The role of AQP4 in the pathogenesis of depression, and possible related mechanisms.

Modulation of the aquaporin 4 (AQP4) water-regulatory channel or production of autoantibodies against this protein have been implicated in a variety of neuropsychiatric conditions, and possible mechanisms have been proposed. However, the nature of the interaction between AQP4 expression and its implications in depression remain elusive. To our knowledge, this is the first review summarising data for the involvement of AQP4 in the context of depression and related mechanisms across a wide range of experimental studies: pre-clinical (KO and wild-type), post-mortem, ex vivo, and clinical studies in depression. Overall, preclinical AQP4 wild-type studies showed that exposure to stress or inflammation, used as models of depression, decreased AQP4 protein and gene expression in various brain regions, including prefrontal cortex (PFC), choroid plexus and, especially, hippocampus. In preclinical AQP4 KO studies, AQP4 expression is necessary to prevent the effect of stress and inflammation on reduced neurogenesis and gliogenesis, and increased apoptosis and depressive-like behaviours. While in post-mortem and ex vivo studies of depression AQP4 expression was usually decreased in the hippocampus, prefrontal cortex and locus coeruleus, in clinical studies, where mRNA AQP4 expression or serum AQP4 autoantibodies were measured, there were no differences in depressed patients when compared with controls. In the future, studies should further investigate the mechanisms underlying the action of AQP4, and continue exploring if AQP4 autoantibodies are either contributing or underlying mechanisms of depression, or whether they are simply a mechanism underlying other autoimmune conditions where depression is present.

Quality of life, anxiety and depression patient-reported outcome measures in testicular cancer: A systematic review.

OBJECTIVES: Several patient-reported outcome measures (PROMs) are available for the assessment of quality of life (QoL), anxiety and depression for testicular cancer (TCa); however, these PROMs have uncertain validation of their psychometric properties for TCa-only cohorts. This systematic review aims to critically analyse and evaluate the psychometric properties of these QoL, anxiety and depression PROMs. METHODS: PubMed, EMBASE and PsycInfo were searched by two independent reviewers from inception to August 2020. Evaluative studies that assessed measurement properties of PROM(s) tools used for measuring QoL, anxiety and depression in TCa patients were included. The COnsensus-based Standards for the selection of health status Measurement Instruments (COSMIN) updated criteria for good measurement properties were used in the evaluation of PROM psychometric quality. This systematic review was registered on the PROSPERO database (CRD42020160232). RESULTS: Of 4,305 abstracts screened, a final eight full-text articles were included in this review. Five general and two TCa-specific PROMs were identified (depression, n = 1; anxiety and depression, n = 2; QoL, n = 4). All studies were incomplete in the validation of nine measurement properties and the modal methodological quality was 'indeterminate'. The European Organisation for Research and Treatment of Cancer Quality -Testicular Cancer 26 questionnaire and CAYA-T had the highest psychometric validation with three out of nine measurement properties being 'sufficient'. CONCLUSION: This systematic review identifies a paucity of PROM-validation studies assessing anxiety, depression and QoL in TCa-only cohorts. We recommend further comprehensive and standardised psychometric validation studies of QoL, anxiety and depression PROMs in TCa-only study populations.

Frailty as a Predictor of Postoperative Morbidity and Mortality in Patients Aged 80 Years and Older Undergoing Instrumented Fusion.

BACKGROUND AND OBJECTIVES: Degenerative spine disease is a leading cause of disability, with increasing prevalence in the older patients. While age has been identified as an independent predictor of outcomes, its predictive value is limited for similar older patients. Here, we aimed to determine the most predictive frailty score of adverse events in patients aged 80 and older undergoing instrumented lumbar fusion. METHODS: We proceeded with a multisite (3 tertiary academic centers) retrospective review including patients undergoing instrumented fusion aged 80 and older from January 2010 to present. A composite end point encompassing 30-day return to operating room, readmission, and mortality was created. We estimated the area under the receiver operating characteristic curve for frailty scores (Modified Frailty Index-5 [MFI-5], Modified Frailty Index-11 [MFI-11], and Charlson Comorbidity Index [CCI]) in relation to that composite score. In addition, we estimated the association between each score and the composite end point by means of logistic regression. RESULTS: A total of 153 patients with an average age of 85 years at the time of surgery were included. We observed a 30-day readmission rate of 11.1%, reoperation of 3.9%, and mortality of 0.6%. The overall rate of the composite end point at 30 days was 25 (15.1%). The AUC for MFI-5 was 0.597 (0.501-0.693), for MFI-11 was 0.620 (0.518-0.723), and for CCI was 0.564 (0.453-0.675). The association between the scores and composite end point did not reach statistical significance for MFI-5 (odds ratio [OR] = 1.45 [0.98-2.15], P = .061) and CCI (OR = 1.13 [0.97-1.31], P = .113) but was statistically significant for MFI-11 (OR = 1.46 [1.07-2.00], P = .018). CONCLUSION: This is the largest study comparing frailty index scores in octogenarians undergoing instrumented lumbar fusion. Our findings suggest that while MFI-11 score correlated with adverse events, the predictive ability of existing scores remains limited, highlighting the need for better approaches to identify select patients at age extremes.