CD11c Participates in Triggering Acute Graft-Versus-Host Disease During Bone Marrow Transplantation

CD11c is a canonical dendritic cell (DC) marker with poorly defined functions in the immune system. Here, we found that blocking CD11c on human peripheral blood mononuclear cell‐derived DCs (MoDCs) inhibited the proliferation of CD4+ T cells and the differentiation into IFN‐γ‐producing T helper 1 (Th1) cells, which were critical in acute graft‐versus‐host disease (aGVHD) pathogenesis. Using allogeneic bone marrow transplantation (allo‐BMT) murine models, we consistently found that CD11c‐deficient recipient mice had alleviated aGVHD symptoms for the decreased IFN‐γ‐expressing CD4+ Th1 cells and CD8+ T cells. Transcriptional analysis showed that CD11c participated in several immune regulation functions including maintaining antigen presentation of APCs. CD11c‐deficient bone marrow‐derived DCs (BMDCs) impaired the antigen presentation function in coculture assay. Mechanistically, CD11c interacted with MHCII and Hsp90 and participated in the phosphorylation of Akt and Erk1/2 in DCs after multiple inflammatory stimulations. Therefore, CD11c played crucial roles in triggering aGVHD and might serve as a potential target for the prevention and treatment of aGVHD

A comparative analysis of clinical outcomes in hematological patients afflicted with bacteremia attributable to carbapenem-resistant Klebsiella pneumoniae versus Escherichia coli

IntroductionCarbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSI) represent a frequent and grave complication among hematological patients, whose prevailing culprits are Carbapenem-Resistant Klebsiella pneumoniae (CRKP) and Escherichia coli bacteremia (EC). Nevertheless, there is a paucity of studies that have undertaken a comparative analysis of clinical outcomes in patients afflicted with CRKP and EC.MethodsThis study was conducted with the aim of identifying the microbiological and clinical characteristics of hematological patients suffering from bacteremia caused by CRKP and CREC.ResultsThe cohort included 90 patients with equal proportions of CRKP BSI and CREC BSI from 2017 to 2022. Among the tested CRE strains (n = 45) for carbapenemase (CP) genes, the KPC gene was most commonly found in CP-CRKP isolates (12/21), while the NDM gene predominated among CP-CREC strains (18/24). A comparison of drug susceptibility showed that CREC was significantly more susceptible to tigecycline than CRKP (97.73% vs. 64.86%, P = 0.018). Patients treated with tigecycline-based therapy had a higher survival rate in the CREC group (18/24,75%) compared to the CRKP group (8/14,57.1%). The CRKP group had a significantly lower rate of prior cephalosporin use within 30 days compared to the CREC group (27% vs. 49%, P = 0.03) and a higher incidence of multi-site infections before BSI (44% vs. 8.9%, P<0.001). Multivariate analysis showed that BSI caused by CRKP was an independent risk factor for survival (P = 0.029), while CAZ-AVI-based therapy emerged as an independent factor improving patient prognosis (P =0.013).ConclusionsOur results found that bacteremia instigated by CRKP was associated with a less favorable prognosis when compared to cases induced by CREC. Moreover, treatment regimens incorporating CAZ-AVI have the potential to enhance the prognosis of patients grappling with CRE BSI

Pseudomonas aeruginosa Detection Using Conventional PCR and Quantitative Real-Time PCR Based on Species-Specific Novel Gene Targets Identified by Pangenome Analysis

Mining novel specific molecular targets and establishing efficient identification methods are significant for detecting Pseudomonas aeruginosa, which can enable P. aeruginosa tracing in food and water. Pangenome analysis was used to analyze the whole genomic sequences of 2017 strains (including 1,000 P. aeruginosa strains and 1,017 other common foodborne pathogen strains) downloaded from gene databases to obtain novel species-specific genes, yielding a total of 11 such genes. Four novel target genes, UCBPP-PA14_00095, UCBPP-PA14_03237, UCBPP-PA14_04976, and UCBPP-PA14_03627, were selected for use, which had 100% coverage in the target strain and were not present in nontarget bacteria. PCR primers (PA1, PA2, PA3, and PA4) and qPCR primers (PA12, PA13, PA14, and PA15) were designed based on these target genes to establish detection methods. For the PCR primer set, the minimum detection limit for DNA was 65.4 fg/μl, which was observed for primer set PA2 of the UCBPP-PA14_03237 gene. The detection limit in pure culture without pre-enrichment was 105 colony-forming units (CFU)/ml for primer set PA1, 103 CFU/ml for primer set PA2, and 104 CFU/ml for primer set PA3 and primer set PA4. Then, qPCR standard curves were established based on the novel species-specific targets. The standard curves showed perfect linear correlations, with R2 values of 0.9901 for primer set PA12, 0.9915 for primer set PA13, 0.9924 for primer set PA14, and 0.9935 for primer set PA15. The minimum detection limit of the real-time PCR (qPCR) assay was 102 CFU/ml for pure cultures of P. aeruginosa. Compared with the endpoint PCR and traditional culture methods, the qPCR assay was more sensitive by one or two orders of magnitude. The feasibility of these methods was satisfactory in terms of sensitivity, specificity, and efficiency after evaluating 29 ready-to-eat vegetable samples and was almost consistent with that of the national standard detection method. The developed assays can be applied for rapid screening and detection of pathogenic P. aeruginosa, providing accurate results to inform effective monitoring measures in order to improve microbiological safety

Impact of platelet transfusion refractoriness in the first 30 days post-hematopoietic stem cell transplantation on outcomes of patients with myelodysplastic syndrome

IntroductionCurrently, no study has determined whether platelet transfusion refractoriness (PTR) post-hematopoietic stem cell transplantation (HSCT) before engraftment in patients with myelodysplastic syndrome (MDS) would impacts clinical outcomes.MethodsWe performed a MDS-specific retrospective analysis to determine whether PTR in one-month post-HSCT in patients with MDS could influence outcomes.Results and discussionAmong the 315 patients enrolled, 110 (34.9 %) had PTR from stem cell infusion to one-month post-HSCT. Baseline characteristics of the PTR and non-PTR groups were similar. We found that patients with PTR had a slower and lower rate of platelet engraftment by day 28, as well as a slower recovery of neutrophils. The median days of neutrophil and platelet engraftment were 14 days (9-23) and 17 days (8-28) in the PTR groups versus 13 days (9-23) and 15 days (7-28) in the non-PTR group (P<0.001). By day 28, 84 of 110 patients (76.4%) with PTR achieved platelet engraftment compared with 181 of 205 patients (88.3%) without PTR achieving platelet engraftment (P=0.007). In addition, patients in the PTR group received significantly more red blood cell (median, 17 units vs. 10 units, P<0.001) and platelet transfusions (median, 13 units vs. 7 units, P<0.001). However, the overall survival was similar between the two groups. PTR in one-month post-HSCT, haploidentical donor, and ferritin level>1041ng/ml (median level) were independent adverse factors of platelet engraftment