Experience of 101 patients with coronavirus infectious disease 2019 (COVID-19) at a tertiary care center in Japan.

INTRODUCTION: Clusters of novel coronavirus infectious disease of 2019 (COVID-19) have spread to become a global pandemic imposing a significant burden on healthcare systems. The lack of an effective treatment and the emergence of varied and complicated clinical courses in certain populations have rendered treatment of patients hospitalized for COVID-19 difficult. METHODS: Tokyo Metropolitan Tama Medical Center, a public tertiary acute care center located in Tokyo, the epicenter of COVID-19 in Japan, has been admitting patients with COVID-19 since February 2020. The present, retrospective, case-series study aimed to investigate the clinical course and outcomes of patients with COVID-19 hospitalized at the study institution. RESULTS: In total, 101 patients with COVID-19 were admitted to our hospital to receive inpatient care. Eleven patients (10.9%) received ECMO, and nine patients (8.9%) died during hospitalization after COVID-19 was diagnosed. A history of smoking and obesity were most commonly encountered among patients with a complicated clinical course. Most patients who died requested to be transferred to advanced palliative care in the early course of their hospitalization. CONCLUSIONS: Our experience of caring for these patients demonstrated a relatively lower mortality rate and higher survival rate in those with extracorporeal membrane oxygenation placement than previous reports from other countries and underscored the importance of proactive, advanced care planning in the early course of hospitalization.

Barriers to Adherence to Antimicrobial Stewardship Postprescription Review and Feedback For Broad-Spectrum Antimicrobial Agents: A Nested Case-Control Study.

BACKGROUND: Postprescription review and feedback (PPRF) is one of the most common strategies in antimicrobial stewardship program (ASP) intervention. However, disagreements between the prescribers and ASP personnel can occur. The aim of the present study was to identify the factors associated with nonadherence to PPRF intervention. METHODS: The present retrospective nested case-control study was performed at a tertiary care center, which has been conducting a once-weekly PPRF for carbapenems and piperacillin/tazobactam since 2014. Nonadherence to ASP recommendations was defined as the failure of the primary care team to modify or stop antimicrobial therapy 72 hours after the issuance of PPRF recommendations. Factors associated with nonadherence to PPRF intervention were identified using multivariate logistic regression analysis. RESULTS: In total, 2466 instances of PPRF in 1714 cases between April 2014 and September 2019 were found. The nonadherence rate was 5.9%, and 44 cases were found in which carbapenems or piperacillin/tazobactam continued to be used against PPRF recommendations. Factors associated with nonadherence to PPRF recommendations were a previous history of hospitalization within 90 days (adjusted odds ratio [aOR], 2.62; 95% confidence interval [CI], 1.18-5.81) and a rapidly fatal McCabe score at the time of PPRF intervention (aOR, 2.87; 95% CI, 1.18-6.98). A review of the narrative comments in the electronic medical records indicated that common reasons for nonadherence were "the patient was sick" (n = 12; 27.3%) and "the antimicrobial seemed to be clinically effective" (n = 9; 20.5%). CONCLUSIONS: Nonadherence to PPRF recommendations was relatively uncommon at the study institution. However, patients with a severe disease condition frequently continued to receive broad-spectrum antimicrobials against PPRF recommendations. Understanding physicians' cognitive process in nonadherence to ASP recommendations and ASP interventions targeting medical subspecialties caring for severely ill patients is needed to improve ASP.

Pericytes as a Source of Osteogenic Cells in Bone Fracture Healing.

Pericytes are mesenchymal cells that surround the endothelial cells of small vessels in various organs. These cells express several markers, such as NG2, CD146, and PDGFRß, and play an important role in the stabilization and maturation of blood vessels. It was also recently revealed that like mesenchymal stem cells (MSCs), pericytes possess multilineage differentiation capacity, especially myogenic, adipogenic, and fibrogenic differentiation capacities. Although some previous studies have reported that pericytes also have osteogenic potential, the osteogenesis of pericytes can still be further elucidated. In the present study, we established novel methods for isolating and culturing primary murine pericytes. An immortalized pericyte line was also established. Multilineage induction of the pericyte line induced osteogenesis, adipogenesis, and chondrogenesis of the cells in vitro. In addition, pericytes that were injected into the fracture site of a bone fracture mouse model contributed to callus formation. Furthermore, in vivo pericyte-lineage-tracing studies demonstrated that endogenous pericytes also differentiate into osteoblasts and osteocytes and contribute to bone fracture healing as a cellular source of osteogenic cells. Pericytes can be a promising therapeutic candidate for treating bone fractures with a delayed union or nonunion as well as bone diseases causing bone defects.

Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A.

Bone metastatic lesions are classified as osteoblastic or osteolytic lesions. Prostate and breast cancer patients frequently exhibit osteoblastic-type and osteolytic-type bone metastasis, respectively. In metastatic lesions, tumor cells interact with many different cell types, including osteoblasts, osteoclasts, and mesenchymal stem cells, resulting in an osteoblastic or osteolytic phenotype. However, the mechanisms responsible for the modification of bone remodeling have not been fully elucidated. MicroRNAs (miRNAs) are transferred between cells via exosomes and serve as intercellular communication tools, and numerous studies have demonstrated that cancer-secreted miRNAs are capable of modifying the tumor microenvironment. Thus, cancer-secreted miRNAs can induce an osteoblastic or osteolytic phenotype in the bone metastatic microenvironment. In this study, we performed a comprehensive expression analysis of exosomal miRNAs secreted by several human cancer cell lines and identified eight types of human miRNAs that were highly expressed in exosomes from osteoblastic phenotype-inducing prostate cancer cell lines. One of these miRNAs, hsa-miR-940, significantly promoted the osteogenic differentiation of human mesenchymal stem cells in vitro by targeting ARHGAP1 and FAM134A Interestingly, although MDA-MB-231 breast cancer cells are commonly known as an osteolytic phenotype-inducing cancer cell line, the implantation of miR-940-overexpressing MDA-MB-231 cells induced extensive osteoblastic lesions in the resulting tumors by facilitating the osteogenic differentiation of host mesenchymal cells. Our results suggest that the phenotypes of bone metastases can be induced by miRNAs secreted by cancer cells in the bone microenvironment.