Medicine by Sfakianakis Alexandros: 02/06/19

Aflatoxin is a potent toxin produced by Aspergillus flavus Link:Fr, an opportunistic ear-rot pathogen of maize (Zea mays L. subsp. Mays). Prior to the discovery of aflatoxin, A. flavus was considered a minor pathogen and was not a priority for maize breeders or pathologists. Aflatoxin was discovered in England in 1961 following an epidemic in poultry. By the early 1970s, surveys of agricultural commodities in the USA found that maize produced in the Southeast was especially vulnerable to aflatoxin contamination. Aflatoxin contamination was initially treated as a post-harvest issue, but pre-harvest contamination was proven by 1975. Pre-harvest contamination meant that genetically based host-plant resistance was a possible solution. The potential magnitude of the problem became apparent in 1977 when the southeastern US maize crop suffered epidemic aflatoxin contamination. The first experiment demonstrating the heritability of host-plant resistance to aflatoxin accumulation was published in 1978. These events combined to make breeding for reduced aflatoxin contamination both a high priority and a rational breeding objective. This review surveys the early scientific literature in order to place research on the genetics of aflatoxin accumulation in maize into historical context. It tells the story of how multi-disciplinary research began with veterinary diseases of unknown etiology and resulted in host-plant resistance to a previously minor plant pathogen becoming a central public sector breeding objective.

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Prevalence and Multivariable Factors Associated With Preoperative Cognitive Impairment in Outpatient Surgery in the United States

Preoperative cognitive impairment increases the risk of adverse events after surgery but its prevalence in outpatient surgery has not been defined. We aimed to determine the prevalence and multivariable factors associated with cognitive impairment in individuals who present for outpatient surgery. We used data from the Health and Retirement Study, a longitudinal panel survey of older Americans. Of 1836 participants who reported having outpatient surgery, we found that 16.1% had evidence of cognitive impairment. Significant multivariable factors associated with preoperative cognitive impairment included non-Hispanic African American race, prior stroke, preoperative functional dependence, and lower socioeconomic status and education level. Accepted for publication December 18, 2018. Funding: This work was supported by a University of Pennsylvania Institute on Aging pilot grant. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Timothy G. Gaulton, MD, MSc, Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, 310 Blockley Hall, 423 Guardian Dr, Philadelphia, PA 19104. Address e-mail to timothy.gaulton2@uphs.upenn.edu. © 2019 International Anesthesia Research Society

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High-Flow Nasal Oxygen Improves Safe Apnea Time in Morbidly Obese Patients Undergoing General Anesthesia: A Randomized Controlled Trial

BACKGROUND: Morbidly obese patients undergoing general anesthesia are at risk of hypoxemia during anesthesia induction. High-flow nasal oxygenation use during anesthesia induction prolongs safe apnea time in nonobese surgical patients. The primary objective of our study was to compare safe apnea time, between patients given high-flow nasal oxygenation or conventional facemask oxygenation during anesthesia induction, in morbidly obese surgical patients. METHODS: Research ethics board approval was obtained. Elective surgical patients ≥18 years with body mass index ≥40 kg·m−2 were included. Patients with severe comorbidity, gastric reflux disease, known difficult airway, or nasal obstruction were excluded. After obtaining informed consent patients were randomized. In the intervention (high-flow nasal oxygenation) group, preoxygenation was provided by 100% nasal oxygen for 3 minutes at 40 L·minute−1; in the control group, preoxygenation was delivered using a facemask with 100% oxygen, targeting end-tidal O2 >85%. Anesthesia was induced with propofol, remifentanil, and rocuronium. Bag-mask ventilation was not performed. At 2 minutes after rocuronium, videolaryngoscopy was performed. If the laryngoscopy grade was I or II, laryngoscope was left in place and the study was continued; if grade III or IV was observed, the patient was excluded from the study. During the apnea period, high-flow nasal oxygenation patients received nasal oxygen at 60 L·minute−1; control group patients received no supplemental oxygen. The primary outcome, safe apnea time, was reached when oxygen saturation measured by pulse oximetry (SpO2) fell to 95% or maximum 6 minutes of apnea. The patient was then intubated. T tests and χ2 analyses were used to compare groups. P

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In Response

No abstract available

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A Multivariable Model Predictive of Unplanned Postoperative Intubation in Infant Surgical Patients

BACKGROUND: Unplanned postoperative intubation is an important quality indicator, and is associated with significantly increased mortality in children. Infant patients are more likely than older pediatric patients to experience unplanned postoperative intubation, yet the literature provides few characterizations of this outcome in our youngest patients. The objective of this study was to identify risk factors for unplanned postoperative intubation and to develop a scoring system to predict this complication in infants undergoing major surgical procedures. METHODS: In this retrospective cohort study, The National Surgical Quality Improvement Program-Pediatric database was surveyed for all infants who underwent noncardiac surgery between January 1, 2012 and December 31, 2015 (derivation cohort, n = 56,962) and between January 1 and December 31, 2016 (validation cohort, n = 20,559). Demographic and perioperative clinical characteristics were examined in association with our primary outcome of unplanned postoperative intubation within 30 days of surgery. Risk factors were analyzed in the derivation cohort (2012–2015 data) using multivariable logistic regression with stepwise selection. Parameters from the final model were used to create a scoring system for predicting unplanned postoperative intubation. Data from the validation cohort were utilized to assess the performance of the scoring system using the area under the receiver operating characteristic curve. RESULTS: In the derivation cohort, 2.2% of the infants experienced unplanned postoperative intubation within 30 days of surgery. Of the 14 risk factors identified in multivariable analysis, 10 (age, prematurity, American Society of Anesthesiologists physical status, inpatient status, operative time >120 minutes, cardiac disease, malignancy, hematologic disorder, oxygen supplementation, and nutritional support) were included in the final multivariable logistic regression model to create the risk score. The area under the receiver operating characteristic curve of the final model was 0.86 (95% CI, 0.85–0.87) for the derivation cohort and 0.83 (95% CI, 0.82–0.85) for the validation cohort. CONCLUSIONS: About 1 in 50 infants undergoing major surgical procedures experiences unplanned postoperative intubation. Our scoring system based on routinely collected perioperative assessment data can predict risk in infants with good accuracy. Further investigation should assess the clinical utility of the scoring system for risk stratification and improvement in perioperative care quality and patient outcomes. Accepted for publication December 20, 2018. Funding: L.D.E. is supported by an institutional training grant from the National Institutes of Health, T32GM008464-26. M.K. is supported by the National Center for Advancing Translational Sciences, National Institutes of Health through Grant Number KL2TR001874. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://bit.ly/KegmMq). Reprints will not be available from the authors. Address correspondence to Lisa D. Eisler, MD, Department of Anesthesiology, Columbia University Medical Center, 622 W 168th St, PH 5, Suite 505C, New York, NY 10032. Address e-mail to LDL2113@cumc.columbia.edu. © 2019 International Anesthesia Research Society

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Cataract Surgery: When the Eyes Are Bigger Than the Stomach

No abstract available

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Editorial by US Food and Drug Administration Attorney Fails to Address Core and Ongoing Issues Seen With Vasopressin Market

No abstract available

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Perioperative Care for Adolescents Undergoing Major Surgery: A Biopsychosocial Conceptual Framework

No abstract available

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American Society for Enhanced Recovery and Perioperative Quality Initiative-4 Joint Consensus Statement on Persistent Postoperative Opioid Use: Definition, Incidence, Risk Factors, and Health Care System Initiatives

Persistent postoperative opioid use is thought to contribute to the ongoing opioid epidemic in the United States. However, efforts to study and address the issue have been stymied by the lack of a standard definition, which has also hampered efforts to measure the incidence of and risk factors for persistent postoperative opioid use. The objective of this systematic review is to (1) determine a clinically relevant definition of persistent postoperative opioid use, and (2) characterize its incidence and risk factors for several common surgeries. Our approach leveraged a group of international experts from the Perioperative Quality Initiative-4, a consensus-building conference that included representation from anesthesiology, surgery, and nursing. A search of the medical literature yielded 46 articles addressing persistent postoperative opioid use in adults after arthroplasty, abdominopelvic surgery, spine surgery, thoracic surgery, mastectomy, and thoracic surgery. In opioid-naive patients, the overall incidence ranged from 2% to 6% based on moderate-level evidence. However, patients who use opioids preoperatively had an incidence of >30%. Preoperative opioid use, depression, factors associated with the diagnosis of substance use disorder, preoperative pain, and tobacco use were reported risk factors. In addition, while anxiety, sex, and psychotropic prescription are associated with persistent postoperative opioid use, these reports are based on lower level evidence. While few articles addressed the health policy or prescriber characteristics that influence persistent postoperative opioid use, efforts to modify prescriber behaviors and health system characteristics are likely to have success in reducing persistent postoperative opioid use. Accepted for publication October 16, 2018. The authors declare no conflicts of interest. Funding: The PeriOperative Quality Initiative (POQI)-4 consensus conference was supported by unrestricted educational grants from the American Society for Enhanced Recovery (ASER) and the POQI, which have received grants from Baxter, Bev MD, Cadence, Cheetah Medical, Edwards, Heron Pharmaceutical, Mallinckrodt, Medtronic, Merck, Pacira, and Trevena. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://bit.ly/KegmMq). Please see Supplemental Digital Content, Appendix 1, http://bit.ly/2GxzQ4N, for a list of the POQI-4 Workgroup members. Reprints will not be available from the authors. Address correspondence to Michael L. Kent, MD, Department of Anesthesiology, Duke University Medical Center, 3094 #4, Durham, NC 27710. Address e-mail to Michael.kent@duke.edu. © 2019 International Anesthesia Research Society

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I Tweet, Therefore I Learn: An Analysis of Twitter Use Across Anesthesiology Conferences

BACKGROUND: Twitter in anesthesiology conferences promotes rapid science dissemination, global audience participation, and real-time updates of simultaneous sessions. We designed this study to determine if an association exists between conference attendance/registration and 4 defined Twitter metrics. METHODS: Using publicly available data through the Symplur Healthcare Hashtags Project and the Symplur Signals, we collected data on total tweets, impressions, retweets, and replies as 4 primary outcome metrics for all registered anesthesiology conferences occurring from May 1, 2016 to April 30, 2017. The number of Twitter participants, defined as users who contributed a tweet, retweet, or reply 3 days before through 3 days after the conference, was collected. We also collected influencer data as determined by mentions (number of times a user is referenced). Two authors independently verified the categories for influencers assigned by Symplur. Conference demographic data were obtained by e-mail inquiries. Associations between meeting attendees/registrants and Twitter metrics, between Twitter participants and the metrics, and between physician influencers and Twitter participants were tested using Spearman rho. RESULTS: Fourteen conferences with 63,180 tweets were included. With the American Society of Anesthesiologists annual meeting included, the correlations between meeting attendance/registration and total tweets (rs = 0.588; P = .074), impressions (rs = 0.527; P = .117), and retweets (rs = 0.539; P = .108) were not statistically significant; for replies, it was moderately positive (rs = 0.648; P = .043). Without the American Society of Anesthesiologists annual meeting, total tweets (rs = 0.433; P = .244), impressions (rs = 0.350; P = .356), retweets (rs = 0.367; P = .332), and replies (rs = 0.517; P = .154) were not statistically significant. Secondary outcomes include a highly positive correlation between Twitter participation and total tweets (rs = 0.855; P

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Contemplating Our Maternity Care Crisis in the United States: Reflections of an Obstetrician Anesthesiologist

No abstract available

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Questions About the Study by Said Et Al

No abstract available

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Arterial thrombosis as primary presentation of endogenous Cushings syndrome

Cushing's syndrome is known to present with a characteristic set of clinical manifestations and complications, well described in literature. However, hypercoagulability remains an under recognised entity in Cushing's syndrome. A 31-year-old woman from Southern India presented with history of fever, left upper quadrant pain and progressive breathing difficulty for 3 weeks. Clinical examination revealed discriminatory features of Cushing's syndrome. Laboratory investigations showed biochemical features of endogenous ACTH-dependent Cushing's syndrome. Imaging of the abdomen revealed splenic collection, left-sided empyema and extensive arterial thrombosis. Gadolinium enhanced dynamic MRI of the pituitary gland revealed no evidence of an adenoma while a Ga-68 DOTATATE positron emission tomography CT scan ruled out an ectopic Cushing's. A diagnosis of endogenous Cushing's syndrome causing a prothrombotic state with extensive arterial thrombosis was made. She was initiated on oral anticoagulation and oral ketoconazole for medical adrenal suppression. She subsequently underwent bilateral adrenalectomy and was well at follow-up.

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High tibial osteotomy in combination with arthroscopic abrasion arthroplasty and autologous adipose-derived mesenchymal stem cell therapy in the treatment of advanced knee osteoarthritis

Osteoarthritis is a progressive and debilitating condition. An increasing number of total knee replacements are being performed under the age of 65. Improved understanding of the action of mesenchymal stem cells (MSC) has seen renewed interest in their role in cartilage repair. A 43-year-old man presented with grade IV medial compartment knee osteoarthritis. The patient underwent high tibial osteotomy (HTO) and arthroscopic abrasion arthroplasty in combination with adipose-derived MSC therapy. The patient reported improvement in pain and function as measured by validated outcome scores. Repeat MRI including T2 mapping techniques showed hyaline-like cartilage regeneration. This case highlights the potential benefit of surgical interventions including HTO in combination with MSC therapy in early-onset severe osteoarthritis. This technique may considerably delay or prevent the need for total knee replacement in young patients. Further controlled trials are needed to confirm the reproducibility of this outcome.

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Intramural oesophageal abscess: an unusual complication of tonsillitis

Tonsillitis is an extremely common condition, usually it is self-limiting, of viral origin, and managed conservatively in general practice. Rarely patients require inpatient management, usually when bacterial infection is present or when the cause is virulent organisms such as Epstein Barr virus. Complications can be divided into non-suppurative; sepsis, scarlet fever, rheumatic fever, glomerulonephritis and Lemierres disease, and suppurative; quinsy, parapharyngeal abscess and retropharyngeal abscess, respectively. Anecdotally, there is concern that modern medical practice that counsels vigilance against overuse of antibiotics, could lead to increased complications of tonsillitis. We report a case of an otherwise healthy man who presented with dysphagia, odynophagia and neck pain following a sore throat. Despite antibiotic treatment he developed an intramural oesophageal abscess, to our knowledge, an unreported complication of tonsillitis.

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Pneumomediastinum, ST elevation and urgent cardiac catheterisation: a crucial triad?

Pneumomediastinum (PNMD) entails the presence of air or other gas in the mediastinum and is also known as mediastinal emphysema. PNMD may cause a wide variety of signs and symptoms, as well as ECG abnormality, including ST segment changes. We present a 56-year-old man admitted to our hospital after a facial trauma. After undergoing tracheostomy, he complained of chest discomfort. A chest X-ray in the posteroanterior view showed PNMD, and an ECG was suggestive of inferior-lateral wall myocardial infarction. An urgent cardiac catheterisation identified a critical obstruction at the origin of the right coronary artery. Following a balloon angioplasty, chest discomfort continued; and the ECG ST segments did not show any dynamic change during the subsequent 72 hours. We urge clinicians to perform a comprehensive workup for every patient presenting with PNMD and ST segment changes, to prevent unnecessary invasive procedures.

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Pins and needles in the groin: an incidental finding of retained needle fragments in an intravenous drug user

A female intravenous drug user was reviewed in A&E following a deliberate overdose. After claiming to have swallowed a razor blade, an abdominal radiograph was performed; this showed a linear metallic density projected over the right side of the pelvis, eventually identified as a needle fragment. Subsequent CT imaging revealed three additional needles situated within the groin. Duplex assessment also identified bilateral arteriovenous fistulae. The patient remained asymptomatic and was managed conservatively. She could recall several occasions when a needle had broken while injecting. This scenario was more likely if the needle had been used many times previously, causing it to become blunt and bent. There are cases reported of adverse patient outcomes secondary to broken needle fragments but awareness among medical professionals remains poor.

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Sharp Foreign Bodies of the Aero-Digestive Tract: Endoscopic Removal by the ‘Kangaroo’ Technique

Abstract

Removal of sharp foreign bodies in the aero-digestive tract may inflict iatrogenic damage to the esophagus, trachea or other vital structures in case of impalement. We describe the 'Kangaroo' technique for safe and effective removal of sharp objects from the upper aero-digestive tracts. Index Case 1: 1-year old boy presented to us with an open (un)safety-pin lodged in the upper esophagus. The technique of removal of the pin by the Kangaroo technique, along-with the mechanics of en-pouching the (un)safety-pin has been described. Index Case 2: 8 years old boy presented with accidental aspiration of a razor blade. The removal of the blade from his trachea was executed by the Kangaroo technique. The Kangaroo technique is described for safe endoscopic extraction of sharp foreign body from the aero-digestive tract while protecting the surrounding tissues, to maintain control of the object during extraction and to avoid causing iatrogenic damage by enclosing the foreign body in a 'kangaroo pouch'. The advantages and limitations of the technique have been discussed. The Kangaroo technique is safe, effective and reproducible way to effect removal of sharp object from the aerodigestive tract while preventing iatrogenic injury to the surrounding organs.

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Laminin-511 Supplementation Enhances Stem Cell Localization with Suppression in the Decline of Cardiac Function in Acute Infarct Rats

Background. The extracellular matrix (ECM), in particular, basement membrane components such as laminins (LMs), is essential for stem cell differentiation and self-renewal. LM511 and LM221 are the main ECM components of the epicardium, where stem cells were abundant. Here, we examined whether LMs affected the regeneration process by modulating stem cell activities. Methods. In vitro, adhesive and proliferative activities of mesenchymal stem cells (MSCs) were evaluated on LM511 and LM221. To examine the effects of LMs in vivo, we established an acute myocardial infarction (MI) model by ligation of the proximal part of the left anterior descending artery at the height of the left atrial appendage and then placed atelocollagen sheets with or without LM511 and LM221 over the anterolateral surface of the left ventricular wall. Four or eight weeks later, cardiac function, histology, and cytokine expressions were analyzed. Results. MSCs showed greater proliferation and adhesive properties on LM511 than on LM221. In vivo, at four weeks, isolectin B4 (ILB4)-positive cells were significantly higher in the LM511-transplanted group than in the control group. Moreover, some ILB4-positive cells expressed both platelet-derived growth factor receptor α and CD90, suggesting that LM511 enhanced MSC recruitment and attachment at the implanted site. After eight weeks, these cells were more abundant than at 4 weeks. Transplantation with LM511-conjugated sheets increased the expression of cardioprotective and angiogenic factors. Conclusion. Transplantation with LM511-conjugated sheets enhanced MSC localization to the implantation site and modulated stem cells activities, leading to angiogenesis in acute MI rat models. Disclosures: The authors disclose no conflict of interest. Funding: This study was supported in part by the New Energy and Industrial Technology Development Organization. *Corresponding author: Professor Yoshiki Sawa, Chairman for Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: +81-6-6879-3154, Fax: +81-6-6879-3163, E-mail: sawa-p@surg1.med.osaka-u.ac.jp Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Sharp Foreign Bodies of the Aero-Digestive Tract: Endoscopic Removal by the ‘Kangaroo’ Technique

Abstract

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Flow-controlled ventilation during ear, nose and throat surgery: A prospective observational study

BACKGROUND Flow-controlled ventilation (FCV) is a new mechanical ventilation mode that maintains constant flow during inspiration and expiration with standard tidal volumes via cuffed narrow-bore endotracheal tubes. Originating in manually operated 'expiratory ventilation assistance', FCV extends this technique by automatic control of airway flow, monitoring of intratracheal pressure and control of peak inspiratory pressure and end-expiratory pressure. FCV has not yet been described in a clinical study. OBJECTIVE The aim of this study was to provide an initial assessment of FCV in mechanically ventilated patients undergoing ear, nose and throat surgery and evaluate its potential for future use. DESIGN An observational study. SETTING Two German academic medical centres from 24 November 2017 to 09 January 2018. PATIENTS Consecutive patients (≥ 18 years) scheduled for elective ear, nose and throat surgery. Exclusion criteria were planned laser surgery, intended fibreoptic awake intubation, emergency procedures, increased risk of aspiration, American Society of Anesthesiologists (ASA) physical status more than III and chronic obstructive pulmonary disease classified as GOLD stage more than II. INTERVENTION Peri-operative use of FCV provided by a new type of ventilator (Evone) via a narrow-bore endotracheal tube (Tritube). MAIN OUTCOME MEASURES Minute volume, respiratory rate, intratidal tracheal pressure amplitude (Δp) and end-tidal CO2 (PetCO2) were recorded every 5 min. All adverse events were noted. Data are presented as median [IQR]. RESULTS Sixteen patients provided 15 evaluable data sets. A minute volume of 5.0 [4.4 to 6.4] l min−1 and a respiratory rate of 9 [8 to 11] min−1 generated a PetCO2 of 4.9 [4.8 to 5.0] kPa. Δp was 10 [9 to 12] cmH2O. Five adverse events were recorded: a tube obstruction due to airway secretions and four tube dislocations (two attributed to coughing, two not study-related). CONCLUSION FCV achieves adequate PetCO2 levels with minute volume and Δp in the normal range. Tritube's high flow resistance may increase the likelihood of tube dislocations if the patient coughs. Although further evaluation is necessary, FCV provides a new option for short-term mechanical ventilation. The successful operation of FCV with narrow-bore tubes contributes to the armamentarium for airway management. TRIAL REGISTRATION DRKS00013312 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://bit.ly/OBJ4xP Correspondence to Dr. Johannes Schmidt, Department of Anaesthesiology and Critical Care, Medical Centre – University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany Tel: +49 761 270 26390; e-mail: johannes.schmidt@uniklinik-freiburg.de Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://bit.ly/2ylyqmW). © 2019 European Society of Anaesthesiology

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Pre-operative assessment of 30-day mortality risk after major surgery: the role of the quick sequential organ failure assessment: A retrospective observational study

BACKGROUND The quick Sequential Organ Failure Assessment (qSOFA) is intended for the assessment of the prognosis and risk of sepsis. It may also help predict the mortality risk of nonseptic patients. OBJECTIVE This study investigated the relationship between pre-operative qSOFA scores and 30-day mortality after major surgery. It also evaluated the predictive value of qSOFA scores combined with the American Society of Anesthesiologists (ASA) physical status and Charlson comorbidity index (CCI). DESIGN A retrospective observational study. SETTING Single tertiary academic hospital. PATIENTS Medical records of patients who underwent major surgery (estimated blood loss >500 ml; surgery time >2 h) between January 2010 and December 2017 were examined. MAIN OUTCOME MEASURES The qSOFA score was measured within 24 h before surgery, and its association with 30-day mortality was analysed using multivariable logistic regression. A receiver-operating characteristic curve analysis was used to investigate the predictive power of the pre-operative qSOFA scores combined with the ASA physical status and with CCI. RESULTS A total of 6336 patients were included in the final analysis, and 91 (1.4%) died within 30 days. The multivariable logistic regression analysis including all covariates indicated that 30-day mortality was 2.43-times higher for the score 1 group than for the score 0 group (P = 0.002), and it was 3.54-times higher for the score at least 2 group than for the score 0 group (P

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‘May you live in interesting times’: blessing or curse for an intensivist?

No abstract available

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Editorial

I would like to extend my warmest New Year's greetings to all our readers as we commence the 31st volume and 30th year of publishing International Immunology. As we acknowledge and celebrate this particular milestone in the journal's history, I am very glad to be able to report on some good news from an eventful 2018. Last year saw International Immunology's Impact Factor rise to 5.189; the journal's highest Impact Factor to date and the first time it has risen above five. Several of the most highly cited papers which contributed to the Impact Factor were from our Special Issue on Antibody-Targeted Therapy, highlighting the global attention that this exciting field of research is currently receiving (1).

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In This Issue

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Vancomycin-associated Drug-Induced Hypersensitivity Syndrome (DIHS)

While hypersensitivity reactions are well-characterized for certain medications, vancomycin-associated drug-induced hypersensitivity syndrome (DIHS), or drug reaction with eosinophilia and systemic symptoms (DRESS), has yet to be defined.

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Corrigendum to 'Abstract 7058' [J Am Acad Dermatol (2018) AB112]

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Reply to: Comment on “Oral diabetes medications other than dipeptidyl peptidase-4 inhibitors are not associated with bullous pemphigoid: A Finnish nationwide case control study” and a case report of glucagon-like peptide-1 receptor agonist induced bullous pemphigoid

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Disposable paper cup as a cheap and ready to use stencil for spot cryo treatment

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Overall and Subgroup Prevalence of Pyoderma Gangrenosum Among Patients with Hidradenitis Suppurativa: a population based analysis in the United States

Hidradenitis suppurativa (HS) and pyoderma gangrenosum (PG) are reported to coexist, although prevalence of PG among HS patients has not been systematically evaluated.

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Abnormal T-cell phenotype in episodic angioedema with hypereosinophilia (Gleich’s syndrome): frequency, clinical implication and prognosis

Episodic Angioedema with eosinophilia (EAE, Gleich's syndrome) is a rare disorder consisting of recurrent episodes of angioedema, hypereosinophilia and frequent elevated serum Immunoglobin M.

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An effective, low-cost technique for photograph and video capture, wireless transmission, and quality assurance assessments for dermatopathology, anatomic pathology, and Mohs micrographic surgery

Dermatopathology, like clinical dermatology, is dependent on effective teaching, mentoring, and quality assurance steps. The advent of digital cameras has allowed dermatologists to easily share clinical images around the world, but expanding this technology to histopathology has been fraught with logistical challenges. Using a standard binocular microscope precludes the ability of the dermatopathologist to easily share live or stored images of glass slides, while privacy considerations and the irreplaceability of slides limit the ability to share original material for quality assurance purposes, and multiheaded microscopes with specialized video camera arrays cost many thousands of dollars.

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“Oral diabetes medications other than dipeptidyl peptidase 4 inhibitors are not associated with bullous pemphigoid: A Finnish nationwide case-control study”

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4 tips for airway management mastery

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Successful airway management is the culmination of preparation, practice and technique mastery

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Trends in Gender of Speakers at the American Academy of Dermatology Annual Meeting, 2010-2018

This retrospective review of American Academy of Dermatology Annual Meeting data for even years between 2010 and 2018 was performed to identify the number of female speakers and associated presentation times.

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Mohs Appropriate Use Criteria for Superficial Basal Cell Carcinoma—Reply

In Reply We thank Drs Montuno and Coldiron, Kantor, and MacFarlane and Perlis for their comments on our Viewpoint. As our colleagues understand, the Mohs appropriate use criteria (MAUC) were created to limit use of Mohs surgery (MS) when simpler treatments would be more appropriate. Our Viewpoint was written with this in mind, reinforcing the importance of MS for more complex tumors, while emphasizing that primary superficial basal cell carcinoma (sBCC) can generally be treated more efficiently and less expensively with simple excision and curettage alone or combined with other modalities.

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Representation of Women Among Physician Authors of Perspectives in High-Impact Dermatology Journals

This cross-sectional, descriptive study analyzes the number of women among physician first authors of articles published in the Journal of the American Academy of Dermatology and JAMA Dermatology across a 5-year period.

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Mohs Appropriate Use Criteria for Primary Superficial Basal Cell Carcinoma

To the Editor Appropriate patient care relies on many factors, including data and judgment. Steinman and colleagues contend that the biological behavior of superficial basal cell carcinomas (sBCCs) should lead to their reclassification by the Mohs surgery appropriate use criteria (MAUC) as "uncertain" or "inappropriate" for Mohs surgery (MS). This type of discussion of hypotheses is essential to optimizing patient care. At its inception, the MAUC were intended to evolve as increasing empirical evidence became available.

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Nonmelanoma Skin Cancer Incidence by Treatment Modality in Recipients of Multiple Kidney Transplants

This study uses Irish national registry data to characterize variation in nonmelanoma skin cancer incidence by treatment modality among patients receiving multiple kidney transplants.

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Mohs Appropriate Use Criteria for Superficial Basal Cell Carcinoma

To the Editor I read with great interest the Viewpoint by Steinman and colleagues on treating superficial basal cell carcinoma (sBCC) with Mohs surgery. The authors rightly point to the paucity of evidence regarding sBCC management, though this limitation applies not just to sBCC but to most other nonmelanoma skin cancers as well.

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Percentage of Women in the Dermatology Workforce Presenting at American Academy of Dermatology Annual Meetings

This study assesses the percentage of female speakers at American Academy of Dermatology conferences from 1992 through 2017 and compares it with the overall percentages of board-certified female dermatologists.

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Mohs Appropriate Use Criteria for Superficial Basal Cell Carcinoma

To the Editor We read with interest the Viewpoint by Steinman and colleagues suggesting a reevaluation of appropriate use criteria for Mohs micrographic surgery (MMS) with respect to primary superficial basal cell carcinoma (sBCC). We must note that MMS is only 1 means of margin control of skin cancers, and perhaps the Viewpoint title would more accurately read "Reevaluation of Excisional Surgery for Primary Basal Cell Carcinoma."

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Pityriasis Rubra Pilaris

This Patient Page describes pityriasis rubra pilaris

http://bit.ly/2BpdFdt

Gender Equity in Clinical Dermatology

It is not news that medicine struggles to achieve gender equity, particularly in leadership, academics, and research. In an analysis of more than 90 000 academics in 2014, only 12% of women were full professors compared with 29% of men. Even when accounting for experience, productivity, specialty, and age, women were still statistically significantly less likely to be full professors. Women are so scarce in senior leadership positions that chairs of academic departments are more likely to be men with mustaches than to be women. Women in medicine also report high levels of discrimination. Junior faculty women receive less start-up support, and women are more likely than men to leave academics. Salaries are lower for women, even when adjusting for specialty, rank, leadership, publications, and research time. Women speakers at grand rounds are introduced informally statistically significantly more often than their male peers.

http://bit.ly/2TA1EsJ

Re: “Association Between Primary Hypothyroidism and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis” by Mantovani et al. (Thyroid 2018;28:1270–1284)

Thyroid, Ahead of Print.

http://bit.ly/2WKe4jE

Metabolic Obesity Phenotypes and Thyroid Cancer Risk: A Cohort Study

Thyroid, Ahead of Print.

http://bit.ly/2RJkGLw

The Role of Sub-mental Ultrasonography in Diagnosing Obstructive Sleep Apnea and Its Correlation With Subjective Scales

Conditions: Obstructive Sleep Apnea; Diagnostic Imaging; Ultrasound
Intervention: Diagnostic Test: Sub-mental ultrasonography
Sponsor: Bartin State Hospital
Recruiting

http://bit.ly/2TAvJZ4

Team-based Ergonomics Educational Model for Workplace WELLNESS Improvement: A Pilot Study

Conditions: MSDs; Muscle Pain
Intervention: Behavioral: stretching exercises
Sponsor: Milton S. Hershey Medical Center
Not yet recruiting

http://bit.ly/2BkSYzy

Validation of Smartphone App for Head and Neck Cancer Control and Patient Support

Condition: Head Neck Cancer
Intervention: Other: Virtual Coach
Sponsors: Vibrent Health; Stanford University; Johns Hopkins University; Massachusetts General Hospital
Not yet recruiting

http://bit.ly/2Tzwm5r

A Study of pING-hHER3FL Vaccine in Cancer Patients WITH ADVANCED MALIGNANCIES

Condition: Advanced Cancer
Intervention: Biological: pING-hHER3FL
Sponsor: Herbert Lyerly
Not yet recruiting

http://bit.ly/2BkSRnC

Einführung der neuen Rubrik „OP-Techniken“

http://bit.ly/2GeaOYN

Hot Topic: Schilddrüse

http://bit.ly/2MTqKR0

Quality of life in Swedish children receiving grommets – An analysis of pre- and postoperative results based on a national quality register

Publication date: Available online 6 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Job van Brink, Marie Gisselsson-Solen

Abstract

Background

Otitis media with effusion (OME) and recurrent otitis media (rAOM) are two common diagnoses in childhood, both of which are treated with grommets, or ventilation tubes. It is known that affected children have a worse quality of life (QoL), and various questionnaires have been used to evaluate this. The national Swedish quality register for grommet insertions contains some QoL questions that have hitherto never been analysed.

Methods

Data from 2010 to 2016 was extracted from the register and analysed with regards to QoL questions, reasons for surgery, hearing levels and number of AOM episodes.

Results

Preoperative QoL data was available for 3835 children. Before surgery, most parents felt that the QoL of their children was negatively affected by the ear disease. Parents of children with OME were more likely to suspect that their child had a hearing loss (ORs 10.1 and 28.2 for suspecting a mild and severe hearing loss, respectively), but less likely to find that the ear disease affected the child's general wellbeing than did parents of children with rAOM (ORs 0.54 and 0.33 for somewhat and much affected, respectively). Many children underwent surgery despite not fulfilling the criteria for surgery as stipulated in the national guidelines. Those who did fulfil criteria, however, had a more severely affected QoL. A significant improvement was seen in individual QoL scores after surgery (p < 0.001). The degree of postoperative improvement in pure tone average correlated with the improvement in QoL (p < 0.001).

Conclusion

This is the first time that the QoL aspect has been analysed in the Swedish grommet register. Though the validity of the questions has not been proven, they provide valuable information. The relevance of the surgical criteria in national guidelines is illustrated by their correlation with the QoL questions, particularly for OME, and the postoperative improvement in QoL suggests parents find that their children benefit from surgery.

http://bit.ly/2Ddo5wX

Outcome Of Drug-Induced Sleep Endoscopy-Directed Surgery For Persistent Obstructive Sleep Apnea After Adenotonsillar Surgery

Publication date: Available online 6 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): E. Esteller, J.C. Villatoro, A. Agüero, E. Matiñó, R. Lopez, Aristimuño A, Nuñez V, M.A. Díaz-Herrera

Abstract

PURPOSE

Drug-induced sleep endoscopy (DISE) is suitable for evaluating persistent obstructive sleep apnea syndrome (OSAS) after adenotonsillar surgery as a means to guide surgical intervention, yet few studies demonstrate its usefulness in resolving the syndrome. We describe our experience of DISE-directed surgery in children with persistent OSAS by analysing objective and subjective outcomes of this treatment.

METHODS

Prospective study of 20 otherwise healthy 2-12 year-old children with OSAS persisting after adenotonsillar surgery. All patients underwent DISE-directed surgery and were followed up clinically and with a polysomnogram at 12±3 months.

RESULTS

All 20 children had an apnea-hypopnea index (AHI) score ≥1 (mean: 6.1±4.9) and 75% had AHI>3 before surgery. We performed a total of 14 total tonsillectomies (70%), 7 with associated pharyngoplasties; 5 radiofrequency turbinate reductions (25%); 7 radiofrequency lingual tonsil reductions (35%); and 10 revision adenoidectomies (50%). No surgery-related complications were observed. AHI scores at follow-up were significantly lower than AHI scores before surgery (1.895±1.11 vs 6.143±4.88; p<0.05) and, in 85% (n=17) of patients, AHI was below 3. There was a significant reduction in the number of children with AHI>3 in follow-up at 12±3 months (15%; n= 3) compared to before surgery (75%; n=15) (p<0.005).

CONCLUSION

DISE-directed surgery for otherwise healthy children with persistent OSAS is a useful and safe technique to decide a therapeutic strategy and to obtain good objective and subjective results regarding resolution of the syndrome.

http://bit.ly/2SvgaVh

Receptive and productive speech and language abilities in hearing-impaired children with German as a second language

Publication date: Available online 6 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Annerose Keilmann, Barbara Friese, Vanessa Hoffmann

Abstract

Objectives

Many studies examining early bilingualism in migrant populations focus on the development of the first language. As language acquisition is closely related to the hearing development, there is a critical need to investigate language development in hearing-impaired children being raised bilingually who were fitted with cochlear implants and/or hearing aids. Therefore, this research project aimed to study the linguistic development of hearing-impaired children being raised with German as a second language who were provided with hearing aids or cochlear implants. Further, the language development of these children is compared with that of hearing-impaired children being raised in a monolingual environment and with normal-hearing children being raised bilingually.

Methods

In this prospective study, we analyzed data from 95 typically developing children with hearing loss (43 bilingual and 52 monolingual) aged 3;0 to 10;11 (years; months) on four language measures in German: receptive vocabulary, productive vocabulary, receptive grammar, productive grammar (sentence repetition). Additionally, 30 bilingual children with normal hearing were included in this study.

Results

44 children were provided with hearing aids in both ears; 34 used cochlear implants bilaterally and 17 were fitted bimodally. Statistical analysis showed that bilingual hearing-impaired children scored significantly poorer than monolingual hearing-impaired children.

Conclusion

Hearing-impaired children being raised bilingually should have speech and language examinations on a regular basis. An examination of both languages would be desirable in order to be able to fully assess speech and language acquisition.

http://bit.ly/2DcXfFm

Does influenza vaccination or RSV prophylaxis impact resource utilization for children after the diagnosis of airway disorders?

Publication date: Available online 6 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Jeffrey Cheng, Congwen Zhao, Hui-Jie Li

Abstract

Objective

Quantify the rates influenza vaccination and RSV prophylaxis for children with airway stenosis and/or other disorders and assess impact on resource utilization.

Methods

This was a retrospective study with data extracted from Duke Enterprise Data Unified Content Explorer (DEDUCE) between January 1, 2006 and December 1, 2017. Children aged 18 years and younger with at least one diagnosis code for airway stenosis and/or disorders were included. The index date was defined as the first date of airway stenosis/disorders diagnosis. Each patient was followed for up to one year after the index date. Influenza vaccination or RSV prophylaxis documented within one year of index date were included. We defined emergency department (ED) visits and/or hospital admissions related to respiratory diagnoses as the primary outcome of increased resource utilization.

Results

A total of 2718 patients were included. In our institution, our results have indicated that there are fairly low vaccination documentation rates of influenza vaccination, RSV prophylaxis, or both provided to children with airway stenosis/disorders, 14.1% (389/2718), 1.1% (30/2718), and 0.6% (17/2718), respectively, within the first year after diagnosis. Around 5% (139/2718) and 10% (269/2718) experienced ED visits or hospitalizations related to respiratory issues within the first year after diagnosis, respectively. Among 139 and 269 patients with ED visits or hospitalizations, 34 (25%) and 54 (20%) had multiple visits, respectively. Very few patients had documented influenza vaccination (11/139, 0.4%) or RSV prophylaxis (5/269, 0.18%) before ED visits or hospitalization.

Conclusions

There is little available evidence at this time for strategies to prevent adverse events or complications in children with airway stenosis/disorders. In our institution, our results have indicated that there are fairly low documented rates of influenza vaccination, RSV prophylaxis, or both provided to children with airway stenosis/disorders in the first year after diagnosis. This is an area of significant clinical interest for potentially limiting adverse events and optimizing resource utilization for children with airway stenosis/disorders.

http://bit.ly/2SuMKqA

Genetic risk of FCRL3 and FCRL5 Polymorphisms in children with asthma and allergic rhinitis in a Chinese Han Population

Publication date: Available online 5 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Zheng Gu, Yang Shen, Xin-Ye Tang, Xia Ke, Hong-Bing Yao, Su-Ling Hong, Hou-Yong Kang

Abstract

Objectives

Asthma and allergic rhinitis (AR) frequently occur as comorbid diseases of the upper airways. Single-nucleotide polymorphisms (SNPs) in the FCRL3 and FCRL5 genes have recently been shown to be associated with various immune-related disorders. This study evaluated the association of FCRL3 and FCRL5 polymorphisms with asthma and allergic rhinitis (AR) in a Han Chinese population.

Methods

Seven single nucleotide polymorphisms (SNPs) of the FCRL3 and FCRL5 were genotyped in 300 asthmatic children, and 206 healthy unrelated individuals using PCR-restriction fragment length polymorphism (PCR-RFLP) assay. Genotyping was validated by direct sequencing.

Results

Our results showed that the frequencies of the rs6692977 CT genotype and T allele within FCRL5 were significantly higher in asthma with comorbid AR compared to healthy controls (Bonferroni-corrected p (Pc) = 3.75 × 10^-6; Pc = 0.006, respectively), whereas these of the CC genotype and C allele were significantly lower (Pc = 4.15 × 10^-5; Pc = 0.006, respectively). The frequencies of the rs7528684 A allele (Pc = 1.80 × 10^-3) and the rs10489678 G allele (Pc = 0.04) within FCRL3 were higher in asthma with comorbid AR than in controls. However, no differences in the tested genetic polymorphisms were detected between asthma and healthy individuals.

Conclusion

This study identified novel SNPs in FCRL3 and FCRL5 significantly associated with the risk for asthma with comorbid AR in the Chinese population. The genetic variants may play role in the development of the asthma phenotype in children with asthma.

http://bit.ly/2DgAWOQ

The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy - A prospective, pilot observational study

Ehler, J; Petzold, A; Wittstock, M; Kolbaske, S; Gloger, M; Henschel, J; Heslegrave, A; ... Sauer, M; + view all Ehler, J; Petzold, A; Wittstock, M; Kolbaske, S; Gloger, M; Henschel, J; Heslegrave, A; Zetterberg, H; Lunn, MP; Rommer, PS; Grossmann, A; Sharshar, T; Richter, G; Nöldge-Schomburg, G; Sauer, M; - view fewer (2019) The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy - A prospective, pilot observational study. PLoS One , 14 (1) , Article e0211184. 10.1371/journal.pone.0211184 . Green open access

http://bit.ly/2I90zqP

Experimental study on frost-formation characteristics on cold surface of arched copper sample

Chen, T; Cong, Q; Jin, J; Choy, K-L; (2018) Experimental study on frost-formation characteristics on cold surface of arched copper sample. PLoS One , 13 (12) , Article e0208721. 10.1371/journal.pone.0208721 . Green open access

http://bit.ly/2DUoXrK

A Bayesian quantification of consistency in correlated data sets

Köhlinger, F; Joachimi, B; Asgari, M; Viola, M; Joudaki, S; Tröster, T; (2019) A Bayesian quantification of consistency in correlated data sets. Monthly Notices of the Royal Astronomical Society , 484 (3) pp. 3126-3153. 10.1093/mnras/stz132 . Green open access

http://bit.ly/2I5n6o2

Cytomegalovirus viral load parameters associated with earlier initiation of pre-emptive therapy after solid organ transplantation

Lumley, S; Green, C; Rafferty, H; Smith, C; Harber, M; O'Beirne, J; Jones, G; ... Griffiths, P; + view all Lumley, S; Green, C; Rafferty, H; Smith, C; Harber, M; O'Beirne, J; Jones, G; Thorburn, D; Marshall, A; Shah, T; Zuhair, M; Rothwell, E; Atabani, S; Haque, T; Griffiths, P; - view fewer (2019) Cytomegalovirus viral load parameters associated with earlier initiation of pre-emptive therapy after solid organ transplantation. PLoS One , 14 (1) , Article e0210420. 10.1371/journal.pone.0210420 . Green open access

http://bit.ly/2DXi7Sv

Abrogation of Stem Loop Binding Protein (Slbp) function leads to a failure of cells to transition from proliferation to differentiation, retinal coloboma and midline axon guidance deficits

Turner, KJ; Hoyle, J; Valdivia, LE; Cerveny, KL; Hart, W; Mangoli, M; Geisler, R; ... Gestri, G; + view all Turner, KJ; Hoyle, J; Valdivia, LE; Cerveny, KL; Hart, W; Mangoli, M; Geisler, R; Rees, M; Houart, C; Poole, RJ; Wilson, SW; Gestri, G; - view fewer (2019) Abrogation of Stem Loop Binding Protein (Slbp) function leads to a failure of cells to transition from proliferation to differentiation, retinal coloboma and midline axon guidance deficits. PLoS One , 14 (1) , Article e0211073. 10.1371/journal.pone.0211073 . Green open access

http://bit.ly/2HVnENw

Symbolic Thickening of Public Culture and the Rise of Right-Wing Populism in Poland

Kotwas, M; Kubik, J; (2019) Symbolic Thickening of Public Culture and the Rise of Right-Wing Populism in Poland. East European Politics and Societies: and Cultures (In press). Green open access

http://bit.ly/2DXyfUa

Million Migrants study of healthcare and mortality outcomes in non-EU migrants and refugees to England: Analysis protocol for a linked population-based cohort study of 1.5 million migrants

Burns, R; Pathak, N; Campos-Matos, I; Zenner, D; Vittal Katikireddi, S; Muzyamba, M; Miranda, J; ... Aldridge, R; + view all Burns, R; Pathak, N; Campos-Matos, I; Zenner, D; Vittal Katikireddi, S; Muzyamba, M; Miranda, J; Gilbert, R; Rutter, H; Jones, L; Williamson, E; Hayward, A; Smeeth, L; Abubakar, I; Hemingway, H; Aldridge, R; - view fewer (2019) Million Migrants study of healthcare and mortality outcomes in non-EU migrants and refugees to England: Analysis protocol for a linked population-based cohort study of 1.5 million migrants. Wellcome Open Research , 4 (4) , Article 15007.1. 10.12688/wellcomeopenres.15007.1 . Green open access

http://bit.ly/2HU9Cvi

Spin readout via spin-to-charge conversion in bulk diamond nitrogen-vacancy ensembles

Jayakumar, H; Dhomkar, S; Henshaw, J; Meriles, CA; (2018) Spin readout via spin-to-charge conversion in bulk diamond nitrogen-vacancy ensembles. Applied Physics Letters , 113 (12) , Article 122404. 10.1063/1.5040261 . Green open access

http://bit.ly/2DWdJDj

Quantitation of Tc-99m-DPD uptake in patients with transthyretin-related cardiac amyloidosis

Ross, JC; Hutt, DF; Burniston, M; Page, J; Steeden, JA; Gillmore, JD; Wechalekar, AD; ... Fontana, M; + view all Ross, JC; Hutt, DF; Burniston, M; Page, J; Steeden, JA; Gillmore, JD; Wechalekar, AD; Hawkins, PN; Fontana, M; - view fewer (2018) Quantitation of Tc-99m-DPD uptake in patients with transthyretin-related cardiac amyloidosis. Amyloid-The Journal of Protein Folding Disorders , 25 (3) pp. 203-210. 10.1080/13506129.2018.1520087 .

http://bit.ly/2HT8dW1

In response to Ballantyne and Schaefer's 'Consent and the ethical duty to participate in health data research'

Hepgul, N; Sleeman, KE; Firth, AM; Johnston, A; Teo, JTH; Bernal, W; Dobson, RJB; Hepgul, N; Sleeman, KE; Firth, AM; Johnston, A; Teo, JTH; Bernal, W; Dobson, RJB; Higginson, IJ; - view fewer (2019) In response to Ballantyne and Schaefer's 'Consent and the ethical duty to participate in health data research'. Journal of Medical Ethics 10.1136/medethics-2018-105271 . (In press). Green open access

http://bit.ly/2DWdyrD

Effects of the synthetic condition on the stability, particle size and redox chemistry of nanoporous CoAlPO-34

Nguyen, HKD; Sankar, G; Catlow, RA; (2017) Effects of the synthetic condition on the stability, particle size and redox chemistry of nanoporous CoAlPO-34. Journal of Porous Materials , 24 (3) pp. 567-572. 10.1007/s10934-016-0292-y . Green open access

http://bit.ly/2HT81pL

A remarkable change of the spectrum of the magnetic Of?p star HD 148937 reveals evidence of an eccentric, high-mass binary

Wade, GA; Smoker, JV; Evans, CJ; Howarth, I; Barba, R; Cox, NL; Morrell, N; ... Gamen, R; + view all Wade, GA; Smoker, JV; Evans, CJ; Howarth, I; Barba, R; Cox, NL; Morrell, N; Nazé, Y; Cami, J; Farhang, A; Walborn, N; Arias, J; Gamen, R; - view fewer (2019) A remarkable change of the spectrum of the magnetic Of?p star HD 148937 reveals evidence of an eccentric, high-mass binary. Monthly Notices of the Royal Astronomical Society , 483 (2) pp. 2581-2591. 10.1093/mnras/sty3304 . Green open access

http://bit.ly/2DWdmIV

Simultaneous co-delivery of neuroprotective drugs from multi-loaded PLGA microspheres for the treatment of glaucoma

Arranz-Romera, A; Davis, BM; Bravo-Osuna, I; Esteban-Pérez, S; Molina-Martínez, IT; Shamsher, E; Ravindran, N; ... Herrero-Vanrell, R; + view all Arranz-Romera, A; Davis, BM; Bravo-Osuna, I; Esteban-Pérez, S; Molina-Martínez, IT; Shamsher, E; Ravindran, N; Guo, L; Cordeiro, MF; Herrero-Vanrell, R; - view fewer (2019) Simultaneous co-delivery of neuroprotective drugs from multi-loaded PLGA microspheres for the treatment of glaucoma. Journal of Controlled Release , 297 pp. 26-38. 10.1016/j.jconrel.2019.01.012 .

http://bit.ly/2HWZcvf

Atomistic insights into the dynamics of binary collisions between gaseous molecules and polycyclic aromatic hydrocarbon dimers

Mao, Q; Zhou, J; Luo, KH; van Duin, ACT; (2019) Atomistic insights into the dynamics of binary collisions between gaseous molecules and polycyclic aromatic hydrocarbon dimers. Physical Chemistry Chemical Physics 10.1039/c8cp07060a . (In press). Green open access

http://bit.ly/2DXyeQ6

A variationally computed room temperature line list for AsH3

Coles, PA; Yurchenko, SN; Kovacich, RP; Hobby, J; Tennyson, J; (2019) A variationally computed room temperature line list for AsH3. Physical Chemistry Chemical Physics 10.1039/c8cp07110a . (In press). Green open access

http://bit.ly/2HWYLRD

High-frequency fluctuations in redox conditions during the latest Permian mass extinction

Mettam, C; Zerkle, AL; Claire, MW; Izon, G; Junium, CJ; Twitchett, RJ; (2017) High-frequency fluctuations in redox conditions during the latest Permian mass extinction. Palaeogeography, Palaeoclimatology, Palaeoecology , 485 pp. 210-223. 10.1016/j.palaeo.2017.06.014 . Green open access

http://bit.ly/2DVdUP4

CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection

Gisslen, M; Heslegrave, A; Veleva, E; Yilmaz, A; Andersson, L-M; Hagberg, L; Spudich, S; ... Zetterberg, H; + view all Gisslen, M; Heslegrave, A; Veleva, E; Yilmaz, A; Andersson, L-M; Hagberg, L; Spudich, S; Fuchs, D; Price, RW; Zetterberg, H; - view fewer (2019) CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection. Neurology, Neuroimmunology and Neuroinflammation , 6 (1) , Article e512. 10.1212/NXI.0000000000000512 . Green open access

http://bit.ly/2HY1Roh

Interactive virtual 3D models of renal cancer patient anatomies alter partial nephrectomy surgical planning decisions and increase surgeon confidence compared to volume-rendered images

Hyde, ER; Berger, LU; Ramachandran, N; Hughes-Hallett, A; Pavithran, NP; Tran, MGB; Ourselin, S; ... Mumtaz, FH; + view all Hyde, ER; Berger, LU; Ramachandran, N; Hughes-Hallett, A; Pavithran, NP; Tran, MGB; Ourselin, S; Bex, A; Mumtaz, FH; - view fewer (2019) Interactive virtual 3D models of renal cancer patient anatomies alter partial nephrectomy surgical planning decisions and increase surgeon confidence compared to volume-rendered images. International Journal of Computer Assisted Radiology and Surgery 10.1007/s11548-019-01913-5 . (In press). Green open access

http://bit.ly/2DXydM2

Development and performance evaluation of the Medicines Optimisation Assessment Tool (MOAT): a prognostic model to target hospital pharmacists' input to prevent medication related problems

Geeson, C; Wei, L; Franklin, B; (2019) Development and performance evaluation of the Medicines Optimisation Assessment Tool (MOAT): a prognostic model to target hospital pharmacists' input to prevent medication related problems. BMJ Quality and Safety (In press).

http://bit.ly/2I90eV5

Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Haworth, S; Shapland, CY; Hayward, C; Prins, BP; Felix, JF; Medina-Gomez, C; Rivadeneira, F; ... St Pourcain, B; + view all Haworth, S; Shapland, CY; Hayward, C; Prins, BP; Felix, JF; Medina-Gomez, C; Rivadeneira, F; Wang, C; Ahluwalia, TS; Vrijheid, M; Guxens, M; Sunyer, J; Tachmazidou, I; Walter, K; Iotchkova, V; Jackson, A; Cleal, L; Huffmann, J; Min, JL; Sass, L; Timmers, PRHJ; Al Turki, S; Anderson, CA; Anney, R; Antony, D; Artigas, MS; Ayub, M; Bala, S; Barrett, JC; Barroso, I; Beales, P; Bentham, J; Bhattacharya, S; Birney, E; Blackwood, D; Bobrow, M; Bochukova, E; Bolton, PF; Bounds, R; Boustred, C; Breen, G; Calissano, M; Carss, K; Charlton, R; Chatterjee, K; Chen, L; Ciampi, A; Cirak, S; Clapham, P; Clement, G; Coates, G; Cocca, M; Collier, DA; Cosgrove, C; Cox, T; Craddock, N; Crooks, L; Curran, S; Curtis, D; Daly, A; Danecek, P; Day, INM; Day-Williams, A; Dominiczak, A; Down, T; Du, Y; Dunham, I; Durbin, R; Edkins, S; Ekong, R; Ellis, P; Evans, DM; Farooqi, IS; Fitzpatrick, DR; Flicek, P; Floyd, J; Foley, AR; Franklin, CS; Futema, M; Gallagher, L; Gaunt, TR; Geihs, M; Geschwind, D; Greenwood, CMT; Griffin, H; Grozeva, D; Guo, X; Guo, X; Gurling, H; Hart, D; Hendricks, AE; Holmans, P; Howie, B; Huang, J; Huang, L; Hubbard, T; Humphries, SE; Hurles, ME; Hysi, P; Jackson, DK; Jamshidi, Y; Joyce, C; Karczewski, KJ; Kaye, J; Keane, T; Kemp, JP; Kennedy, K; Kent, A; Keogh, J; Khawaja, F; van Kogelenberg, M; Kolb-Kokocinski, A; Lachance, G; Langford, C; Lawson, D; Lee, I; Lek, M; Li, R; Li, Y; Liang, J; Lin, H; Liu, R; Lonnqvist, J; Lopes, LR; Lopes, M; MacArthur, DG; Mangino, M; Marchini, J; Marenne, G; Maslen, J; Mathieson, I; McCarthy, S; McGuffin, P; McIntosh, AM; McKechanie, AG; McQuillin, A; Memari, Y; Metrustry, S; Migone, N; Mitchison, HM; Moayyeri, A; Morris, A; Morris, J; Muddyman, D; Muntoni, F; Northstone, K; O'Donovan, MC; O'Rahilly, S; Onoufriadis, A; Oualkacha, K; Owen, MJ; Palotie, A; Panoutsopoulou, K; Parker, V; Parr, JR; Paternoster, L; Paunio, T; Payne, F; Payne, SJ; Perry, JRB; Pietilainen, O; Plagnol, V; Pollitt, RC; Porteous, DJ; Povey, S; Quail, MA; Quaye, L; Raymond, FL; Rehnstrom, K; Richards, JB; Ridout, CK; Ring, S; Ritchie, GRS; Roberts, N; Robinson, RL; Savage, DB; Scambler, P; Schiffels, S; Schmidts, M; Schoenmakers, N; Scott, RH; Semple, RK; Serra, E; Sharp, SI; Shaw, A; Shihab, HA; Shin, S-Y; Skuse, D; Small, KS; Smee, C; Smith, BH; Soranzo, N; Southam, L; Spasic-Boskovic, O; Spector, TD; St Clair, D; Stalker, J; Stevens, E; Sun, J; Surdulescu, G; Suvisaari, J; Syrris, P; Taylor, R; Tian, J; Tobin, MD; Valdes, AM; Vandersteen, AM; Vijayarangakannan, P; Visscher, PM; Wain, LV; Walters, JTR; Wang, G; Wang, J; Wang, Y; Ward, K; Wheeler, E; Whyte, T; Williams, HJ; Williamson, KA; Wilson, C; Wilson, SG; Wong, K; Xu, C; Yang, J; Zhang, F; Zhang, P; Zheng, H-F; Smith, GD; Fisher, SE; Wilson, JF; Cole, TJ; Fernandez-Orth, D; Bonnelykke, K; Bisgaard, H; Pennell, CE; Jaddoe, VWV; Dedoussis, G; Timpson, N; Zeggini, E; Vitart, V; St Pourcain, B; - view fewer (2019) Low-frequency variation in TP53 has large effects on head circumference and intracranial volume. Nature Communications , 10 , Article 357. 10.1038/s41467-018-07863-x . Green open access

http://bit.ly/2DXigW0

Evaluation of bone regeneration in a critical size cortical bone defect in rat mandible using microCT and histological analysis

Publication date: Available online 5 February 2019

Source: Archives of Oral Biology

Author(s): Cynthia G. Trejo-Iriarte, Janeth Serrano-Bello, Rocío Gutiérrez-Escalona, Crisóforo Mercado-Marques, Natalio García-Honduvilla, Julia Buján-Varela, Luis Alberto Medina

Abstract

Goal

Evaluate bone regeneration in a critical size bone defect model in the jaw of healthy rats as a function of gender and defect location.

Design

A series of microCT and histological studies were performed to evaluate the process of bone regeneration in rats with a mandibular critical size defect. Rats were placed in two groups according to gender and sorted in terms of bone defect location. Bone regeneration rate and hydroxyapatite concentration were assessed with microCT imaging at specific times after surgery. Histological analysis was also performed to evaluate bone regeneration.

Results

No more that 85% of bone regeneration was observed after 60 days, with a low rate constant (K) indicating a slow restoration of the defect. Assessment of microCT images showed partial closure of the defect in all cases, which was confirmed by histological analysis. Hydroxyapatite concentration values revealed that regenerated bone was not fully calcified. No statistically significant differences in terms of gender or defect location were found.

Conclusion

The defect model studied here, located in the jaw of healthy rats, shows potential as a preclinical critical size bone defect model to evaluate bone regeneration therapies in the fields of dentistry and maxillofacial surgery.

http://bit.ly/2DgwwaI

Immunotherapy with checkpoint inhibitors in non-small cell lung cancer: insights from long-term survivors

Abstract

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1)–programmed cell death ligand-1 (PD-L1) axis have shown promising results in non-small cell lung cancer (NSCLC) patients, some of them with persistent responses to these agents that form a population of long-term survivors. Despite the variable definition of PD-L1 positivity in tumors, an association between expression and response has been reasonably consistent in advanced NSCLC. In addition, the clinical efficacy of ICIs seems to be related to the genomic landscape of the tumor in terms of mutational burden and clonal neoantigens. Furthermore, increasing evidence shows that excessive activation of the immune response elicited by ICIs, leading to immune-related toxicities, might be associated with an improved response to immunotherapy. There are still many unanswered questions about the proper use of these agents to maximize their efficacy, which may be improved through combination with radiation, chemotherapy, targeted therapies, or other immune mediators, including dual checkpoint blockade. To search for clues for addressing these challenges, this review focused on the characteristics and clinical features of long-term NSCLC survivors and the potential biomarkers of response to ICIs.

http://bit.ly/2UPYYrp

Tumor volume as a predictive parameter in the sequential therapy (induction chemotherapy) of head and neck squamous cell carcinomas

Abstract

Purpose

Tumor volume in locally advanced head and neck squamous cell carcinomas (LAHNSCC) treated by induction chemotherapy (ICT) and followed by radiochemotherapy (RCT) was measured. The presence of potential correlation of initial tumor volume and volume reduction after ICT and RCT with remission status, overall survival (OS) and disease-free survival (DFS) were investigated. Furthermore, reliability of approximation of the tumor volume relying on its diameter to manual three-dimensional measurement was assessed.

Methods

Data of patients with LAHNSCC treated by ICT consisting of docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by definite RCT were retrospectively analyzed. The tumor volume was calculated slice-by-slice in contrast-enhanced CT or MRI before and after ICT as well as after complete treatment. The volume was compared to radiologic remission status, correlated with OS and DFS, and to volume estimation using tumor diameter.

Result

65 patients were included. Primary tumor volume did not correlate with complete remission rate (CR) after ICT and RCT, OS or DFS. The change in tumor volume between baseline imaging and post-RCT had a significant impact on OS (p = 0.026) and DFS (p = 0.028). The agreement between tumor volume and radiologic remission was 72.14%.

Conclusion

The initial tumor volume had no influence on CR, OS or DFS. A severe response to ICT did not predict a powerful RCT outcome. The change in tumor volume post-RCT had an impact on OS and DFS. Tumor volume estimation using its diameter seems to be a reliable method.

http://bit.ly/2GbQaZu

Pediatric otogenic lateral sinus thrombosis: focus on the prognostic role of contralateral venous drainage

http://bit.ly/2MThH2u

Diagnostik und Therapie von Riechstörungen

Zusammenfassung

Hintergrund

Dysosmien zählen zu den häufigsten Störungen/Erkrankungen im HNO-Fachgebiet, epidemiologische Daten fehlen weitgehend, und die Therapiestrategien sind unzureichend standardisiert.

Fragestellung

Erhebung der Ursachen von Riechstörungen und den angewendeten Behandlungsstrategien an HNO-Kliniken im deutschsprachigen Raum. Auswertung und Vergleich mit den Ergebnissen aus der Umfrage im Jahr 2000 und Durchführung einer Literaturanalyse zur Therapie von Riechstörungen.

Material und Methoden

Die Umfrage erfolgte 2010 mit einem zweiseitigen Fragebogen zu Riechstörungen, der an alle HNO-Kliniken im deutschsprachigen Raum verschickt wurde. Die Analyse schloss die Literatur aus PubMed, der Cochrane Library sowie themenrelevanten Leitlinien ein.

Ergebnisse

An HNO-Kliniken wurde die Diagnose Dysosmie seltener gestellt (Rückgang um 52 %) Die 3 am häufigsten genannten Therapieansätze waren Kortikosteroide (topisch und systemisch) und systemische Antibiotika. Bei sinunasalen Dysosmien zeigte sich in der Literaturanalyse ein kleiner bis mittlerer Effekt von topischen Steroiden.

Schlussfolgerung

Da eine Halbierung der Prävalenz von Riechstörungen unwahrscheinlich ist, beruht die geringere Patientenzahl möglicherweise auf einer kritischeren Diagnostik. Die Anwendung des Riechtrainings hat in den Kliniken stark zugenommen (von <6 % auf 29 %). Der Einsatz von topischen Steroiden bei der Behandlung von sinunasalen Dysosmien ist evidenzbasiert. Das Riechtraining stellt besonders bei postinfektiösen und posttraumatischen Riechstörungen eine sichere und effektive Therapieoption dar.

http://bit.ly/2GqfbQ2

Sweet syndrome in metastatic melanoma during treatment with dabrafenib and trametinib

http://bit.ly/2MTgFn8

Dermoscopy of blue naevus on acral volar skin: A review of the literature

http://bit.ly/2DW5tmM

Search for Higgs boson decays into a pair of light bosons in the bbμμ final state in pp collision at √s=13TeV with the ATLAS detector

Aaboud, M; Aad, G; Abbott, B; Abdinov, O; Abeloos, B; Abhayasinghe, DK; Abidi, SH; ... Araujo Ferraz, V; + view all Aaboud, M; Aad, G; Abbott, B; Abdinov, O; Abeloos, B; Abhayasinghe, DK; Abidi, SH; AbouZeid, OS; Abraham, NL; Abramowicz, H; Abreu, H; Abulaiti, Y; Acharya, BS; Adachi, S; Adamczyk, L; Adelman, J; Adersberger, M; Adiguzel, A; Adye, T; Affolder, AA; Afik, Y; Agheorghiesei, C; Aguilar-Saavedra, JA; Ahmadov, F; Aielli, G; Akatsuka, S; Åkesson, TPA; Akilli, E; Akimov, AV; Alberghi, GL; Albert, J; Albicocco, P; Alconada Verzini, MJ; Alderweireldt, S; Aleksa, M; Aleksandrov, IN; Alexa, C; Alexopoulos, T; Alhroob, M; Ali, B; Alimonti, G; Alison, J; Alkire, SP; Allaire, C; Allbrooke, BMM; Allen, BW; Allport, PP; Aloisio, A; Alonso, A; Alonso, F; Alpigiani, C; Alshehri, AA; Alstaty, MI; Alvarez Gonzalez, B; Álvarez Piqueras, D; Alviggi, MG; Amadio, BT; Amaral Coutinho, Y; Ambroz, L; Amelung, C; Amidei, D; Amor Dos Santos, SP; Amoroso, S; Amrouche, CS; Anastopoulos, C; Ancu, LS; Andari, N; Andeen, T; Anders, CF; Anders, JK; Anderson, KJ; Andreazza, A; Andrei, V; Anelli, CR; Angelidakis, S; Angelozzi, I; Angerami, A; Anisenkov, AV; Annovi, A; Antel, C; Anthony, MT; Antonelli, M; Antrim, DJA; Anulli, F; Aoki, M; Aparisi Pozo, JA; Aperio Bella, L; Arabidze, G; Araque, JP; Araujo Ferraz, V; - view fewer (2019) Search for Higgs boson decays into a pair of light bosons in the bbμμ final state in pp collision at √s=13TeV with the ATLAS detector. Physics Letters B , 790 10.1016/j.physletb.2018.10.073 . Green open access

http://bit.ly/2BlrRnZ

Sevoflurane, Propofol and Carvedilol Block Myocardial Protection by Limb Remote Ischemic Preconditioning

Cho, YJ; Nam, K; Kim, TK; Choi, SW; Kim, SJ; Hausenloy, DJ; Jeon, Y; (2019) Sevoflurane, Propofol and Carvedilol Block Myocardial Protection by Limb Remote Ischemic Preconditioning. International Journal of Molecular Sciences , 20 (2) , Article 269. 10.3390/ijms20020269 . Green open access

http://bit.ly/2Ty11jl

Characterization of retinal structure in CNGB3-associated achromatopsia

Georgiou, M; Kalitzeos, A; Litts, KM; Singh, N; Kane, T; Hirji, N; Mastey, R; ... Michaelides, M; + view all Georgiou, M; Kalitzeos, A; Litts, KM; Singh, N; Kane, T; Hirji, N; Mastey, R; Kumaran, N; Dubra, A; Carroll, J; Michaelides, M; - view fewer (2018) Characterization of retinal structure in CNGB3-associated achromatopsia. [Lecture]. Presented at: European Association for Vision and Eye Research Conference (EVER) 2018, Nice, Provence Alpes Cote, France.

http://bit.ly/2Bn9IGl

Aggregating Algorithm for Prediction of Packs

Adamskiy, D; Bellotti, T; Dzhamtyrova, R; Kalnishkan, Y; (2019) Aggregating Algorithm for Prediction of Packs. Machine Learning 10.1007/s10994-018-5769-2 . (In press). Green open access

http://bit.ly/2Tx3YRe

Decreased circulating ErbB4 ectodomain fragments as a read-out of impaired signaling function in amyotrophic lateral sclerosis

Lopez-Font, I; Sogorb-Esteve, A; Javier-Torrent, M; Brinkmalm, G; Herrando-Grabulosa, M; García-Lareu, B; Turon-Sans, J; ... Sáez-Valero, J; + view all Lopez-Font, I; Sogorb-Esteve, A; Javier-Torrent, M; Brinkmalm, G; Herrando-Grabulosa, M; García-Lareu, B; Turon-Sans, J; Rojas-García, R; Lleó, A; Saura, CA; Zetterberg, H; Blennow, K; Bosch, A; Navarro, X; Sáez-Valero, J; - view fewer (2019) Decreased circulating ErbB4 ectodomain fragments as a read-out of impaired signaling function in amyotrophic lateral sclerosis. Neurobiology of Disease , 124 pp. 428-438. 10.1016/j.nbd.2018.12.021 .

http://bit.ly/2Bjgs80

Association of Cerebrospinal Fluid Neurofilament Light Protein Levels With Cognition in Patients With Dementia, Motor Neuron Disease, and Movement Disorders

Olsson, B; Portelius, E; Cullen, NC; Sandelius, Å; Zetterberg, H; Andreasson, U; Höglund, K; ... Blennow, K; + view all Olsson, B; Portelius, E; Cullen, NC; Sandelius, Å; Zetterberg, H; Andreasson, U; Höglund, K; Irwin, DJ; Grossman, M; Weintraub, D; Chen-Plotkin, A; Wolk, D; McCluskey, L; Elman, L; Shaw, LM; Toledo, JB; McBride, J; Hernandez-Con, P; Lee, VM-Y; Trojanowski, JQ; Blennow, K; - view fewer (2019) Association of Cerebrospinal Fluid Neurofilament Light Protein Levels With Cognition in Patients With Dementia, Motor Neuron Disease, and Movement Disorders. JAMA Neurology 10.1001/jamaneurol.2018.3746 . (In press).

http://bit.ly/2TuwZNs

Photocatalytically Active Ladder Polymers

Vogel, A; Forster, M; Wilbraham, L; Smith, C; Cowan, A; Zwijnenburg, MA; Sprick, RSS; Vogel, A; Forster, M; Wilbraham, L; Smith, C; Cowan, A; Zwijnenburg, MA; Sprick, RSS; Cooper, A; - view fewer (2019) Photocatalytically Active Ladder Polymers. Faraday Discussions 10.1039/C8FD00197A . (In press). Green open access

http://bit.ly/2BlV0PY

Progressive cone and cone-rod dystrophies: clinical features, molecular genetics and prospects for therapy

Gill, JS; Georgiou, M; Kalitzeos, A; Moore, AT; Michaelides, M; (2019) Progressive cone and cone-rod dystrophies: clinical features, molecular genetics and prospects for therapy. British Journal of Ophthalmology 10.1136/bjophthalmol-2018-313278 . (In press). Green open access

http://bit.ly/2TyHfV5

In-silico investigation of coding variants potentially affecting the functioning of the glutamatergic N-methyl-D-aspartate receptor in schizophrenia

Tsavou, A; Curtis, D; (2019) In-silico investigation of coding variants potentially affecting the functioning of the glutamatergic N-methyl-D-aspartate receptor in schizophrenia. Psychiatric Genetics 10.1097/YPG.0000000000000216 . (In press).

http://bit.ly/2BnC3wh

Are interventions supporting separated parents father inclusive? Insights and challenges from a review of programme implementation and impact

Philip, G; O'Brien, M; (2017) Are interventions supporting separated parents father inclusive? Insights and challenges from a review of programme implementation and impact. Child and Family Social Work , 22 (2) pp. 1114-1127. 10.1111/cfs.12299 . Green open access

http://bit.ly/2TuoEcF

Comparing χ2 Tables for Separability of Distribution and Effect: Meta-Tests for Comparing Homogeneity and Goodness of Fit Contingency Test Outcomes

Wallis, S; (2019) Comparing χ2 Tables for Separability of Distribution and Effect: Meta-Tests for Comparing Homogeneity and Goodness of Fit Contingency Test Outcomes. Journal of Quantitative Linguistics 10.1080/09296174.2018.1496537 . (In press).

http://bit.ly/2BoGMxx

Acceptability and feasibility of collecting psychosocial data from fathers of very low birth weight infants

Bagge, SR; Westgate, B; Few, K; Clarke, P; Adlam, A; Walsh, J; O'Brien, M; (2017) Acceptability and feasibility of collecting psychosocial data from fathers of very low birth weight infants. Journal of Child Health Care , 21 (3) pp. 283-291. 10.1177/1367493517715147 . Green open access

http://bit.ly/2TyHfo3

Motivational trajectories for early language learning across the primary-secondary school transition

Graham, S; Courtney, L; Tonkyn, A; Marinis, T; (2016) Motivational trajectories for early language learning across the primary-secondary school transition. British Educational Research Journal , 42 (4) pp. 682-702. 10.1002/berj.3230 . Green open access

http://bit.ly/2BoSyIq

Predicting clinical progression in multiple sclerosis after 6 and 12 years

Dekker, I; Eijlers, AJC; Popescu, V; Balk, LJ; Vrenken, H; Wattjes, MP; Uitdehaag, BMJ; ... Schoonheim, MM; + view all Dekker, I; Eijlers, AJC; Popescu, V; Balk, LJ; Vrenken, H; Wattjes, MP; Uitdehaag, BMJ; Killestein, J; Geurts, JJG; Barkhof, F; Schoonheim, MM; - view fewer (2019) Predicting clinical progression in multiple sclerosis after 6 and 12 years. European Journal of Neurology 10.1111/ene.13904 . (In press). Green open access

http://bit.ly/2Tz4vlT

Novel imaging phantom for accurate and robust measurement of brain atrophy rates using clinical MRI

Amiri, H; Brouwer, I; Kuijer, JPA; De Munck, JC; Barkhof, F; Vrenken, H; (2019) Novel imaging phantom for accurate and robust measurement of brain atrophy rates using clinical MRI. NeuroImage: Clinical , 21 , Article 101667. 10.1016/j.nicl.2019.101667 . Green open access

http://bit.ly/2BquDbr

The cutting edge of archaeal transcription

Fouqueau, T; Blombach, F; Cackett, G; Carty, AE; Matelska, DM; Ofer, S; Pilotto, S; ... Werner, F; + view all Fouqueau, T; Blombach, F; Cackett, G; Carty, AE; Matelska, DM; Ofer, S; Pilotto, S; Phung, DK; Werner, F; - view fewer (2018) The cutting edge of archaeal transcription. Emerging Topics in Life Sciences , 2 (4) pp. 517-533. 10.1042/ETLS20180014 . Green open access

http://bit.ly/2TAElPx

Exploring resting state connectivity in patients with psychotic depression

Oudega, ML; Van der Werf, YD; Dols, A; Wattjes, MP; Barkhof, F; Bouckaert, F; Vandenbulcke, M; ... Van Exel, E; + view all Oudega, ML; Van der Werf, YD; Dols, A; Wattjes, MP; Barkhof, F; Bouckaert, F; Vandenbulcke, M; De Winter, F-L; Sienaert, P; Eikelenboom, P; Stek, ML; Van den Heuvel, OA; Emsell, L; Rhebergen, D; Van Exel, E; - view fewer (2019) Exploring resting state connectivity in patients with psychotic depression. PLOS ONE , 14 (1) , Article e0209908. 10.1371/journal.pone.0209908 . Green open access

http://bit.ly/2BoGNl5

Use of a water-based probiotic to treat common gut pathogens

Dodoo, CC; Stapleton, P; Basit, AW; Gaisford, S; (2019) Use of a water-based probiotic to treat common gut pathogens. International Journal of Pharmaceutics , 556 pp. 136-141. 10.1016/j.ijpharm.2018.11.075 .

http://bit.ly/2Tz4myR

Failed Fantasies in a South African Context: the Case of Modderfontein, Johannesburg

Brill, F; Reboredo, R; (2019) Failed Fantasies in a South African Context: the Case of Modderfontein, Johannesburg. Urban Forum 10.1007/s12132-018-9348-1 . (In press). Green open access

http://bit.ly/2BnC2bH

Transition in modern foreign languages: a longitudinal study of motivation for language learning and second language proficiency

Courtney, L; (2017) Transition in modern foreign languages: a longitudinal study of motivation for language learning and second language proficiency. Oxford Review of Education , 43 (4) pp. 462-481. 10.1080/03054985.2017.1329721 . Green open access

http://bit.ly/2Tz49vz

Acute inflammatory and immunologic responses against antigen in chronic bird-related hypersensitivity pneumonitis

Publication date: Available online 6 February 2019

Source: Allergology International

Author(s): Yukihisa Inoue, Masahiro Ishizuka, Haruhiko Furusawa, Takayuki Honda, Tatsuo Kawahara, Tomoya Tateishi, Yasunari Miyazaki

Abstract

Background

Hypersensitivity pneumonitis (HP) is an immune-mediated lung disease induced by the inhalation of a wide variety of antigens and a persistent antigen exposure induces inevitably pulmonary fibrosis in chronic HP. Although neutrophils, Th1 and Th17 cells contribute to lung inflammation in acute phase of HP, there is no clear explanation as to how the immunological reaction occurs just after the inhalation of causative antigens in the chronic phase of HP.

Methods

We examined the inflammatory and immunologic profiles before and after the inhalation provocation test (IPT) in serum and bronchoalveolar lavage fluid (BALF) from patients with chronic bird-related HP (BRHP) and other interstitial lung diseases (ILDs). We analyzed BALF samples from 39 patients (19 BRHP and 20 other ILDs) and serum samples from 25 consecutive patients (20 BRHP and 5 other ILDs) who underwent the IPT.

Results

A significant increase of neutrophils was observed in the BALF from the BRHP patients following the IPT. Neutrophil chemoattractants, namely, granulocyte colony-stimulating factor, IL-6, IL-8, IL-17, and CXCL2 significantly increased in both the serum and BALF of the BRHP patients after the IPT. Serum IFN-γ and CXCL10, cytokines/chemokines that contributed to Th1 inflammation, were also significantly increased in BRHP following the IPT.

Conclusions

This study demonstrated the exposure to the causative antigen provoked acute neutrophilic and Th1 immunologic responses similar to acute HP even in the chronic phase of HP.

http://bit.ly/2SBz6BM

Urban/rural residence effect on emergency department visits arising from food-induced anaphylaxis

Publication date: Available online 5 February 2019

Source: Allergology International

Author(s): Rie Sakai-Bizmark, Scott M.I. Friedlander, Karin Oshima, Eliza J. Webber, Laurie A. Mena, Emily H. Marr, Yoshikazu Ohtsuka

Abstract

Background

Anaphylaxis is a severe and potentially fatal allergic response. Early-life exposure to rural environments may help protect against allergic reaction. This study assesses urban/rural differences by age and race/ethnicity in emergency department (ED) pediatric visit rates for food-induced anaphylaxis.

Methods

This observational study examined 2009–2014 inpatient and ED data from New York and Florida, using ICD-9-CM diagnostic code (995.6) to identify food-induced anaphylaxis cases <18 y/o. Primary predictor of interest was urban/rural setting, with race/ethnicity and age also evaluated. Associations between ED visit rates and urban/rural setting were evaluated by multivariable hierarchical negative binomial regression with state and year fixed effects.

Results

ED visit rates (per 100,000) for food-induced anaphylaxis were 12.31 and 4.60 in urban and rural settings, respectively. Rates were highest among Blacks (15.26) younger urban children (17.29) and older rural children (6.99). Compared to rural, urban children had significantly higher anaphalaxis ED visit rates (IRR 2.77).

Conclusions

Food-induced anaphylaxis ED visit rates were highest among younger urban children and Black children, with a notable contrast in age distribution between urban and rural rates. Higher urban rates may be attributed to Hygiene Hypothesis, though racial, economic and emergency care access disparities may also influence these outcomes.

http://bit.ly/2Gqwhgt

A pilot study of interferon-alpha-2b dose reduction in the adjuvant therapy of high-risk melanoma

http://bit.ly/2t94ucz

Mutations resulting in the formation of hyperactive complement convertases support cytocidal effect of anti-CD20 immunotherapeutics

Abstract

Anti-CD20 monoclonal antibodies (mAbs) rituximab and ofatumumab are potent activators of the classical complement pathway, and have been approved for the treatment of B-cell malignancies. However, complement exhaustion and overexpression of complement inhibitors by cancer cells diminish their therapeutic potential. The strategies of targeting membrane complement inhibitors by function-blocking antibodies and the supplementation with fresh frozen plasma have been proposed to overcome tumour cell resistance. We present a novel approach, which utilizes gain-of-function variants of complement factor B (FB), a component of alternative C3/C5 convertases, which augment mAb-activated reactions through a positive feedback mechanism called an amplification loop. If complement concentration is limited, an addition of quadruple gain-of-function FB mutant p.D279G p.F286L p.K323E p.Y363A (or selected single mutants) results in significantly increased complement-mediated lysis of ofatumumab-resistant tumour cells, as well as the complete lysis of moderately sensitive cells. Importantly, this effect cannot be achieved by further increasing ofatumumab concentration. Potentiation of cytotoxic effect towards moderately sensitive cells was less apparent at physiological serum concentration. However, an addition of hyperactive FB could compensate the loss of cytotoxic potential of serum collected from the NHL and CLL patients after infusion of rituximab. Residual levels of rituximab in such sera, in combination with added FB, were able to efficiently lyse tumour cells. We suggest that the administration of gain-of-function variants of FB can restore CDC potential of complement-exhausted serum and maximize the therapeutic effect of circulating anti-CD20 mAbs.

http://bit.ly/2HU7pjz

Malformations of the lateral semicircular canal correlated with data from the audiogram

Abstract

Objectives

Lateral semicircular canal (LSCC) malformations are one of the most common inner ear malformations. The purpose of this study is to analyze the prevalence and type of hearing losses associated with LSCC malformations, compared to a control group.

Materials and methods

We retrospectively included 109 patients (166 ears) presenting with a CT-confirmed LSCC malformation, compared to a control group (24 patients). The bony island surface and the width of the inner portion of the LSCC were measured to confirm the malformation. There results were correlated to audiogram data: sensorineural (SHNL), mixed (MHL) or conductive hearing loss (CHL) by an otologist.

Results

In the LSCC group, 60.9% of patients presented with an audiogram-confirmed hearing loss, especially SNHL (39.2%, n = 65) and MHL (12.7%, n = 21). Hearing was normal in 39.2% (n = 65) of the cases. Bilateral LSCC malformations (n = 57) were frequently associated with hearing loss (80.7%), SNHL in most of the cases (33.3%). Unilateral LSCC malformations were associated with hearing alterations (51.9%, n = 27), but we also observed a high rate (81%, n = 42) of contralateral abnormalities of the audiogram.

Conclusion

LSCC malformations are commonly associated with hearing loss (61%), especially SHNL (39%). The high rate (81%) of contralateral hearing disturbances in unilateral LSCC malformations should be taken into account in the patient's daily life to avoid triggering or exacerbating any hearing loss. Otologists and radiologists must cooperate to ensure that all malformations are correctly described on CT, especially to improve the patient's education regarding hearing preservation.

http://bit.ly/2HWEETz

Endovascular Treatment of Ruptured Renal Artery Aneurysm: A Case-Based Literature Review

Renal artery aneurysms are extremely uncommon with a reported incidence of less than one percent in general population. They are being more frequently detected due to increasing availability and use of abdominal imaging. Renal artery aneurysm rupture is an extremely unusual cause of acute flank pain with hemodynamic instability. Given the rarity of diagnoses, clinicians may not consider and address this ruptured renal artery aneurysm early which can potentially lead to adverse clinical outcomes. We report the case of a 55-year-old male who presented with retroperitoneal bleeding from a ruptured aneurysm of the interlobular branch of renal artery. He was endovascularly treated with coil embolization. We have also reviewed the inherent literature.

http://bit.ly/2MOQTjE

Maxillary Zoster and Neurotrophic Keratitis following Trigeminal Block

Herpes zoster ophthalmicus is commonly used to describe viral reactivation from the trigeminal ganglia with ocular involvement. The ophthalmic branch is the most commonly involved, whereas the maxillary and mandibular dermatomes are less commonly affected. Neurotrophic ulcer may occur secondary to intentional or inadvertent damage to the trigeminal nucleus, root, ganglion, or any segment of the ophthalmic branch of this cranial nerve. We report a case of reactivated maxillary herpes zoster combined with neurotrophic keratitis due to percutaneous 2nd and 3rd branch of trigeminal nerve block with alcohol to treat trigeminal neuralgia. A 57-year-old female came to the ophthalmology department complaining of decreased visual acuity and skin vesicle over the right lower lid and cheek. She had undergone right trigeminal nerve block for treatment of trigeminal neuralgia. Clinical examination revealed neurotrophic keratitis and maxillary herpes zoster. She was treated with oral and topical antivirals and vigorous lubrication with eye drops. Her neurotrophic keratitis showed a slow recovery. Although a few cases of herpes zoster following nerve block have been described, it would appear that a case of simultaneous maxillary herpes zoster and neurotrophic keratitis following trigeminal block has not yet been documented. It is possible that trigeminal nerve block may cause reactivation of latent virus and refractory neurotrophic keratitis.
Case Rep Ophthalmol 2019;10:61–66

http://bit.ly/2TzRmZI

The Editors' Choice

Publication date: February 2019

Source: Journal of Allergy and Clinical Immunology, Volume 143, Issue 2

Author(s): Zuhair K. Ballas, Associate Editors of the JACI

http://bit.ly/2SwXy7x

Severe combined immunodeficiency in stimulator of interferon genes (STING) V154M/wild-type mice

Publication date: February 2019

Source: Journal of Allergy and Clinical Immunology, Volume 143, Issue 2

Author(s): Delphine Bouis, Peggy Kirstetter, Florent Arbogast, Delphine Lamon, Virginia Delgado, Sophie Jung, Claudine Ebel, Hugues Jacobs, Anne-Marie Knapp, Nadia Jeremiah, Alexandre Belot, Thierry Martin, Yanick J. Crow, Isabelle André-Schmutz, Anne-Sophie Korganow, Frédéric Rieux-Laucat, Pauline Soulas-Sprauel

Background

Autosomal dominant gain-of-function mutations in human stimulator of interferon genes (STING) lead to a severe autoinflammatory disease called STING-associated vasculopathy with onset in infancy that is associated with enhanced expression of interferon-stimulated gene transcripts.

Objective

The goal of this study was to analyze the phenotype of a new mouse model of STING hyperactivation and the role of type I interferons in this system.

Methods

We generated a knock-in model carrying an amino acid substitution (V154M) in mouse STING, corresponding to a recurrent mutation seen in human patients with STING-associated vasculopathy with onset in infancy. Hematopoietic development and tissue histology were analyzed. Lymphocyte activation and proliferation were assessed in vitro. STING V154M/wild-type (WT) mice were crossed to IFN-α/β receptor (IFNAR) knockout mice to evaluate the type I interferon dependence of the mutant Sting phenotype recorded.

Results

In STING V154M/WT mice we detected variable expression of inflammatory infiltrates in the lungs and kidneys. These mice showed a marked decrease in survival and developed a severe combined immunodeficiency disease (SCID) affecting B, T, and natural killer cells, with an almost complete lack of antibodies and a significant expansion of monocytes and granulocytes. The blockade in B- and T-cell development was present from early immature stages in bone marrow and thymus. In addition, in vitro experiments revealed an intrinsic proliferative defect of mature T cells. Although the V154M/WT mutant demonstrated increased expression of interferon-stimulated genes, the SCID phenotype was not reversed in STING V154M/WT IFNAR knockout mice. However, the antiproliferative defect in T cells was rescued partially by IFNAR deficiency.

Conclusions

STING gain-of-function mice developed an interferon-independent SCID phenotype with a T-cell, B-cell, and natural killer cell developmental defect and hypogammaglobulinemia that is associated with signs of inflammation in lungs and kidneys. Only the intrinsic proliferative defect of T cells was partially interferon dependent.

http://bit.ly/2Gccouf

Identification of galectin-3 as an autoantigen in patients with IgG4-related disease

Publication date: February 2019

Source: Journal of Allergy and Clinical Immunology, Volume 143, Issue 2

Author(s): Cory A. Perugino, Sultan B. AlSalem, Hamid Mattoo, Emanuel Della-Torre, Vinay Mahajan, Gayathri Ganesh, Hugues Allard-Chamard, Zachary Wallace, Sydney B. Montesi, Johannes Kreuzer, Wilhelm Haas, John H. Stone, Shiv Pillai

Background

The antigenic trigger that drives expansion of circulating plasmablasts and CD4⁺ cytotoxic T cells in patients with IgG₄-related disease (IgG₄-RD) is presently unknown.

Objective

We sought to sequence immunoglobulin genes from single-cell clones of dominantly expanded plasmablasts and generate recombinant human mAbs to identify relevant antigens in patients with IgG₄-RD by using mass spectrometry.

Methods

Paired heavy and light chain cDNAs from dominant plasmablast clones were expressed as mAbs and used to purify antigens by using immunoaffinity chromatography. Affinity-purified antigens were identified by using mass spectrometry and validated by means of ELISA. Plasma levels of the antigen of interest were also determined by using ELISA.

Results

mAbs expressed from the 2 dominant plasmablast clones of a patient with multiorgan IgG₄-RD stained human pancreatic tissue sections. Galectin-3 was identified as the antigen specifically recognized by both mAbs. Anti–galectin-3 autoantibody responses were predominantly of the IgG₄ isotype (28% of the IgG₄-RD cohort, P = .0001) and IgE isotype (11% of the IgG₄-RD cohort, P = .009). No significant responses were seen from the IgG₁, IgG₂, or IgG₃ isotypes. IgG₄ anti–galectin-3 autoantibodies correlated with increased plasma galectin-3 levels (P = .001), lymphadenopathy (P = .04), total IgG level increase (P = .05), and IgG₄ level increase (P = .03).

Conclusion

Affinity chromatography using patient-derived mAbs identifies relevant autoantigens in patients with IgG₄-RD. IgG₄ galectin-3 autoantibodies are present in a subset of patients with IgG₄-RD and correlate with galectin-3 plasma levels. The marked increases in levels of circulating IgG₄ and IgE observed clinically are, at least in part, caused by the development of IgG₄- and IgE-specific autoantibody responses.

http://bit.ly/2De2cxC

Eleven loci with new reproducible genetic associations with allergic disease risk

Publication date: February 2019

Source: Journal of Allergy and Clinical Immunology, Volume 143, Issue 2

Author(s): Manuel A.R. Ferreira, Judith M. Vonk, Hansjörg Baurecht, Ingo Marenholz, Chao Tian, Joshua D. Hoffman, Quinta Helmer, Annika Tillander, Vilhelmina Ullemar, Yi Lu, Franz Rüschendorf, 23andMe Research Team, SHARE study, David A. Hinds, Norbert Hübner, Stephan Weidinger, Patrik K.E. Magnusson, Eric Jorgenson, Young-Ae Lee, Dorret I. Boomsma, Robert Karlsson, Catarina Almqvist

Background

A recent genome-wide association study (GWAS) identified 99 loci that contain genetic risk variants shared between asthma, hay fever, and eczema. Many more risk loci shared between these common allergic diseases remain to be discovered, which could point to new therapeutic opportunities.

Objective

We sought to identify novel risk loci shared between asthma, hay fever, and eczema by applying a gene-based test of association to results from a published GWAS that included data from 360,838 subjects.

Methods

We used approximate conditional analysis to adjust the results from the published GWAS for the effects of the top risk variants identified in that study. We then analyzed the adjusted GWAS results with the EUGENE gene-based approach, which combines evidence for association with disease risk across regulatory variants identified in different tissues. Novel gene-based associations were followed up in an independent sample of 233,898 subjects from the UK Biobank study.

Results

Of the 19,432 genes tested, 30 had a significant gene-based association at a Bonferroni-corrected P value of 2.5 × 10⁻⁶. Of these, 20 were also significantly associated (P < .05/30 = .0016) with disease risk in the replication sample, including 19 that were located in 11 loci not reported to contain allergy risk variants in previous GWASs. Among these were 9 genes with a known function that is directly relevant to allergic disease: FOSL2, VPRBP, IPCEF1, PRR5L, NCF4, APOBR, IL27, ATXN2L, and LAT. For 4 genes (eg, ATXN2L), a genetically determined decrease in gene expression was associated with decreased allergy risk, and therefore drugs that inhibit gene expression or function are predicted to ameliorate disease symptoms. The opposite directional effect was observed for 14 genes, including IL27, a cytokine known to suppress T_H2 responses.

Conclusion

Using a gene-based approach, we identified 11 risk loci for allergic disease that were not reported in previous GWASs. Functional studies that investigate the contribution of the 19 associated genes to the pathophysiology of allergic disease and assess their therapeutic potential are warranted.

http://bit.ly/2Gsieau

Profilin-mediated food-induced allergic reactions are associated with oral epithelial remodeling

Publication date: February 2019

Source: Journal of Allergy and Clinical Immunology, Volume 143, Issue 2

Author(s): Domenico Rosace, Cristina Gomez-Casado, Paloma Fernandez, Marina Perez-Gordo, María del Carmen Dominguez, Angel Vega, María Teresa Belver, Tania Ramos, Francisco Vega, Guadalupe Marco, Manuel de Pedro, Leticia Sanchez, María de las Mercedes Arnas, Marcela Santaolalla, Miguel Ángel Saez, Sara Benedé, Montserrat Fernandez-Rivas, Carlos Blanco, Maria Isabel Alvarado, María M. Escribese

Background

In areas of high exposure to grass pollen, allergic patients are frequently sensitized to profilin, and some experience severe profilin-mediated food-induced reactions. This specific population of patients is ideal to study the relationship between respiratory and food allergies.

Objective

We sought to determine the role of oral mucosal epithelial barrier integrity in profilin-mediated allergic reactions.

Methods

Thirty-eight patients with profilin allergy stratified into mild or severe according to their clinical history and response to a profilin challenge test and 6 nonallergic subjects were recruited. Oral mucosal biopsies were used for measurement of CD11c, CD3, CD4, tryptase, claudin-1, occludin, E-cadherin, and vascular endothelial growth factor A levels; Masson trichrome staining; and POSTN, IL33, TPSAB, TPSB, and CMA gene expression analysis by using quantitative RT-PCR. Blood samples were used for basophil activation tests.

Results

Distinct features of the group with severe allergy included the following: (1) impaired epithelial integrity with reduced expression of claudin-1, occludin, and E-cadherin and decreased numbers of epithelial cells, which is indicative of acanthosis, higher collagen deposition, and angiogenesis; (2) inflammatory immune response in the mucosa, with an increased number of CD11c⁺ and CD4⁺ infiltrates and increased expression of the cytokine genes POSTN and IL33; and (3) a 10-fold increased sensitivity of basophils to profilin.

Conclusions

Patients with profilin allergy present with significant damage to the oral mucosal epithelial barrier, which might allow profilin penetration into the oral mucosa and induction of local inflammation. Additionally, severely allergic patients presented with increased sensitivity of effector cells.

Graphical abstract

Graphical abstract for this article

http://bit.ly/2Sy2vNl

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Τετάρτη 6 Φεβρουαρίου 2019

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