Cytomegalovirus (CMV) Reactivation and CMV-Specific Cell-Mediated Immunity After Chimeric Antigen Receptor T-Cell Therapy.

BACKGROUND: The epidemiology of cytomegalovirus (CMV) after chimeric antigen receptor-modified T-cell immunotherapy (CARTx) is poorly understood owing to a lack of routine surveillance. METHODS: We prospectively enrolled 72 adult CMV-seropositive CD19-, CD20-, or BCMA-targeted CARTx recipients and tested plasma samples for CMV before and weekly up to 12 weeks after CARTx. We assessed CMV-specific cell-mediated immunity (CMV-CMI) before and 2 and 4 weeks after CARTx, using an interferon γ release assay to quantify T-cell responses to IE-1 and pp65. We tested pre-CARTx samples to calculate a risk score for cytopenias and infection (CAR-HEMATOTOX). We used Cox regression to evaluate CMV risk factors and evaluated the predictive performance of CMV-CMI for CMV reactivation in receiver operator characteristic curves. RESULTS: CMV was detected in 1 patient (1.4%) before and in 18 (25%) after CARTx, for a cumulative incidence of 27% (95% confidence interval, 16.8-38.2). The median CMV viral load (interquartile range) was 127 (interquartile range, 61-276) IU/mL, with no end-organ disease observed; 5 patients received preemptive therapy based on clinical results. CMV-CMI values reached a nadir 2 weeks after infusion and recovered to baseline levels by week 4. In adjusted models, BCMA-CARTx (vs CD19/CD20) and corticosteroid use for >3 days were significantly associated with CMV reactivation, and possible associations were detected for lower week 2 CMV-CMI and more prior antitumor regimens. The cumulative incidence of CMV reactivation almost doubled when stratified by BCMA-CARTx target and use of corticosteroids for >3 days (46% and 49%, respectively). CONCLUSIONS: CMV testing could be considered between 2 and 6 weeks in high-risk CARTx recipients.

Melanic pigmentation and light preference within and between two Drosophila species.

Environmental adaptation and species divergence often involve suites of co-evolving traits. Pigmentation in insects presents a variable, adaptive, and well-characterized class of phenotypes for which correlations with multiple other traits have been demonstrated. In Drosophila, the pigmentation genes ebony and tan have pleiotropic effects on flies' response to light, creating the potential for correlated evolution of pigmentation and vision. Here, we investigate differences in light preference within and between two sister species, Drosophila americana and D. novamexicana, which differ in pigmentation in part because of evolution at ebony and tan and occupy environments that differ in many variables including solar radiation. We hypothesized that lighter pigmentation would be correlated with a greater preference for environmental light and tested this hypothesis using a habitat choice experiment. In a first set of experiments, using males of D. novamexicana line N14 and D. americana line A00, the light-bodied D. novamexicana was found slightly but significantly more often than D. americana in the light habitat. A second experiment, which included additional lines and females as well as males, failed to find any significant difference between D. novamexicana-N14 and D. americana-A00. Additionally, the other dark line of D. americana (A04) was found in the light habitat more often than the light-bodied D. novamexicana-N14, in contrast to our predictions. However, the lightest line of D. americana, A01, was found substantially and significantly more often in the light habitat than the two darker lines of D. americana, thus providing partial support for our hypothesis. Finally, across all four lines, females were found more often in the light habitat than their more darkly pigmented male counterparts. Additional replication is needed to corroborate these findings and evaluate conflicting results, with the consistent effect of sex within and between species providing an especially intriguing avenue for further research.

The utility of smartphone-based, ecological momentary assessment for depressive symptoms.

BACKGROUND: Major Depressive Disorder (MDD) is a common and debilitating mood disorder. Individuals with MDD are often misdiagnosed or diagnosed in an untimely manner, exacerbating existing functional impairments. Ecological momentary assessment (EMA) involves the repeated sampling of an individual's symptoms within their natural environment and has been demonstrated to assist in illness assessment and characterization. Capturing data in this way would set the stage for improved treatment outcomes and serve as a complementary resource in the management and treatment of depressive symptoms. METHODS: Online databases PubMed/MedLine and PsycINFO were searched using PRISMA guidelines and combinations of the following keywords: EMA, depression, smartphone app, diagnosing, symptoms, phone, app, ecological momentary assessment, momentary assessment, data mining, unobtrusive, passive data, GPS, sensor. RESULTS: A total of nineteen original articles were identified using our search parameters and ten articles met the inclusion criteria for full-text review. Among the ten relevant studies, three studies evaluated feasibility, seven evaluated detection, and three evaluated treatment of MDD. LIMITATIONS: Limitations include that the design of all of the studies included in this review are non-randomized. It should be noted that most of the studies included were pilot studies and/or exploratory trials lacking a control group. CONCLUSIONS: Available evidence suggests that the use of passive smartphone-based applications may lead to improved management of depressive symptoms. This review aids the creation of new EMA applications, highlights the potential of EMA usage in clinical settings and drug development, emphasizes the importance for regulation of applications in the mental health field, and provides insight into future directions.

The effect of intravenous, intranasal, and oral ketamine in mood disorders: A meta-analysis.

BACKGROUND: Ketamine is established as a rapid and effective treatment in adults with treatment-resistant depression (TRD). The availability of different formulations and routes of delivery invites the need for evaluating relative effect sizes. METHODS: Effect size with respect to depression symptom reduction for each formulation and route of delivery was compared at discrete time-points (i.e., 24 h, 2-6 days, 7-20 days, 21-28 days) in adults with TRD. A random-effects meta-analysis was conducted to evaluate the effect size across intravenous, intranasal and oral routes of administration. Analysis was also conducted evaluating the effect size of racemic ketamine to esketamine. RESULTS: The pooled effect size for intranasal ketamine/esketamine at 24 h was g = 1.247 (n = 5, 95% CI: 0.591-1.903, p < 0.01). At 2-6 days, the pooled effect size for intravenous ketamine/esketamine was g = 0.949 (n = 14, 95% CI: -0.308-2.206, p = 0.139). At 7-20 days, intranasal ketamine had a pooled effect size of g = 1.018 (n = 4, 95% CI: 0.499-1.538, p < 0.01). At 21-28 days, oral ketamine had a pooled effect size of g = 0.633 (n = 2, 95% CI: 0.368-0.898, p < 0.01). LIMITATIONS: Additional comparative studies are needed with regards to the efficacy of different formulations and routes of delivery. CONCLUSIONS: The short-term efficacy of intravenous and intranasal ketamine/esketamine for adults with TRD was established. Interpreting the efficacy of oral ketamine was limited by the need for studies with larger samples across independent sites. No conclusions regarding comparative efficacy of the disparate formulations and routes of delivery can be derived from this analysis. Direct comparative studies are needed to further inform treatment options for TRD.