Head and Neck Medicine by Alexandros G.Sfakianakis: 08/09/17

Τετάρτη 9 Αυγούστου 2017

Upper airway surgery for obstructive sleep apnea reduces blood pressure

Objectives/Hypothesis

To evaluate if upper airway surgery reduces blood pressure in patients with obstructive sleep apnea (OSA).

Study Design

Prospective series.

Methods

A prospective series of 112 consecutive OSA patients with hypertension (HTN). All patients were > 18 years old, respiratory disturbance index >5, all levels of apnea-hypopnea index (AHI), with a history of HTN treated with medication for at least 6 months. Surgical procedures included septoplasty, turbinate reduction, palate surgery, and tongue base reduction.

Results

There were 92 men and 20 women, with a mean age of 48.6 years, mean body mass index (BMI) was 27.5 (range, 19.7–34.7). Mean follow-up was 16.1 months. The mean preoperative AHI was 32.6 (range, 1.2–104), with the mean lowest oxygen saturation (LSAT) of 79.9% (range, 52%–93%). The mean adjusted preoperative and postoperative systolic blood pressure (SBP) was reduced from 146 ± 15.3 mm Hg to 122 ± 12.5 mm Hg (P < .001), and diastolic blood pressure (DBP) was reduced from 91 ± 10.2 mm Hg to 76 ± 7.8 mm Hg (P < .001). There was a decrease in overall BMI from 27.5 ± 3.6 to 25.5 ± 3.0 (P < .001); however, based on multivariate analysis, the reduction in SBP and DBP was not affected by this BMI reduction. Fifty-eight patients (51.8%) did not require their antihypertensive after surgery. There was poor correlation noted between HTN with AHI, LSAT, and oxygen duration <90%.

Conclusions

Upper airway surgery does reduce SBP and DBP in patients with OSA.

Level of Evidence

4. Laryngoscope, 2017

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First Japanese case report of atypical Spitz tumor with an ALK rearrangement

http://ift.tt/2vQp7Na

A novel method for sex estimation using 3D computed tomography models of tooth roots: A volumetric analysis

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Seyedeh M. Kazzazi, Elena F. Kranioti
Advances in technologies such as computed tomography (CT) scanning have allowed for further examination of dental sexual dimorphism in modern and archaeological populations.

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A novel method for sex estimation using 3D computed tomography models of tooth roots: A volumetric analysis

Issue Information - Contents

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Cover Image

The cover image, by Jacqui Allen et al., is based on the Original Article Assessment of videofluoroscopic swallow study findings before and after cricopharyngeal myotomy, DOI: 10.1002/hed.24846.

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Variations in the labyrinthine segment of facial nerve canal revealed by high-resolution computed tomography

To study variations in the labyrinthine segment of fallopian canal and the associated middle and inner ear malformations.

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Ultrasound versus magnetic resonance imaging of the temporomandibular joint in juvenile idiopathic arthritis: a systematic review

A systematic review of published articles on ultrasound (US) and magnetic resonance imaging (MRI) of the temporomandibular joint (TMJ) in juvenile idiopathic arthritis (JIA) was performed to answer the question "What is the sensitivity and specificity of US as compared to MRI in diagnosing acute and chronic joint changes in patients with JIA?" The most recent evidence was sought in published articles via a search of the PubMed, Ovid, and Embase databases. Article appraisal was performed by two reviewers.

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Clinical application of autogenous partially demineralized dentin matrix prepared immediately after extraction for alveolar bone regeneration in implant dentistry: a pilot study

The aim of this study was to examine the efficacy and safety of autogenous partially demineralized dentin matrix (APDDM) prepared onsite, for clinical application in bone regeneration procedures related to implant dentistry, including socket preservation, alveolar ridge augmentation, and maxillary sinus floor augmentation. In this study, 16 patients underwent dental implant placement using APDDM transplantation. There were no systemic or local complications (including surgical site infection) in any of the cases, and oral rehabilitation using dental implants was successful in all cases for at least 2 years after attachment of the suprastructure.

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Therapie seltener kutaner T‑Zell-Lymphome und der blastären plasmazytoiden dendritischen Zellneoplasie

Zusammenfassung

Unter den primär kutanen Lymphomen existieren definierte Subtypen, die mit extrem niedrigen Inzidenzzahlen auftreten. Basierend auf der Revision der WHO-Klassifikation für lymphoide Neoplasien von 2016, werden in diesem Beitrag die Entitäten der seltenen kutanen T‑Zell-Lymphome (CTCL) und deren Therapieoptionen erläutert. Da die Prognose der verschiedenen Entitäten sehr stark variiert, ist es umso wichtiger, die Therapie entsprechend dem zu erwartenden Verlauf der Erkrankung anzupassen. Bei den indolenten Subtypen sind lokale Maßnahmen, wie z. B. topische Applikation von Glukokortikosteroiden oder Lichttherapie, in vielen Fällen ausreichend. Bei den aggressiven Varianten hingegen ist es umso wichtiger, frühzeitig ggf. aggressivere Therapieoptionen zu diskutieren.

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Jodi Arias: A Case of Extreme Violence

Violence and Gender , Vol. 0, No. 0.

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Higher TSH and Lower FT4 Levels in Pregnant Women Are Associated with Higher Pregestational BMI and Greater Gestational Weight Gain

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 310-311.

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Parathyroid Lesions Can Be Distinguished from Thyroid Lesions on FNA but May Require Ancillary Studies and Molecular Analysis

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 291-293.

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Older Age and Advanced Disease Are Risk Factors for Complications after Thyroid Cancer Surgery

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 294-296.

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How Does the Thyroid Hormone Level Affect the Level of the Apoptosis Regulator TRAIL?

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 315-317.

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The Merits of Ultrasound Screening for Familial Nonmedullary Thyroid Cancer Are Strongly Dependent on the Number of Affected Family Members

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 297-300.

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TSH-Based Levothyroxine Dosage Adjustment Is Superior to Fixed Dosage Adjustments in Pregnant Women with Preexisting Hypothyroidism

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 307-309.

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18F-FDOPA-PET Is More Sensitive than F-18-FDG-PET in Persistent or Recurrent Medullary Thyroid Cancer

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 301-304.

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Thyroid Dysfunction Was Associated with Dyslipidemia, but Not Incident Myocardial Infarction or Stroke in a Large U.S. General Population–Based Cohort

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 312-314.

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Fatal Nonanaplastic Thyroid Cancers Harbor Multiple Oncogenic Mutations

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 305-306.

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CASE REPORT: Two Cases of Impaired Sensitivity to Thyroid Hormone with Wild-Type THRβ Gene

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 318-321.

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Expression of Kallikrein-Related Peptidase 6 in Primary Mucosal Malignant Melanoma of the Head and Neck

Abstract

Mucosal melanomas of the head and neck (MMHN) are aggressive tumors with poor prognosis, different opposed to cutaneous melanoma. In this study, we characterized primary mucosal malignant melanoma for the expression of Kallikrein-related peptidase 6 (KLK6), a member of the KLK family with relevance to the malignant phenotype in various cancer types including cutaneous melanoma. Paraffin-embedded MMHN of 22 patients were stained immunohistochemically for KLK6 and results were correlated with clinical and pathological data. In 77.3% (17/22) of MMHN cases, positive KLK6 staining was found. Staining pattern for tumor cells showed a predominant cytoplasmic staining. However, in six cases we also observed a prominent nuclear staining. MMHN with a high KLK6 expression showed significantly better outcome concerning local recurrence-free survival (p = 0.013) and nuclear KLK6 staining was significantly associated with the survival status (p = 0.027). Overexpression of KLK6 was detected in more than 70% of MMHN and approximately 40% of tumors showed a strong expression pattern. Correlation between clinical outcome of MMHN patients and overexpression of KLK6 has not been addressed so far. Our data demonstrate for the first time increased levels of KLK6 in MMHN and strengthen the hypothesis that there might be a context-specific regulation and function of KLK6 in mucosal melanoma.

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The Great Mimicker: Metastatic Breast Carcinoma to the Head and Neck with Emphasis on Unusual Clinical and Pathologic Features

Abstract

Distant metastases are relatively common in breast cancer, but spread to the head and neck region is uncommon and can be diagnostically challenging. Pathology databases of two academic hospitals were searched for patients. The diagnoses were by morphologic comparison with the primary breast specimen (when available) or through the use of immunohistochemical stains characteristic of breast carcinoma (cytokeratin 7, mammaglobin, GCDFP15, and/or GATA3 positive—excluding new primary tumors at the respective head and neck sites). Of the 25 patients identified, only 22 (88.0 %) had a known history of breast carcinoma. Time from primary diagnosis to head and neck metastasis was highly variable, ranging from 1 to 33 years (mean = 10.9 years). The most common locations were neck lymph nodes (8 cases), orbital soft tissue (5), oral cavity (3), skull base (3), mastoid sinus (2), nasal cavity (1), palatine tonsil (1), and facial skin (1). Clinical presentations were highly variable, ranging from cranial nerve palsies without a mass lesion to oral cavity erythema and swelling to bone pain. Histologically, two cases showed mucosal (or skin)-based mass lesions with associated pagetoid spread in the adjacent epithelium, a feature normally associated with primary carcinomas. Three tumors were misdiagnosed pathologically as new head and neck primary tumors. This series demonstrates the extreme variability in clinical and pathologic features of breast cancer metastatic to the head and neck, including long time intervals to metastasis.

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Head and Neck Rhabdomyosarcoma: Clinical and Pathologic Characterization of Seven Cases

Abstract

Head and neck rhabdomyosarcoma occurs frequently in children and adolescents, and has been well studied in that population. In contrast, it is rare in adults and is not as well characterized clinically and pathologically. Seven cases of adult rhabdomyosarcoma occurring in head and neck were retrieved from the archives of Department of Pathology and Division of Oral Pathology at University of Washington. Radiologic findings and clinical history, as well as pathologic findings from hematoxylin and eosin slides and immunohistochemistry for myogenic markers were reviewed. A total of seven cases of rhabdomyosarcoma (two embryonal, three alveolar and two pleomorphic subtype) were reviewed. Patient ages ranged from 18 to 57 years (median 21 years). Classic and unique histologic features for each subtype, including post-treatment morphologic changes, were identified. Clinical follow-up information was available for 4 patients. 3 of 4 patients experienced recurrence, including two with distant metastasis. One patient died of disease progression 41 months after presentation. Head and neck rhabdomyosarcoma in adults can manifest both classic and unique histologic features for each subtype. In addition, recurrence and distant metastasis were observed, suggesting aggressive clinical behavior regardless of subtype.

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Atopy and prostate cancer: Is there a link between circulating levels of IgE and PSA in humans?

Abstract

Background

Atopy has been investigated as a potential risk factor for prostate cancer. IgE antibodies may be major players in protective responses against tumours, through engendering antigen presentation and enhancing adaptive immune responses targeted towards a specific allergen, but potentially also against tumour-associated antigens such as prostate-specific antigen (PSA). We therefore cross-sectionally investigated associations between circulating levels of PSA and IgE in the National Health and Nutrition Examination Survey 2005–2006.

Methods

We focused on all men aged 40+ years with measurements for PSA and IgE, and no previous diagnosis of prostate cancer (n = 1312). We estimated the association between total and specific IgE concentration and levels of PSA with logistic regression models, adjusted for age, ethnicity/race, education, smoking status, body mass index (BMI), physical activity status, and history of asthma.

Results

Both total IgE and the sum of specific IgE were inversely associated with the risk of having PSA levels ≥10 ng/mL, though most findings were not statistically significant. The odds ratios for the second and third tertile of total IgE as compared to the first were 0.21 (95% CI 0.06–0.72) and 0.42 (0.08–2.31). The odds ratio for sum of abnormal specific IgE measurements was 0.77 (0.44–1.34).

Conclusion

Despite statistical insignificance, the observed trend warrants further research given the increasing evidence of the role of atopy and IgE antibodies in protective responses against tumours. A lifecourse approach of measuring IgE, specific subtypes, and other markers of the humoral immune system (i.e. IgG) could shed more light on its potential anti-cancer characteristics.

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Cranio-cervical junction cerebrospinal fluid leak after microdebrider-assisted adenoidectomy – A rare case report

Publication date: Available online 9 August 2017
Source:Acta Otorrinolaringológica Española
Author(s): Karthikeyan Ramasamy, Hemanth Vamanshankar, Sunil Kumar Saxena, Vignesh Karunakaran, Arun Alexander

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Expression of Kallikrein-Related Peptidase 6 in Primary Mucosal Malignant Melanoma of the Head and Neck

Abstract

http://ift.tt/2vFS9Q1

The Great Mimicker: Metastatic Breast Carcinoma to the Head and Neck with Emphasis on Unusual Clinical and Pathologic Features

Abstract

http://ift.tt/2vns6ug

Head and Neck Rhabdomyosarcoma: Clinical and Pathologic Characterization of Seven Cases

Abstract

http://ift.tt/2vFrzGU

American Thyroid Association Awards Bite Me Cancer Research Grant to Brian P. Danysh, PhD, University of Texas MD Anderson Cancer Center

Brian P Danysh, PhD
The University of Texas MD Anderson Cancer Center
Houston TX Bio

Supported by ATA

The American Thyroid Association has awarded a 2017 Research Grant, funded by Bite Me Cancer, to Brian P. Danysh, PhD, Instructor in Endocrine Neoplasia and Hormonal Disorders at the University of Texas MD Anderson Cancer Center. Dr. Danysh's project is entitled "Novel Alternative Pathways and Mutational Hotspots in Papillary Thyroid Cancer With Acquired Resistance to BRAF Inhibitors."

The BRAF gene is the most frequent mutation found in papillary thyroid cancer (PTC) and is associated with shorter life expectancy. Drugs targeting the BRAF gene are initially effective, but have proven to be less useful over the course of a patient's treatment as the cancer cells find ways to overcome the drug's effectiveness. The goal of this project is to lay the groundwork for the development of new drugs that will extend the lives of people with aggressive forms of thyroid cancer. To that end, the research will investigate the mutations that arise during a patient's treatment that allow cancer cells to continue growing and determine whether the drugs used may be themselves facilitating new gene mutations.

As with melanoma, it appears that acquisition/selection of novel resistance-promoting mutations under kinase-inhibitor therapies appears to occur in PTCs. Therefore, it is imperative to devise treatments to replace or complement current targeted-therapy protocols. The development of new therapies lies in the discovery and analysis of novel mutations and their downstream pathways.

Dr. Danysh received his PhD from the University of Delaware and carried out postdoctoral training at Rice University, Houston, TX, where he collaborated with physicists in the use of nanoparticles and laser irradiation to selectively destroy cancer cells, and at the University of Texas MD Anderson Cancer Center. His current research at MD Anderson involves working with clinicians to examine the mechanisms of acquired inhibitor resistance, with the goal of discovering novel therapeutic targets to recurrent metastatic thyroid cancer.

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Dr. Motoyasu Saji, Chair, ATA Research Committee, says, "The ATA research grant program supports young scientists in thyroid-related research, including clinical, translational, and basic areas. Every year we receive over 50 grant applications from various countries. We are excited to see young thyroid researchers who attack current clinical problems and basic scientific questions using state-of-the-art technologies, new ideas, and new views. Many current leaders in the ATA were award recipients, which shows how important this program is for us. We hope these grants will be gateways to success in their careers as thyroid researchers and that the recipients will become leaders in the next generation of the ATA. Finally, we appreciate all the support we receive from members and various organizations, including thyroid cancer survivors, which makes it possible to create this excellent program."

The American Thyroid Association (ATA) has awarded 92 thyroid research grants totaling over $2.4 million since the inception of the Research Fund. In addition, the ATA rigorously manages the selection of research projects and the distribution of over $1.8 million generously donated to the ATA specifically for research grants from: ThyCa, the Thyroid Cancer Survivors' Association, Inc.; Bite Me Cancer; and the Thyroid Head and Neck Cancer Foundation.

The Thyroid Cancer Survivors' Association, Inc. (ThyCa), has provided funding since 2003 in support of 67 special research grants totaling $1,881,250 focused on thyroid cancer and medullary thyroid cancer. ThyCa is supporting three research grants in 2017 and four renewing grants. ThyCa is a member of the ATA Alliance for Patient Education. Find out more at www.thyca.org.

Bite Me Cancer (BMC) is our newest grant funder, supporting seven thyroid cancer grants since 2014 for a total of $201,250. BMC will be supporting a new thyroid cancer grant in 2017 and one renewing grant. BMC is a member of the ATA Alliance for Patient Education. Find out more at www.bitemecancer.org.

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The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis, and treatment of thyroid disorders and thyroid cancer. ATA is an international, individual membership organization for over 1,700 clinicians and researchers from 43 countries around the world, representing a broad diversity of medical disciplines. It also serves the public, patients and their families through education and awareness efforts.

Celebrating its 94th anniversary, ATA delivers its mission through several key endeavors: the publication of highly regarded monthly journals, THYROID, Clinical Thyroidology, VideoEndocrinology, and Clinical Thyroidology for the Public; annual scientific meetings; biennial clinical and research symposia; research grant programs for young investigators; support of online professional, public, and patient educational programs; and the development of guidelines for clinical management of thyroid disease.

Find out more about ATA at www.thyroid.org.

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American Thyroid Association Awards ThyCa Research Grant to Glenn J. Hanna, M.D., Dana-Farber Cancer Institute’s Center for Head and Neck Oncology

Glenn J. Hanna, M.D.
Dana-Farber Cancer Institute / Brigham & Women's Hospital
Boston, MA 02215 Bio

Supported by ATA

The American Thyroid Association has awarded a 2017 Research Grant, funded by the Thyroid Cancer Survivors' Association, Inc. (ThyCa), to Glenn J. Hanna, MD. Dr. Hanna is a Staff Physician at the Dana-Farber Cancer Institute (DFCI)'s Center for Head & Neck Oncology, as well as an Instructor in Medicine at Harvard Medical School. His project, "Correlating the circulating immune profile with response to dual-immune checkpoint inhibition in advanced thyroid cancer," will evaluate:

How immune cells surrounding an advanced thyroid tumor compare to those circulating in the bloodstream
Whether changes in blood levels of key immune parameters may predict whether an individual patient with such a tumor will respond to immunotherapy

Deaths from thyroid cancer mortality appear to be increasing in the United States. Patients with advanced and incurable thyroid cancers have few options beyond traditional chemotherapy and oral targeted therapies that aim to slow the progression of the disease. But among many other cancer types, we are seeing significant benefits from immunotherapies that unleash normal immune mechanisms against cancer cells.

Immune-checkpoint inhibitors—cancer treatment drugs that prevent immune cells from being turned off by cancer cells—have demonstrated clinical benefit in a wide range of solid tumors. So far, this effect includes a small number of advanced thyroid tumors. We now wish to discover predictors of response or resistance in this set of patients, through clinical trials. Dr. Hanna's study will open an investigator-sponsored, phase II study of the effect of two combined immune-checkpoint inhibitors on advanced thyroid cancer.

In patients treated with the combined drug, the study will detail the tumor microenvironment and correlate that profile with a new immune checkpoint profiling assay. Also, by correlating the patients' circulating immune signature with their immunotherapy response at various points in time, the study group will be able to analyze treatment benefit more cost-effectively than with repeated tumor biopsies. These efforts should enable researchers to identify those patients most likely to benefit from immune checkpoint inhibitors.

Dr. Hanna completed his residency training in internal medicine at Beth Israel Deaconess Medical Center and his fellowship training in hematology and medical oncology at the Dana-Farber Cancer Institute in 2016. He earned his medical degree from Georgetown University School of Medicine in 2010, where he graduated summa cum laude, a member of Alpha Omega Alpha Honor Society, and the Kober Medalist for academic excellence. Dr. Hanna also graduated summa cum laude from the University of Florida. He joined the faculty of the Center for Head & Neck Oncology at the DFCI in 2017.

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The American Thyroid Association (ATA) has awarded 85 thyroid research grants totaling over $2.4 million since the inception of the Research Fund. In addition, the ATA rigorously manages the selection of research projects and the distribution of over $1.8 million generously donated to the ATA specifically for research grants from: ThyCa, the Thyroid Cancer Survivors' Association, Inc.; Bite Me Cancer; and the Thyroid Head and Neck Cancer Foundation.

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Find out more about ATA at www.thyroid.org.

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American Thyroid Association Awards ThyCa Research Grant to Jens Lohr, MD, PhD, Dana Farber Cancer Institute

Jens Lohr, MD, PhD

Jens Lohr, MD, PhD
Dana-Farber Cancer Institute
Boston, MA Bio

Supported by ATA

The American Thyroid Association has awarded a 2017 Research Grant, funded by the Thyroid Cancer Survivors' Association, Inc. (ThyCa), to Jens Lohr, MD, PhD, who is Assistant Professor of Medicine in the Medical Oncology Department at Dana-Farber Cancer Institute in Boston, MA. Dr. Lohr's project, entitled "Characterization of treatment response in thyroid cancer by cfDNA," will explore whether "liquid biopsy" from a vial of blood can be an effective tool to gain insight into the tumor biology of thyroid cancer and, ultimately, will translate these findings into new targeted therapies.

Despite much recent therapeutic progress, thyroid cancer that is resistant to radioactive iodine remains difficult to treat. Patients may respond to initial treatment with newer, targeted therapies but drug resistance still often develops. Therefore, it is urgent that we determine the underlying resistance mechanisms and develop novel biomarkers that allow for early detection of resistant disease.

Dr. Lohr's laboratory has developed a technology to monitor cell-free DNA (cfDNA) that is derived from thyroid cancer in the blood of patients. This project will test whether such monitoring offers a valuable measurement for tumor response, in addition to imaging studies, as a surrogate marker for tumor burden. It has been demonstrated in other types of malignancies that tracking tumor-associated genetic defects in the blood can be used to assess disease or the emergence of resistance to a therapy, but little is known about this approach in thyroid cancer.

Dr. Lohr and his team will establish whether cfDNA can be used as a dynamic biomarker for tumor load, response to therapy, and development of drug resistance. They will define the sensitivity of their approach and determine the number of patients and clinical parameters that allow for sufficient genetic profiling of patients. Follow-up of clinical response parameters will determine whether cfDNA allows comprehensive genomic characterization of thyroid cancer in real-time. The work will establish a blueprint for simultaneous real-time tracking and identification of mechanisms of drug resistance in thyroid cancer. These data may reveal novel drug targets and impact how we design targeted treatment regimens for these patients.

Dr. Lohr received his MD and PhD from Ruprecht-Karls University in Heidelberg, Germany, where he also trained as an immunologist. He completed a residency in internal medicine at UC San Francisco and a medical oncology fellowship at the Dana-Farber/Partners Cancer Care program in Boston. He performed postdoctoral work in immunology at UCSF and in cancer genomics at the Broad Institute, Cambridge, MA. Dr. Lohr is board certified in internal medicine, medical oncology, and hematology and practices as a clinician at Dana-Farber/Partners Cancer Care. Dr. Lohr is specialty chief editor of Precision Medicine for the journal Frontiers in Medicine.

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Celebrating its 94th anniversary, ATA delivers its mission through several key endeavors: the publication of highly regarded monthly journals, THYROID, Clinical Thyroidology, VideoEndocrinology, and Clinical Thyroidology for the Public; annual scientific meetings; biennial clinical and research symposia; research grant programs for young investigators; support of online professional, public, and patient educational programs; and the development of guidelines for clinical management of thyroid disease.

Find out more about ATA at www.thyroid.org.

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American Thyroid Association Awards ThyCa Research Grant to Vicki Emma Smith, PhD, University of Birmingham, UK

Vicki Emma Smith, PhD
University of Birmingham
Edgbaston
Birmingham, UK. Bio

Supported by ATA

The American Thyroid Association has awarded a 2017 Research Grant, funded by the Thyroid Cancer Survivors' Association, Inc. (ThyCa), to Vicki Emma Smith, PhD, Lecturer in Molecular Endocrinology at the University of Birmingham, UK. Dr. Smith's project, "A New Molecular Switch in Thyroid Cancer," undertakes to improve our understanding of thyroid tumors and to consider PBF phosphorylation as a potential new drug target for the treatment of thyroid cancer.

The use of new technologies has allowed researchers to identify the mutations that turn normal cells into cancer cells, which then develop into tumors. These new technologies have also identified many other kinds of molecular changes in cancer cells. Understanding how each of these changes contributes to the growth of cancers and their development into more aggressive, hard-to-treat tumors is essential. Increasing the knowledge of thyroid tumor biology will help to better predict how the tumor will behave and what treatment it will respond to most effectively. It will likely also identify new therapeutic targets.

One of the changes often seen in thyroid cancer cells is an increase in the pituitary tumor-transforming gene-binding factor (PBF) protein. High PBF levels have been linked with more aggressive thyroid tumors and their resistance to radioiodine treatment. We now believe that a modified (phosphorylated) version of this protein contributes to thyroid tumor growth and progression to more aggressive disease. This project aims to fully understand the role of PBF and its phosphorylated form in thyroid tumors. Dr. Smith's research group has already shown that we can use drugs to inhibit PBF phosphorylation; therefore, this project will not only improve our understanding of thyroid tumors but will also consider PBF phosphorylation as a potential new drug target for the treatment of thyroid cancer.

Dr. Smith graduated with an Honors Degree in Medical Biochemistry from the University of Leicester and then spent several years in industry performing genetic association studies of various disorders, including autoimmune thyroid disease. She completed her PhD investigating the downregulation of NIS and critical radioiodine treatment in thyroid cancer, then continued this research as a Medical Research Council-funded Post-Doctoral Researcher in Birmingham. She has published several high-impact papers and received several prestigious academic prizes and awards. Recently she took up her current position at the University of Birmingham and is building an independent research group focused on the molecular pathogenesis of thyroid cancer. Her main research interests include investigating thyroid cancer signaling pathways, improving radioiodine treatment, and identifying novel therapies. She is a member of the Society for Endocrinology Science Committee and the British Thyroid Association Executive Committee.

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Find out more about ATA at www.thyroid.org.

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American Thyroid Association Awards Research Grant to Jason E. Coleman, PhD, University of Florida

Jason E. Coleman, PhD
University of Florida
Gainesville, FL Bio

Supported by ATA

The American Thyroid Association has awarded a 2017 Research Grant to Jason E. Coleman, PhD, Assistant Professor of Pediatrics at the University of Florida in Gainesville. Dr. Coleman's project, "Effects of Early Hypo- and Hyperthyroidism on Long-Term Cortical Circuit Plasticity," will study the effects of hypothyroidism and hyperthyroidism during pregnancy and the long-term consequences on brain function and behavior in offspring.

We already know that the developing fetus relies on a maternal supply of thyroid hormone for normal brain development. However, the more complex changes that arise from thyroid hormone imbalances are not well understood. Many long-term disturbances in brain function are likely the result of subtle changes in brain connections in the cerebral cortex, where information from the outside world is processed to drive behavior. To better understand how thyroid hormones contribute to long-term neuropsychological problems in affected children, it is critical to determine when and where cortical connections are vulnerable to perturbations in thyroid hormone levels and how adaptive behaviors are affected. By examining hormonal effects in the mouse visual cortex, Dr. Coleman expects to 1) determine how the timing and duration of hypo- and hyperthyroidism affect the expression of select genes involved in thyroid hormone signaling to the developing brain and 2) determine how well the visual cortex can adapt to new experiences and how this adaptability in turn affects learning ability.

Dr. Coleman received his PhD in neuroscience from the University of Florida. He has over 10 years of experience in research investigating the visual system and in the development and use of viral vectors for gene transfer for studying the nervous system. At UF, he has established a successful research program studying the effects of perinatal insults on long-term neural structure and function and has already obtained competitive funding from the NIH and NSF.

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Find out more about ATA at www.thyroid.org.

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American Thyroid Association Awards Research Grant to Lawrence A. Shirley, MD, MS, FACS, Ohio State University Wexner Medical Center

Lawrence Shirley, PhD

Lawrence Shirley, MD, MS, FACS
The Ohio State University
Wexner Medical Center
Columbus, OH Bio

Supported by ATA

The American Thyroid Association has awarded a 2017 Research Grant to Lawrence A. Shirley, MD, MS, FACS, Assistant Professor of Surgical Oncology, Ohio State University Wexner Medical Center. Dr. Shirley's project is entitled "Impact of BRAF-Mutated Papillary Thyroid Cancers on Cancer-Associated Fibroblast Genotype and Phenotype." In this project, Dr. Shirley's laboratory plans to:

Perform genomic analysis of cancer-associated fibroblasts (CAFs) from mouse models, expecting to uncover new markers and treatment targets.
Assess how thyroid CAF-secreted factors, as well as cell-cell contact, affect cancer cell function.

Thyroid cancer currently has the highest increase rate and is projected to become by 2030 the fourth most common cancer among all patients and the second most common in women. Most patients are successfully treated with surgical excision and radioactive iodine therapy but, for those whose cancers do not respond, no other curative therapies are available at present. We are uncertain whether to treat these patients more aggressively or more conservatively. We need to discover new biomarkers and novel treatments.

In other cancer types, significant research has been performed on a "normal" cell type that supports cancer growth, the cancer-associated fibroblast. The CAF has been shown to facilitate growth of cancer cells and to aid in their ability to spread to distant sites. Information derived from CAFs has further been shown to help predict how other cancers respond to traditional therapies. However, the role of CAFs in thyroid cancers is largely unknown. Dr. Shirley's laboratory has been able to isolate CAF cells from mouse models of thyroid cancer. This will allow them to study properties of the CAFs themselves, as well as their interactions with primary thyroid cancer cells.

His laboratory has previously found that increased expression of specific markers in thyroid CAFs correlated significantly with patient outcomes, indicating a possible role of CAFs as a tumor-specific biomarker and as an active participant in tumor aggressiveness.

Lawrence A. "Drew" Shirley MD, MS, FACS, is an Assistant Professor in the Division of Surgical Oncology at Ohio State University Wexner Medical Center, as well as the Associate Program Director of the Surgical Oncology Fellowship. Dr. Shirley received his BA in English/Molecular Biology at Vanderbilt University and his MD from the University of Kentucky College of Medicine. He went on to complete his General Surgery Residency at Thomas Jefferson University Hospital and a Surgical Oncology Fellowship at Ohio State University. While in Fellowship, he also received a Master's Degree in Medical Science. He joined the faculty at Ohio State University in October 2014. He is board-certified in general surgery and complex general surgical oncology. His clinical practice focuses on the surgical management of endocrine disease, including thyroid, parathyroid, and adrenal diseases.

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Find out more about ATA at www.thyroid.org.

The post American Thyroid Association Awards Research Grant to Lawrence A. Shirley, MD, MS, FACS, Ohio State University Wexner Medical Center appeared first on American Thyroid Association.

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American Thyroid Association Awards Research Grant to Marco Medici, MD, PhD, MSc, Erasmus Medical Center

Marco Medici, MD, PhD, MSc
Erasmus Medical Center
Rotterdam, The Netherlands Bio

Supported by ATA

The American Thyroid Association has awarded a 2017 Research Grant to Marco Medici, MD, PhD, MSc, a clinical fellow in endocrinology at Erasmus Medical Center in Rotterdam, The Netherlands. In his project, "Personalized Management of Thyroid Disease," Dr. Medici will create a prediction model to estimate an individual patient's TSH (Thyroid Stimulating Hormone) setpoint, which should ultimately lead to personalized care for both hyper- and hypothyroid-diseased patients.

Presently, we treat thyroid disease by attempting to normalize serum TSH levels to within average-population-based ranges. However, individual variabilities lie within much narrower ranges, leaving roughly 15% of thyroid patients with continuing, often disabling symptoms of their diseases and an impaired quality of life. In addition, even subtle variations in thyroid function are associated with cardiovascular disease and mortality. Therefore, it is important to normalize TSH levels to the individual patient's unique TSH setpoint, dictated by his or her hypothalamic-pituitary-thyroid (HPT) axis. To measure that setpoint, we need to know the patient's TSH and free thyroxine (FT4) levels before the onset of thyroid disease. Without a sense of those predisease levels, we cannot know what to aim for post-onset. Unfortunately, pre-disease levels are not available in most patients.

Dr. Medici's research focuses on the genetic basis of the HPT axis. To perform large-scale genetic studies, he initiated an international consortium, which now includes 34 centers with available (epi)genetic and thyroid function data for >80,000 participants. The consortium has identified many new genetic determinants of TSH levels. For this grant project, he will use these markers to:

Create a TSH-setpoint prediction model in thyroid-disease-free populations.
Reclassify thyroid function using the prediction model and test the effect on cardiovascular disease and mortality.
Test the model in thyroid-disease patients.

Dr. Medici completed his PhD (cum laude) in 2014 and did a postdoctoral research fellowship at the Harvard Institutes of Medicine and Brigham and Women's Hospital in Boston, MA.

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Find out more about ATA at www.thyroid.org.

The post American Thyroid Association Awards Research Grant to Marco Medici, MD, PhD, MSc, Erasmus Medical Center appeared first on American Thyroid Association.

http://ift.tt/2vHsYgk

Expression of Kallikrein-Related Peptidase 6 in Primary Mucosal Malignant Melanoma of the Head and Neck

Abstract

http://ift.tt/2vFS9Q1

The Great Mimicker: Metastatic Breast Carcinoma to the Head and Neck with Emphasis on Unusual Clinical and Pathologic Features

Abstract

http://ift.tt/2vns6ug

Head and Neck Rhabdomyosarcoma: Clinical and Pathologic Characterization of Seven Cases

Abstract

http://ift.tt/2vFrzGU

Genotypical Phenotypic Features of BAP1 Cancer Syndrome

This study of 10 patients identified through clinical screening and 205 patients identified through literature review describes 8 new families with germline mutations in BAP1 and provides a comprehensive review of reported cases.

http://ift.tt/2vFsaIv

Corymbiform Lesions in a Young Healthy Man

A young man had asymptomatic cutaneous lesions for 4 months; examination revealed annular red plaques with scale and superficial erosions over the trunk and extremities, and plaques on the arms had a corymbiform pattern with a central and multiple satellite lesions. What is your diagnosis?

http://ift.tt/2vn1vO1

Purpura Annularis Telangiectodes of Majocchi Associated With Apremilast

This case report describes a patient with purpura annularis telangiectodes of Majocchi associated with the initiation and rechallenge of apremilast for psoriasis vulgaris

http://ift.tt/2vEVIGe

Errors in Reported Data

In the Original Investigation titled "Safety and Efficacy of Anakinra in Severe Hidradenitis Suppurativa: A Randomized Clinical Trial," published online on November 18, 2015, and in the January 2016 issue of JAMA Dermatology, some data were reported in error. The originally reported decreased disease activity in 6 (67%) of 9 patients allocated to treatment with anakinra (P = .04) was incorrect. The correct number is 7 (78%) of 9. Thus, in the Abstract and Results section of the main text, as detailed in our accompanying letter, the correct statement should read "The disease activity score was decreased at the end of treatment (week 12) in 20% (2 of 10) of the placebo arm compared with 78% (7 of 9) of the anakinra arm (P = .02)." These 7 patients are those who had also met the Hidradenitis Suppurativa Clinical Response (HiSCR) score efficacy treatment end point reported in Figure 2 of the original article. Based on this clarification, it is now evident that the Fisher 2-sided test provides a P value of significance. Also, it should be noted that HiSCR was assessed retrospectively, and it was not included in the original protocol design because it had not yet been introduced when the study was designed. The statistical analysis for the HiSCR score was performed by the χ² test. This article has been corrected online.

http://ift.tt/2vmGIu5

Significance of Efficacy Results in a Randomized Clinical Trial

To the Editor Dr Tzanetakou and colleagues reported on the results of a placebo-controlled clinical trial of anakinra in hidradenitis suppurativa. The primary efficacy end point was based on decreased disease activity scores from baseline to the end of treatment, and the 2 study arms were also compared regarding the Hidradenitis Suppurativa Clinical Response (HiSCR). The Fisher exact test was performed for both the primary analysis and the HiSCR analysis, as stated in the "Statistical Analysis" section. For the primary analysis, the disease activity score was decreased in 20% (2 of 10) of the placebo arm compared with 67% (6 of 9) of the anakinra arm. For the HiSCR analysis, response was achieved in 30% (3 of 10) of the placebo arm and 78% (7 of 9) of the anakinra arm. A P value of .04 was reported for both the primary analysis and the HiSCR analysis. However, our calculations show that the P value for both analyses should be .07. A χ² test would have resulted in a P value of P = .04 for both analyses. However, a χ² test is known to inflate the type I error rate when the sample size is small and is therefore not appropriate for these analyses (see eg, McDonald, pages 88-89).

http://ift.tt/2vFOWQF

Topical Sinecatechins, 10%, for Superficial Basal Cell Carcinoma

This randomized clinical trial compares topical sinecatechins ointment, 10%, vs placebo in the treatment of superficial basal cell carcinoma.

http://ift.tt/2vnrHbw

TrkA Expression on Merkel Cell Carcinoma Tumor Cells

This case series study determines whether tumor cells express tropomyosin receptor kinase A in patients with Merkel cell carcinoma.

http://ift.tt/2vFId95

Significance of Efficacy Results in a Randomized Clinical Trial—Reply

In Reply On behalf of my coauthors, I am writing to reply to a reader's query regarding the statistics of the primary efficacy end point in our article, "Safety and Efficacy of Anakinra in Severe Hidradenitis Suppurativa: A Randomized Clinical Trial," published online on November 18, 2015, and in the January 2016 issue of JAMA Dermatology. We are grateful to Dr Su for his inquiry.

http://ift.tt/2vn1ucV

The Skin of Our Teeth

Sometimes life brings us great misfortune, yet somehow we escape the calamity, as the popular saying goes, by "the skin of our teeth." This proverbial expression is one of the oldest related to dermatology, dating back to Biblical times and to the Book of Job. The exact quote reads: "My bones cling to my skin and flesh; I have escaped with the skin of my teeth" (Job 19:20). In this verse, the "skin of my teeth" means Job's gums, which were spared from a dermatitis that engulfed Job from "the soles of his feet to the top of his head" (Job 2:7). This skin affliction was 1 of a series of calamities that suddenly befell Job, testing his piety.

http://ift.tt/2vFsarZ

Mohs Micrographic Surgery Use in the United States—Reply

In Reply We appreciate the interest by Dr Kantor in our article describing payments to dermatologists using the 2013 Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File. In our study we noted that the use of Mohs micrographic surgery (MMS) was more frequent than excision or destruction of malignant growths. We did not explicitly suggest that these numbers were inconsistent with Mohs appropriate use criteria (AUC) but merely invited the readers to make their own assessment. We unambiguously stated that definitive interpretation regarding the propriety of these services could not be determined without accompanying clinical information. Notwithstanding, we welcome a discussion about the propriety of MMS utilization.

http://ift.tt/2qTmmsu

Illustrated Analogy to Explain the Mohs Micrographic Surgery Procedure

This Viewpoint examines an analogical tool for educating patients undergoing Mohs micrographic surgery.

http://ift.tt/2px47V9

Association of Sterile Prep Solutions With Postoperative Infection Risk

This study assesses the association between the type of preoperative sterile prep solution used and infection risk after cutaneous surgery of the head and neck in a large cohort of patients.

http://ift.tt/2qcoJHi

Generic Drugs—Changes in Cost and Challenges in Practice

http://ift.tt/2pIqIBP

Misspelling of Coauthor Surname

In the article titled "Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Standard Reporting and Evaluation Guidelines: Results of a National Institutes of Health Working Group," published online March 15, 2017, Dr Tassaneeyakul's surname was misspelled in the byline. This article has been corrected online. This article was also corrected in April 2017 for typographical errors and missing table footnote.

http://ift.tt/2t1EtLi

Medicare Part D Payments for Topical Steroids

This cost analysis assesses Medicare and patient out-of-pocket costs for topical steroids and models potential savings that could result from substitution of the least expensive topical steroid from the corresponding potency class.

http://ift.tt/2p63Qby

August 2017 Issue Highlights

http://ift.tt/2vnb7IC

Sex- and Age-Specific US Prevalence Estimates for Hidradenitis Suppurativa

This population-based analysis establishes standardized overall and sex- and age-specific prevalence estimates for hidradenitis suppurativa in the United States.

http://ift.tt/2qT7gmF

Reaction in Benign Melanocytic Nevi Without Halo During Nivolumab Therapy

This case report describes induction of immune reaction to benign melanocytic nevi without halo during nivolumab therapy in a patient with melanoma.

http://ift.tt/2qTo25v

Contact Allergy in Children With Atopic Dermatitis

This study uses data from the Pediatric Contact Dermatitis Registry to examine the associations and sensitizations among patients with concomitant atopic dermatitis and allergic contact dermatitis.

http://ift.tt/2l8YJWH

Histiocytoid Sweet Syndrome and Myelodysplastic Syndrome—Reply

In Reply We appreciate the interest of Vignon-Pennamen et al in our study on histiocytoid Sweet syndrome (HSS). Like us, they consider the cells of the infiltrate as immature myeloid cells rather than M2 macrophages, and for them, too, this histopathologic variant of Sweet syndrome should not be considered a form of leukemia cutis; these were the 2 main goals of our study.

http://ift.tt/2t2dIGt

EMS1's 10 year anniversary: Watch the top 10 most viewed videos

By EMS1 Staff Ten years ago, on July 1, 2007, EMS1.com was founded. In celebration of the milestone, we rounded up the 10 most viewed videos. Below, you'll find that our readers enjoyed lighthearted parodies as well as more educational-based videos to fine tune their skills. Did we miss one of your favorites" Let us know in the comment section below. 1. Watch: Responders make music video to 'Uptown ...

http://ift.tt/2vOi1ZL

New dietary evidence on medieval rural communities of the Basque Country (Spain) and its surroundings from carbon and nitrogen stable isotope analyses: social insights, diachronic changes and geographic comparison

Abstract

This paper presents the results of palaeodietary reconstruction based on stable carbon and nitrogen isotope analysis on bone collagen of five medieval rural populations from the Basque Country (northern Spain) spanning from 5^th to 15^th centuries AD. One hundred forty-seven human and 47 domestic faunal samples were successfully analysed with the objective of defining agrarian productive strategies and food consumption patterns. The results grouped the five sites in two clusters: on one side Zaballa and Treviño, whose inhabitants followed diets exclusively based on C₃ plants with significant intake of animal protein, and on the other the populations from Aistra and Zornoztegi, who combined C₃ and C₄ plants and consumed lower amounts of animal protein. The isotopic values from Dulantzi were intermediate to these two groups. No differences were detected when individual status markers, such as grave goods, were available. Conversely, some restrictions on the access to certain food resources based on sex were uncovered. A relevant change in δ¹³C values was identified around 10^th century, consequence of a shift in the consumption patterns of C₃ and C₄ plants. Finally, these Basque sites were compared with the medieval Iberian case studies available in the literature. This comparison made evident the distinctive nature of the diet of the Basque medieval rural contexts.

http://ift.tt/2wHJWI5

Prevalence of Rhinitis in Athletes: Systematic Review

Background. Prevalence of rhinitis in athletes has frequently been studied and varies widely from 27% to 74%. The aim of this systematic review was to examine the prevalence of rhinitis in athletes, to specifically compare the evidence of rhinitis in land-based and aquatic athletes. Methods. Systematic search of MEDLINE, EMBASE, and the non-MEDLINE subset of PubMed was performed from inception to March 8, 2016, to identify studies on rhinitis in athletes. Results. Of the 373 identified unique articles, a total of 13 studies satisfied the criteria for this review. The final group contained 9 cohort and 4 case-control studies. We found 10 studies that reported the prevalence of allergic rhinitis (21%–56.5%). In contrast, nonallergic rhinitis was identified by only 1 author (6%). We have also evaluated the prevalence of rhinitis in the separate subgroups (land, water, and cold air) where swimmers seem to be the most affected (40%–74%), followed by cross-country skiers (46%) and track and field athletes (21 to 49%). Conclusion. We did not reveal any convincing trend of a higher prevalence in land-based athletes compared to general population. By contrast, aquatic and cold air athletes demonstrate increased prevalence reflecting the irritant effects of their environment on the nasal mucosa.

http://ift.tt/2wHZADh

PET in Guiding Cervical Lymphadenectomy

Condition: Esophageal Cancer
Intervention: Diagnostic Test: positron emission tomography
Sponsor: Fudan University
Not yet recruiting - verified August 2017

http://ift.tt/2vOSYq4

trūFreeze® Esophageal Cancer

Condition: Esophageal Cancer
Intervention: Device: trūFreeze® System spray cryotherapy
Sponsor: CSA Medical, Inc.
Not yet recruiting - verified August 2017

http://ift.tt/2wHDeln

Transcranial Electrical Stimulation for mTBI

Conditions: Mild Traumatic Brain Injury (mTBI); Post-traumatic Stress Disorder
Intervention: Device: IASIS Micro Current Neurofeedback
Sponsors: VA Office of Research and Development; San Diego Veterans Healthcare System
Not yet recruiting - verified August 2017

http://ift.tt/2vONvjf

Instructions for Authors

Publication date: August 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 2

http://ift.tt/2uGdJzh

Information for Readers

Publication date: August 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 2

http://ift.tt/2uon0AO

Author's response

Publication date: August 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 2
Author(s): Joseph C. Turbyville, Andrew W. Winslow, J. Wesley Sublett, James L. Sublett, Stephen J. Pollard

http://ift.tt/2uG8YWm

Publication date: August 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 2

http://ift.tt/2uoGENd

Editorial Board

Publication date: August 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 2

http://ift.tt/2vNzUYL

Characteristics of severe asthma with fungal sensitization

Publication date: Available online 8 August 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Katsunori Masaki, Koichi Fukunaga, Masako Matsusaka, Hiroki Kabata, Takae Tanosaki, Takao Mochimaru, Takashi Kamatani, Kengo Ohtsuka, Rie Baba, Soichiro Ueda, Yusuke Suzuki, Fumio Sakamaki, Yoshitaka Oyamada, Takashi Inoue, Tsuyoshi Oguma, Koichi Sayama, Hidefumi Koh, Morio Nakamura, Akira Umeda, Katsuhiko Kamei, Kenji Izuhara, Koichiro Asano, Tomoko Betsuyaku
BackgroundSome patients with severe asthma also have fungal sensitization and are considered to have severe asthma with fungal sensitization. However, there is limited information on the clinical features of SAFS.ObjectiveTo investigate the clinical characteristics of severe asthma with fungal sensitization.MethodsThe present study enrolled 124 patients with severe asthma. We evaluated clinical aspects, such as various serum cytokines, fractional exhaled nitric oxide, pulmonary function, and serum immunoglobulin E (IgE). Fungal sensitization was assessed by determining serum levels of IgE specific to fungal allergens (Aspergillus, Alternaria, Candida, Cladosporium, Penicillium, and Trichophyton species and Schizophyllum commune). The protocol was registered at a clinical trial registry (http://ift.tt/1QNm0c9; UMIN 000002980).ResultsThirty-six patients (29%) showed sensitization to at least 1 fungal allergen. The most common species were Candida (16%), Aspergillus (11%), and Trichophyton (11%). The rate of early-onset asthma (<16 years of age) was higher in patients with fungal sensitization than in those without fungal sensitization (45% vs 25%; P = .02). Interleukin-33 levels were higher in patients with fungal sensitization than in those without fungal sensitization. Of patients with atopic asthma, Asthma Control Test scores were worse in patients with multiple fungal sensitizations than in patients with a single fungal sensitization or those without fungal sensitization.ConclusionSevere asthma with fungal sensitization is characterized by early onset of disease and high serum levels of interleukin-33. Multiple fungal sensitizations are associated with poor asthma control.Trial RegistrationUMIN Clinical Trials Registry (UMIN-CTR; http://ift.tt/1QNm0c9): UMIN 000002980.

http://ift.tt/2uoBD3f

Understanding the biology of disease in underserved children with asthma

Publication date: August 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 2
Author(s): Bridgette L. Jones

http://ift.tt/2uoZi3n

Food allergen extracts to diagnose food-induced allergic diseases

1-s2.0-S1081120616X00117-cov150h.gif

Publication date: August 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 2
Author(s): Natalie A. David, Anusha Penumarti, A. Wesley Burks, Jay E. Slater
ObjectiveTo review the manufacturing procedures of food allergen extracts and applicable regulatory requirements from government agencies, potential approaches to standardization, and clinical application of these products. The effects of thermal processing on allergenicity of common food allergens are also considered.Data SourcesA broad literature review was conducted on the natural history of food allergy, the manufacture of allergen extracts, and the allergenicity of heated food. Regulations, guidance documents, and pharmacopoeias related to food allergen extracts from the United States and Europe were also reviewed.Study SelectionsAuthoritative and peer-reviewed research articles relevant to the topic were chosen for review. Selected regulations and guidance documents are current and relevant to food allergen extracts.ResultsPreparation of a food allergen extract may require careful selection and identification of source materials, grinding, defatting, extraction, clarification, sterilization, and product testing. Although extractions for all products licensed in the United States are performed using raw source materials, many foods are not consumed in their raw form. Heating foods may change their allergenicity, and doing so before extraction may change their allergenicity and the composition of the final product.ConclusionThe manufacture of food allergen extracts requires many considerations to achieve the maximal quality of the final product. Allergen extracts for a select number of foods may be inconsistent between manufacturers or unreliable in a clinical setting, indicating a potential area for future improvement.

http://ift.tt/2vNDBxj

Adult-onset food allergies

Publication date: August 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 2
Author(s): Manish Ramesh, Jay A. Lieberman

http://ift.tt/2upe9KY

Immunotherapy and systemic reactions

Publication date: August 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 2
Author(s): Mike S. Tankersley, Linda S. Cox

http://ift.tt/2vNwB3R

Uptake of EpiPen and Allerject (Auvi-Q) epinephrine auto-injectors in Manitoba children

Publication date: August 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 2
Author(s): Herman Tam, F. Estelle R. Simons, Elinor Simons

http://ift.tt/2uoZgsh

Drug–device interaction for systemic effects of fluticasone in patients with asthma

Publication date: August 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 2
Author(s): Brian J. Lipworth, Sunny Jabbal

http://ift.tt/2vNqyfy

Author's response

Publication date: August 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 2
Author(s): Stanley J. Szefler

http://ift.tt/2uoZfVf

Kinase inhibitors in clinical practice: An expanding world

Publication date: Available online 8 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Ruchi Pandey, Reuben Kapur

http://ift.tt/2vlWXr5

Prenatal fine particulate exposure and early childhood asthma: effect of maternal stress and fetal gender

Publication date: Available online 8 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Alison Lee, Hsiao-Hsien Leon Hsu, Yueh-Hsiu Mathilda Chiu, Sonali Bose, Maria José Rosa, Itai Kloog, Ander Wilson, Joel Schwartz, Sheldon Cohen, Brent A. Coull, Robert O. Wright, Rosalind J. Wright
BackgroundThe impact of prenatal ambient air pollution on child asthma may be modified by maternal stress, child sex and exposure dose and timing.ObjectiveWe prospectively examined associations between co-exposure to prenatal particulate matter with an aerodynamic diameter of less than 2.5 microns (PM2.5) and maternal stress on childhood asthma (n=736).MethodsDaily PM2.5 exposure during pregnancy was estimated using a validated satellite-based spatio-temporally resolved prediction model. Prenatal maternal negative life events (NLEs) were dichotomized around the median (high: NLE≥3; low: NLE<3). We employed Bayesian distributed lag interaction models (BDLIMs) to identify sensitive windows for prenatal PM2.5 exposure on children's asthma by age 6, and determine effect modification by maternal stress and child sex.ResultsBDLIMs identified a critical window of exposure (19-23 weeks gestation, cumulative OR=1.15, 95%CI=1.03-1.26; per IQR (1.7 μg/m³) increase in prenatal PM2.5 level) during which children concomitantly exposed to prenatal PM2.5 and maternal stress had increased risk of asthma. No significant association was seen in children born to women reporting low prenatal stress. When examining modifying effects of prenatal stress and fetal sex, we found that boys born to mothers with higher prenatal stress were most vulnerable (19-21 weeks gestation, cumulative OR=1.28, 95%CI=1.15-1.41; per IQR increase in PM2.5).ConclusionPrenatal PM2.5 exposure during sensitive windows is associated with increased risk of child asthma, especially in boys concurrently exposed to elevated maternal stress.

Teaser

These analyses demonstrate that concomitant exposure to prenatal PM2.5 and maternal stress is associated with increased risk of asthma, especially in boys.

http://ift.tt/2vEyIav

Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures

Publication date: Available online 8 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Manel Essaidi-Laziosi, Francisco Brito, Sacha Benaoudia, Léna Royston, Valeria Cagno, Mélanie Fernandes-Rocha, Isabelle Piuz, Evgeny Zdobnov, Song Huang, Samuel Constant, Marc-Olivier Boldi, Laurent Kaiser, Caroline Tapparel
BackgroundLeading etiologies of acute illnesses, respiratory viruses typically cause self-limited diseases, though severe complications can occur in fragile patients. Rhinoviruses, respiratory enteroviruses, influenza virus, respiratory syncytial viruses and coronaviruses are highly prevalent respiratory pathogens, but due to the lack of reliable animal models, their differential pathogenesis remains poorly characterized.ObjectiveTo compare infections by respiratory viruses isolated from clinical specimens using reconstituted human airway epithelia.MethodsTissues were infected with rhinoviruses RV-A55, RV-A49, RV-B48, RV-C8 and RV-C15, respiratory enterovirus EV-D68, influenza virus H3N2, respiratory syncytial virus RSV-B and coronavirus HCoV-OC43. Replication kinetics, cell tropism, impact on tissue integrity and cytokine secretion were compared. Virus adaptation and tissue response were assessed through RNA-sequencing.ResultsRhinoviruses, RSV-B and HCoV-OC43 infected ciliated cells and caused no major cell death while H3N2 and EV-D68 induced ciliated cell loss and tissue integrity disruption. H3N2 was also detected in rare goblet and basal cells. All viruses except RV-B48 and HCoV-OC43 altered cilia beating and MCC. H3N2 was the strongest cytokine-inducer and HCoV-OC43 the weakest. Persistent infection was observed in all cases. RNA-sequencing highlighted perturbation of tissue metabolism and induction of a transient but important immune response at 4-days post-infection. No majority mutations emerged in the viral population.ConclusionOur results highlight the differential in vitro pathogenesis of respiratory viruses during the acute infection-phase and their ability to persist under immune tolerance. These data help to appreciate the range of disease severity observed in vivo and the occurrence of chronic respiratory infections in immunocompromised hosts.

Teaser

Using reconstituted airway epithelia, we highlight marked differences in in vitro pathogenesis of respiratory viruses. In the absence of immune cells, we observe viral persistence linked to a contained tissue-response rather than to viral mutations.

http://ift.tt/2vm0Qwa

Acute traumatic coagulopathy: pathophysiology and resuscitation

British Journal of Anaesthesia, 2016; 117(S3): iii31–iii43, DOI 10.1093/bja/aew328

http://ift.tt/2up4tR1

NPS 2143, a selective calcium-sensing receptor antagonist inhibits lipopolysaccharide-induced pulmonary inflammation

Publication date: October 2017
Source:Molecular Immunology, Volume 90
Author(s): Jae-Won Lee, Hyun Ah Park, Ok-Kyoung Kwon, Ji-Won Park, Gilhye Lee, Hee Jae Lee, Seung Jin Lee, Sei-Ryang Oh, Kyung-Seop Ahn
NPS 2143, a novel and selective antagonist of calcium-sensing receptor (CaSR) has been reported to possess anti-inflammatory activity. In the present study, we examined the protective effect of NPS 2143 on lipopolysaccharide (LPS)-induced acute lung injury (ALI). NPS 2143 pretreatment significantly inhibited the influx of inflammatory cells and the expression of monocyte chemoattractant protein-1 (MCP-1) in the lung of mice with LPS-induced ALI. NPS 2143 decreased the levels of neutrophil elastase (NE) and protein concentration in the bronchoalveolar lavage fluid (BALF). NPS 2143 also reduced the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the BALF and serum. In addition, NPS 2143 attenuated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and increased the activation of AMP-activated protein kinase (AMPK) in the lung. NPS 2143 also downregulated the activation of nuclear factor-kappa B (NF-κB) in the lung. In LPS-stimulated H292 airway epithelial cells, NPS 2143 attenuated the releases of IL-6 and MCP-1. Furthermore, NPS 2143 upregulated the activation of AMPK and downregulated the activation of NF-κB. These results suggest that NPS 2143 could be potential agent for the treatment of inflammatory diseases including ALI.

Graphical abstract

http://ift.tt/2wtciXi

Biological, immunological and functional properties of two novel multi-variant chimeric recombinant proteins of CSP antigens for vaccine development against Plasmodium vivax infection

Publication date: October 2017
Source:Molecular Immunology, Volume 90
Author(s): Samaneh H. Shabani, Sedigheh Zakeri, Ali H. Salmanian, Jafar Amani, Akram A. Mehrizi, Georges Snounou, François Nosten, Chiara Andolina, Yousef Mourtazavi, Navid D. Djadid
The circumsporozoite protein (CSP) of the malaria parasite Plasmodium vivax is a major pre-erythrocyte vaccine candidate. The protein has a central repeat region that belongs to one of repeat families (VK210, VK247, and the P. vivax-like). In the present study, computer modelling was employed to select chimeric proteins, comprising the conserved regions and different arrangements of the repeat elements (VK210 and VK247), whose structure is similar to that of the native counterparts. DNA encoding the selected chimeras (named CS127 and CS712) were synthetically constructed based on E. coli codons, then cloned and expressed. Mouse monoclonal antibodies (mAbs; anti-Pv-210-CDC and −Pv-247-CDC), recognized the chimeric antigens in ELISA, indicating correct conformation and accessibility of the B-cell epitopes. ELISA using IgG from plasma samples collected from 221 Iranian patients with acute P. vivax showed that only 49.32% of the samples reacted to both CS127 and CS712 proteins. The dominant subclass for the two chimeras was IgG1 (48% of the positive responders, OD492=0.777±0.420 for CS127; 48.41% of the positive responders, OD492=0.862±0.423 for CS712, with no statistically significant difference P>0.05; Wilcoxon signed ranks test). Binding assays showed that both chimeric proteins bound to immobilized heparan sulphate and HepG2 hepatocyte cells in a concentration-dependent manner, saturable at 80μg/mL. Additionally, anti-CS127 and −CS712 antibodies raised in mice recognized the native protein on the surface of P. vivax sporozoite with high intensity, confirming the presence of common epitopes between the recombinant forms and the native proteins. In summary, despite structural differences at the molecular level, the expression levels of both chimeras were satisfactory, and their conformational structure retained biological function, thus supporting their potential for use in the development of vivax-based vaccine.

http://ift.tt/2wtJMob

Derp1-modified dendritic cells attenuate allergic inflammation by regulating the development of T helper type1(Th1)/Th2 cells and regulatory T cells in a murine model of allergic rhinitis

Publication date: October 2017
Source:Molecular Immunology, Volume 90
Author(s): Shaoqing Yu, Bing Han, Shuangxi Liu, Hong Wang, Wenjie Zhuang, Yu Huang, Ruxin Zhang
The CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs) are known to regulate Th2-induced allergic rhinitis (AR). In this study, we evaluated the efficacy of Derp1-modified dendritic cells (DCs) in AR immunotherapy. Derp1 was synthesized and transfected into DCs to generate Derp1-modified DCs. Phenotypes of Derp1-modified DCs were analyzed with flow cytometry using antibodies against DC markers CD11c, CD11b, CD59, CD103 and Toll-like receptor 1(TLR1). Four groups of subject mice were formed; the controls were treated with immature DCs, while the AR mice models were sensitized with Derp1(AR) and treated with DCs(DC-AR) or Derp1-modified DCs (Derp1DC-AR). The frequency of sneezing and scratching, eosinophil cell count, and Th1/Th2 ratio in the spleen were measured for all groups. The percentage of CD4⁺CD25⁺Foxp3⁺ Tregs in peripheral blood mononuclear cells was measured using flow cytometry; serum IgE, IgG1, and histamine were measured using enzyme-linked immunosorbent assay; expression levels of transcription factors T-bet, GATA3, Foxp3+ and IL-10 were analyzed using reverse transcription-polymerase chain reaction, and Western blot used in analyzed expression of Foxp3+ and IL-10 in nasal mucosa. Treatment with Derp1-modified DCs ameliorated the allergic response. The Derp1DC-AR group had significantly lower eosinophil cell count and the IgE, IgG1, and histamine levels than the AR and DC-AR groups, and higher mRNA levels of Th1 transcription factors T-bet, IL-10 and Foxp3 in nasal mucosa than DC-AR mice, but Th2 transcription factors GATA3 mRNA expression level has the opposite results. Furthermore, the Th1/Th2 ratio and percentage of CD4⁺CD25⁺Foxp3⁺ Tregs was significantly lower in the AR group (p<0.05), but higher in the Derp1DC-AR group than in the control group (p<0.01). Thus, the Derp1-modified DCs increased the percentage of CD4⁺CD25⁺Foxp3⁺Tregs and influenced the balance of Th1/Th2, showing an immunotherapeutic effect against AR.

http://ift.tt/2viG42o

Investigations on the molecular mode of action of the novel immunostimulator ZelNate: Activation of the cGAS-STING pathway in mammalian cells

Publication date: October 2017
Source:Molecular Immunology, Volume 90
Author(s): Thomas Ilg
Bovine respiratory disease (BRD) is usually prevented or treated with vaccines and/or antibiotics. The use of antibiotics is, however, of concern due to the potential promotion of microbial resistance and the occurrence of residues. Recently an alternative aid in the treatment of BRD, the cationic lipid/bacterial plasmid DNA liposome-based immunomodulator ZelNate, has entered the veterinary market. In the present study, we provide data on the molecular mode of action of ZelNate. Despite the presence of numerous non-methylated CpG motifs in its plasmid DNA, ZelNate proved to be inactive on human and mouse toll-like receptor 9 (TLR9) in cell culture, in both recombinant and natural cellular receptor settings. However, in the human monocyte cell line THP1 and in the mouse melanoma cell line B16, ZelNate activates strongly the stimulator of interferon genes (STING) pathway, which is known to lead predominantly to interferon response factor 3 (IRF3) activation. Further analysis in THP1 cells suggests that the ZelNate plasmid DNA activates STING via interaction with cyclic guanylate adenylate synthase (cGAS), but not via interferon induced gene 16 (IFI16). Our in vitro observations suggest that ZelNate may act predominantly via the cGAS/STING/IRF3 pathway.

http://ift.tt/2wt0pjS

Αρχειοθήκη ιστολογίου

Τετάρτη 9 Αυγούστου 2017

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