Diagnosis of Adrenocortical Carcinoma with Hypercortisolism in a Patient Presenting with Hypokalemic Metabolic Alkalosis.

Adrenocortical carcinoma (ACC) is a rare malignancy with an estimated annual incidence of 0.7-2 cases per million. Most patients present with steroid hormone excess or abdominal mass effects, but 15% of patients with ACC are diagnosed incidentally. A careful history, physical exam, and pertinent lab investigations are necessary to reach the diagnosis. Surgical resection is the cornerstone of treatment in localized ACC; however, systemic chemotherapy with mitotane is preferred in patients with widespread disease or those who are not ideal candidates for surgery.

Epigenetic chromatin conformation changes in peripheral blood can detect thyroid cancer.

BACKGROUND: Fine needle aspiration has been the traditional method for diagnosing thyroid cancer. Epigenetic chromatin conformation changes offer an alternative method of diagnosing cancer. The purpose of this study is to evaluate an EpiSwitch assay of epigenetic markers that can be used to diagnose thyroid cancer in blood samples. METHODS: From 2014 to 2016, adult patients with thyroid nodules having thyroidectomy were recruited and grouped based on benign, malignant, and atypia of undetermined significance or follicular lesions of undetermined significance fine needle aspiration cytology. Blood samples were collected before surgery. Final pathologic diagnosis was made from the thyroid specimens. Patients' blood samples were analyzed using the EpiSwitch assay, (Oxford Biodynamics, Oxford, UK), and the results were compared with surgical pathology to determine assay performance. RESULTS: In total, 58 patients were recruited: 20 benign, 20 malignant, and 18 atypia or follicular lesions of undetermined significance. An analysis of the malignant and benign fine needle aspiration groups found 6 epigenetic markers for thyroid. A total of 28 (48%) patients had thyroid cancer. The assay was able to correctly identify 25 of the 28 malignant nodules, showing sensitivity of 89.3% and specificity of 66.7%. The positive predictive value for the assay was 71.4%, whereas the negative predictive value was 87.0%. CONCLUSION: An epigenetic assay of peripheral blood shows high sensitivity in detecting thyroid cancer and provides an additional method for its diagnosis.

Long-term Outcomes After Pediatric Free Flap Reconstruction.

INTRODUCTION: Whereas free tissue transfer has evolved to minimize morbidity in adults, less is known about outcomes after free flaps in children. This study sought to assess short- and long-term outcomes after microvascular reconstruction in the pediatric population. METHODS: Short- and long-term outcomes of free tissue transfer were assessed using chart-review and quality-of-life surveys. The Pediatric Outcomes Data Collection Instrument was used to evaluate overall health, pain, and ability to participate in normal daily and more vigorous activities. Patient or parent responses were compared against normative data. RESULTS: Forty-two patients underwent 48 flap reconstructions at a mean age of 8 years. Median follow-up was 14.9 years. Indications included congenital nevi (n = 19, 42%), lymphatic/vascular malformations (n = 8, 19%), and trauma/burns (n = 6, 14%). There were 21 fasciocutaneous (44%), 19 muscle/myocutaneous (40%), 6 fascial/peritoneal (13%), and 2 osteocutaneous flaps (4%). Major flap complications were observed in 4 patients (9%), whereas major donor-site complications occurred in 2% (1 patient). Valid contact information was available for 25 patients; 16 of these completed surveys (64%). Pediatric Outcomes Data Collection Instrument scores for mobility (median, 52), sports/physical functioning (median, 56), happiness (median, 50), and pain/comfort (median, 56) were not significantly different from normative population score of 50. Similarly, median global functioning score was 99 (maximum, 100) and did not differ between flap types. DISCUSSION: Free tissue transfer in the pediatric population is reliable and well-tolerated over time. Surgeons should not hesitate to use free flaps when clinically indicated for pediatric patients.

A Case of Factitious Hyperglycemia in a Patient on Intravenous Ascorbic Acid.

Finger stick blood glucose meters are widely used in outpatient and inpatient settings. However, various factors can affect accuracy of readings from these meters. Here we present a patient who had spurious glucose elevation on these meters while being on intravenous ascorbic acid.

Antineutrophilic Cytoplasmic Antibody Positive Vasculitis Associated with Methimazole Use.

ANCA-associated vasculitis (AAV) is a rare and potentially life threatening complication associated with antithyroid drug use. It is more commonly reported with propylthiouracil, with fewer cases reported with methimazole use. We present the case of a 55-year-old man with toxic multinodular goiter which was treated with methimazole for 6 months. He developed ANCA positive leukocytoclastic vasculitis with hemorrhagic and necrotic bullous lesions of lower extremities. The vasculitis was initially thought to be secondary to recent cephalosporin use; however, the skin lesions progressed despite stopping the cephalosporin and treatment with steroids, and he developed osteomyelitis. His vasculitis resolved after cessation of methimazole use. This case highlights the importance of careful monitoring for variable manifestations of AAV in patients treated with methimazole.

R-Ras is required for murine dendritic cell maturation and CD4+ T-cell priming.

R-Ras is a member of the RAS superfamily of small GTP-binding proteins. The physiologic function of R-Ras has not been fully elucidated. We found that R-Ras is expressed by lymphoid and nonlymphoid tissues and drastically up-regulated when bone marrow progenitors are induced to differentiate into dendritic cells (DCs). To address the role of R-Ras in DC functions, we generated a R-Ras-deficient mouse strain. We found that tumors induced in Rras(-/-) mice formed with shorter latency and attained greater tumor volumes. This finding has prompted the investigation of a role for R-Ras in the immune system. Indeed, Rras(-/-) mice were impaired in their ability to prime allogeneic and antigen-specific T-cell responses. Rras(-/-) DCs expressed lower levels of surface MHC class II and CD86 in response to lipopolysaccharide compared with wild-type DCs. This was correlated with a reduced phosphorylation of p38 and Akt. Consistently, R-Ras-GTP level was increased within 10 minutes of lipopolysaccharide stimulation. Furthermore, Rras(-/-) DCs have attenuated capacity to spread on fibronectin and form stable immunologic synapses with T cells. Altogether, these findings provide the first demonstration of a role for R-Ras in cell-mediated immunity and further expand on the complexity of small G-protein signaling in DCs.

Atypical pituitary adenoma with malignant features.

Pituitary carcinoma is characterized by the presence of systemic or central nervous system metastases rather than malignant histological features, making it an anomaly amongst carcinomas. In contrast, aggressive or atypical pituitary adenomas often have a relatively bland histological appearance despite their malignant growth patterns. We now report a case of a 67-years-old male with a giant pituitary tumor with overt pathologic and phenotypic features of malignancy, but the absence of metastases, that evolved from a benign non-functioning gonadotroph macroadenoma treated 10 years earlier. This case represents the first report of a pituitary adenoma with overt malignant histology that does not meet criteria for classification as pituitary carcinoma, helping to complete the pathological spectrum of disease observed with pituitary tumors.

The neurosurvival factor Humanin inhibits beta-cell apoptosis via signal transducer and activator of transcription 3 activation and delays and ameliorates diabetes in nonobese diabetic mice.

Pancreatic beta-cell apoptosis is important in the pathogenesis and potential treatment of type 1 diabetes mellitus. We investigated whether Humanin, a recently described survival factor for neurons, could improve the survival of beta-cells and delay or treat diabetes in the nonobese diabetic (NOD) model. Humanin reduced apoptosis induced by serum starvation in NIT-1 cells and decreased apoptosis induced by cytokine treatment. Humanin induced signal transducer and activator of transcription 3 and extracellular signal-regulated kinase phosphorylation over a 24-hour time course. Specific inhibition of signal transducer and activator of transcription 3 resulted in nullifying the protective effect of Humanin. Humanin normalized glucose tolerance in NOD mice treated for 6 weeks, and their pancreata revealed decreased lymphocyte infiltration and severity. In addition, Humanin delayed/prevented the onset of diabetes in NOD mice treated for 20 weeks. In summary, Humanin treatment decreases cytokine-induced apoptosis in beta-cells in vitro and improved glucose tolerance and onset of diabetes in NOD mice in vivo. This indicates that Humanin may be useful for islet protection and survival in a spectrum of diabetes-related therapeutics.

National emergency response programs for dental health care professionals.

BACKGROUND: Members of the established public health systems and medical community must understand that, in medical surge events, members of the dental profession and other non-traditional disaster health care personnel are an additional source of assistance in response activities. METHODS: The authors relied on hands-on experience, expert consultations, literature reviews and Web searches to identify disaster response training programs appropriate for members of the dental profession and other health care personnel. RESULTS: The authors identified multiple governmental and professional disaster training programs. CONCLUSIONS: Five key national-level programs address the training and organization of health care professionals to support a large-scale disaster program. Because of their training and skills, dental professionals would be valuable additions to these programs and could make significant contributions if natural disasters and/or terrorist events were to occur.

Proposed educational objectives for hospital-based dentists during catastrophic events and disaster response.

The purpose of this project was to define education and training requirements for hospital-based dentists to efficiently and meaningfully participate in a hospital disaster response. Eight dental faculty with hospital-based training and/or military command and CBRNE (chemical, biological, radiological, nuclear, and explosive) expertise were recruited as an expert panel. A consensus set of recommended educational objectives for hospital-based dentists was established using the following process: 1) identify assumptions supported by all expert panelists, 2) determine current advanced dental educational training requirements, and 3) conduct additional training and literature review by various panelists and discussions with other content and systems experts. Using this three-step process, educational objectives that the development group believed necessary for hospital-based dentists to be effective in treatment or management roles in times of a catastrophic event were established. These educational objectives are categorized into five thematic areas: 1) disaster systems, 2) triage/medical assessment, 3) blast and burn injuries, 4) chemical agents, and 5) biological agents. Creation of training programs to help dentists acquire these educational objectives would benefit hospital-based dental training programs and strengthen hospital surge manpower needs. The proposed educational objectives are designed to stimulate discussion and debate among dental, medical, and public health professionals about the roles of dentists in meeting hospital surge manpower needs.

Insulin-like growth factor I (IGF-I) measurements in growth hormone (GH) therapy of idiopathic short stature (ISS).

Growth hormone (GH) therapy has evolved rapidly over the past decade. Ongoing research has demonstrated a clear role for therapeutic GH in a wide spectrum of pediatric disorders involving both poor growth and abnormal body composition. Although guidelines for GH dosing are not fully established, a series of key studies has delineated the range of dosages that are useful in the treatment of children with growth disorders. The recent approval of idiopathic short stature (ISS) as an indication for GH therapy presents further challenges in optimizing the care of GH-treated patients. ISS is now recognized as a diverse collection of environmental and molecular abnormalities, some of which involve the GH-IGF axis. Emerging data indicate that serum IGF-I measurements are not only useful in the diagnosis of growth abnormalities but, in conjunction with auxological measurements, are also a powerful tool for assessing GH efficacy. While it is clear that many ISS patients respond to GH, some individuals will not show a satisfactory response. Monitoring IGF-I levels and change in height SDS during treatment can assist the physician in distinguishing those patients in whom GH successfully and safely induces statural growth from those with partial or complete GH insensitivity who might benefit from modified GH treatment protocols or alternate therapies. In addition, serum IGF-I measurements are increasingly used as part of a rational monitoring strategy to ensure safety of GH dosing in light of cumulative data associating high IGF-I levels with potential malignancy risk, and low IGF-I levels with cardiovascular disease risk.

The role of insulin-like growth factor I monitoring in growth hormone-treated children.

Growth hormone (GH) therapy has evolved rapidly over the past decade, and continuing research has established a clear role for therapeutic GH in a wide spectrum of disorders, including idiopathic GH deficiency (childhood- and adult-onset), Turner syndrome, Prader-Willi syndrome, small-for-gestational age children with failure of catch-up growth, AIDS-related catabolism, children with chronic renal failure, and idiopathic short stature. Although GH is used therapeutically in a wide variety of conditions, actual guidelines regarding the logistics of GH dosing continue to evolve, with data emerging regarding efficacy and safety. This review proposes a role for insulin-like growth factor I measurement in optimizing GH dosing.