Abstract Background and Aims Despite prior studies on the clinical impact of COVID-19 and the documented efficacy of COVID-19 vaccinations in hemodialysis (HD) patients, the exact effects of COVID-19 vaccinations on various clinical biomarkers before and after the diagnosis of COVID-19 have not been established. In particular, the longitudinal trajectories of clinical and laboratory parameters remain unknown. We aim to investigate clinical and laboratory variables around the time of COVID-19 diagnosis and how vaccination impacts population trajectories. Method We studied 53,223 HD patients from Fresenius Kidney Care, a large U.S. dialysis organization, who received COVID-19 vaccination between January 1, 2021 and August 2, 2021. Depending on whether or not COVID-19 diagnosis happened after the first dose of vaccination for Johnson & Johnson or after the second dose for all other vaccines, we created two patient cohorts comprising patients infected before (N = 47,443) and after (N = 5780) full vaccination. A nonparametric cubic spline model for flexibility was fitted to the patient data averaged for each day between 60 days before and 60 days after the COVID-19 diagnosis. Clinical parameters include ones that are recorded at each HD treatment (pre-HD temperature, TEMP; pre-HD systolic blood pressure, SBP; pre-HD weight, WT; pre-HD pulse rate, PULSE; intradialytic weight gain, IDWG) and ones that are recorded less frequently (hemoglobin, HGB; white blood cell, WBC; neutrophil-lymphocyte ratio, NLR; platelet count, PLA; albumin, ALB). Results All longitudinal trajectory patterns undergo changes in the days before and after the diagnosis of COVID-19. In both the vaccinated and unvaccinated cohorts, there is an initial increase in TEMP, PULSE, and NLR up to 14 days preceding the diagnosis of COVID-19, followed by a subsequent decrease. Conversely, WT and IDWG exhibit a decline up to 14 days before the diagnosis of COVID-19 and an increase thereafter. ALB maintains a decreasing trend from 14 days prior until 20 days after before increasing again. In the unvaccinated cohort, SBP and WBC start decreasing up to 20 days ahead of diagnosis of COVID-19, whereas the unvaccinated cohort maintains a steady trend, increasing for SBP and decreasing for WBC. The lasting effects of COVID-19 can be found up to 60 days after diagnosis, e.g., WT, PULSE, and HGB. Variations in trend shapes are evident between the vaccinated and unvaccinated cohorts across all variables. Notably, all variables in the vaccinated cohort demonstrate smaller changes around the days of COVID-19 diagnosis. Conclusion We discovered trend changes in multiple variables in the days leading up to COVID-19 diagnosis, corroborating earlier findings. This finding lays the foundation for early detection ahead of regular COVID-19 tests. Prior COVID-19 vaccination mitigates the effect of COVID-19 on several important clinical and laboratory indicators, supporting the need for continued vaccination efforts. Lasting effects from infection are prevalent, extending beyond 60 days after confirmation. Further research is warranted to understand their long-term impact.
A 3D‐Bioprinted Vascularized Glioblastoma‐on‐a‐Chip for Studying the Impact of Simulated Microgravity as a Novel Pre‐Clinical Approach in Brain Tumor Therapy
AbstractGlioblastoma multiforme (GBM) is one of the most aggressive malignant brain tumors and urgently requires the development of new therapeutic strategies. In this study, an innovative hybrid in vitro vascularized GBM‐on‐a‐chip model is presented as a strategic integration of microfluidics and 3D bioprinting technologies. The system can recreate the compartmentalized brain tumor microenvironment, comprising the functional blood brain barrier (BBB) and the adjacent 3D perivascular tumor niche, by selectively mimicking physiological shear stress and cell–cell, cell–matrix mechanical interaction. The GBM‐on‐a‐chip model was evaluated under simulated microgravity (µG) condition as a form of mechanical unloading showing a significant cell morphological and mechanotransduction response thereby indicating that gravitational forces play an important role in glioblastoma mechanical regulation. The proposed GBM‐on‐a‐chip represents a meaningful biological tool for further research in cancer mechanobiology and pre‐clinical approach in brain tumor therapy.