Publications

Growth hormone (GH) is known to affect insulin and glucose metabolism.  Blocking its effects in acromegalic patients improves diabetes and glucose metabolism. We aimed to determine the effect of pegvisomant, a GH receptor antagonist, on insulin resistance, endogenous glucose production (EGP) and lipolysis in insulin resistant non-diabetic men.  Four men between the ages of 18-62 with a BMI of 18-35kg/m , with insulin resistance as defined by a HOMA-IR > 2.77, were treated for four weeks with pegvisomant 20 mg daily.  Inpatient metabolic assessments were performed before and after treatment. The main outcome measurements were: change after pegvisomant therapy in insulin sensitivity as measured by hyperinsulinemic euglycemic clamp; and EGP and lipolysis assessed by stable isotope tracer techniques. Insulin like growth factor-1 (IGF-1) concentrations decreased from 134.0 ± 41.5 (mean ± SD) to 72.0 ± 11.7 ng/mL (p = 0.04) after 4 weeks of therapy. Whole body insulin sensitivity index (M/I 3.2 ± 1.3 3.4 ± 2.4; = 0.82), as well as suppression of EGP (89.7 ± 26.9 83.5 ± 21.6%; p = 0.10) and Ra glycerol (59.4 ± 22.1% 61.2 ± 14.4%; p = 0.67) during the clamp were not changed significantly with pegvisomant treatment. Blockade of the GH receptor with pegvisomant for four weeks had no significant effect on insulin/glucose metabolism in a small phase II pilot study of non-diabetic insulin resistant participants without acromegaly.

OBJECTIVE

To evaluate the prevalence of frailty, a known predictor of poor outcomes, among patients presenting to an academic nononcologic urology practice and to examine whether frailty differs among patients who did and did not undergo urologic surgery.

METHODS

The Timed Up and Go Test (TUGT), a parsimonious measure of frailty, was administered to patients ages ≥65. The TUGT, demographic data, urologic diagnoses, and procedural history were abstracted from the medical record into a prospective database. TUGT times were categorized as nonfrail (≤10 seconds), prefrail (11-14 seconds), and frail (≥15 seconds). These times were evaluated across age and urologic diagnoses and compared between patients who did and did not undergo urologic surgery using chi-square and t tests.

RESULTS

The TUGT was recorded for 78.9% of patient visits from December 2015 to May 2016. For 1089 patients, average age was 73.3 ± 6.3 years; average TUGT time was 11.6 ± 6.0 seconds; 30.0% were categorized as prefrail and 15.2% as frail. TUGT times increased with age, with 56.9% of patients age 86 and over categorized as frail. Times varied across diagnoses (highest average TUGT was 14.3 ± 11.9 seconds for patients with urinary tract infections); however, no difference existed between patients who did and did not undergo surgery (P = .94).

CONCLUSION

Among our population, prefrailty and frailty were common, TUGT times increased with age and varied by urologic diagnosis, but did not differ between patients who did and did not undergo urologic surgery, presenting an opportunity to consider frailty in preoperative surgical decision making.

Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB. The workshop addressed early infection events, the impact of Mtb evolution on the development and maintenance of an adaptive immune response, and the factors that influence protection against and progression to active disease. Scientific gaps and areas of study to revitalize and accelerate TB vaccine design were discussed and prioritized. These included a comprehensive evaluation of innate and Mtb-specific adaptive immune responses in the lung at different stages of disease; determining the role of B cells and antibodies (Abs) during Mtb infection; development of better assays to measure Mtb burden following exposure, infection, during latency and after treatment, and approaches to improving current animal models to study Mtb immunogenicity, TB disease and transmission.