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Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable success as an immunotherapy for hematological malignancies, and its potential for treating solid tumors is an active area of research. However, limited trafficking and mobility of T cells within the tumor microenvironment (TME) present challenges for CAR T cell therapy in solid tumors. To gain a better understanding of CAR T cell function in solid tumors, we subjected CD70-specific CAR T cells to a challenge by evaluating their immune trafficking and infiltration through a confined 3D microchannel network in a bio-conjugated liquid-like solid (LLS) medium. Our results demonstrated successful CAR T cell migration and anti-tumor activity against CD70-expressing glioblastoma and osteosarcoma tumors. Through comprehensive analysis of cytokines and chemokines, combined with in situ imaging, we elucidated that immune recruitment occurred via chemotaxis, and the effector-to-target ratio plays an important role in overall antitumor function. Furthermore, through single-cell collection and transcriptomic profiling, we identified differential gene expression among the immune subpopulations. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach. STATEMENT OF SIGNIFICANCE: The use of specialized immune cells named CAR T cells to combat cancers has demonstrated remarkable success against blood cancers. However, this success is not replicated in solid tumors, such as brain or bone cancers, mainly due to the physical barriers of these solid tumors. Currently, preclinical technologies do not allow for reliable evaluation of tumor-immune cell interactions. To better study these specialized CAR T cells, we have developed an innovative in vitro three-dimensional model that promises to dissect the interactions between tumors and CAR T cells at the single-cell level. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the impact of clinical pharmacist-led interventions on the switch from intravenous (IV) to oral (PO) antibiotics among inpatients with infectious diseases., Methods: A before-and-after study was conducted among inpatients aged 18 or older who were diagnosed with infectious diseases and received IV antibiotics for at least 24 h at the Thong Nhat Hospital during the pre-intervention (between January 2021 and June 2021) and intervention (between January 2022 and June 2022) periods. Information on patient characteristics, antibiotic usage, length of hospital stay and treatment outcomes was obtained from medical records. The interventions included introducing IV-to-PO switch guidelines to physicians and clinical pharmacists' feedback on eligible cases. The impact of the pharmacists' interventions was evaluated by comparing primary outcomes (switch rate and appropriateness of switching) and secondary outcomes (duration of IV therapy, length of hospital stay and treatment outcomes) between the two study periods., Results: We included 99 patients in the pre-intervention and 80 patients in the intervention period. The proportion of patients who switched from IV-to-PO antibiotics increased from 44.4% in the pre-intervention period to 67.8% in the intervention period (p = 0.008). The overall rate of appropriate conversion increased significantly from 43.8% to 67.5% (p = 0.043). There were no statistically significant differences between the two periods with respect to the median duration of IV therapy (9 days vs. 8 days), length of hospital stay (10 days vs. 9 days) and treatment outcomes. Logistic regression analysis showed that the interventions resulted in a higher switch rate, whereas age was negatively associated with the switching rate., Conclusions: The implementation of clinical pharmacist-led interventions was effective in promoting IV-to-PO antibiotic conversion., (© 2023 John Wiley & Sons Ltd.)

Tumor invasion is likely driven by the product of intrinsic and extrinsic stresses, reduced intercellular adhesion, and reciprocal interactions between the cancer cells and the extracellular matrix (ECM). The ECM is a dynamic material system that is continuously evolving with the tumor microenvironment. Although it is widely reported that cancer cells degrade the ECM to create paths for migration using membrane-bound and soluble enzymes, other nonenzymatic mechanisms of invasion are less studied and not clearly understood. To explore tumor invasion that is independent of enzymatic degradation, we have created an open three-dimensional (3D) microchannel network using a novel bioconjugated liquid-like solid (LLS) medium to mimic both the tortuosity and the permeability of a loose capillary-like network. The LLS is made from an ensemble of soft granular microgels, which provides an accessible platform to investigate the 3D invasion of glioblastoma (GBM) tumor spheroids using in situ scanning confocal microscopy. The surface conjugation of the LLS microgels with type 1 collagen (COL1-LLS) enables cell adhesion and migration. In this model, invasive fronts of the GBM microtumor protruded into the proximal interstitial space and may have locally reorganized the surrounding COL1-LLS. Characterization of the invasive paths revealed a super-diffusive behavior of these fronts. Numerical simulations suggest that the interstitial space guided tumor invasion by restricting available paths, and this physical restriction is responsible for the super-diffusive behavior. This study also presents evidence that cancer cells utilize anchorage-dependent migration to explore their surroundings, and geometrical cues guide 3D tumor invasion along the accessible paths independent of proteolytic ability.

Objectives: We investigated the characteristics of prophylactic antimicrobial use in clean and clean-contaminated surgical procedures and assessed the efficacy of a prophylactic antimicrobial stewardship intervention at Thong Nhat Hospital, Ho Chi Minh City, Vietnam., Methods: A cross-sectional study was conducted on 354 patients who underwent either clean or clean-contaminated surgical procedures at Thong Nhat Hospital. Eligible patients were classified with respect to three periods of intervention from 2017 to 2020. Data collection included surgical procedures, patient characteristics, and prophylactic antimicrobial usage. We determined the efficacy of antimicrobial stewardship intervention based on comparisons among the primary outcome (the appropriateness of prophylactic antimicrobials) and secondary outcomes (postoperative antimicrobial prophylaxis (AP) prolongation, length of postoperative hospital stay, and cost of antimicrobials)., Results: The mean age of patients in periods 1, 2, and 3 was 54.5 ± 16.6, 50.2 ± 16.5, and 52.8 ± 17.3 years, respectively, with an overall male/female ratio of 1.1/1. No significant differences were detected in basic patient characteristics during the three periods. Majority of the surgical procedures were clean (56%-59%) and scheduled (85%-86%). Prophylactic antimicrobial stewardship intervention enhanced AP appropriateness (by 12.7%, 12.7%, and 39.0% in periods 1, 2, and 3, respectively, p < 0.001), decreased postoperative prophylactic antimicrobial duration [3.0 (0-6), 1.5 (0-5), and 0.0 (0-1) days, respectively, p < 0.001], and reduced average antimicrobial expenses (p < 0.001)., Conclusions: The prophylactic antimicrobial stewardship interventions introduced at Thong Nhat Hospital had several positive impacts on the appropriateness of prophylactic antimicrobial use and treatment costs., (© 2022 John Wiley & Sons Ltd.)

Objectives: End-stage renal disease (ESRD) is a chronic disease that can adversely affect the patient's quality of life (QoL) in terms of functional limitation and cognitive impairment. This study aimed to identify the factors associated with QoL in patients with ESRD undergoing dialysis at a national hospital in Vietnam., Methods: A descriptive cross-sectional study was conducted among outpatients aged ≥18 years who underwent haemodialysis (HD) or peritoneal dialysis (PD) for at least 3 months at Thong Nhat Hospital, Ho Chi Minh City, Vietnam from May 2020 to July 2021. QoL was measured using the validated Vietnamese version of the EuroQol-5 Dimensional-5 Level (EQ-5D-5L). The factors associated with the QoL of patients with ESRD undergoing dialysis were identified using multiple linear regression analysis., Results: In total, 131 (73.6%) and 47 (26.4%) patients underwent HD and PD, respectively. Overall, 178 (55.6%) patients were men (median age, 66 [56-79] years). The mean EQ-5D-5L score was significantly higher in patients undergoing PD than in those undergoing HD (0.848 ± 0.183 vs. 0.766 ± 0.231; p = 0.030). Older age (β = -0.006; p < 0.001) and peptic ulcer disease (β = -0.083; p = 0.029) were associated with lower QoL scores. PD treatment was associated with higher QoL scores (β = 0.065; p = 0.046)., Conclusions: It is necessary to improve the QoL of patients undergoing dialysis, especially of elderly patients and patients with peptic ulcer disease. PD may be a better method for maintenance dialysis, if applicable, in terms of QoL., (© 2021 John Wiley & Sons Ltd.)