International Journal of Otolaryngology and Head & Neck Surgery Vol.6,No.2 (March 2017)

Reinke's Oedema Presenting as Stridor: Implications for Otolaryngologists in Difficult Airway
Reinke's Oedema, Stridor, Difficult Airway and Micro Laryngeal Surgery
Paper Information Full Paper: PDF (Size:340KB)
DOI: 10.4236/ijohns.2017.62003

A Pedunculated Fibrolipomatous Polyp of Tonsil: A Rare Case Report
Palatine Tonsil, Lipoma, Fibrolipoma
Paper Information Full Paper: PDF (Size:765KB)
DOI: 10.4236/ijohns.2017.62004

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Prophylactic atropine administration attenuates the negative haemodynamic effects of induction of anaesthesia with propofol and high-dose remifentanil: A randomised controlled trial.

BACKGROUND: Induction of anaesthesia with propofol and remifentanil often induces unwanted bradycardia and hypotension, raising concerns regarding tissue oxygenation. The electrophysiological cardiac effects of remifentanil can be reversed by atropine. OBJECTIVE: To investigate if prophylactic administration of atropine can attenuate the negative haemodynamic effects of propofol and a high dose of remifentanil during induction of anaesthesia. DESIGN: A double-blind, randomised controlled trial. SETTING: Single-centre, University Medical Center Groningen, The Netherlands. PATIENTS: Sixty euvolaemic patients scheduled for surgery under general anaesthesia. INTERVENTIONS: Anaesthesia was induced and maintained with a target-controlled infusion of propofol with a target effect-site concentration (Ce) of 2.5 [mu]g ml-1, remifentanil (target-controlled infusion), (Ce 8 ng ml-1) and cis-atracurium. Methylatropine (500 [mu]g) or 0.9% saline was administered at immediately before induction of anaesthesia. MAIN OUTCOME MEASURES: The changes ([DELTA]) in mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), rate pressure product, cerebral tissue oxygenation and peripheral tissue oxygenation between induction of anaesthesia (T0) and 10 min later (T10). RESULTS: Atropine significantly attenuated the changes in the outcome measures between T0 and T10. Median (inter-quartile range) changes were MAP, [DELTA] = -24 (-40 to -21) vs. [DELTA] = -37 mmHg (-41 to -31) (P = 0.02); HR, [DELTA] = 0 +/- 13 vs. -19 +/- 11 bpm (P

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Effects of different fresh gas flows with or without a heat and moisture exchanger on inhaled gas humidity in adults undergoing general anaesthesia: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The minimum inhaled gas absolute humidity level is 20 mgH2O l-1 for short-duration use in general anaesthesia and 30 mgH2O l-1 for long-duration use in intensive care to avoid respiratory tract dehydration. OBJECTIVE: The aim is to compare the effects of different fresh gas flows (FGFs) through a circle rebreathing system with or without a heat and moisture exchanger (HME) on inhaled gas absolute humidity in adults undergoing general anaesthesia. DESIGN: Systematic review and meta-analyses of randomised controlled trials. We defined FGF (l min-1) as minimal (0.25 to 0.5), low (0.6 to 1.0) or high (>=2). We extracted the inhaled gas absolute humidity data at 60 and 120 min after connection of the patient to the breathing circuit. The effect size is expressed as the mean differences and corresponding 95% confidence intervals (CI). DATA SOURCES: PubMed, EMBASE, SciELO, LILACS and CENTRAL until January 2016. RESULTS: We included 10 studies. The inhaled gas absolute humidity was higher with minimal flow compared with low flow at 120 min [mean differences 2.51 (95%CI: 0.32 to 4.70); P = 0.02] but not at 60 min [mean differences 2.95 (95%CI: -0.95 to 6.84); P = 0.14], and higher with low flow compared with high flow at 120 min [mean differences 7.19 (95%CI: 4.53 to 9.86); P

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Differential Regulation of chTLR3 by Infectious Bursal Disease Viruses with Different Virulence In Vitro and In Vivo

Viral Immunology , Vol. 0, No. 0.


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Food labeling issues in patients with severe food allergies: solving a hamlet-like doubt.

Purpose of review: We review the laws on labeling in the international community, the difficulties they pose to the food manufacturers to prepare the food labels and the methodologies to determine the concentration of potential allergens in foods. Recent findings: European Food Safety Authority and International Life Sciences Institute Europe are evaluating strategies to identify the threshold level of allergen that can trigger a reaction in individuals. The most used techniques to detect the presence of protein in food are Enzyme-linked immunosorbent assay, polymerase chain reaction and real time polymerase chain reaction. Researchers are now trying to apply proteomics to estimate the amount of protein within the food. In order to protect the health of consumers, the Codex Alimentarius Commission updates constantly the list of allergens. In response to these regulations, some industries have also added some precautionary allergen labeling (PAL). It was generally agreed that PAL statements needed to be visible, simple, and safe. It was suggested that PAL be standardized, an action that would occur if the 'Voluntary Incidental Trace Allergen Labelling' process was made mandatory. Summary: So far, no laboratory technique is able to reassure the consumers about the composition of foods found on the packaging. International authorities produced increasingly stringent laws, but more is still to do. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Food labeling issues in patients with severe food allergies: solving a hamlet-like doubt.

Purpose of review: We review the laws on labeling in the international community, the difficulties they pose to the food manufacturers to prepare the food labels and the methodologies to determine the concentration of potential allergens in foods. Recent findings: European Food Safety Authority and International Life Sciences Institute Europe are evaluating strategies to identify the threshold level of allergen that can trigger a reaction in individuals. The most used techniques to detect the presence of protein in food are Enzyme-linked immunosorbent assay, polymerase chain reaction and real time polymerase chain reaction. Researchers are now trying to apply proteomics to estimate the amount of protein within the food. In order to protect the health of consumers, the Codex Alimentarius Commission updates constantly the list of allergens. In response to these regulations, some industries have also added some precautionary allergen labeling (PAL). It was generally agreed that PAL statements needed to be visible, simple, and safe. It was suggested that PAL be standardized, an action that would occur if the 'Voluntary Incidental Trace Allergen Labelling' process was made mandatory. Summary: So far, no laboratory technique is able to reassure the consumers about the composition of foods found on the packaging. International authorities produced increasingly stringent laws, but more is still to do. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Role of Postoperative Stimulated Thyroglobulin as Prognostic Factor for Differentiated Thyroid Cancer in Children and Adolescents

Thyroid , Vol. 0, No. 0.


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Clear Cell Change in Thyroid Carcinoma: A Clinicopathologic and Molecular Study with Identification of Variable Genetic Anomalies

Thyroid , Vol. 0, No. 0.


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Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer

Abstract

In this study, we investigated the clinical relevance of CD274 (PD-L1) protein expression by tumor cells and tumor-infiltrating immune cells in colorectal cancer (CRC). To this end, 186 microsatellite instability-high (MSI-H) and 153 microsatellite stable (MSS) CRCs were subjected to immunohistochemistry (IHC) analysis for the expression of CD274 and mismatch repair proteins. CD274 expression was evaluated in tumor cells at the center (TC) and periphery (TP), and immune cells at the center (IC) and periphery (IP) of CRC. IHC slides stained for CD3 and CD8 were scanned using an Aperio ScanScope for precise calculation of tumor-infiltrating T cell density. Additionally, samples were screened for the B-Raf (BRAF)-V600E mutation using a Cobas 4800 System and IHC. In total, CD274^TC, CD274^TP, CD274^IC, and CD274^IP were observed in 43 (23.1%), 47 (25.3%), 107 (57.5%), and 102 (54.8%) of the MSI-H CRCs examined, and in three (2.0%), four (2.6%), 47 (30.7%), and 56 (36.6%) of the 153 MSS CRCs tested. Meanwhile, intratumoral heterogeneity of CD274 expression in tumor cells and immune cells was detected in 24 (12.9%) and 47 (25.3%) MSI-H CRCs, respectively. Notably, in both MSI-H and MSS CRC, CD274^IC and CD274^IP were independently associated with improved prognosis (P < 0.05), while BRAF mutation was associated with CD274^TP, poor differentiation, sporadic type, and hMLH1(−)/hMSH2(+)/hMSH6(+)/PMS2(−) in MSI-H CRC (P < 0.006). In conclusion, CD274 expression in tumor-infiltrating immune cells was an independent factor for improved prognosis in CRC patients. A deeper understanding of CD274 status may yield improved responses to future CRC immunotherapies.

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Coexpressed modular gene expression reveals inverse correlation between immune responsive transcription and aggressiveness in gastric tumours

Abstract

The existing large number of gene expression profiles of tumour samples offers a great advantage for the integrative functional genomic exploration of molecular dysregulation in cancers. The clusters of genes (modules) derived from a gastric cancer (GC) coexpression network were explored to understand their clinical and functional significance. Among the modules derived from the GC mRNA expression network, six modules were relatively highly expressed in diffuse type gastric tumours. Elevated expression of genes related to extracellular matrix (ECM), angiogenesis, collagen and intracellular cytoskeletal components and immune response were identified in these modules. ECM-related modules exhibited an inverse correlation with modules representing the expression of immune response genes. A reduced expression of immune response genes was identified as the key factor associated with the aggressive features of diffuse gastric tumours, which is indicative of tumour progression involving the escape from immune surveillance in diffuse tumours. A part of the identified aggressive factors was common between intestinal and diffuse type tumours. The coexpressed modules and their expression patterns delineate the fine transition involved in cancer progression in the later stages of tumours. The identified modules could serve as surrogate gene-sets, indicating the molecular staging of GC aggressiveness with underlying biological interaction.

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Why Designing Is Not Experimenting: Design Methods, Epistemic Praxis and Strategies of Knowledge Acquisition in Architecture

Abstract

Using the example of architecture, this article defends the thesis that designing should not be regarded as a kind of experimenting. This is in contrast to a widespread methodological claim that design processes are equivalent to experimentation processes. The contrary thesis can be proven by focusing on actual practices, techniques and design strategies. Closely connected with the thesis is an even more important epistemological claim, which contends that designing serves not only to develop artefacts but is also a means of acquiring genuine knowledge. When the epistemic relevance of said practices, techniques and strategies is reassessed, designing emerges clearly as an independent epistemic praxis. To defend the thesis, the present article draws on and analyses empirical material from an ethnographic field study in order to back up the conceptual analysis.

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Application of gene detection technique in the antenatal diagnosis of hereditary hearing loss

OBJECTIVE: Gene chip and gene sequencing techniques were used to detect the main pathogenic genes in pregnant women with hereditary hearing loss.

PATIENTS AND METHODS: From May 2015 to May 2016, 1080 pregnant in Xuzhou Maternal and Child Health Hospital were enrolled in this study. Women age range was 18 to 40 years. 4 genes and 9 mutation sites, including 4 sites (35delG, 176, 235delC and 299) in GJB2 gene, 2 sites (2168A>G and IVS-7-2A>G) in SLC26A4 (PDS) gene, 2 sites (1494C>T and 1555A>G) in 12s rRNA gene and 1 site (538C>T) in GJB3 gene, were detected using the GeeDom® 9-item hereditary hearing loss gene detection kit. Deafness genes in the husband of the pregnant woman with GJB2 and SLC26A4 positive gene mutations were verified using Sanger sequencing. Fetuses with the same deafness genes as their parents were diagnosed before delivery using amniocentesis.

RESULTS: 48 patients (4.45 %) were detected positive for hereditary hearing loss. Most of them (28 cases) were identified with GJB2 gene mutation (1 case with 176 site mutation, 22 cases with 235delC site mutation and 5 cases with 299 site mutation). We had 15 cases of the SLC26A4 gene mutation (3 cases of 2168A>G site mutation and 12 cases of IVS-7-2A>G site mutation), 2 cases of 538C>T site mutation of GJB3 gene and 3 cases of 1555A>G site mutation of 12s rRNA gene.

CONCLUSIONS: The gene detection technique has a great health-economic significance in screening the main pathogenic genes involved in the hereditary hearing loss.

L'articolo Application of gene detection technique in the antenatal diagnosis of hereditary hearing loss sembra essere il primo su European Review.

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NY-ESO-1 Protein Cancer Vaccine With Poly-ICLC and OK-432: Rapid and Strong Induction of NY-ESO-1-specific Immune Responses by Poly-ICLC

We conducted a clinical trial of a cancer vaccine using NY-ESO-1 protein with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) and/or OK-432 against solid tumors. A total of 15 patients were sequentially enrolled in 4 cohorts. Patients in cohort 1 received NY-ESO-1 protein; cohort 2a received NY-ESO-1 protein+OK-432; cohort 2b received NY-ESO-1 protein+poly-ICLC; cohort 3 received NY-ESO-1 protein+OK-432+poly-ICLC with Montanide ISA-51. The endpoints of this trial were safety, NY-ESO-1 immune responses, and clinical response. Vaccine-related adverse events observed were fever and injection-site reaction (grade 1). Two patients showed stable disease after vaccination. NY-ESO-1 antibodies were observed in 4 patients at the baseline (sero-positive) and augmented in all patients after vaccination. Eleven patients showed a conversion of negative antibody responses at baseline to positive after vaccination (seroconversion). The seroconversions were observed in all 11 sero-negative patients by the fourth immunization; in particular, it was observed by the second immunization in patients with poly-ICLC, and these induced antibody responses were stronger than those in patients immunized without poly-ICLC. The number of NY-ESO-1–specific interferon (IFN)γ-producing T cells was increased in patients immunized with poly-ICLC and/or OK-432, and furthermore, the increase of IFNγ-producing CD8 T cells in patients immunized with poly-ICLC was significantly higher than that in patients without poly-ICLC. Nonspecific activations of T-cell or antigen presenting cells were not observed. Our present study showed that poly-ICLC is a promising adjuvant for cancer vaccines.

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Nivolumab Causing a Polymyalgia Rheumatica in a Patient With a Squamous Non–Small Cell Lung Cancer

The anti-programmed cell-death-1 antibody, nivolumab, has been recently approved for the treatment of advanced non–small cell lung cancer. Although, today, immune-related adverse effects such as dermatologic, digestive, hepatic, and endocrine toxicities are well-known with immune checkpoint inhibitors, rheumatic diseases are less well described. Herein, we report the case of a patient without a history of arthritis who developed polymyalgia rheumatica after 13 cycles of nivolumab used for the treatment of advanced non–small cell lung cancer. Laboratory evidence of inflammatory syndrome, articular echography, and clinical presentation with classical symptoms and also distal manifestations were suggestive of this chronic inflammatory disorder. Because of a relevant pain, clinicians were forced to suspend immunotherapy. Nevertheless, due to glucocorticoid therapy, the patient's symptoms have decreased progressively. Moreover, nivolumab was reintroduced 8 weeks later, whereas prednisone (10 mg) was continued, without any recurrence symptoms. To conclude, our case suggests that polymyalgia rheumatica might be a very disabling anti-programmed cell-death-1 immune-related adverse effect.

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Superior Suppression of ErbB2-positive Tumor Cells by a Novel Human Triparatopic Tribody

Downregulation of the epidermal growth factor receptor family of receptors is improved by combining different antibodies to noncompetitive epitopes. For ErbB2/HER2 this has already been translated into clinical practice by using a combination of trastuzumab and pertuzumab. Moreover, cocktails of 2 or 3 anti-epidermal growth factor receptor antibodies show an enhanced downregulation of the receptor due to the induction of matrix formation. A more efficient method for inducing matrix formation and receptor downregulation might include the use of trispecific reagents. A triparatopic Tribody consisting of 3 noncompeting ErbB2 binders was compared with equivalent trivalent monoparatopic counterparts, as well as to a cocktail of 3 monoclonal antibodies for its effects on downregulation of the ErbB2 receptor's kinase activity and survival of several ErbB2-expressing cancer cell lines. The triparatopic Tribody was significantly more efficient in downregulating ErbB2 and inhibiting tumor cell growth than either the control monoparatope tribodies or the combinatorial treatment with the 3 different parental antibodies on all the tested tumor cells, including trastuzumab-resistant cell lines. The enhancement of effectivity was dependent on all 3 binding moieties. Because the novel Tribody allows reduction of the costs of production (as only 1 construct provides the antitumor effects of 3 antibodies) and has an intermediate molecular size (∼100 kDa) well suited for both tumor penetration and acceptable half-life, it has the potential to become a precious tool for therapeutic use particularly in trastuzumab-resistant cancer patients.

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A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients With Pancreatic Cancer

We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT. Both TAAs were highly expressed in the original tumor tissue suggesting that HSCT promoted a clinically relevant, long-lasting cellular immune response. In contrast to untreated controls, who succumbed to progressive disease, both patients are tumor-free 9 years after diagnosis. Radical surgery combined with HSCT may cure pancreatic adenocarcinoma and change the cellular immune repertoire capable of responding to clinically and biologically relevant TAAs.

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Treatment of Cervical Intraepithelial Neoplasia: Patients Preferences for Surgery or Immunotherapy with Imiquimod

Imiquimod has been studied as a noninvasive pharmacological treatment alternative to large loop excision of the transformation zone (LLETZ) for high-grade cervical intraepithelial neoplasia (CIN), to prevent long-term obstetric complications from surgical treatment. This study aims to investigate womens' preferences for treatment of high-grade CIN with imiquimod or LLETZ. A labeled discrete choice experiment was conducted among 100 women with abnormal cervical cytology in 5 hospitals in the Netherlands between March 2014 and December 2015. Participants were asked to choose between imiquimod treatment or standard surgical treatment in 9 separate scenarios, based on the following treatment characteristics: treatment success rate, rate of side effects, risk of premature birth in subsequent pregnancies, and risk of subfertility after treatment. The levels of these characteristics differed for the imiquimod alternatives. Women assigned a positive utility to LLETZ compared with imiquimod. When making a choice for imiquimod, women preferred a higher treatment success rate and a lower risk of premature birth, infertility and side effects. The choice for imiquimod treatment was also influenced by the intention of a future pregnancy. Subgroup analyses revealed that a lower efficacy regarding imiquimod might be more acceptable for women who desired a future pregnancy compared with women who did not desire a future pregnancy. Women with a future pregnancy wish may prefer treatment of high-grade CIN with imiquimod cream over LLETZ, if the risk of subfertility and premature birth is low.

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Paul Rothman and Arturo Casadevall Elected to the American Academy of Arts and Sciences

The American Academy of Arts and Sciences today announced the election of 228 new members, including Paul B. Rothman, M.D. and Arturo Casadevall, M.D., of The Johns Hopkins University. 

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Vitamin D and Sjögren syndrome

Publication date: Available online 12 April 2017
Source:Autoimmunity Reviews
Author(s): Mario Garcia-Carrasco, Erick Alejandro Jiménez-Herrera, Jose Luis Gálvez-Romero, Luis Vázquez de Lara, Claudia Mendoza-Pinto, Ivet Etchegaray-Morales, Pamela Munguía-Realpozo, Alejandro Ruíz-Argüelles, Rosas Jose, Mauricio Vera-Recabarren, Ricard Cervera
The immunomodulatory effects of vitamin D have been extensively studied in the context of autoimmunity. Multiple studies have demonstrated a high prevalence of vitamin D deficiency in autoimmune diseases. Recently, a possible protective role of vitamin D in autoimmunity has been described; however, this function remains controversial. Few studies have investigated the role of vitamin D in patients with Sjögren syndrome (SS). In this review, we compiled the main features of SS pathogenesis, the vitamin D immunomodulatory effects and the possible interaction between both. Data suggests that vitamin D may play a role in the SS pathogenesis. In addition, vitamin D low levels have been found in SS patients, which are associated with extra-glandular manifestations, such as lymphoma or neuropathy, suggesting a possible benefit effect of vitamin D in SS.



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Mast cells in rheumatoid arthritis: Friends or foes?

Publication date: Available online 12 April 2017
Source:Autoimmunity Reviews
Author(s): Felice Rivellese, Alessandra Nerviani, Francesca Wanda Rossi, Gianni Marone, Marco Matucci-Cerinic, Amato de Paulis, Costantino Pitzalis
Mast cells are tissue-resident cells of the innate immunity, implicated in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). They are present in synovia and their activation has been linked to the potentiation of inflammation in the course of RA. However, recent investigations questioned the role of mast cells in arthritis. In particular, animal models generated conflicting results, so that many of their pro-inflammatory, i.e. pro-arthritogenic functions, even though supported by robust experimental evidences, have been labelled as redundant. At the same time, a growing body of evidences suggests that mast cells can act as tunable immunomodulatory cells. These characteristics, not yet fully understood in the context of RA, could partially explain the inconsistent results obtained with experimental models, which do not account for the pro- and anti-inflammatory functions exerted in more chronic heterogeneous conditions such as RA. Here we present an overview of the current knowledge on mast cell involvement in RA, including the intriguing hypothesis of mast cells acting as subtle immunomodulatory cells and the emerging concept of synovial mast cells as potential biomarkers for patient stratification.



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Antiphospholipid Antibodies Can Identify Lupus Patients At Risk Of Pulmonary Hypertension: A Systematic Review And Meta-Analysis

Publication date: Available online 12 April 2017
Source:Autoimmunity Reviews
Author(s): Stéphane Zuily, Vinicius Domingues, Christine Suty-Selton, Valérie Eschwège, Laurent Bertoletti, Ari Chaouat, François Chabot, Véronique Regnault, Evelyn M. Horn, Doruk Erkan, Denis Wahl
BackgroundPulmonary hypertension (PH) is a life-threatening condition that may affect outcomes in patients with systemic lupus erythematosus (SLE). The role of antiphospholipid antibodies (aPL) on the risk of PH is controversial. Therefore our objective was to estimate the risk of PH (WHO groups 1-5) including associated pulmonary arterial hypertension (APAH, WHO group 1 only) related to aPL in patients with SLE.MethodsSystematic review and meta-analysis were performed: MEDLINE, EMBASE, Cochrane Library, congress abstracts, and reference lists of eligible studies were searched through 2015. Studies were selected if they included SLE patients with descriptions of the exposure to aPL and the outcomes (PH including APAH). Two reviewers extracted study characteristics and outcome data from published reports. Estimates were pooled using random effects models and sensitivity analyses. PROSPERO registration number: CRD42015016872.ResultsOf 984 identified abstracts, 31 primary studies (five cohorts, 13 case-control, 13 cross-sectional) met inclusion criteria, including 4480 SLE patients. Prevalence of PH in aPL-positive vs. aPL-negative SLE patients was 12.3% vs. 7.3%, respectively. The overall pooled odds ratio (OR) for PH was 2.28 (95% CI, 1.65 to 3.15) (I²=39%). The risk of APAH was also significantly increased (OR=2.62 [95% CI, 1.11-6.15]). The risk of PH was the highest for lupus anticoagulant (OR=1.96 [95% CI, 1.31-2.92]) and IgG anticardiolipin antibodies (OR=2.64 [95% CI, 1.30-5.36]) while other antibodies were not significantly associated with PH.ConclusionsAmong SLE patients, aPL can identify patients at risk for PH and APAH. These findings warrant implementation of effective screening and early treatment strategies.



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The impact of immunogenicity of TNFα inhibitors in autoimmune inflammatory disease. A systematic review and meta-analysis

Publication date: Available online 12 April 2017
Source:Autoimmunity Reviews
Author(s): Valentina Pecoraro, Elena De Santis, Alessandra Melegari, Tommaso Trenti
BackgroundMonoclonal antibodies drugs directed against TNFα, TNFα inhibitors, are immunogenic, and consequent anti-drug antibodies (ADA) formation may decrease the functional drug concentration, resulting in a loss of response. We evaluated the impact of ADA on TNFα therapeutic response.MethodsWe considered studies enrolling adult patients affected by autoimmune inflammatory disease in therapy with TNFα inhibitors. We collected data about study and population characteristics, treatment dosage, determination of ADA and adverse events (AE). We combined data in meta-analysis, calculating risk ratios (RR) for each study. P-values <0.05 were considered as statistically significant. Methodological quality was evaluated. Analyses were performed with the STATA 11 and RevMan 5.3 softwares.ResultsWe included 34 studies enrolling 4273 patients. Of these, 794 (18.6%) developed ADA. Our analysis showed a significant reduction of response (RR 0.43, 95%CI 0.3–0.63) in patients with ADA respect to patients without, especially in patients treated with infliximab (RR 0.37) or adalimumab (RR 0.40). Furthermore, the administration of TNFα inhibitors produced a reaction at the infusion site in 17%, infection in 30% and serious AE in 5% of patients.ConclusionDetectable ADA significantly reduced TNFα inhibitors response. Drug administration can also cause injection site reaction and infections. Early detection of serum ADA levels may improve patients' management. Currently, there are many indications about the use of immunogenicity tests to guide the therapy, but information regarding how to implement it in clinical practice is needed.



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Assessing cumulative acute toxicity of chemoradiotherapy in head and neck cancer with or without induction chemotherapy

Publication date: Available online 12 April 2017
Source:American Journal of Otolaryngology
Author(s): Bhartesh A. Shah, Muhammad M. Qureshi, Jennifer M. Logue, Timothy P. Cooley, Ken S. Zaner, Scharukh Jalisi, Minh Tam Truong
BackgroundTo compare cumulative acute toxicity in head and neck cancer patients treated with concurrent chemoradiotherapy alone (CCRT) versus induction chemotherapy (IC) followed by CCRT (I/CCRT).Methods77 patients underwent definitive CCRT (30 I/CCRT and 47 CCRT). Toxicity was graded using the Common Terminology Criteria for Adverse Events version 4.0. Using the TAME adverse event reporting system, short-term toxicity (T) scores were generated for IC (TIC), CCRT (TCCRT), total treatment duration (TRx), post-treatment period (TPT) and an overall score (Toverall) from treatment start to post treatment period.ResultsAcute toxicity other than dysphagia, odynophagia, or dermatitis was reported in 90.0% and 66.0% of I/CCRT and CCRT patients, respectively (P=0.02). Compared to CCRT group, I/CCRT patients reported greater mean TRx (TRx: 2.11 vs. 2.87, P=0.01) and Toverall (Toverall: 2.60 vs. 3.70, P=0.003).ConclusionI/CCRT patients reported more cumulative acute toxicity during treatment compared to CCRT patients using the TAME reporting system.



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Improving resident familiarity with the translabyrinthine approach to the internal auditory canal

Publication date: Available online 12 April 2017
Source:American Journal of Otolaryngology
Author(s): Matthew M. Dedmon, Brendan P. O'Connell, Austin S. Adams, George P. Wanna, David S. Haynes
ObjectiveTo increase otolaryngology resident experience with drilling and dissection of the internal auditory canal (IAC) via a translabyrinthine approach.Study designPilot study involving temporal bone education and drilling with completion of pre- and post-drilling surveys.MethodsParticipants observed an educational presentation on IAC anatomy and drilling, followed by manipulation of IAC nerves using a prosected cadaveric temporal bone. Participants then drilled the IAC and identified nerves using temporal bones with previously drilled mastoidectomies and labyrinthectomies. Pre- and post-drilling 5-point Likert-based surveys were completed.Results7 participants were included in this study ranging in experience from PGY1 through PGY 5. The median number of times the IAC had been drilled previously was 0. Participants reported statistically significantly improved familiarity with the translabyrinthine approach after the session with median scores increasing from 2 to 3 (p=0.02), and a near-significant increase in familiarity with IAC anatomy with median scores increasing from 3 to 4 (p=0.06). Prior to the session, 71% of participants either disagreed or strongly disagreed that they had an idea of what the procedure would be like in a real operating room, whereas after the session 0% reported disagreement. 100% of participants were very satisfied with the overall experience.ConclusionsAn educational session and temporal bone drilling experience using prosected bones significantly increased the reported familiarity with the translabyrinthine approach. Experiences such as this may enhance resident exposure to advanced lateral skull base approaches in a safe environment, and increase comprehension of the complex anatomic relationships of the IAC.



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Significance of intraoperative findings in revision tympanomastoidectomy

Publication date: Available online 12 April 2017
Source:American Journal of Otolaryngology
Author(s): Andro Košec, Iva Kelava, Jakov Ajduk, Mihael Ries, Robert Trotić, Vladimir Bedeković
PurposeThe study was designed to assess correlations between intraoperative findings in revision tympanomastoidectomy as predictors of cholesteatoma recurrence.Materials and methodsA retrospective single-institution cohort of 101 patients who underwent surgical treatment for recurrent chronic otitis media in a tertiary referral otology centre.ResultsOut of 101 patients, 65 had canal wall up and 36 canal wall down revision surgery. There were 35 cholesteatoma recurrences. Sites most commonly associated with recurrent disease were residual facial ridge cells in 46 (45.5%), ossicular chain sites in 46 (45.5%) patients, posterior external auditory canal wall erosions in 38 (37.6%) patients and mastoid apex recurrence in 35 (34.7%) patients. Ossicular and posterior external auditory canal wall erosion and incomplete removal of mastoid apex cells correlate well with cholesteatoma recurrence accompanied by canal wall up surgery (p=0.009). Residual mastoid apex cells, posterior external auditory canal wall erosion and presence of residual facial ridge cells were identified as the strongest positive predictors of cholesteatoma recurrence, identifying high risk patients associated with canal wall down procedures (p=0.0036).ConclusionsCorrelations between intraoperative findings and cholesteatoma recurrence could improve preoperative and intraoperative planning and reduce the rates of postoperative failures1 due to mismanagement of high risk areas.



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Correlation of frontal sinus recess anatomy with ethnicity, gender, and pathology

Publication date: Available online 12 April 2017
Source:American Journal of Otolaryngology
Author(s): Laura K. House, Scott P. Stringer, Samantha Seals
PurposeResearch on frontal sinus cells has been conflicting regarding relationship between frontal sinus cells and frontal sinus disease. There are no published studies regarding gender differences in frontal sinus disease. No comparisons between African Americans and Caucasians and frontal sinus disease have been published. This study attempts to define the above relationships as well as the relationship between number and types of cells and disease.MethodsA retrospective chart review was performed on sinus CT scans done from 2003 to 2011 at an academic medical center. Exclusion criteria included previous frontal sinus surgery, sinus malignancy, obvious trauma, congenital anomalies, and poor quality of scan. Number and type of frontal cells were recorded for 602 scans. Statistical analysis performed demographic comparisons and compared number and types of cells to evidence of disease.ResultsMales were more likely than females to have frontal sinus disease. Patients with Type 3 and Type 4 cells were more likely to have disease. No significant ethnic related differences in disease were found using a multivariate logistic regression model. Total number of cells did not significantly affect likelihood of disease.ConclusionsThis is one of the largest collections of data on frontal sinus cells as predictors of frontal sinus disease. These results suggest that gender and certain types of cells affect likelihood of disease. This study is the first to demonstrate a lack of difference in disease in African Americans and Caucasians. These results are significant regarding gender, race, number and type of cells as predictors of disease.



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Myocardial Inactivation of Thyroid Hormones in Patients with Aortic Stenosis

Thyroid , Vol. 0, No. 0.


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Generation and Application of Monoclonal Antibody Against Lycopene

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy , Vol. 0, No. 0.


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April 2017 Issue Highlights

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Teens, Acne, and Oral Contraceptive Pills

This Viewpoint discusses the need for greater clarity on the issue of whether minor teens can consent to use of oral contraceptive pills for the indication of acne.

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Secukinumab for Acrodermatitis Continua of Hallopeau

This case report describes the use of secukinumab to treat acrodermatitis continua of Hallopeau.

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Helping Patients Decide on Treatment Options for Actinic Keratosis

The senior author (D.J.E.) saw the patient one time over 20 years ago, but remembers the visit vividly. A short, dapper, articulate 90-year-old retired executive, the man related an appointment he had with another dermatologist in the Southern state he wintered in. The doctor entered the examination room, cryotherapy spray bottle in hand, and with little preamble, liberally administered the sacrament of liquid nitrogen; then turned to leave. "Wait, I have some questions," the patient said. "Sir," the dermatologist replied, "I'm a very busy man. Make another appointment." The patient held his right thumb and index finger a centimeter apart in front of him and said, "He made me feel this small." At a loss for words, Dr Elpern teared up.

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Bradycardia in a Child After Using Brimonidine as Toothpaste

This case report describes the occurrence of bradycardia in a child after using brimonidine as toothpaste.

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Keratinocyte Cancer Therapies Enter the Era of Targeted and Immunotherapy

In the past 5 years, major advancements have been made in the systemic therapy of advanced and metastatic melanoma. As opposed to the robust research and clinical trials in melanoma, progress in the treatment of locally advanced and metastatic keratinocyte cancers (KC), such as cutaneous squamous cell carcinomas (cSCC) and basal cell carcinomas (BCC), has been lagging behind. The first targeted therapy was successfully introduced for advanced BCC using hedgehog pathway inhibitors and demonstrated good responses and a decent adverse effects profile. In this issue of JAMA Dermatology, 3 groups of authors discuss their findings about targeted therapy for sSCC and immunotherapy for cSCC and BCC.

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The Use of Ivy in Dermatology

The common English ivy, or Hedera helix, is a modest woody evergreen climbing plant that is ubiquitous in Britain. Although commonplace and humble, it had religious and magical connections in the past. The Greek god of wine, Bacchus, wore a wreath woven from ivy leaves that provided him immunity from intoxication. A bush of ivy is often commonly seen outside British taverns, hence the cheeky saying "a good wine needs no bush." Interestingly, ivy has also been used extensively in folk medicine to treat dermatological conditions. Corns were a particularly common condition treated by ivy; the leaves were soaked in vinegar or simply worn inside one's socks. There is even a myth from Norfolk, England, that an ivy leaf growing on an ash tree is a cure for corns, perhaps reminiscent of the importance of the ash tree in folk medicine globally.

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Variation in the Cost of Managing Actinic Keratosis

This retrospective cohort study evaluates geographic variation in health care cost for management of actinic keratosis and the association with patient-related and health-related factors.

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Main Characteristics of Zika Virus Exanthema

This study reports on the clinical characteristics of the Zika virus in Guadeloupean adults and children with confirmed cases.

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Comparison of Physical Pretreatment Regimens to Enhance Protoporphyrin IX Uptake

This randomized clinical trial compares the relative potential of different physical pretreatments to enhance protoporphyrin IX fluorescence among participants with normal skin before photodynamic therapy.

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Cutaneous Pseudolymphoma Induced by a GM-CSF–Producing Tumor Cell Vaccine

This report describes 2 cases of injection-site cutaneous pseudolymphoma induced by a GM-CSF–producing tumor cell vaccine.

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Efficiency of Ugly Duckling Sign in Melanoma Detection

This experimental study assesses the agreement of dermatologists on identification of the ugly duckling sign and estimates the contribution of intrapatient comparative analysis to the diagnosis of melanoma.

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Statistical Concerns on Vismodegib for Basal Cell Carcinoma Meta-Analysis—Reply

In Reply Regarding our article "Hedgehog Pathway Inhibitor Therapy for Locally Advanced and Metastatic Basal Cell Carcinoma: A Systematic Review and Pooled Analysis of Interventional Studies," Dr Lima draws attention to our pooled analysis methodology and applies a methodology for meta-analysis, thereby identifying a difference in confidence intervals while noting a small difference in mean values. He appropriately illustrates that it is very important for both authors and readers to understand the complex approaches in these types of studies.

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Association Between PD-L1 Expression in BCCs and Treatment Modalities

This cross-sectional study assesses programmed death ligand 1 expression in treatment-naive and treated patients with basal cell carcinomas.

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Pediatric Skin Eruptions and Allergic Reaction to Breast Milk

Oribasius (circa ad 325-403) was born in the Kingdom of Pergamon and studied medicine at the Alexandrian School in Egypt under Zeno of Cyprus. He practiced in Asia Minor and gained the reputation of an expert before he became the personal physician of the emperor Julian (ad 330-363). He was interested in pediatric diseases and was the first to recognize skin eruptions after breastfeeding as a common allergy among newborn infants. He knew that every woman's milk should be tested for its quality and for conditions that would be pathological for the newborns. He proposed several methods to test the milk, such as the "seashell-fat formation," in which the milk rested inside a seashell for 1 day and a fatty crust appeared, or the same test but with a clay vase, named "cream-judger" (Greek: κρεματοκρίτης). Both tests assessed the flavor, odor, and hue. He noted "… for rashes presenting on the baby's skin, most are due to poor quality of the maternal milk, or when the newborn's organisms could not properly digest the milk, or sometimes the skin's maleficence begins intrauterine. Mothers or wet nurses (Greek: τροφóς, τίτθη, a nurse that breastfeeds another woman's newborn) must therefore both let it manifest itself, as this is the only way to redemption from greatest evils that could happen to the baby. If you don't allow rashes to fully grow, they could be really dangerous. You should begin the treatment when the rashes are in exultation, only then you could heal them, by applying a water solution with myrtle (myrtus), or schinus. The best way is for the woman to be fed as gently as possible, and as for the baby, it must live daily without an overfilled stomach, so that it could better digest the milk, and avoid the unpleasant feeling of a poor mood." Oribasius clearly understood that this was a congenital or acquired disorder related to milk's digestion. Although he did not observe a fully oral allergy syndrome, but only a skin anaphylaxis, he gave specific instructions to minimize the fatality of the disease.

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Association of Oncogenic Mutations in Advanced cSCC Treated With Cetuximab

This study examines the association of HRAS, KRAS, NRAS, BRAF, and EGFR mutations in 31 patients with advanced cutaneous squamous cell carcinomas treated with cetuximab.

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Enhanced Removal of Phenol With Lidocaine vs Alcohol

This in vitro study examines intraoperative irrigation of the nail bed, comparing the effect of 3 aqueous solutions for the neutralization of phenol.

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Expression of Programmed Cell Death Ligand in Cutaneous Squamous Cell Carcinoma

This brief report assesses the efficacy of pembrolizumab, an inhibitor of programmed cell death 1 protein and its ligands, in a patient and in biopsy specimens of a series of patients with locally advanced cutaneous squamous cell carcinoma.

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Tattoo Artists’ Approach to Melanocytic Nevi

This study examines tattoo artists' awareness of skin cancer and whether this influences the decision to refer clients with a suspicious lesion to a dermatologist.

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Anti-Interleukin 23 as a Targeted Treatment Option for Pityriasis Rubra Pilaris

This case report describes a targeted treatment option in a patient with pityriasis rubra pilaris using blockade of the interleukin 23–helper T cell 17 pathway.

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TWEAK/Fn14 promotes pro-inflammatory cytokine secretion in hepatic stellate cells via NF-κB/STAT3 pathways

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Aixiu Wang, Feng Zhang, Hui Xu, Mingcui Xu, Yu Cao, Chen Wang, Yuanyuan Xu, Min Su, Ming Zhang, Yuzheng Zhuge
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) have been associated with liver disease. Hepatic stellate cells (HSCs) play a critical role in the hepatic wound-healing response after liver injury, but there is little information available on the role of the TWEAK/Fn14 pathway in human HSCs. In this study, we explored the role of TWEAK/Fn14 in activated human HSCs. The LX-2 cells were treated with TWEAK, and the expression of pro-inflammatory cytokines was assayed by enzyme-linked immunosorbent assay (ELISA) and real-time PCR (RT-PCR). Western blotting and RT-PCR were performed to evaluate the expression of Fn14 after TWEAK stimulation. Total and phosphorylated of inhibitor-κB (I-κB), nuclear factor kappa B (NF-κB), Janus kinase 2 (JAK2), and signal transducers and activators of transcription 3 (STAT3) were examined by western blotting after TWEAK stimulation and small interfering RNA (siRNA) transfection. The result showed that TWEAK upregulated the expression of Fn14 and pro-inflammatory factors interleukin-8 (IL-8), interleukin-6 (IL-6), regulated upon activation normal T cell expressed and secreted (RANTES), and monocyte chemotactic protein-1 (MCP-1). In LX-2 cells, the pro-inflammatory cytokine secretion was closely related to the activation of the NF-κB and STAT3 pathways. Furthermore, our research showed that STAT3 and NF-κB could interact with each other, which resulted in a significant increase of pro-inflammatory cytokine secretion. The activation of NF-κB and STAT3 signalling-dependent pro-inflammatory cytokine expression may be responsible for such a novel principle and new therapeutic targets in chronic liver disease.



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A Randomized Controlled Clinical Trial Comparing Belatacept With Tacrolimus After De Novo Kidney Transplantation.

Background: Belatacept, an inhibitor of the CD28-CD80/86 co-stimulatory pathway, allows for calcineurin-inhibitor free immunosuppressive therapy in kidney transplantation but is associated with a higher acute rejection risk than ciclosporin. Thus, no biomarker for belatacept-resistant rejection has been validated. In this randomized controlled trial, acute rejection-rate was compared between belatacept- and tacrolimus-treated patients and immunological biomarkers for acute rejection were investigated. Methods: Forty kidney-transplant recipients were 1:1 randomized to belatacept or tacrolimus combined with basiliximab, mycophenolate mofetil and prednisolone. The 1-year incidence of biopsy-proven acute rejection was monitored. Potential biomarkers, namely CD8+CD28-, CD4+CD57+PD1- and CD8+CD28++ EMRA T cells were measured pre and posttransplantation and correlated to rejection. Pharmacodynamic monitoring of belatacept was performed by measuring free CD86 on monocytes. Results: The rejection incidence was higher in belatacept-treated than tacrolimus-treated patients: 55% vs. 10%; p = 0.006. All 3 graft losses, due to rejection, occurred in the belatacept group. Although 4 of 5 belatacept-treated patients with >35 cells CD8+CD28++ EMRA T cells/[mu]L rejected, median pretransplant values of the biomarkers did not differ between belatacept-treated rejectors and nonrejectors. In univariable Cox regressions, the studied cell subsets were not associated with rejection-risk. CD86 molecules on circulating monocytes in belatacept-treated patients were saturated at all time points. Conclusions: Belatacept-based immunosuppressive therapy resulted in higher and more severe acute rejection compared to tacrolimus-based therapy. This trial did not identify cellular biomarkers predictive of rejection. In addition, the CD28-CD80/86 co-stimulatory pathway appeared to be sufficiently blocked by belatacept and did not predict rejection. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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An Oxygenated and Transportable Machine Perfusion System Fully Rescues Liver Grafts Exposed to Lethal Ischemic Damage in a Pig Model of DCD Liver Transplantation.

Background: Control of warm ischemia (WI) lesions that occur with donation after circulatory death (DCD) would significantly increase the donor pool for liver transplantation. We aimed to determine whether a novel, oxygenated and hypothermic machine perfusion device (HMP Airdrive system) improves the quality of livers derived from DCDs using a large animal model. Methods: Cardiac arrest was induced in female large white pigs by IV injection of potassium chloride. After 60min of WI, livers were flushed in situ with HTK and subsequently preserved either by simple cold storage (WI-SCS group) or HMP (WI-HMP group) using Belzer-MPSTM solution. Liver grafts procured from heart-beating donors and preserved by SCS served as controls. After 4hr of preservation, all livers were transplanted. Results: All recipients in WI-SCS group died within 6 hours after transplantation. In contrast, the HMP device fully protected the liver against lethal ischemia/reperfusion injury, allowing 100% survival rate. A postreperfusion syndrome was observed in all animals of the WI-SCS group but none of the control or WI-HMP groups. After reperfusion, HMP-preserved livers functioned better, and showed less hepatocellular and endothelial cell injury, in agreement with better-preserved liver histology relative to WI-SCS group. In addition to improved energy metabolism, this protective effect was associated with an attenuation of inflammatory response, oxidative load, endoplasmic reticulum stress, mitochondrial damage and apoptosis. Conclusions: This study demonstrates for the 1st time the efficacy of the HMP Airdrive system to protect liver grafts from lethal ischemic damage prior to transplantation in a clinically relevant DCD model. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Singing a New SONG: Outcomes for Clinical Trials.

No abstract available

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Effector Antitumor and Regulatory T Cell Responses Influence the Development of Nonmelanoma Skin Cancer in Kidney Transplant Patients.

Background: Chronic immunosuppression promotes Nonmelanocytic Squamous Cell Carcinoma (SCC) after kidney transplantation. Adaptive and innate immunity play a key role controlling tumor growth and are influenced by different immunosuppressive agents. We hypothesized that functional impairment of tumor-specific T cell responses due to CNI could contribute to SCC development, whereas conversion to mTOR-i could recover this protective immune response. Methods: Peripheral tumor-specific T cell responses against main SCC-derived antigens using the IFN-[gamma] ELISPOT assay and intratumor and circulating immune phenotypes (CD4+T, CD8+T, CD20+B, CD56+NK, FOXP3+Tregs) were explored in a cross-sectional analysis in 59 kidney transplant patients with SCC on CNI (KT-CNI-SCC) or mTOR-i (KT-mTORi-SCC), 25 nontransplants developing SCC (NoKT-SCC) and 6 healthy controls. Moreover, 25 KT-CNI-SCC were switched to mTOR-i and evaluated after 12 months. Results: Kidney transplant patients showed lower intratumor infiltrates and tumor-specific T cell responses than NoKT-SCC, and intratumoral and circulating FOXP3+Treg were higher in KT-mTORi-SCC (p

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Pruritus der Kopfhaut

Zusammenfassung

Pruritus der Kopfhaut ist ein häufig beklagtes Symptom und kann durch Dermatosen, Kontaktallergien sowie neurologische, psychiatrische/somatoforme oder systemische Erkrankungen ausgelöst sein. In etlichen Fällen bleibt die Ursache unklar. In der täglichen Praxis stellt der Pruritus capitis immer wieder eine diagnostische und therapeutische Herausforderung dar, insbesondere wenn keine Effloreszenzen erkennbar sind. Eine gründliche Anamnese und eine Untersuchung des Capillitiums, aber auch des gesamten Integuments sind daher essenziell. Befundabhängig sollten eine erweiterte dermatologische Diagnostik, Laboruntersuchungen, bildgebende Maßnahmen sowie eine interdisziplinäre Diagnostik vorgenommen werden. Die Therapie der zugrunde liegenden Ursache ist der erste wichtige therapeutische Schritt, gefolgt von symptomatisch antipruritischen, lokalen und ggf. systemischen Therapien. Dabei ist darauf zu achten, dass gerade bei dichter Kopfbehaarung die Therapie gut umsetzbar sein sollte.

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Superficial black onychomycosis due to Neoscytalidium dimidiatum

Abstract

Onychomycosis is the most common onychopathy observed in adults and the elderly, and it is a frequent reason for medical visits.¹ Its prevalence ranges from 2.0–26.9%, depending on the population and geographic region.^1,2 Non-dermatophyte molds are responsible for 1.5–17.6% of onychomycosis cases, with higher prevalence in tropical and subtropical countries.

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Decrease of serum IL-32 level in patients with atopic dermatitis after cyclosporine treatment

Abstract

Interleukin (IL)-32 is a proinflammatory cytokine that is involved in the inflammatory processes of rheumatoid arthritis, chronic obstructive pulmonary disease, and Crohn disease. [1] Recent studies have reported that IL-32 also contributes to the pathophysiology of atopic dermatitis (AD) in the early stages. [2] IL-32 is expressed in the lesional skin of patients with AD and that serum levels of IL-32 in patients with AD are elevated.

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Autologous cell suspension grafting in segmental vitiligo and piebaldism: a randomised controlled trial comparing full-surface and fractional CO2 laser recipient site preparations

Summary

Background

Autologous non-cultured cell suspension transplantation is an effective treatment for repigmentation in segmental vitiligo and piebaldism. Full surface laser ablation is frequently used to prepare the recipient site before cell suspension transplantation, even though optimal laser settings and ablation depth are unknown.

Objectives

To assess the efficacy and safety of less invasive recipient site preparations.

Methods

In a randomised, observer-blinded, controlled trial we compared different recipient site preparations before cell suspension transplantation in segmental vitiligo and piebaldism. In each patient, we randomly allocated three CO₂ laser recipient site preparations (i.e. 209 and 144 μm full surface, fractional) and a control (no treatment) to four depigmentations. After six months we assessed repigmentation and side effects.

Results

We included 10 patients with vitiligo (n=3) and piebaldism (n=7). Compared to the control site, we found more repigmentation after 209 μm (median 68.7%, p=0.01) and 144 μm (median 58.3%, p=0.007) full surface ablation, but no repigmentation after fractional ablation (median 0.0%, p=0.14).

Conclusion

Superficial full surface ablation with a depth of 144 μm is an effective recipient site preparation before cell suspension transplantation while fractional CO₂ laser is not. #NCT02458417.

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Reflectance confocal microscopy of vulvar epithelial neoplasia: a pilot study

Abstract

vulvar intraepithelial neoplasia (VIN), a subtype of in situ squamous cell carcinoma (SCC), is a common problem particularly among women in their 40s. Two main variants exist: VIN of usual type (uVIN) occurs in young women, and is associated with HPV infection. VIN of differentiated type (dVIN) occurs in post-menopausal women, and is associated with lichen sclerosus.

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‘New to me’ – changing patient understanding of psoriasis and identifying mechanisms of change: The Pso Well® patient materials mixed methods feasibility study

Summary

Background

Psoriasis is an inflammatory, long-term condition (LTC) involving co-morbidities, unhealthy lifestyle and significant life impact. Patients' understanding of psoriasis is limited and support lacking. The Common-Sense Self-Regulatory Model emphasises the role of illness/treatment beliefs on coping/self-management. New 'Pso Well^®' patient materials informed by the model addressed: psoriasis as a LTC; medications management; and lifestyle behaviours.

Objectives

To investigate whether Pso Well^® materials: 1) broaden understanding of psoriasis without increasing anxiety; 2) are acceptable and; 3) comprise features that appear to effect change.

Methods

The Revised Illness Perceptions Questionnaire (IPQ-R modified) and the Hospital Anxiety and Depression Scale (HADS) were administered in patients pre-/post-intervention. Numerical Rating Scales (NRSs) assessed perceptions of change in understanding/anxiety. Qualitative interviews explored acceptability and perceived 'active ingredients'.

Results

Fifty five patients completed pre-/post-intervention questionnaires (56% female; median age 59 years). Post-intervention, a large effect size was indicated in two IPQ-R domains: illness coherence (t [55] = -3.48, p=.001 [two-tailed], eta² =0.19) and personal control (t [55] = -2.98, p=.004 [two-tailed], eta² =0.14); and a medium effect in one: treatment control (t [55] = -2.08, p=.042 [two-tailed], eta² =0.08). HADS scores did not change. For NRSs, 80% of participants reported increased understanding of psoriasis and no increased anxiety. Interviews with 19 patients indicated materials were acceptable/usable. Factors reported to broaden understanding/promote engagement with self-management included: linking of related disease aspects; personally relevant content; and high quality design.

Conclusions

High quality, theory-based psoriasis materials are acceptable to patients and can improve understanding/sense of control without increasing anxiety.

This article is protected by copyright. All rights reserved.

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Endothelial Dysfunction and Mechanobiology in Pathological Cutaneous Scarring: Lessons Learned from Soft Tissue Fibrosis

Abstract

Hypertrophic scars/keloids are pathogenic scars that are characterized by collagen and fibroblast accumulation. The endothelia in the lesions are mechanosensitive and participate actively in the pathogenesis of these scars. The present review summarizes how endothelium responds to mechanical stimuli such as shear, stretch, and hydrostatic pressure. It also shows that in heart, liver, kidney, and lung fibrosis, endothelial dysfunctions (EDs) associate with changes in vascular tone, endothelial permeability, coagulation, and vasomodulation that result in inflammation, hypertension, and coagulation. Pathological scars exhibit similar EDs during their development and progression. Mechanopharmaceutical or mechanotherapeutic interventions that rescue EDs may be useful scar treatments.

This article is protected by copyright. All rights reserved.

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Novel autoantibody against the β2-glycoprotein I/HLA-DR complex in patients with refractory cutaneous ulcers

Abstract

Chronic skin ulcers in the lower legs, feet, toes, and digits are sometimes idiopathic and intractable, and occasionally cause limb gangrene. Although there are many conditions that can cause chronic limb ulcers, including primary or secondary vascular diseases, the reasons why specific patients develop chronic skin ulcers have still remained unclear.¹ Antiphospholipid syndrome (APS) is an acquired coagulation disorder occurring as vascular thrombosis or pregnancy complications.

This article is protected by copyright. All rights reserved.

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Phenotypic Spectrum of Autosomal Recessive Congenital Ichthyosis Due to PNPLA1 Mutation

Abstract

The ichthyoses are rare skin disorders linked by the common finding of scale and concomitant barrier function abnormalities. Recently, mutations in PNPLA1 which encodes patatin-like phopholipase domain containing 1, and plays a role in the formation of the epidermal lipid barrier, have been identified as rare cause of non-syndromic ARCI^1-6.

This article is protected by copyright. All rights reserved.

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Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signaling pathways

Abstract

Background

Male androgenetic alopecia (AGA) is the most common form of hair loss in men and is characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be defined.

Objectives

Herein, molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless/bald men with premature AGA and healthy volunteers.

Results

This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory and immunoglobulin-associated immune mediators were significantly over-expressed in AGA. In contrast, under-expressed genes appear to be associated with the Wnt/β-catenin and BMP/TGF-β signaling pathways. Although involvement of these pathways in hair follicle regeneration is well-described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin (POMC), as confirmed by RT-qPCR and immunohistochemistry. In addition, lower expression of CYP27B1 in AGA subjects supports the notion that changes in vitamin D metabolism contributes to hair loss.

Conclusion

This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave way for new therapeutic approaches.

This article is protected by copyright. All rights reserved.

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Multimodale Therapie des SCLC in den Stadien I–III

Zusammenfassung

Hintergrund

Das kleinzellige Lungenkarzinom (SCLC, „small cell lung cancer") zeichnet sich durch ein rasches Tumorwachstum, eine frühe Metastasierung und eine sehr schlechte Prognose aus. Die chirurgische Therapie war in den letzten Jahrzehnten kein etablierter Bestandteil des multimodalen Behandlungskonzepts, nachdem zwei prospektive randomisierte Studien vor 45 Jahren keine Vorteile für das Überleben der Patienten nach chirurgischer Therapie aufzeigen konnten. In den letzten Jahren konnte jedoch bei hoch selektionierten Patienten in einem frühen Tumorstadium (IA/B) nach vollständiger chirurgischer Resektion des Tumors in Kombination mit einer platinhaltigen Chemotherapie ein vorteilhafter Verlauf der Erkrankung erreicht werden.

Ziel

Der Stellenwert der Chirurgie soll im Rahmen der multimodalen Therapie bei der Behandlung des SCLC analysiert werden. Im Besonderen soll untersucht werden, bei welchen Patienten, in welchem Tumorstadium, zu welchem Zeitpunkt und in welchem Kontext die chirurgische Therapie eine Rolle spielen kann.

Material und Methoden

Eine selektive Literaturrecherche erfolgte in der Datenbank PubMed zum Thema „Chirurgie, kleinzelliges Lungenkarzinom (SCLC) und multimodale Therapiekonzepte bei der Behandlung des kleinzelligen Lungenkarzinom". Arbeiten, die vor 1960 erschienen, wurden ausgeschlossen.

Ergebnisse und Schlussfolgerungen

Das exakte Staging von Patienten mit einem SCLC ist schwierig. Im Besonderen die radiologische Bewertung der mediastinalen Lymphknoten ist häufig falsch-negativ. Dieses unterstreicht die Bedeutung der systematischen histologischen Abklärung der mediastinalen Lymphknoten vor Therapieplanung. Patienten mit einem histologisch gesicherten nodalnegativen (N0), frühen Tumorstadium (T1–2) eines SCLC profitieren, sofern bei der limitierten Datenlage beurteilbar, von einer operativen Resektion des Tumors, wenn vor der Operation ein Vorliegen von Fernmetastasen ausgeschlossen werden kann und die Patienten funktionell operabel sind. Auch bei Vorliegen von mediastinalen Lymphknotenmetastasen (N2) kann eine operative Resektion des Tumors das Überleben verbessern, wenn durch eine platinbasierte Induktionsradiochemotherapie ein Downstaging der mediastinalen Lymphknoten gelingt. Das Überleben der operierten Patienten ist nach einer Lobektomie besser als nach einer limitierten sublobären Resektion oder einer Pneumonektomie. Postoperativ sollte im Rahmen einer multimodalen Therapie eine platinbasierte adjuvante Chemotherapie durchgeführt werden. Wurden im Rahmen der operativen Resektion histologisch mediastinale Lymphknotenmetastasen nachgewiesen, sollte eine platinbasierte adjuvante Chemotherapie sowie eine mediastinale Bestrahlung erfolgen.

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Antiinfektiöse Therapieprinzipien bei akuten Leukämien

Zusammenfassung

Hintergrund

Patienten mit akuten Leukämien sind insbesondere in der Neutropeniephase nach myelosuppressiver Chemotherapie durch Infektionen bedroht.

Ziel der Arbeit

Häufige Infektkomplikationen sowie diagnostische, prophylaktische und therapeutische Strategien werden dargestellt.

Material und Methoden

Aktuelle Leitlinien zum Infektmanagement bei Patienten mit akuten Leukämien wurden zusammengefasst.

Ergebnisse

Von den Leukämiepatienten mit lang anhaltender Neutropenie entwickeln 80 % eine Fieberepisode, deren vermutlich bakterielle Genese immer eine empirische Antibiotikatherapie erfordert. Invasive Pilzinfektionen stellen ebenfalls eine relevante Bedrohung dar, während Virusinfektionen relativ selten sind. Strategien zu Prophylaxe, Diagnostik und Therapie werden erläutert.

Schlussfolgerung

Infektkomplikationen sind bei Leukämiepatienten häufig, aber in der Regel gut behandelbar, wenn ein adäquates Management erfolgt.

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IDH-Inhibitoren

Zusammenfassung

Hintergrund

Mutationen in den Genen IDH1 und IDH2 (IDH, Isocitrat-Dehydrogenase) kommen bei Patienten mit Gliomen, AML (akute myeloische Leukämie) und MDS (myelodysplastisches Syndrom) vor, aber auch bei Patienten mit angioimmunoblastischem T‑Zell-Lymphom, Chondrosarkom, cholangiozellulärem Karzinom und anderen Tumorarten.

Ziel

Die vorliegende Übersichtsarbeit fasst die aktuelle Datenlage zum Einsatz von IDH-Inhibitoren bei Tumorerkrankungen mit IDH1/2-Mutationen zusammen. Es wird außerdem Stellung zur Mutationsdiagnostik genommen, die letztlich zur Therapieentscheidung führt.

Methoden

Klinische Daten zur Behandlung von Patienten mit mutationsspezifischen IDH-Inhibitoren liegen derzeit für einen IDH2-Inhibitor und zwei IDH1-Inhibitoren bei AML- und MDS-Patienten sowie für einen IDH1-Inhibitor bei Gliom-Patienten vor und wurden ausgewertet.

Ergebnisse

Die Gesamtansprechraten bei AML- und MDS-Patienten unterscheiden sich für die verschiedenen Inhibitoren kaum und liegen bei 35–40 %. Ein großer Teil der Patienten profitiert darüber hinaus von einer Zunahme funktionell aktiver neutrophiler Granulozyten, die mit einer reduzierten Infektrate einhergeht. Die häufigsten Nebenwirkungen sind Hyperbilirubinämie, Transaminasenanstieg und Übelkeit.

Diskussion

Da derzeit mehrere Studien mit mutationsspezifischen IDH1- und IDH2-Inhibitoren in Deutschland aktiv sind, sollten alle Patienten mit AML, MDS und Gliomen frühzeitig auf Mutationen in IDH1 und IDH2 getestet und in Studien eingebracht werden, in denen künftig nicht nur die Monotherapie, sondern auch Kombinationstherapien, z. B. mit Azacitidin oder intensiver Chemotherapie, sowohl bei vorbehandelten als auch neu diagnostizierten Patienten untersucht werden. IDH-Inhibitoren stellen derzeit die vielversprechendste Neuentwicklung in der Therapie von AML- und MDS-Patienten dar.

http://ift.tt/2oXmkPA

Checkpointinhibitoren

Zusammenfassung

Hintergrund

Die medikamentöse Onkologie steht am Beginn eines bedeutenden Umbruchs mit einer Vielzahl von neuen Wirkstoffen und veränderten Behandlungsalgorithmen. Die Behandlung metastasierter Tumoren stellt weiterhin eine große Herausforderung dar, jedoch zeigt der kontinuierliche Erkenntnisgewinn in der Molekularpathologie und Immunbiologie therapeutische Ansatzpunkte auf, deren Umsetzung beim Patienten angekommen ist. Abseits der konventionellen Chemotherapie führten diese einerseits zur Entwicklung von molekular zielgerichteten Hemmstoffen des Tumorwachstums und andererseits zum Prinzip der sog. Checkpointinhibitoren, welche körpereigene, immunologische Tumorabwehrreaktionen nutzen.

Ziel

Der aktuelle Status zur biologischen Rationale und zum klinischen Einsatz von Checkpointinhibitoren wird dargestellt.

Methoden

Eine selektive Literaturrecherche wurde durchgeführt.

Ergebnisse

Es liegen fundierte präklinische Erkenntnisse zum Wirkmechanismus von Checkpointinhibitoren vor, deren Validierung in der Klinik jedoch zurückbleibt. Dennoch sind Checkpointinhibitoren bereits in multiplen Entitäten zugelassen (Melanom, Lungenkarzinome, Nierenzellkarzinom, M. Hodgkin, Blasenkarzinom) und weitere Zulassungen stehen unmittelbar bevor (z. B. Kopf-Hals-Tumoren, Merkel-Zell-Tumoren, Magenkarzinom). Eine Vielzahl von Fragen zu diesem neuen Therapieprinzip ist noch ungeklärt wie z. B. richtige Patientenauswahl, Charakteristika besonders profitierender Subgruppen, Biomarkerselektion oder Platzierung im Behandlungsalgorithmus, die durch die Forschung der nächsten Jahre zu beantworten sind.

Schlussfolgerungen

Checkpointinhibitoren sind bereits als neue Säule der medikamentösen onkologischen Therapie fest etabliert. Ein besseres mechanistisches Verständnis insbesondere von Kombinationstherapie und präzise Biomarker werden das Indikationsspektrum und den klinischen Einsatz optimieren.

http://ift.tt/2o6cXsM

Behandlungsalgorithmus kleinzelliger Lungenkarzinome

http://ift.tt/2ozF5I7

Management of Odontogenic Cysts by Endonasal Endoscopic Techniques: A Systematic Review and Case Series

Poster presented at the 2017 American Rhinologic Society Spring Meeting (San Diego, CA).

Video Channel

 

 

 

http://ift.tt/2oYq4QV

Complement Components Are Expressed by Infiltrating Macrophages/Activated Microglia Early Following Viral Infection

Viral Immunology , Vol. 0, No. 0.


http://ift.tt/2p9gEin

Mice Antibody Response to Conserved Nonadjuvanted Multiple Antigenic Peptides Derived from E1/E2 Regions of Hepatitis C Virus

Viral Immunology , Vol. 0, No. 0.


http://ift.tt/2nFbnSB

Antiviral Effect of IDO in Mouse Fibroblast Cells During Influenza Virus Infection

Viral Immunology , Vol. 0, No. 0.


http://ift.tt/2p93RMR

Should My Children Be Watching The News?

 

Difficult times force many parents to question whether they should allow their children to watch the news. On this episode of MomDocs, Dr. Dehra Harris explains what important factors you should consider before making a decision. Also, have your children identify their fears and then make a plan together so that they don't feel overwhelmed from the news.

The post Should My Children Be Watching The News? appeared first on ChildrensMD.

http://ift.tt/2p6rpVN

Humane psychiatrische zorg in de Meander: een kwestie van ethiek

This article describes a number of concrete initiatives taken in the De Meander in Melle (near Ghent, Belgium), a psychiatric ward for patients with a mental disability or an acquired brain injury, with the aim of introducing and safeguarding a psychoanalytic ethic. In the latter, the particularity of the patient plays a central role. De Meander tried to achieve this by abolishing many of the ward rules, allowing more space for the singular solution of the patient. Furthermore, the author describes how aggression is addressed differently, in order to learn how to read this rather than punish it. From an ethical perspective, the values and standards of mainstream society are no longer strictly adhered to, but the starting point is the suffering and the questioning of the patient as a unique subject. The author describes how patients of De Meander are given more responsibility for their lives and future. Hierarchical positions are lifted by creating the possibility of circulation between different team members and by using the therapeutic potential of patients. Finally, the author describes how, via volunteer work, an opening to the outside world is created for so-called chronic patients. These various concrete initiatives are illustrated using clinical vignettes.

http://ift.tt/2p8V2D5

Central Nervous System Depression and Topical Brimonidine

This case series from a private practice evaluated the risk of systemic toxic effects of topical brimonidine, 0.33%, gel when used for hemostasis.

http://ift.tt/2oY4JHB

Eruption of Yellow- and Red-Brown Papules in a Young Adult

A woman in her 20s presented with numerous grouped yellow- and red-brown papules on the upper eyelids, infraorbital rims, bilateral axillae, infamammary creases, lower back, buttocks, hips, inguinal folds, and proximal thighs; she also noted a 3-month history of polyuria, polydipsia, and nocturia. What is your diagnosis?

http://ift.tt/2p8JVcZ

Estimated Cost of Emergency Sunburn Visits—Reply

In Reply We appreciate the interest in our analysis by Xia and colleagues and their discussion of our use of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) for code validation. As they have indicated, the positive predictive values of ICD-9-CM codes 692.71 (first-degree sunburn) and 692.76 (second-degree sunburn) support our search criteria. The remaining code used in our search criteria, ICD-9-CM code 692.77, is for third-degree sunburn. This event is highly unusual, so it is not a surprise that they found no cases with this code in their data set. Although we did not analyze our data by specific codes, we did note that there were only 11 (0.15%) visits in our data set with a code of 692.77.

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Targeted Therapy for Advanced Cutaneous Cancers

Now is an exciting time in the field of cutaneous oncology. More advances in the treatment of metastatic melanoma, advanced basal and squamous cell carcinomas, and Merkel cell carcinoma have been made in the past 5 years than in the previous 5 decades. As in other fields of oncology, the discovery of targeted therapies has revolutionized our treatment of patients with advanced disease. Older cytotoxic agents with substantial morbidity have been replaced with therapies directed at specific aberrant pathways to minimize the adverse-effect profile and maximize efficacy. Drugs are no longer selected via trial and error; specific pretreatment genetic testing can alert the clinician to the driving mutation(s), and a personalized treatment plan can be based on each patient's particular profile. As a result, patients with metastatic skin cancer are living longer, sometimes even achieving complete remission. A diagnosis of metastatic melanoma, advanced basal or squamous cell carcinoma, or Merkel cell carcinoma is no longer a death sentence. Patients and their families can have greater hope. And while each therapy may extend a patient's life expectancy by only a few months, as new therapeutic options become available, patients may live long enough for the next great breakthrough. The future of cutaneous oncology is quite promising.

http://ift.tt/2oz6Hgm

Estimated Cost of Emergency Sunburn Visits

To the Editor We applaud the evaluation by Guy and colleagues of costs for sunburn-associated visits to US emergency departments. Their analysis was performed using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) primary and secondary billing codes for sunburn (692.71, 692.76, and 692.77) in discharge records from the National Emergency Department Sample database.

http://ift.tt/2p8Enzv

Sex Hormones and Hair Loss

This cohort study of German men investigates cross-sectional associations between a panel of liquid chromatography mass–spectrometry-measured sex hormones and hair loss.

http://ift.tt/2oYcXPI

Expanding the Genotypic Spectrum of Bathing Suit Ichthyosis

This cohort study uses targeted sequencing of the TGM1 gene to evaluate mutations for their specificity to bathing suit ichthyosis and their temperature sensitivity.

http://ift.tt/2p8LGao

Molecular Profiling of Multiple Primary Merkel Cell Carcinoma

This case series evaluates genetic relatedness in 4 cases with the clinical diagnosis of multiple primary Merkel cell carcinomas.

http://ift.tt/2p8LI20

Atherogenic Indices Are Increased in Elderly Patients with Unipolar Depression—Case–Control Analysis

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.


http://ift.tt/2p8tZrq

Investigating tensile rate-dependence in composite laminates using a hydraulic pulse test bench

http://ift.tt/2o5MuLq

On the arguments between Dr Shinichi Watanabe and Drs Tsunemi and Hiruma concerning the efficacy of the Dermatophyte Test Strip

http://ift.tt/2p5ZK7i

Modelling three-dimensional fungal growth in response to environmental stimuli

http://ift.tt/2nEqEmM

Applying an active lumbopelvic control strategy during lumbar extension exercises: Effect on muscle recruitment patterns of the lumbopelvic region

OBJECTIVE: Examine whether implementing an active lumbopelvic control strategy during high load prone lumbar extension exercises affects posterior extensor chain recruitment and lumbopelvic kinematics. METHODS: Thirteen healthy adults acquired an optimal active lumbopelvic control strategy during guided/home-based training sessions. During the experimental session electromyography was used to evaluate the activity of the posterior extensor chain muscles during high load trunk/bilateral leg extension exercises with/without application of the strategy. Video-analysis was used to evaluate thoracic/lumbar/hip angles. RESULTS: Implementing the active lumbopelvic control strategy decreased the lordotic angle during trunk (p=0.045; -3.2°) and leg extension exercises (p=0.019; -10°). The hip angle was solely affected during trunk extension (p<0.001;+9.2°). The posterior extensor chain (i.e. mean of the relative activity of all muscles (%MVIC) was recruited to a higher extent (p=0.026;+9%) during trunk extension exercises performed with active lumbopelvic control. Applying the strategy during leg extension exercises lead to less activity of longissimus thoracic (p=0.015; -10.2%) and latissimus dorsi (p=0.010; -4.4%), and increased gluteus maximus activity (p≤0.001;+16.8%). CONCLUSIONS: When healthy people are taught/instructed to apply an active lumbopelvic control strategy, this will decrease the degree of lumbar (hyper)lordosis and this influences the recruitment patterns of trunk and hip extensors. Hence, the possible impact on predetermined training goals should be taken into account by trainers.

http://ift.tt/2p8diwf

Variation in theriogenology teaching methodology in Europe

http://ift.tt/2nEtSqc

Temporal fluctuation in the abundance of alginate-degrading bacteria in the gut of abalone Haliotis gigantea over 1year

In this study, we identified and enumerated alginate-degrading bacteria in the gut of abalone over 1-year period. From a total of 360 colonies growing on agar medium enriched with alginate, 251 isolates (70%) had the ability to degrade alginate. In addition, a high number of viable alginate-degrading bacteria were detected throughout the survey period. Alginate-degrading bacteria were more abundant in the cold season relative to thesummer season (10(7) vs. 10(4)CFUg(-1), respectively). Strong positive correlation was also observed between the number of alginate-degrading bacteria and feed intake (R=0.854; P<0.01). The identified alginate-degrading bacteria comprised of 35 species grouped into 11 genera including Algibacter, Formosa, Polarybacter, Tamlana, Tenacibaculum (CFB group), Roseobacter, Ruegeria, Silicibacter (-proteobacteria), Agarivorans, Shewanella and Vibrio (-proteobacteria) respectively. More than 80% of the isolated alginate-degrading bacteria belonged to the genus Vibrio, showing high homology to Vibrio cyclotorophicus, Vibrio splendidus, Vibrio halioticoli and Vibrio neonatus. Based on the results, it was suggested that algal-polysaccharide (alginate) degrading bacteria (mainly Vibrio) commonly exist in the gut of abalone and may play an important role in the degradation and digestion of the host's feed.

http://ift.tt/2p8jd4p

Induction Chemotherapy for Locally Advanced Esophageal Cancer

Condition:   Esophageal Carcinoma
Interventions:   Drug: mFOLFOX6;   Combination Product: Chemoradiation
Sponsor:   University of Rochester
Not yet recruiting - verified April 2017

http://ift.tt/2oyMCqD

NC-6004 With 5-FU and Cetuximab for Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Condition:   Carcinoma, Squamous Cell of Head and Neck
Interventions:   Drug: NC-6004;   Drug: Cetuximab;   Drug: 5-FU
Sponsor:   NanoCarrier Co., Ltd.
Recruiting - verified April 2017

http://ift.tt/2o5ltYn

Metformin Hydrochloride in Affecting Cytokines and Exosomes in Patients With Head and Neck Cancer

Conditions:   Larynx;   Lip;   Oral Cavity;   Pharynx
Interventions:   Radiation: External Beam Radiation Therapy;   Drug: Metformin Hydrochloride;   Other: Placebo
Sponsor:   Sidney Kimmel Cancer Center at Thomas Jefferson University
Recruiting - verified April 2017

http://ift.tt/2o5zh4Z

A Study to Assess the Safety and Tolerability of Atezolizumab in Combination With Other Immune-Modulating Therapies in Participants With Locally Advanced or Metastatic Solid Tumors

Condition:   Solid Cancers
Interventions:   Drug: Atezolizumab;   Drug: Bevacizumab;   Drug: Interferon alfa-2b;   Drug: Ipilimumab;   Drug: Obinutuzumab;   Drug: PEG-interferon alfa-2a
Sponsor:   Hoffmann-La Roche
Recruiting - verified April 2017

http://ift.tt/2oz58ir

Universal Health Coverage, Priority Setting and the Human Right to Health

Rumbold, B; Baker, R; Hawkes, S; Norheim, O; Ferraz, O; Krubiner, C; Littlejohns, P; Rumbold, B; Baker, R; Hawkes, S; Norheim, O; Ferraz, O; Krubiner, C; Littlejohns, P; Pegram, T; Rid, A; Venkatapuram, S; Voorhoeve, A; Wang, D; Yamin, A; Wilson, JGS; Hunt, P; - view fewer (2017) Universal Health Coverage, Priority Setting and the Human Right to Health. Lancet (In press).

http://ift.tt/2nEwpRm

Investigating the Physical Stability of Repackaged Medicine Stored into Commercially Available Multi-Compartment Compliance Aids (MCAs)

Raimi-Abraham, BT; del Valle, AG; Galcera, CV; Barker, SA; Orlu, M; (2017) Investigating the Physical Stability of Repackaged Medicine Stored into Commercially Available Multi-Compartment Compliance Aids (MCAs). Journal of Pharmaceutical Health Services Research (In press).

http://ift.tt/2ptjBtx

Stability and dynamics of membrane-spanning DNA nanopores

Maingi, V; Burns, JR; Uusitalo, JJ; Howorka, S; Marrink, SJ; Sansom, MSP; (2017) Stability and dynamics of membrane-spanning DNA nanopores. NATURE COMMUNICATIONS , 8 , Article 14784. 10.1038/ncomms14784 . Green open access

http://ift.tt/2nEoiV1

Design, Analysis and Testing of a Novel Mitral Valve for Transcatheter Implantation

Bozkurt, S; Preston-Maher, GL; Torii, R; Burriesci, G; (2017) Design, Analysis and Testing of a Novel Mitral Valve for Transcatheter Implantation. Annals of Biomedical Engineering 10.1007/s10439-017-1828-2 . (In press). Green open access

http://ift.tt/2ptwzaT

Cosmology from the EoR/Cosmic Dawn with the SKA

Pritchard, J; Ichiki, K; Mesinger, A; Metcalf, RB; Pourtsidou, A; Santos, M; Abdalla, F; Pritchard, J; Ichiki, K; Mesinger, A; Metcalf, RB; Pourtsidou, A; Santos, M; Abdalla, F; Chang, T-C; Chen, X; Weller, J; Zaroubi, S; - view fewer Cosmology from the EoR/Cosmic Dawn with the SKA.

http://ift.tt/2nEe6vK

The measurement of OCD in children and young people in clinical practice

Bennett, SD; Coughtrey, AE; Shafran, R; Heyman, I; (2017) The measurement of OCD in children and young people in clinical practice. Child and Adolescent Mental Health

http://ift.tt/2ptGlcQ

PET-CMR in heart failure - synergistic or redundant imaging?

Quail, MA; Sinusas, AJ; (2017) PET-CMR in heart failure - synergistic or redundant imaging? Heart Failure Reviews 10.1007/s10741-017-9607-6 . (In press). Green open access

http://ift.tt/2nEtMiv

Lancet Commission: Stem Cells and Regenerative Medicine

Cossu, G; Birchall, M; Brown, T; De Coppi, P; Culme-Seymour, E; Gibbon, S; Hitchcock, J; Cossu, G; Birchall, M; Brown, T; De Coppi, P; Culme-Seymour, E; Gibbon, S; Hitchcock, J; Mason, C; Montgomery, J; Morris, S; Muntoni, F; Napier, D; Owji, N; Prasad, A; Round, J; Saprai, P; Stilgoe, J; Thrasher, A; Wilson, JGS; - view fewer (2017) Lancet Commission: Stem Cells and Regenerative Medicine. Lancet (In press).

http://ift.tt/2ptAq7D

Treatment planning optimisation in proton therapy

McGowan, SE; Burnet, NG; Lomax, AJ; (2013) Treatment planning optimisation in proton therapy. The British Journal of Radiology , 86 (1021) , Article 20120288. 10.1259/bjr.20120288 . Green open access

http://ift.tt/2nEmjQk

Economic Education in Schools and Universities in England

Davies, P; Durden, G; (2010) Economic Education in Schools and Universities in England. The Journal of Economic Education , 41 (4) pp. 413-424. 10.1080/00220485.2010.510400 .

http://ift.tt/2ptAnZv

Symptom clusters for revising scale membership in the analysis of prostate cancer patient reported outcome measures: a secondary data analysis of the Medical Research Council RT01 trial (ISCRTN47772397)

Lemanska, A; Chen, T; Dearnaley, DP; Jena, R; Sydes, MR; Faithfull, S; (2017) Symptom clusters for revising scale membership in the analysis of prostate cancer patient reported outcome measures: a secondary data analysis of the Medical Research Council RT01 trial (ISCRTN47772397). Quality of Life Research 10.1007/s11136-017-1548-y . (In press). Green open access

http://ift.tt/2nEk5kf

Using Invariances in Geometrical Diagrams: Della Porta, Kepler and Descartes on Refraction

http://ift.tt/2o578v0

Three cases of OXA-48-like carbapenemase producing Enterobacteriaceae (not) detected using Xpert® Carba-R

http://ift.tt/2p5s8GL

Recommendations for further improvement of the deceased organ donation process in Belgium

Belgium has achieved high deceased organ donation rates but according to the medical record data in the Donor Action database, deceased potential donors are still missed along the pathway. Between 2010 and 2014, 12.9 ± 3.3% of the potential donors after brain death (DBD) and 24.6 ± 1.8% of the potential donors after circulatory (DCD) death were not identified. Conversion rates of 41.7 ± 2.1% for DBD and 7.9 ± 0.9% for DCD indicate room for further improvement. We identify and discuss different issues in the monitoring of donation activities, practices and outcomes; donor pool; legislation on deceased organ donation; registration; financial reimbursement; educational and training programs; donor detection and practice clinical guidance. The overall aim of this position paper, elaborated by a Belgian expert panel, is to provide recommendations for further improvement of the deceased organ donation process up to organ procurement in Belgium.

http://ift.tt/2o5mbFd

Prevalence and effect of subclinical endometritis on the pregnancy outcome of nulliparous dairy heifers

http://ift.tt/2p5tzop

Inactivation of ferric uptake regulator (Fur) attenuates Helicobacter pylori J99 motility by disturbing the flagellar motor switch and autoinducer-2 production

Abstract

Background

Flagellar motility of Helicobacter pylori has been shown to be important for the bacteria to establish initial colonization. The ferric uptake regulator (Fur) is a global regulator that has been identified in H. pylori which is involved in the processes of iron uptake and establishing colonization. However, the role of Fur in H. pylori motility is still unclear.

Materials and Methods

Motility of the wild-type, fur mutant, and fur revertant J99 were determined by a soft-agar motility assay and direct video observation. The bacterial shape and flagellar structure were evaluated by transmission electron microscopy. Single bacterial motility and flagellar switching were observed by phase-contrast microscopy. Autoinducer-2 (AI-2) production in bacterial culture supernatant was analyzed by a bioluminescence assay.

Results

The fur mutant showed impaired motility in the soft-agar assay compared with the wild-type J99 and fur revertant. The numbers and lengths of flagellar filaments on the fur mutant cells were similar to those of the wild-type and revertant cells. Phenotypic characterization showed similar swimming speed but reduction in switching rate in the fur mutant. The AI-2 production of the fur mutant was dramatically reduced compared with wild-type J99 in log-phase culture medium.

Conclusions

These results indicate that Fur positively modulates H. pylori J99 motility through interfering with bacterial flagellar switching.

http://ift.tt/2p5lFLK

Sensitivity of Helicobacter pylori detection by Giemsa staining is poor in comparison with immunohistochemistry and fluorescent in situ hybridization and strongly depends on inflammatory activity

Abstract

Background

Conventional stainings (including H&E and special stains like Giemsa) are the most widely applied histopathologic detection methods of Helicobacter pylori (HP).

Materials and Methods

We aimed to compare the diagnostic performance of Giemsa staining with immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) on a monocentric cohort of 2896 gastric biopsies and relate results to histologic alterations in order to find such histopathologic subgroups in which these methods underperform. All cases were categorized regarding presence or absence of chronic gastritis, inflammatory activity, and mucosal structural alterations.

Results

Giemsa revealed 687 cases (23.7%), IHC 795 cases (27.5%), and FISH 788 cases (27.2%) as being HP positive. Giemsa showed significantly lower overall sensitivity (83.3%) compared to IHC (98.8%) and FISH (98.0%). Moreover, the sensitivity of Giemsa dramatically dropped to 33.6% in the nonactive cases. We found that sensitivity of Giemsa strongly depends on HP density and, accordingly, on the presence of activity. Structural alterations (intestinal metaplasia, atrophy, etc.) had only no or weak effect on sensitivity of the three stainings. Both IHC and FISH proved to be equally reliable HP detecting techniques whose diagnostic performance is minimally influenced by mucosal inflammatory and structural alterations contrary to conventional stainings.

Conclusions

We highly recommend immunohistochemistry for clinically susceptible, nonactive chronic gastritis cases, if the conventional stain-based HP detection is negative. Moreover, we recommend to use IHC more widely as basic HP stain. Helicobacter pylori FISH technique is primarily recommended to determine bacterial clarithromycin resistance. Furthermore, it is another accurate diagnostic tool for HP.

http://ift.tt/2o4WbJS

Survival of Helicobacter pylori in gastric acidic territory

Abstract

Background

Helicobacter pylori is well adapted to colonize the epithelial surface of the human gastric mucosa and can cause persistent infections. In order to infect the gastric mucosa, it has to survive in the gastric acidic pH. This organism has well developed mechanisms to neutralize the effects of acidic pH.

Objective

This review article was designed to summarize the various functional and molecular aspects by which the bacterium can combat and survive the gastric acidic pH in order to establish the persistent infections.

Methods

We used the keywords (acid acclimation, gastric acidic environment, H. pylori and survival) in combination or alone for pubmed search of recent scientific literatures. One hundred and forty one papers published between 1989 and 2016 were sorted out. The articles published with only abstracts, other than in English language, case reports and reviews were excluded.

Results

Many literatures describing the role of several factors in acid survival were found. Recently, the role of several other factors has been claimed to participate in acid survival.

Conclusion

In conclusion, this organism has well characterized mechanisms for acid survival.

http://ift.tt/2p5twcq

Motion and Proportion in Simon Stevin’s Mechanics

http://ift.tt/2oyz1iU

Transmission of hepatitis E virus infection to human-liver chimeric FRG mice using patient plasma

Hepatitis E virus (HEV) is considered as an important pathogen in developing countries but there is growing evidence of its increasing significance and prevalence in the Western world. Although most acute HEV infections resolve spontaneously, chronicity has been observed in immunocompromised patients. The study of HEV has been hampered by the absence of practical animal models. Because the in vivo study of HEV was essentially limited to primates and pigs we recently established the human-liver chimeric uPA-SCID mouse model as a useful tool to study HEV infection. Because the humanized FRG mouse model, another type of mouse with humanized liver, is more easily accessible to the scientific community, we investigated its susceptibility to HEV infection. FRG mice were transplanted with human hepatocytes and challenged with different HEV genotypes using different routes of exposure. Our data clearly shows that the humanized FRG mouse is an alternative animal model for the study HEV infection. As observed in the uPA-SCID model, controlled oral inoculation did not lead to active infection. However, intrasplenic injection of genotype 3-infected patient plasma did result into persistent infection. Although the efficiency of transmission was low, this observation corroborates previously published case reports of blood transfusion associated HEV transmission.

http://ift.tt/2p7XMQP

A new high-sensitive nephelometric method for assaying serum C-reactive protein based on phosphocholine interaction

Background: The measurement of C-reactive protein (CRP) concentrations has been of interest as a classical marker of acute phase response; in addition, it has been of particular interest in cardiovascular risk stratification where high-sensitive measurements are necessary. Since CRP is able to bind phospholipids (mainly phosphocholine) in the presence of calcium ions, we explored the possibilities of developing a high-sensitive affordable nephelometric CRP assay based on diluted soy oil emulsions. Methods: Serum (or heparinized plasma) was mixed with Intralipid 20% in Tris-calcium buffer (pH 7.5). After 12 min of incubation at 37 degrees C, the CRP-phospholipid complexes were measured by nephelometry (840 nm) using a BN II nephelometer (Siemens). Results (n=97) were compared with those obtained using a typical immunoturbidimetric method (Roche). Results: Imprecision of the functional nephelometric assay was evaluated using three human serum pools. Within-run coefficients of variation (CVs) for level 1, 2 and 3 were 6.1%, 4.7% and 4.5%, respectively, and between-run CVs were 17.6%, 18.8% and 11.3%, respectively. Good agreement was obtained between the functional nephelometric and the immunoturbidimetric CRP assay in a concentration range from 0.1 mg/L to 50 mg/L (r=0.884). A logit-log calibration curve was made between 0.056 mg/L and 1.785 mg/L. The limit of detection was 0.5 mg/L. Conclusions: The functional nephelometric CRP assay allowed high-sensitive CRP determinations in serum and plasma. Since the assay is species independent, the described functional CRP assay could be used for veterinary purposes as well.

http://ift.tt/2oykjZi

Small steps for large arteries : bringing arterial structure and function measurements to daily clinical practice

http://ift.tt/2p7E4EM

New insights into the molecular diagnosis and management of heritable thoracic aortic aneurysms and dissections

Since the identification of the fibrillin-1 gene as the causal gene for Marfan syndrome, our knowledge of molecular genetics and the applicability of genetic testing for heritable thoracic aneurysms and dissections (H-TAD) in clinical practice have increased substantially. Several new syndromes related to H-TAD have been described and the list of mutated genes in syndromal and nonsyndromal H-TAD is rapidly expanding. This knowledge has led to a significant improvement of our insight into the underlying pathophysiology of H-TAD resulting in new opportunities for targeted treatment, as well as in improved risk stratification. Clinicians involved in the care for H-TAD patients require a basic knowledge of the disease entities and need to be correctly informed on the applicability of genetic testing in their patients and families. Gene-tailored treatment and management should now be considered as part of good clinical practice. We provide a systematic overview of genetic H-TAD entities and practical recommendations for genetic testing and patient management.

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Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

Introduction: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Conclusions: Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. Trial registration: ClinicalTrials.gov number NCT01209169.

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Aortic stiffness and central wave reflections predict outcome in renal transplant recipients

Although renal transplantation improves survival, cardiovascular morbidity and mortality remain significantly elevated compared with nonrenal populations. The negative impact of traditional, uremia-related, and transplantation-related risk factors in this process remains, however, largely unexplored. Surrogate markers such as aortic stiffness and central wave reflections may lead to more accurate cardiovascular risk stratification, but outcome data in renal transplant recipients are scarce. We aimed to establish the prognostic significance of these markers for fatal and nonfatal cardiovascular events in renal transplant recipients. Carotid-femoral pulse wave velocity, central augmentation pressure, and central augmentation index were measured in a cohort of 512 renal transplant recipients using the SphygmoCor system. After a mean follow-up of 5 years, 20 fatal and 75 nonfatal cardiovascular events were recorded. Using receiver operating characteristic curves, the area under the curve for predicting cardiovascular events was 0.718 (95% CI 0.659-0.776) for pulse wave velocity, 0.670 (95% CI 0.604-0.736) for central augmentation pressure, and 0.595 (95% CI 0.529-0.660) for central augmentation index. When we accounted for age, gender, and C-reactive protein in Cox-regression analysis, pulse wave velocity (hazard ratio: 1.349 per 1 SD increase; 95% CI 1.104-1.649; P = 0.003) and central augmentation pressure (hazard ratio: 1.487 per 1 SD increase; 95% CI 1.219-1.814; P < 0.001) remained independent predictors of outcome. Aortic stiffness and increased wave reflections are independent predictors of cardiovascular events in renal transplant recipients. As single parameter of wave reflection, central augmentation pressure was better than central augmentation index. Combined measurement of pulse wave velocity and central augmentation pressure may contribute to an accurate cardiovascular risk estimation in this heterogeneous population.

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