL were randomized (2:2:1) to onabotulinumtoxinA 40 U, onabotulinumtoxinA 64 U, or placebo. After 180 days, subjects could receive up to 2 additional open-label onabotulinumtoxinA 64 U treatments. RESULTS The intent-to-treat (ITT) population comprised 787 subjects, and the modified ITT (mITT) population (subjects with psychological impact) comprised 568. After 30 days, onabotulinumtoxinA 40 U and 64 U significantly improved investigator- and subject-assessed FHL severity by at least 2 Facial Wrinkle Scale (FWS) grades in 45.6% and 53.0% of ITT subjects, respectively, versus 0.6% receiving placebo (both, p

https://ift.tt/2vWQ4ND

Efficacy of 1,550-nm Erbium-Glass Fractional Laser Treatment and Its Effect on the Expression of Insulin-Like Growth Factor 1 and Wnt/β-Catenin in Androgenetic Alopecia

BACKGROUND A new treatment for androgenetic alopecia (AGA) is 1,550-nm erbium-glass (Er:Glass) fractional laser. The wound healing process associated with this treatment is believed to be due to the stimulation of hair regrowth. Both the Wingless-related integration site (Wnt) proteins and insulin-like growth factor 1 (IGF-1) are important molecules that promote new hair growth. OBJECTIVE The aim of this study was to evaluate the efficacy of 1,550-nm Er:Glass fractional laser treatment and determine the gene expression of IGF-1 and Wnt/β-catenin in patients with AGA. METHODS Twenty-three patients with AGA were enrolled. They received 12 treatments at 2-week intervals. A scalp biopsy was performed to evaluate mRNA levels of Wnt10A and IGF-1. Histopathologic samples were collected. RESULTS Significant increases in hair count and shaft diameter that occurred from Month 4 until the end of the study were observed. Histological results showed increases in the follicular unit, anagen hair count, and the anagen:telogen ratio. No up-regulation of Wnt10A and IGF-1 mRNA was observed. CONCLUSION The 1,550-nm Er:Glass fractional laser treatment can increase hair density and shaft diameter in patients with AGA. The mechanisms by which 1,550-nm Er:Glass laser treatment induces new hair growth may not be limited to Wnt10A/β-catenin or IGF-1 expression. Address correspondence and reprint requests to: Jitlada Meephansan, MD, PhD, Division of Dermatology, Chulabhorn International College of Medicine, Thammasat University, Rangsit Campus, Klong Luang, Pathum Thani 12120, Thailand, or e-mail: kae_mdcu@yahoo.com The authors have indicated no significant interest with commercial supporters. © 2018 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2ntoUuf

Clinical Application of Cultured Stratified Epithelial Sheets Grown Under Feeder or Feeder-Free Conditions for Stable Vitiligo

BACKGROUND Autologous cultured therapy has emerged as an effective treatment for stable vitiligo. However, culture methods may include harmful agents and be unsuitable for therapeutic use in humans. OBJECTIVE To investigate the safety and efficacy of autologous cultured epithelial sheets propagated under serum-free and feeder-free conditions for the treatment of stable vitiligo. METHODS Twenty-eight patients with stable vitiligo were included in this study. Keratinocytes and melanocytes from 14 patients were cultured under serum-free, feeder-free conditions (Group A). Epithelial cells from the remaining 14 patients were cultured according to Rheinward and Green's technique (Group B). Patients were followed up at 1, 3, 6, and 12 months after transplantation. RESULTS The epithelial sheets cultured in Group A were thinner and more fragile than Group B, but there were no significant differences in repigmentation between the 2 groups. At 12-month follow-up, in Group A, repigmentation at graft sites was classified as excellent in 9 patients and good in 2 patients. In Group B, repigmentation was excellent in 8 patients and good in 4 patients. Scars at the donor sites were the most frequent adverse events associated with the procedure. CONCLUSION Autologous epithelial sheet cultured in serum-free, feeder-free conditions is a safe and efficacious approach to cure stable vitiligo. Address correspondence and reprint requests to: Jinhua Xu, MD, PhD, Department of Dermatology, Huashan Hospital of Fudan University, No. 12 Wulumuqi Zhong Road, Shanghai 200040, China, or e-mail: lijian1979@medmail.com.cn Supported by Medical Guide Subject of Shanghai Science and Technology Committee (subject number: 124119a1002) and Clinical Priority Specialized Subject of the Ministry of Health of China (2013). The authors have indicated no significant interest with commercial supporters. J. Li and S. Chen have contributed equally to this work. In this current study, patients and skin samples were collected according to Huashan Hospital of Fudan University Research Ethics Service Study Protocol (Ethical approval number: Huashan ethics committee 2012(007)), and this study was approved by Huashan Hospital of Fudan University ethics committee. Written informed consent was obtained from all patients. © 2018 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2vZ6AN5

Trust in Police and Fear of Crime Among Young People from a Gender Perspective: The Case of Mexico

Violence and Gender, Ahead of Print.


https://ift.tt/2P05zgI

Effect of cabergoline monotherapy in Cushing’s disease: an individual participant data meta-analysis

Abstract

Context

The primary treatment of choice for Cushing's disease (CD) is the removal of the pituitary adenoma by transsphenoidal surgery (TSS). The surgical failure is seen in up to 75% of cases depending on the experience of the surgeon in different studies. Medical therapy is one of the options for the treatment of recurrent or persistent CD.

Methodology

The primary outcome of this meta-analysis was to find the proportion of patients achieving normalisation of 24-h urinary free cortisol (remission of CD) following cabergoline monotherapy. Literature search was conducted in January 2018 in PubMed/MEDLINE database from its date of inception to 31st December 2017. The search strategy used was "[(cushing) OR Cushing's] AND cabergoline". Individual participant data were extracted from the included studies and risk of bias was analysed by review checklist proposed by MOOSE.

Results

The individual participant data of 124 patients from six observational studies were included in this meta-analysis. 92 patients (74.2%) had past pituitary surgery. The proportion of patients achieving remission of CD with cabergoline monotherapy was 39.4% (95% confidence interval 0.31–0.49; P = 0.026). The previous surgery [odds ratio (OR) 28.4], duration of cabergoline monotherapy (OR 1.31) and maximum cabergoline dose (OR 0.19) were predictors for remission of CD. Mild and severe side effects were reported in 37.3% and 5.6% of patients, respectively, during cabergoline monotherapy.

Conclusions

This meta-analysis shows that cabergoline monotherapy is a reasonable alternative for subjects with persistent or recurrent CD after TSS. It can also be used in CD patients either as a bridge therapy while waiting for surgery or in those unwilling for surgery or have contraindication to it.

https://ift.tt/2vxezl4

Free Gracilis Transfer and Static Facial Suspension for Midfacial Reanimation in Long-Standing Flaccid Facial Palsy

This article presents an approach to reanimation of the midface in long-standing flaccid facial palsy by means of functional free gracilis transfer and static facial suspension.

https://ift.tt/2vvgeb5

The Importance and Psychology of Facial Expression

Facial expression is of critical importance in interpersonal interactions. Thus, patients with impaired facial expression due to facial paralysis experience impaired social interactions. Numerous studies have shown that patients with facial paralysis and impaired facial expression suffer social consequences as demonstrated by being rated negatively with regards to attractiveness, affect display, and other traits. This has been demonstrated subjectively and objectively. Fortunately, reconstructive surgeries that restore the ability to express emotion can restore normalcy in these patients.

https://ift.tt/2MyWOIN

Prospective pilot evaluation of the efficacy and safety of adjuvant topical ingenol mebutate gel for localized patch/plaque-stage mycosis fungoides

Introduction: Whether ingenol mebutate (IM) is effective as adjuvant topical treatment for mycosis fungoides (MF) remains undetermined.

https://ift.tt/2AXTzJJ

Paraneoplastic angiomatosis: A new entity

Paraneoplastic syndromes result from tumor secretion of hormones, peptides, or cytokines or from immunologic cross reactions between malignant and normal cells. Numerous organ systems may be affected by paraneoplastic conditions, including the skin. We report 2 cases of benign cutaneous vascular proliferations occurring in the setting of malignancy and propose the term paraneoplastic angiomatosis. Case 1: A 62-year-old man with multiple comorbidities presented with a large, irregular, blanching erythematous abdominal plaque.

https://ift.tt/2OZXqsE

Pilot evaluation of safety, efficacy, and tolerability of a new topical formulation for facial hyperpigmentation, combining ascorbyl tetraisopalmitate and crosslinked resilient hyaluronic acid

This study evaluated therapy of facial hyperpigmentation with a novel topical formulation combining two synergistic melanogenesis inhibitors: ascorbyl tetraisopalmitate (ATIP), the esterified form of vitamin C (concentration equivalent to 8% L-ascorbic acid), and crosslinked resilient hyaluronic acid (RHA). Vitamin C inhibits multiple oxidative steps during melanogenesis, diminishing tyrosinase activity. Clinical challenges with L-ascorbic acid include low skin penetrance, instability due to oxidation, and potential irritation.

https://ift.tt/2AXT9mD

No disclosure of support by ISDIN SA on poster

"Antiaging facial serum containing melatonin, bakuchiol, and ascorbyl tetraisopalmitate up-regulates antioxidant gene expression in medaka embryos"

https://ift.tt/2vBuBup

Predictors of response to tildrakizumab for moderate-to-severe chronic plaque psoriasis

Introduction: Efficacy of tildrakizumab (TIL), a high-affinity, humanized, IgG1/κ monoclonal antibody against IL-23p19, has been evaluated for chronic plaque psoriasis (Pso) in 2 phase 3 randomized controlled trials. The objective of this analysis was to determine predictors of response to TIL treatment in the 2 trials.

https://ift.tt/2AZXiWX

Pembrolizumab-induced bullous pemphigoid

Background: Bullous pemphigoid (BP) is an autoimmune blistering disorder characterized by autoantibody deposition at the epithelial basement membrane zone. It classically presents in elderly adults and can be idiopathic or drug-induced. The 2 major bullous pemphigoid antigens do not differ between the drug-induced and idiopathic variants of the disease, nor do the direct and indirect immunofluorescence (DIF and IIF) findings. Pembrolizumab is an anti–programmed cell death 1 (PD-1) antibody which inhibits the negative immune regulation caused by PD-1 receptor signaling resulting in reversal of T-cell suppression and induction of antitumor responses.

https://ift.tt/2vAhbyK

Omalizumab for chronic spontaneous urticaria in real-life practice

Background: Omalizumab has been shown to be highly effective in phase III clinical trials in treatment of chronic spontaneous urticaria (CSU).

https://ift.tt/2AZX9Tp

National trends in staphylococcal scalded skin syndrome

Background: Staphylococcal scalded skin syndrome (SSSS) is a potentially fatal superficial blistering disorder caused by infection with exfoliative toxin producing strains of Staphylococcus aureus.

https://ift.tt/2vwHPsw

Comparison of Er:YAG laser, short pulse-duration pulsed dye laser, and long pulse-duration pulsed dye laser in treating sebaceous hyperplasia

Background: Patients of sebaceous hyperplasia (SH) usually seek treatment due to cosmetic concern. A few nonsurgical ablative devices are effective in treating SH, including carbon dioxide laser and erbium-doped yttrium aluminium garnetlaser (Er:YAG) laser. But these options bear the considerable risk of postoperative discoloration and scar formation. Pulsed dye laser (PDL) has been reported effective in treating SH. However, only short pulse-duration PDL (SPDL) has been used in previous studies.

https://ift.tt/2B1VBby

Pseudomelanocytic nests leading to a misdiagnosis of lentigo maligna

Introduction: Dermoscopy of facial pigmented lesions is sometimes challenging and clinical-histologic correlation is essential.

https://ift.tt/2OXgUOt

Primary cutaneous mucinous carcinoma: Incidence and survival

Background: Primary cutaneous mucinous carcinoma (PCMC) is a rare eccrine carcinoma with a propensity to affect the head, especially the eyelid. It has the potential to be locally destructive with high rates of recurrence but low metastatic potential. Owing to its rarity, demographic and cancer-related data for PCMC are limited.

https://ift.tt/2B1VAV2

Poly-L-lactic injectable acid in the treatment of facial and extra facial flaccid areas: A case series

Poly-L-lactic acid (PLLA) is a synthetic, biocompatible and biodegradable polymer used as a sterile injectable solution to stimulate collagen production, leading to cutaneous filling, but do not act as a true volumizer. It has been used in facial and extrafacial areas to correct flaccidity, loss of volume, improve contour and skin elasticity. We report four female patients treated with PLLA, one vial per session. The final dilution was 10 cc for facial and 20 cc for extra facial injections. Case 1: 56 yo, treatment of medial region of the arms in 3 sessions.

https://ift.tt/2vycrty

Phase II study of KX2-391 ointment 1%, a novel field treatment for actinic keratosis, based on Src/tubulin polymerization inhibition

Background: KX2-391, a dual Src tyrosine kinase and tubulin polymerization inhibitor, inhibits the growth of human keratinocytes with IC50 of 32 nM and induces apoptosis in dividing cells. A phase I study demonstrated that KX2-391 ointment 1% reduced actinic keratosis (AK) lesion counts and was well tolerated following 3 or 5 days of treatment on the forearm. Aim: To determine the activity, safety and pharmacokinetics of KX2-391 ointment 1% (5 or 3 days) in adults with AK on the face or scalp.

https://ift.tt/2AXlQQE

Patient-reported global severity of atopic dermatitis is valid in adults

Atopic dermatitis (AD) is associated with a heterogeneous presentation and clinical course. There are many different patient-reported outcome measures available that measure different aspects of the disease. However, there are few simple, intuitive and validated severity assessments that are feasible for clinical practice and epidemiologic research. We sought to validate patient-reported global AD severity in adults. We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 265).

https://ift.tt/2OWQzAh

Oral Polypodium leucotomos extract and its impact on visible light–induced pigmentation

Background: Visible light has multiple effects on the skin including erythema, DNA damage secondary to free radical production, and pigmentation. Few sunscreens protect against visible light, which can exacerbate photodermatoses. Polypodium leucotomos extract (PLE) has antioxidant, photoprotective, chemoprotective, antiinflammatory, and immunomodulatory properties that may offer protection against visible light induced effects.

https://ift.tt/2AWDUds

Objective assessment of dry skin roughness in a pediatric population

Introduction and objectives: Dry skin is a common condition during childhood. Clinical scoring of dry skin includes tactile evaluation of the skin surface to assess roughness. It also includes visual examination of the appearance of the skin and for severe cases the presence of dander. To our knowledge, no instrumental evaluation of roughness has ever been performed to objectively score skin dryness in a pediatric population, nor to document the clinical efficacy of skin care products specifically developed to address dry skin condition.

https://ift.tt/2vveNtd

Neurofibromatosis type 1 and birth size: A retrospective registry-based total population study in Finland

Neurofibromatosis type 1 (NF1) is the most common dominantly inherited cancer predisposition syndrome with prevalence of ∼1:2,000. It is caused by mutations in NF1 gene on chromosome 17. The protein product of NF1 gene is neurofibromin, which acts as a tumor suppressor protein inhibiting Ras signaling pathway. The hallmark signs of the disorder are found on the skin, but NF1 is a multisystem disorder with increased risk for e.g., cancer, pregnancy complications, osteoporosis and learning difficulties.

https://ift.tt/2BbvW0r

T-helper cell phenotype expression in cutaneous lesions of angioimmunoblastic T-cell lymphoma

Background: Angioimmunoblastic T-cell lymphoma (AITL) is a common type of peripheral T-cell lymphoma. AITL can be missed until lymphadenopathy develops in patients initially presenting with skin lesions, as skin biopsy may lack conclusive findings. The expression of follicular helper T-cell (THF) markers in the skin can be an important diagnostic clue. We present a case of AITL with skin lesions positive for CD10 and dim PD-1 T cells, with the purpose of highlighting the potential for diagnosing cutaneous AITL via skin biopsy.

https://ift.tt/2OZ06qk

A facewash containing specific plant-derived monoterpenes reduced Propionibacterium acnes burden and improved acne symptoms

The pathogenesis of acne is multifactorial, including increased sebum production, ductal epidermal proliferation, bacterial colonization and inflammation. While the sequence of events involved in acne pathogenesis have not yet been established, there is a strong corelationship between the presence of acne and growth of the microorganism Propionibacterium acnes (P. acnes) leading to suggestions that P. acnes is associated with acne. Recent studies have also shown an increased level of Staphylococcus epidermidis (S.

https://ift.tt/2AW4vrb

A Twenty-two-year Experience with Hymenoptera Venom Immunotherapy in a US Pediatric Tertiary Care Center: 1996-2018

The severity of allergic reactions to insect stings ranges from mild, local reactions to systemic, life-threatening anaphylaxis.1, 2 Systemic reactions (SRs) to Hymenoptera stings can occur in 0.5-3.3% of adults in the US and 0.3-7.5% of adults in Europe.3, 4 In pediatric patients, the prevalence of SRs is lower, from 0.15-0.8%.5-8 In addition, in children, the majority of SRs from sting consist of exclusively cutaneous symptoms.9 Venom immunotherapy (VIT) is very effective in decreasing the SR risk after subsequent sting and is generally indicated in subjects with histories of SRs to Hymenoptera stings with extra-cutaneous symptoms.

https://ift.tt/2ntQhnC

A Phase 2a Study of Toreforant, a Histamine H4 Receptor Antagonist, in Eosinophilic Asthma

Histamine appears to play a role in the pathophysiology of asthma. In patients with allergic asthma, there is an increase in histamine in bronchoalveolar lavage fluid that is negatively correlated with airway function.1-6 In addition, histamine levels rapidly increase in the plasma of antigen-challenged patients,7 and plasma histamine levels are lowered by effective management of asthma.8

https://ift.tt/2vXcHBQ

Evaluation of the effect of pre-operative oral midazolam on post-operative oral fluid intake after tonsillectomy

Publication date: Available online 10 August 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Cynthia M. Schwartz, Kristen Honsinger, Beth A. Fischer, Charles A. Elmaraghy

Abstract

Introduction

The objective of this study was to determine if pre-operative oral midazolam administration decreased postoperative oral fluid intake after tonsillectomy with or without adenoidectomy.

Methods

A retrospective chart review identified 104 patients who were undergoing tonsillectomy with and without adenoidectomy who were not given midazolam preoperatively and 182 who were given midazolam preoperatively. Indications for tonsillectomy with or without adenoidectomy included obstructive sleep apnea, recurrent acute streptococcal pharyngotonsillitis, and, in selected cases, periodic fever with aphthous stomatitis, pharyngitis and adenopathy. All patients were evaluated in the pre-operative area by the attending anesthesiologist, who then determined whether or not he/she felt the patient would benefit from premedication with oral midazolam prior to surgery. Patients whom the attending anesthesiologist judged would benefit from midazolam were then given a 0.12 to 1.06 mg/kg dose (mean 0.35 mg/kg, STD 0.12), at the discretion of the anesthesiologist. Various methods were used to perform tonsillectomy, such as coblation and electrocautery, at the discretion of the otolaryngologist. Results were not stratified by surgical technique. Oral fluid intake was calculated by establishing the time of return to the floor from surgery and determining the documented oral fluid intake for the next 12 h. Oral fluid intake per kg per hour was then calculated. The amount of midazolam given was documented.

Results

There was no significant difference in oral fluid intake by group when adjusting for age and weight, F(1, 282)=.383, p=0.537. Also, there was no significant difference in ml/kg/hr by group when adjusting for age and weight, F(1, 282)=2.813, p=0.095.

Conclusions

There was no significant difference in oral fluid intake between the no midazolam and midazolam groups, indicating that clinicians can continue to use their judgement in administering midazolam to select anxious patients prior to tonsillectomy with or without adenoidectomy. Future work could include multi-center retrospective reviews or a randomized placebo-controlled trial to examine more carefully the effects of midazolam on postoperative oral fluid intake.

https://ift.tt/2vzhvhg

Predictive Factors Associated With Spontaenous Passage Of Coins: A Ten-Year Analysis Of Paediatric Coin Ingestion In Australia

Publication date: Available online 10 August 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Dr Narinder Singh, Dr Jessica Chong, Dr Joyce Ho, Dr Shruti Jayachandra, Dr Daron Cope, Dr Fred Azimi, Guy D. Eslick, Dr Eugene Wong

Abstract

Objectives

Coins are the commonest foreign body ingested in paediatric populations. Although most ingested coins are either spontaneously passed or retrieved with medical intervention without serious consequence, there is potential for serious morbidity and mortality related to paediatric coin ingestion. We performed a 10-year retrospective review of Australian denomination coin ingestion at a tertiary paediatric hospital in Sydney, Australia. We attempted to determine whether a relationship exists between coin size, patient age, coin ingestion and spontaneous passage.

Methods

Hospital records of all children presenting in a 10-year period to a paediatric tertiary care centre for coin ingestion were reviewed. Demographic information, coin denomination, previous history, symptoms, investigations, management, outcome and complications were recorded.

Results

241 cases were identified. The majority (55%) of cases occurred in children ≤3 years of age (range 7 months to 11 years, mean 3.39 years). The most common location where coins were identified was in the proximal third of the oesophagus or at the cricopharyngeus (65%). Spontaneous passage occurred in 84 cases (34.9%) while 167 cases (69.3%) required intervention. Children ≤3 years were more likely to ingest small coins (<22 mm) (OR: 2.44; 1.39-4.17) and children >3 years were more likely to ingest larger coins (22-26 mm) (OR: 2.17; 1.39-4.35).

Conclusions

Coin size, coin weight and age of the child appear to be predictors for both likelihood of ingestion and spontaneous passage in paediatric coin ingestion cases. A child with minimal symptoms, witnessed ingestion and radiographic identification of the coin in the lower oesophagus or more distal can often be safety observed for up to 24 h in anticipation of spontaneous passage.

https://ift.tt/2MEhten

Extramedullary Hematopoiesis of the Sphenoid Sinus Associated with Hereditary Spherocytosis: A Case Report

Publication date: Available online 10 August 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Jaron Densky, Tirth Patel, Ashleigh Halderman, Prashant Malhotra

Abstract

Extramedullary hematopoiesis is a rare cause of a sinonasal mass that presents unique diagnostic and treatment challenges. While there are numerous reports of patients with hereditary spherocytosis developing extramedullary hematopoiesis in the posterior mediastinum, involvement in the paranasal sinuses has not previously been described. Here, we present the first case of a patient with hereditary spherocytosis developing extramedullary hematopoiesis in the sphenoid sinus.

https://ift.tt/2MgGvna

Editorial Board

Publication date: September 2018

Source: Clinical Immunology, Volume 194

Author(s):

https://ift.tt/2MBXLQC

Geographic and demographic variations of inhalant allergen sensitization in Koreans and non-Koreans

Publication date: Available online 10 August 2018

Source: Allergology International

Author(s): Sang Chul Park, Chi Sang Hwang, Hyo Jin Chung, Munkhbaatar Purev, Salma Saud Al Sharhan, Hyung-Ju Cho, Joo-Heon Yoon, Chang-Hoon Kim

Abstract

Background

To diagnose and treat respiratory allergic diseases, it is important to identify the specific allergens involved. Many differences exist between common inhalant allergens depending on the residential environment and demographic factors. This study aimed to compare common inhalant allergens between Koreans and non-Koreans according to their residential region, age, and sex.

Methods

This study evaluated 15,334 individuals who underwent serum tests for multiple allergen-specific immunoglobulin E at a tertiary academic medical center between January 2010 and December 2016. The individuals included 14,786 Koreans and 548 non-Koreans. The AdvanSure™ Allostation assay (LG Life Science, Korea) was used to test for 33 inhalant allergens.

Results

The house dust mite (HDM) was the most common allergen in both Koreans and non-Koreans, although the proportion of individuals with HDM sensitization was greater among Koreans. High sensitization rates for various pollen types were detected among Koreans in Gangwon region, whereas Japanese cedar pollen was unique among Koreans in Jeju region. Grass pollen and animal dander were relatively common among individuals from the Americas, whereas weed and grass pollen accounted for the 10 most common allergens for individuals from Central Asia. The total sensitization rate, sensitization to HDM, and sensitization to animal dander peaked among adolescents and young adults, then subsequently decreased with age.

Conclusions

This large-scale study demonstrates that various regional and age-related differences exist in the allergen sensitization rates of Koreans and non-Koreans. These data could be useful for development of avoidance measures, immunotherapy for causative allergens, and policymaking regarding allergic diseases.

https://ift.tt/2MAK0Si

Treatment of erythematotelangiectatic rosacea, facial erythema, and facial telangiectasia with a 577-nm pro-yellow laser: a case series

Abstract

Various lasers have been used for the treatment of erythematotelangiectatic rosacea (ETR), facial erythema (FE), and facial telangiectasias (FT). The assessment of the treatments of all of these conditions with a 577-nm pro-yellow laser has not been reported yet. The aim of this work was to assess the efficacy and safety of the 577-nm pro-yellow laser in ETR, FE, and FT. Forty patients suffering from ETR, FE, and FT (25 female and 15 male) were enrolled in this study. All of the patients were treated with 577-nm pro-yellow laser (QuadroStarPRO YELLOW® Asclepion Laser Technologies, Germany) at 4-week intervals, for one to four sessions. The assessment of the treatment was made based on the digital photographs and the percentage of fading of the erythema and telangiectasias in the lesions. Significant clinical improvement (80–100%) was observed in the first or second sessions of the treatment in FE and ETR patients and in second and fourth sessions of the treatment in FT patients. The treatment was very well tolerated. No side effect was observed except for a few patients who had mild to moderate erythema fading away in 12–24 h. This case series has shown that the pro-yellow laser is a very effective, safe, and well-tolerated treatment for ETR, FE, and FT.

https://ift.tt/2vW3olG

Molecular and cellular pathogenesis of heparin-induced thrombocytopenia (HIT)

Publication date: Available online 10 August 2018

Source: Autoimmunity Reviews

Author(s): Lubica Raouva, Gowthamy Arepally, Mortimer Poncz, Douglas B. Cines

https://ift.tt/2M8rILW

Rheumatic immune-related adverse events in patients on anti-PD-1 inhibitors: Fasciitis with myositis syndrome as a new complication of immunotherapy

Publication date: Available online 10 August 2018

Source: Autoimmunity Reviews

Author(s): Javier Narváez, Pablo Juarez López, Judit LLuch, José Antonio Narváez, Ramón Palmero, Xavier García del Muro, Joan Miquel Nolla, Eva Domingo-Domenech

Abstract

Objective

To evaluate the prevalence and type of rheumatic immune-related adverse events (IRAEs) in patients receiving programmed cell death protein-1 (PD-1) inhibitors.

Methods

This is a single-center prospective observational study, including all cancer patients receiving PD-1 inhibitors between January 2016 and January 2018.

Results

During the period analyzed, we evaluated a total of 11 patients. No patient had pre-existing rheumatic or autoimmune disease. In this period, a total of 220 patients were treated with PD1 inhibitors in our center; therefore, the estimated minimum prevalence of rheumatic IRAEs related to these therapies in our population was 5%.

The rheumatic IRAEs evaluated included 5 cases of oligo- or polyarthritis, 1 with a polymialgia rheumatica-type syndrome, 2 cases of immunotherapy-induced sicca syndrome, 2 patients who presented symptomatic inflammatory myositis with fasciitis in lower extremities, and 1 patient with a paraneoplastic acral vascular syndrome. The median time to IRAE after anti-PD1 exposure was 8 weeks (range: 2–24). In 5 patients, immunotherapy was discontinued (due to the adverse effect in three and cancer progression in two).

In general terms the symptoms resolved completely with symptomatic treatment. Disease-modifying antirheumatic drugs were needed for 2 patients.

Conclusion

Rheumatic IRAEs should be kept in mind during the follow-up and evaluation of patients treated with PD-1 inhibitors. The concomitant development of symptomatic inflammatory myositis with fasciitis in lower extremities appears to be a new adverse effect of anti-PD-1 immunotherapy. Additional studies are needed to determine how to adequately control and manage these complications.

https://ift.tt/2OlWQ7a

Clinical and immunological parameters of Sjögren's syndrome

Publication date: Available online 10 August 2018

Source: Autoimmunity Reviews

Author(s): Konstantia Psianou, Ioannis Panagoulias, Anastasios D. Papanastasiou, Anne-Lise de Lastic, Maria Rodi, Panagiota I. Spantidea, Søren E. Degn, Panagiotis Georgiou, Athanasia Mouzaki

Abstract

Sjögren's syndrome (SS) is a chronic autoimmune disease that primarily affects the exocrine glands, resulting in their functional impairment. In SS, lymphocytic infiltration of salivary and lacrimal glands, and deposition of several types of autoantibodies, mainly anti-SS-A (anti-Ro) and anti-SS-B (anti-La), lead to chronic inflammation, with xerostomia and keratoconjunctivitis sicca. In its primary form (pSS), SS does not involve additional connective tissue diseases, whereas in its secondary and more common form (sSS), SS presents in association with other rheumatic autoimmune diseases, mainly rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). As in most autoimmune diseases, environmental, hormonal and genetic factors are implicated in SS pathogenesis. In SS T cells predominate in mild lesions, whereas B cells predominate in advanced lesions. Th1, Th2, Th17, follicular helper T (Tfh) cells and regulatory cells (Tregs/Bregs), with their characteristic cytokine profiles, have been implicated in the pathogenesis of SS. It has been suggested that Th1 and Th17 cells initiate SS and, as the disease progresses, Th2 and Tfh cells predominate. It is assumed that, as in all autoimmune and inflammatory conditions, tolerance defects contribute to SS pathogenesis. It is intriguing that in SS it remains unclear which types of regulatory cells are functional and whether they ameliorate or worsen the disease. In this review we present a comprehensive update on SS with emphasis on immune system involvement, and suggest new insights into SS immunopathogenesis.

https://ift.tt/2M8rrbS

Letter to the Editor: New insights into the etiology of Hashimoto's Thyroiditis: the role of genetics and epigenetics

Publication date: Available online 10 August 2018

Source: Autoimmunity Reviews

Author(s): Massimo Ralli, Armando De Virgilio, Marco Artico, Lucia Longo, Marco de Vincentiis, Antonio Greco

https://ift.tt/2KJHh73

Molecular and cellular pathogenesis of heparin-induced thrombocytopenia (HIT)

Publication date: Available online 10 August 2018

Source: Autoimmunity Reviews

Author(s): Lubica Raouva, Gowthamy Arepally, Mortimer Poncz, Douglas B. Cines

https://ift.tt/2M8rILW

Rheumatic immune-related adverse events in patients on anti-PD-1 inhibitors: Fasciitis with myositis syndrome as a new complication of immunotherapy

Publication date: Available online 10 August 2018

Source: Autoimmunity Reviews

Author(s): Javier Narváez, Pablo Juarez López, Judit LLuch, José Antonio Narváez, Ramón Palmero, Xavier García del Muro, Joan Miquel Nolla, Eva Domingo-Domenech

Abstract

Objective

To evaluate the prevalence and type of rheumatic immune-related adverse events (IRAEs) in patients receiving programmed cell death protein-1 (PD-1) inhibitors.

Methods

This is a single-center prospective observational study, including all cancer patients receiving PD-1 inhibitors between January 2016 and January 2018.

Results

During the period analyzed, we evaluated a total of 11 patients. No patient had pre-existing rheumatic or autoimmune disease. In this period, a total of 220 patients were treated with PD1 inhibitors in our center; therefore, the estimated minimum prevalence of rheumatic IRAEs related to these therapies in our population was 5%.

The rheumatic IRAEs evaluated included 5 cases of oligo- or polyarthritis, 1 with a polymialgia rheumatica-type syndrome, 2 cases of immunotherapy-induced sicca syndrome, 2 patients who presented symptomatic inflammatory myositis with fasciitis in lower extremities, and 1 patient with a paraneoplastic acral vascular syndrome. The median time to IRAE after anti-PD1 exposure was 8 weeks (range: 2–24). In 5 patients, immunotherapy was discontinued (due to the adverse effect in three and cancer progression in two).

In general terms the symptoms resolved completely with symptomatic treatment. Disease-modifying antirheumatic drugs were needed for 2 patients.

Conclusion

Rheumatic IRAEs should be kept in mind during the follow-up and evaluation of patients treated with PD-1 inhibitors. The concomitant development of symptomatic inflammatory myositis with fasciitis in lower extremities appears to be a new adverse effect of anti-PD-1 immunotherapy. Additional studies are needed to determine how to adequately control and manage these complications.

https://ift.tt/2OlWQ7a

Clinical and immunological parameters of Sjögren's syndrome

Publication date: Available online 10 August 2018

Source: Autoimmunity Reviews

Author(s): Konstantia Psianou, Ioannis Panagoulias, Anastasios D. Papanastasiou, Anne-Lise de Lastic, Maria Rodi, Panagiota I. Spantidea, Søren E. Degn, Panagiotis Georgiou, Athanasia Mouzaki

Abstract

Sjögren's syndrome (SS) is a chronic autoimmune disease that primarily affects the exocrine glands, resulting in their functional impairment. In SS, lymphocytic infiltration of salivary and lacrimal glands, and deposition of several types of autoantibodies, mainly anti-SS-A (anti-Ro) and anti-SS-B (anti-La), lead to chronic inflammation, with xerostomia and keratoconjunctivitis sicca. In its primary form (pSS), SS does not involve additional connective tissue diseases, whereas in its secondary and more common form (sSS), SS presents in association with other rheumatic autoimmune diseases, mainly rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). As in most autoimmune diseases, environmental, hormonal and genetic factors are implicated in SS pathogenesis. In SS T cells predominate in mild lesions, whereas B cells predominate in advanced lesions. Th1, Th2, Th17, follicular helper T (Tfh) cells and regulatory cells (Tregs/Bregs), with their characteristic cytokine profiles, have been implicated in the pathogenesis of SS. It has been suggested that Th1 and Th17 cells initiate SS and, as the disease progresses, Th2 and Tfh cells predominate. It is assumed that, as in all autoimmune and inflammatory conditions, tolerance defects contribute to SS pathogenesis. It is intriguing that in SS it remains unclear which types of regulatory cells are functional and whether they ameliorate or worsen the disease. In this review we present a comprehensive update on SS with emphasis on immune system involvement, and suggest new insights into SS immunopathogenesis.

https://ift.tt/2M8rrbS

Letter to the Editor: New insights into the etiology of Hashimoto's Thyroiditis: the role of genetics and epigenetics

Publication date: Available online 10 August 2018

Source: Autoimmunity Reviews

Author(s): Massimo Ralli, Armando De Virgilio, Marco Artico, Lucia Longo, Marco de Vincentiis, Antonio Greco

https://ift.tt/2KJHh73

School Absenteeism Associated with Asthma and Allergic Diseases in Korean School-Aged Children

Pediatric Allergy, Immunology, and Pulmonology, Ahead of Print.


https://ift.tt/2Mc3Gj6

Immunogenicity of a Candidate Ebola Hemorrhagic Fever Vaccine in Mice Based on Controlled In Vitro Expression of Ebolavirus Glycoprotein

Viral Immunology, Ahead of Print.


https://ift.tt/2B7T0NA

Transgenerational Epigenetic Mechanisms in Adipose Tissue Development

Publication date: Available online 10 August 2018

Source: Trends in Endocrinology & Metabolism

Author(s): Simon Lecoutre, Paul Petrus, Mikael Rydén, Christophe Breton

An adverse nutritional environment during the perinatal period increases the risk of adult-onset metabolic diseases, such as obesity, which may persist across generations. Adipose tissue (AT) from offspring of malnourished dams has been shown to display altered adipogenesis, lipogenesis, and adipokine expression, impaired thermogenesis, and low-grade inflammation. Although the exact mechanisms underlying these alterations remain unclear, epigenetic processes are believed to have an important role. In this review, we focus on epigenetic mechanisms in AT that may account for transgenerational dysregulation of adipocyte formation and adipose function. Understanding the complex interactions between maternal diet and epigenetic regulation of the AT in offspring may be valuable in improving preventive strategies against the obesity pandemic.

https://ift.tt/2nrGRsU

Frontmatter

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 8
Pages: i-iv

https://ift.tt/2McFjRL

Resistance exercise alone improves muscle strength in growth hormone deficient males in the transition phase

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 8
Pages: 887-894

https://ift.tt/2Or61mO

Molecular genetics of tetrahydrobiopterin deficiency in Chinese patients

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 8
Pages: 911-916

https://ift.tt/2MfEuHF

Next-generation sequencing as a second-tier diagnostic test for newborn screening

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 8
Pages: 927-931

https://ift.tt/2MwsPRI

Refractory hypoglycemia in a pediatric patient with desmoplastic small round cell tumor

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 8
Pages: 947-950

https://ift.tt/2vzheen

Relationship Between Platelet Count and Insulin Resistance in Korean Adolescents: A Nationwide Population-Based Study

Metabolic Syndrome and Related Disorders, Ahead of Print.


https://ift.tt/2MczV0Z

Moisturizers vs. Barrier Repair in the Management of Atopic Dermatitis

Publication date: Available online 10 August 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Peter M. Elias, Jeffrey Sugarman

https://ift.tt/2nqIWVV

Novel combined method of biosorption and chemical precipitation for recovery of Pb 2+ from wastewater

Abstract

A novel combined biosorption-precipitation process has been designed and applied to recycle Pb²⁺ from low concentration lead containing wastewater. Pb²⁺ was firstly removed selectively from wastewater by pyromellitic dianhydride (PMDA) modified sugarcane bagasse (SB) fixed-bed column, and then, it was desorbed into the concentrated eluate and recycled by adding chemical precipitant. Adsorption performance of the column and optimum desorption and precipitation condition for Pb²⁺ were investigated in detail. Results showed that the as-prepared column could efficiently remove Pb²⁺ from aqueous solution and optimum condition for Pb²⁺ precipitation in eluate was at pH 3.0 and molar ratio of precipitant to Pb²⁺ of 5:1 by using Na₃PO₄ as precipitant. Recovery experiment illustrated that Pb²⁺ was selectively removed from wastewater containing ions of Pb²⁺, Zn²⁺, Cd²⁺, Ca²⁺, K⁺, and Na⁺ through competitive substitution adsorption on the modified SB, and mass ratio of the five metal ions in eluate was 96.8:0.7:0.7:0.7:0.5:0.5. Pb²⁺ in this concentrated and purified eluate solution was recycled efficiently by adding Na₃PO₄. The combined method had great potential in application of heavy metal recovery from wastewater.

https://ift.tt/2nqPl3t

Shadow over abdomen

Description  

Male neonate was born by normal vaginal delivery at 38 weeks. He was antenatally diagnosed to have dextrocardia, congenitally corrected transposition of great arteries, moderate ventricular septal defect and pulmonary atresia. He was born in good condition and cried at birth. However, he was noted to have saturation of 65%–70% in air and started on continuous positive airway pressure and transferred to neonatal intensive care unit for further monitoring. Postnatal echocardiography confirmed the diagnosis, and he was started on prostaglandin E1 (PGE1) at 5 nanogram/kg/min.

On day 3 of life, he underwent a cardiac gated CT angiography (CTA) for further understanding of anatomy and confirmation of diagnosis. In view of need for PGE1 until transfer to tertiary cardiac surgical centre, a peripherally inserted central venous catheter was inserted in the following 12 hours. He underwent an abdominal X-ray to check long line position (figure 1).

...

https://ift.tt/2vB3LT3

Unexpected cause for eyelid swelling and ptosis: rigid gas permeable contact lens migration following a 28-year-old trauma

A patient presented with left upper eyelid swelling and ptosis. The MRI reported a cyst with proteinaceous content. On surgical excision of the cyst, a rigid gas permeable (RGP) contact lens was found. The RGP lens was encapsulated within the upper eyelid soft tissue. It was later revealed that the patient experienced childhood trauma while wearing RGP contact lenses 28 years previously. The patient assumed that the RGP lens fell out and was lost; however, it can be inferred that the lens migrated into the eyelid and resided there asymptomatically for 28 years.

https://ift.tt/2AZ0ylp

Kikuchi-Fujimoto disease: a rare cause of cervical lymphadenopathy and fever

A 28-year-old Pakistani man with previously treated latent tuberculosis (TB) presented with a 3-month history of productive cough, fever, drenching night sweats, anorexia, sore throat and tender left cervical lymphadenopathy. Extensive biochemical and microbiological tests, and imaging studies were all inconclusive. Lymph node biopsy revealed the diagnosis of Kikuchi-Fujimoto disease (KFD). He had persistent fever and anorexia during admission despite supportive measures which resolved quickly on starting prednisolone. He remained well after being weaned off steroids on 18 weeks' follow-up. KFD is a rare, self-limiting disease which can mimic several serious conditions such as TB and lymphoma. Prompt diagnosis with lymph node biopsy is paramount in addressing diagnostic uncertainty and avoids starting potentially toxic treatment on these patients.

https://ift.tt/2vz73pR

Bitter experience with liquorice sweetening agent resulting in apparent mineralocorticoid excess with periodic paralysis

Chronic liquorice ingestion is a rare cause of secondary hypertension and hypokalaemia with periodic paralysis. We report the case of a middle-aged Indian man who presented with hypertension and hypokalaemic alkalosis with recurrent bouts of periodic paralysis. Biochemical investigations revealed suppressed plasma renin and aldosterone concentrations with normal cortisol concentration. A detailed history revealed that he was addicted for the last 5 years to a form of chewing tobacco mixed with herbal preparations as a sweetening agent which on analysis revealed active principles of glycyrrhizin using the thin liquid chromatography method. The hypokalaemia resolved and hypertension control improved significantly after discontinuing liquorice consumption, and the patient was asymptomatic at 1-year follow-up. Long-term liquorice ingestion should be kept in mind as a reversible cause of hypokalaemic periodic paralysis, with a meticulous history and biochemical evaluation helping in identifying this recognisable and curable medical disorder.

https://ift.tt/2AWPPYE

Johanson-Blizzard syndrome with associated urogenital anomalies

We present a case of a child with pancreatic insufficiency and facial defects typical of Johanson-Blizzard syndrome (JBS), along with the more facultative anomalies of the JBS, such as those of the urogenital system including persistent urogenital sinus, urethral duplication and dysplastic kidneys. Fetal ultrasound in a 21-year-old G1P1 woman revealed ambiguous genitalia. Examination at birth revealed a phallic structure with urethral meatus, non-palpable gonads, two orifices in close proximity in the perineum, with the anterior being a common urogenital channel and the posterior, the rectum. A voiding cystourethrogram/genitogram showed bilateral high-grade vesicoureteral reflux and a common urogenital sinus extending 1.5 cm before dividing into three channels: the native urethra, an accessory urethra directed anteriorly towards the clitoris and a septate vagina with uterus didelphys. JBS was suspected by clinical presentation and confirmed by UBR1 molecular testing (46,XX). At 16 months of age, she underwent feminising genitoplasty and posterior sagittal anorectoplasty.

https://ift.tt/2vwlOtw

Post-traumatic bony impingement into vagina: a rare cause of urethrovaginal fistula

A 22-year-old woman met with road traffic accident 6 months back following which she underwent exploratory laparotomy with intraperitoneal bladder rupture repair. She presented with urethrovaginal fistula due to a fragment of fractured pubic bone impinging into the anterior vaginal wall. The findings were confirmed on CT scan and cystoscopy. The patient was managed with removal of the bony spicule and transvaginal repair of urethrovaginal fistula with Martius fat pad interposition.

https://ift.tt/2AZ0qlV

Mediastinal lipoblastoma: a rare entity discovered on physical exam

Description 

A 3-year-old male with no significant medical or surgical history presents to his paediatrician for annual examination. On auscultation, he was noted to have diminished left-sided breath sounds and heart sounds displaced to the right. The patient had no complaints of pain, difficulty swallowing, shortness of breath or dyspnoea on exertion. An initial chest X-ray was performed which demonstrated complete opacification of the left hemithorax with mediastinal shift towards the right. This was followed by a radiation dose reduced CT of the chest with intravenous contrast, which demonstrated a 7.8x7.4x13.3 cm fat density mass filling the majority of the left lung and extending to the pleura and mediastinum (figure 1A). The patient was optimised for the operating room and underwent a left lateral thoracotomy. Intraoperatively, the mass was identified and noted to have fusion to the pericardium and pleura in its superior margin with all other...

https://ift.tt/2vz5okb

Cross-leg free flap for limb salvage in the setting of radiation

Limb salvage in an irradiated patient with limited recipient vessels leaves few options for reconstruction. Cross-leg free flaps have been used to reconstruct defects that would otherwise lead to amputation in patients with no ipsilateral recipient vessels. We present the first documented case of a cross-leg free flap for limb salvage in a radiated bed after infection and tumour resection.

https://ift.tt/2AZ0m5F

Allergen-specific sublingual immunotherapy is dose- and duration-dependent in a murine allergic rhinitis model

Publication date: Available online 10 August 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Soichi Tofukuji, Kazufumi Katayama, Yoshiyuki Nakano, Satoru Ishida, Junji Tsuchida, Minako Tajiri, Yusuke Shimo, Hidekazu Tanaka, Michitaka Shichijo

https://ift.tt/2KI25vG

Immunoglobulin D-Activated Mast Cells Induce IgE Synthesis in B Cells in Nasal Polyps

Publication date: Available online 10 August 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Guan-Ting Zhai, Hai Wang, Jing-Xian Li, Ping-Ping Cao, Wen-Xiu Jiang, Jia Song, Yin Yao, Zhi-Chao Wang, Zhe-Zheng Wang, Meng-Chen Wang, Bo Liao, Qi-Miao Feng, Xiang Lu, Heng Wang, Peisong Gao, Zheng Liu

Abstract

Background

Although up-regulated expression of local IgD has been reported in chronic rhinosinusitis (CRS), its function is unclear.

Objective

To explore the expression and function of soluble IgD in CRS, particularly CRS with nasal polyps (CRSwNP).

Methods

IgD levels in sinonasal mucosa were analyzed by RT-PCR and ELISA. The numbers and phenotypes of IgD⁺ cells were studied by immunohistochemistry, immunofluorescence, and flow cytometry. HMC-1 cells, a human mast cell line, and mast cells purified from eosinophilic polyps were culture alone or with naïve B cells purified from peripheral bloods. The antigen specificity of nasal IgD was investigated by ELISA.

Results

The mRNA expression of immunoglobulin heavy constant delta gene, the numbers of IgD⁺ cells, and the protein levels of secretory IgD in sinonasal mucosa were increased in CRS patients with or without nasal polyps compared to controls. The numbers of IgD⁺ plasmablasts were increased in both eosinophilic and non-eosinophilic polyps, whereas the numbers of IgD⁺ mast cells were only increased in eosinophilic polyps. Crosslinking IgD induced serum pre-incubated HMC-1 cells and polyp mast cells to produce B-cell activating factor, IL-21, IL-4 and IL-13, and to promote IgM, IgG, IgA, and IgE production from B cells. In eosinophilic polyps, the expression of those B cell-stimulating factors in mast cells and close contacts between mast cells and B cells were found. Moreover, positive correlations of total IgD with total IgE and eosinophilia, and up-regulation of specific IgD against house dust mites were discovered in eosinophilic polyps.

Conclusion

IgD-activated mast cells may facilitate IgE production and eosinophilic inflammation in CRSwNP.

https://ift.tt/2M9z1Dc

Low-level ozone has both respiratory & systemic effects in African-American adolescents with asthma despite asthma controller therapy

Publication date: Available online 10 August 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Michelle L. Hernandez, Radhika Dhingra, Allison J. Burbank, Krista Todorich, Ceila E. Loughlin, Marcia Frye, Kelly Duncan, Carole Robinette, Katherine Mills, Robert B. Devlin, David B. Peden, David Diaz-Sanchez

https://ift.tt/2KH3sep

Mutations of deubiquitinase OTUD1 are associated with autoimmune disorders

Publication date: Available online 10 August 2018

Source: Journal of Autoimmunity

Author(s): Dan Lu, Jia Song, Yizhe Sun, Fang Qi, Liang Liu, Yan Jin, Michael A. McNutt, Yuxin Yin

Abstract

Dysregulation of innate immunity accompanied by excessive interferon production contributes to autoimmune disease. However, the mechanism by which the immune response is modulated in autoimmune disorders is largely unknown. Here we identified loss-of-function mutations of OTUD1 associated with multiple autoimmune diseases. Under inflammatory conditions, inducible OTUD1 acts as an immune checkpoint and blocks RIG-I-like receptors signaling. As a deubiquitinase, OTUD1 directly interacts with transcription factor IRF3 and removes the K63-linked poly-ubiquitin chains on IRF3 Lysine 98, which inhibits IRF3 nuclear translocation and transcriptional activity. In contrast, OTUD1 mutants impair its suppressive effects on IRF3 via attenuating the OTUD1 deubiquinase activity or its association with IRF3. Moreover, we found FOXO3 signaling is required for OTUD1 induction upon antigenic stimulation. Our data demonstrate that OTUD1 is involved in maintaining immune homeostasis and loss-of-function mutations of OTUD1 enhance the immune response and are associated with autoimmunity.

https://ift.tt/2AZJyf7

Appropriateness of chronic asthma management and medication adherence in patients visiting ambulatory clinic of Gondar University Hospital: a cross-sectional study

Although asthma cannot be cured, appropriate management can ensure adequate control of the disease, prevent disease progression and even reverse the illness, enabling people to enjoy good quality of life. Pred...

https://ift.tt/2KGUX2Z

First Report of Klein-Waardenburg Syndrome in Iran and a Novel Pathogenic Splice Site Variant in PAX3 Gene

Publication date: Available online 10 August 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Mohammad Saberi, Zahra Golchehre, Hamzeh Salmani, Arezou Karamzade, Seyed Ziaeddin Tabatabaie, Mohammad Keramatipour

Abstract

Objectives

Waardenburg Syndrome (WS) as a congenital auditory-pigmentary syndrome is a clinically and genetically heterogeneous disorder. Based upon clinical manifestations, it can be classified into four types. Loss of function mutations in PAX3 gene cause WS1 and WS3 (Klein-Waardenburg syndrome). While WS2 and WS4 have locus heterogeneity with multiple causative genes. Here we report a novel splice site variant in a pedigree with multiple affected members. Based on diagnostic criteria, three of them are associated with WS3. The remained patients classified as type 1.

Methods

PCR amplification and Sanger sequencing were performed for all exons and all exon-intron boundaries of PAX3 (NM_181459) gene of the proband. Then available symptomatic and asymptomatic members were screened for the detected variant. Interpretation and classification of the variant were done based on ACMG guidelines.

Results

We identified a novel heterozygous splice site variant (c.586+2T>C) in donor site of intron 4 of PAX3 gene in our proband. Moreover, this variant was co-segregated with the disease in other available five affected members. Also, the detected variant was not detected in any of the investigated asymptomatic members. This variant was classified as a pathogenic variant based on the current guidelines for variant interpretation.

Conclusions

This study shows significant intra-familial clinical heterogeneity and absence of phenotype-genotype correlation in a pedigree with Waardenburg Syndrome. However, severity of phenotypes and additional symptoms in the patients can be related to alternative splicing and different levels of PAX3 expression. Detailed evaluation of more cases can shed light on this and case-reports are valuable traffic sign in the road. This article is the first report of Waardenburg syndrome type 3 in Iran.

https://ift.tt/2AZx479

Organic contaminants in the effluent of Chinese wastewater treatment plants

Abstract

The effluents of wastewater treatment plants (WWTPs) are the important sources for pollutants. These pollutants may entry into surface water, groundwater, and soil by recharging and irrigation then pose risk to human beings. Using reports from the past 20 years (n = 58), we conducted this review of organic contaminants (OCs) in the effluent of Chinese WWTPs. All the studies were during 2005 to 2017 and more than two papers were conducted in every year. Nineteen provinces (20 cities) were covered and most of the studies were located in the eastern part of China, especially the most developed and highest density of population areas. Two hundred eighty-four OCs were contained. E antibiotics, endocrine-disrupting chemicals (EDCs), and pharmaceuticals were the most commonly studied groups of OCs, and ofloxacin, norfloxacin, and sulfamethoxazole were the three most commonly reported OCs. The highest concentration appeared for bisphenol A (BPA). The relative standard deviations (RSDs) of concentrations of the most commonly studied compounds were high. In the future, more studies should pay attention on national analysis and more pollutants.

https://ift.tt/2MbrLGX

Effect of amendments on contaminated soil of multiple heavy metals and accumulation of heavy metals in plants

Abstract

The contamination of soil with heavy metals is a severe problem due to adverse impact of heavy metals on environmental safety and human health. It is essential to remediate soil contaminated with heavy metals. This study has evaluated the effects of pine biochar, kaolin, and triple super phosphate (TSP) on multiple heavy metals (Ni, Zn, Cu, and Cd) in contaminated soil and accumulation of heavy metals in plants. The amendments can reduce availability of heavy metals in soil by increasing pH, adsorption, complexation, or co-precipitation. Different amendments have variable effects on accumulation of heavy metals in plants and in soil due to its diverse mechanism of stability. The results showed that application of triple super phosphate (TSP) has significant reduced soil Cd exchangeable (EXC) fraction from 58.59 to 21.30%. Bound to carbonates (CAR) fraction decreased from 9.84 to 5.11%, and bound to Fe-Mn oxides (OX) fraction increased from 29.61 to 69.86%. The triple super phosphate (TSP) has the ability to stabilize Cu and especially Cd. However, triple super phosphate (TSP) has enhanced ecological risk of Zn and Ni. Application of pine biochar has significantly enhanced soil pH. The kaolin has significantly reduced EXC fraction of Cd and increased OX fraction of Cu. The amendments and heavy metals have not caused significant effect on SPAD value of Buxus microphylla Siebold & Zucc (B. microphylla). The triple super phosphate (TSP) has significant decreased biomass of B. microphylla and bamboo-williow (Salix sp.) by 24.91 and 57.43%, respectively. Pine biochar and kaolin have increased the accumulation of Zn and Cd in plants. It is concluded that triple super phosphate (TSP) was effective in remediation of Cd and kaolin was effective in remediation of Cd and Cu. Pine biochar was effective in remediation of Cd, Cu, and Zn.

https://ift.tt/2OsHy0O

Short-term efficacy of high intensity group and individual education in patients with type 2 diabetes: a randomized single-center trial

Abstract

Purpose

The aim of this randomized study was to examine the efficacy of two high intensity educational programs: the conversation maps-based (CM™) education and the individual education (IE), compared to usual care (UC) in a cohort of type 2 diabetic (T2DM) patients.

Methods

Ninety T2DM outpatients (30 per group) were randomized and 79 finished the study and were analyzed. The CM™ and IE groups received four educational sessions at 0, 4, 8 and 12 weeks, while the UC group received two brief individual sessions at 0 and 12 weeks. We evaluated glycemic control (HbA1c), diabetes treatment, body mass index (BMI) and carried out a questionnaire survey at three time points (before intervention, at 12 and at 32 weeks) to assess patients' satisfaction, attitudes toward diabetes and dietary knowledge.

Results

All the three groups showed a significant and comparable reduction of both HbA1c and BMI. Diabetes therapy needed to be reinforced in a higher percentage of cases (39.3%) among UC patients compared to the IE (14.8%; p = 0.04) and the CM™ (8.3%; p = 0.01) groups. At 32 weeks Diabetes Treatment Satisfaction (DTSQ Q1 + Q4–8) significantly improved in the CM™ group (25.8 ± 4.5 vs. 22.4 ± 6.0; p < 0.01) and attitudes toward diabetes (ATT19) significantly improved in the IE group (58.0 ± 4.7 vs. 55.3 ± 5.1; p = 0.02).

Conclusions

Our trial provides preliminary data regarding the efficacy of structured group and individual education on achieving better glyco-metabolic control without drug therapy reinforcement and with positive effects on patients' attitude and treatment satisfaction.

https://ift.tt/2Oukij1

Follow up for Patients With Thyroid Cancer Planed for Radioiodine Scan or Treatment

Condition:   Thyroid Cancer
Intervention:   Radiation: radioiodine
Sponsor:   Taichung Veterans General Hospital
Recruiting

https://ift.tt/2MAkNaH

Assessment of the Effects of Concussion on Adolescent Rugby Union Players

Conditions:   Concussion, Mild;   Concussion, Intermediate;   Concussion, Severe
Intervention:  
Sponsor:   Sports Surgery Clinic, Santry, Dublin
Recruiting

https://ift.tt/2Miq4qe

Feasibility & Efficacy of Durvalumab+Tremelimumab+RT and Durvalumab+RT in Non-resect. Locally Advanced HPVnegativ HNSCC

Condition:   Squamous Cell Carcinoma of the Head and Neck
Interventions:   Drug: Durvalumab;   Drug: Tremelimumab;   Radiation: Radiotherapy
Sponsors:   Ulrich Keilholz;   Charite University, Berlin, Germany;   AstraZeneca
Not yet recruiting

https://ift.tt/2MAxHoV

Combination Study With Soluble LAG-3 Fusion Protein Eftilagimod Alpha (IMP321) and Pembrolizumab in Patients With Previously Untreated Unresectable or Metastatic NSCLC, or Recurrent PD-X Refractory NSCLC or With Recurrent or Metastatic HNSCC

Conditions:   NSCLC;   HNSCC
Interventions:   Drug: Eftilagimod alpha;   Drug: Pembrolizumab
Sponsors:   Immutep S.A.;   Merck Sharp & Dohme Corp.
Not yet recruiting

https://ift.tt/2MilKY0

Follow up for Patients With Thyroid Cancer Planed for Radioiodine Scan or Treatment

Condition:   Thyroid Cancer
Intervention:   Radiation: radioiodine
Sponsor:   Taichung Veterans General Hospital
Recruiting

https://ift.tt/2MAkNaH

Assessment of the Effects of Concussion on Adolescent Rugby Union Players

Conditions:   Concussion, Mild;   Concussion, Intermediate;   Concussion, Severe
Intervention:  
Sponsor:   Sports Surgery Clinic, Santry, Dublin
Recruiting

https://ift.tt/2Miq4qe

Feasibility & Efficacy of Durvalumab+Tremelimumab+RT and Durvalumab+RT in Non-resect. Locally Advanced HPVnegativ HNSCC

Condition:   Squamous Cell Carcinoma of the Head and Neck
Interventions:   Drug: Durvalumab;   Drug: Tremelimumab;   Radiation: Radiotherapy
Sponsors:   Ulrich Keilholz;   Charite University, Berlin, Germany;   AstraZeneca
Not yet recruiting

https://ift.tt/2MAxHoV

Combination Study With Soluble LAG-3 Fusion Protein Eftilagimod Alpha (IMP321) and Pembrolizumab in Patients With Previously Untreated Unresectable or Metastatic NSCLC, or Recurrent PD-X Refractory NSCLC or With Recurrent or Metastatic HNSCC

Conditions:   NSCLC;   HNSCC
Interventions:   Drug: Eftilagimod alpha;   Drug: Pembrolizumab
Sponsors:   Immutep S.A.;   Merck Sharp & Dohme Corp.
Not yet recruiting

https://ift.tt/2MilKY0

Complete lymph node dissection or observation in melanoma patients with multiple positive sentinel lymph nodes: A single‐center retrospective analysis

The Journal of Dermatology, EarlyView.


https://ift.tt/2MyOclm

Twice-daily red and blue light treatment for Candida albicans biofilm matrix development control

Abstract

Phototherapy has been proposed as a direct means of affecting local bacterial infections. However, the use of phototherapy to prevent fungal biofilm development has received comparatively less attention. This study aimed to determine the effects of red light treatment and blue light treatment, without a photosensitizer, on the development of Candida albicans biofilm. During the development of 48-h biofilms of C. albicans SN 425 (n = 10), the biofilms were exposed twice-daily to noncoherent blue and red light (LumaCare; 420 nm and 635 nm). The energy density applied was 72 J cm⁻² for blue light and 43.8 J cm², 87.6 J cm², and 175.5 J cm² for red light. Positive control (PC) and negative control (NC) groups were treated twice-daily for 1 min with 0.12% chlorhexidine (CHX) and 0.89% NaCl respectively. Biofilms were analyzed for colony forming units (CFU), dry-weight, and exopolysaccharides (EPS-soluble and EPS-insoluble). Data was analyzed by one-way ANOVA and Tukey post hoc test (α = 0.05). Dry-weight was lower than NC (p < 0.001) and approached PC levels with both red and blue light treatments. CFU were also lower in groups exposed to blue light and higher durations of red light (p < 0.05). EPS-soluble and EPS-insoluble measures were variably reduced by these light exposures. In conclusion, twice-daily exposure to both blue and red lights affect the biofilm development and physiology of polysaccharide production and are potential mechanisms for the control of C. albicans biofilm matrix development.

https://ift.tt/2MaWiVi

MECHANISMS IN ENDOCRINOLOGY: Rare defects in adrenal steroidogenesis

Congenital adrenal hyperplasia (CAH) is a group of genetic disorders of adrenal steroidogenesis that impair cortisol synthesis, with compensatory increases in ACTH leading to hyperplastic adrenals. The term 'CAH' is generally used to mean 'steroid 21-hydroxylase deficiency' (21OHD) as 21OHD accounts for about 95% of CAH in most populations; the incidences of the rare forms of CAH vary with ethnicity and geography. These forms of CAH are easily understood on the basis of the biochemistry of steroidogenesis. Defects in the steroidogenic acute regulatory protein, StAR, disrupt all steroidogenesis and are the second-most common form of CAH in Japan and Korea; very rare defects in the cholesterol side-chain cleavage enzyme, P450scc, are clinically indistinguishable from StAR defects. Defects in 3β-hydroxysteroid dehydrogenase, which also causes disordered sexual development, were once thought to be fairly common, but genetic analyses show that steroid measurements are generally unreliable for this disorder. Defects in 17-hydroxylase/17,20-lyase ablate synthesis of sex steroids and also cause mineralocorticoid hypertension; these are common in Brazil and in China. Isolated 17,20-lyase deficiency can be caused by rare mutations in at least three different proteins. P450 oxidoreductase (POR) is a co-factor used by 21-hydroxylase, 17-hydroxylase/17,20-lyase and aromatase; various POR defects, found in different populations, affect these enzymes differently. 11-Hydroxylase deficiency is the second-most common form of CAH in European populations but the retention of aldosterone synthesis distinguishes it from 21OHD. Aldosterone synthase deficiency is a rare salt-losing disorder. Mild, 'non-classic' defects in all of these factors have been described. Both the severe and non-classic disorders can be treated if recognized.

https://ift.tt/2MgoyVL

GENETICS IN ENDOCRINOLOGY: Genetic diagnosis of endocrine diseases by NGS: novel scenarios and unpredictable results and risks

The technological advancements in genetics produced a profound impact on the research and diagnostics of non-communicable diseases. The availability of next-generation sequencing (NGS) allowed the identification of novel candidate genes but also an in-depth modification of the understanding of the architecture of several endocrine diseases. Several different NGS approaches are available allowing the sequencing of several regions of interest or the whole exome or genome (WGS, WES or targeted NGS), with highly variable costs, potentials and limitations that should be clearly known before designing the experiment. Here, we illustrate the NGS scenario, describe the advantages and limitations of the different protocols and review some of the NGS results obtained in different endocrine conditions. We finally give insights on the terminology and requirements for the implementation of NGS in research and diagnostic labs.

https://ift.tt/2MzDcnV

MECHANISMS IN ENDOCRINOLOGY: Hormonal regulation of spermatogenesis: mutant mice challenging old paradigms

The two pituitary gonadotrophins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and in particular LH-stimulated high intratesticular testosterone (ITT) concentration, are considered crucial for spermatogenesis. We have revisited these concepts in genetically modified mice, one being the LH receptor (R)-knockout mouse (LuRKO), the other a transgenic mouse expressing in Sertoli cells a highly constitutively active mutated Fshr (Fshr-CAM). It was found that full spermatogenesis was induced by exogenous testosterone treatment in LuRKO mice at doses that restored ITT concentration to a level corresponding to the normal circulating testosterone level in WT mice, 5 nmol/L, which is 1.4% of the normal high ITT concentration. When hypogonadal LuRKO and Fshr-CAM mice were crossed, the double-mutant mice with strong FSH signaling, but minimal testosterone production, showed near-normal spermatogenesis, even when their residual androgen action was blocked with the strong antiandrogen flutamide. In conclusion, our findings challenge two dogmas of the hormonal regulation of male fertility: (1) high ITT concentration is not necessary for spermatogenesis and (2) strong FSH stimulation can maintain spermatogenesis without testosterone. These findings have clinical relevance for the development of hormonal male contraception and for the treatment of idiopathic oligozoospermia.

https://ift.tt/2MfpQ3o

Diagnosis and follow-up of type 2 diabetes in women with PCOS: a role for OGTT?

Polycystic ovary syndrome (PCOS) is common in premenopausal women. The majority of women with PCOS have insulin resistance and the risk of type 2 diabetes mellitus (T2D) is higher in women with PCOS compared to controls. In non-pregnant women with PCOS, glycemic status may be assessed by oral glucose tolerance test (OGTT), fasting plasma glucose (FPG) or HbA1c. OGTT has been reckoned gold standard test for diagnosing T2D, but OGTT is rarely used for diagnostic purpose in other non-pregnant individuals at risk of T2D, apart from PCOS. OGTT has questionable reproducibility, and high sensitivity of the 2-h glucose value is at the expense of relatively low specificity, especially regarding impaired glucose tolerance (IGT). Furthermore, lean women with PCOS are rarely diagnosed with T2D and only few percent of normal-weight women have prediabetes. Glycemic status is necessary at diagnosis and during follow-up of PCOS, especially in women with high risk of T2D (obesity, previous gestational diabetes (GDM)). We suggest that OGTT should be used in the same situations in PCOS as in other patient groups at risk of T2D. OGTT is indicated for diagnosing GDM; however, OGTT during pregnancy may not be indicated in lean women with PCOS without other risk factors for GDM.

https://ift.tt/2KHrsxO

Should 45,X/46,XY boys with no or mild anomaly of external genitalia be investigated and followed up?

Objective

Few studies of patients with a 45,X/46,XY mosaicism have considered those with normal male phenotype. The purpose of this study was to evaluate the clinical outcome of 45,X/46,XY boys born with normal or minor abnormalities of external genitalia, notably in terms of growth and pubertal development.

Methods

Retrospective longitudinal study of 40 patients followed between 1982 and 2017 in France.

Results

Twenty patients had a prenatal diagnosis, whereas 20 patients had a postnatal diagnosis, mainly for short stature. Most patients had stunted growth, with abnormal growth spurt during puberty and a mean adult height of 158 ± 7.6 cm, i.e. –2.3 DS with correction for target height. Seventy percent of patients presented Turner-like syndrome features including cardiac (6/23 patients investigated) and renal malformations (3/19 patients investigated). Twenty-two patients had minor abnormalities of external genitalia. One patient developed a testicular embryonic carcinoma, suggesting evidence of partial gonadal dysgenesis. Moreover, puberty occurred spontaneously in 93% of patients but 71% (n = 5) of those evaluated at the end of puberty presented signs of declined Sertoli cell function (low inhibin B levels and increased FSH levels).

Conclusion

This study emphasizes the need to identify and follow-up 45,X/46,XY patients born with normal male phenotype until adulthood, as they present similar prognosis than those born with severe genital anomalies. Currently, most patients are diagnosed in adulthood with azoospermia, consistent with our observations of decreased testicular function at the end of puberty. Early management of these patients may lead to fertility preservation strategies.

https://ift.tt/2OWDMxF

MRI texture analysis as a predictor of tumor recurrence or progression in patients with clinically non-functioning pituitary adenomas

Background

There are limited predictors of prognosis in patients with clinically non-functioning pituitary adenomas (NFPAs). We hypothesized that MRI texture analysis may predict tumor recurrence or progression in patients with NFPAs undergoing transsphenoidal pituitary surgery (TSS).

Objective

To characterize texture parameters on preoperative MRI examinations in patients with NFPAs in relation to prognosis.

Methods

Retrospective study of patients with NFPAs who underwent TSS at our institution between 2009 and 2010. Clinical, radiological and histopathological data were extracted from electronic medical records. MRI texture analysis was performed on coronal T1-weighted non-enhanced MR images using ImageJ (NIH). MRI texture parameters were used to predict tumor recurrence or progression. Both logistic regression and Cox proportional hazard analyses were conducted to adjust for potential confounders.

Results

Data on 78 patients were analyzed. On both crude and multivariable-adjusted analyses, mean, median, mode, minimum and maximum pixel intensity were associated with the risk of pituitary tumor recurrence or progression after TSS. Patients whose tumor mean pixel intensity was above the median for the population had a hazard ratio of 0.44 (95% CI: 0.21–0.94, P = 0.034) for recurrence or progression in comparison with tumors below the median.

Conclusions

Our data suggest that MRI texture analysis can predict the risk of tumor recurrence or progression in patients with NFPAs.

https://ift.tt/2KELBo9

Gender disparities in screening for congenital hypothyroidism using thyroxine as a primary screen

Objective

Newborn screening for congenital hypothyroidism (CH) is based on testing for the markers thyroxine (T4) and/or thyroid-stimulating hormone (TSH). Diagnosis of CH is complicated because many factors affect the levels of these hormones including infant birth weight, prematurity and age at specimen collection. We investigated whether the sex of the newborn affected the levels of T4 and TSH and consequently the outcome of newborn screening.

Design

In New York State, the Newborn Screening program initially tests all infants for T4 and any baby with a result in the lowest 10% is triaged for TSH screening. We analyzed data from 2008 to 2016 to determine mean and median T4 and TSH values and how these results correlate with the sex of infants who are reported as borderline, referred and confirmed with CH.

Methods

T4 and TSH concentrations in dried blood spots were measured using commercially available fluoroimmunoassays.

Results

From 2008 to 2016, of the 2.4 million specimens tested for thyroxine, 51.5% were from male and 48.5% were from female infants. Male infants constituted 60% of specimens triaged for TSH testing, 64.9% of repeat requests and 59.6% of referrals, but only 49% of confirmed CH cases. The mean and median T4 values were lower (a difference of approximately 0.8–1.1 μg/dL each year) and the median TSH values were higher in male compared to female infants.

Conclusions

Natural differences in thyroid hormone levels in male and female infants leads to male infants being disproportionately represented in the false-positive category.

https://ift.tt/2MiaYky

Long-acting FC-fusion rhGH (GX-H9) shows potential for up to twice-monthly administration in GH-deficient adults

Objective

Hybrid Fc-fused rhGH (GX-H9) is a long-acting recombinant human growth hormone (GH) under clinical development for both adults and children with GH deficiency (GHD). We compared the safety, pharmacokinetics and pharmacodynamics of weekly and every other week (EOW) dosages of GX-H9 with those of daily GH administration in adult GHD (AGHD) patients.

Design

This was a randomized, open-label, active-controlled and dose-escalation study conducted in 16 endocrinology centers in Europe and Korea.

Methods

Forty-five AGHD patients with or without prior GH treatment were enrolled. Patients with prior GH treatments were required to have received the last GH administration at least 1 month prior to randomization. Subjects were sequentially assigned to treatment groups. Fifteen subjects were enrolled to each treatment group and randomly assigned to receive either GX-H9 or Genotropin (4:1 ratio). GX-H9 dosage regimens for Groups 1, 2 and 3 were 0.1 mg/kg weekly, 0.3 mg/kg EOW and 0.2 mg/kg EOW, respectively. All Genotropin-assigned subjects received 6 µg/kg Genotropin, regardless of treatment group. Main outcome analyses included measurements of serum insulin-like growth factor 1 (IGF-I), safety, pharmacokinetics, pharmacodynamics and immunogenicity.

Results

Mean GX-H9 peak and total exposure increased with an increase in dose after a single-dose administration. The mean IGF-I response was sustained above baseline over the intended dose interval of 168 h for the weekly and 336 h for the EOW GX-H9 groups. Safety profiles and immunogenicity were not different across the treatment groups and with Genotropin.

Conclusions

GX-H9 has the potential for up to twice-monthly administration.

https://ift.tt/2MAjbNS

Possible delayed diagnosis and treatment of metastatic differentiated thyroid cancer by adopting the 2015 ATA guidelines

Objective

According to the 2015 American Thyroid Association (ATA) guidelines, thyroid ablation by iodine-131 (I-131) therapy is absolutely recommended only in patients with high-risk differentiated thyroid cancer (DTC). Often distant metastases are not recognized early and they can stay silent for long time. The aim of our study was to retrospectively analyze the prevalence of metastatic disease before and after I-131 and to evaluate the influence of the new ATA guidelines in the management of DTC.

Methods

We retrospectively analyzed 140 patients showing distant metastases. All metastases were detected by whole-body scan after I-131 and confirmed by histology and/or other imaging modalities.

Results

In 26/140 patients metastases were detected before I-131, while in 114/140 were discovered after I-131. Comparing patients with metastases detected before and after I-131, no differences were demonstrated considering age, sex, histotype, tumor size, multifocality of cancer and metastatic localization. Metastatic DTC discovered before radioiodine had higher thyroglobulin and received a higher radioiodine total activity and number of treatments. Considering patients with distant metastases, according to the 2015 ATA guidelines, 38 patients would have been categorized as high risk, 22 as low risk and 80 as intermediate risk. Among intermediate-risk patients, only in 25 cases (31%) I-131 treatment would have been appropriate according to 2015 ATA recommendations; in the remaining 56 cases (69%), I-131 would not have been recommended.

Conclusions

According to the 2015 ATA guidelines, most of metastatic patients would not have been treated after surgery, with the risk of late diagnosis and delayed treatment.

https://ift.tt/2P01Tf1

Do aggressive variants of papillary thyroid carcinoma have worse clinical outcome than classic papillary thyroid carcinoma?

Objective

Evidence for unfavorable outcomes of each type of aggressive variant papillary thyroid carcinoma (AV-PTC) is not clear because most previous studies are focused on tall cell variant (TCV) and did not control for other major confounding factors contributing to clinical outcomes.

Design

Retrospective cohort study.

Methods

This study included 763 patients with classical PTC (cPTC) and 144 with AV-PTC, including TCV, columnar cell variant (CCV) and hobnail variants. Disease-free survival (DFS) and dynamic risk stratification (DRS) were compared after two-to-one propensity score matching by age, sex, tumor size, lymph node metastasis and extrathyroidal extension.

Results

The AV-PTC group had significantly lower DFS rates than its matched cPTC group (HR = 2.16, 95% CI: 1.12–4.16, P = 0.018). When TCV and CCV were evaluated separately, there was no significant differences in DFS and DRS between patients with TCV (n = 121) and matched cPTC. However, CCV group (n = 18) had significantly poorer DFS than matched cPTC group (HR = 12.19, 95% CI: 2.11–70.33, P = 0.005). In DRS, there were significantly more patients with structural incomplete responses in CCV group compared by matched cPTC group (P = 0.047). CCV was an independent risk factor for structural persistent/recurrent disease in multivariate analysis (HR = 4.28; 95% CI: 1.66–11.00, P = 0.001).

Conclusions

When other clinicopathological factors were similar, patients with TCV did not exhibit unfavorable clinical outcome, whereas those with CCV had significantly poorer clinical outcome. Individualized therapeutic approach might be necessary for each type of AV-PTCs.

https://ift.tt/2KDpOgN

DNA methylation profiling in MEN1-related pancreatic neuroendocrine tumors reveals a potential epigenetic target for treatment

Objective

Epigenetic changes contribute to pancreatic neuroendocrine tumor (PanNET) development. Hypermethylation of promoter DNA as a cause of tumor suppressor gene silencing is a well-established oncogenic mechanism that is potentially reversible and therefore an interesting therapeutic target. Multiple endocrine neoplasia type 1 (MEN1) is the most frequent cause of inherited PanNETs. The aim of this study was to determine promoter methylation profiles in MEN1-related PanNETs.

Design and methods

Methylation-specific multiplex ligation-dependent probe amplification was used to assess promoter methylation of 56 tumor suppressor genes in MEN1-related (n = 61) and sporadic (n = 34) PanNETs. Differences in cumulative methylation index (CMI), individual methylation percentages and frequency of promoter hypermethylation between subgroups were analyzed.

Results

We found promoter methylation of a large number of potential tumor suppressor genes. CMI (median CMI: 912 vs 876, P = 0.207) was the same in MEN1-related and sporadic PanNETs. We found higher methylation percentages of CASP8 in MEN1-related PanNETs (median: 59% vs 16.5%, P = 0.002). In MEN1-related non-functioning PanNETs, the CMI was higher in larger PanNETs (>2 cm) (median: 969.5 vs 838.5; P = 0.021) and in PanNETs with liver metastases (median: 1036 vs 869; P = 0.013). Hypermethylation of MGMT2 was more frequent in non-functioning PanNETs compared to insulinomas (median: 44.7% vs 8.3%; P = 0.022). Hypermethylation of the Von Hippel–Lindau gene promoter was observed in one MEN1-related PanNET and was associated with loss of protein expression.

Conclusion

Promoter hypermethylation is a frequent event in MEN1-related and sporadic PanNETs. Targeting DNA methylation could be of therapeutic value in MEN1 patients with advanced PanNETs.

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