Cardiac fibroblast paracrine factors modulate mouse embryonic stem cells.

The study aims to investigate the effects of cardiac fibroblast (CF) paracrine factors on murine embryonic stem cells (ESCs). Conditioned mediums from either neonatal cardiac fibroblasts (ConM-NCF) or adult cardiac fibroblasts (ConM-ACF) were diluted by 1:50 and 1:5, respectively, to investigate whether these conditioned mediums impact murine ESCs distinctly with RT-real time PCR techniques, cell proliferation essay, ELISA and by counting percentage of beating embryoid bodies (EBs) during ESCs differentiation. The data showed that the paracrine ability of CFs changed dramatically during development, in which interleukin 6 (IL6) increased with maturation. ConM-NCF 1:50 and ConM-NCF 1:5 had opposite effects on the pluripotent markers, although they both reduced mouse ESC proliferation. ConM-ACF 1:50 promoted ESCs pluripotent markers and proliferation, while ConM-ACF 1:5 exerted negative effects. All CF-derived conditioned mediums inhibited cardiac differentiation, but with distinguishable features: ConM-NCF 1:50 slightly decreased the early cardiac differentiation without altering the maturation tendency or cardiac specific markers in EBs at differentiation of day 17; ConM-ACF 1:50 had more significant inhibitory effects on early cardiac differentiation than ConM-NCF 1:50 and impeded cardiac maturation with upregulation of cardiac specific markers. In addition, IL6 neutralization antibody attenuated positive effect of ConM-ACF 1:50 on ESCs proliferation, but had no effects on ConM-NCF 1:50. Long-term IL6 neutralization reduced the percentage of beating EBs at early developmental stage, but did not alter the late cardiac differentiation. Taken together, both the quality and quantity of factors and cytokines secreted by CFs are critical for the ESC fate. IL6 could be a favorable cytokine for ESC pluripotency and the early cardiac differentiation.

Evaluation of the Diagnostic Performance of Plasma Metagenomic Next-Generation Sequencing in Febrile Events in the First 30 Days after Chimeric Antigen Receptor T Cell Infusion.

Chimeric antigen receptor-modified T cell (CAR-T) therapy is a promising novel immunotherapy for hematologic malignancies, and the diagnosis of infection after CAR-T infusion (CTI) presents challenges for clinicians. Plasma metagenomic next-generation sequencing (mNGS) has been shown to be a reliable diagnostic approach for infection, especially in immunocompromised patients. We aimed to investigate the diagnostic performance of plasma mNGS for infection in the first 30 days after CTI. A cohort of 153 patients who experienced a total of 170 febrile events during the first 30 days post-CTI were enrolled. Of these events, 51 were evaluated with both mNGS and CDM and 119 were assessed by conventional detection methods (CDM) only. We also explored the epidemiology of infections and differences in infection complications in cases with severe (>2) and moderate (≤2) cytokine release syndrome (CRS). Cases with febrile events were clinically divided into an infection group (IG) (95 of 170; 55.9%) and a noninfection group (NIG) (75 of 170; 44.1%). The sensitivity and specificity of mNGS for the diagnosis of infectious complications in the first 30 days after CTI were 69.2% and 89.2%, respectively, with the sensitivity superior to that of culture (P < .001). More infection cases assessed with both mNGS and CDM than those assessed with CDM only were laboratory-confirmed (63.9% versus 11.9%; P < .001). The serum C-reactive protein level was higher and the IFN-γ level was lower in the IG group, particularly in cases with CRS grade ≤2. Infection is a common complication in the first 30 days after CTI. The addition of mNGS to CDM improved the diagnostic yield, and mNGS showed relatively high sensitivity and specificity in post-CAR-T therapy febrile events.

Comparison of clinical outcomes between peripheral blood stem cells and peripheral blood stem cells plus bone marrow in myelodysplastic syndrome patients with haploidentical transplantation.

The comparison of haploidentical G-CSF-mobilized peripheral blood and bone marrow transplantation (HBMT) for patients with myelodysplastic syndrome (MDS) and haploidentical G-CSF-primed peripheral blood stem cell transplantation (HPBSCT) remains unclear. We performed a retrospective analysis using a propensity score method on 140 MDS patients who received HPBSCT (n = 46) or HBMT (n = 94) with BU/CY as a conditioning regimen prior to transplantation at our center between June 2016 and June 2021. HBMT recipients were associated with a reduced incidence of grade III-IV acute GVHD (17.22% vs. 30.57%, p = 0.019) within 100 days, reduced 2-year transplant-related mortality (TRM) (14.29% vs. 28.94%, p = 0.045) and superior 2-year overall survival (OS) (81.6% vs. 66.0%, p = 0.027), progression-free survival (PFS) (80.9% vs. 61.2%, p = 0.015), and GVHD relapse-free survival (GRFS) (64.6% vs. 53.3%, p = 0.062) compared with HPBSCT, but 2-year relapse incidence (RI) (5.96% vs. 9.39%, p = 0.445) was not affected. Multivariate analysis revealed that a GPB/GBM mixture was the independent factor for a reduced incidence of grade III-IV acute GVHD (p = 0.018) and TRM (p = 0.048), improved OS (p = 0.029), PFS (p = 0.019) and GRFS (p = 0.072). Collectively, the use of a GPB/GBM mixture as stem cell grafts for haplo-HSCT in patients with MDS appears to be an optimal choice.

The Clinical Value of Procalcitonin in the Neutropenic Period After Allogeneic Hematopoietic Stem Cell Transplantation.

The diagnostic value of procalcitonin and the prognostic role of PCT clearance remain unclear in neutropenic period after allogeneic hematopoietic stem cell transplantation introduction. This study evaluated 219 febrile neutropenic patients (116, retrospectively; 103, prospectively) who underwent allo-HSCT from April 2014 to March 2016. The area under the receiver operator characteristic curve (AUC) of PCT for detecting documented infection (DI) was 0.637, and that of bloodstream infection (BSI) was 0.811. In multivariate analysis, the inability to decrease PCT by more than 80% within 5-7 days after the onset of fever independently predicted poor 100-day survival following allo-HSCT (P = 0.036). Furthermore, the prognostic nomogram combining PCTc and clinical parameters showed a stable predictive performance, supported by the C-index of 0.808 and AUC of 0.813 in the primary cohort, and C-index of 0.691 and AUC of 0.697 in the validation cohort. This study demonstrated the diagnostic role of PCT in documented and bloodstream infection during the neutropenic period after allo-HSCT. PCTc might serve as a predictive indicator of post-HSCT 100-day mortality. A nomogram based on PCTc and several clinical factors effectively predicted the 100-day survival of febrile patients and may help physicians identify high-risk patients in the post-HSCT neutropenic period.