Propofol TCI Reductions Do Not Attenuate Significant Falls in Cardiac Output Associated With Anesthesia Induction and Knee-Chest Positioning in Spinal Surgery

Background: Induction of anesthesia and the knee-chest position are associated with hemodynamic changes that may impact patient outcomes. The aim of this study was to assess whether planned reductions in target-controlled infusion propofol concentrations attenuate the hemodynamic changes associated with anesthesia induction and knee-chest position. Materilas and Methods: A total of 20 patients scheduled for elective lumbar spinal surgery in the knee-chest position were included. In addition to standard anesthesia monitoring, bispectral index and noninvasive cardiac output (CO) monitoring were undertaken. The study was carried out in 2 parts. In phase 1, target-controlled infusion propofol anesthesia was adjusted to maintain BIS 40 to 60. In phase 2, there were 2 planned reductions in propofol target concentration: (1) immediately after loss of consciousness—reduction calculated using a predefined formula, and (2) before positioning—reduction equal to the average percentage decrease in CO after knee-chest position in phase 1. Changes from baseline in CO and other hemodynamic variables following induction of anesthesia and knee-chest positioning were compared. Results: Induction of anesthesia led to decreases of 25.6% and 19.8% in CO from baseline in phases 1 and 2, respectively (P

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Journal Club

No abstract available

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Cognitive Prehabilitation: Supercharged Mind or Wishful Thinking?

No abstract available

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Role of Frailty and Comorbidity in Determination of Operability for Patients With Oral and Oropharyngeal Squamous Cell Carcinoma

Abstract

Purpose of Review

To review the role of frailty and comorbidities in determining operability and associated outcomes in patients with oral and oropharyngeal squamous cell carcinoma.

Recent Findings

Frailty and comorbidity have been linked to multiple adverse outcome measures including risk of mortality, surgical complications, length of stay, intensity of care needs, discharge disposition, risk of readmission, and cost of healthcare delivery. There are diverse objective and validated measures of comorbidity and frailty. Addition of comorbidity and objective frailty measurements has been demonstrated to improve predictive power of nomograms and clinical staging systems for patients with oral and oropharyngeal squamous cell carcinoma. The use of predictive tools that assess frailty may contribute to shared decision making, realistic expectations, and facilitation of appropriate level of care. While emerging literature supports the role of prehabilitation, there is paucity of data in support of such interventions for patients afflicted by oral and oropharyngeal cancer.

Summary

Frailty assesses operability beyond anatomic resectability and incorporates key determinants of physical, nutritional, and cognitive well-being. Objective measurements of frailty predict meaningful outcomes following surgery for cancers of the oral cavity and oropharynx. This paper suggests that clinicians should objectively and routinely assess frailty, which may facilitate patient counseling, improved risk stratification, informed decision making, and further research to elucidate relationship of frailty with outcomes in head and neck specific populations.

http://bit.ly/2HleOID

Hypokalaemic metabolic alkalosis, hypertension and diabetes: what is the link

Two years after diagnosis of a metastatic neuroendocrine gastrin-secreting tumour and after several cycles of chemotherapy and peptide receptor radionuclide therapy, a 56-year-old woman presented with hypokalaemic metabolic alkalosis, hypertension, leg oedema and new-onset diabetes mellitus. Further investigations revealed renal potassium loss confirmed by a transtubular potassium gradient of 16, fully suppressed serum aldosterone, but instead highly elevated blood levels of morning cortisol and adrenocorticotropic hormone as well as increased urinary excretion of glucocorticoid and mineralocorticoid metabolites. Ruling out other causes, paraneoplastic hypercortisolism was diagnosed. Pharmacological inhibition of the steroid 11β-hydroxylase with metyrapone resulted in complete resolution of metabolic alkalosis, hypokalaemia, hypertension, hyperglycaemia and leg oedema within 1 week.

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Oncocytic cyst of the larynx: a rare finding

A 75-year-old woman presented with an 18-month history of severe, slowly worsening dysphonia. She was a smoker and known to have multiple benign cystic thyroid lesions. She reported no associated symptoms and other medical and social history was unremarkable. Fibreoptic nasendoscopy revealed a right-sided supraglottic cyst appearing to arise from the right false vocal cord. Further bedside examination was unremarkable. She underwent microlaryngoscopy and biopsy which showed a cyst originating from the right anterior ventricle, successfully removed without rupture using cold steel. Formal histopathology revealed a 14x10x7 mm unilocular, completely excised cyst lined by oncocytic epithelium and composed of columnar cells with darkly stained nuclei and abundant granular, eosinophilic cytoplasm. Three weeks postoperatively the patient's voice had returned to normal. To date, 11 months postoperatively, there is no evidence of recurrence, and she will continue long-term follow-up.

http://bit.ly/2FJkoSt

Inguinal hernia containing a native orthotopic kidney

We report a rare case of an inguinal hernia containing part of a native kidney and present a review of the literature with regard to urological findings in patients with inguinal hernias. This case involves an elderly man with known bilateral inguinal hernias with an incidental radiographic finding of a large right inguinal hernia containing the inferior pole of the right kidney. The patient was not symptomatic from the hernia and given his overall frailty, no surgical intervention was offered.

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Early diagnosis of cutaneous mastocytosis in an infant: the importance of a clinical sign

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Monocytopenia in clozapine-induced agranulocytosis: insights into pathophysiology and treatment

A 26-year-old man with history of schizophrenia was admitted for neutropaenia. He was started on clozapine 3 months prior to admission. As a result he had weekly monitoring of his blood counts and on day of admission was noted to have an absolute neutrophil count (ANC) of 450 cells/μL. He was admitted for clozapine-induced agranulocytosis. Clozapine was held and the patient was started on granulocyte colony-stimulating factor (G-CSF) filgrastim and received two doses without any signs of ANC recovery. On further review, it was noted that the absolute monocyte count (AMC) was also low and tracked with the trend of ANC. We then theorised that the impact of clozapine was on a haematopoietic precursor (colony-forming unit granulocyte-macrophage, CFU-GM) which gives rise to both monocytic and myeloid lineages. Therefore, sargramostim GM-CSF was started. After two doses, the ANC and AMC started trending up and by the third dose, both counts had fully recovered. He was discharged from the hospital and there are no plans to rechallenge with clozapine. Thus, we demonstrate a case of monocytopenia accompanying clozapine-induced agranulocytosis with successful use of GM-CSF. At least in this case, the target of the clozapine injury appears to be the CFU-GM, explaining the rapid and full response to GM-CSF after lack of response to G-CSF.

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Focal myositis and contracture secondary to amiodarone extravasation from a peripheral cannula

A 63-year-old man underwent cardioversion of atrial fibrillation with intravenous amiodarone through an antecubital fossa cannula. Mid-infusion, the cannula tissued. He developed immediate pain and swelling. At 3 weeks, he continued to have significant pain and had developed a fixed flexion deformity. MRI demonstrated focal myositis of the biceps and brachialis muscles. Treatment included physiotherapy and plastic surgery but sadly in spite of this, the patient has had minimal symptomatic improvement at 1 year. Amiodarone extravasation is well recognised to cause local injection site reactions. Involvement of deeper tissues is rare. To our knowledge, this is only the second description of a consequent focal myositis in the literature.

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Rare case of bladder chondroma causing lower urinary tract symptoms

An extraosseous or soft tissue chondroma is a rare, benign cartilaginous tumour characterised by the formation of mature hyaline cartilage. The majority of osseous chondromas are located within the medullary cavity of long bones. Soft tissue chondromas are extremely rare with only five cases affecting the bladder being reported in the literature. Soft tissue chondroma of the bladder is a rare cause of lower urinary tract symptoms and abdominopelvic pain. All reported cases of soft tissue chondromas of the bladder have occurred in women in their fifth to seventh decades of life. We describe the case of a 65-year-old woman diagnosed with a soft tissue chondroma of her bladder while being investigated for lower urinary tract symptoms.

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Urothelial carcinoma with villoglandular differentiation (UCVGD) with small cell neuroendocrine carcinoma of urinary bladder

Urothelial carcinoma with villoglandular differentiation (UCVGD) is a rare aggressive variant of urothelial carcinoma. It is usually associated with high-grade urothelial carcinoma or rarely adenocarcinoma. There is only one other previous report of UCVGD associated with small cell neuroendocrine carcinoma of urinary bladder. We report the second case of UCVGD with small cell neuroendocrine carcinoma of urinary bladder in a 74-year-old non-smoker male patient. The mass was muscle invasive and also invaded the prostate. This entity needs to be confidently diagnosed due to its prognostic and therapeutic implications.

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Spontaneous anterior dislocation of lens in a case of ectopia lentis et pupillae: a rare entity treated by a novel technique of microscope integrated optical coherence tomography (MIOCT) guided intralenticular lens aspiration

A 7-year-old girl presented with watering and redness in the left eye for 2 months. Her parents reported poor vision in both eyes for 4 years. Visual acuity was finger counting at 1 m and finger counting close to face in the right and left eyes, respectively. Slit lamp examination of the right eye revealed corectopia, aphakia in the pupillary area, temporally subluxated clear crystalline lens, persistent pupillary membrane, irido-hyaloidal adhesion and poorly dilating pupil. Left eye revealed central corneal oedema with descemet scarring, anteriorly dislocated clear crystalline lens with lenticulo-corneal touch. Ultrasound examination of the left eye was normal. Hence a diagnosis of ectopia lentis et pupillae with left eye spontaneous anterior dislocation of the lens along with corneal decompensation was made. The child underwent microscope integrated intraoperative optical coherence tomography guided intralenticular lens aspiration with optical iridectomy in the left eye. Postoperative visual rehabilitation was done with aphakic glasses.

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Comparison of pre-oxygenation using spontaneous breathing through face mask and high-flow nasal oxygen: A prospective randomised crossover controlled study in healthy volunteers

BACKGROUND High-flow nasal oxygen (HFNO) therapy has been proposed for pre-oxygenation before intubation, but the end-tidal fraction of oxygen (ETO2) obtained remains unknown. OBJECTIVE(S) To compare the ETO2 following a 3 min pre-oxygenation with HFNO and face mask. SETTING Operating room in a primary university hospital. DESIGN A prospective, randomised crossover study. PARTICIPANTS Fifty healthy volunteers. INTERVENTIONS Participants were randomly pre-oxygenated through spontaneous breathing 100% oxygen in a face mask and with HFNO (mouth closed, heated and humidified gas flow at 60 l min–1). In the face mask group, the ETO2 was measured continuously. In the HFNO group, the nasal cannula was quickly exchanged with a face mask while the subject held their breath at end inspiration and the ETO2 was measured after a deep expiration. The protocol ended when ETO2 reached 90% or otherwise at 6 min. MAIN OUTCOME MEASURES The primary endpoint was the ETO2 after 3 min of pre-oxygenation. Secondary endpoints were the proportion of participants with an ETO2 at least 90% and the time until the ETO2 at least 90%. RESULTS The ETO2 after 3 min of pre-oxygenation was 89 (2) % and 77 (12) % in the face mask and HFNO groups [difference 12% (95% confidence interval, 95% CI: 8 to 15]; P 

http://bit.ly/2FEaz9t

Central venous-to-arterial PCO2 difference, arteriovenous oxygen content and outcome after adult cardiac surgery with cardiopulmonary bypass: A prospective observational study

BACKGROUND Rapid identification and treatment of tissue hypoxia reaching anaerobiosis (dysoxia) may reduce organ failure and the occurrence of major postoperative complications (MPC) after cardiac surgery. The predictive ability of PCO2-based dysoxia biomarkers, central venous-to-arterial PCO2 difference (ΔPCO2) and ΔPCO2 to arteriovenous oxygen content difference ratio, is poorly studied in this setting. OBJECTIVES We evaluated the ability of PCO2-based tissue dysoxia biomarkers, blood lactate concentration and central venous oxygen saturation measured 2 h after admission to the ICU as predictors of MPC. DESIGN A prospective, observational cohort study. SETTING Single-centre, academic hospital cardiovascular ICU. PATIENTS We included adult patients undergoing cardiac surgery with cardiopulmonary bypass and measured dysoxia biomarkers at ICU admission, and after 2, 6 and 24 h. MAIN OUTCOME MEASURES The primary endpoint was MPC, a composite of cardiac and noncardiac MPC evaluated in the 48 h following surgery. After univariate analysis of MPC covariates including dysoxia biomarkers measured at 2 h, multivariate logistic regression analyses were performed to identify the association of these biomarkers with MPC for confounders. Areas under the receiver operating characteristic curves were determined for biomarkers which remained independently associated with MPC. RESULTS MPC occurred in 56.5% of the 308 patients analysed. ΔPCO2, blood lactate concentration and central venous oxygen saturation measured at 2 h, but not ΔPCO2 to arteriovenous oxygen content difference ratio, were significantly associated with MPC. However, only ΔPCO2 was independently associated with MPC after multivariate analysis. The areas under the receiver operating characteristic curves of ΔPCO2 measured at 2 h for MPC prediction was 0.64 (95% CI 0.57 to 0.70, P 

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Programmed intermittent bolus infusion versus continuous infusion of 0.2% levobupivacaine after ultrasound-guided thoracic paravertebral block for video-assisted thoracoscopic surgery: A randomised controlled trial

BACKGROUND The analgesic benefits of programmed intermittent bolus infusion for thoracic paravertebral block remain unknown. OBJECTIVE The aim of this study was to compare the analgesia from intermittent bolus infusion with that of a continuous infusion after thoracic paravertebral block. DESIGN A randomised controlled study. SETTING A single centre between December 2016 and November 2017. Seventy patients scheduled for video-assisted thoracoscopic surgery were included in the study. INTERVENTION(S) Patients were randomly assigned to receive 0.2% levobupivacaine via continuous infusion (5 ml h−1, continuous group) or programmed intermittent bolus infusion (15 ml every 3 h, bolus group) after an initial 15-ml bolus injection of 0.2% levobupivacaine. MAIN OUTCOME MEASURES The main outcome was the amount of rescue fentanyl (per kg of body weight) consumed within 24 h after surgery. Secondary outcomes were postoperative pain scores, plasma levobupivacaine concentrations and the number of dermatomes anaesthetised. RESULTS There was no significant difference between the continuous and bolus groups in the postoperative consumption of fentanyl (median [interquartile range] 5.5 [4 to 9.5] μg kg−1 versus 6 [3.5 to 9] μg kg−1 respectively, P = 0.45) and postoperative pain scores within 24 h. At 20 h after initiating the infusions, there was no statistically significant difference between the two groups in terms of the plasma levobupivacaine concentration. The number of dermatomes anaesthetised to pinprick and cold testing was significantly greater in the bolus group. CONCLUSION Our findings suggest that postoperative pain and opioid usage are similar with either programmed intermittent bolus infusion or continuous infusion after thoracic paravertebral block. Programmed intermittent bolus infusion provides a wider sensory blockade and could benefit patients requiring a wider extent of anaesthesia. TRIAL REGISTRATION UMIN Clinical Trials Registry (UMIN-CTR; URL: http://umin.ac.jp/ctr/, ID: UMIN000023378). Correspondence to Dr. Yasuko Taketa, Department of Anesthesiology and Critical Care, Ehime Prefectural Central Hospital, 83 Kasuga-machi, Matsuyama-City, Ehime 790-0024, Japan. E-mail: suko1231@yahoo.co.jp © 2019 European Society of Anaesthesiology

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Pre-operative ultrasonographic evaluation of inferior vena cava collapsibility index and caval aorta index as new predictors for hypotension after induction of spinal anaesthesia: A prospective observational study

BACKGROUND Hypotension after spinal anaesthesia is a common side effect that may be harmful. Patients' susceptibility to intra-operative hypotension can be affected by many pre-operative factors. OBJECTIVES The current study aimed to evaluate the efficacy of both pre-operative inferior vena cava collapsibility index (IVCCI) and inferior vena cava to aorta diameter (IVC : Ao) index for predicting postspinal anaesthesia hypotension (PSAH). DESIGN Prospective observational blinded study. SETTING Operating room from June 2017 to February 2018. PATIENTS One hundred adult patients of both sexes, American Society of Anesthesiologists' physical status 1 or 2 scheduled for elective surgery under spinal anaesthesia were included in this study. INTERVENTIONS Patients received spinal anaesthesia performed at the level of L3 to 4 or L4 to 5 intervertebral space with the patient in the sitting position then placed in the supine position immediately after neuraxial block and kept supine throughout the study period (30 min). IVCCI and IVC : Ao index were assessed pre-operatively. Baseline noninvasive blood pressure was recorded before administration of spinal anaesthesia then every minute after spinal blockade for 30 min. MAIN OUTCOME MEASURES The primary outcome was to evaluate the predictive values of both IVCCI and IVC : Ao index for detecting PSAH and the secondary outcomes were to compare the predictive values of both IVCCI and IVC : Ao index and to detect other clinical predictors for PSAH using logistic regression analysis. RESULTS Forty-five patients developed PSAH (45%). IVCCI was significantly higher in patients who developed PSAH than in patients who did not, while IVC : Ao index was significantly lower in patients who developed PSAH than in patients who did not. Hypotension after induction of spinal anaesthesia was defined as an absolute value of SBP less than 90 mmHg, a decrease in SBP more than 30% of the baseline value or an absolute value of arterial blood pressure less than 60 mmHg. Logistic regression analysis revealed that IVCCI and IVC : Ao index were good predictors of the occurrence of PSAH. Receiver operating characteristic curve analysis showed that IVC : Ao index had a sensitivity of 96%, a specificity of 88%, and an accuracy of 95% to predict PSAH at a cut-off point less than 1.2. IVCCI had a sensitivity of 84%, a specificity of 77%, and an accuracy of 84% to predict PSAH at a cut-off point more than 44.7%. CONCLUSION Pre-operative IVCCI and IVC : Ao index are good predictors of the occurrence of PSAH. However, IVC : Ao index is a more powerful predictor than IVCCI. TRIAL REGISTRATION This study evaluate accuracy of two diagnostic methods for the occurrence of postspinal anaesthesia hypotension, so not a clinical trial as no intervention is present and no outcome of intervention is measured. Correspondence to Dr Eman Ramadan Salama, MD, Anaesthesia and Surgical ICU, Tanta University Hospital, Tanta, Egypt Tel: +20 1277886405; fax: +20 402231671; e-mail: dr.ers1975@yahoo.com © 2019 European Society of Anaesthesiology

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Pressure Ulcers: Pathophysiology, Epidemiology, Risk Factors, and Presentation

Though preventable in the vast majority of cases, pressure ulcers continue to pose a major burden to the individual and society, affecting up to 3 million adults annually in the United States alone. Despite increased national attention over the past 20 years, the prevalence of pressure ulcers has largely remained unchanged, while associated costs of care continue to increase. Dermatologists can play a significant role in pressure ulcer prevention by becoming aware of at-risk populations and implementing suitable preventive strategies.

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A novel technique to safely maximize botulinum toxin extraction from 50 unit vials

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Pressure Ulcers: Prevention and Management

Prevention has been a primary goal of pressure ulcer research. Despite such efforts, pressure ulcers remain common in hospitals and the community. Moreover, pressure ulcers often become chronic wounds that are difficult to treat and tend to recur after healing. Especially given these challenges, dermatologists should have the knowledge and skills to implement pressure ulcer prevention strategies and to effectively treat pressure ulcers in their patients. This continuing medical education article will focus on pressure ulcer prevention and management, with a particular emphasis on the evidence for commonly accepted practices.

http://bit.ly/2Fzizbv

Tonsillectomy plus steroid pulse therapy is the most effective treatment in adult patients with C-Grade I IgA nephropathy, and the weight of the extracted palatine tonsils and Yamamoto scale have no significant correlation with the effects of this treatment

We studied patients who underwent tonsillectomy plus steroid pulse therapy (TSP) for immunoglobulin A nephropathy (IgAN), in order to investigate the clinical factors associated with a positive response to this treatment.

http://bit.ly/2RQFFAg

Subcostal approach to anterior quadratus lumborum block for pain control following open urological procedures

Abstract

In the case of open urological surgeries, analgesic coverage at mid thoracic dermatomal levels is required. As shown in cadaveric studies, the site of QL block injection is an important determinant of the extent of dye spread and presumably local anesthetic dermatomal coverage. In this case series, we evaluated dermatomal blockade and analgesic efficacy of a subcostal approach to anterior QL block following open urological surgeries. Twenty-two adult patients undergoing renal transplant surgery (60%) and open nephrectomy (40%) received unilateral ultrasound-guided subcostal anterior QL block with catheter insertion. Sensory level, pain score (numeric rating scale, NRS), local anesthetic consumption, and opioid consumption (morphine equivalent dose, MED) were assessed daily for 3 days. The block achieved sensory blockade between T6-7 and L1-2. The most frequently affected dermatomes were T8 -T12 and the number of blocked segments was 3 (mean 2.8). The median (interquartile range Q1, Q3) of NRS pain score was 3.7 (2.8–5.5), 3.3 (2.4–4.7), 2.9 (1.9–3.6), and 2.3 (1.0–4.2) on POD0, POD1, POD2, and POD3, respectively. Our preliminary data showed that the subcostal approach to anterior QL block provides appropriate thoracic dermatome level needed for analgesia following open urological surgical procedures between T6-7 and L1-2.

http://bit.ly/2CrDaKW

Car Seat Inspection with Safety Stop

Did you know our Safety Stop team can perform car seat safety checks? In this episode, we'll walk you through the different car seat types and how to properly install each one.

Learn more about the Safety Stop team and how to book an appointment at one of our area locations.

The post Car Seat Inspection with Safety Stop appeared first on ChildrensMD.

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Author Guidelines

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Progress in Dermatology and Venereology – Editor's pick of the year 2018

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Announcement

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Forthcoming Events

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Pioneers in dermatology and venereology: an interview with Prof. Alberto Giannetti

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Stratum corneum hydration regulates key epidermal function and serves as an indicator and contributor to other conditions

http://bit.ly/2FzWdqi

Fast‐growing melanoma: a distinct entity or a superficial spreading melanoma with a brief horizontal phase?

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Diagnostic Cutaneous Pathology: Clinical‐Pathological Correlation of Inflammatory and Other Non‐Neoplastic Skin Diseases, 2 Vols. Kerl H, Cerroni L, Kokol R, Requena L, Kutzner H, Metze D, Fried I, Stieber W, Wolf IH, ed. Graz: Vhj Verlagshaus Jakomini, 2017; 1488 pp. ISBN: 978‐3‐902920‐24‐9. Price EUR 660,00

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Journal of the European Academy of Dermatology and Venereology welcomes our 10 new Section Editors!

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Issue Information

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A Randomized Pilot Trial of a School‐Based Psychoeducational Intervention for Children with Asthma

Abstract

Background

Asthma is a common childhood illness with high morbidity and mortality among minority and socioeconomically disadvantaged children. Disparities are not fully accounted for by differences in asthma prevalence, highlighting a need for interventions targeting factors associated with poorer asthma control. One such factor is psychological stress.

Objective

Here, we examine the feasibility and acceptability of "I Can Cope (ICC)," a school‐based stress management and coping intervention for children with asthma.

Methods

A parallel randomized pilot trial was conducted. One hundred and four low income children (mean age 10 years; 54% male; 70% African American) with persistent asthma were recruited from 12 urban schools and randomized to: (1) ICC or one of two control conditions: (2) "Open Airways for Schools (OAS)" – an asthma education intervention or (3) no treatment.

Results

71% of eligible children participated in the study, with a dropout rate of 12%. ICC was rated as highly acceptable by participating children and parents. Preliminary efficacy data suggest that when compared with no treatment, ICC resulted in decreased symptoms of depression, perceived stress, and child‐reported symptoms of asthma, and improvements in sleep quality and child‐reported asthma control. There were no intervention‐related changes in objective measures of asthma morbidity. The magnitude of intervention effects on psychological function did not differ between the ICC and OAS groups.

Conclusions

Results support the feasibility and acceptability of utilizing school‐based interventions to access hard to reach children with asthma. Preliminary findings offer support for future, large‐scale efficacy studies of school‐based interventions designed to target multiple factors that contribute to asthma disparities.

This article is protected by copyright. All rights reserved.

http://bit.ly/2W2K8iA

Longitudinal analysis to better characterize Asthma‐COPD Overlap Syndrome (ACOS): Findings from an adult asthma cohort in Korea (COREA)

Abstract

Background

Asthma‐chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), which has received much attention, has not been unanimously defined.

Objective

In this study, we tried to demonstrate that longitudinally defined ACOS is more useful in the real‐world than blending patients with asthma and COPD.

Methods

The study patients had undergone two consecutive pulmonary function tests measured at least 3 months apart (n = 1,889). We selected the patients who had positive bronchodilator response or methacholine provocation tests (n = 959). Next, we defined ACOS as a patient with a persistent airflow obstruction [forced expiratory volume in 1 sec (FEV1)/forced vital capacity < 0.7] that was identified twice consecutively by an interval of at least 3 months (n = 228).

Results

The proportions of patients who were older, male, and smokers were significantly higher, and baseline lung function was lower in patients with ACOS. In the longitudinal analysis, the mean change in lung function was high, and a greater decline in FEV1 was observed in patients with ACOS. In addition, we compared ACOS and severe asthma, and we also performed a cluster analysis and compared the results with our definition of ACOS. According to our definition, ACOS is an independent subtype with distinctive characteristics. Finally, a genome‐wide association study (GWAS) was performed to identify genetic variations associated with ACOS, but no significant single nucleotide polymorphisms were identified.

Conclusion

Our findings suggest that ACOS should be defined longitudinally and considered as an independent subgroup distinguished by inherited environmental factors rather than as a genetically distinct independent group.

This article is protected by copyright. All rights reserved.

http://bit.ly/2QWwJow

Identification and characterization of a naïve CD8+ T‐cell repertoire for benzylpenicillin

Abstract

Background

Beta‐lactams allergy is the most commonly reported drug allergy and constitutes an important health problem. We previously showed the pre‐existence of a naïve CD4+ T‐cell repertoire for benzylpenicillin (BP) coupled to human serum albumin (HSA) but little is known about the naïve CD8+ T‐cell repertoire specific for BP.

Objective

The purpose of this work was to identify naïve CD8+ T cells specific for BP and to explore mechanisms dictating their activation.

Methods

Co‐cultures were established with naïve CD8+ T cells and autologous dendritic cells (DCs) loaded with HSA‐BP or free BP. T cells were restimulated once a week with autologous DCs loaded with HSA‐BP or BP. The specific CD8+ T cell response was measured using an IFN‐γ ELISpot assay.

Results

When using free BP, we were able to detect a naïve CD8+ T‐cell repertoire for BP in the 6 out of 7 tested healthy donors. However, our results showed that HSA‐BP was recognized by naïve CD8+ T cells in only one donor out of five tested healthy donors. Using free BP, we evidenced its binding to cellular proteins in DCs that was concentration dependent and was correlated with BP‐specific CD8+ T‐cell activation. Moreover, the BP‐specific CD8+ T‐cell response was MHC class I dependent and required intracellular processing and proteasome activity.

Conclusion and clinical relevance

This work showed the existence of a naïve CD8+ T‐cell repertoire for BP when DCs were treated with free BP suggesting that patients could be immunized by haptenated peptides from cellular proteins generated in antigen‐presenting cells.

This article is protected by copyright. All rights reserved.

http://bit.ly/2W4HV6m

Validation of childhood asthma predictive tools: a systematic review

Abstract

Background

There is uncertainty about the clinical usefulness of currently available asthma predictive tools. Validation of predictive tools in different populations and clinical settings is an essential requirement for the assessment of their predictive performance, reproducibility and generalizability. We aimed to critically appraise asthma predictive tools which have been validated in external studies.

Methods

We searched MEDLINE and EMBASE (1946‐2017) for all available childhood asthma prediction models and focused on externally validated predictive tools alongside the studies in which they were originally developed. We excluded non‐English and non‐original studies. PROSPERO registration number is CRD42016035727.

Results

From 946 screened papers, 8 were included in the review. Statistical approaches for creation of prediction tools included chisquare tests, logistic regression models and the least absolute shrinkage and selection operator. Predictive models were developed and validated in general and high‐risk populations. Only three prediction tools were externally validated: the Asthma Predictive Index, the PIAMA, and the Leicester asthma prediction tool. A variety of predictors has been tested, but no studies examined the same combination. There was heterogeneity in definition of the primary outcome among development and validation studies, and no objective measurements were used for asthma diagnosis. The performance of tools varied at different ages of outcome assessment. We observed a discrepancy between the development and validation studies in the tools' predictive performance in terms of sensitivity and positive predictive values.

Conclusions

Validated asthma predictive tools, reviewed in this paper, provided poor predictive accuracy with performance variation in sensitivity and positive predictive value.

This article is protected by copyright. All rights reserved.

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Air Methods’ airway management tool published in leading trauma textbook

Air Methods' HEAVEN Criteria was established as the gold standard process for airway management in a book for NAEMT's CE program

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Altered NOX expression does not seem to account for epidermal NLRP3 inflammasome activation in Hidradenitis Suppurativa

Abstract

Hidradenitis Suppurativa (HS)/ acne inversa is defined as a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep‐seated, inflamed lesions in the apocrine gland‐bearing areas of the body, most commonly the axillae, inguinal and anogenital regions (Dessau definition). It is associated with systemic comorbidities and influenced by genetic predisposition while triggering of the disease occurs by environmental factors. Consecutively, innate immune events appear to play a role. Recently, van der Zee et al. reported increased production of the proinflammatory cytokine IL‐1β in HS.

This article is protected by copyright. All rights reserved.

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A retrospective cohort study evaluating the accuracy of clinical diagnosis compared to immunofluorescence and electron microscopy in children with inherited epidermolysis bullosa

Abstract

Traditionally, the diagnosis of epidermolysis bullosa (EB) was made using electron microscopy (EM), and immunofluorescence mapping (IFM). Increasingly, genomics plays a role in the diagnosis of EB, and other genetic conditions, with a result turn‐around‐time as little as 1‐3 weeks. The rapid turn around time and accuracy of genetic testing mandates a rethink on the way that we currently assess infants and children with EB. A biopsy is invasive and can be distressing for caregivers. Given the limitations of skin biopsy in some situations, the future should see genetic testing as a first‐line investigation. However, it is important to note that currently, in severe neonates and infants with EB, a biopsy remains a first line investigation since clinical diagnosis is not accurate using current scoring systems and even when assessed by experts in EB.

This article is protected by copyright. All rights reserved.

http://bit.ly/2T1A6w5

A qualitative examination of the experience of skin camouflage by people living with visible skin conditions

Abstract

Background

People with a visible skin conditions can experience anxiety and intrusive reactions from others when in social situations. The use of products to conceal marks on the skin is provided in a number of different hospital services and by charities. However, little is known about the experience of people using camouflage as a tool for enhancing quality of life.

Aim

This study aimed to examine the experience of using skin camouflage to cover a visible mark on the skin. It sought to gain a detailed account of the issues associated with camouflage use and the needs of people using it.

Methods

Interpretative Phenomenological Analysis (IPA) was used to gain a detailed understanding of the meaning of camouflage use for participants. Six skin camouflage service‐users completed semi‐structured interviews.

Results

The IPA analysis revealed that the experience of using camouflage was influenced by socio‐cultural factors and the views of others. The use of camouflage was linked to investment in appearance maintenance and functioned to give a sense of control over social interactions, increase social confidence and manage concern about the responses of others.

Conclusions

This study provides an in‐depth insight into the experience of using skin camouflage and suggests that camouflage can play a valuable role in maintaining wellbeing in those living with a visible skin condition.

This article is protected by copyright. All rights reserved.

http://bit.ly/2AS47au

Severe disseminated Nocardia infection associated with ustekinumab treatment for psoriasis

Abstract

Ustekinumab is one of the newer biologic agents on the market, and most clinical experience associated with this agent has been accumulated with the treatment of psoriasis. It exerts its effect through IL‐12/IL‐23p40 antagonism. This immune signaling pathway is associated with Mendelian Susceptibility to Mycobacterial Disease, a genetic condition predisposing to opportunistic infections with mycobacteria and other select organisms. Nonetheless, clinical trial safety data for this agent has suggested its safety, with very few case reports of severe opportunistic infections. It is sometimes considered to be associated with a lesser infectious risk compared to some other biologic agents such as tumor necrosis factor inhibitors. We report a 56‐year‐old patient presenting with an unusually severe disseminated Nocardia farcinica infection associated with ustekinumab treatment: sustained bacteremia, disseminated skin lesions, large renal abscess, septic renal vein thrombosis and pulmonary and cerebral lesions . To our knowledge, this is the first report of disseminated nocardiosis associated with this monoclonal antibody.

This article is protected by copyright. All rights reserved.

http://bit.ly/2SXcw3D

The anti‐inflammatory potency of biologics targeting TNF‐α, IL‐17A, IL‐12/23 and CD20 in hidradenitis suppurativa: an ex vivo study

Abstract

Background

Biologics targeting inflammatory mediators are able to clinically improve hidradenitis suppurativa (HS). However, their clinical efficacy shows great inter‐patient variability in daily practice.

Objective

To investigate the anti‐inflammatory potency of a selection of currently available biologics for the treatment of HS in an ex vivo skin culture system using lesional HS biopsies.

Methods

Lesional skin samples of ten HS patients and skin samples of five healthy controls were cultured ex vivo and exposed to prednisolone or biologics targeting TNF‐α, IL‐17A, IL‐12/23p40, or CD20, respectively adalimumab, infliximab, secukinumab, ustekinumab and rituximab. Real‐Time quantitative PCR and cytokine bead arrays were used to measure the inhibitory effect of the biologics on cytokines and antimicrobial peptides (AMPs).

Results

The relative mRNA expression of all tested cytokines and AMPs was significantly downregulated by all anti‐inflammatory agents (p<0·0001). The protein production of the pro‐inflammatory cytokines TNF‐α, IFN‐ɣ, IL‐1ß, IL‐6, and IL‐17A was significantly inhibited by adalimumab, infliximab, ustekinumab, prednisolone (all p<0·0001) and rituximab (p=0·0071), but not by secukinumab (p=0·0663). On both mRNA and protein level, adalimumab, infliximab and prednisolone reduced the levels of a broader mix of individual cytokines than secukinumab, ustekinumab and rituximab. Moreover, a significant inhibitory effect on the mRNA expression levels of inflammatory markers in healthy control skin was observed only for prednisolone (p=0·0015) and the TNF‐α inhibitors (p<0·0001).

Conclusions

This ex vivo study suggests that TNF‐α inhibitors and prednisolone are the most powerful inhibitors of pro‐inflammatory cytokines and AMPs in HS lesional skin, which is in accordance with our clinical experience in patients with HS.

This article is protected by copyright. All rights reserved.

http://bit.ly/2ARS2SJ

Competence of final year otolaryngology residents with the bedside head impulse test

Abstract

Background

The bedside head impulse test (bHIT) is a clinical method of assessing the vestibulo-ocular reflex (VOR). It is a critical component of the bedside assessment of dizzy patients, and can help differentiate acute stroke from vestibular neuritis. However, there is evidence showing the bHIT is often not performed in appropriate clinical settings or is performed poorly. To date, there have been no studies evaluating the bHIT competence of graduating physicians.

Methods

23 final year Otolaryngology –Head &Neck Surgery (OTL-HNS) residents in Canada were evaluated on the use of bHIT using a written multiple-choice examination, interpretation of bHIT videos, and performance of a bHIT. Ratings of subject bHIT performance were completed by two expert examiners (DT, DL) using the previously published Ottawa Clinic Assessment Tool (OCAT).

Results

Using a cut-off of an OCAT score of 4 or greater, only 22% (rater DT) and 39% (rater DL) of residents were found able to perform the bHIT independently. Inter-rater reliability was fair (0.51, interclass correlation). The mean scores were 65% (14.1% standard deviation) on the video interpretation and 71% (20.2% standard deviation) on the multiple-choice questions. The scores on multiple choice examination did not correlate with bHIT ratings (Pearson r = 0.07) but there was fair correlation between video interpretation and bHIT ratings (Pearson r = 0.45).

Conclusion

Final year OTL-HNS residents in Canada are not adequately trained in performing the bHIT, though low interrater reliability may limit the evaluation of this bedside skill. Multiple choice examinations do not reflect bHIT skill. These findings have implications for development of competency-based curricula and evaluations in Canada in critical physical exam skills.

http://bit.ly/2Cxe0dO

Structure of Nano-sized CeO2 Materials: Combined Scattering and Spectroscopic Investigations

Marchbank, HR; Clark, AH; Hyde, TI; Playford, HY; Tucker, MG; Thompsett, D; Fisher, JM; ... Sankar, G; + view all Marchbank, HR; Clark, AH; Hyde, TI; Playford, HY; Tucker, MG; Thompsett, D; Fisher, JM; Chapman, KW; Beyer, KA; Monte, M; Longo, A; Sankar, G; - view fewer (2016) Structure of Nano-sized CeO2 Materials: Combined Scattering and Spectroscopic Investigations. ChemPhysChem , 17 (21) pp. 3494-3503. 10.1002/cphc.201600697 . Green open access

http://bit.ly/2FBmmVU

Sipho Gongxeka’s Skeem’ Saka: composing masculinity and protest in contemporary Soweto

Bonzon, J; (2019) Sipho Gongxeka's Skeem' Saka: composing masculinity and protest in contemporary Soweto. Object , 20 (20) pp. 9-32. 10.14324/111.2396-9008.036 . Green open access

http://bit.ly/2FGWMhm

Elucidation of thermally induced internal porosity in zinc oxide nanorods

Handoko, AD; Liew, L-L; Lin, M; Sankar, G; Du, Y; Su, H; Dong, Z; Handoko, AD; Liew, L-L; Lin, M; Sankar, G; Du, Y; Su, H; Dong, Z; Goh, GKL; - view fewer (2018) Elucidation of thermally induced internal porosity in zinc oxide nanorods. Nano Research , 11 (5) pp. 2412-2423. 10.1007/s12274-017-1862-2 .

http://bit.ly/2FBgThA

Very low depth whole genome sequencing in complex trait association studies

Gilly, A; Southam, L; Suveges, D; Kuchenbaecker, K; Moore, R; Melloni, GEM; Hatzikotoulas, K; ... Zeggini, E; + view all Gilly, A; Southam, L; Suveges, D; Kuchenbaecker, K; Moore, R; Melloni, GEM; Hatzikotoulas, K; Farmaki, A-E; Ritchie, G; Schwartzentruber, J; Danecek, P; Kilian, B; Pollard, MO; Ge, X; Tsafantakis, E; Dedoussis, G; Zeggini, E; - view fewer (2018) Very low depth whole genome sequencing in complex trait association studies. Bioinformatics 10.1093/bioinformatics/bty1032 . (In press). Green open access

http://bit.ly/2FGWx5W

On the synthesis and performance of hierarchical nanoporous TS-1 catalysts

Adedigba, A-L; Sankar, G; Catlow, CRA; Du, Y; Xi, S; Borgna, A; (2017) On the synthesis and performance of hierarchical nanoporous TS-1 catalysts. Microporous and Mesoporous Materials , 244 pp. 83-92. 10.1016/j.micromeso.2017.02.048 . Green open access

http://bit.ly/2Fyo2iV

PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28γ

Jonik-Nowak, B; Menneteau, T; Fesquet, D; Baldin, V; Bonne-Andrea, C; Méchali, F; Fabre, B; ... Coux, O; + view all Jonik-Nowak, B; Menneteau, T; Fesquet, D; Baldin, V; Bonne-Andrea, C; Méchali, F; Fabre, B; Boisguerin, P; de Rossi, S; Henriquet, C; Pugnière, M; Ducoux-Petit, M; Burlet-Schiltz, O; Lamond, AI; Fort, P; Boulon, S; Bousquet, M-P; Coux, O; - view fewer (2018) PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28γ. Proceedings of the National Academy of Sciences of the United States of America , 115 (28) E6477-E6486. 10.1073/pnas.1722299115 . Green open access

http://bit.ly/2FKkmtt

Using thematic analysis to explore symbolism in transport choice across national cultures

Ashmore, DP; Thoreau, R; Kwami, C; Christie, N; Tyler, NA; (2018) Using thematic analysis to explore symbolism in transport choice across national cultures. Transportation pp. 1-34. 10.1007/s11116-018-9902-7 . (In press).

http://bit.ly/2FwJCV7

Development of novel apoferritin formulations for antitumour benzothiazoles

Breen, A; Wells, G; Turyanska, L; Bradshaw, T; (2019) Development of novel apoferritin formulations for antitumour benzothiazoles. Cancer Reports , Article e1155. 10.1002/cnr2.1155 . (In press). Green open access

http://bit.ly/2FG6a4V

The symbolism of 'eco cars' across national cultures: Potential implications for policy formulation and transfer

Ashmore, DP; Pojani, D; Thoreau, R; Christie, N; Tyler, NA; (2018) The symbolism of 'eco cars' across national cultures: Potential implications for policy formulation and transfer. Transportation Research Part D: Transport and Environment , 63 pp. 560-575. 10.1016/j.trd.2018.06.024 .

http://bit.ly/2FwqvKA

Socio-spatial and temporal dimensions of transport equity for London's Night Time Economy

McArthur, JM; Robin, E; Smeds, E; (2019) Socio-spatial and temporal dimensions of transport equity for London's Night Time Economy. Transportation Research Part A: Policy and Practice (In press).

http://bit.ly/2FIS2HZ

Potential benefits of incorporating energy information when estimating attenuation from PET data

Brusaferri, L; Bousse, A; Efthimiou, N; Emond, E; Atkinson, D; Ourselin, S; Hutton, BF; ... Thielemans, K; + view all Brusaferri, L; Bousse, A; Efthimiou, N; Emond, E; Atkinson, D; Ourselin, S; Hutton, BF; Arridge, S; Thielemans, K; - view fewer (2018) Potential benefits of incorporating energy information when estimating attenuation from PET data. In: 2017 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC). IEEE Green open access

http://bit.ly/2FzUl0L

Novel methodology to discern predictors of remission and patterns of disease activity over time using rheumatoid arthritis clinical trials data

RA-MAP Consortium, .; (2018) Novel methodology to discern predictors of remission and patterns of disease activity over time using rheumatoid arthritis clinical trials data. RMD Open , 4 (2) , Article e000721. 10.1136/rmdopen-2018-000721 . Green open access

http://bit.ly/2FIY9fw

Why we need to view road safety through a public health lens?

Christie, N; (2017) Why we need to view road safety through a public health lens? Transport Reviews , 38 (2) pp. 139-141. 10.1080/01441647.2018.1411226 .

http://bit.ly/2FAkOez

A Longitudinal Investigation of the Relationship between Motivation and Late Second Language Speech Learning in Classroom Settings

Saito, K; Dewaele, J-M; Hanzawa, K; (2017) A Longitudinal Investigation of the Relationship between Motivation and Late Second Language Speech Learning in Classroom Settings. Language and Speech , 60 (4) pp. 614-632. 10.1177/0023830916687793 . Green open access

http://bit.ly/2FMyrGO

Is Vision Zero important for promoting health?

Christie, N; (2018) Is Vision Zero important for promoting health? Journal of Transport & Health , 9 pp. 5-6. 10.1016/j.jth.2018.05.006 .

http://bit.ly/2FynZDL

Global patterns of mortality in international migrants: a systematic review and meta-analysis

Aldridge, RW; Nellums, L; Bartlett, S; Barr, A; Patel, P; Burns, R; Hargreaves, S; ... Abubakar, I; + view all Aldridge, RW; Nellums, L; Bartlett, S; Barr, A; Patel, P; Burns, R; Hargreaves, S; Miranda, J; Tollman, S; Friedland, J; Abubakar, I; - view fewer (2018) Global patterns of mortality in international migrants: a systematic review and meta-analysis. The Lancet , 392 (10164) pp. 2553-2566. 10.1016/S0140-6736(18)32781-8 . Green open access

http://bit.ly/2FHFe4F

Managerial identity work in action: Formalised narratives and anecdotal stories of innovation

Sergeeva, N; Green, S; (2019) Managerial identity work in action: Formalised narratives and anecdotal stories of innovation. Construction Management and Economics (In press).

http://bit.ly/2FB4Jpd

Energy-Aware Routing in Software-Defined Network using Compression

Giroire, F; Huin, N; Moulierac, J; Truong, KP; (2018) Energy-Aware Routing in Software-Defined Network using Compression. The Computer Journal , 61 (10) pp. 1537-1556. 10.1093/comjnl/bxy029 . Green open access

http://bit.ly/2FMxZZ8

Resilience of the Eastern African electricity sector to climate driven changes in hydropower generation

Sridharan, V; Broad, OWT; Shivakumar, A; Howells, M; Boehlert, B; Groves, DG; Rogner, H-H; ... Cervigni, R; + view all Sridharan, V; Broad, OWT; Shivakumar, A; Howells, M; Boehlert, B; Groves, DG; Rogner, H-H; Taliotis, C; Neumann, JE; Strzepek, K; Lempert, R; Joyce, B; Huber-Lee, A; Cervigni, R; - view fewer (2019) Resilience of the Eastern African electricity sector to climate driven changes in hydropower generation. Nature Communications , 10 , Article 302. 10.1038/s41467-018-08275-7 . Green open access

http://bit.ly/2FCUBMC

Acoustic characteristics and learner profiles of low-, mid- and high-level second language fluency

Saito, Kazuya; Ilkan, Meltem; Magne, Vicktoria; Tran, Mai Ngoc; Suzuki, Shungo; (2018) Acoustic characteristics and learner profiles of low-, mid- and high-level second language fluency. Applied Psycholinguistics , 39 (3) pp. 593-617. 10.1017/S0142716417000571 . Green open access

http://bit.ly/2FNikcr

Pediatric Laryngeal Electromyography Technique for Vocal Fold Immobility Using Bipolar Double Hookwire Electrodes

Publication date: Available online 18 January 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Sarah N. Bowe, Carissa J. Wentland, Christopher J. Hartnick

Abstract

Vocal fold immobility (VFI) is a common cause of dysphonia and dysphagia in children. Laryngeal electromyography (LEMG) is an important adjunctive test in its diagnosis and treatment. In this study, we present an alternative technique in which bipolar double hookwire electrodes allow simultaneous placement and recordings from the bilateral thyroarytenoid and posterior cricoarytenoid muscles. Details of the technique are shown for a 5 y/o F with history of Neurofibromatosis Type 2 with left VFI and aspiration and dysphonia. This modified technique for pediatric LEMG has the potential to be a useful tool in predicting return of laryngeal function.

http://bit.ly/2FMuv90

Caregiver perception of speech quality in patients with ankyloglossia: comparison between surgery and non-treatment

Publication date: Available online 18 January 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Srihari Daggumati, Jason E. Cohn, Matthew J. Brennan, Marissa Evarts, Brian J. McKinnon, Alyssa R. Terk

Abstract

Objectives

Our objective was to determine if there are differences in caregiver perception of speech for patients that undergo frenulectomy compared to patients that were not surgically treated.

Introduction

Ankyloglossia is a controversial topic without standardized treatment guidelines. Although there have been several studies suggesting that breastfeeding does improve after frenulectomy, there is a paucity of literature that investigates the relationship between ankyloglossia and speech.

Methods

A retrospective chart review was conducted to identify patients with ankyloglossia. Patients were categorized into surgical treatment (frenulectomy) and non-treatment groups. Caregivers of both groups were contacted by phone and surveyed on speech quality and tongue mobility using Likert scores. Mann Whitney-U testing was used to determine if there were significant differences in perceived speech quality between the surgical and non-surgical groups.

Results

The caregivers of seventy-seven patients participated in the phone survey: 46 (60%) children in the surgical group and 31 (40%) children in the non-surgical group who participated in the phone survey. There were no differences in difficulty with speech (p=0.484) and tongue mobility (p=0.064) between the two groups. However, patients that underwent surgical intervention for ankyloglossia reported less difficulty with tongue tasks (p<0.001) compared to those who were not surgically treated. Additionally, 50% of patients that underwent surgery had a documented family history of ankyloglossia which was significantly higher than 16.1% in the non-surgical group (p=0.002).

Conclusions

It appears that children with ankyloglossia might have similar speech quality following frenulectomy in comparison to speech quality without treatment. Children who undergo frenulectomy may experience improvements in tongue tasks. This data should encourage further research on the management of speech concerns in children with ankyloglossia.

http://bit.ly/2Fzbyro

Editorial Board

Publication date: February 2019

Source: Archives of Oral Biology, Volume 98

Author(s):

http://bit.ly/2CwfOnD

Effect of Er,Cr:YSGG Laser Associated with Fluoride on the Control of Enamel Erosion Progression

Publication date: Available online 17 January 2019

Source: Archives of Oral Biology

Author(s): Vilmara Rocha Mendes da Silva, Ítallo Emídio Lira Viana, Raquel Marianna Lopes, Denise Maria Zezell, Taís Scaramucci, Ana Cecília Corrêa Aranha

Abstract

Objective

To evaluate the effect of Er,Cr:YSGG laser associated or not with acidulated phosphate fluoride (APF) on the control of enamel erosion progression. Design: Enamel slabs (4 mm × 4 mm×2 mm) from bovine incisors were flattened, polished, and received a tape on their test surfaces, leaving a 4 mm x 1 mm area exposed. Specimens were eroded (10 min in 1% citric acid solution) and randomly assigned into 8 experimental groups (n = 10): Control (no treatment); F (APF gel, 1.23% F, pH 3.6-3.9); Er,Cr:YSGG laser irradiation (P1: 0.25 W, 20 Hz, 2.8 J/cm², 56 W/cm²); Er,Cr:YSGG laser irradiation (P2: 0.50 W, 20 Hz, 5.7 J/cm², 113,6 W/cm²); Er,Cr:YSGG laser irradiation (P3: 0.75 W, 20 Hz, 8.5 J/cm², 170,4 W/cm²); F + Laser P1; F + Laser P2; F + Laser P3. Specimens were then subjected to erosive cycling (5 min immersion in 0.3% citric acid solution, followed by immersion in artificial saliva for 60 min; 4×/day for 5 days). At the end of cycling, surface loss (SL, in μm) was determined with optical profilometry. Selected specimens were further evaluated by environmental scanning electron microscopy (n = 3). Data were analyzed using Kruskal-Wallis and Tukey tests (α = 0.05). Results: Group F + Laser P2 had the lowest SL value, differing significantly from the control; however, with no significant difference from the other groups. All groups, except F + Laser P2, showed no significant difference in SL when compared with the control. An irregular and rough surface, suggestive of a melting action of laser, was observed on enamel in Laser P2 and F + Laser P2 groups. Conclusions: Association of the Er,Cr:YSGG laser in parameter 2 with fluoride was the only treatment capable of controlling the progression of enamel erosion.

http://bit.ly/2RAaGcu

Cellular senescence in dental pulp stem cells

Publication date: Available online 17 January 2019

Source: Archives of Oral Biology

Author(s): Christian Morsczeck

Abstract

Objective

This short review summarizes our current knowledge about dental stem cell aging and about possible targets for the regulation of cellular senescence.

Design

A literature search was performed using a combination of keywords, e.g., stem cells, replicative senescence, differentiation potential, dental pulp, dental follicle and periodontal ligament

Results

Previous studies have shown that cellular senescence occurs while the proliferation of dental stem cells. Moreover, the differentiation potential was significantly decreased in senescent stem cells and senescent cells secrete also factors that are harmful to the adjacent tissue cells. Moreover, many targets for the regulation of cellular senescence are considered; for example pathways related to the nutrient sensing such as the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway.

Conclusions

The regulation of cellular senescence will play a crucial role in the clinical use of stem cells. However, there is no cell culture protocol available that prevents dental stem cell senescence. Therefore, more knowledge about molecular processes in stem cells is needed before and after the induction of senescence.

http://bit.ly/2CxT3iP

Hydrochlorothiazid und nichtmelanozytärer Hautkrebs

http://bit.ly/2FI3943

Psychoonkologie in dermatologischen Praxen

Zusammenfassung

Hintergrund

Im nationalen Krebsplan ist eine psychoonkologische Betreuung fester Bestandteil einer umfassenden Betreuung von Krebspatienten. Dieses Ziel ist auch im Strategiepapier der Nationalen Versorgungskonferenz Hautkrebs enthalten. In zertifizierten Hautkrebszentren konnten die wesentlichen Voraussetzungen für eine psychoonkologische Versorgung geschaffen werden. Ein großer Anteil von Hautkrebspatienten wird jedoch in dermatologischen Praxen versorgt. Für dieses Versorgungssegment liegen bisher keine Daten zur psychoonkologischen Versorgung vor.

Material und Methoden

In einer deskriptiven Querschnittstudie in Form eines schriftlichen Surveys wurden niedergelassene Dermatologen zur psychoonkologischen Versorgung von Hautkrebspatienten im Erhebungszeitraum Oktober 2016 bis Februar 2017 befragt.

Ergebnisse

Den psychoonkologischen Fragebogen haben 171 Praxen beantwortet; 19,4 % der Praxen gaben einen onkologischen Schwerpunkt an. Die mittlere Anzahl jährlich betreuter Hautkrebspatienten wurde mit 554,3 ± 659,1 und die der Melanompatienten mit 62,4 ± 73,6 angegeben. Ein Großteil der Praxiskollegen schätzt den Anteil psychoonkologisch betreuungsbedürftiger Patienten gering ein (≤5 %). In 21,9 % der Praxen wird über psychoonkologische Unterstützungsangebote aktiv informiert; 26,1 % der Praxen kooperieren bezüglich psychoonkologischer Unterstützungsangebote mit anderen Einrichtungen; 29,3 % der Praxen haben Interesse an einem psychoonkologischen Versorgungskonzept.

Diskussion

In dermatologischen Praxen ist nur von gelegentlicher und teils defizitärer psychoonkologischer Versorgung und einer Zuweisung zu psychoonkologischen Einrichtungen auszugehen. Dies zeigt die Notwendigkeit einer Sensibilisierung für das Thema, um eine Integration der psychoonkologischen Beratung auch in der dermatologischen Routineversorgung zu ermöglichen.

http://bit.ly/2FyObOv

Luftverschmutzung und atopisches Ekzem

Zusammenfassung

Hintergrund

Unter zahlreichen Risikofaktoren für die Entstehung eines atopischen Ekzems (AE) wird neuerdings der Einfluss von Luftverschmutzung vermehrt diskutiert. Ein systematisches Review hierzu liegt aber bisher nicht vor.

Fragestellung

Welche Effekte von Außenluftverschmutzung (Partikel, Stickstoffoxide, Schwefeldioxid, Ozon oder allgemeine Straßenverkehrsemissionen) auf AE zeigen sich in einer systematischen Analyse verfügbarer umweltepidemiologischer Studien?

Methodik

Alle umweltepidemiologischen Studien zu AE und Luftverschmutzung aus der Literaturdatenbank PubMed wurden identifiziert, ihre wichtigsten Kenngrößen tabellarisch zusammengefasst, qualitativ nach Evidenzgraden beurteilt und beschrieben.

Ergebnisse

Es wurden 57 entsprechende Studien identifiziert. Nur in einer der 15 Querschnittstudien, bei denen die Exposition großräumig erfasst wurde, zeigte sich ein signifikanter Zusammenhang zwischen AE und Luftverschmutzung. Dagegen fanden sich signifikante positive Assoziationen von AE mit straßenverkehrsbedingten Emissionen – insbesondere aus LKWs – in 23 von 30 Studien mit kleinräumiger Expositionserfassung. Von diesen 30 Studien waren 14 Kohortenstudien (1-mal Erwachsene, 13-mal Geburtskohorten). Die einzige Kohortenstudie bei Erwachsenen zeigte eine Assoziation insbesondere mit einem intrinsischen AE. In ostasiatischen Geburtskohorten (alle in den letzten 3 Jahren veröffentlicht) war eine Verkehrsbelastung der Mutter während der Schwangerschaft mit einer erhöhten Inzidenz von AE beim Kind assoziiert. In den älteren Kohortenstudien aus Europa/USA war dies nicht so klar oder wurde nicht untersucht. In 5/5 Panelstudien (alle aus Korea) fand sich ein positiver Zusammenhang zwischen dem Schweregrad von Ekzem und der Außenluftbelastung.

Schlussfolgerung

In der systematischen Analyse umweltepidemiologischer Studien zeigte sich eine eher gute Evidenz dafür, dass Belastungen mit Straßenverkehrsemissionen, die kleinräumig variieren, die Prävalenz von AE erhöhen, während großräumige Belastung mit groben Partikeln (PM10) oder SO₂ keinen Einfluss zeigte. Unter pathophysiologischen Aspekten scheinen Verkehrsemissionen sowohl über Einflüsse auf die Hautbarriere als auch auf die Aktivierung von Immunreaktionen zu wirken.

http://bit.ly/2FJ5UlO

Ewing’s Sarcoma of the Sinonasal Tract: A Report of Two Challenging Cases

Abstract

Ewing's sarcoma (ES) is a malignant small round cell tumor that belongs to the primitive neuroectodermal tumor class. ES generally arises in the long bones of the extremities (skeletal form) and less frequently in the soft tissue of the trunk and extremities (extra-skeletal form). Sinonasal localization of ES is an extremely rare event. About 80% of the patients are less than 20 years old with the highest incidence in the second decade of life. The combination of histopathological examination and ancillary methods (such as immunohistochemistry and molecular genetics) is extremely important to establish the diagnosis of ES. The most effective treatment plan for ES includes a multidisciplinary approach with surgery, radiotherapy and chemotherapy. This is a report of two challenging cases of sinonasal ES in two different age groups. The first case is a 13-years old female patient who presented with right nasal obstruction, anosmia, intermittent epistaxis and hearing loss. The second case is a 24-years old male patient who presented with a history of right nasal obstruction, right eye pain and periorbital edema. We present these cases due to the rarity of the disease and the difficulty of diagnosis.

http://bit.ly/2ARXrcJ

Management des lokal fortgeschrittenen Zervixkarzinoms

Zusammenfassung

Das lokal fortgeschrittene Zervixkarzinom erfordert eine besonders intensive interdisziplinäre Absprache. In der Definition des Stadiums spielen neben der klassischen FIGO-Einteilung (FIGO: „Fédération Internationale de Gynécologie et d'Obstétrique") Risikofaktoren eine wichtige Rolle. Dabei ist der Lymphknotenstatus entscheidend. In frühen Stadien wird operativ vorgegangen, bei weiter fortgeschrittener Erkrankung bis hin zum Stadium IVA wird die Radiochemotherapie präferiert. In jedem Fall ist eine frühzeitige Besprechung innerhalb eines Tumorboards erforderlich. Kontroversen betreffen z. B. den Einsatz moderner bildgebender Verfahren, die Therapie bei befallenen paraaortalen Lymphknoten, den Stellenwert einer neoadjuvanten Chemotherapie und die Versuche, die klassische Radiochemotherapie mit Cisplatin zu intensivieren. Der Artikel gibt dazu einen Überblick, unter besonderer Berücksichtigung aktueller Studiendaten und unter Bezugnahme auf die derzeit gültigen Leitlinien.

http://bit.ly/2QXptZf

Ebi3 promotes T- and B-cell division and differentiation via STAT3

Publication date: March 2019

Source: Molecular Immunology, Volume 107

Author(s): Ning Ma, Ying Fang, Ruonan Xu, Bing Zhai, Chunmei Hou, Xiaoqian Wang, Zhenyu Jiang, Liang Wang, Qilin Liu, Gencheng Han, Renxi Wang

Abstract

Although sharing the same subunit Ebi3, IL-27 (p28/Ebi3) and IL-35 (p35/Ebi3) have different biological functions, suggesting that Ebi3 subunit may functions as a carrier. Our data demonstrated that activated T cells and B cells effectively up-regulated Ebi3 expression. In addition, Ebi3 effectively promoted T-cell activation and the differentiation of helper T 1 (Th1), Th17, and Foxp3⁺ regulatory T (Treg) cells induced by Th1, Th17, and Treg polarizing condition, respectively. Naturally, Ebi3 could promote B-cell activation and the production of CD138⁺ plasma cells (PC) induced by LPS. Conversely, neutralizing anti-Ebi3 antibody could significantly suppress T/B-cell activation and production of Th1, Th17, Tregs, and PC induced by Th1, Th17, Treg polarizing condition, and LPS, respectively. Furthermore, we found that Ebi3 time-dependently induced STAT3 activation in CD4⁺T cells and B cells. Conversely, STAT3^−/− effectively reduced Ebi3 expression and the production of Th1, Th17, Tregs, and plasma cells. Finally, we showed that gp130 but not IL-27Rα mediates Ebi3-induced STAT3 activation. These results suggest that Ebi3 promotes Th- and B-cell differentiation via gp130-STAT3 signaling pathway. Thus, autocrine Ebi3 may play an important role in the differentiation of Th and B cells and thus in infection, inflammation, and autoimmune disorders.

http://bit.ly/2FFFilo

Anagliptin ameliorates high glucose- induced endothelial dysfunction via suppression of NLRP3 inflammasome activation mediated by SIRT1

Publication date: March 2019

Source: Molecular Immunology, Volume 107

Author(s): Tiechao Jiang, Dongli Jiang, Lirong Zhang, Mei Ding, Hui Zhou

Abstract

High glucose- induced endothelial dysregulation has been recognized as an initiation of vascular complications in Type 2 diabetes mellitus (T2DM). Anagliptin is a novel licensed dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of T2DM. The effects of anagliptin in high glucose- induced endothelial dysfunction are less reported. In the current study, we found that treatment with anagliptin prevented high glucose- induced reduction of cell viability and increase in LDH release in human umbilical vein endothelial cells (HUVECs). Our results indicate that anagliptin- reduced high glucose- induced increase in mitochondrial ROS and NOX-4 expression. Additionally, anagliptin treatment inhibited high glucose- induced expressions of TXNIP in HUVECs. Importantly, anagliptin treatment downregulated high glucose- induced NLRP3 inflammasome activation, as evidenced by reducing the expressions of NLRP3, ASC, and cleaved caspase-1 (P10). Also, ELISA results demonstrate that anagliptin treatment significantly abolished high glucose- induced maturation of IL-1β and IL-18. Mechanistically, we found that anagliptin treatment restored high glucose- induced reduction of SIRT1 expression. Silencing of SIRT1 by transfection with SIRT1 siRNA abolished the inhibitory effects of anagliptin in NLRP3 inflammasome activation. These results display that anagliptin may confer protection against high glucose- induced endothelial injury via SIRT1-dependent inhibition of NLRP3 infammasome activation.

http://bit.ly/2FzHgEH

Apport de la microscopie confocale par réflectance et de l’OCT dans le diagnostic d’un carcinome basocellulaire nodulaire kystique

Publication date: Available online 17 January 2019

Source: Annales de Dermatologie et de Vénéréologie

Author(s): L. Huppert, E. Cinotti, C. Habougit, D. Grivet, L. Tognetti, A. Gâillot, F. Cambazard, P. Rubegni, J.L. Perrot

http://bit.ly/2sxQOYn

Inexpensive and Non-Fluorinated Superhydrophobic Concrete Coating for Anti-Icing and Anti-Corrosion

Lu, Y; (2019) Inexpensive and Non-Fluorinated Superhydrophobic Concrete Coating for Anti-Icing and Anti-Corrosion. Journal of Colloid and Interface Science 10.1016/j.jcis.2019.01.014 .

http://bit.ly/2QXGGll

Development of Comprehensibility and its Linguistic Correlates: A Longitudinal Study of Video-Mediated Telecollaboration

Akiyama, Y; Saito, K; (2016) Development of Comprehensibility and its Linguistic Correlates: A Longitudinal Study of Video-Mediated Telecollaboration. Modern Language Journal , 100 (3) pp. 585-609. 10.1111/modl.12338 . Green open access

http://bit.ly/2W0eP82

'The Italian Factor': Representations of Italy in Selma Lagerlöf's Legends and Hans Ernst Kinck's Novellas

Carbone, E; (2019) 'The Italian Factor': Representations of Italy in Selma Lagerlöf's Legends and Hans Ernst Kinck's Novellas. Scandinavica , 57 (2) pp. 61-90. (In press).

http://bit.ly/2QW3C4I

Cold sensing by NaV1.8-positive and NaV1.8-negative sensory neurons

Luiz, AP; Macdonald, DI; Santana-Varela, S; Millet, Q; Sikandar, S; Wood, JN; Emery, EC; (2019) Cold sensing by NaV1.8-positive and NaV1.8-negative sensory neurons. Proceedings of the National Academy of Sciences of The United States of America (In press).

http://bit.ly/2W2kKtd

Investigation of the pentathiepin functionality as an inhibitor of Feline Immunodeficiency Virus (FIV) via a potential zinc ejection mechanism, as a model for HIV infection

Asquith, C; laitinen, T; Konstantinova, L; Tizzard, G; Poso, A; Rakitin, O; Hofmann-Lehmann, R; Asquith, C; laitinen, T; Konstantinova, L; Tizzard, G; Poso, A; Rakitin, O; Hofmann-Lehmann, R; Hilton, ST; - view fewer (2019) Investigation of the pentathiepin functionality as an inhibitor of Feline Immunodeficiency Virus (FIV) via a potential zinc ejection mechanism, as a model for HIV infection. ChemMedChem 10.1002/cmdc.201800718 . (In press).

http://bit.ly/2QUlhd3

¿“Forjando Patria”? Las políticas del Estado revolucionario y el ocaso de los vínculos intercomunales coras en la Sierra del Nayar

Morris, N; (2019) ¿"Forjando Patria"? Las políticas del Estado revolucionario y el ocaso de los vínculos intercomunales coras en la Sierra del Nayar. Relaciones Estudios de Historia y Sociedad 10.24901/rehs.v39i156.316 . (In press).

http://bit.ly/2W3y6Fp

Joint Material and Illumination Estimation from Photo Sets in the Wild

Wang, TY; Ritschel, T; Mitra, NJ; (2018) Joint Material and Illumination Estimation from Photo Sets in the Wild. In: 2018 International Conference on 3D Vision (3DV). (pp. pp. 22-31). IEEE Green open access

http://bit.ly/2QY1R6W

Devil's staircases without particle-hole symmetry

(2018) Devil's staircases without particle-hole symmetry. Physical Review B , 97 (7) , Article 075117. 10.1103/PhysRevB.97.075117 . Green open access

http://bit.ly/2VYjnMh

Foreign language enjoyment and anxiety: The effect of teacher and learner variables

Dewaele, JM; Witney, J; Saito, K; Dewaele, L; (2017) Foreign language enjoyment and anxiety: The effect of teacher and learner variables. Language Teaching Research , 22 (6) pp. 676-697. 10.1177/1362168817692161 . Green open access

http://bit.ly/2QY1Kbw

Effects of recasts and prompts on L2 pronunciation development: Teaching English /ɹ/ to Korean adult EFL learners

Gooch, R; Saito, K; Lyster, R; (2016) Effects of recasts and prompts on L2 pronunciation development: Teaching English /ɹ/ to Korean adult EFL learners. System , 60 pp. 117-127. 10.1016/j.system.2016.06.007 . Green open access

http://bit.ly/2W1f1nC

Exploring the relationship between productive vocabulary knowledge and second language oral ability

(2016) Exploring the relationship between productive vocabulary knowledge and second language oral ability. Language Learning Journal , 47 pp. 64-75. 10.1080/09571736.2016.1191527 . Green open access

http://bit.ly/2QY1xoK

Eigenstate thermalization hypothesis in quantum dimer models

(2017) Eigenstate thermalization hypothesis in quantum dimer models. Physical Review B , 96 (11) 10.1103/PhysRevB.96.115140 . Green open access

http://bit.ly/2VZme7r

On the k-Anonymization of Time-Varying and Multi-Layer Social Graphs

Rossi, L; Musolesi, M; Torsello, A; (2015) On the k-Anonymization of Time-Varying and Multi-Layer Social Graphs. In: Cha, M and Mascolo, C and Sandvig, C, (eds.) (Proceedings) The Ninth International Conference on Web and Social Media (ICWSM). (pp. pp. 377-386). AAAI Press Green open access

http://bit.ly/2QWK6F9

Privacy and the City: User Identification and Location Semantics in Location-Based Social Networks

Rossi, L; Williams, MJ; Stich, C; Musolesi, M; (2015) Privacy and the City: User Identification and Location Semantics in Location-Based Social Networks. In: Cha, M and Mascolo, C and Sandvig, C, (eds.) (Proceedings) The Ninth International Conference on Web and Social Media (ICWSM). (pp. pp. 387-396). AAAI Press Green open access

http://bit.ly/2W3y4xh

Keep Your Friends Close and Your Facebook Friends Closer: A Multiplex Network Approach to the Analysis of Offline and Online Social Ties

Hristova, D; Musolesi, M; Mascolo, C; (2014) Keep Your Friends Close and Your Facebook Friends Closer: A Multiplex Network Approach to the Analysis of Offline and Online Social Ties. In: Adar, E and Resnick, P and Choudhury, MD and Hogan, B and Oh, AH, (eds.) Proceedings of the Eighth International AAAI Conference on Weblogs and Social Media. (pp. pp. 206-215). The AAAI Press Green open access

http://bit.ly/2QZJvm6

Monte Carlo Convolution for Learning on Non-Uniformly Sampled Point Clouds

Hermosilla, P; Ritschel, T; Vázquez, P-P; Vinacua, A; Ropinski, T; (2018) Monte Carlo Convolution for Learning on Non-Uniformly Sampled Point Clouds. ACM Transactions on Graphics , 37 (6) , Article 235. 10.1145/3272127.3275110 . Green open access

http://bit.ly/2VYjfMN

Microbial population heterogeneity versus bioreactor heterogeneity: Evaluation of Redox Sensor Green as an exogenous metabolic biosensor

Baert, J; Delepierre, A; Telek, S; Fickers, P; Toye, D; Delamotte, A; Lara, AR; ... Delvigne, F; + view all Baert, J; Delepierre, A; Telek, S; Fickers, P; Toye, D; Delamotte, A; Lara, AR; Jaen, KE; Gosset, G; Jensen, PR; Delvigne, F; - view fewer (2016) Microbial population heterogeneity versus bioreactor heterogeneity: Evaluation of Redox Sensor Green as an exogenous metabolic biosensor. Engineering in Life Sciences , 16 (7) pp. 643-651. 10.1002/elsc.201500149 . Green open access

http://bit.ly/2QYqGj2

Site-selective protein conjugation at histidine

Peciak, K; Laurine, E; Tommasi, R; Choi, J-W; Brocchini, S; (2019) Site-selective protein conjugation at histidine. Chemical Science , 10 (2) pp. 427-439. 10.1039/c8sc03355b . Green open access

http://bit.ly/2W3mKBi

Shale gas well blowout fire and explosion modelling

Buaprommart, K; Mahgerefteh, H; Martynov, S; Striolo, A; (2019) Shale gas well blowout fire and explosion modelling. Applied Thermal Engineering , 149 pp. 1061-1068. 10.1016/j.applthermaleng.2018.12.105 .

http://bit.ly/2QVX5a3

The impact of habitat quality inside protected areas on distribution of the Dominican Republic’s last endemic non-volant land mammals

Kennerley, RJ; Nicoll, MAC; Young, RP; Turvey, ST; Nuñez-Miño, JM; Brocca, JL; Butler, SJ; (2019) The impact of habitat quality inside protected areas on distribution of the Dominican Republic's last endemic non-volant land mammals. Journal of Mammalogy (In press).

http://bit.ly/2VYVVOO

Perioperative Teaching and Feedback: How are we doing in Canadian OTL-HNS programs?

Discrepancies between resident and faculty perceptions regarding optimal teaching and feedback during surgery are well known but these differences have not yet been described in Otolaryngology - Head and Neck ...

http://bit.ly/2TWAmN2

Double-strand break repair through homologous recombination in autosomal recessive BCL10 deficiency

Publication date: Available online 18 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Sonia García-Gómez, Rebeca Chaparro, Amin Safa, Ana Van Den Rym, Rubén Martinez-Barricarte, Lazaro Lorenzo, Silvia Sánchez-Ramón, Victor Toledano, Carolina Cubillos-Zapata, Eduardo López-Collazo, Maria Dolores Martín-Arranz, Eduardo Martín-Arranz, Maria Vela, Pablo Gonzalez-Navarro, Antonio Pérez-Martínez, Jean-Laurent Casanova, Maria José Recio, Rebeca Pérez de Diego

http://bit.ly/2RT7HuZ

Challenges in Assessing the Efficacy of Systemic Corticosteroids for Severe Wheezing Episodes in Preschool Children

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Theresa W. Guilbert, Leonard B. Bacharier, David T. Mauger, Wanda Phipatanakul, Stanley J. Szefler, Susan Boehmer, Avraham Beigelman, Anne M. Fitzpatrick, Daniel J. Jackson, Sachin N. Baxi, Mindy Benson, Carey-Ann D. Burnham, Michael D. Cabana, Mario Castro, James F. Chmiel, Ronina Covar, Michael Daines, Jonathan M. Gaffin, Deborah A. Gentile, Fernando Holguin

Summary

This letter addresses the controversial issue of the use of oral corticosteroids during wheezing exacerbations in preschool-aged children by demonstrating findings of a prematurely terminated multi-center clinical trial, discussing lessons learned, and suggesting future directions.

http://bit.ly/2HgvT6p

Allergen challenge increases capsaicin evoked cough responses in allergic asthma

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Imran Satia, Richard Watson, Tara Scime, Rachel J. Dockry, Shilpi Sen, James W. Ford, Patrick D. Mitchell, Stephen J. Fowler, Gail M. Gauvreau, Paul M. O'Byrne, Jaclyn A. Smith

Abstract

Background

Cough is a common and troublesome symptom in asthma but little is known about the neuronal pathways that trigger cough. The mechanisms by which airway inflammation, airway hyper-responsiveness and variable airflow obstruction cause cough are unclear.

Objective

To investigate the effects of allergen exposure on cough reflex sensitivity.

Methods

We performed a nine visit, randomised, single-blind, placebo-controlled, two-way cross-over study comparing cough responses to inhaled capsaicin in mild atopic asthmatics after allergen challenge compared with diluent control. Full dose capsaicin challenge was performed at screening to determine the excitatory dose evoking half the maximum cough response (ED₅₀), which was subsequently administered at 30mins and 24-hours after inhaled allergen/diluent challenge. Spontaneous coughing was measured for 24-hours after allergen/diluent. Methacholine challenge and induced sputum was performed before and after allergen/diluent challenge.

Results

Twelve steroid naïve subjects completed the study (6 female, mean age 34.8yrs) Allergen inhalation caused both an early (mean 38.2±S.D.13.0%) and late (23.7±13.2%) fall in FEV₁ and an increase in sputum eosinophils 24-hours later [median 1.9(IQR 0.8-5.8) % post-diluent to 14.9(8.9-37.3) % post-allergen, p=0.005]. There was also an increase in capsaicin evoked coughs after allergen exposure compared to diluent at both 30 mins [geometric mean coughs 21.9(95% C.I 16.5-29.20) versus 12.1(8.3-17.7), p<0.001], and at 24hrs [geometric mean coughs 16.1(95% C.I 11.3-23.0) versus 9.8(6.1-15.8), p=0.001]. Allergen exposure was also associated with an increase in spontaneous coughs over 24-hours.

Conclusion

Allergen induced bronchoconstriction and airway eosinophilia results in increased cough reflex sensitivity to capsaicin associated with an increase in 24-hour spontaneous coughing.

Graphical abstract

http://bit.ly/2RYBAda

Hematopoietic stem cell transplantation for CD40 ligand deficiency: results from an EBMT/ESID-IEWP-SCETIDE-PIDTC Study

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Francesca Ferrua, Stefania Galimberti, Virginie Courteille, Mary Anne Slatter, Claire Booth, Despina Moshous, Benedicte Neven, Stephane Blanche, Alexandra Laberko, Anna Shcherbina, Dmitry Balashov, Elena Soncini, Fulvio Porta, Hamoud Al-Mousa, Bandar Al-Saud, Hasan Al-Dhekri, Rand Arnaout, Renata Formankova, Yves Bertrand, Andrzej Lange

Abstract

Background

CD40 ligand (CD40L) deficiency, an X-linked primary immunodeficiency, causes recurrent sinopulmonary, Pneumocystis and Cryptosporidium infections. Long-term survival with supportive therapy is poor. Currently, the only curative treatment is hematopoietic stem cell transplantation (HSCT).

Objective

We performed an international collaborative study to improve patients' management, aiming to individualize risk factors and determine optimal HSCT characteristics.

Methods

We retrospectively collected data on 130 patients who underwent HSCT for CD40L deficiency between 1993-2015. We analyzed outcome and variables relevance with respect to survival and cure.

Results

Overall survival (OS), event-free survival (EFS) and disease-free survival (DFS) were 78.2%, 58.1% and 72.3% 5 years post-HSCT. Results were better in transplants performed ≥2000 and in children <10 years old at HSCT. Pre-existing organ damage negatively influenced outcome. Sclerosing cholangitis was the most important risk factor. After 2000, superior OS was achieved with matched donors. Use of myeloablative regimens and HSCT ≤2 years from diagnosis associated with higher OS and DFS. EFS was best with matched sibling donors, myeloablative conditioning (MAC) and bone marrow-derived stem cells. Most rejections occurred after reduced intensity or non-myeloablative conditioning, which associated with poor donor cell engraftment. Mortality occurred mainly early after HSCT, predominantly from infections. Among survivors who ceased immunoglobulin replacement, T-lymphocyte chimerism was ≥50% donor in 85.2%.

Conclusion

HSCT is curative in CD40L deficiency, with improved outcome if performed before organ damage development. MAC is associated with better OS, EFS and DFS. Prospective studies are required to compare risks of HSCT with those of life-long supportive therapy.

Graphical abstract

http://bit.ly/2Hjxqsv

Hypoxia Enhances CD8+ Tc2 Dependent Airway Hyperresponsiveness and Inflammation Through Hypoxia Inducible Factor 1α

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Fangkun Ning, Katsuyuki Takeda, Michaela Schedel, Joanne Domenico, Anthony Joetham, Erwin W. Gelfand

Abstract

Background

CD8+ T cells (Tc2) become potent, steroid-insensitive pathogenic effector cells in experimental asthma undergoing transcriptional reprogramming to IL-13 production in the presence of IL-4. However, no studies have described the effects of hypoxia exposure on Tc2 differentiation.

Objective

We determined the effects of hypoxia exposure on IL-13-producing CD8+ Tc2 cells.

Methods

CD8+ transgenic OT1 cells, differentiated with IL-2 and IL-4 (Tc2 cells) were exposed to normoxia (21% O₂) or hypoxia (3% O₂) and IL-13 production in vitro was monitored. Following differentiation under these conditions, cells were adoptively transferred into CD8-deficient mice and lung allergic responses including airway hyperesponsiveness to inhaled methacholine were assessed. The effects of pharmacologic inhibitors of hypoxia inducible factor 1α (HIF-1α) and HIF-2α were determined as were responses in HIF-1α-deficient OT1 cells.

Results

Under hypoxic conditioning, CD8+ Tc2 differentiation was significantly enhanced with increased numbers of IL-13+ T cells and increased production of IL-13 in vitro. Adoptive transfer of Tc2 cells differentiated under hypoxia restored lung allergic responses in sensitized and challenged CD8-deficient recipients to a greater degree than seen in recipients of Tc2 cells differentiated under normoxia. Pharmacologic inhibition of HIF-1α or genetic manipulation to reduce HIF-1α expression reduced the hypoxia-enhanced differentiation of Tc2 cells, IL-13 production, and the capacity of transferred cells to restore lung allergic responses in vivo. IL-4-dependent, hypoxia-mediated increases in HIF-1α and Tc2 differentiation were shown to be mediated through activation of JAK1/3 kinase and GATA3.

Conclusions

Hypoxia enhances CD8+ Tc2-dependent airway hyperresponsiveness and inflammation through activation of HIF-1α. These findings coupled with the known insensitivity of CD8+ T cells to corticosteroids suggests that activation of the IL-4-HIF-1α-IL-13 axis may play a role in the development of steroid-refractory asthma.

Graphical abstract

http://bit.ly/2RRvPOG

Vitamin D is no substitute for the sun

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Yoshiaki Matsushima, Kento Mizutani, Yukie Yamaguchi, Keiichi Yamanaka

http://bit.ly/2Hm9p3R

Dermatomyositis associated with omalizumab therapy for severe asthma: a case report

Omalizumab is a humanized monoclonal antibody widely used for treatment of persistent allergic asthma and antihistamine-refractory chronic urticaria. Immediate adverse events to omalizumab are well characteriz...

http://bit.ly/2W45ig3

A retrospective study of clinical features of cough variant asthma in Chinese adults

Clinical features of cough variant asthma (CVA) in Chinese adults are largely uncertain.

http://bit.ly/2QX6TQZ

Severe rhabdomyolysis developing in an advanced melanoma patient treated by pembrolizumab followed by dabrafenib trametinib combined therapy

http://bit.ly/2DiMans

An analysis of RUC methodology for determining the RVU valuation of sinus surgery

Background

The Relative Value Scale Update Committee, commonly known as the RUC, is responsible for defining the value of Current Procedural Terminology (CPT) codes. The RUC process uses survey responses reporting operative times to determine procedure reimbursement, but it is limited by low response rates, small sample sizes, and unclear generalizability of the results. By comparing actual reported intraoperative times to the times determined by the RUC process, in this study we sought to assess the performance of RUC methodology in endoscopic sinus surgery (ESS).

Methods

The ESS CPT codes that were reassessed in 2016 using the RUC method were examined in this study. Intraoperative time data for these codes were retrospectively collected from 14 medical facilities, using time stamps in the electronic health record. These actual intraoperative times were compared with the 2016 RUC survey results.

Results

There were 143 RUC physician survey responses and 446 actual procedure times included in the final analysis. There was significant variability within the RUC survey responses (ie, unilateral anterior ethmoidectomy times varied from 5 to 90 minutes). There was also a significant difference between the RUC survey results and actual intraoperative times (p < 0.001). For example, frontal sinus surgeries showed a particularly poor correlation between actual and RUC times.

Conclusion

The RUC process may not accurately estimate or value actual intraoperative times. Real‐world intraoperative times are readily accessible and may be an alternative to survey‐based methodology in the future.

http://bit.ly/2QTQflu

Multiple melanocytic nevi restricted to mycosis fungoides patches in pediatric and young‐adult patients. The potential role of local immunosuppression

Abstract

We described the development of multiple melanocytic nevi within long‐standing MF patches in four young patients. Mycosis fungoides (MF) patches are characterized by a regulatory‐like cytokine profile leading to local immune suppression. The proliferation of nevomelanocytes is regulated by cellular senescence mechanisms mediated by immune system. The immunosuppressive effect of MF infiltrate in conjunction with the systemic effect of treatments may play a specific role in the nevomelanogenesis of the patients herein described.

http://bit.ly/2U4sNnJ

Tropisetron via α7 nicotinic acetylcholine receptor suppresses tumor necrosis factor‐α‐mediated cell responses of human keratinocytes

Abstract

Tropisetron is a serotonin receptor (5‐HT‐R)‐modulating agent and approved as an antiemetic for patients undergoing chemotherapy. In the gut it acts via specific serotonin receptors, 5‐HT₃‐R, to elicit its beneficial effects against nausea. We investigated whether tropisetron can affect inflammatory cell responses of human primary epidermal keratinocytes (NHK) which are key cells in the regulation of skin homeostasis. Tropisetron significantly and dose‐dependently suppressed tumor necrosis factor (TNF)‐α‐mediated mRNA expression and protein secretion of interleukin (IL)‐6 and IL‐8 in these cells. This effect of tropisetron was independent of p65/NF‐κB as shown by various NF‐κB signal transduction read‐outs. Importantly, the anti‐inflammatory tropisetron effect on NHK was neither mediated by 5‐HT₃‐R nor 5‐HT₄‐R since these receptors were absent in NHK. In contrast, NHK expressed α7 nicotinic acetylcholine receptors (α7nAchR) which previously were found to bind tropisetron. The α7nAchR antagonist α‐bungarotoxin neutralized whereas AR‐R17779, a specific α7nAchR agonist, mimicked the suppressive effect of tropisetron on TNF‐α‐mediated IL‐6 and IL‐8 expression in NHK. Our findings suggest that tropisetron and probably other α7nAchR‐activating agents could be useful for the future therapy of inflammatory skin diseases.

This article is protected by copyright. All rights reserved.

http://bit.ly/2QTZz8R

Skin damage by tropospheric ozone

Abstract

Tropospheric (ground level) ozone (O₃) is a secondary pollutant, emerging from other pollutants in the sunshine. Exposure to O₃ correlates with higher pulmonary and cardiovascular mortality and affects reproductive health and the central nervous system acutely and chronically. Skin might be a potentially overlooked target organ of ambient O₃. The experimental evidence suggests a positive correlation of O₃ exposure with oxidative damage, impaired antioxidant defence and proinflammatory response in the skin. In time series studies it was observed that acute rises in O₃ levels correlated with seeking medical help for skin conditions; however, whether these findings are specific to O₃, is not yet clear. There is preliminary epidemiological evidence that long-term exposure to O₃ is associated with premature skin aging. This finding was independent of co-exposure to other environmental factors affecting skin (e.g. ultraviolet radiation and air pollution). As concentrations of O₃ are rising in many regions of the world, adverse cutaneous effects of O₃ present a relevant public health concern.

http://bit.ly/2FMIPib

Usefulness of a specialized « tattoo » consultation in a tertiary care hospital: a one‐year experience

Abstract

Seventeen percent of the French have tattoos [1]. The frequency of tattoo complications ranges broadly from 2 to 27% [2‐4]. The management of these complications may leave the physician puzzled. Besides, physicians could feel uncomfortable at properly advising patients with chronic conditions who wish to have a tattoo [5]. We report the one‐year experience of a monthly consultation in Bichat‐Claude Bernard University Hospital in Paris [6].

This article is protected by copyright. All rights reserved.

http://bit.ly/2QWPIyZ

Complete response is reversible upon vismodegib withdrawal and re‐inducible upon vismodegib re‐administration in a patient with locally advanced BCC

Abstract

Recurrence after the discontinuation of Hedgehog pathway inhibitor (HPI) treatment in responding patients with advanced basal cell carcinoma (BCC) is an emerging clinical challenge. A 54‐year old female patient presented in 2016 with an histologically proven BCC on the right peri‐auricular area, extending to the ear, that was present for 6 years (Figure 1, upper panel). Due to considerable deformity expected with surgery, the patient was treated with vismodegib 150 mg/day.

This article is protected by copyright. All rights reserved.

http://bit.ly/2W1ANaP

Cervical cutaneous sclerosis: the stomach is not far from the skin

Abstract

Here in, we report a particular case presenting an erythematous and indurated plaque of the neck that has revealed gastric linitis plastic (GLP).

An 80‐year‐old man presented to the Department of Dermatology in November 2015 with a 2‐month history of a sclerotic inflammatory infiltration of the skin located on the anterior cervical region (Figure 1a, b) associated with a general impaired condition. Medical history revealed a partial gastrectomy for peptic ulcer 30 years ago. A punch biopsy specimen was performed, and the associated histologic findings are shown in the Figure 2a, b, c.

This article is protected by copyright. All rights reserved.

http://bit.ly/2QZGzWN

Polymorphisms associated with anti‐TNF drugs response in patients with psoriasis and psoriatic arthritis

Abstract

Psoriatic arthritis (PsA) has been classified as an inflammatory musculoskeletal disease with a strong genetic background. Although anti‐TNF drugs are effective for PsA and moderate‐to‐severe psoriasis up to 30‐40% of patients do not respond to them. We evaluated the possible association between 13 single‐nucleotide polymorphisms (SNPs) and anti‐TNF drug response in psoriasis and PsA patients.

This article is protected by copyright. All rights reserved.

http://bit.ly/2VW40nv

Dental metal allergy is not the main cause of palmoplantar Pustulosis

Abstract

Metal allergy as a possible cause of Palmoplantar pustulosis (PPP) is a controversial issue, ^1‐6 and in particular there is insufficient evidence that removal of dental metal leads to resolution of PPP.　This study involved 257 PPP patients (86 males and 171 females, 20‐78 years old) who underwent patch testing for metal allergy between 2000 and 2014 at Niigata University Medical and Dental Hospital. Patients who had suffered repeated eruptions of non‐infectious pustules on the palms and soles were diagnosed as having PPP. Arthralgia was observed in 21% of the patients and 75.1% (193 patients) had a history of smoking.

This article is protected by copyright. All rights reserved.

http://bit.ly/2QVoUiU

Li‐Fraumeni syndrome presenting as cutaneous melanoma in a child: case report and review of literature

Abstract

Li‐Fraumeni syndrome (LFS) is a rare, autosomal dominant inherited cancer predisposition syndrome associated with germline mutation of the TP53 tumor suppressor gene [1, 2]. It is traditionally characterized by early‐onset of multiple primary tumors: sarcoma, breast cancer, brain tumor, leukemia, and adrenocortical carcinoma. [2] Classically, LFS is clinically diagnosed when a patient present with sarcoma diagnosed before age 45 years with a first‐degree relative with any cancer before age 45 years and an additional first‐ or second‐degree relative with any cancer before age 45 years or a sarcoma at any age.

This article is protected by copyright. All rights reserved.

http://bit.ly/2W0Xdc3

Saint Valentine's melanoma

Abstract

On Saint Valentine's day, a couple of spouses sought our consultation to evaluate their nevi. Clinical examination surprisingly revealed in both of them an atypical pigmented lesion of the right shoulder, that dermoscopically showed clear‐cut melanoma features (fig. 1). They immediately underwent surgical excision and histopathology confirmed respectively a 1.3 mm Breslow thickness melanoma for the husband and a 0.8 mm Breslow thickness melanoma for his wife.

This article is protected by copyright. All rights reserved.

http://bit.ly/2QWp0Xw

Mycosis fungoides presenting as vulvar plaques

Abstract

Mycosis fungoides (MF), the most frequent type of cutaneous T‐cell lymphoma, is characterized in the early stage by patches and plaques that predominate in sun‐protected areas. MF is rarely associated with vulvar involvement. We report two cases of MF with predominant vulvar lesions.

An 81‐year‐old female presented with a 2‐year history of erythematous and erosive tongue lesions and an ulcerated infiltrated lesion of the left cheek mucosa. The physical examination also revealed isolated violaceous plaques of the inguinal folds and vulva (Figure 1A).

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Study of Human Leukocyte Antigen (HLA) in 13 cases of familial frontal fibrosing alopecia: CYP21A2 gene p.V281L mutation from congenital adrenal hyperplasia linked to HLA class I haplotype HLA‐A*33:01; B*14:02; C*08:02 as a genetic marker

Abstract

Background/Objectives

The aetiology of frontal fibrosing alopecia is unknown, and its genetic aspect remains uncharacterised. The aim of this report is to elucidate if major histocompatibility complex is associated with familial frontal fibrosing alopecia.

Methods

A case–control study was performed of 13 patients with frontal fibrosing alopecia belonging to six families. Their human leukocyte antigen profiles were compared to the data of 636 healthy controls without frontal fibrosing alopecia. Patients underwent high‐resolution genomic typing for human leukocyte antigen class I and II loci by PCR‐SSO for Luminex. In addition, CYP21A2 gene (major histocompatibility complex class III) mutations were detected by PCR‐SSO on strips.

Results

61.5% of patients shared CYP21A2 gene p.V281L linked to the F16A human leukocyte antigen class I haplotype (HLA‐A*33:01; B*14:02; C*08:02; Pc < 0.000001). The patients F16A‐negative shared other human leukocyte antigen class I haplotypes: Y16A (3/13) and S26 (2/13).

Conclusion

CYP21A2 gene p.V281L mutation can be used as a genetic marker for susceptibility to familial frontal fibrosing alopecia. Both the linkage of the mutation to F16A and the fact that F16A‐negative patients share other human leukocyte antigen class I haplotype, point to an antigen‐driven mechanism in susceptible patients with these haplotypes.

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Deep fungal infection caused by Trichophyton rubrum after heart transplantation: A case report with dermoscopy

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Granulomatous mycosis fungoides responsive to acitretin and UVA1 treatment

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PLACK syndrome shows remarkable phenotypic homogeneity

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Nicastrin haploinsufficiency alters expression of type I interferon‐stimulated genes: the relationship to familial hidradenitis suppurativa

Summary

Background

Hidradenitis suppurativa (HS), also called acne inversa, is a chronic skin disease. The symptoms can be severe, and include intensely painful nodules and abscesses in apocrine‐gland rich inverse skin, such as the buttocks, under the arms and in the groin. Autosomal dominant forms of HS exist, but are rare. Some of these kindred have heterozygous loss‐of‐function rare variants in the γ‐secretase complex component nicastrin (NCSTN).

Aim

To investigate the effect of NCSTN haploinsufficiency on human keratinocytes and assess potential mechanisms for lesion development.

Methods

NCSTN was knocked down using a small hairpin RNA construct in both a keratinocyte cell line (HEK001) and an embryonic kidney cell line (HEK293), and differential gene expression was assessed using RNA microarray. Using the HEK293 line, a heterozygous deletion of NCSTN was created with CRISPR/Cas9 genome editing, and nuclear factor kappa B activity was assessed using a luciferase reporter.

Results

Compared with controls, the keratinocyte NCSTN knockdown cell line showed a significantly increased expression of genes related to the type I interferon response pathway. Both HEK001 and HEK293 knockdowns demonstrated evidence of altered growth. There was a small but significant increase in nuclear factor kappa B signalling in response to tumour necrosis factor treatment in HEK293 cells genome‐edited for reduced NCSTN.

Conclusions

Our data suggest a role for increased keratinocyte inflammatory responsiveness in familial HS. Confirming this phenotype and characterizing additional effects in different cell types will require study beyond cell lines, such as in primary cells and tissues.

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Lipoedematous scalp

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Psoriasis induced by dupilumab therapy

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Acne conglobata and necrotizing scleritis: a previously unreported association

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Dermoscopy of naevi in patients with oculocutaneous albinism

Summary

Oculocutaneous albinism (OCA) increases predisposition to skin malignancies. Nevertheless, the differential diagnosis between melanoma and naevi in patients with OCA is still challenging, because pigmentary lesions have rarely been described in this population. We aimed to describe the dermoscopic patterns of naevi in patients with OCA. We prospectively evaluated 83 naevi from 37 patients with OCA in a single centre in Brazil. Lesions were analysed by eye and by dermoscopy and were grouped by dermoscopic pattern. Eight main patterns were identified: homogeneous structureless pattern (n = 28; 33.7%), globular pattern (n = 27; 32.5%), reticular pattern (n = 8; 9.6%), peripheral reticular pattern with central hypopigmentation (n = 8; 9.6%), peripheral globules (n = 8; 9.6%), irregular brown globules with pink background (n = 2; 2.4%), reticular globular disorganized pattern (n = 1; 1.2%) and peripheral reticular globular with central hypopigmentation (n = 1; 1.2%). We found previously undescribed dermoscopic patterns in patients with OCA, in addition to confirming previously described patterns. These descriptions may help the understanding of pigmented naevi in patients with OCA.

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Malignant peripheral nerve sheath tumor of the transverse colon with peritoneal metastasis: a case report

Malignant peripheral nerve sheath tumors are malignant tumors arising from a peripheral nerve or displaying nerve sheath differentiation. Gastrointestinal malignant peripheral nerve sheath tumors are rare and ...

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British Association of Dermatologists guidelines for the safe and effective prescribing of oral ciclosporin in dermatology 2018

Abstract

The overall objective of the guideline is to provide up‐to‐date, evidence‐based recommendations for the safe and effective use of oral ciclosporin in the field of dermatology. The document aims to:

offer an appraisal of all relevant literature since 1970 focusing on any key developments

address important, practical clinical questions relating to the primary guideline objective

provide guideline recommendations and, where appropriate, with some health economic implications

discuss potential developments and future directions

The guideline is presented as a detailed review with highlighted recommendations for practical use in the clinic (see section 14), in addition to an updated Patient Information Leaflet (PIL; available on the BAD website, www.bad.org.uk/leaflets).

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