Clinical and radiographic presentation and surgical outcomes of TPIT+ silent corticotroph pituitary neuroendocrine tumors: a multi-institutional experience and review of the literature.

Background: Accurate lineage identification of pituitary neuroendocrine tumors (PitNETs) is critical to inform our understanding of tumor biology and aggressiveness. While this was previously performed using immunohistochemistry for anterior pituitary hormones, the recent WHO update using lineage specific transcription factors (PIT-1, SF-1, TPIT) has led to improved classification of PitNETs. Although the identification of TPIT, a T-box pituitary transcription factor, has afforded improved classification of corticotroph PitNETs from what were previously thought to be null cell adenomas, the standardization of lineage specific transcription factor staining has yet to be fully adopted and as a result the clinical aggressivness and outcomes of these newly classified silent TPIT+ PitNETs has yet to be fully described.

Evaluating the Impact of Inadequate Meal Consumption on Insulin-Related Hypoglycemia in Hospitalized Patients.

Objective: Meal intake is sometimes reduced in hospitalized patients. Meal-time insulin administration can cause hypoglycemia when a meal is not consumed. Inpatient providers may avoid ordering meal-time insulin due to hypoglycemia concerns, which can result in hyperglycemia.

Validation of an equation for energy expenditure that does not require the respiratory quotient.

Background: Energy expenditure (EE) calculated from respirometric indirect calorimetry is most accurate when based on oxygen consumption (VO2), carbon dioxide production (VCO2) and estimated protein metabolism (PM). EE has a substantial dependence of ~7% on the respiratory quotient (RQ, VCO2/VO2) and a lesser dependence on PM, yet many studies have instead estimated EE from VO2 only while PM has often been ignored, thus reducing accuracy. In 1949 Weir proposed a method to accurately calculate EE without using RQ, which also adjusts for estimated PM based on dietary composition.

What Can We Learn From Point-of-Care Blood Glucose Values Deleted and Repeated by Nurses?

Background: Hospitals rely on point-of-care (POC) blood glucose (BG) values to guide important decisions related to insulin administration and glycemic control. Evaluation of POC BG in hospitalized patients is associated with measurement and operator errors. Based on a previous quality improvement (QI) project we introduced an option for operators to delete and repeat POC BG values suspected as erroneous.

Use of a Mental Health Center Collaborative Care Team to Improve Diabetes Care and Outcomes for Patients With Psychosis.

Objective: This study aimed to evaluate the feasibility, acceptability, and preliminary effectiveness (compared with usual care) of a collaborative care model to treat community mental health center (CMHC) patients with psychosis and poorly controlled diabetes.

Methods: Stakeholder input was used to adapt a primary care-based collaborative care intervention for CMHC settings. Thirty-five adult CMHC clients with type II diabetes and hemoglobin A1c (HbA1c) >8% or blood pressure >140/90 were randomized to receive either collaborative care or usual care.

Cancer-induced anorexia and malaise are mediated by CGRP neurons in the parabrachial nucleus.

Anorexia is a common manifestation of chronic diseases, including cancer. Here we investigate the contribution to cancer anorexia made by calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) that transmit anorexic signals. We show that CGRP neurons are activated in mice implanted with Lewis lung carcinoma cells.

Perioperative Glycemic Control During Colorectal Surgery.

Hyperglycemia occurs frequently among patients undergoing colorectal surgery and is associated with increased risk of poor clinical outcomes, especially related to surgical site infections. Treating hyperglycemia has become a target of many enhanced recovery after surgery programs developed for colorectal procedures. There are several unique considerations for patients undergoing colorectal surgery including bowel preparations and alterations in oral intake.

Clinical management of comorbid diabetes and psychotic disorders.

Individuals with psychotic disorders experience substantial health disparities with respect to diabetes, including increased risk of incident diabetes and of poor diabetes outcomes (eg, diabetes complications and mortality). Low-quality medical care for diabetes is a significant contributor to these poor health outcomes. A thoughtful approach to both diabetes pharmacotherapy and drug management for psychotic disorders is essential, irrespective of whether treatment is given by a psychiatrist, a primary care provider, or an endocrinologist.

Point-of-care blood glucose measurement errors overestimate hypoglycaemia rates in critically ill patients.

Background: Hypoglycaemia is associated with morbidity and mortality in critically ill patients, and many hospitals have programmes to minimize hypoglycaemia rates. Recent studies have established the hypoglycaemic patient-day as a key metric and have published benchmark inpatient hypoglycaemia rates on the basis of point-of-care blood glucose data even though these values are prone to measurement errors.

Methods: A retrospective, cohort study including all patients admitted to Harborview Medical Center Intensive Care Units (ICUs) during 2010 and 2011 was conducted to evaluate a quality improvement programme to reduce inappropriate documentation of point-of-care blood glucose measurement errors.

Efficacy of diabetes nurse expert team program to improve nursing confidence and expertise in caring for hospitalized patients with diabetes mellitus.

Nursing care for hospitalized patients with diabetes has become more complex as evidence accumulates that inpatient glycemic control improves outcomes. Previous studies have highlighted challenges for educators in providing inpatient diabetes education to nurses. In this article, the authors show that a unit-based diabetes nurse expert team model, developed and led by a diabetes clinical nurse specialist, effectively increased nurses' confidence and expertise in inpatient diabetes care.

Evaluation of point-of-care blood glucose measurements in patients with diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome admitted to a critical care unit.

Background: Point-of-care (POC) blood glucose (BG) measurement is currently not recommended in the treatment of patients presenting with diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS).

Methods: We prospectively evaluated and compared capillary and venous POC BG values with laboratory venous glucose in patients with DKA or HHS admitted to one critical care unit over 8 months.

Results: Venous laboratory glucose was strongly correlated with venous (r = 0.

In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue.

Recent advances in human brown adipose tissue (BAT) imaging technology have renewed interest in the identification of BAT activators for the treatment of obesity and diabetes. In uncontrolled diabetes (uDM), activation of BAT is implicated in glucose lowering mediated by intracerebroventricular (icv) administration of leptin, which normalizes blood glucose levels in streptozotocin (STZ)-induced diabetic rats. The potent effect of icv leptin to increase BAT glucose uptake in STZ-diabetes is accompanied by the return of reduced plasma thyroxine (T4) levels and BAT uncoupling protein-1 (Ucp1) mRNA levels to nondiabetic controls.

BDNF action in the brain attenuates diabetic hyperglycemia via insulin-independent inhibition of hepatic glucose production.

Recent evidence suggests that central leptin administration fully normalizes hyperglycemia in a rodent model of uncontrolled insulin-deficient diabetes by reducing hepatic glucose production (HGP) and by increasing glucose uptake. The current studies were undertaken to determine whether brain-derived neurotrophic factor (BDNF) action in the brain lowers blood glucose in uncontrolled insulin-deficient diabetes and to investigate the mechanisms mediating this effect. Adult male rats implanted with cannulas to either the lateral cerebral ventricle or the ventromedial hypothalamic nucleus (VMN) received either vehicle or streptozotocin to induce uncontrolled insulin-deficient diabetes.

Lipopolysaccharide-induced lung injury is independent of serum vitamin D concentration.

Vitamin D deficiency is increasing in incidence around the world. Vitamin D, a fat-soluble vitamin, has documented effects on the innate and adaptive immune system, including macrophage and T regulatory (Treg) cell function. Since Treg cells are important in acute lung injury resolution, we hypothesized that vitamin D deficiency increases the severity of injury and delays injury resolution in lipopolysaccharide (LPS) induced acute lung injury.

Acutely decreased thermoregulatory energy expenditure or decreased activity energy expenditure both acutely reduce food intake in mice.

Despite the suggestion that reduced energy expenditure may be a key contributor to the obesity pandemic, few studies have tested whether acutely reduced energy expenditure is associated with a compensatory reduction in food intake. The homeostatic mechanisms that control food intake and energy expenditure remain controversial and are thought to act over days to weeks. We evaluated food intake in mice using two models of acutely decreased energy expenditure: 1) increasing ambient temperature to thermoneutrality in mice acclimated to standard laboratory temperature or 2) exercise cessation in mice accustomed to wheel running.

The impact of inpatient point-of-care blood glucose quality control testing.

Analyze the effectiveness of mandated point-of-care (POC) blood glucose (BG) meter quality control (QC) testing. All POC BG QC tests were analyzed to evaluate operator and strip/meter error rates and institutional cost. POC BG QC test failure (17/103,580 over 24 months) was low and no meters failed subsequent linearity testing.

Obesity is associated with hypothalamic injury in rodents and humans.

Rodent models of obesity induced by consuming high-fat diet (HFD) are characterized by inflammation both in peripheral tissues and in hypothalamic areas critical for energy homeostasis. Here we report that unlike inflammation in peripheral tissues, which develops as a consequence of obesity, hypothalamic inflammatory signaling was evident in both rats and mice within 1 to 3 days of HFD onset, prior to substantial weight gain. Furthermore, both reactive gliosis and markers suggestive of neuron injury were evident in the hypothalamic arcuate nucleus of rats and mice within the first week of HFD feeding.

Increased energy expenditure and leptin sensitivity account for low fat mass in myostatin-deficient mice.

Myostatin deficiency causes dramatically increased skeletal muscle mass and reduced fat mass. Previously, myostatin-deficient mice were reported to have unexpectedly low total energy expenditure (EE) after normalizing to body mass, and thus, a metabolic cause for low fat mass was discounted. To clarify how myostatin deficiency affects the control of body fat mass and energy balance, we compared rates of oxygen consumption, body composition, and food intake in young myostatin-deficient mice relative to wild-type (WT) and heterozygous (HET) controls.

Leptin activates a novel CNS mechanism for insulin-independent normalization of severe diabetic hyperglycemia.

The brain has emerged as a target for the insulin-sensitizing effects of several hormonal and nutrient-related signals. The current studies were undertaken to investigate mechanisms whereby leptin lowers circulating blood glucose levels independently of insulin. After extending previous evidence that leptin infusion directly into the lateral cerebral ventricle ameliorates hyperglycemia in rats with streptozotocin-induced uncontrolled diabetes mellitus, we showed that the underlying mechanism is independent of changes of food intake, urinary glucose excretion, or recovery of pancreatic β-cells.

Identification of a physiological role for leptin in the regulation of ambulatory activity and wheel running in mice.

Mechanisms regulating spontaneous physical activity remain poorly characterized despite evidence of influential genetic and acquired factors. We evaluated ambulatory activity and wheel running in leptin-deficient ob/ob mice and in wild-type mice rendered hypoleptinemic by fasting in both the presence and absence of subcutaneous leptin administration. In ob/ob mice, leptin treatment to plasma levels characteristic of wild-type mice acutely increased both ambulatory activity (by 4,000 ± 200 beam breaks/dark cycle, P < 0.

Leptin deficiency causes insulin resistance induced by uncontrolled diabetes.

Objective: Depletion of body fat stores during uncontrolled, insulin-deficient diabetes (uDM) results in markedly reduced plasma leptin levels. This study investigated the role of leptin deficiency in the genesis of severe insulin resistance and related metabolic and neuroendocrine derangements induced by uDM.

Research Design And Methods: Adult male Wistar rats remained nondiabetic or were injected with the beta-cell toxin, streptozotocin (STZ) to induce uDM and subsequently underwent subcutaneous implantation of an osmotic minipump containing either vehicle or leptin at a dose (150 microg/kg/day) designed to replace leptin at nondiabetic plasma levels.

Identification of body fat mass as a major determinant of metabolic rate in mice.

Objective: Analysis of energy expenditure (EE) in mice is essential to obesity research. Since EE varies with body mass, comparisons between lean and obese mice are confounded unless EE is normalized to account for body mass differences. We 1) assessed the validity of ratio-based EE normalization involving division of EE by either total body mass (TBM) or lean body mass (LBM), 2) compared the independent contributions of LBM and fat mass (FM) to EE, and 3) investigated whether leptin contributes to the link between FM and EE.

Central administration of interleukin-4 exacerbates hypothalamic inflammation and weight gain during high-fat feeding.

In peripheral tissues, the link between obesity and insulin resistance involves low-grade inflammation induced by macrophage activation and proinflammatory cytokine signaling. Since proinflammatory cytokines are also induced in the hypothalamus of animals placed on a high-fat (HF) diet and can inhibit neuronal signal transduction pathways required for normal energy homeostasis, hypothalamic inflammation is hypothesized to contribute to the pathogenesis of diet-induced obesity (DIO). We addressed this hypothesis by perturbing the inflammatory milieu of the hypothalamus in adult male Wistar rats using intracerebroventricular (icv) administration of interleukin-4 (IL-4), a Th2 cytokine that promotes alternative activation (M2) of macrophages and microglia.

Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids.

Hypothalamic inflammation induced by high-fat feeding causes insulin and leptin resistance and contributes to the pathogenesis of obesity. Since in vitro exposure to saturated fatty acids causes inflammation and insulin resistance in many cultured cell types, we determined how cultured hypothalamic neurons respond to this stimulus. Two murine hypothalamic neuronal cell cultures, N43/5 and GT1-7, were exposed to escalating concentrations of saturated fatty acids for up to 24 h.