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.
Lower dose of ATG combined with basiliximab for haploidentical hematopoietic stem cell transplantation is associated with effective control of GVHD and less CMV viremia
Huang, Z., Yan, H., Teng, Y., Shi, W., Xia, L.
Frontiers in immunology. 2022;13:1017850
Abstract
Currently, the graft-versus-host disease (GVHD) prophylaxis consists of an immunosuppressive therapy mainly based on antithymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy). GVHD remains a major complication and limitation to successful allogeneic haploidentical hematopoietic stem cell transplantation (haplo-HSCT). We modified the ATG-based GVHD prophylaxis with the addition of basiliximab in the setting of haplo-HSCT and attempted to explore the appropriate dosages. We conducted a retrospective analysis of 239 patients with intermediate- or high-risk hematologic malignancies who received haplo-HSCT with unmanipulated peripheral blood stem cells combined or not with bone marrow. All patients received the same GVHD prophylaxis consisting of the combination of methotrexate, cyclosporine or tacrolimus, mycofenolate-mofetil, and basiliximab with different doses of ATG (5-9mg/kg). With a median time of 11 days (range, 7-40 days), the rate of neutrophil engraftment was 96.65%. The 100-day cumulative incidences (CIs) of grade II-IV and III-IV aGVHD were 15.8 ± 2.5% and 5.0 ± 1.5%, while the 2-year CIs of total cGVHD and extensive cGVHD were 9.8 ± 2.2% and 4.1 ± 1.5%, respectively. The 3-year CIs of treatment-related mortality (TRM), relapse, overall survival (OS), and disease-free survival (DFS) were 14.6 ± 2.6%, 28.1 ± 3.4%, 60.9 ± 3.4%, 57.3 ± 3.4%, respectively. Furthermore, the impact of the reduction of the ATG dose to 6 mg/kg or less in combination with basiliximab on GVHD prevention and transplant outcomes among patients was analyzed. Compared to higher dose of ATG(>6mg/kg), lower dose of ATG (≤6mg/kg) was associated with a significant reduced risk of CMV viremia (52.38% vs 79.35%, P<0.001), while the incidences of aGVHD and cGVHD were similar between the two dose levels. No significant effect was found with regard to the risk of relapse, TRM, and OS. ATG combined with basiliximab could prevent GVHD efficiently and safely. The optimal scheme of using this combined regimen of ATG and basiliximab is that administration of lower dose ATG (≤6mg/kg), which seems to be more appropriate for balancing infection control and GVHD prophylaxis.