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Aerobic exercise in type 1 diabetes (T1D) causes rapid increase in glucose utilization due to muscle work during exercise, followed by increased insulin sensitivity after exercise. Better understanding of these changes is necessary for models of exercise in T1D. Twenty-six individuals with T1D underwent three sessions at three insulin rates (100%, 150%, 300% of basal). After 3-h run-in, participants performed 45 min aerobic exercise (moderate or intense). We determined area under the curve for endogenous glucose production (AUCEGP) and rate of glucose disappearance (AUCRd) over 45 min from exercise start. A novel application of linear regression of Rd across the three insulin sessions allowed separation of insulin-mediated from non-insulin-mediated glucose uptake before, during, and after exercise. AUCRd increased 12.45 mmol/L (CI = 10.33-14.58, P less then 0.001) and 13.13 mmol/L (CI = 11.01-15.26, P less then 0.001) whereas AUCEGP increased 1.66 mmol/L (CI = 1.01-2.31, P less then 0.001) and 3.46 mmollinear regression method, over three insulin infusion sessions, to perform this separation and can graph these components before, during, and after exercise for the first time.Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide critical to the regulation of the stress response, including having a role in energy homeostasis. Mice lacking PACAP are cold-sensitive and have impaired adrenergic-induced thermogenesis. Interestingly, Pacap null mice can survive cold housing if acclimated slowly, similar to observations in uncoupling protein 1 (UCP1)-deficient mice. We hypothesized that Pacap null mice use alternate thermogenic pathways to compensate for impaired adaptive thermogenesis when acclimated to cold. Observations of behavior and assessment of fiber type in skeletal muscles did not show evidence of prolonged burst shivering or changes in oxidative metabolism in male or female Pacap-/- mice during cold acclimation compared with Pacap+/+ mice. Despite previous work that has established impaired capacity for adaptive thermogenesis in Pacap null mice, adaptive thermogenesis can be induced in mice lacking PACAP to support survival with cold housing. Interestingly, sex-specific morphological and molecular differences in adipose tissue remodeling were observed in Pacap null mice compared with controls. Thus, sexual dimorphisms are highlighted in adipose tissue remodeling and thermogenesis with cold acclimation in the absence of PACAP.NEW & NOTEWORTHY This manuscript adds to the literature of endocrine regulation of adaptive thermogenesis and energy balance. It specifically describes the role of pituitary adenylate cyclase-activating polypeptide on the regulation of brown adipose tissue via the sympathetic nervous system with a focus on compensatory mechanisms of thermogenesis. check details We highlight sex-specific differences in energy metabolism.
Bing-Neel syndrome (BNS) is a rare complication of of Waldenström macroglobulinemia (WM) identified by involvement of central nervous system (CNS) lymphoplasmacytic cells.
We present a patient who was diagnosed with Bing-Neel syndrome four years after the diagnosis of Waldenström macroglobulinemia.
The patient was admitted with neurological symptoms. There were lesions associated with WM involvement on brain imaging. The diagnosis was made by brain biopsy. High dose methotrexate treatment was given.
CNS infiltrating agents such as fludarabine, methotrexate and cytarabine are often used in BNS treatment. Ibrutinib, which is a new bruton tyrosine kinase inhibitor, has recently started to be used in BNS treatment, as it has been shown to be effective and penetrate the CNS.
CNS infiltrating agents such as fludarabine, methotrexate and cytarabine are often used in BNS treatment. Ibrutinib, which is a new bruton tyrosine kinase inhibitor, has recently started to be used in BNS treatment, as it has been shown to be effective and penetrate the CNS.
Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate indicated for the treatment of HER2-positive breast cancer. The 2012 American Society of Clinical Oncology guidelines on chemotherapy dosing in obesity recommend using full weight-based cytotoxic chemotherapy doses to treat obese patients with cancer. These guidelines were published prior to the advent of anticancer antibody-drug conjugates. There is a need to investigate the safety of T-DM1 in obese patients.
This retrospective chart review included adult patients with breast cancer receiving T-DM1. The primary endpoint was a composite of the incidence of T-DM1 treatment modifications secondary to an adverse event. Secondary outcomes included the incidence of dose reductions, dose delays, treatment discontinuations, and adverse events.
A total of 119 patients with HER2-positive breast cancer who received T-DM1 therapy were included in this study 44 obese patients and 75 non-obese patients. The composite outcome of treatment modifications due to toxicity was significantly higher in obese patients compared to non-obese patients (45% vs 25%, p = 0.024). Treatment delays were significantly higher in obese patients (36% vs 16%, p = 0.011). All-grade adverse events with a higher incidence in obese patients included left ventricular ejection fraction decrease (11% vs 5%), bilirubin increase (32% vs 12%), thrombocytopenia (61% vs 55%), and peripheral neuropathy (34% vs 27%).
This study suggests obese patients receiving T-DM1 may require more treatment modifications secondary to adverse events compared to non-obese patients. Larger studies are needed to determine if obese patients are at higher risk for specific T-DM1-induced adverse events.
This study suggests obese patients receiving T-DM1 may require more treatment modifications secondary to adverse events compared to non-obese patients. Larger studies are needed to determine if obese patients are at higher risk for specific T-DM1-induced adverse events.The aim of this paper was to assess the drug costs of the different biotechnologies (intranasal fentanyl spray (INFS), oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablet (FBT)) in the treatment of breakthrough cancer pain (BTCP). We have calculated the mean drug costs (expressed in euros (€)) for patients treated for BTCP. INFS resulted the less expensive towards OTFC and FBT, with 697 440 €versus (vs.) 809 552 €vs. 779 662 €every 100 patients treated for BTCP, respectively. In conclusion, combining drug costs of different biotechnologies (INFS, OTFC and FBT) with the measure of efficacy represented by the reduction of BTCP avoided (incremental cost-effectiveness ratio, ICER), INFS resulted in better cost-effectiveness.