Profiling of Skeletal Muscle and Adipose Tissue Depots in Men with Advanced Prostate Cancer Receiving Different Forms of Androgen Deprivation Therapy.

Background: Androgen deprivation therapy (ADT) is a common treatment modality for men with prostate cancer. Increases in adipose tissue mass and decreases in skeletal muscle mass are known on-target adverse effects of standard ADT. The effects of newer agents such as abiraterone acetate (ABI) and enzalutamide (ENZA) on body composition and how these compare with standard luteinizing hormone-releasing hormone agonists (aLHRHs) are unclear. Objective: To assess the effects of different forms of androgen deprivation therapy on body composition in men with prostate cancer. Design setting and participants: Using a retrospective design, 229 patients receiving aLHRHs alone (n = 120) or in combination with ABI (n = 53) or ENZA (n = 56) were studied. Outcome measurements and statistical analysis: Muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were assessed at baseline, 6 mo, and 18 mo after initiating therapy using a cross-sectional densitometry analysis performed on standard of care computed tomography images. Response trajectories for all treatment groups were calculated via a two-way analysis of variance post hoc test, for both within-group and between-group differences. Results and limitations: Treatment with aLHRHs, ABI, and ENZA was associated with a median muscle volume loss of -1.4%, -4.8%, and -5.5% at 6 mo, and -7.1%, -8.1%, and -8.3% at 18 mo, respectively. Therapy with aLHRHs was associated with minimal changes in VAT (0.3% at 6 mo and -0.1% at 18 mo). ABI therapy was associated with significant increases in VAT at 6 mo (4.9%) but not at 18 mo (0.5%), and ENZA therapy was associated with significant decreases in VAT (-4.6% at 6 mo and -5.4% at 18 mo). With respect to SAT, treatment with aLHRHs was associated with increases over time (8.6% at 6 mo and 4.7% at 18 mo), ABI was associated with decreases over time (-3.6% at 6 mo and -6.8% at 18 mo), and ENZA had no clear effects (1.7% at 6 mo and 3.3% at 18 mo). Conclusions: ADT regimens cause significant short-term losses in muscle mass, with the most rapid effects occurring with ABI and ENZA. The three regimens have disparate effects on SAT and VAT, suggesting distinct roles of androgens in these tissues. Patient summary: Androgen deprivation therapy alters body composition in men with prostate cancer. Abiraterone and enzalutamide are associated with losses in muscle mass compared with luteinizing hormone-releasing hormone agonists. These treatments impact subcutaneous and visceral fat mass, suggesting distinct roles of androgens in these tissues.

Treating Alpelisib-Induced Hyperglycemia with Very Low Carbohydrate Diets and Sodium-Glucose Co-Transporter 2 Inhibitors: A Case Series.

Alpelisib is a α-selective phosphatidylinositol 3-kinase (PI3K) inhibitor approved for treatment of postmenopausal women, and men, with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), PIK3CA-mutated, advanced breast cancer (ABC). Hyperglycemia is a common, on-target adverse effect that impairs treatment efficacy and increases the rate of treatment delays, dose reductions, and discontinuation. Currently, there are no clear guidelines on how to manage hyperglycemia due to alpelisib when metformin is not effective. In this case series, we review 3 subjects with ABC that developed hyperglycemia during alpelisib-fulvestrant therapy and were successfully managed with dietary and pharmacologic interventions. These cases provide anecdotal evidence to support the use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and very low carbohydrate diets to minimize hyperglycemia during alpelisib therapy.

Elemental and configural threat learning bias extinction generalization.

Emotional experiences often contain a multitude of details that may be represented in memory as individual elements or integrated into a single representation. How details associated with a negative emotional event are represented in memory can have important implications for extinction strategies designed to reduce emotional responses. For example, is extinguishing one cue associated with an aversive outcome sufficient to reduce learned behavior to other cues present at the time of learning that were not directly extinguished? Here, we used a between-subjects multi-day threat conditioning and extinction task to assess whether participants generalize extinction from one cue to unextinguished cues. On Day 1, one group of participants learned that a compound conditioned stimulus, composed of a tone and colored square, predicted an uncomfortable shock to the wrist (Compound group). A second group learned that the tone and square separately predicted shock (Separate group). On Day 2, participants in both groups were exposed to the tone in the absence of shocks (cue extinction). On Day 3, we tested whether extinction generalized from the extinguished to the unextinguished cue, as well as to a compound composed of both cues. Results showed that configural and elemental learning had unique and opposite effects on extinction generalization. Subjects who initially learned that a compound cue predicted shock successfully generalized extinction learning from the tone to the square, but exhibited threat relapse to the compound cue. In contrast, subjects who initially learned that each cue individually predicted shock did not generalize extinction learning from the tone to the square, but threat responses to the compound were low. These results highlight the importance of whether details of an aversive event are represented as integrated or separated memories, as these representations affect the success or limits of extinction generalization.