Hypothalamic connectivities predict individual differences in ADT-elicited changes in working memory and quality of life in prostate cancer patients.

Androgen deprivation therapy (ADT) has been associated with adverse effects on cognition. However, we currently lack understanding of the neurobiology and prognostic markers of these effects. Given that ADT acts via the hypothalamus-pituitary-gonadal axis, we assessed whether baseline hypothalamic resting state functional connectivity (rsFC) could predict changes in working memory and quality of life in prostate cancer patients following androgen deprivation. In a prospective observational study, 28 men with non-metastatic prostate cancer receiving ADT and 38 patients not receiving ADT (controls), matched in age, years of education and Montreal Cognitive Assessment score, participated in brain imaging at baseline, and N-back task and quality-of-life (QoL) assessments at baseline and at 6 months follow-up. Imaging data were processed with published routines and evaluated at a corrected threshold. ADT and control groups did not differ in N-back performance or QoL across time points. In ADT, the changes in 0-back correct response rate (follow-up-baseline) were correlated with baseline hypothalamus-precentral gyrus rsFC; the changes in 1-back correct response rate and reaction time were each correlated with hypothalamus-middle frontal gyrus and superior parietal lobule rsFC. The changes in physical well-being subscore of QoL were correlated with baseline hypothalamus-anterior cingulate and cuneus rsFC. The hypothalamus rsFCs predicted N-back and QoL change with an area under the receiver operating characteristic curve of 0.93 and 0.73, respectively. Baseline hypothalamus-frontoparietal and salience network rsFC's predict inter-subject variations in the changes in working-memory and QoL following 6 months of ADT. Whether and how hypothalamic rsFCs may predict the cognitive and QoL effects with longer-term ADT remain to be investigated.

The effects of androgen deprivation on working memory and quality of life in prostate cancer patients: The roles of hypothalamic connectivity.

BACKGROUND: Androgen deprivation therapy (ADT) has been associated with adverse effects on the brain. ADT alters testosterone levels via its action on the hypothalamus-pituitary-gonadal axis and may influence hypothalamic functions. Given the wide regional connectivity of the hypothalamus and its role in regulating cognition and behavior, we assessed the effects of ADT on hypothalamic resting state functional connectivity (rsFC) and their cognitive and clinical correlates. METHODS: In a prospective observational study, 22 men with nonmetastatic prostate cancer receiving ADT and 28 patients not receiving ADT (controls), matched in age, years of education, and Montreal Cognitive Assessment score, participated in N-back task and quality of life (QoL) assessments and brain imaging at baseline and at 6 months. Imaging data were processed with published routines and the results of a group by time flexible factorial analysis were evaluated at a corrected threshold. RESULTS: ADT and control groups did not differ in N-back performance or QoL across time points. Relative to controls, patients receiving ADT showed significantly higher hypothalamus-right mid-cingulate cortex (MCC) and precentral gyrus (PCG) rsFC during follow-up versus baseline. Further, the changes in MCC and PCG rsFC were correlated positively with the change in QoL score and 0-back correct response rate, respectively, in patients with undergoing ADT. CONCLUSION: Six-month ADT affects hypothalamic functional connectivity with brain regions critical to cognitive motor and affective functions. Elevated hypothalamic MCC and PCG connectivity likely serve to functionally compensate for the effects of ADT and sustain attention and overall QoL. The longer-term effects of ADT remain to be investigated.

Impact of Hematology Electronic Consultations on Utilization of Referrals and Patient Outcomes in an Integrated Health Care System.

INTRODUCTION: Electronic consultations (e-consults) may be a valuable tool in the current era of increased demand for hematologists. Despite the increasing use of e-consults in hematology, their optimal utilization and impact on patient outcomes and workload are largely unknown. METHODS: In this retrospective cohort study, we studied the hematology consult experience at Veterans Affairs Connecticut from 2006 to 2018. We included 7,664 hematology consults (3,240 e-consults and 4,424 face-to-face [FTF] consults) requested by 1,089 unique clinicians. RESULTS: We found that e-consults were rapidly adopted and used equally among physicians of different degrees of experience. The number of FTF consults did not decrease after the introduction of e-consult services. E-consults were preferentially used for milder laboratory abnormalities that had been less likely to result in a consult before their availability. Referring clinicians used e-consults preferentially for periprocedural management, anemia, leukopenia, and anticoagulation questions. Eighty-three percent of e-consults were resolved without needing an FTF visit in the year after the consult. Consults for pancytopenia, gammopathy, leukocytosis, and for patients with known malignancy were less likely to be resolved by e-consult. Among patients who were diagnosed with a new hematologic malignancy after their consult, having an e-consult before an FTF visit did not adversely affect survival. CONCLUSION: In summary, e-consults safely expanded delivery of hematology services in our health care system but increased total consult volume. We report novel data on what types of consults may be best suited to the electronic modality, the impact of e-consults on workload, and their optimal use and implementation.