Perinatal antibiotic exposure alters composition of murine gut microbiota and may influence later responses to peanut antigen

Accumulating evidence suggests that the gut microbiota shapes developmental processes within the immune system. Early life antibiotic use is one factor which may contribute to immune dysfunction and the recent...

https://ift.tt/2DeWKwQ

Anaphylactic reaction in patient allergic to mango

An allergy to mango is extremely rare. The antigenic composition of the fruit is not fully known. Profilin from mango has a structure similar to birch tree profiling: it is responsible for cross-reactions betw...

https://ift.tt/2Jvgmgv

Alternative adsorbents applied to the removal of natural hormones from pig farming effluents and characterization of the biofertilizer

Abstract

Pig farming has a very strong economic importance in Brazil. The residues from this activity are applied to the soil because of their excellent characteristics as biofertilizers. The present study aimed at studying the estrone, 17β-estradiol, and estriol natural hormones, emerging contaminants present in this type of residue that are not mentioned in the current legislation. The characterization of the pig farming effluent presented high concentrations of hormones (mg L⁻¹). The objective was to apply the biosorbents to the removal of the hormones in batch systems directly in the manure heaps without affecting the potential of the effluent as a fertilizer. It was verified that the adsorption of hormones using the rice husk biomass in natura and soybean hull in natura, abundant alternative adsorbents, presented a good capacity of removal of hormones. The presence of the organic materials (rice husk and soybean hull) caused few alterations in the biofertilizer characteristics, demonstrating that these adsorbents present a potential of application in batch treatment systems, with possible applications related to pig farming effluents containing natural hormones.

https://ift.tt/2zfcKdM

Inequalities in healthcare access: how a man with exstrophy in rural India coped

We report a case of a 22-year-old man with adult exstrophy. The patient made a self-made urine collection device, which helped him to lead a normal life, carrying out his routine as well as occupational activities smoothly. This patient is a prime example of inequalities in healthcare distribution in low-income and middle-income countries. He was never taken to a proper medical centre to correct his condition nor was his mother ever given proper antenatal healthcare access. His background of being a poor person from rural India highlights the problems of inequalities in healthcare access.

https://ift.tt/2SyH5g9

Self-Reported Benefit and Satisfaction with a Beamforming Body-Worn Hearing Aid for Elderly Adults

Hearing impairment is a leading cause of disability globally and is particularly prevalent in elderly populations. Hearing aids are commonly recommended to mitigate the adverse effects on communication associated with hearing loss. However, the acceptability of hearing aids to elderly individuals is low and the majority of potential users do not wear hearing aids. Most hearing aids are designed with a discreet form factor in mind, to minimize device visibility. Given the range of comorbidities associated with hearing loss in the elderly, this conventional form factor may not always be optimal. The present study examined the experiences of elderly individuals with a recently developed, unconventional, body-worn hearing instrument, the EasyHear™ Grand (Logital Co. Ltd., Hong Kong). The bilaterally fitted instrument incorporates large controls, a color display, beamforming sound processing, and Bluetooth capabilities. Forty-three elderly participants (mean age=71; range 46-88 years) were surveyed to gauge level of benefit and satisfaction with the device and opinions regarding the hearing aid. They were assessed using three standardized questionnaires (the International Outcome Inventory-Hearing Aids, the Profile of Hearing Aid Benefit, and the Client Oriented Scale of Improvement) and through open-ended, structured interviews. Participants rated their EasyHear device fitting highly for hours of use and improved quality of life and rated the device favorably for improved communication and benefit in background noise. A majority of users felt the device improved listening ability in their expressed area of greatest need, and also for their second highest prioritized area of greatest need. Less than 10% of users felt their listening was only occasionally or hardly ever improved when using the body-worn device. Benefit and satisfaction ratings with the EasyHear Grand were comparable to those in studies involving conventional form factor devices. Interviews highlighted areas where users felt the device could be improved—extra noise reduction, changes to device dimensions, receiver/eartip fit, and cableless technology were among the areas mentioned. Many participants valued smartphone linkage and Bluetooth capability. The EasyHear Grand, with its body-worn design and large, simple controls, was well accepted by the majority of participants. Hearing aids that break from conventional design formats may benefit many elderly individuals with hearing impairment and promote increased user acceptability.

https://ift.tt/2Jtdi4l

Determination of effective half-life of 131 I in patients with differentiated thyroid carcinoma: comparison of cystatin C and creatinine-based estimation of renal function

Abstract

Purpose

Renal function and effective half-life (t_1/2,eff) of I-131 have not been fully elucidated in patients undergoing radioiodine therapy (RAIT) for differentiated thyroid cancer (DTC). Aim of the present analysis was to evaluate the potential of cystatin C-based estimated glomerular filtration rate (eGFR_CysC) in comparison to conventional creatinine (eGFR_Crea) and to verify which methods to determine t_1/2,eff are most accurate to predict t_1/2,eff.

Methods

Forty-eight patients receiving whole-body I-131-scintigraphy were included. eGFR_CysC was compared to eGFR_Crea with regard to accuracy of t_1/2,eff prediction. Three different methods (i.e. blood-based, gamma camera-based and probe-based) and two protocols with either three (short period,SP; up to 42 h) or four (long period,LP; up to 114 h) time points were compared using the Akaike's information criterion.

Results

The eGFR_CysC measurement is more likely than eGFR_Crea in predicting the t_1/2,eff. High correlation coefficients were found between t_1/2,eff assessed by gamma camera and probe measurements and blood-based determination revealed lower values. Patients with normal eGFR showed higher values of t_1/2,eff of LP compared to SP.

Conclusions

eGFR_CysC should be included in further study protocols. As camera and probe measurements lead to almost superimposable results, one of the methods is expendable. Blood-based results of t_1/2,eff were lower, presumably due to unspecific iodine retention, whereas the lower correlation with renal function may be caused by individual differences in intestinal iodine resorption. SP-protocols up to 42 h after I-131 administration are sufficient to determine t_1/2,eff. Further studies are necessary for specific recommendations regarding I-131 activity reduction during RAIT in patients with DTC and renal insufficiency.

https://ift.tt/2Qg7ePy

Clinical Indices to Drive Quality Improvement in Otolaryngology

A Pediatric Tracheostomy Care Index (PTCI) was developed by the authors to standardize care and drive quality improvement efforts at their institution. The PTCI comprises 9 elements deemed essential for safe care of children with a tracheostomy tube. Based on the PTCI scores, the number of missed opportunities per patient was tracked, and interventions through a "Plan-Do-Study-Act" approach were performed. The establishment of the PTCI has been successful at standardizing, quantifying, and monitoring the consistency and documentation of care provided at the authors' institution.

https://ift.tt/2OiSA8m

Patient Engagement in Otolaryngology

Patient engagement, which involves incorporating the patient and family as partners in their care, is a growing focus in otolaryngology and surgery. Attention to patient and family centeredness, shared decision making, and patient experience together improves the overall tenor of patient engagement. Patient engagement promotes safety through improving quality of electronic health record data, error detection, and treatment decisions and adherence. In this article, we review specific areas of importance for patient engagement in otolaryngology as well as areas needing more research and development.

https://ift.tt/2yLfwrN

Forthcoming Issues

Implantable Auditory Devices

https://ift.tt/2Okun1v

Copyright

Elsevier

https://ift.tt/2yLIvM0

CME Accreditation Page

https://ift.tt/2Of0csd

Contents

Sujana S. Chandrasekhar

https://ift.tt/2yGXRS4

Contributors

SUJANA S. CHANDRASEKHAR, MD, FACS, FAAOHNS

https://ift.tt/2Of05Nj

Patient Safety and Quality Improvement

OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA

https://ift.tt/2yHAuba

Regional Node Distribution in Papillary Thyroid Cancer with Microscopic Metastasis

Background. Optimal neck lymphadenectomy in patients with papillary thyroid cancer (PTC) and microscopic lymph node metastasis needs to be defined in order to aid surgeons in their decision about the best way to proceed in these cases. Methods. Patients who underwent total thyroidectomy and lymphadenectomy at levels IIa to VI were divided into two groups: Group 1 (G1) with macroscopic metastasis detected before surgery and Group 2 (G2) with microscopic metastasis detected in sentinel node during surgery. Odds ratio (OR) was computed for age, sex, tumor size, multicentricity, capsular invasion, vascular/lymphatic permeation, and nodes with metastasis. Results. Primary tumor size was (G1 versus G2, respectively) 3.8 cm versus 1.98 cm (P

https://ift.tt/2OfYOpj

Determination of effective half-life of 131 I in patients with differentiated thyroid carcinoma: comparison of cystatin C and creatinine-based estimation of renal function

Abstract

Purpose

Renal function and effective half-life (t_1/2,eff) of I-131 have not been fully elucidated in patients undergoing radioiodine therapy (RAIT) for differentiated thyroid cancer (DTC). Aim of the present analysis was to evaluate the potential of cystatin C-based estimated glomerular filtration rate (eGFR_CysC) in comparison to conventional creatinine (eGFR_Crea) and to verify which methods to determine t_1/2,eff are most accurate to predict t_1/2,eff.

Methods

Forty-eight patients receiving whole-body I-131-scintigraphy were included. eGFR_CysC was compared to eGFR_Crea with regard to accuracy of t_1/2,eff prediction. Three different methods (i.e. blood-based, gamma camera-based and probe-based) and two protocols with either three (short period,SP; up to 42 h) or four (long period,LP; up to 114 h) time points were compared using the Akaike's information criterion.

Results

The eGFR_CysC measurement is more likely than eGFR_Crea in predicting the t_1/2,eff. High correlation coefficients were found between t_1/2,eff assessed by gamma camera and probe measurements and blood-based determination revealed lower values. Patients with normal eGFR showed higher values of t_1/2,eff of LP compared to SP.

Conclusions

eGFR_CysC should be included in further study protocols. As camera and probe measurements lead to almost superimposable results, one of the methods is expendable. Blood-based results of t_1/2,eff were lower, presumably due to unspecific iodine retention, whereas the lower correlation with renal function may be caused by individual differences in intestinal iodine resorption. SP-protocols up to 42 h after I-131 administration are sufficient to determine t_1/2,eff. Further studies are necessary for specific recommendations regarding I-131 activity reduction during RAIT in patients with DTC and renal insufficiency.

https://ift.tt/2Qg7ePy

What can food-image tasks teach us about anorexia nervosa? A systematic review

Abstract

A salient feature of anorexia nervosa (AN) is the persistent and severe restriction of food, such that dietary intake is inadequate to maintain a healthy body weight. Experimental tasks and paradigms have used illness-relevant stimuli, namely food images, to study the eating-specific neurocognitive mechanisms that promote food avoidance. This systematic review, completed in accordance with PRISMA guidelines, identified and critically evaluated paradigms involving images of food that have been used to study AN. There were 50 eligible studies, published before March 10^th 2018, identified from Medline and PsychINFO searches, and reference screening. Studies using food image-based paradigms were categorised into three methodologic approaches: neuropsychology, neurophysiology, and functional magnetic resonance imaging (fMRI). Paradigms were reviewed with a focus on how well they address phenomena central to AN. Across tasks, differences between individuals with AN and healthy peers have been identified, with the most consistent findings in the area of reward processing. Measuring task performance alongside actual eating behaviour, and using experimental manipulations to probe causality, may advance understanding of the mechanisms of illness in AN.

https://ift.tt/2SB71Ys

Themes arising during implementation consultation with teams applying family-based treatment: a qualitative study

Abstract

Background

This study describes themes arising during implementation consultation with teams providing Family-Based Treatment (FBT) to adolescents with eating disorders.

Methods

Participants were implementation teams (one lead therapist, one medical practitioner and one administrator) at four sites. These teams agreed to support the implementation of FBT, and participated in monthly consultation calls which were audio-recorded, transcribed verbatim and coded for themes. Twenty percent of the transcripts were double-coded to ensure consistency. Fundamental qualitative description guided the sampling and data collection.

Results

Twenty-five (average per site = 6) transcripts were coded using thematic content analysis. Six major themes emerged: 1) system barriers and facilitators 2) the role of the medical practitioner, 3) research implementation, 4) appropriate cases, 5) communication, and 6) program impact.

Conclusions

Implementation themes aligned with previous research examining the adoption of FBT, and provide additional insight for clinical programs seeking to implement FBT, emphasizing the importance of role clarity, and team communication.

https://ift.tt/2zj4vNX

Doxercalciferol Alleviates Bone Deteriorations and Cartilage Degeneration in Aging Mice

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0754-1956

Background Age-related bone deteriorations are the common endocrine disorders in the elderly population, leading to an increased risk of fractures. Therefore, effective treatment strategies provide a way to prevent bone loss and improve the quality of life in the elderly population. The present study aimed to investigate the anti-osteoporotic effects of doxercalciferol (DOX) in aging mice. Methods Bone metabolism-related markers were measured by ELISA assay. The expression of bone formation and resorption-related genes was performed by RT-qPCR analysis. Hematoxylin and eosin (H&E) and Safranin O staining were performed to analyze the trabecular bone and cartilage degeneration. Results Aging resulted in urine Ca excretion, a decrease in bone Ca content and reduction of biomechanical strength in mice. We also found that the level of PTH was increased in aging mice, while DOX administration markedly down-regulated serum PTH in aging mice. H&E and Safranin O staining showed that DOX protected against aging-induced bone loss and cartilage regeneration in the tibia from aging mice. Furthermore, DOX treatment resulted in an increase in Runx2, osterix and Col1a1 mRNA expression and a decrease in Ctsk, MMP-9 and CAII mRNA expression in the tibia from aging mice. Conclusion These findings indicated that DOX had a beneficial effect on age-related bone deteriorations in aging mice by promoting osteoblast activity and cartilage regeneration and inhibiting osteoclast-specific genes expression.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2Q4YD1Q

Case 33-2018: A 57-Year-Old Man with Confusion, Fever, Malaise, and Weight Loss

Presentation of Case. Dr. Joshua A. Cohen (Medicine): A 57-year-old man presented to this hospital with confusion, cough, fever, and unintentional weight loss. The patient had been in his usual state of health until approximately 7 weeks before this presentation, when malaise and anorexia…

https://ift.tt/2qmn1kd

Broadening the operative field: the extent of surgery beyond the patient`s informed consent (the so-called therapeutic exception)

W artykule omówiono przesłanki tzw. wyjątku terapeutycznego, uregulowanego w art. 35 ustawy z dnia 5 grudnia 1996 r. o zawodach lekarza i lekarza dentysty. Konstrukcja ta pozwala lekarzowi, w trakcie operacji, na zmianę zakresu zabiegu ponad zgodę wyrażoną przez pacjenta. Ponadto poruszono kwestię tzw. zgody antycypacyjnej oraz warunki jej skuteczności oraz wyjaśniono, czy w wypadku realizacji przesłanek wyjątku terapeutycznego lekarz jedynie może dokonać odpowiedniej modyfikacji czynności operacyjnych, czy też jest to jego obowiązek. Wskazano również, że w omawianej sytuacji lekarz nie może powoływać się na tzw. stan wyższej konieczności. Prezentowane treści zostały wzbogacone o przedstawienie konkretnych spraw sądowych i ich rozstrzygnięć.

https://ift.tt/2qnoIOm

Inter-arm differences in blood pressure among subjects with disseminated atherosclerosis scheduled for vascular surgery

Background: The measurement of blood pressure (BP) is routinely performed in perioperative care. The reliability of results is essential for the implementation of treatment ensuring haemodynamic stability. The aim of the present study was to assess the prevalence and basic determinants of inter-arm BP differences among patients with advanced peripheral atherosclerosis undergoing vascular surgical procedures of the lower limbs. Methods: The prospective study was carried out in patients scheduled for elective lower limb vascular surgery. One-time non-invasive BP measurements were performed sequentially on the brachial arteries of both upper extremities before the induction of anaesthesia, maintaining the shortest possible interval between measurements. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were recorded. Results: The results of 173 patients (including 123 men aged 67 ± 8 years) were analysed. In 16 (9.3%) patients, an inter-arm difference in BP was already observed during the preoperative examination. SBP and DBP was higher in the right limb in 86 (49.7%) an 80 (46.3%) patients, respectively. Moreover, the medians of inter-arm differences in SBP, DBP and MAP were 9 (IQR 4–17), 5 (IQR 3–10) and 7 mm Hg (IQR 3–12), respectively. An evaluation of the determinants of BP differences related to the presence of additional diseases demonstrated that patients with arterial hypertension were characterised by higher SBP and MAP disproportions (P = 0.04 and P = 0.01). Conclusions: In the population of patients with disseminated atherosclerosis, the inter-arm differences in BP substantially exceed the measurement error limits and are likely to be associated with arterial hypertension. If in doubt about BP disproportions, intraoperative monitoring of BP should be recommended using an invasive method on the limb presenting higher non-invasively measured values.

https://ift.tt/2QaqQnU

Risk factors for occurrence of failed interscalene brachial plexus blocks for shoulder arthroscopy using 20 mL 0.5% ropivacaine: a randomised trial

Background: The red blood cell distribution width index (RDW) is one of several parameters routinely analysed in peripheral blood counts. The aim of the study was to assess the usefulness of RDW in the prediction of in-hospital mortality in patients undergoing high-risk gastroenterological surgery. Methods: Prospective observation covered 229 patients who underwent surgery, for whom the risk of cardiovascular complications was high due to the type of procedure. The patient's individual risk was assessed using the criteria of the American Society of Anesthesiologists (ASA-PS). Peripheral blood for morphological examination was collected preoperatively. The following parameters of the red blood cell system were evaluated: red blood cell count (RBC), haemoglobin (Hgb), haematocrit (Hct), mean corpuscular volume (MCV), RDW expressed as a standard deviation (SD) and a coefficient of variation (CV). The occurrence of hospital death was the main endpoint. Results: Patients who died had had statistically significantly lower RBC, Hgb and Hct values, as well as higher RDW-SD and RDW-CV values. Both the preoperative RDW-SD and RDW-CV values predicted the outcome, respectively: AUC_RDW-SD = 0.744 (95% CI: 0.683–0.799; P RDW-CV = 0.762 (95% CI: 0.702–0.816; P RDW-SD = 1.21; P RDW-CV = 1.62; P = 0.01), even after adjustment for individual risk and other erythrocyte parameters. Conclusion: RDW is a valuable screening predictor of in-hospital mortality in patients undergoing high-risk gastroenterological surgery, regardless of the estimated individual risk and the value of other erythrocyte parameters. Evaluation of the RDW may be helpful in the identification of patients requiring correction of haematological disorders in the pre-operative period, as well as, in particular, surveillance in the perioperative period.

https://ift.tt/2qnoB5o

Use of noninvasive mechanical ventilation with pressure support guaranteed with average volume in de novo hypoxaemic respiratory failure. A pilot study

Background: This study was designed to determine the results associated with the use of noninvasive mechanical ventilation (NIV) using the BiPAP S/T-AVAPS ventilation strategy in subjects with mild to moderate de novo hypoxaemic respiratory failure. Methods: This is a prospective study that includes subjects with de novo hypoxaemic respiratory failure (not produced by acute exacerbations of COPD, chronic lung disease, or congestive heart failure) with mild to moderate PaO₂/FiO₂, who were admitted to the Intensive Care Unit (ICU) of Santa Maria Clinic in Guayaquil, Ecuador. Subjects were divided into two groups and compared according to their PaO₂/FiO₂: higher than 100 and up to 200 mm Hg (moderate ARDS) or between 200 and 300 mm Hg (mild ARDS) (both groups were ventilated with the BiPAP S/T-AVAPS strategy). A value of P Results: A total of 38 subjects were analysed in this study. The total rate of intubation was 34.2% while the mortality rate was 28.9%. Significant differences were observed when comparing success versus failure in exhaled tidal volumes (P = 0.04), peak inspired pressure (P 2 (P 2 (P 2/FiO₂ (P P P = 0.029) measured at baseline and at 12-hour, 24-hour and 48-hour intervals. Conclusion: The BiPAP S/T-AVAPS ventilatory mode can be used in subjects with de novo hypoxaemic respiratory failure with special vigilance concerning exhaled tidal volumes and inspired pressure.

https://ift.tt/2QbLyUn

Peri-anaesthetic cardiac arrest with administration of enalapril, spironolactone and β-blocker

none

https://ift.tt/2qk11GN

Postoperative pain after spinal surgery in the paediatric population

Introduction: Postoperative pain is a major aftereffect of surgery. Especially severe occurs after extensive operations within the spine. The goal of the study was to investigate the laboratory predictive factors of intensive postoperative pain in children undergoing extensive surgery Patients and methods: We recruited 41 children, age median 13 years (IQR:10-15 years) undergoing extensive spine surgery. The subjects were divided into two groups based on the intensity of postoperative pain measured using the 10-point numerical rating scale (NRS), visual analog scale (VAS) or faces pain scale-revised (FPS-R). Patients with a score of 5 or higher were included in the study group and those with NRS of less than 5 were included in the control group. We collected detailed clinical and laboratory data before, during and after surgery. Results: The highest intensity of pain was observed in the first 6 hours after surgery. The postoperative pain was associated with a higher drop in hemoglobin concentration and hematocrit level in peri-operative period (p=0.006 and p=0.019 respectively) as well as higher changes in mean arterial pressure during surgery. Additionally, we found that children with intensive pain had higher total protein concentration after surgery. Conclusions: We reported that the drop in hemoglobin and hematocrit level, fluctuation in mean arterial pressure as well as total protein concentration could be useful prognostic factors of early postoperative pain.

https://ift.tt/2QazYJk

A case report of inadvertent intranasal submucosal injection of concentrated epinephrine with no long-term sequelae

https://ift.tt/2qjCUYM

How do you stop unwanted hair growth?

Unwanted hair growth on the body or face has a range of causes linked to hormones. Some growth is typical and has no links to conditions that cause hirsutism. Natural treatments include diet changes and weight management. Medical treatments can also help. Learn more about excessive or unwanted hair in women here.

https://ift.tt/2RpyE5G

Homage to Mechnikov – the phagocytic system: past and present

https://ift.tt/2Ohu4EA

How do you stop unwanted hair growth?

Unwanted hair growth on the body or face has a range of causes linked to hormones. Some growth is typical and has no links to conditions that cause hirsutism. Natural treatments include diet changes and weight management. Medical treatments can also help. Learn more about excessive or unwanted hair in women here.

https://ift.tt/2RpyE5G

Evaluation of Prevention Interventions for Taxane-Induced Dermatologic Adverse Events

This systematic review summarizes evidence on the effectiveness and safety of current cryotherapy methods to prevent hair, skin, and nail changes associated with chemotherapy.

https://ift.tt/2RoVsSU

Necrotizing Neutrophilic Dermatitis, an Often-Misdiagnosed Entity With Potentially Severe Consequences

I first became aware of the diagnosis of pyoderma gangrenosum (PG) early in my dermatology residency when I encountered a patient diagnosed with ulcerative colitis who presented with fever and hundreds of vesiculopustular lesions on her face, trunk, and extremities, several of which developed into typical lesions of classic PG. Within weeks of seeing that patient, I cared for another patient with a known diagnosis of agnogenic myeloid metaplasia with an atypical, superficial variant of PG that has been described more frequently on the upper extremities and face in association with a myeloid preleukemic process. This rare ulcerative disease, first described in 1930 by Brunsting et al, was something I heard little of during medical school or my medicine residency. However, within the initial year of my dermatology residency I had become involved with multiple cases of PG and I was hooked on investigating the literature, writing about my experiences with misdiagnoses and management of patients beyond the use of systemic corticosteroids. From 1977, when my first publication on this entity appeared in this journal, until today, I have been an author or coauthor on 28 publications about PG. The most recent publication is part of a Delphi project to develop improved diagnostic criteria that went beyond the statement by Perry in 1969 that "the diagnosis of a skin lesion as pyoderma gangrenosum (PG) is dependent entirely upon the clinical evaluation of the lesion. Unfortunately, there are no characteristic histopathologic changes or abnormalities on laboratory tests."^(p899)

https://ift.tt/2PsTDan

Clinical Features of Neutrophilic Dermatosis Variants Resembling Necrotizing Fasciitis

This case series examines 6 previously unreported patients and published reports of 48 patients with necrotizing neutrophilic dermatosis to identify the traits and infection-mimicking features of a new subset of necrotizing neutrophilic dermatosis.

https://ift.tt/2Rxaer1

Lipoid Proteinosis

This case report describes a classic presentation of lipoid proteinosis.

https://ift.tt/2PzF6JK

Assessment of Response to B-Cell Depletion Using Rituximab in Cutaneous Lupus Erythematosus

This cohort study evaluates outcomes of rituximab treatment in patients with different clinical subtypes of cutaneous lupus erythematosus and associated systemic disease.

https://ift.tt/2RsT51y

Early Diagnosis of Skin Melanoma Metastasis by Means of Dermoscopy and Confocal Microscopy

This case report describes the early diagnosis of skin melanoma metastasis by means of dermoscopy and confocal microscopy.

https://ift.tt/2PvU43x

Pityriasis Rosea

This Patient Page provides information on pityriasis rosea, a common cutaneous erruption that is more prevelent in older children and young adults.

https://ift.tt/2RqF7Nt

Association Between Market Competition and Prices of Generic Topical Dermatology Drugs

This cost analysis uses National Average Drug Acquisition Cost data and US Food and Drug Administration Orange Book data to assess whether an association exists between changes in drug prices and the number of approved manufacturers for the most commonly prescribed topical dermatologic generic drugs.

https://ift.tt/2PymUAr

ZnO:SBA-15 Nanocomposites for Potential Use in Sunscreen: Preparation, Properties, Human Skin Penetration and Toxicity

Aim: We evaluated the effects of the incorporation of zinc oxide (ZnO) nanoparticles in a mesoporous matrix, aiming to improve the textural, structural and morphological properties and verify their safety so that they can be applied in sunscreen cosmetics. Materials and Methods: ZnO nano­particles were incorporated into an ordered mesoporous silica matrix known as Santa Barbara Amorphous-15 (SBA-15), using post-synthesis methodology. The resulting nanocomposites were characterized using X-ray diffraction, small angle X-ray scattering, N₂ adsorption-desorption isotherms, Fourier transform infrared spectroscopy, scanning electron microscopy and predicted in vitro sun protector factor (SPF) estimation. Effectiveness and safety were evaluated by antimicrobial activity, in vitro cell toxicity and non-invasive multi-photon tomography with fluorescence lifetime imaging. Results: The structure of the nanocomposites was similar to that of SBA-15, with little perturbation caused by ZnO incorporation. Nanocomposites had an increased in vitro SPF, reduced cytotoxic activity and favourable antimicrobial properties compared to ZnO. ZnO:SBA-15 nanocomposites exhibited no measurable toxicity when applied to human skin in vivo. Conclusion: Due to their suitable physicochemical properties and improved safety compared to bare ZnO nanoparticles, the ZnO:SBA-15 nanocomposites show promise for use in cosmetic applications.
Skin Pharmacol Physiol 2019;32:32–42

https://ift.tt/2RpQ5CO

In vivo Human Skin Penetration of the UV Filter Ethylhexyl Triazone: Effect of Lipid Microparticle Encapsulation

Background/Aims: The data available on the skin permeability of ethylhexyl triazone (EHT), a widely used high-molecular-weight (823.1-Da) UV filter, are scarce and obtained only via in vitro studies. Therefore, we evaluated in vivo the penetration of EHT in human stratum corneum by the tape stripping technique. Moreover, the effect of EHT encapsulation in lipid microparticles (LMs) on its diffusion through the stratum corneum was examined. Methods: LMs loaded with EHT were prepared using glyceryl behenate and phosphatidylcholine. Creams containing EHT free or encapsulated in LMs in conjunction with the two most commonly used UV filters, octyl methoxycinnamate (OMC) and butyl methoxydibenzoylmethane (BMDBM), were applied to human volunteers and the fraction of the applied sunscreen dose having penetrated into different stratum corneum layers was measured. Results and Conclusion: For the cream with the nonencapsulated sunscreen agent, the percentage of the applied EHT dose diffused into the stratum corneum was 21.9 ± 4.9%, not significantly different from that of the smaller-molecular-weight OMC (22.2 ± 7.6%) and BMDBM (20.5 ± 3.7%). A marked (45.7%) and statistically significant reduction in the in vivo skin penetration of EHT was attained with the cream containing microencapsulated EHT. The decreased percutaneous penetration provided by the LMs should favor the efficacy of EHT and limit potential toxicological risks.
Skin Pharmacol Physiol 2019;32:22–31

https://ift.tt/2PvH26k

Case of extranodal natural killer/T‐cell lymphoma, nasal type, accompanied by Epstein–Barr virus‐positive nasopharyngeal carcinoma

The Journal of Dermatology, EarlyView.


https://onlinelibrary.wiley.com/doi/abs/10.1111/1346-8138.14701?af=R

The Influence of Breast Cancer on the Distribution of Cherry Angiomas on the Anterior Thoracic Wall: A Case Series Study

Background/Aims: Cherry angiomas (CAs) are one of the most common vascular manifestations of the skin. By and large, these benign lesions often only represent an aesthetic problem. In the literature, few authors have focused on the pathogenesis of these lesions, and some risk factors have been identified, such as the presence of cutaneous and non-skin neoplasias. In this study, the correlation between the distribution of CAs and breast cancer was investigated. Methods: We carried out a study whereby 50 women with unilateral breast cancer and the presence of CAs on the anterior thoracic wall were evaluated, with a particular focus on the difference in the number of CAs between the two haemithoraces. The data was elaborated using the Wilcoxon signed-rank test in order to evaluate whether there was a statistical significance in the distribution of CAs. Results: In 31 patients we found that the number of CAs was greater on the cancerous breast than on the contralateral one (p value #x3c;0.0001). This was confirmed both in the group of patients suffering from ductal breast cancer and in the group with early invasive breast tumours. Conclusion: It is not clear whether CAs develop prior to or following breast cancer, indicating the possibility that this cutaneous manifestation could take on a predictive, prognostic development or represent only an epiphenomenon. Further in-depth studies into the pathogenesis of CAs and the relationship with breast cancer could lead to noteworthy diagnostic-therapeutic advances.
Dermatology

https://ift.tt/2qlM8E4

Arterial Stiffness in a Toddler with Neurofibromatosis Type 1 and Refractory Hypertension

Arterial hypertension is a common finding in patients with neurofibromatosis (NF) type 1. Renovascular hypertension due to renal artery stenosis or midaortic syndrome could be the underlying cause. We report the case of a 4-year-old girl with NF type 1 and midaortic syndrome whose changes in blood pressure and pulse wave velocity suggested the evolution of vasculopathy, diagnosis of renovascular hypertension, and provided insights of response to treatment. Hypertension persisted after percutaneous transluminal angioplasty in the abdominal aorta, requiring escalation of antihypertensive treatment, while arterial stiffness demonstrated a mild decrease. Regular assessment of blood pressure using ambulatory blood pressure monitoring and noninvasive assessment of arterial stiffness may enhance the medical care of patients with NF type 1.

https://ift.tt/2qmz8xI

Trial Evaluating the Tolerance and Safety of Durvalumab - RT Combination for Treatment in SCCHN

Condition:   HNSCC
Intervention:   Drug: Durvalumab
Sponsors:   Groupe Oncologie Radiotherapie Tete et Cou;   UNICANCER;   Center Eugene Marquis
Not yet recruiting

https://ift.tt/2Jtt9zY

Trial Evaluating the Tolerance and Safety of Durvalumab - RT Combination for Treatment in SCCHN

Condition:   HNSCC
Intervention:   Drug: Durvalumab
Sponsors:   Groupe Oncologie Radiotherapie Tete et Cou;   UNICANCER;   Center Eugene Marquis
Not yet recruiting

https://ift.tt/2Jtt9zY

Sialendoscopy for Definitive Management of a Submandibular Abscess following Radiotherapy for Oropharyngeal Squamous Cell Carcinoma

Background/Aims: Sialendoscopy has as yet been shown to be ideal for the management of sialolithiasis and chronic inflammatory diseases of the salivary gland. However, its applicability to the management of a broad range of salivary gland disease is continually growing. Methods: Here we present a case report where sialendoscopy was used to successfully manage an intraparenchymal submandibular gland abscess in a patient with oropharyngeal squamous cell carcinoma managed with primary chemoradiation. Results: The use of sialendoscopy enabled visualization of the patency of salivary ducts, drainage of abscess, and irrigation of antibiotic-impregnated fluid. In this particular patient, we were able to avoid a transcervical approach through a previously irradiated field, which would have necessitated concurrent tracheostomy and placed undue risk to surrounding neurovascular structures. Conclusion: Sialendoscopy should thus, in select patients, be considered as an initial intervention for patients with intraparenchymal salivary gland abscesses in which prior therapy creates an increased risk of complication from an open transcervical approach.
ORL

https://ift.tt/2qmdM3M

Posttraumatic sigmoid sinus thrombosis secondary to transmastoid foreign body

Publication date: Available online 30 October 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): G. Badidi, S. Chabrier, J.M. Prades, A. Karkas

https://ift.tt/2PEjnAN

Cosmetics, Vol. 5, Pages 64: Hydration and Barrier Properties of Emulsions with the Addition of Keratin Hydrolysate

Cosmetics, Vol. 5, Pages 64: Hydration and Barrier Properties of Emulsions with the Addition of Keratin Hydrolysate

Cosmetics doi: 10.3390/cosmetics5040064

Authors: Pavel Mokrejš Jana Pavlačková Dagmar Janáčová Matouš Huťťa

Although keratin hydrolysates (KH) are added to skin care agents, detailed studies on the moisturising effects of KH are lacking. The aim of this study is to test whether adding KH into an ointment base (OB) heighten hydration of the skin and diminish transepidermal loss of water (TEWL). Formulations containing 2%, 4%, and 6% of KH (based on OB weight) were prepared. Hydration, TEWL and skin pH were measured; intervals of measurements were as follows: 1, 2, 3, 4, 24 and 48 h. Testing was carried out on 10 men. In terms of hydration, supplementing the OB with 2% KH is optimal, as an 11–19% increase occurs in hydration of stratum corneum (SC). All the formulations with added KH as tested caused TEWL to decline after application. Keratin hydrolysate makes for an excellent occlusive; adding it to OB results in a 30–50% reduction in TEWL after application. KH functions as a humectant as well, as it helps to bind water from the lower layers of the epidermis to the SC. Formulations with additions of 2–6% of KH were stable in structure and did not cause phase separation even after 6 months storage.

https://ift.tt/2RrbE5Z

New role for the modern allergist in drug allergy: Assess, diagnose, and de-label

Publication date: November 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5

Author(s): Mariana Castells

https://ift.tt/2qkEFEY

Authors’ response

Publication date: November 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5

Author(s): Sten Dreborg, Harold Kim

https://ift.tt/2Q96P0Y

Clarification of epicutaneous immunotherapy trial phase 3 results and methods for qualitative survey design

Publication date: November 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5

Author(s): John G. Matthews, Rezi Zawadzki, Tmirah Haselkorn, Karin Rosén

https://ift.tt/2qlHMMX

Qualitative evaluation of caregiver preferences for peanut immunotherapy products: Methods and timing count

Publication date: November 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5

Author(s): Stephen A. Tilles

https://ift.tt/2Q96NWU

Penicillin allergy

Publication date: November 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5

Author(s): David Lang, Chitra Dinakar, John J. Oppenheimer, Vivian Hernandez-Trujillio

https://ift.tt/2qkDXYk

High-risk drug rashes

Publication date: November 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5

Author(s): Sasha A. Alvarado, Diana Muñoz-Mendoza, Sami L. Bahna

Abstract

Objective

To provide a brief overview of the clinical presentation, common offending agents, management, prognosis, and mortality of 6 selected high-risk drug rashes, namely, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, multiple drug hypersensitivity (MDH) syndrome, acute generalized exanthematous pustulosis (AGEP), and drug-induced bullous pemphigoid (DIBP).

Data Sources

A review of the published literature was performed with PubMed and supplemented with our clinical experience.

Study Selections

The most recent clinically relevant studies and older seminal works were selected.

Results

Most of the published data on these uncommon rashes were based on small observational series or case reports. SJS and TEN have specific genotypes association with certain drugs, have high morbidity and mortality, and require aggressive management by a team of multiple specialists. DRESS syndrome is a severe, prolonged multiorgan reaction, yet it has a better prognosis than TEN. MDH is a syndrome of repeated reactions to unrelated drugs that often imposes diagnostic and management difficulties. AGEP consists of generalized sterile small pustules, usually mistaken for infection with subsequent inappropriate treatment. Bullous pemphigoid presents with tense pruritic bullae and characteristic linear basement membrane deposition of IgG and C3. DIBP has much better prognosis than the autoimmune variety.

Conclusion

In such high-risk drug rashes, early recognition, immediate withdrawal of the suspected drug(s), prompt individualized management, and monitoring of vital organs function are mandatory for reducing morbidity and mortality. The lack of reliable tests for identification of the causative agent imposes difficulty, particularly in patients receiving multiple medications.

https://ift.tt/2Q96M5i

Systematic review of professional liability when prescribing β-lactams for patients with a known penicillin allergy

Publication date: November 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5

Author(s): Meghan N. Jeffres, Elizabeth A. Hall-Lipsy, S. Travis King, John D. Cleary

Abstract

Objective

To describe medical negligence and malpractice cases in which a patient with a known penicillin allergy received a β-lactam and experienced an adverse reaction related to the β-lactam.

Data Sources

Lexis-Nexus, Westlaw, and Google Scholar were searched.

Study Selections

Medical negligence and malpractice cases were eligible for inclusion if they met the following criteria: the plaintiff had a known penicillin allergy, received a β-lactam, and experienced an adverse event. All United States federal and state cases were eligible.

Results

Twenty-seven unique cases met the inclusion criteria. Eighteen cases involved the receipt of a penicillin-based antibiotic; of these cases with a known legal outcome, the plaintiff (patient or representative) prevailed or settled in 3 cases and defendants (providers) prevailed in 7 cases. Seven cases involved the receipt of a cephalosporin; of these cases with a known legal outcome, the plaintiff settled with physicians before trial in 1 case and defendants prevailed in 3 cases. Two cases involved the receipt of a carbapenem. Defendants prevailed in one case and the legal outcome of the other case is unknown. In cases in which the defense successfully moved for summary judgment, judges cited a lack of scientific evidence demonstrating a cephalosporin or carbapenem was contraindicated for a patient with a penicillin allergy.

Conclusion

The cases with published legal outcomes found limited professional liability for clinicians who prescribed cephalosporins or carbapenems to a patient with a known penicillin allergy. These results may decrease the litigation fears of practitioners and risk managers within health care systems.

https://ift.tt/2qkECZO

Penicillin allergy and the law

Publication date: November 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5

Author(s): Roland Solensky

https://ift.tt/2Q96Kuc

Authors’ response

Publication date: November 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5

Author(s): Matthew Greenhawt, Rebekah Marsh, Hannah Gilbert, Daniel Matlock

https://ift.tt/2qgZS2O

Editorial Board

Publication date: November 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5

Author(s):

https://ift.tt/2QcF9IV

Information for Authors

Publication date: November 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5

Author(s):

https://ift.tt/2qm7RM6

Table of Contents

Publication date: November 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5

Author(s):

https://ift.tt/2Q9hgBZ

Information for Readers

Publication date: November 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5

Author(s):

https://ift.tt/2qkExFu

Pressure, trigger forces, and epinephrine auto-injectors

Publication date: November 2018

Source: Annals of Allergy, Asthma & Immunology, Volume 121, Issue 5

Author(s): Julie Brown

https://ift.tt/2Q9W0vK

Syndrome de Griscelli de type 3 : un nouveau cas

Publication date: Available online 30 October 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): H. Kassem Youssef, C. Ramstein, E. Ginglinger, F. Chouta Ngaha, H. Nojavan, C. Michel

Résumé

Introduction

Le syndrome de Griscelli (SG) est une maladie génétique autosomique récessive rare, caractérisée par une dilution pigmentaire des cheveux et de la peau. Nous rapportons un cas de syndrome de Griscelli de type 3 diagnostiqué à un âge tardif.

Observation

Une femme de 31 ans présentait depuis l'enfance une dépigmentation des cheveux et des sourcils avec une discrète leucodermie diffuse. L'étude microscopique du cheveu mettait en évidence des agrégats de mélanine irrégulièrement distribués le long de la tige pilaire. Le séquençage de l'ADN montrait une mutation homozygote C103T (R35W) dans l'exon 1 du gène MLPH, correspondant au syndrome de Griscelli type 3.

Discussion

Trois phénotypes cliniques de SG ont été décrits selon le défaut moléculaire sous-jacent. Les SG types 1 et 2 sont associés respectivement à un dysfonctionnement du système nerveux central et à un déficit immunitaire. Le SG type 3 est une forme cutanée isolée. L'examen microscopique des cheveux permet de poser le diagnostic. Seuls 15 cas de SG type 3 ont été décrits dans la littérature, neuf de sexe masculin et six de sexe féminin. L'âge moyen au diagnostic est de 12 ans. Dix des cas sont d'origine arabe, quatre d'origine turque et un d'origine indienne. La mutation R35W a été observée dans neuf cas et les mutations E98X et R35Q chacune dans un cas.

Conclusion

Le syndrome de Griscelli doit être évoqué devant tout aspect de cheveux gris argentés, plus particulièrement chez des patients d'origine arabe ou turque.

Summary

Introduction

Griscelli syndrome (GS) is a rare autosomal-recessive genetic disease characterized by hypopigmentation of skin and hair. We report a case of GS type 3 with late diagnosis.

Observation

A 31-year-old female patient had presented depigmentation of the hair and eyebrows as well as diffuse skin hypopigmentation during childhood. Microscopic analysis of a hair shaft revealed irregularly distributed clumps of melanin. DNA sequencing showed a homozygous C103T (R35W) transition in exon 1 of MLPH, confirming Griscelli syndrome type 3.

Discussion

Three clinical phenotypes of GS have been described based on the underlying genetic defect. GS type 1 and 2 are associated respectively with a central nervous system dysfunction and an immune defect. GS type 3 is an isolated cutaneous form. Diagnosis is confirmed on microscopic examination of hair shafts. 15 cases of GS type 3 have been reported: 9 in males and 6 in females. Mean age at diagnosis is around 12 years. Nine of the reported patients were of Arab origin, four of Turkish origin, and one of Indian origin. R35W mutation was described in 9 cases and E98X and R35Q mutations were each found in one case.

Conclusion

GS should be suspected in patients presenting gray silvery hair, particularly when these patients are of Arab or Turkish origin.

https://ift.tt/2JteQeB

Parent Perspectives on Multidisciplinary Pediatric Hearing Healthcare

Publication date: Available online 31 October 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Ursula M. Findlen, Prashant S. Malhotra, Oliver F. Adunka

Abstract

Introduction

Family-centered healthcare demands that families provide input regarding the care of their children. Very little is known, however, about how families perceive their experience in different types of multidisciplinary team models, and specifically, in the multidisciplinary setting currently utilized in many pediatric hearing clinics.

Methods

Quantitative and qualitative parent survey responses were collected and analyzed in a tertiary care pediatric medical center after a one-day multidisciplinary assessment clinical appointment. Questions pertained to information across five domains, including overall experience, diagnosis, treatment plan formulation, additional testing, and resources. Quantitative responses were analyzed descriptively while qualitative responses were evaluated using content analysis to derive themes. Quantitative and qualitative data were evaluated separately and then compared to delineate themes for strengths and weaknesses.

Results

Overall, high satisfaction was evident in both quantitative and qualitative responses. Results suggested that a one-day multidisciplinary assessment appointment may contribute to parents feeling overwhelmed by information shared and not fully understanding which disciplines are providing care. Analysis revealed a specific area of weakness in our particular setting was inadequate provision of information about functional hearing (e.g., listening socially and academically). Results contributed to a change from a multidisciplinary team model to an interdisciplinary care coordination approach to pediatric hearing healthcare.

Conclusions

Understanding parent perspectives and expectations is the corner stone of family-centered care and may ultimately influence a child's developmental outcome. A systematic way of evaluating parent perspectives on the clinical process can influence service delivery and help children with hearing loss meet their potential.

https://ift.tt/2CU530d

Characteristics of Children with Refractory Acute Otitis Media Treated at the Pediatric Emergency Department

Publication date: Available online 31 October 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Jacob Pitaro, Sofia Waissbluth, Marie-Claude Quintal, Anthony Abela, Annie Lapointe

https://ift.tt/2qlGGRl

Cost-effectiveness of nivolumab in the treatment of head and neck cancer

Publication date: December 2018

Source: Oral Oncology, Volume 87

Author(s): A. Hirschmann, J.E. Lupatsch, M. Schwenkglenks, C.M. Panje, K. Matter-Walstra, V. Espeli, K.J. Dedes, M. Siano, for the Swiss Group of Clinical Cancer Research (SAKK)

Abstract

Background

Until recently, no second-line treatment for recurrent and/or metastatic head and neck squamous cell cancer (r/mHNSCC) was able to improve overall survival (OS). Nivolumab has become a promising treatment for r/mHNSCC. The CheckMate-141 trial showed that nivolumab improves OS compared to investigator's choice (IC) (cetuximab, methotrexate, docetaxel). Treatment with immune checkpoint inhibitors is however expensive. The aim of this analysis was to assess the cost-effectiveness of nivolumab as second-line treatment for r/mHNSCC in Switzerland.

Methods

Based on the CheckMate-141 trial, we constructed a Markov model comparing nivolumab to IC, including follow-up data up to 24 months. We assessed costs for treatments from the perspective of the Swiss health system with a 60 months' time horizon. PD-L1 and p16 testing were considered in scenarios. Incremental cost-effectiveness ratios (ICER) were compared to an informal willingness-to-pay of CHF (Swiss Francs) 100,000 per QALY gained.

Results

For the base case we estimated an incremental effectiveness of 0.35 QALYs and incremental costs of CHF 35,562 with nivolumab, resulting in an ICER of CHF 102,957 per QALY gained. Most influential drivers for the ICER were the price of nivolumab and the progressive disease state utility weights. In 45.5% of probabilistic sensitivity analysis simulations nivolumab was estimated below 100,000 CHF/QALY. Reducing the price of nivolumab according to a consented payback by 4.75%, resulted in an ICER of CHF 98,325/QALY gained.

Conclusions

At current prices nivolumab has an ICER of around CHF 100,000 per QALY gained in the second line treatment of r/mHNSCC patients in Switzerland.

https://ift.tt/2P0WQ1v

Activation of the language control network in bilingual visual word recognition

Publication date: Available online 31 October 2018

Source: Cortex

Author(s): David Peeters, Flora Vanlangendonck, Shirley-Ann Rueschemeyer, Ton Dijkstra

Abstract

Research into bilingual language production has identified a language control network that subserves control operations when bilinguals produce speech. Here we explore which brain areas are recruited for control purposes in bilingual language comprehension. In two experimental fMRI sessions, Dutch-English unbalanced bilinguals read words that differed in cross-linguistic form and meaning overlap across their two languages. The need for control operations was further manipulated by varying stimulus list composition across the two experimental sessions. We observed activation of the language control network in bilingual language comprehension as a function of both cross-linguistic form and meaning overlap and stimulus list composition. These findings suggest that the language control network is shared across bilingual language production and comprehension. We argue that activation of the language control network in language comprehension allows bilinguals to quickly and efficiently grasp the context-relevant meaning of words.

https://ift.tt/2SwpwgN

IVIG induces apoptotic cell death in CD56dim NK cells resulting in inhibition of ADCC effector activity of human PBMC

Publication date: Available online 31 October 2018

Source: Clinical Immunology

Author(s): Sebastian Bunk, Padmapriya Ponnuswamy, Azra Trbic, Mantas Malisauskas, Heinz Anderle, Alfred Weber, Josenato Ilas, Anna M. Winkler, H. Arno Butterweck, Wolfgang Teschner, Friedrich Scheiflinger, Corinna Hermann, Birgit M. Reipert

Abstract

The mechanism of the efficacy of Intravenous immunoglobulins (IVIG) in autoimmune and inflammatory diseases is not well understood. This study aimed at understanding mechanisms of IVIG-mediated suppression of effector cell activities of peripheral blood mononuclear cells (PBMC) in antibody-dependent cellular cytotoxicity (ADCC). We were particularly interested in CD56^dim NK cells, the main ADCC effector cells in PBMC. Exposure of PBMC to IVIG for at least 48 h induced a caspase-3-dependent apoptotic cell death of CD56^dim NK cells without affecting CD56^bright NK cells. Induction of apoptosis in CD56^dim NK cells and concomitant suppression of ADCC effector activities of PBMC was associated with the monomer fraction of IVIG. Moreover, it was independent of IgG sialyation, did not depend on engagement of FcγRIII and could not be mimicked by IVIG (Fab')₂ or IVIG Fc preparations. The described effect could contribute to the reduction of peripheral NK cells observed during IVIG therapy in patients.

https://ift.tt/2Dei1H1

Migraine increases the proportion of sudden sensorineural hearing loss: A longitudinal follow-up study

Publication date: Available online 30 October 2018

Source: Auris Nasus Larynx

Author(s): So Young Kim, Mi Kyung Kim, Jae-Sung Lim, Il Gyu Kong, Hyo Geun Choi

Abstract

Objective

The aim of the present study was to investigate the proportion of sudden sensorineural hearing loss (SSNHL) patients in a representative population cohort with migraine.

Methods

The Korean National Health Insurance Service-National Sample Cohort was collected from 2002 to 2013. A total of 45,114 migraine participants (the migraine group) were matched according to age, sex, income, region of residence, hypertension, diabetes, and dyslipidemia with 180,456 controls (the control group). The migraine group included participants diagnosed with migraine (International Classification of Disease [ICD]-10: G43) who underwent treatment ≥2 times. The SSNHL was investigated based on the ICD-10 (H912) code and confirmed by an audiometry exam and steroid treatment. Histories of hypertension, diabetes, dyslipidemia, ischemic heart disease, stroke, depression, Meniere's disease, and tinnitus were evaluated using ICD-10 codes. Crude (simple) and adjusted hazard ratios (HRs) of SSNHL associated with migraine were analyzed using the Cox proportional hazards model. Subgroup analyses were conducted according to age and sex.

Results

In total, 0.9% (399/44,714) of the migraine patients and 0.6% (1,169/179,287) of the controls were diagnosed with SSNHL (P < 0.001). The adjusted HR of migraine for SSNHL was 1.34 (95% confidence interval [CI] = 1.19–1.50, P < 0.001). Both patient age subgroups (20–59 years old and ≥60 years old) showed high adjusted HRs for SSNHL. Both the men and women presented an elevated proportion of SSNHL cases.

Conclusion

Migraine patients had a higher likelihood of SSNHL. All age and sex migraine subgroups showed an elevated proportion of SSNHL cases.

https://ift.tt/2AC2PAN

Evaluation of folded amniotic membrane and injectable amniotic membrane pieces as soft tissue filler materials

Publication date: Available online 30 October 2018

Source: Auris Nasus Larynx

Author(s): Mustafa Caglar Buday, Murat Ozturk

Abstract

Objective

The search for safe and effective tissue fillers has been an ongoing effort for many years. Obtaining biological materials from patients can require additional incisions and brings surgical and cosmetic risks as a major disadvantage. The aim of this experimental study was, therefore, to evaluate the efficacy of folded amniotic membrane as a soft tissue filler and to assess its volume, and to investigate the possible usage of injectable amniotic membrane for augmentation.

Methods

Multi-layer amniotic membranes are transplanted to the subcutaneous tunnels created in the rat's back, and the amniotic membrane transformed into the injection material is inoculated transcutaneously under the rat's skin. At the end of two months, the amount of volume loss and histopathological changes in the grafts were examined under light microscope.

Results

The multi-layer amniotic membrane grafts maintain its volume around 92%. It has been shown that the injectable amniotic membrane maintains its presence in the tissue, can augment it, and can be used as a soft tissue filler. The availability of using amniotic membrane for injection material is shown. No foreign body reaction to the amnion grafts, fibrosis, and necrosis were observed in our study.

Conclusion

According to our study results, multi-layer amnion graft and amnion injection seem to be used as camouflage grafts and soft tissue augmentation materials. Although further clinical trials are mandatory before considering the use of amniotic membrane as a tissue filler material in humans, we are hopeful about its long-term safety and efficacy.

https://ift.tt/2EShYC9

Sekundär erworbene Tränenwegsstenose und zervikale Lymphadenopathie

https://ift.tt/2Q7KKQA

Vestibuläre Störungen

https://ift.tt/2qizaXk

Stapes hypermobility as a possible cause of hyperacusis

Publication date: Available online 31 October 2018

Source: American Journal of Otolaryngology

Author(s): Herbert Silverstein, Joshua Smith, Brian Kellermeyer

Abstract

Objective

Hyperacusis is a reduction of normal tolerances for everyday sounds. Although several publications have been produced demonstrating that minimally invasive surgical procedures may improve patient symptoms, the precise etiology of hyperacusis often remains elusive. This study describes 21 patients, 7 of whom stapes hypermobility is believed to be a mechanical genesis of their hyperacusis symptoms.

Study design

A prospective, repeated-measure single-arm design was used for this study.

Setting

All patients were evaluated and treated at a tertiary level otologic referral center.

Subjects and methods

21 patients (Cohort A) with severe hyperacusis underwent oval and round window reinforcement. Seven patients (Cohort B) intraoperatively appeared to have subjective hypermobility of the stapes. Additional reinforcement of the stapes superstructure was performed in these patients.

Results

In Cohort A, loudness discomfort level (LDL) values improved on average from 72.7 dB to 81.9 dB. Hyperacusis questionnaire (HQ) scores improved from 30.1 to 14.7. Numeric Rating Scale scores (0−10) decreased from 8.5 to 4.0. In Cohort B, values similarly improved from an average of 72.4 dB to 88.2 dB. HQ scores improved from 35.8 to 18.9. Numeric Rating Scale scores fell from 10.0 to 3.7. Postoperatively there were no complaints of hearing loss. Sixteen out of 21(76%) reported improved quality of life and diminished symptoms of hyperacusis.

Conclusion

It is possible that patients suffering from hyperacusis may have a mechanical cause for their symptoms. Further research is necessary to clarify stapes mobility in patients with these symptoms. Excess temporalis tissue reinforcement of the stapes along with round window reinforcement shows promise as a minimally invasive surgical option for patients suffering from hyperacusis.

https://ift.tt/2OgqFFL

Game Changer: Oral tranexamic acid (TA) in the treatment of melasma: A retrospective analysis

Publication date: Available online 31 October 2018

Source: Journal of the American Academy of Dermatology

Author(s): Eden Lake

https://ift.tt/2Q8V0I8

Game Changer: Oral tranexamic acid (TA) in the treatment of melasma: A retrospective analysis

Publication date: Available online 31 October 2018

Source: Journal of the American Academy of Dermatology

Author(s): Eden Lake

https://ift.tt/2qinl3y

Game Changer: Oral tranexamic acid (TA) in the treatment of melasma: A retrospective analysis

Publication date: Available online 31 October 2018

Source: Journal of the American Academy of Dermatology

Author(s): Eden Lake

https://ift.tt/2Q9g2Xk

Game Changer: Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): A phase IIb, randomized, placebo-controlled, clinical trial in adult patients with moderate to severe atopic dermatitis (AD)

Publication date: Available online 31 October 2018

Source: Journal of the American Academy of Dermatology

Author(s): Eden Lake

https://ift.tt/2qlzTaj

Roles of functional strain and capsule compression on mandibular cyst expansion and cortication

Publication date: Available online 30 October 2018

Source: Archives of Oral Biology

Author(s): Babak Sarrafpour, Charbel El-Bacha, Qing Li, Hans Zoellner

Abstract

Objective

Cyst expansion in bone involves bone resorption but is often accompanied by adjacent bone formation with cortication. The mechanisms for these two apparently opposite processes remain unclear. From a mechanobiological perspective, functional strain drives bone remodeling, which involves both bone apposition and resorption. In this study, we explore the role of functional strain in cyst growth.

Design

Using a three-dimensional finite element analysis model of a simulated cyst at the of right first mandibular molar mesial apex, we examined three loading conditions, representing biting on the right molar, left molar and incisors, respectively. Comparison was made with an identical finite element model without the simulated cyst.

Results

Under all loading conditions, finite element analysis revealed higher strain energy density within the bone lining the cyst compared with the non-cyst model, which is consistent with bone formation and cortication observed clinically. Further analysis demonstrated overall compression of the simulated cyst capsule under all loading conditions.We interpret compression of the capsule as indicating resorption of the adjacent bone surface.

Conclusions

We conclude that functional stress results in dominant compression of the soft tissue capsules of bony cysts, contributing to cyst expansion. Also, functional strain becomes elevated in the bone immediately adjacent to the soft tissue cyst capsule, which may drive bone formation and cortication.

https://ift.tt/2F2LhSy

Epicutaneous immunotherapy for peanut allergy modifies IgG4 responses to major peanut allergens

Publication date: Available online 31 October 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Stef J. Koppelman, Aurélie Peillon, Wenceslas Agbotounou, Hugh A. Sampson, Laurent Martin

https://ift.tt/2zgIm2H

Multicenter, randomized, double-blind, placebo-controlled clinical trial of vital wheat gluten oral immunotherapy

Publication date: Available online 30 October 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Anna Nowak-Węgrzyn, Robert A. Wood, Kari C. Nadeau, Jacqueline A. Pongracic, Alice K. Henning, Robert W. Lindblad, Kirsten Beyer, Hugh A. Sampson

Background

Wheat is a common food allergen that can cause anaphylaxis.

Objective

We sought to determine the efficacy and safety of vital wheat gluten (VWG) oral immunotherapy (OIT).

Methods

After baseline double-blind, placebo-controlled food challenge (DBPCFC), 46 patients with wheat allergy (median age, 8.7 years; range, 4.2-22.3 years) were randomized 1:1 to low-dose VWG OIT or placebo, with biweekly escalation to 1445 mg of wheat protein (WP). After a year 1 DBPCFC, active subjects continued low-dose VWG OIT for another year and underwent a year 2 DBPCFC and, if passed, a subsequent off-therapy DBPCFC. Placebo-treated subjects crossed over to high-dose VWG OIT (maximum, 2748 mg of WP).

Results

The median baseline successfully consumed dose (SCD) was 43 mg of WP in both groups. At year 1, 12 (52.2%) of 23 low-dose VWG OIT–treated and 0 (0%) of 23 placebo-treated subjects achieved the primary end point of an SCD of 4443 mg of WP or greater (P < .0001); median SCDs were 4443 and 143 mg, respectively. At year 2, 7 (30.4%) of 23 low-dose VWG OIT–treated subjects were desensitized to an SCD of 7443 mg of WP; 3 (13%) achieved sustained unresponsiveness 8 to 10 weeks off therapy. Among placebo-treated subjects who crossed over to high-dose VWG OIT, 12 (57.1%) of 21 were desensitized after 1 year (median SCD, 7443 mg of WP; nonsignificant vs low-dose VWG OIT). At year 1, skin prick test responses and wheat- and omega-5 gliadin–specific IgE levels did not differ between groups; the low-dose VWG OIT median specific IgG₄ level was greater than placebo (wheat, P = .0005; omega-5 gliadin, P = .0001). Year 1 SCDs correlated with wheat-specific (rho = 0.55, P = .0003) and omega-5 gliadin–specific (rho = 0.51, P = .001) IgG₄ levels in all subjects. Among 7822 low-dose VWG OIT doses in year 1, 15.4% were associated with adverse reactions: 0.04% were severe, and 0.08% subjects received epinephrine. Among 7921 placebo doses, 5.8% were associated with adverse reactions; none were severe.

Conclusions

Low- and high-dose VWG OIT induced desensitization in about one half of the subjects after 1 year of treatment. Two years of low-dose VWG OIT resulted in 30% desensitization, and 13% had sustained unresponsiveness.

Graphical abstract

https://ift.tt/2SyrzB4

Non-operative management of isolated spontaneous superior mesenteric artery dissection

Abstract

Isolated spontaneous superior mesenteric artery (SMA) dissection is a rare differential for patients presenting with abdominal pain. Due to limited cases reported, management strategies have been poorly defined. We present the case of a 49-year-old male with history of hypertension and ischemic colitis, presenting with abdominal pain. CT imaging demonstrated a thrombosed dissection of the SMA extending into second and third order braches. He was managed conservatively with therapeutic anticoagulation. His symptoms improved and upon discharge he was transitioned to aspirin and warfarin. Repeat CT imaging continued to show the dissection with resolution of the SMA thrombus. Spontaneous SMA dissection is exceedingly rare with no universally agreed upon standard of care for treatment. Operative intervention should be reserved for failed conservative management or vascular compromise. Understanding the current treatment options helps ensure a favorable patient outcome.

https://ift.tt/2Q6fcKM

Malignant proliferating trichilemmal tumor of the forearm: a case report of an unusual location of a rare cutaneous adnexal tumor

Abstract

Proliferating trichilemmal tumor (PTT) is a rare cutaneous adnexal neoplasm of the hair follicle that undergoes outer root sheath differentiation in the isthmus. Histological hallmarks include trichilemmal keratinization, lack of granular layer and lobular proliferation of squamous epithelium with glycogenated clear cells. It affects predominantly elderly women, especially over the scalp. In some cases, malignant transformation can occur. However, only a few cases are reported in the literature. We hereby describe the case of a patient diagnosed with malignant PTT (MPTT) in the dorsal forearm, 2 years after undergoing surgical excision of a squamous cell carcinoma in the same topography. Thus, providing a thorough description of the clinical presentation of MPTT will assist surgeons in diagnosing and treating this rare tumor.

https://ift.tt/2qiDgPn

Resection of a mature cystic teratoma of the liver harboring a carcinoid tumor

Abstract

Cystic teratomas are rare pluripotent embryonic tumors which most commonly originate in gonadal organs. Extra-gonadal cystic teratomas are exceedingly uncommon, accounting for only 1% of all cystic teratomas, and have been reported in unusual locations including the kidney, mediastinum and liver. These extra-ovarian cystic teratomas have also been known to harbor other neoplasms including carcinoid tumors. In this report, we describe a unique case of a hepatic cystic teratoma occurring as a combined tumor with a carcinoid in a young female. The patient underwent elective laparoscopic resection of her tumor after extensive radiographic and endoscopic work-up for chronic, non-localizable abdominal pain. We believe the carcinoid tumor arose de novofrom committed differentiation of a cell line within the teratoma, and not metastatic spread.

https://ift.tt/2Q6f1iA

Decompressive laparotomy for a patient on VA-ECMO for massive pulmonary embolism that suffered traumatic liver laceration after mechanical CPR

Abstract

Massive pulmonary embolism (PE) is an embolus sufficiently obstructing pulmonary blood flow to cause right ventricular (RV) failure and hemodynamic instability. We have utilized veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for early and aggressive intervention for massive PE patients. We present a case of a 61-year-old female placed on VA-ECMO for a massive PE while presenting in cardiac arrest and receiving mechanical cardiopulmonary resuscitation (CPR) via the LUCAS 2.0 device (Physio-Control Inc., Lund, Sweden). The patient suffered a severe liver laceration secondary to mechanical CPR and required a decompressive laparotomy. This case highlights that mechanical CPR during other interventions can lead to malposition of the device and could result in solid organ injury.

https://ift.tt/2qnr5k9

Rhabdomyolysis-Induced Acute Kidney Injury in Diabetic Emergency: Underdiagnosed and an Important Association to Be Aware of

Rhabdomyolysis is a potentially life-threatening clinical syndrome associated with muscle injury which can cause a leakage of intracellular contents, manifested from the range of being asymptomatic to a life-threatening condition causing acute kidney injury and severe electrolyte abnormalities. Rhabdomyolysis has been associated with both diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic nonketotic syndrome, though there is an increased association with rhabdomyolysis and acute kidney injury with hyperosmolar nonketonic state compared with patients with diabetic ketoacidosis. Common clinical manifestations are muscle pain, dark urine, and generalized weakness. The causes of rhabdomyolysis are broadly categorized into three groups: traumatic, nontraumatic exertional, and nontraumatic nonexertional. Here, we present a case of rhabdomyolysis-induced acute kidney injury in a patient with hyperosmolar hyperglycemic state. The patient was discharged on insulin and needed intermittent dialysis for two months. Our case highlights the importance of the rare association of rhabdomyolysis causing acute kidney injury in a diabetic emergency.

https://ift.tt/2zgpm4h

Erratum

Dermatology 2018;234:1

https://ift.tt/2P1p387

Cover Image

Clinical &Experimental Allergy, Volume 48, Issue 11, Page i-i, November 2018.


https://ift.tt/2yIIXup

Presented at the 2018 Annual Meeting of the British Society for Allergy and Clinical Immunology

Clinical &Experimental Allergy, Volume 48, Issue 11, Page 1524-1574, November 2018.


https://ift.tt/2OeonHj

Issue Information

Clinical &Experimental Allergy, Volume 48, Issue 11, Page 1373-1375, November 2018.


https://ift.tt/2yIITLb

Forthcoming Meetings

Clinical &Experimental Allergy, Volume 48, Issue 11, Page 1575-1575, November 2018.


https://ift.tt/2OhkAsR

Fatal anaphylaxis to food allergens: Learning from tragedies

Clinical &Experimental Allergy, Volume 48, Issue 11, Page 1376-1377, November 2018.


https://ift.tt/2yIcsMZ

Best of the Other Journals

Clinical &Experimental Allergy, Volume 48, Issue 11, Page 1576-1577, November 2018.


https://ift.tt/2Of6KqT

Independent predictive factors for the persistence and tolerance of cow's milk allergy

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2Q7frFr

Surgical simulation of a catastrophic internal carotid artery injury: a laser‐sintered model

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2qkVrDX

Glucose metabolism in patients with psoriasis

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Q7bfpb

Risk factors for treatment failure in scabies: a cohort study

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2qn184t

Glucose metabolism in patients with psoriasis

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Q7bfpb

Risk factors for treatment failure in scabies: a cohort study

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2qn184t

Characteristics and Outcomes of Liver Transplantation for Primary Biliary Cholangitis (PBC) in Young patients: Analysis of the United Network for Organ Sharing Database

Background Primary biliary cholangitis (PBC) in younger patients has been suggested to require liver transplantation (LT) in early adulthood, but data is limited on its outcomes. We aimed to evaluate the characteristics and outcome of LT in young patients with PBC in comparison with older adults. Methods The United Network for Organ Sharing (UNOS) database was analyzed for all patients with PBC who underwent LT between 2000 and 2012. Based on age at the time of LT subjects were divided into two groups: young patients (≤ 40 years) and older adults (≥ 41 years). Baseline demographics, clinical parameters, and outcomes of LT were then compared between the two groups. Univariable and multivariable analyses were performed to assess the factors associated with outcomes of LT. Results A total of 2,084 patients with PBC were included in the analysis with 158 young patients. Compared to older adults, younger patients were more likely to be male (27.2% vs. 15.4%) and non-white (43.7% vs. 21.5%) but they were less likely to have obesity, diabetes, or hypertension (p

https://ift.tt/2P0GhTm

Antiphospholipid Syndrome And Renal Allograft Thrombosis

Renal allograft thrombosis is the most frequent and devastating complication in the early postrenal transplantation period. Several risk factors to develop graft thrombosis depending on donors and recipients are well known. Antiphospholipid syndrome (APS) is well recognized as an important cause of kidney injury, with specific clinical and histological features that may lead to renal injury caused by thrombosis at any location within the renal vasculature. There are 3 forms of APS, primary (the most common form), associated to other systemic autoimmune diseases (SAD-APS) and catastrophic. Nevertheless, patients with SAD-APS and renal failure only represent 2-5% in hemodialysis or transplantation. The presence of pretransplant antiphospholipid antibodies (APL) increases risk of graft thrombosis. A new form of APS based on IgA anti-Beta-2-Glycoprotein-I(B2GPI) antibodies, representing up to 30% of patients in ESRD and renal transplantation, is the main independent risk factor for graft thrombosis and early graft loss after renal transplantation. In addition, B2GP1 bound to IgA aB2GP1 immunocomplexes have been described as a marker to predict thrombosis after renal transplantation in patients with antiphospholipid antibodies. Anticoagulation remains the main treatment to prevent renal allograft thrombosis, although new preventive strategies are coming. Future studies may help to identify better therapeutic targets. Correspondence to: Jose M Morales, Prof. of Medicine. Consultant Investigator, Healthcare Research Institute Hospital 12 de Octubre, 28041 Madrid, Spain, E-Mail: jmorales@h12o.es Phone: 34-607469173 Authors: JMM, MS and AS designed the structure of the review, discussed the relevant literature and wrote the manuscript. JAMF and DP worked in the pathophysiology of renal allograft thrombosis. Finally all authors discussed the complete manuscript and all agree with the final text. JMM and MS collaborated equally to this work. The authors declare no conflict of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2CUZu1B

Favorable outcome of an exclusively posttransplant prophylactic strategy after heart transplantation in recipients with high immunological risk

Background Management of the increasing number of sensitised heart transplant candidates has become a recurrent issue. Rather than using pretransplant desensitisation therapies, we used a posttransplant prophylactic strategy. Our aim was to describe outcomes in transplant recipients with preformed donor-specific anti-HLA antibodies (pfDSA) managed with this strategy. Methods A posttransplant protocol was applied to patients transplanted with pfDSA, consisting of perioperative management of DSA (polyvalent immunoglobulins +/- perioperative plasmapheresis sessions, according to DSA level, as well as induction therapy) and systematic treatment of subsequent antibody-mediated rejection (ABMR), even when subclinical. We performed a retrospective analysis of this prospective protocol. The study included all consecutive first recipients of a noncombined heart transplant performed between 2009 and 2015 at our centre. The primary endpoint was all-cause mortality. Secondary endpoints included primary graft dysfunction, early posttransplant bleeding, rejection and cardiac allograft vasculopathy-free survival. Results A total of 523 patients were studied, including 88 (17%) and 194 (37%) transplanted with DSA mean fluorescence intensity (MFI) of 500–1000 and >1000, respectively. The median follow-up period was 4.06 years. Survival was not significantly different between groups. Rejection-free survival was worse in patients with pfDSA MFI >1000, evidenced by a fourfold increase in the risk of ABMR. The incidence of primary graft dysfunction and cardiac allograft vasculopathy-free survival did not significantly differ between groups. Perioperative plasmapheresis increased the risk for transfusion of packed red blood cells. Conclusions This exclusively posttransplant prophylactic strategy achieved favourable outcomes in heart transplant recipients with pfDSA. Institute of cardiology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP). Paris, France. Corresponding author: Dr Guillaume Coutance, Service de Chirurgie Thoracique et Cardio-Vasculaire, Institut de Cardiologie - Groupe hospitalier Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital - 75651 Paris Cedex 13. Tel: +33 1/42-16-56-08, Fax: +33 1/42-16-55-76. Mail: guillaume.coutance@gmail.com Authorship page Guillaume Coutance participated in the performance of the research, in data analysis and in the writing of the paper. Virginie d'Orio participated in the performance of the research and in data analysis. Lisa Belin participated in data analysis and in the writing of the paper. Nicolas Bréchot participated in research design and in the performance of the research. Samir Saheb participated in research design and in the performance of the research. Guillaume Lebreton participated in research design and in the writing of the paper. Adrien Bouglé participated in the performance of the research and in the writing of the paper. Philippe Rouvier participated in the performance of the research and in the writing of the paper. Chantal Gautreau participated in the performance of the research and in the writing of the paper. Salima Ouldammar participated in the performance of the research. Xavier Chamillard participated in the performance of the research. Mélanie Huot participated in the performance of the research. Julien Amour participated in research design and in the writing of the paper. Alain Combes participated in research design and in the writing of the paper. Pascal Leprince participated in research design and in the writing of the paper. Shaida Varnous participated in research design and in the writing of the paper. Disclosure: The authors declare no conflicts of interest. Funding Source: Guillaume Coutance received research grants from the ADICARE association (2017). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2OZ8ytw

Development of CDX-1140, an agonist CD40 antibody for cancer immunotherapy

Abstract

Limitations of immunotherapy include poorly functioning events early in the immune response cycle, such as efficient antigen presentation and T cell priming. CD40 signaling in dendritic cells leads to upregulation of cell surface costimulatory and MHC molecules and the generation of cytokines, which promotes effective priming of CD8⁺ effector T cells while minimizing T cell anergy and the generation of regulatory T cells. This naturally occurs through interaction with CD40 ligand (CD40L) expressed on CD4⁺ T-helper cells. CD40 signaling can also be achieved using specific antibodies, leading to several agonist CD40 antibodies entering clinical development. Our approach to select a CD40 agonist antibody was to define a balanced profile between sufficiently strong immune stimulation and the untoward effects of systemic immune activation. CDX-1140 is a human IgG2 antibody that activates DCs and B cells and drives NFkB stimulation in a CD40-expressing reporter cell line. These activities are Fc-independent and are maintained using an F(ab′)2 fragment of the antibody. CDX-1140 binds outside of the CD40L binding site, and addition of recombinant CD40L greatly enhances DC and B activation by CDX-1140, suggesting that CDX-1140 may act synergistically with naturally expressed CD40L. CDX-1140 also has both direct and immune-mediated anti-tumor activity in xenograft models. CDX-1140 does not promote cytokine production in whole blood assays and has good pharmacodynamic and safety profiles in cynomolgus macaques. These data support the potential of CDX-1140 as part of a cancer therapy regimen, and a phase 1 trial has recently commenced.

https://ift.tt/2EPQlcT

Multiple myeloma presenting as cutaneous leukocytoclastic vasculitis and eosinophilia disclosing a T helper type 1/T helper type 2 imbalance: a case report

Multiple myeloma is a very heterogeneous disease comprising a number of genetic entities that differ from each other in their evolution, mode of presentation, response to therapy, and prognosis. Due to its mor...

https://ift.tt/2qlXuYq

Langerhans and inflammatory dendritic epidermal cells in atopic dermatitis are tolerized toward TLR2 activation

Allergy, EarlyView.


https://ift.tt/2CPfqSG

Modulation of allergic responses by mitochondrial STAT3 inhibitors

Allergy, EarlyView.


https://ift.tt/2OXvN74

Reduction in polyamine catabolism leads to spermine‐mediated airway epithelial injury and induces asthma features

Allergy, Volume 73, Issue 10, Page 2033-2045, October 2018.


https://ift.tt/2CPfqCa

Low frequency of acetyl salicylic acid hypersensitivity in mastocytosis: The results of a double‐blind, placebo‐controlled challenge study

Allergy, Volume 73, Issue 10, Page 2055-2062, October 2018.


https://ift.tt/2OZR00c

Issue Information ‐ TOC

Allergy, Volume 73, Issue 10, Page 1933-1934, October 2018.


https://ift.tt/2CS2Bas

Multiple drug intolerance syndrome and multiple drug allergy syndrome: Epidemiology and associations with anxiety and depression

Allergy, Volume 73, Issue 10, Page 2012-2023, October 2018.


https://ift.tt/2P2CUeA

Issue Information ‐ Cover and Editorial Board

Allergy, Volume 73, Issue 10, Page 1931-1931, October 2018.


https://ift.tt/2CTdvgb

In this Issue: Graphical Abstracts

Allergy, Volume 73, Issue 10, Page 1935-1938, October 2018.


https://ift.tt/2OYPifJ

16th Indonesian Society of Dermatology and Venereology Annual Meeting Together with the 23rd Asian–Australasian Regional Conference of Dermatology, Surabaya, Indonesia

Dermatologic Therapy, EarlyView.


https://ift.tt/2yHiiy4

Topical urea in skincare: A review

Dermatologic Therapy, EarlyView.


https://ift.tt/2OgOi11

16th Indonesian Society of Dermatology and Venereology Annual Meeting Together with the 23rd Asian–Australasian Regional Conference of Dermatology, Surabaya, Indonesia

Dermatologic Therapy, EarlyView.


https://ift.tt/2yHiiy4

Topical urea in skincare: A review

Dermatologic Therapy, EarlyView.


https://ift.tt/2OgOi11

Increased Mortality and Morbidity in Patients with Chronic Hypoparathyroidism: A population based study

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Rrs4vn