Future Meetings

Thyroid, Volume 28, Issue 4, Page 549-550, April 2018.


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Hypothyroidism During Tyrosine Kinase Inhibitor Therapy Is Associated with Longer Survival in Patients with Advanced Nonthyroidal Cancers

Thyroid, Volume 28, Issue 4, Page 445-453, April 2018.


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Risk Factors for New Hypothyroidism During Tyrosine Kinase Inhibitor Therapy in Advanced Nonthyroidal Cancer Patients

Thyroid, Volume 28, Issue 4, Page 437-444, April 2018.


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The Effectiveness of Progressive Aerobic Interval Training in Cardiac Rehabilitation

Introduction Aerobic interval training (AIT) has recently emerged as a more effective strategy than moderate-intensity continuous exercise (MICE) for improving peak oxygen consumption (V˙O2peak) in coronary artery disease (CAD) patients. The primary purpose of this retrospective study was to describe the change in V˙O2peak, and cardiovascular (CV) risk profile characteristics (secondary outcomes) after progressive AIT practiced in the largest, outpatient cardiac rehabilitation (CR) program in North America compared with usual care CR involving MICE. Methods Electronic database records were retrieved from consecutively enrolled patients with CAD who attended the Toronto Rehabilitation Institute, between January 1, 2005, and December 31, 2015. Patients were then separated into two, age and sex propensity score-matched groups: 772 patients were prescribed 26 wk of MICE (60%–80% of V˙O2peak, five times per week) as per usual care CR (56.0 ± 9.2 yr; 12% female/88% male; V˙O2peak: 20.8 ± 5.9 mL·kg−1·min−1), and 772 patients were prescribed 26 wk of progressive walk/jog intervals (15 min·mile−1 walking pace, 12 min·mile−1 jogging pace, five times per week) (55.9 ± 9.3 yr; 12% female/88% male; V˙O2peak: 24.8 ± 5.7 mL·kg−1 ·min−1). Treatment effect analysis of AIT on V˙O2peak and CV risk profile characteristics was performed using multiple regression with baseline values as covariates. Results Treatment effect analysis revealed a 3.84-mL·kg−1·min−1 superior improvement in V˙O2peak in the AIT group compared to usual care MICE group (P

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Three Weeks of Overload Training Increases Resting Muscle Sympathetic Activity

Purpose Overload training is hypothesized to alter autonomic regulation, although interpretations using indirect measures of heart rate variability are conflicting. The aim of the present study was to examine the effects of overload training on muscle sympathetic nerve activity (MSNA), a direct measure of central sympathetic outflow, in recreational endurance athletes. Methods Measurements of heart rate variability, cardiac baroreflex sensitivity (BRS), MSNA (microneurography), and sympathetic BRS were obtained in 17 healthy triathletes and cyclists after 1 wk of reduced training (baseline) and again after 3 wk of either regular (n = 7) or overload (n = 10) training. Results After training, the changes (Δ) in peak power output (10 ± 10 vs −12 ± 9 W, P 0.05). Conclusions Overload training increased MSNA and attenuated increases in cardiac BRS and heart rate variability observed with regular training. These results support neural adaptations after overload training and suggest that increased central sympathetic outflow may be linked with decreased exercise performance.

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Exercise Increases Glucose Transporter-4 Levels on Peripheral Blood Mononuclear Cells

Purpose Glucose transporter 4 (GLUT4) plays a key role in the pathophysiology of type 2 diabetes. Glucose transporter 4 is upregulated in response to exercise, enhancing cellular glucose transport in skeletal muscle tissue. This mechanism appears to remain intact in individuals with insulin resistance. Details of the mechanism are poorly understood and are challenging to study due to the invasive nature of muscle biopsy. Peripheral blood mononuclear cells (PBMC) have documented insulin-sensitive GLUT4 activity and may serve as a proxy tissue for studying skeletal muscle GLUT4. The purpose of this study was to investigate whether GLUT4 in PBMC is affected by conditioning. Methods We recruited 16 student athletes from the cross-country running and skiing teams and fifteen sedentary students matched for age and sex from the University of Alaska Fairbanks. Peripheral blood mononuclear cells were collected with mononuclear cell separation tubes. The GLUT4 concentrations were measured using a commercially available enzyme linked immunosorbent assay. Additionally, correlations between PBMC GLUT4 and common indicators of insulin resistance were examined. Results Results indicate significantly higher PBMC GLUT4 levels in conditioned athletes than in their sedentary counterparts, similar to what has been documented in myocytes. Females were observed to have higher PBMC GLUT4 levels than males. Correlations were not detected between PBMC GLUT4 and hemoglobin A1c, glucose, insulin, homeostatic model assessment of insulin resistance, body mass index, or body fat. Conclusions This study provides evidence to support exploration of PBMC as a proxy tissue for studying GLUT4 response to exercise or other noninsulin factors.

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Nasal polyposis (or chronic olfactory rhinitis)

Publication date: Available online 13 April 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): R. Jankowski, C. Rumeau, P. Gallet, D.T. Nguyen
The concept of chronic rhinosinusitis with or without polyps is founded on the structural and functional unicity of the pituitary mucosa and its united response to environmental aggression by allergens, viruses, bacteria, pollution, etc. The present review sets this concept against the evo-devo three-nose theory, in which nasal polyposis is distinguished as specific to the olfactory nose and in particular to the non-olfactory mucosa of the ethmoid, which is considered to be not a sinus but rather the skull-base bone harboring the olfactory mucosa. The evo-devo approach enables simple and precise positive diagnosis of nasal polyposis and its various clinical forms, improves differential diagnosis by distinguishing chronic diseases of the respiratory nose and those of the paranasal sinuses, hypothesizes an autoimmune origin specifically aimed at olfactory system auto-antigens, and supports the surgical concept of nasalization against that of functional sinus and ostiomeatal-complex surgery. The ventilation function of the sinuses seems minor compared to their production, storage and active release of nitric oxide (NO) serving to oxygenate arterial blood in the pulmonary alveoli. This respiratory function of the paranasal sinuses may indeed be their most important. NO trapped in the ethmoidal spaces also accounts for certain radiographic aspects associated with nasal polyposis.



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Office-based endoscopic botulinum toxin injection in laryngeal movement disorders

Publication date: Available online 13 April 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): A. Kaderbay, C.A. Righini, P.F. Castellanos, I. Atallah
IntroductionBotulinum toxin injection is widely used for the treatment of laryngeal movement disorders. Electromyography-guided percutaneous injection is the technique most commonly used to perform intralaryngeal botulinum toxin injection.ObjectiveWe describe an endoscopic approach for intralaryngeal botulinum toxin injection under local anaesthesia without using electromyography.TechniqueA flexible video-endoscope with an operating channel is used. After local anaesthesia of the larynx by instillation of lidocaine, a flexible needle is inserted into the operating channel in order to inject the desired dose of botulinum toxin into the vocal and/or vestibular folds.ConclusionEndoscopic botulinum toxin injection under local anaesthesia is a reliable technique for the treatment of laryngeal movement disorders. It can be performed by any laryngologist without the need for electromyography. It is easy to perform for the operator and comfortable for the patient.



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Updates on antibody functions in Mycobacterium tuberculosis infection and their relevance for developing a vaccine against tuberculosis

Jacqueline M Achkar | Rafael Prados-Rosales

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Editorial Board

Publication date: April 2018
Source:Clinical Immunology, Volume 189





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Contribution of MTHFR gene variants in lupus related subclinical atherosclerosis

Publication date: Available online 6 March 2018
Source:Clinical Immunology
Author(s): Maira Giannelou, Andrianos Nezos, Sofia Fragkioudaki, Dimitra Kasara, Kyriaki Maselou, Nikolaos Drakoulis, Dimitris Ioakeimidis, Haralampos M. Moutsopoulos, Clio P. Mavragani
ObjectiveElevated concentrations of homocysteine have been previously identified as an independent risk factor for subclinical atherosclerosis in patients with systemic lupus erythematosus (SLE). Given that heightened homocysteine levels are known to be strongly influenced by genetic factors, in the current study we investigated the contribution of high homocysteine levels as well as of functional polymorphisms of the gene encoding for the enzyme 5, 10- methylenetetrahydrofolate reductase to atherosclerotic disease characterizing SLE patients.MethodsPeripheral DNA samples from 150 SLE patients, 214 rheumatoid arthritis (RA) patients and 561 age/sex matched apparently healthy volunteers (HC) were genotyped by PCR-based assays for the detection of the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (c. 677C > T and c. 1298A > C). All SLE patients and 30 age sex matched RA patients underwent assessment for subclinical atherosclerosis [ultrasound measurement of intima-media thickness scores (IMT) and detection of carotid and/or femoral (C/F) plaque] and complete clinical and laboratory evaluation including serum homocysteine levels. Data were analyzed using univariate and multivariate models (SPSS 21.0).ResultsHyperhomocysteinemia was detected in 26.0% of SLE patients compared to 6.7% of age/sex matched RA controls (p = 0.02). Higher serum B12 levels and decreased frequency of the MTHFR 677TT variant in RA patients could potentially account for the observed differences between the groups. In SLE patients, both hyperhomocysteinemia and MTHFR677TT genotype were identified as independent contributors for plaque formation, following adjustment for traditional cardiovascular risk factors and disease related features, including age, sex, BMI, cholesterol and triglyceride levels, presence of arterial hypertension, smoking (pack/years), disease duration and total steroid dose [OR 95% (CI): 5.8 (1.0–35.8) and 5.2 (1.1–24.0), respectively]. MTHFR677TT genotype, but not hyperhomocysteinemia was also found to confer increased risk for arterial wall thickening, after the above confounders were taken into account [OR (95%) CI: 4.9 (1.2–20.6)].ConclusionsHyperhomocysteinemia and MTHFR677TT genetic variant emerged as independent risk factors for subclinical atherosclerosis in SLE patients, implying genetic influences as potential contributors to the increased burden of atherosclerotic disease characterizing SLE.



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Phase Ib trial of folate binding protein (FBP)-derived peptide vaccines, E39 and an attenuated version, E39’: An analysis of safety and immune response

Publication date: July 2018
Source:Clinical Immunology, Volume 192
Author(s): Timothy J. Vreeland, Jennifer K. Litton, Na Qiao, Anne V. Philips, Gheath Alatrash, Diane F. Hale, Doreen O. Jackson, Kaitlin M. Peace, Julia M. Greene, John S. Berry, Guy T. Clifton, George E. Peoples, Elizabeth A. Mittendorf
In this randomized phase Ib trial, we tested combining the E39 peptide vaccine with a vaccine created from E39', an attenuated version of E39.Patients with breast or ovarian cancer, who were disease-free after standard of care therapy, were enrolled and randomized to one of three arms. Arm EE received six E39 inoculations; arm EE' received three E39 inoculations followed by three E39'; and arm E'E received three E39' inoculations, followed by three E39. Within each arm, the first five patients received 500 μg of peptide and the remainder received 1000 μg. Patients were followed for toxicity, and immune responses were measured.This initial analysis after completion of the primary vaccination series has confirmed the safety of both vaccines. Immune analyses suggest incorporating the attenuated version of the peptide improves immune responses and that sequencing of E39 followed by E39' might produce the optimal immune response.Trial Registration: NCT02019524



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Elevated expression of TSLP and IL-33 in Behçet's disease skin lesions: IL-37 alleviate inflammatory effect of TSLP

Publication date: July 2018
Source:Clinical Immunology, Volume 192
Author(s): Olfa Kacem, Wajih Kaabachi, Imen Ben Dhifallah, Agnes Hamzaoui, Kamel Hamzaoui
The release of TSLP and IL-33 affect the skin integrity, which unsettled transcription factor regulators. We investigate TSLP and IL-33 in Behçet disease (BD) and we prove the effect of the anti-inflammatory cytokine IL-37 in BD skin lesions on TSLP production. TSLP, IL-33 and GATA-3/T-bet, were measured using PCR in BD skin lesions. We tested the suppressive effect of IL-37 on skin samples stimulated with a cytokine mixture inducing TSLP expression. TSLP and IL-33 were increased in BD patients particularly in patients having skin manifestations and correlate with indexed skin lesions. TSLP expression in BD with skin lesions correlates significantly with the transcription factors GATA3/Tbet ratio. The anti-inflammatory mediator IL-37 acted as a suppressor of TSLP-skin synthesis. The microenvironment in cutaneous lesions of BD patients' skin lesions is dominated by the expression of IL-33 and TSLP along an inflammatory Th2-type current. IL-37 acts as a booster to restore homeostasis.



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Immune senescence, epigenetics and autoimmunity

Publication date: Available online 11 April 2018
Source:Clinical Immunology
Author(s): Donna Ray, Raymond Yung
Aging of the immune system in humans and animals is characterized by a decline in both adaptive and innate immune responses. Paradoxically, aging is also associated with a state of chronic inflammation ("inflammaging") and an increased likelihood of developing autoimmune diseases. Epigenetic changes in non-dividing and dividing cells, including immune cells, due to environmental factors contribute to the inflammation and autoimmunity that characterize both the state and diseases of aging. Here, we review the epigenetic mechanisms involved in the development of immune senescence and autoimmunity in old age.



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More intensive CMV-infection in chronic heart failure patients contributes to higher T-lymphocyte differentiation degree

Publication date: Available online 30 March 2018
Source:Clinical Immunology
Author(s): Marco Antonio Moro-García, Fernando López-Iglesias, Raquel Marcos-Fernández, Eva Bueno-García, Beatriz Díaz-Molina, José Luis Lambert, Francisco Manuel Suárez-García, Cesar Morís de la Tassa, Rebeca Alonso-Arias
Immunosenescence in chronic heart failure (CHF) is characterized by a high frequency of differentiated T-lymphocytes, contributing to an inflammatory status and a deficient ability to generate immunocompetent responses. CMV is the best known inducer of T-lymphocyte differentiation, and is associated with the phenomenon of immunosenescence. In this study, we included 58 elderly chronic heart failure patients (ECHF), 60 healthy elderly controls (HEC), 40 young chronic heart failure patients (YCHF) and 40 healthy young controls (HYC). High differentiation of CD8+ T-lymphocytes was found in CMV-seropositive patients; however, the differentiation of CD4+ T-lymphocytes was increased in CMV-seropositive but also in CHF patients. Anti-CMV antibody titers showed positive correlation with more differentiated CD4+ and CD8+ subsets and inverse correlation with CD4/CD8 ratio. Immunosenescence found in CHF patients is mainly due to the dynamics of CMV-infection, since the differentiation of T-lymphocyte subsets is related not only to CMV-infection, but also to anti-CMV antibody titers.



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Patients with core antibody positive and surface antigen negative Hepatitis B (anti-HBc+, HBsAg−) on anti-TNF therapy have a low rate of reactivation

Publication date: June 2018
Source:Clinical Immunology, Volume 191
Author(s): William T. Clarke, Shreya S. Amin, Konstantinos Papamichael, Joseph D. Feuerstein, Adam S. Cheifetz
Anti-TNF agents are widely used to treat immune-mediated disorders. Reactivation of Hepatitis B virus (HBV) is associated with immunosuppressive agents and biologics such as anti-TNF. There are limited data and differing guidelines for patients with negative hepatitis B surface antigen (HBsAg−) but positive antibody to hepatitis B core antigen (anti-HBc+) on anti-TNF with regards to outcomes and need for anti-viral prophylaxis. We examined the prevalence of HBV reactivation in a single-center retrospective cohort study of 120 HBsAg−, anti-HBc+ patients on anti-TNF, totaling 346.6 patient years. One patient (0.8%) who had a detectable VL (<20 IU) prior to starting anti-TNF had reactivation of HBV with sero-conversion to positive HBsAg. Three patients (2.5%) had undetectable HBV VL prior to anti-TNF and developed detectable VL while on anti-TNF. In conclusion, there was a low rate of HBV reactivation or development of detectable HBV DNA in HBsAg−, anti-HBc+ patients on anti-TNF.



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The interaction between environmental triggers and epigenetics in autoimmunity

Publication date: July 2018
Source:Clinical Immunology, Volume 192
Author(s): Bruce Richardson
Systemic lupus erythematosus flares when genetically predisposed people encounter environmental agents that cause oxidative stress, such as infections and sunlight. How these modify the immune system to initiate flares is unclear. Drug induced lupus models demonstrate that CD4+ T cells epigenetically altered with DNA methylation inhibitors cause lupus in animal models, and similar T cells are found in patients with active lupus. How infections and sun exposure inhibit T cell DNA methylation is unclear. DNA methylation patterns are replicated each time a cell divides in a process that requires DNA methyltransferase one (Dnmt1), which is upregulated as cells enter mitosis, as well as the methyl donor S-adenosylmethionine, created from dietary sources. Reactive oxygen species that inhibit Dnmt1 upregulation, and a diet poor in methyl donors, combine to cause lupus in animal models. Similar changes are found in patients with active lupus, indicating a mechanism contributing to lupus flares.



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Reversibility of peripheral blood leukocyte phenotypic and functional changes after exposure to and withdrawal from tofacitinib, a Janus kinase inhibitor, in healthy volunteers

Publication date: June 2018
Source:Clinical Immunology, Volume 191
Author(s): Kent J. Weinhold, Jack F. Bukowski, Todd V. Brennan, Robert J. Noveck, Janet S. Staats, Liwen Lin, Linda Stempora, Constance Hammond, Ann Wouters, Christopher F. Mojcik, John Cheng, Mark Collinge, Michael I. Jesson, Anasuya Hazra, Pinaki Biswas, Shuping Lan, James D. Clark, Jennifer A. Hodge
This study evaluated the short-term effects of tofacitinib treatment on peripheral blood leukocyte phenotype and function, and the reversibility of any such effects following treatment withdrawal in healthy volunteers. Cytomegalovirus (CMV)-seropositive subjects received oral tofacitinib 10 mg twice daily for 4 weeks and were followed for 4 weeks after drug withdrawal. There were slight increases in total lymphocyte and total T-cell counts during tofacitinib treatment, and B-cell counts increased by up to 26%. There were no significant changes in granulocyte or monocyte counts, or granulocyte function. Naïve and central memory T-cell counts increased during treatment, while all subsets of activated T cells were decreased by up to 69%. T-cell subsets other than effector memory cluster of differentiation (CD)4+, activated naïve CD4+ and effector CD8+ T-cell counts and B-cell counts, normalized 4 weeks after withdrawal. Following ex vivo activation, measures of CMV-specific T-cell responses, and antigen non-specific T-cell-mediated cytotoxicity and interferon (IFN)-γ production, decreased slightly. These T-cell functional changes were most pronounced at Day 15, partially normalized while still on tofacitinib and returned to baseline after drug withdrawal. Total natural killer (NK)-cell counts decreased by 33%, returning towards baseline after drug withdrawal. NK-cell function decreased during tofacitinib treatment, but without a consistent time course across measured parameters. However, markers of NK-cell-mediated cytotoxicity, antibody-dependent cellular cytotoxicity and IFN-γ production were decreased up to 42% 1 month after drug withdrawal. CMV DNA was not detectable in whole blood, and there were no cases of herpes zoster reactivation. No new safety concerns arose. In conclusion, the effect of short-term tofacitinib treatment on leukocyte composition and function in healthy CMV+ volunteers is modest and largely reversible 4 weeks after withdrawal.



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Epigenetic alterations in primary Sjögren's syndrome – An overview

Publication date: Available online 9 April 2018
Source:Clinical Immunology
Author(s): Juliana Imgenberg-Kreuz, Johanna K. Sandling, Gunnel Nordmark
Primary Sjögren's syndrome (pSS) is a chronic autoimmune rheumatic disease characterized by inflammation of exocrine glands, mainly salivary and lacrimal glands. In addition, pSS may affect multiple other organs resulting in systemic manifestations. Although the precise etiology of pSS remains elusive, pSS is considered to be a multi-factorial disease, where underlying genetic predisposition, environmental factors and epigenetic mechanisms contribute to disease development. Epigenetic mechanisms, such as DNA methylation, histone modifications and non-coding RNAs, may constitute a dynamic link between genome, environment and phenotypic manifestation by their modulating effects on gene expression. A growing body of studies reporting altered epigenetic landscapes in pSS suggests that epigenetic mechanisms play a role in the pathogenesis of pSS, and the reversible nature of epigenetic modifications suggests therapeutic strategies targeting epigenetic dysregulation in pSS. This article reviews our current understanding of epigenetic mechanisms in pSS and discusses implications for novel diagnostic and therapeutic approaches.



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Characterization of a large UNC13D gene duplication in a patient with familial hemophagocytic lymphohistiocytosis type 3

Publication date: June 2018
Source:Clinical Immunology, Volume 191
Author(s): Eitaro Hiejima, Hirofumi Shibata, Takahiro Yasumi, Saeko Shimodera, Masayuki Hori, Kazushi Izawa, Tomoki Kawai, Masaki Matsuoka, Yasuko Kojima, Akira Ohara, Ryuta Nishikomori, Osamu Ohara, Toshio Heike
Familial hemophagocytic lymphohistiocytosis (FHL) type 3 is a life-threatening immune dysregulation syndrome caused by mutations in the UNC13D gene, encoding the munc13–4 protein, which is important for function of cytotoxic lymphocytes. FHL3 accounts for 30–40% of FHL cases, and more than 100 mutations in the UNC13D gene have been described to date. We describe the first case of FHL3 carrying an intragenic duplication of UNC13D, apparently mediated by recombination of Alu elements. NK cell degranulation and munc13–4 protein expression assays are useful for early identification of such mutations, which may be missed by analysis of genomic DNA alone.



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Thrombomodulin (TM) in tumor cell differentiation and periphery blood immune microenvironment in oral squamous cell carcinoma

Publication date: June 2018
Source:Clinical Immunology, Volume 191
Author(s): Jingjing Song, Da Ma, Xiangqi Liu, Yichen Chen, Juan Fang, Vivian Wai Yan Lui, Sijia Zhao, Juan Xia, Bin Cheng, Zhi Wang
Thrombomodulin (TM, also known as CD141), which functions as an anticoagulant, is widely expressed on cell surface of a variety of cell types, including human blood cells as well as certain immune cells. To determine whether TM could be a potential marker for OSCC diagnosis as well as a molecular target for OSCC therapy, we examined the expression of TM in an oral cancer tissue microarray with 153 oral cancer tissues. Further, we also analyzed the expression of TM on DCs of 36 OSCC patients and 36 healthy donors. The expression of TM was determined using standard immunohistochemistry on a tissue microarray of 153 OSCC patients. Flow cytometric analyses were performed to determine the proportions of CD141⁺ DCs in the PBMC of 36 OSCC patients and 36 healthy donors. Clinicopathological correlations were performed based on the available clinical data. Our results showed that in the univariate analysis, high TM expression was significantly associated with well differentiation of tumor cells (P=.001), but not correlated with overall survival and disease-free survival (P>.05). In addition, CD141⁺ DCs were both present in OSCC patients and healthy donors with about 0.04%. There was no significant difference with the percentages of CD141⁺ DCs in the PBMC of OSCC patients and that of the normal control group (P>.05). This study indicates that TM expression might play the most critical role in the differentiation of OSCC tumors. Functional distinctions of CD141⁺ DCs in OSCC patients deserve further investigation to provide important therapeutic understandings for future immunotherapy.



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OAS1 is not associated with MHC class I hyperexpression in the islets of donors with T1D regardless of disease duration

Publication date: June 2018
Source:Clinical Immunology, Volume 191
Author(s): Somayeh Sabouri, Zbigniew Mikulski, Matthias G. von Herrath




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Immunomodulating peptides derived from different human endogenous retroviruses (HERVs) show dissimilar impact on pathogenesis of a multiple sclerosis animal disease model

Publication date: June 2018
Source:Clinical Immunology, Volume 191
Author(s): Shervin Bahrami, Elzbieta Anna Gryz, Jonas Heilskov Graversen, Anne Troldborg, Kristian Stengaard Pedersen, Magdalena Janina Laska
Retroviruses including Human Endogenous Retroviruses (HERVs), contain a conserved region with highly immunomodulatory functions in the transmembrane proteins in envelope gene (env) named immunosuppressive domain (ISU).In this report, we demonstrate that Env59-GP3 peptide holds therapeutic potential in a mouse model of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). The results show that this specific HERV-H derived ISU peptide, but not peptide derived from another env gene HERV-K, decreased the development of EAE in C57BL/6 mice, accompanied by reduced demyelination and inhibition of inflammatory cells. Moreover, here we tested the effect of peptides on macrophages differentiation. The treatment with Env59-GPS peptide modulate the pro-inflammatory M1 profile and anti-inflammatory M2 macrophages, being shown by inhibiting inflammatory M1 hallmark genes/cytokines expression and enhancing expression of M2 associated markers. These results demonstrate that Env59-GP3 ISU peptide has therapeutic potential in EAE possibly through inducing the polarization of M2 macrophages and inhibiting inflammatory responses.



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Epigenetics as biomarkers in autoimmune diseases

Publication date: Available online 21 March 2018
Source:Clinical Immunology
Author(s): Haijing Wu, Jieyue Liao, Qianwen Li, Ming Yang, Ming Zhao, Qianjin Lu
Autoimmune diseases are immune system disorders in which immune cells cannot distinguish self-antigens from foreign ones. The current criteria for autoimmune disease diagnosis are based on clinical manifestations and laboratory tests. However, none of these markers shows both high sensitivity and specificity. In addition, some autoimmune diseases, for example, systemic lupus erythematosus (SLE), are highly heterogeneous and often exhibit various manifestations. On the other hand, certain autoimmune diseases, such as Sjogren's syndrome versus SLE, share similar symptoms and autoantibodies, which also causes difficulties in diagnosis. Therefore, biomarkers that have both high sensitivity and high specificity for diagnosis, reflect disease activity and predict drug response are necessary. An increasing number of publications have proposed the abnormal epigenetic modifications as biomarkers of autoimmune diseases. Therefore, this review will comprehensively summarize the epigenetic progress in the pathogenesis of autoimmune disorders and unearth potential biomarkers that might be appropriate for disease diagnosis and prediction.



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TNFAIP3 haploinsufficiency is the cause of autoinflammatory manifestations in a patient with a deletion of 13Mb on chromosome 6

Publication date: June 2018
Source:Clinical Immunology, Volume 191
Author(s): Clara Franco-Jarava, Hongying Wang, Andrea Martin-Nalda, de la Sierra Daniel Alvarez, Marina García-Prat, Domingo Bodet, Vicenç García-Patos, Alberto Plaja, Francesc Rudilla, Victor Rodriguez-Sureda, Laura García-Latorre, Ivona Aksentijevich, Roger Colobran, Pere Soler-Palacín
There is scarce literature about autoinflammation in syndromic patients. We describe a patient who, in addition to psychomotor and growth delay, presented with fevers, neutrophilic dermatosis, and recurrent orogenital ulcers. Comparative Genomic Hybridization (CGH) array permitted to identify a 13.13Mb deletion on chromosome 6, encompassing 53 genes, and including TNFAIP3 gene (A20). A20 is a potent inhibitor of the NF-kB signalling pathway and restricts inflammation via its deubiquitinase activity. Western blotting and immunoprecipitation assays showed decreased A20 expression and increased phosphorylation of p65 and IkBa. Patient's cells displayed increased levels of total K63-linked ubiquitin and increased levels of ubiquitinated RIP and NEMO after stimulation with TNF. We describe the molecular characterization of an autoinflammatory disease due to a large chromosomal deletion and review the phenotypes of patients with A20 haploinsufficiency. CGH arrays should be the first diagnostic method for comprehensive analysis of patients with syndromic features and immune dysregulation.



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Treatment of antiphospholipid syndrome beyond anticoagulation

Publication date: Available online 3 March 2018
Source:Clinical Immunology
Author(s): Chrisanna Dobrowolski, Doruk Erkan
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder marked by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). At the present time, treatment is primarily focused on anticoagulation. However, there is increasing awareness of the mechanisms involved in APS pathogenesis, which has led to the trial of novel therapies targeting those mechanisms. Following a brief review of the etiopathogenesis of and current management strategies in APS, this paper focuses on the evidence for these potential, targeted APS treatments, e.g., hydroxychloroquine, statins, rituximab, belimumab, eculizumab, defibrotide, sirolimus, and peptide therapy.



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IPEX due to an exon 7 skipping FOXP3 mutation with autoimmune diabetes mellitus cured by selective TReg cell engraftment

Publication date: June 2018
Source:Clinical Immunology, Volume 191
Author(s): Thomas Magg, Volker Wiebking, Raffaele Conca, Stefan Krebs, Stefan Arens, Irene Schmid, Christoph Klein, Michael H. Albert, Fabian Hauck
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare inherited disorder leading to severe organ-specific autoimmunity. IPEX is caused by hemizygous mutations in FOXP3, which codes for a master transcription factor of regulatory T (TReg) cell development and function.We describe a four-year-old boy with typical but slightly delayed-onset of IPEX with autoimmune diabetes mellitus, enteropathy, hepatitis and skin disease. We found the unreported FOXP3 splice site mutation c.816+2T>A that leads to the loss of leucine-zipper coding exon 7. RNA-Seq revealed that FOXP3Δ7 leads to differential expression of FOXP3 regulated genes. After myeloablative conditioning the patient underwent allogeneic HSCT from a matched unrelated donor. HSCT led to the resolution of all IPEX symptoms including insulin requirement despite persisting autoantibody levels. After initial full donor engraftment nearly complete autologous reconstitution was documented, but donor-derived TReg cells persisted with a lineage-specific chimerism of >70% and the patient remained in clinical remission.



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Progressive severe B cell and NK cell deficiency with T cell senescence in adult CD40L deficiency

Publication date: May 2018
Source:Clinical Immunology, Volume 190
Author(s): Vassilios Lougaris, Gaetana Lanzi, Manuela Baronio, Luisa Gazzurelli, Donatella Vairo, Tiziana Lorenzini, Raffaele Badolato, Lucia Dora Notarangelo, Andrea Boschi, Daniele Moratto, Alessandro Plebani




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Comparison of efficacy of TNF inhibitors and abatacept in patients with rheumatoid arthritis; Adjusted with propensity score matching

Publication date: June 2018
Source:Clinical Immunology, Volume 191
Author(s): Satoshi Kubo, Shingo Nakayamada, Kazuhisa Nakano, Norifumi Sawamukai, Shintaro Hirata, Kentaro Hanami, Kazuyoshi Saito, Yoshiya Tanaka
The aim of this study was to compare the clinical outcome of patients with rheumatoid arthritis seen in routine clinical practice treated with either TNF inhibitors or abatacept. To overcome potential bias, both propensity score matching and Inverse Probability of Treatment Weighting were used for patient selection. The propensity score matching procedure selected 315 matched pairs of patients who were treated with TNF inhibitors or abatacept. At week 52, SDAI in TNF inhibitors was lower than abatacept. In contrast, analysis of biologics-naive patients using the propensity-score matching (n = 150; in each group) showed comparable clinical efficacy. Consistent results were obtained by the use of Inverse Probability of Treatment Weighting (581 patients treated with TNF inhibitors and 353 patients treated with abatacept). The predictors of response to each treatment were different; abatacept appeared to benefit patients with high baseline RF titers while TNF inhibitors appeared to benefit patients with low baseline HAQ-DI.



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Anatomic factors affecting the use of ultrasound to predict vocal fold motion: A pilot study

Ultrasonography is a well-established modality for visualization of head and neck anatomy. Using ultrasound to detect vocal fold mobility has been described before, but no study has evaluated factors affecting the exam reliability. The aim of the study is to determine anatomic factors influencing the reliability of ultrasound to detect vocal fold motion.Methods and materialsPatients underwent ultrasound evaluation and flexible laryngoscopy to assess vocal fold motion from August 2015 to March 2016.

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Aspergillus fumigatus viability drives allergic responses to inhaled conidia

Aspergillus fumigatus induced allergic airway disease has been shown to involve conidial germination in vivo but the immunological mechanisms remain uncharacterized.

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Dermoscopic features of onychotillomania: A study of 36 cases

Onychotillomania is a nail-picking disorder that is likely underreported and often misdiagnosed, The dermoscopic features of onychotillomania include scales, absence of the nail plate, wavy lines, hemorrhages, speckled dots, melanonychia, and nail bed pigmentation, Recognizing the common dermoscopic features of onychotillomania will assist the clinician in the diagnosis and management of this disorder.

https://ift.tt/2quSQIi

Certolizumab Pegol for the Treatment of Chronic Plaque Psoriasis: Results Through 48 Weeks of a Phase 3, Multicenter, Randomized, Double-Blinded, Etanercept- and Placebo-Controlled Study (CIMPACT)

Certolizumab pegol is an Fc-free, PEGylated anti-tumor necrosis factor biologic.; In this phase 3 study, both certolizumab doses improved psoriasis symptoms at Week 12 that was maintained, following re-randomization, through Week 48 with a safety profile consistent with its class.; The higher dose of certolizumab may provide superior efficacy.

https://ift.tt/2GWT7ht

CME Part 1: Hair disorders in cancer patients

Cytotoxic chemotherapies, molecularly targeted therapies, immunotherapies, radiotherapy, stem cell transplants, and endocrine therapies may lead to hair disorders (including alopecia, hirsutism, hypertrichosis, pigmentary and textural hair changes). The mechanisms underlying these changes are varied and remain incompletely understood, hampering the development of preventive or therapeutic guidelines. The psychosocial impact of chemotherapy -induced alopecia has been well-documented mainly in the oncology literature, however the effect of other alterations such as radiation-induced alopecia, hirsutism, changes in hair color or texture on quality of life have not been described.

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Tracking tumor kinetics in patients with germline CYLD mutations

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Certolizumab Pegol for the Treatment of Chronic Plaque Psoriasis: Results through 48 Weeks from Two Phase 3, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Studies (CIMPASI-1 and CIMPASI-2)

Certolizumab pegol is an Fc-Free, PEGylated anti-tumor necrosis factor biologic. In these phase 3 psoriasis studies, certolizumab pegol 200 mg and 400 mg every 2 weeks demonstrated statistically significant and clinically meaningful improvements versus placebo; no new safety signals were observed. Certolizumab pegol affords additional psoriasis treatment options.

https://ift.tt/2qw65ro

CME Part 2: Hair disorders in cancer survivors Persistent chemotherapy-induced alopecia, persistent radiotherapy-induced alopecia, and hair growth disorders related to endocrine therapy or cancer surgery

With increasing survival rates across all cancers, survivors represent a growing population that is frequently affected by persistent or permanent hair growth disorders as a result of systemic therapies, radiotherapy, surgical procedures, and therapeutic transplants. These hair disorders include persistent chemotherapy-induced alopecia, persistent radiotherapy-induced alopecia, endocrine therapy-induced alopecia and hirsutism, post-surgery alopecia and localized hypertrichosis, alopecia attributed to therapeutic transplants, and to novel anticancer therapies.

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Severe perineal lacerations after vaginal delivery: are they an anesthesiologist's problem?

Purpose of review Perineal tears or lacerations are common occurrences after vaginal delivery. Understanding the degree of severity of these tears and the immediate and long-term complications of severe perineal lacerations can assist anesthesiologists with the management of these patients in the immediate postpartum period. Recent findings Severe perineal lacerations have a high degree of association with postpartum depression. The presence of neuraxial labor analgesia decreases the odds of severe perineal lacerations. Summary Neuraxial labor analgesia does not directly predispose parturients to the development of perineal lacerations, and may even be protective against these injuries. Correspondence to Feyce Peralta, MD, 251 E. Huron St. F5-704, Chicago, IL 60611, USA. Tel: +1 312 472 3585; e-mail: feyce.peralta@northwestern.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Clinical pearls part 3: anaesthetic management of abnormally invasive placentation

Purpose of review Abnormal placentation is a clinical condition seen increasingly in the pregnant population. It is associated with significant morbidity and mortality, which may be mitigated through robust multidisciplinary care for these patients. The role of maternal critical care for these patients has largely been ignored in the literature. Recent findings Advances in pharmacological management of bleeding with recent publications of large multicentre trials in addition to new technologies in the management of massive obstetric haemorrhage (MOH) have revolutionized the management of abnormal placentation. These include the use of tranexamic acid, interventional radiology, cell saver technology, and point-of-care coagulation tests. The role of maternal critical care for the optimization of postoperative complications and physiological derangements has not been considered widely in the literature. This article summarizes the current evidence for interventions and suggests a protocol for the management of these high-risk patients. Summary A robust protocol outlining the key elements of the management of placenta accreta, including optimizing postoperative care, should be in place to promote desired outcomes. Correspondence to Dr Vinod Patil, Consultant Obstetric Anaesthetist, Department of Anesthesiology, Queens Hospital, BHR University Hospital NHS Trust Romford, Romford RM7 0AG, UK. Tel: 44 1708503727; e-mail: Vinodpatiluk@gmail.com Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Anatomic factors affecting the use of ultrasound to predict vocal fold motion: A pilot study

Publication date: Available online 13 April 2018
Source:American Journal of Otolaryngology
Author(s): Maheer M. Masood, Benjamin Huang, Allie Goins, Trevor G. Hackman
PurposeUltrasonography is a well-established modality for visualization of head and neck anatomy. Using ultrasound to detect vocal fold mobility has been described before, but no study has evaluated factors affecting the exam reliability. The aim of the study is to determine anatomic factors influencing the reliability of ultrasound to detect vocal fold motion.Methods and materialsPatients underwent ultrasound evaluation and flexible laryngoscopy to assess vocal fold motion from August 2015 to March 2016. Length, accuracy, and clarity of ultrasound examination were assessed, compared to flexible laryngoscopy. For patients with prior neck CT scan imaging, laryngeal anatomy was independently assessed by a blinded neuroradiologist.ResultsA total of 23 patients, 21 with bilateral vocal fold motion and two with unilateral paralysis, were enrolled. Vocal folds were visible in 19 patients (82%). Eight patients (42%) had good/excellent view and 11 patients (58%) had fair/difficult view. The ultrasound correctly detected absent movement of the vocal fold in the two patients with unilateral paralysis. A total of 19 patients had CT scans, and a linear correlation (r² = 0.65) was noted between the anterior thyroid cartilage angle measured on CT and the grade of view on ultrasound.ConclusionUltrasound was able to detect vocal fold motion in 82% of randomly screened patients. Ease of detection of vocal fold motion correlated with the anterior thyroid angle. Further studies are warranted to investigate the reproducibility of our results and how this might impact use of ultrasound for detection of vocal fold motion in the operative setting.



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Risk of Methotrexate Dosing Errors Prompts EMA Review

A recent routine assessment found that serious adverse events related to overdose, including fatalities, are still occurring, despite measures already in place to reduce dosing errors.
News Alerts

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Analysis of microRNA expression in the thymus of Myasthenia Gravis patients opens new research avenues

Publication date: Available online 13 April 2018
Source:Autoimmunity Reviews
Author(s): Mélanie A. Cron, Solène Maillard, Fabien Delisle, Nolwenn Samson, Frédérique Truffault, Maria Foti, Elie Fadel, Julien Guihaire, Sonia Berrih-Aknin, Rozen Le Panse
In early-onset Myasthenia Gravis (MG) with anti-acetylcholine receptor antibodies, thymic abnormalities associated with ectopic germinal centers are frequent. miRNAs by acting as post-transcriptional regulators are involved in autoimmunity. To investigate the implication of miRNAs in thymic changes associated with early-onset MG, we performed a miRnome study and data were analyzed with different approaches. miRNAs of interest were further investigated by RT-PCR and transfection experiments for functional tests.First, analyzing specific dysregulated miRNAs, we focused our attention on miR-7-5p and miR-125a-5p, and confirmed by RT-PCR their respective down- and up-regulation in MG thymuses. miR-7 was the most down-regulated thymic miRNA in MG and we observed an inverse correlation between its expression and CCL21 mRNA expression. We next showed that miR-7 down-regulation was due to thymic epithelial cells and by transfecting these cells with miR-7, we demonstrated that it controlled CCL21 release. As CCL21 is essential for germinal center development, we suggested that miR-7 could be involved in thymic changes associated with MG. miR-125a was up-regulated in MG thymuses and is of great interest as it is known to regulate FoxP3 expression, and to modulate the different inflammatory signaling pathways.Thanks to this thymic miRnome study, we also showed the specific dysregulation of miRNA clusters. In particular, we observed that miRNAs localized at the extremity of the X chromosome were down-regulated. This effect seemed linked to their close localization to the fragile X mental retardation 1 gene (FMR1) and the DNA methylation status.Altogether, this miRnome analysis demonstrated that specific thymic miRNAs can be associated with MG and provides novel insights into the pathogenesis of MG.



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Impact of intra-operative fluid and noradrenaline administration on early postoperative renal function after cystectomy and urinary diversion: A retrospective observational cohort study

BACKGROUND The use of noradrenaline to enable a restrictive approach to intra-operative fluid therapy to avoid salt and water overload has gained increasing acceptance. However, concerns have been raised about the impact of this approach on renal function. OBJECTIVES To identify risk factors for acute kidney injury (AKI) in patients undergoing cystectomy with urinary diversion and determine whether administration of noradrenaline and intra-operative hydration regimens affect early postoperative renal function. DESIGN Retrospective observational cohort study. SETTING University hospital, from 2007 to 2016. PATIENTS A total of 769 consecutive patients scheduled for cystectomy and urinary diversion. Those with incomplete data and having pre-operative haemodialysis were excluded. MAIN OUTCOME MEASURES AKI was defined as a serum creatinine increase of more than 50% over 72 postoperative hours. Multiple logistic regression analysis was performed to model the association between risk factors and AKI. RESULTS Postoperative AKI was diagnosed in 86/769 patients (11.1%). Independent predictors for AKI were the amount of crystalloid administered (odds ratio (OR) 0.79 [95% confidence interval (CI), 0.68 to 0.91], P = 0.002), antihypertensive medication (OR 2.07 [95% CI, 1.25 to 3.43], P = 0.005), pre-operative haemoglobin value (OR 1.02 [95% CI, 1.01 to 1.03], P = 0.010), duration of surgery (OR 1.01 [95% CI, 1.00 to 1.01], P = 0.002), age (OR 1.32 [95% CI, 1.44 to 1.79], P = 0.002) but not the administration of noradrenaline (OR 1.09 [95% CI, 0.94 to 1.21], P = 0.097). Postoperative AKI was associated with longer hospital stay (18 [15 to 22] vs. 16 [15 to 19] days; P = 0.035) and a higher 90-day major postoperative complication rate (41.9 vs. 27.5%; P = 0.002). CONCLUSION Noradrenaline administration did not increase the risk for AKI. A too restrictive approach to administration of crystalloids was associated with an increased risk for AKI, particularly in older patients, those receiving antihypertensive medication, and those whose surgery was prolonged. As AKI was associated with longer hospital stay and increased postoperative morbidity, these observations should be taken into account to improve outcome when addressing peri-operative fluid management. TRIAL REGISTRATION Not applicable. Correspondence to Patrick Y. Wuethrich, MD, Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland Tel: +41 316322725; fax: +41 316320554; e-mail: patrick.wuethrich@insel.ch © 2018 European Society of Anaesthesiology

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Aspergillus fumigatus viability drives allergic responses to inhaled conidia

Publication date: Available online 13 April 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Ajay P. Nayak, Tara L. Croston, Angela R. Lemons, W.T. Goldsmith, Nikki B. Marshall, Michael L. Kashon, Dori R. Germolec, Donald H. Beezhold, Brett J. Green
BackgroundAspergillus fumigatus induced allergic airway disease has been shown to involve conidial germination in vivo but the immunological mechanisms remain uncharacterized.ObjectiveA subchronic murine exposure model was used to examine the immunological mediators that are regulated in response to either culturable or non-culturable A. fumigatus conidia.MethodsFemale B6C3F1/N mice were repeatedly dosed via inhalation with 1 x 105 viable or heat inactivated conidia (HIC), twice a week for 13 weeks (26 exposures). Control mice inhaled HEPA-filtered air. The influence of A. fumigatus conidial germination on the pulmonary immunopathological outcomes was evaluated by flow cytometry analysis of cellular infiltration in the airways, assessment of lung mRNA expression, and quantitative proteomics and histopathology of whole lung tissue.ResultsRepeated inhalation of viable conidia, but not HIC, resulted in allergic inflammation marked by vascular remodeling, extensive eosinophilia, and accumulation of alternatively activated macrophages (AAMs) in the murine airways. More specifically, mice that inhaled viableconidia resulted in a mixed TH1 and TH2 (IL-13) cytokine response. Recruitment of eosinophils corresponded with increased Ccl11 transcripts. Furthermore, genes associated with M2 or alternatively activated macrophage polarization (e.g. Arg1, Chil3 and Retnla) were significantly upregulated in viable A. fumigatus exposed mice. In mice inhaling HIC, CD4+ T cells expressing IFN-γ (TH1) dominated the lymphocytic infiltration. Quantitative proteomics of the lung revealed metabolic reprogramming accompanied by mitochondrial dysfunction and endoplasmic reticulum stress stimulated by oxidative stress from repetitive microbial insult.ConclusionOur studies demonstrate that A. fumigatus conidial viability in vivo is critical to the immunopathological presentation of chronic fungal allergic disease.



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Protocol incorporating airway CT decreases negative bronchoscopy rates for suspected foreign bodies in pediatric patients

Publication date: June 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 109
Author(s): Omar G. Ahmed, Robert P. Guillerman, Carla M. Giannoni
Background: Foreign body aspiration (FBA) is the 4th leading cause of death in children between the ages 1-5. Although direct laryngoscopy and bronchoscopy (DL&B) is the reference standard for diagnosis of pediatric airway foreign bodies, there is a high negative bronchoscopy rate, exposing patients to unnecessary operative and anesthetic risks and costs.Methods: A clinical care protocol entailing the selective use of low-dose non-contrast airway computed tomography (CT) for children with an intermediate risk for FBA on the basis of clinical exam and chest radiography was implemented to decrease the negative DL&B rate. A retrospective review was conducted to compare negative bronchoscopy rates before and after implementation of the new protocol and the diagnostic performance characteristics of airway CT for airway foreign bodies were analyzed.Results: After implementation of the airway FB clinical care protocol entailing selective airway CT, the overall negative bronchoscopy rate decreased from an institutional historical rate of 37% (54/145) to 17% (10/56) (p = .06). The overall sensitivity, specificity, and positive and negative predictive value of airway CT for FB was 91%, 100%, 100%, and 97% respectively.Conclusions: Low-dose non-contrast airway CT is highly sensitive and specific for airway foreign bodies, and its selective use in a clinical care protocol for children with suspected foreign body aspiration could greatly reduce the negative bronchoscopy rate, thereby decreasing operative risks and costs.



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Impact of supraglottoplasty on parental preception of swallowing using a 10 question swallowing index

Publication date: June 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 109
Author(s): Sohit Paul Kanotra, Vil Vaitaitis, Hunter Hopkins, Meghan Fletcher, Courtney K. Gonsoulin, Brent Keith
IntroductionLaryngomalacia can have a significant impact on swallowing function. Most of the studies in literature have focused on evaluating swallowing dysfunction in children with Laryngomalacia using clinical assessment and swallowing studies i.e. functional endoscopic evaluation of swallowing or videofluroscopic evaluation of swallowing.ObjectiveThe objective of the current study was to evaluate the parental perception of swallowing using a newly devised 10-point swallowing index before and after supraglottoplasty.Material and methodsThis was a prospective study performed at a tertiary care Aerodigestive center over a period of 18 months. A total of 51 supraglottoplasties were performed by a single surgeon over an 18-month period. Parents were asked to fill a non validated 10-point questionnaire before and after supraglottoplasty. Of the 51 surgeries, 34 surveys were completed, and 28 surveys were included in the study. All the patients were classified in to mild, moderate and severe laryngomalacia based on the established criterion. Each point in the index was graded on the Likert scale.ResultsA total of 28 patients who underwent supraglottoplasty were included in the study. There was a significant improvement in the overall parental perception in the swallowing of children with laryngomalacia following supraglottoplasty. There was statistically significant improvement in 9 out of 10 indices on the questionnaire.ConclusionSupraglottoplasty has an overall positive impact on parental perception of swallowing in children with Laryngomalacia. Caregivers had fewer concerns postoperatively, with fewer choking spells and breathing issues during feeds, and a greater satisfaction with the amount consumed at each feed. This Index adds a valuable subjective component to pediatric swallowing assessments pre and post supraglottoplasty. This tool could be used in conjunction with MBSS and FEES measures to provide a more comprehensive assessment.



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Guía clínica sobre implantes de conducción de vía ósea

Publication date: Available online 13 April 2018
Source:Acta Otorrinolaringológica Española
Author(s): María José Lavilla Martín de Valmaseda, Laura Cavalle Garrido, Alicia Huarte Irujo, Faustino Núñez Batalla, Manuel Manrique Rodriguez, Ángel Ramos Macías, Carlos de Paula Vernetta, Elisa Gil-Carcedo Sañudo, Luis Lassaleta, Isabel Sánchez-Cuadrado, Juan Manuel Espinosa Sánchez, Ángel Batuecas Caletrio, Carlos Cenjor Español
Introducción y objetivosEn la última década se han producido numerosos y relevantes avances en el tratamiento de la hipoacusia transmisiva y mixta que han desembocado en una ampliación de las indicaciones de los implantes de conducción de vía ósea y la aparición de nuevos dispositivos. La Comisión Científica de Audiología de la Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello (SEORL-CCC), junto con las comisiones de Otología y Otoneurología, ha llevado a cabo una revisión del estado actual de los implantes de vía ósea con la finalidad de ofrecer a los especialistas de Otorrinolaringología, a los profesionales de la sanidad, a las autoridades sanitarias y a la sociedad en general una guía clínica sobre implantes de conducción de vía ósea.MétodosEsta guía clínica sobre implantes de conducción ósea contiene información sobre los siguientes temas: 1) definición y descripción de los implantes auditivos de vía ósea; 2) indicaciones actuales y emergentes de los implantes de vía ósea; compatibilidad y resonancia magnética, y 3) requisitos organizativos para un programa de implantes de vía ósea.Resultado y conclusionesLa finalidad de esta guía es describir los diferentes sistemas de conducción ósea, sus particularidades e indicaciones, con el objeto de aportar unas coordenadas que ayuden a todos estos agentes en las tomas de decisiones que deban asumir en los diferentes ámbitos de responsabilidad en los que están enmarcados en sus áreas de trabajo.Introduction and goalsDuring the last decade there have been multiple and relevant advances in conduction and mixed hearing loss treatment. These advances and the appearance of new devices have extended the indications for bone-conduction implants.The Scientific Committee of Audiology of the Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello SEORL-CCC (Spanish Society of Otolaryngology and Head and Neck Surgery), together with the Otology and Otoneurology Committees, have undertaken a review of the current state of bone-conduction devices with updated information, to provide a clinical guideline on bone-conduction implants for otorhinolaryngology specialists, health professionals, health authorities and society in general.MethodsThis clinical guideline on bone-conduction implants contains information on the following: 1) Definition and description of bone-conduction devices; 2) Current and upcoming indications for bone conduction devices: Magnetic resonance compatibility; 3) Organization requirements for a bone-conduction implant programme.Results and conclusionsThe purpose of this guideline is to describe the different bone-conduction implants, their characteristics and their indications, and to provide coordinated instructions for all the above-mentioned agents for decision making within their specific work areas.



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Acute acalculous cholecystitis of an intrahepatic gallbladder causing Mirizzis syndrome

We present the case of a young female with symptoms of biliary colic and a biochemical profile consistent with biliary obstruction. Imaging was suspicious for Mirizzi's syndrome. Intraoperatively, the patient was found to have a complete intrahepatic gallbladder causing common hepatic duct compression with final pathology confirming acute cholecystitis. We review the embryological development of the gallbladder as well as clinical presentation of Mirizzi's syndrome. Special consideration for clinical workup and surgical management is discussed.

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Embryonal rhabdomyosarcoma of urinary bladder in an adult patient: an unusual manifestation

An adult man presented with off and on painless haematuria, which was diagnosed as bladder mass on contrast-enhanced CT. He underwent transurethral resection of bladder tumour with complete resection. A diagnosis of embryonal rhabdomyosarcoma was made following histopathology and immunohistochemistry report. The patient was planned for radical cystectomy but was found to have large recurrent infiltrating bladder mass with liver and bone metastasis. Hence, the plan for radical cystectomy was deferred and the patient was counselled regarding chemotherapy (vincristine, cisplatin and doxorubicin regime). The patient tolerated the first cycle of chemotherapy, but his condition deteriorated prior to the second cycle and the patient expired.

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Malignant rhabdoid tumour of the neck in a neonate

Fetal neck masses are rare, and present a challenge antenatally, during delivery and in making a diagnosis. In this report, we detail the presentation of a neonate with a neck mass diagnosed in the third trimester. The baby was delivered by ex utero intrapartum therapy (EXIT). Investigations sent included an MRI with limited CT cuts, and a biopsy, which lead to the diagnosis of a malignant rhabdoid tumour. This is rare and the overall survival is low.

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Infertility: an out-of-the-box cause of postmenopausal endometrial thickening

Description

The presence of intrauterine foreign bodies (IFBs) is a rare condition that may lead to chronic endometritis through local inflammation. According to literature, IFB may be the cause of 0.02% to 0.15% of the cases of infertility, and of abnormal uterine bleeding, pelvic pain and abnormal vaginal discharge.1

We present the case of a 63-year-old, nulligravida, postmenopausal woman who complained of scarce genital bleeding and vaginal discharge for about 1 year. The patient denied other symptoms like fever, pelvic pain, dyspareunia or weight loss. In terms of relevant previous history, this patient had a laparotomy and myomectomy performed 30 years before because of a transmural uterine leiomyoma diagnosed in the workup for primary infertility. Even after surgery, no pregnancy was achieved. Menopause occurred at 52 years of age and no hormonal replacement therapy was used. No other relevant previous medical or surgical history was found.

On...

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Anti-TNF therapy-induced lupus erythematosus-like syndrome in a patient treated with adalimumab for cutaneous psoriasis

A 44-year-old woman with cutaneous psoriasis and no history of joint involvement recently treated with adalimumab was admitted to the inpatient Internal Medicine service for uncontrolled, severe joint pain so debilitating that it limited her activities of daily living and prevented her from working as a medical technologist. She had stopped taking adalimumab 3 weeks prior to presentation after receiving approximately 2.5 months of therapy for cutaneous psoriasis unresponsive to trials of topical steroids and methotrexate. Antinuclear antibody and anti-double-stranded DNA antibodies were positive at high titres. She received a course of oral corticosteroids with improvement in her symptoms.

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Ruptured choledochal cyst during early pregnancy with successful fetomaternal outcome

Choledochal cyst is a rare congenital malformation which is usually found in young children and adolescents but can rarely present in the adult age group. It can present with several complications like cholangitis, pancreatitis, biliary cirrhosis, portal hypertension, liver abscess, malignancy and rarely spontaneous rupture (in 2% of cases) causing biliary peritonitis. A case of spontaneous rupture of choledochal cyst during second trimester of pregnancy is reported where the patient was managed by minimal surgery, peritoneal washout, placement of T-tube and planned for definitive treatment in the postpartum period. The pregnancy continued till 35 weeks with favourable fetomaternal outcome.

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Orbital cystic schwannoma masquerading as hydatid cyst

Gradually increasing abaxial proptosis in a middle-aged female patient revealed a large well-defined cystic lesion behind the globe extending till the orbital apex. B scan ultrasound and CT findings were favouring a diagnosis of orbital hydatid cyst. Thus as a diagnostic/curative surgical protocol, the cystic lesion was removed in total. However, intraoperative gross specimen examination was not classical of hydatid cyst, thus a further histopathological evaluation was carried out, which confirmed the diagnosis of orbital schwannoma with extensive cystic degeneration. Postoperatively the clinical course was uneventful at the end of 1 year.

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Meningitis due to scrub typhus: the importance of a differential diagnosis in an endemic area

A patient with fever and neck stiffness was treated as partially treated bacterial meningitis based on history, examination and cerebrospinal fluid analysis. After initial improvement with ceftriaxone, vancomycin and dexamethasone, symptoms recurred. Fever resolved promptly after treatment was started with doxycycline, when scrub typhus immunoglobulin M test came positive. Meningitis is a well-known complication of scrub typhus. However, scrub typhus is seldom considered in the differential diagnosis of meningitis in the Indian subcontinent. Early diagnosis and prompt institution of doxycycline therapy may lead to early cure of scrub typhus even when features of meningitis supervene. However, ceftriaxone which is commonly used to treat bacterial meningitis is suboptimal in the treatmenwgt36t of scrub typhus.

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Misguided urinary catheter: an uncommon complication of a common solution

Description 

A 61-year-old man was wheeled in to our emergency triage bleeding profusely from his mouth and nose in an unconscious state. His Glasgow Coma Scale was 7 and was intubated for airway safety. A failed anterior nasal packing was followed by insertion of a Foley urinary catheter through the right nostril to secure posterior nasal packing and haemostasis. CT of the brain following nasal packing showed diffuse traumatic subarachnoid haemorrhage and basifrontal contusions with multiple fractures of the anterior cranial fossa, cribriform plate including the frontal sinus. Multiple specs of air in the frontal lobe was initially mistaken as pneumocephalus (Hounsfield unit –971) (figure 1). The Foley catheter had inadvertently found its way to the brain through the cribriform plate, and the bulb was inflated just above the defect (figure 2). The catheter was deflated and removed soon after imaging. The patient underwent a...

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Liver Failure in Advanced Adult-onset Polycystic Kidney Disease

Polycystic liver disease is the most common extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). Hepatic cysts are typically incidental findings, with occasional complications including cyst haemorrhage, infection and rupture. In contrast to the typically benign course of polycystic liver disease, we present a rare case of fatal decompensated liver failure in a patient with ADPKD. This is a case of a 58-year-old man with end-stage renal disease on haemodialysis presenting with new-onset ascites and decompensated liver failure following bilateral nephrectomy. Cirrhosis in ADPKD is a late manifestation of the disease, but it should be considered in the perioperative risk of patients with ADPKD.

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Applying Unique Molecular Identifiers in Next Generation Sequencing Reveals a Constrained Viral Quasispecies Evolution under Cross-Reactive Antibody Pressure Targeting Long Alpha Helix of Hemagglutinin.

Hauck, NC; Kirpach, J; Kiefer, C; Farinelle, S; Maucourant, S; Morris, SA; Rosenberg, W; ... Lu, I-N; + view all Hauck, NC; Kirpach, J; Kiefer, C; Farinelle, S; Maucourant, S; Morris, SA; Rosenberg, W; He, FQ; Muller, CP; Lu, I-N; - view fewer (2018) Applying Unique Molecular Identifiers in Next Generation Sequencing Reveals a Constrained Viral Quasispecies Evolution under Cross-Reactive Antibody Pressure Targeting Long Alpha Helix of Hemagglutinin. Viruses , 10 (4) , Article 148. 10.3390/v10040148 . Green open access

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Weaving the health and pharmaceutical care agenda through the themes of the commonwealth heads of government meeting (CHOGM), London 2018

Rutter, V; Chan, AHY; Tuck, C; Bader, L; Baber, Z; Bates, I; (2018) Weaving the health and pharmaceutical care agenda through the themes of the commonwealth heads of government meeting (CHOGM), London 2018. Journal of Pharmaceutical Policy and Practice , 11 , Article 10. 10.1186/s40545-018-0140-3 . Green open access

https://ift.tt/2qvktkc

Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution

Baker, A-M; Huang, W; Wang, X-MM; Jansen, M; Ma, X-J; Kim, J; Anderson, CM; ... Graham, TA; + view all Baker, A-M; Huang, W; Wang, X-MM; Jansen, M; Ma, X-J; Kim, J; Anderson, CM; Wu, X; Pan, L; Su, N; Luo, Y; Domingo, E; Heide, T; Sottoriva, A; Lewis, A; Beggs, AD; Wright, NA; Rodriguez-Justo, M; Park, E; Tomlinson, I; Graham, TA; - view fewer (2017) Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution. Nature Communications , 8 , Article 1998. 10.1038/s41467-017-02295-5 . Green open access

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Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure

Sands, SA; Mebrate, Y; Edwards, BA; Nernati, S; Manisty, CH; Desai, AS; Wellman, A; ... Malhotra, A; + view all Sands, SA; Mebrate, Y; Edwards, BA; Nernati, S; Manisty, CH; Desai, AS; Wellman, A; Willson, K; Francis, DP; Butler, JP; Malhotra, A; - view fewer (2017) Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure. American Journal of Respiratory and Critical Care Medicine , 195 (2) pp. 237-246. 10.1164/rccm.201604-07610C . Green open access

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The Enlightened Brain: Novel Imaging Methods Focus on Epileptic Networks at Multiple Scales

Rossi, LF; Kullmann, DM; Wykes, RC; (2018) The Enlightened Brain: Novel Imaging Methods Focus on Epileptic Networks at Multiple Scales. Frontiers in Cellular Neuroscience , 12 , Article 82. 10.3389/fncel.2018.00082 . Green open access

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No way out: when RNA elements promote nuclear retention

Agostini, F; Ule, J; Zagalak, JA; (2018) No way out: when RNA elements promote nuclear retention. EMBO Journal , 37 (6) , Article e99123. 10.15252/embj.201899123 .

https://ift.tt/2HkYBSs

Diagnosis and Prognosis in Sudden Cardiac Arrest Survivors Without Coronary Artery Disease: Utility of a Clinical Approach Using Cardiac Magnetic Resonance Imaging

Rodrigues, P; Joshi, A; Williams, H; Westwood, M; Petersen, SE; Zemrak, F; Schilling, RJ; ... Mohiddin, S; + view all Rodrigues, P; Joshi, A; Williams, H; Westwood, M; Petersen, SE; Zemrak, F; Schilling, RJ; Kirkby, C; Wragg, A; Manisty, C; Mohiddin, S; - view fewer (2017) Diagnosis and Prognosis in Sudden Cardiac Arrest Survivors Without Coronary Artery Disease: Utility of a Clinical Approach Using Cardiac Magnetic Resonance Imaging. Circulation: Cardiovascular Imaging , 10 (12) , Article e006709. 10.1161/CIRCIMAGING.117.006709 .

https://ift.tt/2v7kK1u

Affective problems and decline in cognitive state in older adults: A systematic review and meta-analysis

John, A; Patel, U; Rusted, J; Richards, M; Gaysina, D; (2018) Affective problems and decline in cognitive state in older adults: A systematic review and meta-analysis. Psychological Medicine (In press). Green open access

https://ift.tt/2Hevb8D

Building motivation to participate in a quality improvement collaborative in NHS hospital trusts in Southeast England: a qualitative participatory evaluation.

Lalani, M; Hall, K; Skrypak, M; Laing, C; Welch, J; Toohey, P; Seaholme, S; ... Marshall, M; + view all Lalani, M; Hall, K; Skrypak, M; Laing, C; Welch, J; Toohey, P; Seaholme, S; Weijburg, T; Eyre, L; Marshall, M; - view fewer (2018) Building motivation to participate in a quality improvement collaborative in NHS hospital trusts in Southeast England: a qualitative participatory evaluation. BMJ Open , 8 (4) , Article e020930. 10.1136/bmjopen-2017-020930 . Green open access

https://ift.tt/2vbe2rx

Provision of magnetic resonance imaging for patients with 'MR-conditional' cardiac implantable electronic devices: an unmet clinical need

Sabzevari, K; Oldman, J; Herrey, AS; Moon, JC; Kydd, AC; Manisty, C; (2016) Provision of magnetic resonance imaging for patients with 'MR-conditional' cardiac implantable electronic devices: an unmet clinical need. Europace , 19 (3) pp. 425-431. 10.1093/europace/euw063 . Green open access

https://ift.tt/2JJfzs2

Tailoring the surface of polymeric nanofibres generated by pressurised gyration

Illangakoon, UE; Mahalingam, S; Colombo, P; Edirisinghe, M; (2016) Tailoring the surface of polymeric nanofibres generated by pressurised gyration. Surface Innovations , 4 (3) pp. 167-178. 10.1680/jsuin.16.00007 . Green open access

https://ift.tt/2EIYf2v

Patient-Reported Outcomes following Single- and Multiple-Radius Total Knee Replacement: A Randomized, Controlled Trial

Mushtaq, N; Liddle, AD; Isaac, D; Dillow, K; Gill, P; (2018) Patient-Reported Outcomes following Single- and Multiple-Radius Total Knee Replacement: A Randomized, Controlled Trial. The Journal of Knee Surgery , 31 (1) pp. 87-91. 10.1055/s-0037-1602132 .

https://ift.tt/2JJkCZh

Contemporary Comparative Anthropology – The Why We Post Project

Miller, D; Costa, E; Haapio-Kirk, L; Haynes, N; Sinanan, J; McDonald, T; Nicolescu, R; ... Wang, X; + view all Miller, D; Costa, E; Haapio-Kirk, L; Haynes, N; Sinanan, J; McDonald, T; Nicolescu, R; Spyer, J; Venkatraman, S; Wang, X; - view fewer (2017) Contemporary Comparative Anthropology – The Why We Post Project. Ethnos 10.1080/00141844.2017.1397044 . (In press).

https://ift.tt/2EIuXRQ

Nanocomposites: Suitable Alternatives as Antimicrobial Agents

Matharu, RK; Ciric, L; Edirisinghe, MJ; (2018) Nanocomposites: Suitable Alternatives as Antimicrobial Agents. Nanotechnology 10.1088/1361-6528/aabbff . (In press).

https://ift.tt/2JJQAEY

Cavity assisted spin reconfiguration in a quantum wire

Yan, C; Kumar, S; Pepper, M; See, P; Farrer, I; Ritchie, D; Griffiths, J; Yan, C; Kumar, S; Pepper, M; See, P; Farrer, I; Ritchie, D; Griffiths, J; Jones, G; - view fewer (2018) Cavity assisted spin reconfiguration in a quantum wire. In: (pp. 012003). Green open access

https://ift.tt/2ve19gi

Surface ruptures following the 30 October 2016 Mw 6.5 Norcia earthquake, central Italy

Civico, R; Pucci, S; Villani, F; Pizzimenti, L; De Martini, PM; Nappi, R; Agosta, F; ... Point, J; + view all Civico, R; Pucci, S; Villani, F; Pizzimenti, L; De Martini, PM; Nappi, R; Agosta, F; Alessio, G; Alfonsi, L; Amanti, M; Amoroso, S; Aringoli, D; Auciello, E; Azzaro, R; Baize, S; Bello, S; Benedetti, L; Bertagnini, A; Binda, G; Bisson, M; Blumetti, AM; Bonadeo, L; Boncio, P; Bornemann, P; Branca, S; Braun, T; Brozzetti, F; Bru-Nori, CA; Burrato, P; Caciagli, M; Campobasso, C; Carafa, M; Cinti, FR; Cirillo, D; Comerci, V; Cucci, L; De Ritis, R; Deiana, G; Del Carlo, P; Del Rio, L; Delorme, A; Di Manna, P; Di Naccio, D; Falconi, L; Falcucci, E; Farabollini, P; Faure Walker, JP; Ferrarini, F; Ferrario, MF; Ferry, M; Feuillet, N; Fleury, J; Fracassi, U; Frigerio, C; Galluzzo, F; Gambillara, R; Gaudiosi, G; Goodall, H; Gori, S; Gregory, LC; Guerrieri, L; Hailemikael, S; Iezzi, F; Invernizzi, C; Jablonská, D; Jacques, E; Jomard, H; Kastelic, V; Klinger, Y; Lavecchia, G; Leclerc, F; Liberi, F; Lisi, A; Livio, F; Lo Sardo, L; Malet, JP; Mariucci, MT; Materazzi, M; Mazzarini, F; McCaffrey, KJW; Michetti, AM; Mildon, ZK; Montone, P; Moro, M; Nave, R; Odin, M; Pace, B; Paggi, S; Pagliuca, N; Pambianchi, G; Pantosti, D; Patera, A; Pérouse, E; Pezzo, G; Piccardi, L; Pierantoni, PP; Pignone, M; Pinzi, S; Pistolesi, E; Point, J; - view fewer (2018) Surface ruptures following the 30 October 2016 Mw 6.5 Norcia earthquake, central Italy. Journal of Maps , 14 (2) pp. 151-160. 10.1080/17445647.2018.1441756 . Green open access

https://ift.tt/2JJEZpB

Taking forward the Stop TB Partnership and World Health Organization Joint Theme for World TB Day March 24th 2018 — “Wanted: Leaders for a TB-Free World. You can make history. End TB”

Tiberi, S; Petersen, E; Maeurer, M; Ntoumi, F; Yeboa-Manu, D; Mwaba, P; Vilaplana, C; ... Zumla, A; + view all Tiberi, S; Petersen, E; Maeurer, M; Ntoumi, F; Yeboa-Manu, D; Mwaba, P; Vilaplana, C; Dar, O; Bates, M; Corrah, T; Rao, M; Kapata, N; Azhar, EI; Memish, ZA; Mfinanga, S; Aseffa, A; Ippolito, G; Migliori, GB; Zumla, A; - view fewer (2018) Taking forward the Stop TB Partnership and World Health Organization Joint Theme for World TB Day March 24th 2018 — "Wanted: Leaders for a TB-Free World. You can make history. End TB". International Journal of Infectious Diseases , 68 pp. 122-124. 10.1016/j.ijid.2018.03.002 . Green open access

https://ift.tt/2vbouPQ

Rapid ex vivo examination of Mohs specimens using optical coherence tomography

Rashed, D; Shah, D; Freeman, A; Cook, RJ; Hopper, C; Perrett, CM; (2017) Rapid ex vivo examination of Mohs specimens using optical coherence tomography. Photodiagnosis and Photodynamic Therapy , 19 pp. 243-248. 10.1016/j.pdpdt.2017.06.006 .

https://ift.tt/2JJEL1J

Cell-wall synthesis and ribosome maturation are co-regulated by an RNA switch in Mycobacterium tuberculosis

Schwenk, S; Moores, A; Nobeli, I; McHugh, TD; Arnvig, KB; (2018) Cell-wall synthesis and ribosome maturation are co-regulated by an RNA switch in Mycobacterium tuberculosis. Nucleic Acids Research 10.1093/nar/gky226 . (In press). Green open access

https://ift.tt/2EI1lnB

The Typhoid Vaccine Acceleration Consortium (TyVAC): Vaccine effectiveness study designs: Accelerating the introduction of typhoid conjugate vaccines and reducing the global burden of enteric fever. Report from a meeting held on 26-27 October 2016, Oxford, UK

Meiring, JE; Gibani, M; Basnyat, B; Bentsi-Enchill, AD; Clemens, J; Darton, TC; Date, K; ... TyVAC Consortium Meeting Group, .; + view all Meiring, JE; Gibani, M; Basnyat, B; Bentsi-Enchill, AD; Clemens, J; Darton, TC; Date, K; Dougan, G; Garrett, D; Gessner, BD; Gordon, MA; Heyderman, RS; Hombach, J; Kotloff, KL; Levine, MM; Luby, SP; Mohan, VK; Marfin, AA; Mulholland, K; Neuzil, K; Pitzer, VE; Pollard, AJ; Qadri, F; Salisbury, D; Zaidi, A; TyVAC Consortium Meeting Group, .; - view fewer (2017) The Typhoid Vaccine Acceleration Consortium (TyVAC): Vaccine effectiveness study designs: Accelerating the introduction of typhoid conjugate vaccines and reducing the global burden of enteric fever. Report from a meeting held on 26-27 October 2016, Oxford, UK. Vaccine , 35 (38) pp. 5081-5088. 10.1016/j.vaccine.2017.08.001 .

https://ift.tt/2JJQ4a0

A rare presentation of pulmonary sarcoidosis as a solitary lung mass: a case report

Sarcoidosis is a multisystem, chronic granulomatous disease of unknown etiology that predominantly affects the lungs. Pulmonary sarcoidosis classically presents with constitutional symptoms and computed tomogr...

https://ift.tt/2GZ8JRl

Making a Difference with Individual Patients-Health Equity, Power, and Dignity

By Nathan Douthit

   At another session of CUGH's Annual Meeting, Richard Horton, Editor in Chief of the Lancet, debated Cheryl Heaton, director of New York University's Global Institute of Public Health, on the subject: Equity is the defining objective of global health in the 21st century. Heaton argued in favour of the motion, saying that our past neglect has created high reservoirs of need around the world. She made the point that equity creates hope and optimism in vulnerable populations, which turn motivate their ability to bring about change.

   While Horton agreed that equity is a valuable and admirable goal, he argued that global health, as it is currently framed, makes this impossible to achieve. He argued that global health "is not about equity; it is about power", with power held by the privileged. He continued "before there can be equity, individuals must have liberty and power over their lives." Further, liberty requires that all humans be recognized for their dignity. Dignity affirms that every individual is an end unto themselves; not a means to our ends. "Without dignity, there can be no equity." Horton concluded that our obligation is to challenge authorities that deny liberty. We must discharge this obligation if we are to see the dignity of individual patients recognized.

   BMJ Case Reports is committed to recognizing the dignity and worth of individual patients. Our case reports focus on patients at the center of clinical medicine and global health. While our clinical case reports highlight the challenges of dealing with disease, our global health case reports shed light on the determinants of health and disease: the environments in which patients live and work; education and financial well-being; access to healthcare; local and national politics; instability and conflict; the practice of corporations and industry; and, ethnic and cultural histories. Our authors argue for better living conditions and improvements in health at the level of the individual – working towards global health one patient at a time. Each patient is an end unto themselves. We encourage our authors to work with their patients in writing each global health case report and want to be not merely a repository of global health problems and solutions but a repository of patient voices from across the world.

   BMJ Case Reports invites authors to submit global health case reports that give voice to individual patients and uphold their dignity. These reports should examine the determinants of health:

• The effects of culture and environment
• Education and literacy
• How occupation may exacerbate or cause disease
• The effects of conflict, disaster, migration and poverty
• Access to healthcare
• The interventions and innovations put into place in global health to treat individual patients.
• The disproportional effect of social determinants of health on vulnerable communities

   Manuscripts may be submitted by students, physicians, nurses and allied health professionals to BMJ Case Reports via the submission system. For more information, review our guidance on how to write a global health case report and look through our online collection.

Competing Interests

None Declared

https://ift.tt/2JFhNZg

Value of the Combination Ultrasonography With Ti-RADS Score / Dual Tracer Scintigraphy MIBI-Tc99m/Iodine-123 in the Detection of Malignancy of Thyroid Nodules (≥15 mm) Classified Bethesda III or IV on Cytology

Condition:   Malignancy of Thyroid Nodules
Intervention:   Drug: MIBI-Tc99m/Iodine-123
Sponsor:   Nantes University Hospital
Not yet recruiting

https://ift.tt/2HjIoN6

Avelumab, Cetuximab, and Palbociclib in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Condition:   Head and Neck Squamous Cell Carcinoma
Interventions:   Drug: Avelumab;   Drug: Palbociclib;   Drug: Cetuximab
Sponsors:   Kathryn Gold;   Pfizer
Not yet recruiting

https://ift.tt/2vbvDiR

The emerging role of anti-CD25 directed therapies as both immune modulators and targeted agents in cancer

Flynn, MJ; Hartley, JA; (2017) The emerging role of anti-CD25 directed therapies as both immune modulators and targeted agents in cancer. [Review]. British Journal of Haematology , 179 (1) pp. 20-35. 10.1111/bjh.14770 .

https://ift.tt/2GXdZku

Psychological characteristics and household savings behavior: The importance of accounting for latent heterogeneity

Gerhard, P; Gladstone, JJ; Hoffmann, AOI; (2018) Psychological characteristics and household savings behavior: The importance of accounting for latent heterogeneity. Journal of Economic Behavior and Organization , 148 pp. 66-82. 10.1016/j.jebo.2018.02.013 .

https://ift.tt/2Hxp5xE

An analytical model for the detection of levitated nanoparticles in optomechanics

Rahman, ATMA; Frangeskou, AC; Barker, PF; Morley, GW; (2018) An analytical model for the detection of levitated nanoparticles in optomechanics. Review of Scientific Instruments , 89 (2) , Article 023109. 10.1063/1.5008396 . Green open access

https://ift.tt/2GUY46a

A new approach to assess the effect of photodamage on corneocyte envelope maturity using combined hydrophobicity and mechanical fragility assays

Guneri, D; Voegeli, R; Gurgul, SJ; Munday, MR; Rawlings, AV; (2018) A new approach to assess the effect of photodamage on corneocyte envelope maturity using combined hydrophobicity and mechanical fragility assays. International Journsal of Cosmet Science 10.1111/ics.12454 . (In press).

https://ift.tt/2HxoQme

Community perceptions of the socio-economic structural context influencing HIV and TB risk, prevention and treatment in a high prevalence area in the era of antiretroviral therapy

Ngwenya, N; Gumede, D; Shahmanesh, M; McGrath, N; Grant, A; Seeley, J; (2018) Community perceptions of the socio-economic structural context influencing HIV and TB risk, prevention and treatment in a high prevalence area in the era of antiretroviral therapy. African Journal of AIDS Research , 17 (1) pp. 72-81. 10.2989/16085906.2017.1415214 . Green open access

https://ift.tt/2GY1tRN

A speaker adaptive DNN training approach for speaker-independent acoustic inversion

Badino, L; Franceschi, L; Arora, R; Donini, M; Pontil, M; (2017) A speaker adaptive DNN training approach for speaker-independent acoustic inversion. In: Lacerda, Francisco, (ed.) Proceedings of Interspeech 2017. (pp. pp. 984-988). International Speech Communication Association: Stockholm, Sweden.

https://ift.tt/2HxoEDw

Concurrent Data Structures Linked in Time (Artifact)

Delbianco, GA; Sergey, I; Nanevski, A; Banerjee, A; (2017) Concurrent Data Structures Linked in Time (Artifact). Dagstuhl Artifacts Series , 3 (2) 4:1-4:4. 10.4230/DARTS.3.2.4 . Green open access

https://ift.tt/2GYOxei

Short-interval intracortical inhibition: Comparison between conventional and threshold-tracking techniques

Samusyte, G; Bostock, H; Rothwell, J; Koltzenburg, M; (2018) Short-interval intracortical inhibition: Comparison between conventional and threshold-tracking techniques. Brain Stimulation 10.1016/j.brs.2018.03.002 . (In press). Green open access

https://ift.tt/2HyGO7M

Gaussian basis functions for highly oscillatory scattering wavefunctions

Mant, BP; Law, MM; (2018) Gaussian basis functions for highly oscillatory scattering wavefunctions. Journal of Physics B: Atomic, Molecular and Optical Physics , 51 (7) , Article 075203. 10.1088/1361-6455/aab19f . Green open access

https://ift.tt/2GX8br7

Ataxia With Oculomotor Apraxia Is Associated With the DNA Damage Repair Pathway

Ganos, C; Bras, J; (2017) Ataxia With Oculomotor Apraxia Is Associated With the DNA Damage Repair Pathway. Movement Disorders , 32 (5) p. 720. 10.1002/mds.26971 .

https://ift.tt/2HwPifP

A novel high-throughput immunofluorescence analysis method for quantifying dystrophin intensity in entire transverse sections of Duchenne muscular dystrophy muscle biopsy samples

Sardone, V; Ellis, M; Torelli, S; Feng, L; Chambers, D; Eastwood, D; Sewry, C; ... Muntoni, F; + view all Sardone, V; Ellis, M; Torelli, S; Feng, L; Chambers, D; Eastwood, D; Sewry, C; Phadke, R; Morgan, JE; Muntoni, F; - view fewer (2018) A novel high-throughput immunofluorescence analysis method for quantifying dystrophin intensity in entire transverse sections of Duchenne muscular dystrophy muscle biopsy samples. PLoS One , 13 (3) , Article e0194540. 10.1371/journal.pone.0194540 . Green open access

https://ift.tt/2GVwTIh

Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris article

Rhodes, J; Abdolrasouli, A; Farrer, RA; Cuomo, CA; Aanensen, DM; Armstrong-James, D; Fisher, MC; Rhodes, J; Abdolrasouli, A; Farrer, RA; Cuomo, CA; Aanensen, DM; Armstrong-James, D; Fisher, MC; Schelenz, S; - view fewer (2018) Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris article. Emerging Microbes and Infections , 7 (1) , Article 43. 10.1038/s41426-018-0045-x . Green open access

https://ift.tt/2HBuoMI

Analysis of the red and green optical absorption spectrum of gas phase ammonia

Zobov, NF; Coles, PA; Ovsyannikov, RI; Kyuberis, AA; Hargreaves, RJ; Bernath, PF; Tennyson, J; ... Polyansky, OL; + view all Zobov, NF; Coles, PA; Ovsyannikov, RI; Kyuberis, AA; Hargreaves, RJ; Bernath, PF; Tennyson, J; Yurchenko, SN; Polyansky, OL; - view fewer (2018) Analysis of the red and green optical absorption spectrum of gas phase ammonia. Journal of Quantitative Spectroscopy and Radiative Transfer , 209 pp. 224-231. 10.1016/j.jqsrt.2018.02.001 . Green open access

https://ift.tt/2GV9SoV

Agnosia for bird calls

Muhammed, L; Hardy, CJD; Russell, LL; Marshall, CR; Clark, CN; Bond, RL; Warrington, EK; Muhammed, L; Hardy, CJD; Russell, LL; Marshall, CR; Clark, CN; Bond, RL; Warrington, EK; Warren, JD; - view fewer (2018) Agnosia for bird calls. Neuropsychologia , 113 pp. 61-67. 10.1016/j.neuropsychologia.2018.03.024 . Green open access

https://ift.tt/2HwclHt

3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial

Iveson, TJ; Kerr, RS; Saunders, MP; Cassidy, J; Henrik Hollander, N; Tabernero, J; Haydon, A; ... Paul, J; + view all Iveson, TJ; Kerr, RS; Saunders, MP; Cassidy, J; Henrik Hollander, N; Tabernero, J; Haydon, A; Glimelius, B; Harkin, A; Allan, K; McQueen, J; Scudder, C; Boyd, KA; Briggs, A; Waterston, A; Medley, L; Wilson, C; Ellis, R; Essapen, S; Dhadda, AS; Harrison, M; Falk, S; Raouf, S; Rees, C; Olesen, RK; Propper, D; Bridgewater, J; Azzabi, A; Farrugia, D; Webb, A; Cunningham, D; Hickish, T; Weaver, A; Gollins, S; Wasan, HS; Paul, J; - view fewer (2018) 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial. Lancet Oncology , 19 (4) pp. 562-578. 10.1016/S1470-2045(18)30093-7 . Green open access

https://ift.tt/2GV9Du1

Dorsal and ventral horn atrophy is associated with clinical outcome after spinal cord injury

Huber, E; David, G; Thompson, AJ; Weiskopf, N; Mohammadi, S; Freund, P; (2018) Dorsal and ventral horn atrophy is associated with clinical outcome after spinal cord injury. Neurology 10.1212/WNL.0000000000005361 . (In press). Green open access

https://ift.tt/2HBu5By

Cure-induced deformation of ultra-thin composite laminates

Bosi, F; Schlothauer, A; Leclerc, C; Pellegrino, S; (2018) Cure-induced deformation of ultra-thin composite laminates. In: 2018 AIAA/ASCE/AHS/ASC Structures, Structural Dynamics, and Materials Conference. American Institute of Aeronautics and Astronautics (AIAA): Kissimmee, Florida.

https://ift.tt/2GUfJLj

Vangl2 disruption alters the biomechanics of late spinal neurulation leading to spina bifida in mouse embryos

Galea, GL; Nychyk, O; Mole, MA; Moulding, D; Savery, D; Nikolopoulou, E; Henderson, DJ; ... Copp, AJ; + view all Galea, GL; Nychyk, O; Mole, MA; Moulding, D; Savery, D; Nikolopoulou, E; Henderson, DJ; Greene, NDE; Copp, AJ; - view fewer (2018) Vangl2 disruption alters the biomechanics of late spinal neurulation leading to spina bifida in mouse embryos. Disease Models & Mechanisms , 11 (3) , Article dmm032219. 10.1242/dmm.032219 . Green open access

https://ift.tt/2HBtK1K

Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With RAS and BRAF Mutational Status

Taieb, J; Kourie, HR; Emile, J-F; Le Malicot, K; Balogoun, R; Tabernero, J; Mini, E; ... Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 Invest, ; + view all Taieb, J; Kourie, HR; Emile, J-F; Le Malicot, K; Balogoun, R; Tabernero, J; Mini, E; Folprecht, G; Van Laethem, J-L; Mulot, C; Bouché, O; Aparicio, T; Michel, P; Thaler, J; Bridgewater, J; Van Cutsem, E; Perkins, G; Lepage, C; Salazar, R; Laurent-Puig, P; Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 Invest, ; - view fewer (2017) Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With RAS and BRAF Mutational Status. JAMA Oncology 10.1001/jamaoncol.2017.3695 . (In press).

https://ift.tt/2GV9kiR

Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer

Laethem, J-LV; Riess, H; Jassem, J; Haas, M; Martens, UM; Weekes, C; Peeters, M; ... Childs, BH; + view all Laethem, J-LV; Riess, H; Jassem, J; Haas, M; Martens, UM; Weekes, C; Peeters, M; Ross, P; Bridgewater, J; Melichar, B; Cascinu, S; Saramak, P; Michl, P; Van Brummelen, D; Zaniboni, A; Schmiegel, W; Dueland, S; Giurescu, M; Garosi, VL; Roth, K; Schulz, A; Seidel, H; Rajagopalan, P; Teufel, M; Childs, BH; - view fewer (2016) Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer. Targeted Oncology , 12 (1) pp. 97-109. 10.1007/s11523-016-0469-y . Green open access

https://ift.tt/2EIMMA7

Integrative taxonomy and the operationalization of evolutionary independence

Abstract

There is growing agreement among taxonomists that species are independently evolving lineages. The central notion of this conception, evolutionary independence, is commonly operationalized by taxonomists in multiple, diverging ways. This leads to a problem of operationalization-dependency in species classification, as species delimitation is not only dependent on the properties of the investigated groups, but also on how taxonomists choose to operationalize evolutionary independence. The question then is how the operationalization-dependency of species delimitation is compatible with its objectivity and reliability. In response to this problem, various taxonomists have proposed to integrate multiple operationalizations of evolutionary independence for delimiting species. This paper first distinguishes between a standard and a sophisticated integrative approach to taxonomy, and argues that it is unclear how either of these can support the reliability and objectivity of species delimitation. It then draws a parallel between the measurement of physical quantities and species delimitation to argue that species delimitation can be considered objective and reliable if we understand the sophisticated integrative approach as assessing the coherence between the idealized models of multiple operationalizations of evolutionary independence.

https://ift.tt/2GSmjG6

Solitary Plasmacytoma of Frontal Bone: A Case Report

Abstract

A 42 years old male presenting with complaints of swelling on the left supraorbital region since—5 months. Swelling was gradual in onset and progressive in nature. On examination it was a single swelling 5 × 6 cm, with diffuse margins, skin over the swelling was red and stretched, swelling is firm in consistency, fixed, tender on touch, non pulsatile with diffuse irregular margin. FNAC. Smears are positive for malignancy. Bone marrow examination was normal. Excision of the mass from the left frontal sinus, orbit and supraorbital region under GA and sent for HPR. Definitive treatment of choice is: radiotherary 45–50 Gy/4–5 weeks, chemotherapy and surgery. Prognosis is good with local recurrence (< 10%).

https://ift.tt/2v9bzO6

Congenital Cholesteatoma in Adults-Interesting Presentations and Management

Abstract

To report a series of adult patients diagnosed with congenital cholesteatoma (CC) with respect to symptoms, different varieties of presentation, surgical findings and approach used, complications and the postoperative results. A retrospective chart review of adult cases of CC who were treated in the period from January 2014–2017 was carried out in a tertiary care center. Levenson's criteria were used for diagnosis. Diagnosis was confirmed by imaging and intraoperatively. Postoperative results and complications were also analyzed. Six adult cases of CC were studied with a mean follow up of 10 months. Interesting presentations included otitis media with effusion, non-resolving facial nerve palsy, post aural discharge and meningitis. It included 3 cases of petrous apex cholesteatoma, 2 patients with cholesteatoma involving both the middle ear and mastoid and 1 patient with mastoid cholesteatoma. The operative procedures included canal wall up mastoidectomy (1 patient), atticotomy (1 patient), canal wall down mastoidectomy (1 patient), translabyrinthine and transotic excision of mass with blind sac closure (2 patients) and partial labyrinthectomy (1 patient). Complications encountered during surgery were cerebrospinal fluid leak and worsening of hearing in 2 patients and 1 patient respectively. CC can have variety of interesting presentations in adult population and they may or may not have the classical white mass behind the tympanic membrane. Appropriate individualized surgical planning and intervention gives good results.

https://ift.tt/2v8GASz

Choices of Screws in Medial Malleolar Fractures

Cheng, Y; (2018) Choices of Screws in Medial Malleolar Fractures. Presented at: Annual Meeting of American Academy of Orthopaedic Surgeons (AAOS 2018), New Orleans, USA. (In press).

https://ift.tt/2JJhKf5

Is there potential for using beatboxing in supporting laryngectomees?: findings from a public engagement project

Himonides, E; Moors, T; Maraschin, D; Radio, M; (2018) Is there potential for using beatboxing in supporting laryngectomees?: findings from a public engagement project. In: Himonides, E and King, A and Cuadrado, F, (eds.) Proceedings of Researching Music - Education - Technology (Sempre MET 2018). (pp. pp. 165-168). International Music Education Research Centre (iMerc) Press: London, UK.

https://ift.tt/2EHYDhM

Can Software Engineering be Taught by Making (and) Music? a proposed empirical study

Gold, N; Himonides, E; (2018) Can Software Engineering be Taught by Making (and) Music? a proposed empirical study. In: Himonides, E and King, A and Cuadrado, F, (eds.) Proceedings of Researching Music - Education - Technology (MET 2018). (pp. pp. 169-172). International Music Education (iMerc) Press: London, UK.

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BigSUR: Large-scale Structured Urban Reconstruction

Kelly, T; Femiani, J; Wonka, P; Mitra, NJ; (2017) BigSUR: Large-scale Structured Urban Reconstruction. ACM Transactions on Graphics , 36 (6) , Article 204. 10.1145/3130800.3130823 . Green open access

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Native T1 and Extracellular Volume in Transthyretin Amyloidosis

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Why Do Hearing Aids Fail to Restore Normal Auditory Perception?

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Decellularised skeletal muscles allow functional muscle regeneration by promoting host cell migration

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Advances in systemic lupus erythematosus

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Gene therapy for Leber congenital amaurosis

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Controlling the Outgrowth and Functions of Neural Stem Cells: The Effect of Surface Topography

Simitzi, C; Karali, K; Ranella, A; Stratakis, E; (2018) Controlling the Outgrowth and Functions of Neural Stem Cells: The Effect of Surface Topography. Chemphyschem , 19 pp. 2-23. 10.1002/cphc.201701175 . (In press).

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Progress and current trends in local authority housing provision

Morphet, JR; Clifford, B; (2018) Progress and current trends in local authority housing provision. Journal of Urban Regeneration and Renewal (In press).

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Full-Duplex Small-Cell Networks: A Physical-Layer Security Perspective

Babaei, A; Aghvami, AH; Shojaeifard, A; Wong, KK; (2018) Full-Duplex Small-Cell Networks: A Physical-Layer Security Perspective. IEEE Transactions on Communications 10.1109/TCOMM.2018.2811495 . (In press). Green open access

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Evidence summary: The relationship between oral diseases and diabetes

D'Aiuto, F; Gable, D; Syed, Z; Allen, Y; Wanyonyi, KL; White, S; Gallagher, JE; (2017) Evidence summary: The relationship between oral diseases and diabetes. British Dental Journal , 222 (12) pp. 944-948. 10.1038/sj.bdj.2017.544 . Green open access

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Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future

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Movie Pirates of the Caribbean: Exploring Illegal Streaming Cyberlockers

Ibosiola, D; Steer, B; Garcia-Recuero, A; Stringhini, G; Uhlig, S; Tyson, G; (2018) Movie Pirates of the Caribbean: Exploring Illegal Streaming Cyberlockers. In: (Proceedings) AAAI Conference on Web and Social Media (ICWSM). AAAI (In press).

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You are your Metadata: Identification and Obfuscation of Social Media Users using Metadata Information

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Efficient photoconductive terahertz detector with all-dielectric optical metasurface

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