Head and Neck Diseases by Alexandros G.Sfakianakis: 08/16/18

Πέμπτη 16 Αυγούστου 2018

Abstracts

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Necrotizing fasciitis of the head and neck: our experience with vacuum-assisted closure therapy

Abstract

Objectives

To present the outcomes of our case series of head and neck necrotizing fasciitis (HNNF) in which vacuum-assisted closure (VAC) is used in most of the cases in the treatment.

Methods

Case series in a tertiary referral center.

Results

Eleven patients were treated for HNNF between January 2008 and January 2017. Patients were two females and nine males, the mean age was 57.1. Oral cavity and tracheotomy/tracheostomy sites were the main aetiological foci of the infection. Three patients were treated with aggressive debridements and conventional dressing, whereas eight patients were treated with incision and exploration followed by limited skin excisions and VAC dressing. The mean number of surgical debridements was 2.3. The mean length of hospital stay was 41.8 days. Complications were observed in all patients except one. The mortality rate of HNNF in our series was 18%. The cause of death was severe sepsis and multi-organ failure in one case and mediastinitis followed by respiratory distress syndrome in the other case.

Conclusion

HNNF is still a mortal disease and surgical debridements are crucial. The current study is the only case series in the literature in which VAC treatment was used in consecutive cases of HNNF. VAC treatment can play a major role in the post-operative care of HNNF patients. It reduces the amount of excised skin during debridements and stimulates wound healing. VAC treatment may be included in the treatment protocol of HNNF alongside surgical debridements and medical therapy.

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Comments on “Applications and limitations of using patient-specific 3D printed molds in autologous breast reconstruction” by S. Hummelink et al.

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Current practice in the surgical management of parathyroid disorders: a United Kingdom survey

Abstract

Purpose

Surgery for primary hyperparathyroidism is undertaken by many specialties but predominantly endocrine and ear, nose and throat (ENT) surgeons. There is currently no consensus on the peri-operative management of primary hyperparathyroidism. We sought to determine current surgical practice and identify any inter-specialty variation in the United Kingdom (UK).

Methods

An online survey was disseminated to members of the British Association of Endocrine & Thyroid Surgeons (BAETS) in the UK.

Results

78 surgeons responded (40 Endocrine, 37 ENT and 1 maxillofacial). 90% of surgeons used ultrasound and sestamibi for pre-operative localisation. Intraoperative frozen section (31%) and parathyroid hormone monitoring (41%) were the most common adjuncts used intraoperatively. 68% of surgeons did not use any wound drains. Nearly two-thirds of surgeons (64%) discharged patients from the clinic within 3 months, There were some significant differences (p < 0.05) in particular areas of practice between endocrine and ENT surgeons (%, p): use of single-photon emission computed tomography (SPECT) (Endocrine 25% vs. ENT 5%), preoperative laryngeal assessment (endocrine 58% vs. ENT 95%), intraoperative laryngeal nerve monitoring (endocrine 35% vs. ENT 68%), use of monopolar diathermy (endocrine 58% vs. ENT 22%), bipolar diathermy (endocrine 60% vs. 89%) and surgical ties (endocrine 48% vs. ENT 19%).

Conclusion

Our study demonstrates some similarities as well as some notable differences in practice between endocrine and ENT surgeons, and therefore, highlights the need for national consensus with respect to some key areas in parathyroid surgery.

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Perception of Pulmonary Function in Children with Asthma and Cystic Fibrosis

Pediatric Allergy, Immunology, and Pulmonology, Ahead of Print.

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Flexible Bronchoscopy Under Bronchoscopist-Administered Moderate Sedation Versus General Anesthesia: A Comparative Study in Children

Pediatric Allergy, Immunology, and Pulmonology, Ahead of Print.

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Perception of Pulmonary Function in Children with Asthma and Cystic Fibrosis

Pediatric Allergy, Immunology, and Pulmonology, Ahead of Print.

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Flexible Bronchoscopy Under Bronchoscopist-Administered Moderate Sedation Versus General Anesthesia: A Comparative Study in Children

Pediatric Allergy, Immunology, and Pulmonology, Ahead of Print.

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Development of a UHPLC-FLD method for the analysis of ergot alkaloids and application to different types of cereals from Luxembourg

Abstract

Ergot alkaloids are toxins produced by some species of fungi in the genus Claviceps, that may infect rye and triticale and, in a minor degree, other types of cereals. In this study, a new UHPLC-FLD method for the quantification of the six major ergot alkaloids as well as their corresponding epimers was developed. The sample preparation was done by a solid-liquid extraction with acetonitrile and clean-up via freeze-out. The method was fully validated and then applied to 39 samples (wheat, rye, triticale, and barley) harvested in Luxembourg in 2016. Samples were sieved (1.9 × 20 mm) prior to analysis in order to remove sclerotia, hosting the alkaloids. However, 23 samples still contained at least one ergot alkaloid > LOQ and concentrations of the sum of the 6 ergot alkaloids ranged from 0.3 to 2530.1 μg/kg. Interestingly, the highest concentrations were measured in wheat and not in rye or triticale, suggesting that all kinds of cereals should be included in monitoring programs. The outcome of this study allowed giving a first overview of ergot alkaloid concentrations in cereals harvested in Luxembourg, and the measured concentrations were in similar ranges than in other parts of the world (e.g., Canada, France, Germany).

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FDA Approval Summary: Midostaurin for the Treatment of Advanced Systemic Mastocytosis

AbstractIn April 2017, the U.S. Food and Drug Administration granted regular approval to midostaurin for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM‐AHN), or mast cell leukemia (MCL). Approval was based on results from CPKC412D2201, a single‐arm trial of midostaurin (100 mg orally twice daily) in previously treated or untreated patients. For the patients with ASM and SM‐AHN, efficacy was established on the basis of confirmed complete remission (CR) plus incomplete remission (ICR) by modified Valent criteria with six cycles of midostaurin. There were no CRs reported; ICR was achieved by 6 of 16 patients (38%; 95% confidence interval [CI]: 15%–65%) with ASM and by 9 of 57 patients (16%; 95% CI: 7%–28%) with SM‐AHN. Within the follow‐up period, the median duration of response was not reached for the patients with ASM (range, 12.1+ to 36.8+ months) or with SM‐AHN (range, 6.6+ to 52.1+ months). For the patients with MCL, efficacy was established on the basis of confirmed CR using modified 2013 International Working Group‐Myeloproliferative Neoplasms Research and Treatment‐European Competence Network on Mastocytosis criteria. Of 21 patients with MCL, 1 (5%) achieved a CR. Of 142 patients with SM evaluated for safety, 56% had dose modifications for toxicity, and 21% discontinued treatment due to a toxicity. Over 50% reported nausea, vomiting, or diarrhea, and ≥30% reported edema, musculoskeletal pain, fatigue, abdominal pain, or upper respiratory tract infection. New or worsening grade ≥3 lymphopenia, anemia, thrombocytopenia, or neutropenia developed in ≥20%. Although midostaurin is an active drug for treatment of advanced SM, it is not clear that the optimal dose has been identified.Implications for Practice.Midostaurin is the only U.S. Food and Drug Administration‐approved therapy for patients with systemic mastocytosis with associated hematological neoplasm and mast cell leukemia and is the only therapy approved for patients with aggressive systemic mastocytosis regardless of KIT D816V mutation status. Based on response rate and duration, midostaurin has meaningful clinical activity in these rare, life‐threatening diseases.

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Randomized, Open‐Label Phase II Study Comparing Capecitabine‐Cisplatin Every 3 Weeks with S‐1‐Cisplatin Every 5 Weeks in Chemotherapy‐Naïve Patients with HER2‐Negative Advanced Gastric Cancer: OGSG1105, HERBIS‐4A Trial

AbstractLessons Learned. Evidence has suggested that capecitabine‐cisplatin is similar or possibly superior to S‐1‐cisplatin in terms of safety and efficacy for Japanese patients with advanced gastric cancer (AGC).As far as we are aware, our study is the first randomized trial of two regimens consisting of an oral fluoropyrimidine plus cisplatin in human epidermal growth receptor 2‐negative AGC patients with measurable lesions.Background.We performed a phase II study to evaluate the safety and efficacy of capecitabine plus cisplatin in comparison with S‐1 plus cisplatin for first‐line treatment of human epidermal growth receptor 2 (HER2)‐negative advanced gastric cancer in Japan.Methods.Eligible patients were randomly assigned to receive either capecitabine at 1,000 mg/m2 twice daily for 14 days plus cisplatin at 80 mg/m2 on day 1 every 3 weeks (n = 43) or S‐1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/m2 on day 8 every 5 weeks (n = 41). The primary endpoint of the study was response rate.Results.Response rate did not differ significantly between the capecitabine‐cisplatin and S‐1‐cisplatin groups (53.5% vs. 51.2%, respectively, p > .999). S‐1‐cisplatin tended to confer a better progression‐free survival (PFS; median of 5.9 vs. 4.1 months, p = .284), overall survival (OS; median of 13.5 vs. 10.0 months, p = .290), and time to treatment failure (TTF; median of 4.5 vs. 3.1 months, p = .052) compared with capecitabine‐cisplatin. Common hematologic toxicities of grade 3 or 4 included anemia and neutropenia in both groups. However, anorexia, fatigue, and hyponatremia of grade 3 or 4 occurred more frequently in the capecitabine‐cisplatin group.Conclusion.Capecitabine‐cisplatin failed to demonstrate superior efficacy compared with S‐1‐cisplatin. The higher incidence of severe adverse events with capecitabine‐cisplatin suggests that S‐1‐cisplatin should remain the standard first‐line chemotherapy for HER2‐negative advanced gastric cancer in Japan.

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A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab‐Paclitaxel and Gemcitabine in Advanced Solid Tumors

AbstractLessons Learned. Itacitinib in combination with nab‐paclitaxel plus gemcitabine demonstrated an acceptable safety profile with clinical activity in patients with advanced solid tumors including pancreatic cancer.The results support future studies of itacitinib as a component of combination regimens with other immunologic and targeted small molecule anticancer agents.Background.Cytokine‐mediated signaling via JAK/STAT is central to tumor growth, survival, and systemic inflammation, which is associated with cancer cachexia, particularly in pancreatic cancer. Because of their centrality in the pathogenesis of cancer cachexia and progression, JAK isozymes have emerged as promising therapeutic targets. Preclinical studies have demonstrated antiproliferative effects of JAK/STAT pathway inhibition in both in vitro and in vivo models of cancer, including pancreatic cancer.Methods.This phase Ib/II dose‐optimization study assessed itacitinib, a selective JAK1 inhibitor, combined with nab‐paclitaxel plus gemcitabine in adults with treatment‐naïve advanced/metastatic disease (Part 1) or pancreatic adenocarcinoma (Parts 2/2A; NCT01858883). Starting doses (Part 1) were itacitinib 400 mg, nab‐paclitaxel 125 mg/m2, and gemcitabine 1,000 mg/m2. Additional dose levels incorporated were granulocyte colony‐stimulating factor, de‐escalations of itacitinib to 300 mg once daily (QD), nab‐paclitaxel to 100 mg/m2, and gemcitabine to 750 mg/m2.Results.Among 55 patients in Part 1, 6 developed seven hematologic dose‐limiting toxicities (Cycle 1). Itacitinib 300 mg plus nab‐paclitaxel 125 mg/m2 and gemcitabine 1,000 mg/m2 was tolerated and expanded in Part 2. Treatment discontinuation and grade 3/4 neutropenia rates prompted itacitinib de‐escalation to 200 mg QD in Part 2A. The most common grade 3/4 toxicities were fatigue and neutropenia. Partial responses occurred across all itacitinib doses and several tumor types (overall response rate, 24%).Conclusion.Itacitinib plus chemotherapy demonstrated acceptable safety and clinical activity in patients with advanced solid tumors including pancreatic cancers. This study was terminated early (sponsor's decision) based on negative phase III results for a JAK1/2 inhibitor in previously treated advanced pancreatic cancer.

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Rectal perforation following paclitaxel and carboplatin chemotherapy for advanced ovarian cancer: a case report and review of the literature

Paclitaxel is a chemotherapy drug commonly used in the management of ovarian cancer. Colonic perforation is an extremely rare complication of paclitaxel administration with few case reports in the medical lite...

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A quadricuspid aortic valve in an asymptomatic 40-year-old man: a case report

Integrated transthoracic and transesophageal echocardiography enables identification and characterization of a quadricuspid aortic valve anomaly.

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Low-grade inflammation in the relationship between sleep disruption, dysfunctional adiposity, and cognitive decline in aging

Aging is characterized by a progressive increase in proinflammatory status. This state, known as inflammaging, has been associated with cognitive decline in normal and pathological aging. However, this relationship has been inconsistently reported, likely because it is conditioned by other factors also affected by the aging process. Sleep and adiposity are two factors in particular that show significant alterations with aging and have been related to both cognitive decline and inflammaging. Given the consequences this state also has for brain integrity and cognition, we discuss here evidence supporting the potential mediating role of chronic low-grade systemic inflammation in the complex relationship between impaired sleep, dysfunctional adiposity, and cognitive decline through the common pathway of neuroinflammation.

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Two siblings with PRKDC defect who presented with cutaneous granulomas and review of the literature

Publication date: Available online 16 August 2018

Source: Clinical Immunology

Author(s): Saliha Esenboga, Can Akal, Betül Karaatmaca, Baran Erman, Sibel Dogan, Diclehan Orhan, Kaan Boztug, Deniz Ayvaz, İlhan Tezcan

Abstract

V(D)J recombination, during which recognition and repair of broken DNA chains are accomplished by non-homologous end joining pathway, is a critical process in B and T cell development.Null mutations of each enzyme or protein of this pathway result in T- B- NK+ severe combined immunodeficiency whereas hypomorphic mutations result in atypical(leaky)severe combined immunodeficiency forms. We present two siblings with PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide) mutation who presented with granulomatous skin lesions and recurrent lung infections. Primary immune deficiencies may initially present with skin findings. Disruption in central and peripheral B-cell tolerance and impaired intrathymic T-cell maturation,a central player in T-cell tolerance, have been identified as the mechanism of autoimmunity and granuloma seen in patients. The variation in clinical phenotypes of patients with PRKDC mutation suggests that additional factors such as modifying genes, epigenetic and environmental factors may affect the severity and clinical phenotype of the disease. Functional studies during the follow-up and evaluation before and after hematopoeitic stem cell transplantation will hopefully increase our knowledge about the autoimmune and inflammatory process of the disease spectrum.

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Generation of Pancreatic β-cells From iPSCs and their Potential for Type 1 Diabetes Mellitus Replacement Therapy and Modelling

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0661-5873

Diabetes type 1 (T1D) is a common autoimmune disease characterized by permanent destruction of the insulin-secreting β-cells in pancreatic islets, resulting in a deficiency of the glucose-lowering hormone insulin and persisting high blood glucose levels. Insulin has to be replaced by regular subcutaneous injections, and blood glucose level must be monitored due to the risk of hyperglycemia. Recently, transplantation of new pancreatic β-cells into T1D patients has come to be considered one of the most potentially effective treatments for this disease. Therefore, much effort has focused on understanding the regulation of β-cells. Induced pluripotent stem cells (iPSCs) represent a valuable source for T1D modelling and cell replacement therapy because of their ability to differentiate into all cell types in vitro. Recent advances in stem cell-based therapy and gene-editing tools have enabled the generation of functionally adult pancreatic β-cells derived from iPSCs. Although animal and human pancreatic development and β-cell physiology have significant differences, animal models represent an important tool in evaluating the therapeutic potential of iPSC-derived β-cells on type 1 diabetes treatment. This review outlines the recent progress in iPSC-derived β-cell differentiation methods, disease modelling, and future perspectives.
[...]

Article in Thieme eJournals:
Table of contents | Abstract | Full text

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Biomatrix for upper and lower airway biomarker in allergic asthma

Publication date: Available online 16 August 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Ulrich M. Zissler, Moritz Ulrich, Constanze A. Jakwerth, Sandra Rothkirch, Ferdinand Guerth, Markus Weckmann, Matthias Schiemann, Bernhard Haller, Carsten B. Schmidt-Weber, Adam M. Chaker

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FPIES in Adults

Publication date: Available online 16 August 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Yue (Jennifer) Du, Anna Nowak-Węgrzyn, Peter Vadas

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Chimeric antigen receptor (CAR) T cells targeting a pathogenic MHC class II:peptide complex modulate the progression of autoimmune diabetes

Publication date: Available online 16 August 2018

Source: Journal of Autoimmunity

Author(s): Li Zhang, Tomasz Sosinowski, R. Aaron, Joseph Ray Cepeda, Nitin S. Sekhar, Sean M. Hartig, Dongmei Miao, Liping Yu, Massimo Pietropaolo, Howard W. Davidson

Abstract

A primary initiating epitope in the NOD mouse model of Type 1 Diabetes (T1D) lies between residues 9 and 23 of the insulin B chain. The B:9-23 peptide can bind to the NOD MHC class II molecule (I-A^g7) in multiple registers, but only one, (register 3, R3), creates complexes able to stimulate the majority of pathogenic B:9-23-specific CD4⁺ T cells. Previously we generated a monoclonal antibody (mAb287) that targets this critical I-A^g7-B:9-23(R3) complex. When given weekly to pre-diabetic mice at either early or late stages of disease, mAb287 was able to delay or prevent T1D in the treated animals. Although the precise mechanism of action of mAb287 remains unclear, we hypothesized that it may involve deletion of antigen presenting cells (APCs) bearing the pathogenic IA^g7-B:9-23(R3) complexes, and that this process might be rendered more efficient by re-directing cytotoxic T cells using a mAb287 chimeric antigen receptor (287-CAR). As anticipated, 287-CAR T cells secreted IFN-γ in response to stimulation by I-A^g7-B:9-23(R3) complexes expressed on artificial APCs, but not I-A^g7 loaded with other peptides, and killed the presenting cells in vitro. A single infusion of 287-CAR CD8⁺ T cells to young (5 week old) NOD mice significantly delayed the onset of overt hyperglycemia compared to untreated animals (p = 0.022). None of the 287-CAR CD8⁺ T cell treated mice developed diabetes before 18 weeks of age, while 29% of control-CAR T cell treated mice (p = 0.044) and 52% of the un-treated mice (p = 0.0001) had developed T1D by this time. However, the protection provided by 287-CAR CD8⁺ T cells declined with time, and no significant difference in overall incidence by 30 weeks between the 3 groups was observed. Mechanistic studies indicated that the adoptively transferred 287-CAR T cells selectively homed to pancreatic lymph nodes, and in some animals could persist for at least 1–2 weeks post-transfer, but were essentially undetectable 10–15 weeks later. Our study demonstrates that CAR T cells specific for a pathogenic MHC class II:peptide complex can be effective in vivo, but that a single infusion of the current iteration can only delay, but not prevent, the development of T1D. Future studies should therefore be directed towards optimizing strategies designed to improve the longevity of the transferred cells.

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Generation of trichogenic adipose-derived stem cells by expression of three factors

Publication date: Available online 16 August 2018

Source: Journal of Dermatological Science

Author(s): Nahyun Choi, JunJeong Choi, Ji Hye Kim, Yaeji Jang, Joo Hye Yeo, Juwon Kang, Seung Yong Song, Jinu Lee, Jong-Hyuk Sung

Abstract

Background

Previous studies demonstrated that adipose-derived stem cells (ASCs) can promote hair growth, but unmet needs exist for enhancing ASC hair inductivity.

Objective

Therefore, we introduced three trichogenic factors platelet-derived growth factor-A, SOX2, and β-catenin to ASCs (tfASCs) and evaluated whether tfASCs have similar characteristics as dermal papilla (DP) cells.

Method

Global gene expression was examined using NGS analysis. Telogen-to-anagen induction, vibrissae hair follicle organ culture and patch assay were used.

Results

tfASC cell size is smaller than that of ASCs, and they exhibit short doubling time. tfASCs also resist aging and can be expanded until passage 12. Cell proportion in S and G₂/M increases in tfASCs, and tfASCs express high mRNA levels of cell cycle related genes. The mRNA expression of DP markers was notably higher in tfASCs. Moreover, NGS analysis revealed that the global gene expression of tfASCs is similar to that of DP cells. The injection of tfASCs accelerated the telogen-to-anagen transition and conditioned medium of tfASCs increased the anagen phase of vibrissal hair follicles. Finally, we found that the injection of 3D-cultured tfASCs at p 9 generated new hair follicles in nude mice.

Conclusion

Collectively, these results indicate that 1) tfASCs have similar characteristics as DP cells, 2) tfASCs have enhanced hair-regenerative potential compared with ASCs, and 3) tfASCs even at late passage can make new hair follicles in a hair reconstitution assay. Because DP cells are difficult to isolate/expand and ASCs have low hair inductivity, tfASCs and tfASC-CM are clinically good candidates for hair regeneration.

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How to Use Oral and Topical Cosmeceuticals to Prevent and Treat Skin Aging

Skin aging is caused by DNA damage in nuclei and mitochondria, inflammation, glycation, decreased function of keratinocytes and fibroblasts and breakdown of heparan sulfate, hyaluronic acid, collagen, and elastin. Identifying patients at an increased risk of skin aging using a standardized methodology to diagnose the Baumann Skin Type will allow doctors to prescribe an efficacious antiaging skin care regimen. Cosmeceuticals can activate LGR6+ stem cells, improve cell response to signals such as growth factors, stimulate collagen genes, neutralize free radicals, and decrease breakdown of collagen and elastin. Giving written instructions will increase patient compliance and improve outcomes.

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Mesothelial Stem Cells and Stromal Vascular Fraction for Skin Rejuvenation

The use of stem cells in regenerative medicine and specifically facial rejuvenation is thought provoking and controversial. Today there is increased emphasis on tissue engineering and regenerative medicine, which translates into a need for a reliable source of stem cells in addition to biomaterial scaffolds and cytokine growth factors. Adipose tissue is currently recognized as an accessible and abundant source for adult stem cells. Cellular therapies and tissue engineering are still in their infancy, and additional basic science and preclinical studies are needed before cosmetic and reconstructive surgical applications can be routinely undertaken and satisfactory levels of patient safety achieved.

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Research Grant for Study of Resistance to Precision Medication for Medullary Thyroid Cancer Is Awarded to Brendan Frett, PhD, by the American Thyroid Association

Brendan Frett, PhD

Brendan Frett, PhD
University of Arkansas for Medical Sciences
Little Rock, AR
Bio

The American Thyroid Association has awarded a 2018 Research Grant to Brendan Frett, PhD, Assistant Professor in the College of Pharmacy at the University of Arkansas for Medical Sciences. The title of Dr. Frett's project is "Dual Inhibition of RET and Aurora B to Study the Simultaneous Regulation of Multiple Oncogene Pathways in Medullary Thyroid Cancer."

Since its inception in 1971, the War on Cancer has resulted in significant treatment breakthroughs. One of the most important was the discovery of cancer-promoting oncogenes (genes with the potential to cause cancer). Researchers theorized that oncogenes could be strategically targeted while sparing normal cells, which sparked the era of precision medicine for oncology. Early medicine discoveries were quickly followed by the realization that secondary mutations in cancers often resulted in resistance to the drugs and relapse of the disease. This was solved by generating inhibitors that achieved activity on multiple forms of the oncogenes. However, additional cancer-promoting pathways were activated by the oncogenes. Therefore, although precision medicine for oncology has had great upfront success, the onset and degree of resistance lowers the effectiveness of many treatments. How is it possible to avoid this resistance?

The majority of thyroid cancers (TC) are curable through surgery, radiation, and chemotherapy, with a five-year survival rate of 98%. However, TC can present in certain forms that are highly aggressive, such as metastatic medullary thyroid cancer (MTC). Researchers have identified drivers specific to MTC (RET and VEGFR2, among others) through comprehensive investigation, which led to the clinical development of precision-medicine therapies that target those oncogenes. However, through RET-oncogene mutations and other cancer-promoting pathways, MTC tumors can develop resistance to precision medicine, in which case treatment benefit becomes limited.

The ultimate goal for this project is to uncover pioneering precision-medicine strategies and innovative biology and treatment paradigms that can be used to more effectively combat resistant thyroid disease. More specifically, Dr. Frett's laboratory plans to develop a dual-targeted compound that acts on both RET and cell cycle oncogenes, employing single-agent polypharmacology (SAP) and synergistic medicinal chemistry (SMC). They will focus on understanding MTC-resistance mechanisms. As medicinal chemists, they specialize in the design and development of unique tools to help analyze MTC biology. For this project, they want to investigate the use of precision medicine to target multiple, unrelated cancer-promoting pathways.

First, they will design tractable inhibitors to block the RET oncogene, because MTC is heavily promoted by the RET oncogene.
Second, they will expand the RET inhibitor to block the ability of MTC cells to divide, since uncontrolled cell growth is a hallmark of cancer.
They will repeat the two-step process with cell cycle oncogenes.

Dr. Frett expects that this method of targeting MTC will significantly help delay the degree and onset of resistance to precision medicine.

In 2014, Dr. Brendan Frett received his PhD in Pharmaceutical Sciences, with an emphasis in Drug Discovery and Development, from the University of Arizona. He also received postdoctoral training in Medicinal Chemistry and in Pharmaceutics at the University of Arizona. He has successfully transferred academic-based discoveries to pharmaceutical companies for clinical development, specializing in the development of therapies for orphan diseases (those that offer little financial incentive for the private sector to develop and sell new medications that would treat or prevent them, either because the diseases are rare or because they are not common in the "developed" world). Dr. Frett is interested in pursuing translational research projects, where research completed in his laboratory can directly help patients. Specifically, he investigates resistance mechanisms and the design of next-generation precision-medicine therapies for thyroid cancer. He is interested in tailoring precision medicine to the unique pathology of MTC to generate "synergistic" medicine.

Dr. Antonio Di Cristofano, Chair, ATA Research Committee, says, "The ATA research grant program represents a unique and invaluable mechanism to foster the development of a new generation of basic, translational, and clinical researchers. Through this program, we allow these outstanding young scientists to test innovative hypotheses and generate preliminary data that will give them a significant competitive advantage when applying for traditional NIH-type funding.

This year we received 63 applications from 18 countries, spanning the whole spectrum of thyroid-related research. While, through a rigorous process, we have selected the most promising projects for funding, at the same time we regret we had to leave behind a number of excellent proposals. We are extremely thankful for the support we receive from members and organizations, including thyroid cancer survivors, which makes this outstanding program possible and allows the ATA to nurture the next generation of leaders in thyroidology."

The American Thyroid Association (ATA) has awarded 99 thyroid research grants totaling over $2.8 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 72.5 special research grants totaling $2,084,375 focused on thyroid cancer and medullary thyroid cancer. In 2018 ThyCa is supporting half of a new medullary thyroid cancer grant with Bite Me Cancer, two new thyroid cancer research grants, 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 8.5 thyroid cancer grants since 2014 for a total of $201,250. BMC will be supporting a half of a new medullary thyroid cancer grant in 2018 with ThyCa and one renewing thyroid cancer 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 95th 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.

The post Research Grant for Study of Resistance to Precision Medication for Medullary Thyroid Cancer Is Awarded to Brendan Frett, PhD, by the American Thyroid Association appeared first on American Thyroid Association.

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Research Grant to Determine the Genes Responsible for Survival and Growth of Medullary Thyroid Cancer Is Awarded to Wayne Miles, PhD, by the American Thyroid Association

Wayne Miles, Ph.D.

Wayne Miles, Ph.D.
The Ohio State University
Columbus, OH
Bio

The American Thyroid Association has awarded a 2018 Research Grant to Wayne Miles, PhD, Assistant Professor of Molecular Genetics at the Ohio State University. Dr. Miles's research project is entitled "Proteomic-led discovery of essential genes in Medullary Thyroid Cancer."

Medullary thyroid cancer (MTC) is caused by the malignant growth of C-cells. Although MTC represents only a small fraction (2-4%) of all thyroid cancer cases and overall survival rates from MTC are good, patients diagnosed with advanced disease have poor five-year survival rates (28%). The genetic aberrations of the cancer result in C-cells receiving a continuous signal to grow and proliferate. To sustain their elevated growth rates, MTC cells adapt their genome (DNA), transcriptome (RNA), and proteome (the entire set of proteins expressed by a cell, tissue, or organism).

Dr. Miles's laboratory has specialized in profiling the protein changes in human MTC cancer cell lines, revealing many exciting and potentially exploitable changes within these cells. However, before they begin to translate these specific MTC cell-line changes into new strategies to treat human MTC, they first need to determine: (1) whether these changes are also seen in preclinical mouse models of MTC and (2) which of the protein changes are essential for the survival of human MTC cells.

Using quantitative proteomics, they will measure the protein composition of mouse MTC tumors and normal mouse thyroids. With Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), a genome editing technology, they will then conduct a genome-wide screen to determine the genes responsible for the survival and growth of MTC and C-cells. This unbiased methodology systematically disables one gene per cell and enables the identification of essential genes. With this approach, the project will profile a C-cell line and two human MTC cancer cell lines. Collectively, these results will generate new insights into MTC biology and uncover opportunities to therapeutically target MTC cells.

Dr. Miles's research has long focused on understanding how loss of the Retinoblastoma 1 or RB tumor-suppressor gene contributes to cancer growth. His laboratory's previous work has found that RB loss results in widespread cellular reprogramming that effects not only transcription but also metabolism and the proteome. These discoveries were made possible by utilizing cutting-edge quantitative proteomic approaches and these past projects have been excellent training for the upcoming project. More recently, their research has expanded to investigate the roles of RB-inactivation in Medullary Thyroid Cancer.

Wayne Miles received his PhD in 2008 from the University of Manchester (UK), and pursued postdoctoral work the following year at Harvard Medical School and the Massachusetts General Hospital Cancer Center. In 2016 he was appointed Assistant Professor at The James Comprehensive Cancer Center, Ohio State University.

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

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Research Grant to Determine the Genes Responsible for Survival and Growth of Medullary Thyroid Cancer Is Awarded to Wayne Miles, PhD, by the American Thyroid Association

Wayne Miles, Ph.D.

Wayne Miles, Ph.D.
The Ohio State University
Columbus, OH
Bio

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Research Grant for Study of Resistance to Precision Medication for Medullary Thyroid Cancer Is Awarded to Brendan Frett, PhD, by the American Thyroid Association

Brendan Frett, PhD

Brendan Frett, PhD
University of Arkansas for Medical Sciences
Little Rock, AR
Bio

First, they will design tractable inhibitors to block the RET oncogene, because MTC is heavily promoted by the RET oncogene.
Second, they will expand the RET inhibitor to block the ability of MTC cells to divide, since uncontrolled cell growth is a hallmark of cancer.
They will repeat the two-step process with cell cycle oncogenes.

Dr. Frett expects that this method of targeting MTC will significantly help delay the degree and onset of resistance to precision medicine.

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Research Grant Focused on Identifying T3-Forming Sites in Thyroglobulin Is Awarded to Cintia Eliana Citterio, PhD, by the American Thyroid Association

Cintia Eliana Citterio, Ph.D.

Cintia Eliana Citterio, Ph.D.
Instituto de Inmunología, Genética y Metabolismo (INIGEM), Universidad de Buenos Aires (UBA) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
Buenos Aires, Argentina
Bio

The American Thyroid Association has awarded a 2018 Research Grant to Cintia Eliana Citterio, PhD, Assistant Professor of Genetics and Molecular Biology at the Instituto de Inmunología, Genética y Metabolismo (INIGEM), Universidad de Buenos Aires (UBA) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Dr. Citterio's project is called "De novo triiodothyronine (T₃) formation in T₃ toxicosis of Graves' Disease."

The project focuses on identifying T₃-forming sites in thyroglobulin (TG, the protein from which thyroid hormone is made) that are responsible for excess T₃ production in patients with autoimmune hyperthyroidism or Graves' Disease (GD). The long-term objectives are:

To dissect the molecular mechanisms that underlie de novo T₃ synthesis in GD and in other thyroid conditions that are characterized by hyperactive thyroid TSH-receptors and preferential T₃ formation within thyroglobulin
To understand these mechanisms
To develop treatments that will repair them, if possible

Although thyroid hormone is perhaps the smallest chemical hormone known, the TG protein is a very large, complex molecule that has been very difficult to understand. Thyroid stimulating hormone (TSH) stimulates synthesis of the hormone by binding to a receptor (called TSH-receptor), which triggers many responses in the thyroid gland, including making more of the active thyroid hormone called T₃. For reasons yet to be discovered, the TG protein sometimes makes too much T₃, causing the anxiety, irritability, weight loss, enlargement of the thyroid gland, bulging eyes, and/or other symptoms that combine to indicate Graves' Disease or related diseases.

Dr. Citterio proposes that, when TSH stimulates the thyroid gland, the TG protein structure is modified by a special enzyme that increases the ability of TG to make T₃. She has evidence that this special enzyme, named Fam20C, can add a phosphate residue at a particular site on the TG molecule, changing its structure. Increasing the amount of Fam20C in thyroid cells results in those cells making a TG protein that produces more T₃; inhibiting the enzyme results in less T₃ production. In GD, the stimulated thyroid gland makes more of the Fam20C enzyme; Dr. Citterio believes this is why patients end up with too much T₃ in their blood.

This project will attempt to find the specific location on the TG molecule where the extra T₃ is released, which is likely from one of three sites. Using mutagenesis to eliminate each of those sites one at a time, Dr. Citterio will then test the TG protein to see whether it still makes more T₃ in cells that express more of the Fam20C enzyme, or in thyroid cells stimulated with a lot of TSH. The long-term objective is to understand, at a molecular level, why patients with Graves' disease (and some other diseases) make too much T₃.

Dr. Citterio received her undergraduate degree from the UBA with a double major in biochemistry (Certificate of Honor) and pharmaceutical sciences. Her interest in thyroid function and disease began during her PhD research (completed in 2014, Summa Cum Laude) under the direction of Dr. Héctor M. Targovnik at the UBA. She has since published her research in 16 publications. In 2014, she was named a Fulbright Scholar to conduct postdoctoral studies in Dr. Peter Arvan's lab at the University of Michigan, where she developed a new assay to measure de novo T₃ formation within thyroglobulin secreted from hyperstimulated thyrocytes (Citterio et al., 2017) and characterized the molecular mechanisms of T₃ formation at the antepenultimate tyrosine residue of thyroglobulin (Citterio et al., 2018).

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Research Grant to Determine How Specific Drugs Work or Fail in Anaplastic Thyroid Cancer Is Awarded to Miles Miller, PhD, by the American Thyroid Association

Miles Miller, PhD

Miles Miller, PhD
Massachusetts General Hospital and Harvard Medical School
Boston, MA
Bio

The American Thyroid Association has awarded a 2018 Research Grant to Miles Miller, PhD, principal investigator at the Massachusetts General Hospital Center for Systems Biology and Assistant Professor of Radiology at Harvard Medical School. Dr. Miller's research project is titled "Co-opting tumor-associated macrophages in anaplastic thyroid cancer to enhance immune-checkpoint blockade response."

Treatment of advanced metastatic cancer has seen a revolution over the last several years, as new therapeutic strategies have become successful at harnessing the power of the immune system to durably attack malignant and mutated cancer cells. Immune-checkpoint blockade therapies targeting programmed-death 1 (PD1) signaling on T-cells have been successful in the treatment of solid cancers, including heavily mutated melanomas and lung cancers. Unfortunately, these treatments only work in a fraction of patients, and resistance is often associated with the presence of a type of tumor-promoting immune cell: the tumor-associated macrophage. Highly aggressive anaplastic thyroid cancers (ATC) can contain extremely high levels of these macrophages, which may be why drug resistance is so common in these cancers.

Although ATC represents less than 10% of thyroid malignancies worldwide, it contributes to a disproportionately high fraction of deaths from thyroid cancer, ranging from 15 to 50% by some estimates. Ongoing clinical trials are testing PD1-targeted immunotherapy, but initial indications suggest large numbers of patients will not see durable responses. Thus, a clear need exists to understand the mechanisms: Why doesn't ATC respond better to immune-checkpoint blockade or to other advanced biologic therapies? New strategies against the disease are urgently needed.

This project will bring together new techniques for simultaneously imaging the delivery and action of biologics in tumors in vivo, combined with expertise in mouse models of metastatic thyroid cancer, to offer fundamental, mechanistic knowledge of how specific drugs work or fail in ATC. Strikingly little is known about how much of a given drug accumulates in ATC, what the heterogeneity of drug accumulation is across primary tumors and metastases, and how drug exposure ultimately impacts response or nonresponse.

Dr. Miller's laboratory recently discovered that tumor-associated macrophages critically influence the delivery and action of biologic therapies (including PD1-targeted drugs) and may be co-opted to synergistically improve drug response. ATC shows special promise for this approach, as macrophages outnumber tumor cells themselves in some ATC cases. New unpublished findings reveal ATC-macrophage content can increase substantially with targeted therapy. Dr. Miller's approach promises to clarify the relationships between drug exposure and trajectories of cell response or resistance, which are monitored over time using fluorescent readouts of immune activity and tumor-cell killing. Dr. Miller hypothesizes that variability in local macrophage levels will play a key role in mediated drug response, especially at sites of metastasis, and aims to test whether combination treatments can repurpose macrophages for enhancing treatment efficacy.

This project will leverage the recent discoveries of Miller's lab into the function and therapeutic potential of tumor-associated macrophages, along with expertise and compelling new observations from Sareh Parangi, MD, Director of the MGH Thyroid Cancer Research Laboratory, who for over a decade has developed and tested treatment strategies in an impressive array of advanced, preclinical, metastatic thyroid cancer models.

In addition to serving as a principal investigator at the Massachusetts General Hospital Center for Systems Biology and Assistant Professor of Radiology at Harvard Medical School, Dr. Miller is also a faculty member of the Harvard Bioinformatics and Integrative Genomics PhD Program. For the last 10 years he has developed new approaches and technologies for parsing mechanisms of drug action and cancer behavior in disease microenvironments from a quantitative, network-level perspective. He has extensive training and publications in computational modeling, multivariate statistics, in vivo microscopy, nanotechnology, and cancer pharmacology. As an NIH-funded postdoctoral fellow, he developed new techniques for imaging the in vivo transport, cellular uptake, and pharmacodynamics of novel chemotherapeutic formulations at a single-cell level within live tumor models. Dr. Miller received a Ph.D. from the Massachusetts Institute of Technology Department of Biological Engineering. He graduated summa cum laude from Princeton University.

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Research Grant to Identify the Source and Mechanism of Thyroid and Kidney Comorbidity Is Awarded to Nicholas Tardi, PhD, by the American Thyroid Association

Nicholas J. Tardi,Ph.D.

Nicholas J. Tardi,Ph.D.
Rush University Medical Center
Chicago, IL Bio

The American Thyroid Association has awarded a 2018 Research Grant to Nicholas J. Tardi, PhD, Instructor in Internal Medicine at Rush University Medical Center in Chicago. Dr. Tardi's project is titled "Deiodinase 3: A Thyroid Hormone-Associated Renoprotective Protein."

The long-term goal of this project is to identify the source and mechanism of kidney and thyroid comorbidity. Thyroid hormone (TH) is a circulating, lipid-soluble molecule that plays an important physiological and developmental role in nearly all cells. Accordingly, precise control of TH activity is crucial to maintain metabolic homeostasis in several tissues.

Scientists have known for 30 years about the interplay between kidney disease and TH disorders, yet the underlying mechanism that links these two diseases has yet to be defined. Studying the effect of poor enzyme regulation of TH activity in the kidney may identify a causative disease mechanism. Dr. Tardi's lab has previously shown that deiodinase 3 (D3), an enzyme that deactivates TH, is highly expressed in podocytes, which wrap around the capillaries of kidney filtration units and filter toxins from blood. This suggests that low TH activity is required for proper podocyte function. Mature podocytes cannot divide and cannot be replaced, so it is especially important that they continue to function properly. Unfortunately, they are a primary target of kidney disease. D3-deficient podocytes are more susceptible to injury, indicating that TH stability is important in preventing kidney disease.

Dr. Tardi's laboratory will study the local effect of TH imbalance in both cell and mouse models to determine how D3 protects podocytes from injury. Additionally, they will define the prevalence of D3 misexpression in patients suffering from various kidney diseases. Identifying a local regulatory mechanism causing TH metabolism dysfunction will aid in developing targeted therapies to combat kidney and/or thyroid diseases that share a disease source.

Patients with hyperthyroidism show increased kidney filtration pressure and absorption capacity, while those with hypothyroidism show thickening of the glomerular basement membrane and reduced filtration rate. Despite the prevalence of overlapping complications of thyroid hormone disorders and kidney disease, a unifying mechanism regulating T₃ stability in the kidney is absent. Though well studied in endocrine tissues, the role of D3 in the regulation of thyroid hormone in renal tissue has not been addressed in the past. This study will use samples from clinical patients and representative disease models to define a therapeutic target.

Specifically, Dr. Tardi's study will aim to:

Identify pathways associated with D3 dysfunction in podocytes: The laboratory will use microarray experiments to identify D3-responsive genes in podocytes and to screen potential activators and inactivators of D3. They will compare gene-expression profiles under healthy and injury-promoting conditions and set priorities to guide future studies of the signaling events that regulate D3 activity.
Establish the renoprotective mechanism of D3: The lab will use molecular biology-based experiments and morphological analysis to identify the mechanism by which D3 protects against podocyte injury. With confocal microscopy, they will examine cytoskeletal structure for hallmarks of podocyte injury. Protein analysis on known markers of podocyte health, metabolic processes, cellular stress, and protein trafficking will help to determine the mechanism of D3. They will correlate these cellular-level effects with the heavy proteinuria observed in D3-knockout mice models.
Define the prevalence of D3 misexpression in patients with kidney disease at single stages of its development: Dr. Tardi's lab will analyze patient samples from the nephrology clinic at Rush University Medical Center to assess D3 as a potential biomarker for TH-associated kidney disease. They will use this data to develop studies targeting specific deiodinases to treat kidney disease. This is different from current therapeutic approaches that attempt to balance systemic TH levels to prevent the development of overlapping kidney disease.

Dr. Nicholas Tardi earned his PhD in Molecular and Cellular Biology in 2013 from Illinois State University, where he developed expertise in cell signaling, molecular mechanisms of disease, protein biology, and analytical processing to answer questions about cellular regulation of growth control pathways. Since joining Rush University, he has been investigating the molecular mechanisms of thyroid hormone imbalance in kidney disease and characterizing pharmacologically active agents to rescue kidney disease in mice. Recently, he has worked closely with two mentors to develop a niche to study kidney and thyroid comorbidity. Dr. Tardi's passion for research, scientific expertise, and unusual technical perspective is reflected in publications in Nature Medicine, Science, Cell, and Genetics.

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Research Grant to Study Common Resistance to Papillary Thyroid Cancer Treatment Is Awarded to Ann-Kathrin Eisfeld, MD, by the American Thyroid Association

Ann-Kathrin Eisfeld, M.D.

Ann-Kathrin Eisfeld, M.D.
The Ohio State University
Columbus, OH
Bio

The American Thyroid Association has awarded a 2018 Research Grant to Ann-Kathrin Eisfeld, MD, Clinical Fellow in Internal Medicine at Ohio State University. The topic of Dr. Eisfeld's project is "Novel NRAS isoform mediates BRAF-inhibitor resistance in papillary thyroid cancer—thinking outside the box to overcome 'inevitable' treatment failure."

Papillary thyroid cancer (PTC) is one of the 10 most common malignancies in the United States, with almost 60,000 new people diagnosed each year. While almost all patients initially respond well to the current standard treatment with radioactive iodine, almost half of them will eventually develop resistance. Therapies that can provide additional treatment options for those patients are greatly needed.

The BRAF oncogene is the BRAF gene mutated from its natural state, which may contribute to tumor growth. Because about 60% of PTC patients harbor the BRAF oncogene, targeted treatment with a BRAF inhibitor seemed to be a promising treatment option for these patients. The BRAF^V600E-inhibitor Vemurafenib was initially effective in many patients, but eventually all patients developed resistance. It seems apparent that resistance and escape mechanisms exist that prevent complete response to selective BRAF inhibitors. Several resistance mechanisms have already been identified, including increased expression of BRAF's upstream regulator, RAS. Eisfeld's laboratory recently pioneered the discovery of five splice variants of the NRAS gene, among which NRAS isoform 2 appears likely to facilitate resistance to Vemurafenib.

In this project, the laboratory will perform comprehensive in vitro and in vivo studies in mice to:

Understand whether and how NRAS isoform 2 contributes to the development of resistance to Vemurafenib
Understand the pathobiology of the new isoform of this major human oncogene

They will use a range of methods including gene splicing, RNA sequencing, and mass spectrometry, among others.

This novel approach may eventually lead to new treatment options for PTC patients who develop resistance to the current standard therapy.

Dr. Eisfeld grew up in Northern Germany watching her father practice medicine and wanting to do the same. However, she did not discover her passion for research until attending medical school at the University of Leipzig, Germany, and realized the power that translational genetics has on cancer treatment. There she began research projects that eventually led to a hematology residency/fellowship in Leipzig. Her passion for genetics led her to pause her fellowship in 2009 to take a research position in Albert de la Chapelle's and Clara D. Bloomfield's Laboratories at The Ohio State University. Together they undertook studies focused on genetics in acute myeloid leukemia and solid tumors, for which Dr. Eisfeld assumed a senior role. In 2016 she resumed her clinical training in the OSU Physician-Scientist-Training Program, so she could maintain a research lab. She plans to finish her clinical training and finally unite her two passions—research and patient care—as a Physician Scientist.

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Research Grant to Study the Action of T-Regulatory Cells in Thyroid-Antibody-Positive Pregnant Women Awarded to Stephanie Behringer-Massera, MD, by the American Thyroid Association

Stephanie Behringer-Massera, MD

Stephanie Behringer-Massera, MD
Icahn School of Medicine at Mount Sinai
New York, NY
Bio

The American Thyroid Association has awarded a 2018 Research Grant to Stephanie Behringer-Massera, MD, Clinical Fellow at the Icahn School of Medicine at Mount Sinai. Dr. Behringer-Massera's project is titled "T regulatory cells in thyroid-antibody-positive pregnant women."

A fetus, which shares half its genetic material with the father, is considered a foreign body in the mother's womb. The only way that it can implant in the uterus without being rejected is if the mother's immune system is suppressed, which happens through T-regulatory-cell action. The more T regulatory cells (Tregs) are released, the more the immune system is suppressed and the more likely the pregnancy can successfully be brought to term. In women with autoimmune thyroid disease, this process is disrupted. These women are found to have an abnormal Treg response to pregnancy and have Treg levels as low as women who are not pregnant. They are more likely to have miscarriages in the first trimester.

Through this project, Dr. Behringer-Massera hopes to understand the underlying pathology in this immune response to the fetus, enabling the development of targeted therapies to prevent these miscarriages. She plans to measure the proportion of Tregs in pregnant women during each trimester and in those who are 6-weeks postpartum, comparing the proportions in thyroid-antibody-positive versus thyroid-antibody-negative women, as well as in a control group of normal nonpregnant women. Her laboratory will also examine the functional status of Treg cells in both normal and thyroid-antibody positive women during pregnancy to determine their effectiveness at immune control. They will also analyze the Treg cells isolated from the control group and from the antibody-positive women to evaluate clonal expansion during and after pregnancy.

Dr. Behringer-Massera's previous studies of patients with increased thyroid autoantibodies during the first trimester of pregnancy demonstrated the increased rate of miscarriage and led to her proposed further studies.

Dr. Behringer-Massera completed her medical studies at the University of Heidelberg in Germany in December 2009. She continued her medical training as a resident in Internal Medicine at the St. Josef Hospital in Heidelberg. In 2011 she was accepted for a residency in Internal Medicine at Montefiore Medical Center, Bronx, New York. She successfully completed her Internal Medicine training in 2014 and was awarded a research fellowship in the Empire Clinical Research Investigator Program (ECRIP) at the Albert Einstein College of Medicine, where she joined a multi-center clinical trial on glycemia-reduction approaches in diabetes (GRADE) funded by the NIH. During this time she also conducted a qualitative study on barriers to enrollment into research studies. In 2016 she started training as a Clinical Fellow in Endocrinology at the Mount Sinai Hospital in New York. When she completes her fellowship in June 2018, she will begin a position as Assistant Professor at the Icahn School of Medicine at Mount Sinai with clinical duties at Mount Sinai Beth Israel Medical Center.

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Celebrating its 95th 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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Πέμπτη 16 Αυγούστου 2018

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