Effects of preprandial versus postprandial nutritional insulin administration in the inpatient setting.

AIMS: Hospitalized patients can have inconsistent nutritional intake due to acute illness, changing diet, or unpredictable meal delivery. The aim of this study was to evaluate whether implementation of a hospital-wide policy shifting nutritional insulin administration from pre-meal to post-meal was associated with changes in glycemic control or length of stay (LOS). METHODS: This retrospective study performed at a community hospital evaluated adult inpatients receiving nutritional insulin across three time periods. pre-intervention, immediate post-intervention, and distant post-intervention. Outcomes included rates of hypoglycemia (glucose ≤ 70 mg/dL), moderate hypoglycemia (< 54 mg/dL), severe hypoglycemia (≤ 40 mg/dL), severe hyperglycemia (≥ 300 mg/dL), daily mean glucose level, and LOS. RESULTS: The number of patient-days analyzed across the cohorts were 1948, 1751, and 3244, respectively. After multivariate adjustment, risk of developing any hypoglycemia and severe hypoglycemia significantly decreased over time (p = 0.001 and p = 0.009, respectively). Daily mean glucose increased over time (194.6 ± 62.5 vs 196.8 ± 65.5 vs 199.3 ± 61.5 mg/dL; p = 0.003), but there were no significant differences among rates of severe hyperglycemia (p = 0.10) or LOS (p = 0.74). CONCLUSIONS: Implementing a hospital-wide shift to postprandial nutritional insulin administration significantly reduced hypoglycemia rates without increasing severe hyperglycemia. This suggests a promising strategy for improving patient safety, but further prospective randomized controlled trials are warranted to confirm these findings.

Technical pitfalls when collecting, cryopreserving, thawing, and stimulating human T-cells.

The collection, cryopreservation, thawing, and culture of peripheral blood mononuclear cells (PBMCs) can profoundly influence T cell viability and immunogenicity. Gold-standard PBMC processing protocols have been developed by the Office of HIV/AIDS Network Coordination (HANC); however, these protocols are not universally observed. Herein, we have explored the current literature assessing how technical variation during PBMC processing can influence cellular viability and T cell immunogenicity, noting inconsistent findings between many of these studies. Amid the mounting concerns over scientific replicability, there is growing acknowledgement that improved methodological rigour and transparent reporting is required to facilitate independent reproducibility. This review highlights that in human T cell studies, this entails adopting stringent standardised operating procedures (SOPs) for PBMC processing. We specifically propose the use of HANC's Cross-Network PBMC Processing SOP, when collecting and cryopreserving PBMCs, and the HANC member network International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) PBMC Thawing SOP when thawing PBMCs. These stringent and detailed protocols include comprehensive reporting procedures to document unavoidable technical variations, such as delayed processing times. Additionally, we make further standardisation and reporting recommendations to minimise and document variability during this critical experimental period. This review provides a detailed overview of the challenges inherent to a procedure often considered routine, highlighting the importance of carefully considering each aspect of SOPs for PBMC collection, cryopreservation, thawing, and culture to ensure accurate interpretation and comparison between studies.

Engineering the Signal Resolution of a Paper-Based Cell-Free Glutamine Biosensor with Genetic Engineering, Metabolic Engineering, and Process Optimization.

Specialized cancer treatments have the potential to exploit glutamine dependence to increase patient survival rates. Glutamine diagnostics capable of tracking a patient's response to treatment would enable a personalized treatment dosage to optimize the tradeoff between treatment success and dangerous side effects. Current clinical glutamine testing requires sophisticated and expensive lab-based tests, which are not broadly available on a frequent, individualized basis. To address the need for a low-cost, portable glutamine diagnostic, this work engineers a cell-free glutamine biosensor to overcome assay background and signal-to-noise limitations evident in previously reported studies. The findings from this work culminate in the development of a shelf-stable, paper-based, colorimetric glutamine test with a high signal strength and a high signal-to-background ratio for dramatically improved signal resolution. While the engineered glutamine test is important progress towards improving the management of cancer and other health conditions, this work also expands the assay development field of the promising cell-free biosensing platform, which can facilitate the low-cost detection of a broad variety of target molecules with high clinical value.

The Role of Temperature, Wind Speed, and Precipitation on the Abundance of Culex Species and West Nile Virus Infection Rate in Rural West-Central Illinois.

While most research on West Nile virus (WNV) and its main vector, the Culex mosquito, has been conducted in laboratory or urban settings, studies with field-caught mosquitoes in rural areas, such as west-central Illinois, are lacking. The objective of this research was to investigate key abiotic factors using macroclimate data, including temperature, precipitation, and wind speed, to determine their influence on field-caught mosquito abundance in 4 rural counties in Illinois from 2014 to 2016. Additionally, the relationship between minimum infection rate (MIR) and thermal time was examined. Using gravid traps at 15 sites, Culex mosquitoes were collected twice a week. A total of 5,255 adult female Culex mosquitoes (Cx. pipiens, Cx. quinquefasciatus, and Cx. restuans) were collected in 2014; 9,138 in 2015; and 5,702 in 2016. Regression models were developed based on outcomes of relationships between field-caught mosquitoes and abiotic factors. Precipitation and thermal time had the most significant relationship with mosquito abundance (r2 = 0.993 and r2 = 0.993, respectively), while wind speed was less (r2 = 0.714). The greatest number of Culex and the highest annual MIR were observed in 2015, which was also the driest of the 3 sampling seasons. Mosquito abundance was observed to increase with warmer degree days and MIR was found to increase with abundance in mosquitoes. These models can be used for other mosquito surveillance and monitoring studies in various climate types and environments.

Long-term follow-up of VIALE-A: Venetoclax and azacitidine in chemotherapy-ineligible untreated acute myeloid leukemia.

Venetoclax-azacitidine is approved for treatment of patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy based on the interim overall survival (OS) analysis of the VIALE-A study (NCT02993523). Here, long-term follow-up is presented to address survival benefit and long-term outcomes with venetoclax-azacitidine. Patients with newly diagnosed AML who were ineligible for intensive chemotherapy were randomized 2:1 to receive venetoclax-azacitidine or placebo-azacitidine. OS was the primary endpoint; complete remission with/without blood count recovery (CR/CRi) was a key secondary endpoint. This final analysis was conducted when 100% of the predefined 360 OS events occurred. In VIALE-A, 431 patients were enrolled to venetoclax-azacitidine (n = 286) or placebo-azacitidine (n = 145). At 43.2 months median follow-up, median OS was 14.7 months (95% confidence interval [CI], 12.1-18.7) with venetoclax-azacitidine, and 9.6 months (95% CI, 7.4-12.7) with placebo-azacitidine (hazard ratio, 0.58 [95% CI, 0.47-0.72], p < .001); the estimated 24-month OS rate was 37.5% and 16.9%, respectively. Median OS for patients with IDH1/2 mutations and those with measurable residual disease responses was reached in this final analysis. CR/CRi rate was similar to interim analysis. Any-grade hematologic and gastrointestinal adverse events were most common in venetoclax-azacitidine and placebo-azacitidine arms, including thrombocytopenia (47% and 42%) and neutropenia (43% and 29%). No new safety signals were identified. Long-term efficacy and safety confirm venetoclax-azacitidine is an improvement in standard-of-care for patients with AML who are not eligible for intensive chemotherapy because of advanced age or comorbidities.

Long-Term Safety and Efficacy of Initial and Repeat Treatment Courses With Zuranolone in Adult Patients With Major Depressive Disorder: Interim Results From the Open-Label, Phase 3 SHORELINE Study.

Objective: Zuranolone is a positive allosteric modulator of both synaptic and extrasynaptic γ-aminobutyric acid (GABA) type A receptors and a neuroactive steroid approved in the United States as an oral, once-daily, 14-day treatment course for adults with postpartum depression and under investigation for adults with major depressive disorder (MDD). Interim results from the open-label, longitudinal, phase 3 SHORELINE Study (NCT03864614) that evaluated the long-term safety and efficacy of zuranolone in adults with MDD are reported.Methods: This interim report includes patients who were enrolled and had the opportunity to be on study for up to 1 year between February 2019 and September 2021. Adults aged 18-75 years with MDD diagnosed per DSM-5 criteria and a 17-item Hamilton Rating Scale for Depression (HAMD-17) total score ≥ 20 received an initial 30-mg or 50-mg 14-day zuranolone course. HAMD-17 responders (≥ 50% reduction from baseline) at Day (D)15 of the initial treatment period were allowed to continue in the study beyond D28 and were followed up for ≤ 1 year, during which repeat treatment courses were permitted. The primary endpoint was safety and tolerability of the initial and repeat treatment courses through 1 year. Secondary endpoints included change from baseline (CFB) in HAMD-17 total score and need for repeat treatment course(s).Results: As of September 2021, among patients in the 30-mg (n = 725) and 50-mg (n = 199) Cohorts who received a zuranolone dose, 493 (68.0%) and 137 (68.8%), respectively, reported a treatment-emergent adverse event (TEAE); most patients who experienced TEAEs reported mild/moderate events (30-mg Cohort, 90.9% [448/493]; 50-mg Cohort, 85.4% [117/137]). Mean (standard deviation) CFB HAMD-17 total score at D15 of the initial treatment period was -15.2 (7.1) and -16.0 (6.0) for the 30-mg and 50-mg Cohorts, respectively; similar improvements were observed after repeat treatment courses. The proportion of patients who received only 1 treatment course during their time on study was 42.9% (210/489) in the 30-mg Cohort and 54.8% (80/146) in the 50-mg Cohort; 57.1% (279/489) and 45.2% (66/146) patients, respectively, received 2-5 total treatment courses. The majority of patients who initially responded to zuranolone received ≤ 2 total treatment courses (30-mg Cohort, 68.5% [335/489]; 50-mg Cohort, 79.5% [116/146]).Conclusions: Of patients who experienced TEAEs, most reported mild or moderately severe events, and responders to zuranolone experienced improvements in depressive symptoms with initial and repeat treatment courses.Trial Registration: ClinicalTrials.gov identifier: NCT03864614.