Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers.

Background: Thyroid nodules are an extremely common entity, and surgery is considered the ultimate diagnostic strategy in those with unclear malignant potential. Unfortunately, strategies aiming to predict the risk of malignancy have inadequate specificity. Our group recently found that the microenvironment of thyroid cancer is characterized by an enhanced immune invasion and activated immune response mediated by double-negative T lymphocytes (DN T) (CD3CD4CD8), which are believed to enable or promote tumorigenesis.

Hyperinsulinemia Associated Depression.

Hyperinsulinemia promotes fat accumulation, causing obesity. Being an inflammatory state, obesity can induce further inflammation and is a risk factor for HPA (hypothalamic pituitary axis) dysregulation through hypercortisolism-related hyperglycemia. In another hypothesis, the sympathetic nervous system (SNS) plays a significant role in the regulation of hormone secretion from the pancreas such as an increase in catecholamines and glucagon as well as a decrease in plasma insulin levels, a disruption on SNS activity increases insulin levels, and induces glycogenolysis in the liver and lipolysis in adipose tissue during hypoglycemia.

Large, Slowly Growing, Benign Thyroid Nodules Frequently Coexist With Synchronous Thyroid Cancers.

Context: Thyroid nodules' size should not be the sole criterion for thyroidectomy; however, many patients undergo surgery for large or slowly growing nodules.

Objective: We evaluated risk for clinically significant thyroid cancer in patients with large or slowly growing nodules.

Methods: We reviewed data from 2 prospectively collected databases of patients undergoing thyroidectomies in tertiary referral centers in the USA and Greece over 14 consecutive years.

Intractable Seizures and Limbic Encephalitis, Unaccounted Complications of Type 1 Diabetes Autoimmunity.

Glutamic acid decarboxylase 65kD autoantibody (GAD65Ab) is frequently detected in patients with refractory epilepsy and stiff person syndrome. In contrast to T1D, the pathological role of GAD65Ab in neurological disorders is still debatable. As a result, the implementation of possible immunotherapy is usually delayed.

Immune Cell Plasticity Allows for Resetting of Phenotype From Effector to Regulator With Combined Inhibition of Notch/eIF5A Pathways.

Type 1 diabetes (T1D) results from the destruction of pancreatic β-cells caused by an altered immune balance in the pancreatic microenvironment. In humans as well as in mouse models, T cells are well recognized as key orchestrators of T1D, which is characterized by T helper (Th) 1 and Th17 cell bias and/or low/defective T-regulatory cells (Treg), and culminates in cytotoxic T-cell (CTL)-mediated destruction of β-cells. Refitting of immune cells toward the non-inflammatory phenotype in the pancreas may represent a way to prevent/treat T1D.

Higher TSH Is Not Associated With Thyroid Cancer Risk in the Presence of Thyroid Autoimmunity.

Background: Higher-but-within-normal thyrotropin (thyroid-stimulating hormone, TSH) is associated with higher risk for differentiated thyroid cancer (DTC) in surgical series. Our recent clinical observations suggest that this is not the case in the presence of autoimmune thyroid disease (AITD). We designed the present study to clarify this controversy.

Incidentally Discovered Papillary Thyroid Microcarcinomas Are More Frequently Found in Patients with Chronic Lymphocytic Thyroiditis Than with Multinodular Goiter or Graves' Disease.

Incidental finding of differentiated thyroid microcarcinomas (DTMc) in patients undergoing thyroid surgery for benign indications has become increasingly common. Even though carcinogenesis might relate to the background disease of the gland, the incidence of DTMc in the setting of various thyroid disorders remains unclear. We designed the present study to address this question.

An Artificial Neural Network-based Predictive Model to Support Optimization of Inpatient Glycemic Control.

Achieving glycemic control in critical care patients is of paramount importance, and has been linked to reductions in mortality, intensive care unit (ICU) length of stay, and morbidities such as infection. The myriad of illnesses and patient conditions render maintenance of glycemic control very challenging in this setting. This study involved collection of continuous glucose monitoring (CGM) data, and other associated measures, from the electronic medical records of 127 patients for the first 72 h of ICU care who upon admission to the ICU had a diagnosis of type 1 ( = 8) or type 2 diabetes ( = 97) or a glucose value >150 mg/dL ( = 22).

The non-interventional approach to papillary thyroid microcarcinomas. An "active surveillance" dilemma.

Background: Recent studies suggest that papillary-thyroid-microcarcinomas (PTMi) and follicular-variant-papillary-thyroid-cancers (FVPTC) are less aggressive overall. Our observations argue against.

Objectives: To assess whether PTMi and FVPTC are indeed low-risk and could be safely followed without intervention.

eIF5A inhibition influences T cell dynamics in the pancreatic microenvironment of the humanized mouse model of Type 1 Diabetes.

We have developed a transgenic mouse model of Type 1 Diabetes (T1D) in which human GAD65 is expressed in pancreatic β-cells, and human MHC-II is expressed on antigen presenting cells. Induced GAD65 antigen presentation activates T-cells, which initiates the downstream events leading to diabetes. In our humanized mice, we have shown downregulation of eukaryotic translation initiation factor 5 A (elF5A), expressed only in actively dividing mammalian cells.

Nature of coexisting thyroid autoimmune disease determines success or failure of tumor immunity in thyroid cancer.

Background: Thyroid cancer and thyroid autoimmunity are considered opposite extremes of immune-responses. However, several studies have suggested that thyroid cancer coexists with autoimmune thyroid diseases like Hashimoto Thyroiditis (HT) and Graves disease (GD). We have shown that the risk of developing thyroid cancer is higher in patients with a silent form of autoimmune thyroid disease -Euthyroid Hashimoto Thyroiditis-(EHT).

LOCALLY INVASIVE PHEOCHROMOCYTOMA COMBINED WITH PRIMARY MALIGNANT ADRENAL LYMPHOMA.

Objective: Pheochromocytoma (PHEO) combined with primary adrenal lymphoma is extremely rare. We describe a case of locally invasive PHEO combined with primary malignant lymphoma.

Methods: We provide a case description with biochemical analyses, imaging, and pathologic findings.

Posttransplant Tacrolimus-Induced Diabetic Ketoacidosis: Review of the Literature.

Diabetic ketoacidosis (DKA) in patients receiving tacrolimus as part of their immunosuppressive regimen is a rarely reported adverse event. We report a patient with autosomal dominant polycystic kidney disease (ADPKD) and no known history of diabetes mellitus who presented with DKA, 3 months after kidney transplantation.

Bacterial flagellin-a potent immunomodulatory agent.

Flagellin is a subunit protein of the flagellum, a whip-like appendage that enables bacterial motility. Traditionally, flagellin was viewed as a virulence factor that contributes to the adhesion and invasion of host cells, but now it has emerged as a potent immune activator, shaping both the innate and adaptive arms of immunity during microbial infections. In this review, we summarize our understanding of bacterial flagellin and host immune system interactions and the role flagellin as an adjuvant, anti-tumor and radioprotective agent, and we address important areas of future research interests.

Novel approaches in anaplastic thyroid cancer therapy.

Anaplastic thyroid cancer (ATC), accounting for less than 2% of all thyroid cancer, is responsible for the majority of death from all thyroid malignancies and has a median survival of 6 months. The resistance of ATC to conventional thyroid cancer therapies, including radioiodine and thyroid-stimulating hormone suppression, contributes to the very poor prognosis of this malignancy. This review will cover several cellular signaling pathways and mechanisms, including RET/PTC, RAS, BRAF, Notch, p53, and histone deacetylase, which are identified to play roles in the transformation and dedifferentiation process, and therapies that target these pathways.

Hashimoto's thyroiditis pathology and risk for thyroid cancer.

Background: Hashimoto's thyroiditis (HT) has been found to coexist with differentiated thyroid cancer (DTC) in surgical specimens, but an association between the two conditions has been discounted by the medical literature. Therefore, we performed this study to determine any potential relationship between HT and the risk of developing DTC.

Methods: We collected data for thyrotropin (TSH), thyroxine (T4), thyroid peroxidase antibody (TPO-Ab) titers, surgical pathology, and weight-based levothyroxine (LT4) replacement dose for patients who were referred for thyroid surgery.

Lymphocytic profiling in thyroid cancer provides clues for failure of tumor immunity.

Thyroid cancers are usually surrounded by a significant number of immune-reactive cells. Tumor-associated lymphocytes as well as background lymphocytic thyroiditis are frequently mentioned in pathology reports of patients who have undergone surgery for thyroid cancer. The nature of this lymphocytic reaction is not well understood.

Eukaryotic translation initiation factor 5A inhibition alters physiopathology and immune responses in a "humanized" transgenic mouse model of type 1 diabetes.

Therapeutic options for treatment of type 1 diabetes (T1D) are still missing. New avenues for immune modulation need to be developed. Here we attempted at altering the diabetes outcome of our humanized model of T1D by inhibiting translation-initiation factor eIF5A hypusination in vivo.

Diabetes-associated dry eye syndrome in a new humanized transgenic model of type 1 diabetes.

Purpose: Patients with Type 1 Diabetes (T1D) are at high risk of developing lacrimal gland dysfunction. We have developed a new model of human T1D using double-transgenic mice carrying HLA-DQ8 diabetes-susceptibility haplotype instead of mouse MHC-class II and expressing the human beta cell autoantigen Glutamic Acid Decarboxylase in pancreatic beta cells. We report here the development of dry eye syndrome (DES) after diabetes induction in our humanized transgenic model.