1.
Nanopore-Targeted Sequencing Improves the Diagnosis and Treatment of Patients with Serious Infections
Zhang, Y., Lu, X., Tang, L. V., Xia, L., Hu, Y.
mBio. 2023;14(1):e0305522
Abstract
Serious infections are characterized by rapid progression, poor prognosis, and difficulty in diagnosis. Recently, a new technique known as nanopore-targeted sequencing (NTS) was developed that facilitates the rapid and accurate detection of pathogenic microorganisms and is extremely suitable for patients with serious infections. The aim of our study was to evaluate the clinical application of NTS in the diagnosis and treatment of patients with serious infections. We developed an NTS technology that could detect microorganisms within a 6-h window based on the amplification of the 16S rRNA gene of bacteria, the internal transcribed spacer region of fungi, and the rpoB gene of Mycobacterium. The NTS detection results were compared with those of blood cultures and anal swabs from 50 patients with blood diseases suffering serious infections. The patient's condition before and after NTS was compared. The response rate and the infection-related mortality after the adjustment of antibiotics based on NTS were calculated. The positivity rate of pathogens was highest in NTS (90%), followed by blood culture (32.6%) and anal swabs (14.6%). After adjusting antibiotics for bacteria and fungi detected by NTS, the patients' condition improved significantly. Moreover, the response rate of anti-infective treatment based on NTS was 93.02% (40/43), and infection-related mortality was reduced to 0. NTS is an effective method to identify pathogens in the blood specimens of patients with serious infections and can guide anti-infection treatment and reduce infection-related mortality. IMPORTANCE We introduce the application of NTS in blood samples of patients with serious infections and expound the efficiency and accuracy of NTS in detecting pathogenic microorganisms. Our work builds on the considerable interest of the scientific community in the management of serious infection. This issue is becoming more pressing, especially since the incidence of blood diseases is increasing year by year and hematopoietic stem cell transplantation (HSCT) has been widely used in benign and malignant blood diseases in recent years. The infection progression of these patients is faster, and the study further demonstrates the effectiveness of NTS in guiding the diagnosis and treatment of patients with severe infections. We firmly believe that this method will guide clinicians to adjust anti-infection strategies and bring significant benefits to patients, and our study will have implications for the future clinical application of NTS in all kinds of patients with serious infections.
2.
Influence of graft composition in patients with hematological malignancies undergoing ATG-based haploidentical stem cell transplantation
Zhang, R., Lu, X., Tang, L. V., Wang, H., Yan, H., You, Y., Zhong, Z., Shi, W., Xia, L.
Frontiers in immunology. 2022;13:993419
Abstract
To determine the influence of graft composition in haplo-HSCT, we summarized the long-term consequences of 251 consecutive transplantations from haploidentical donors. For donor-recipient HLA3/6-matched setting, 125 cases used G-CSF-mobilized BM and PBSCs mixtures, while 126 cases only used G-CSF-mobilized PBSCs in HLA4/6-matched transplantation. On the one hand, we wanted to explore the effect of harvests (CD34+ cells and TNCs dosages) on transplantation outcome in the context of haplo-HSCT no matter HLA4/6 or HLA3/6-matched setting. On the other hand, for patients using G-CSF-mobilized BM and PBSCs combination in HLA3/6-matched setting, we attempted to analyze whether TNCs or CD34+ cells from G-CSF-mobilized BM or G-CSF-mobilized PBSCs play the most paramount role on transplantation prognosis. Collectively, patients with hematologic malignancies receiving G-CSF-primed BM and PBSCs harvests had comparable consequences with patients only receiving G-CSF-mobilized PBSCs. Moreover, when divided all patients averagely according to the total amount of transfused nucleated cells, 3-year TRM of the intermediate group (13.06-18.05×10(8)/kg) was only 4.9%, which was remarkably reduced when compared to lower and higher groups with corresponding values 18.3%, 19.6% (P=0.026). The 3-year probabilities of OS and DFS of this intermediate group were 72.6% and 66.5%, which were slightly improved than the lower and higher groups. Most importantly, these data suggest that the transfused nucleated cells from G-CSF-primed BM above than 5.20×10(8)/kg could achieve remarkably lower TRM in haplo-HSCT receiving G-CSF-mobilized BM and PBSCs harvests. These encouraging results suggested that we could improve the efficacy of haplo-HSCT by adjusting the component and relative ratio of transfused graft cells. Nevertheless, the above findings should be confirmed in a randomized prospective comparative research with adequate follow-up.