•The effects of hybrid fibers on the local bond performance were investigated.•Improvements in bond strength, slip and energy dissipation capacity were observed.•Empirical laws for monotonic and ...cyclic bond stress–slip relations were developed.
The performance of the bond between reinforcing bars and fiber reinforced concrete (FRC) plays an important role in determining the mechanical behavior of FRC structures when they are subjected to static or dynamic loadings. This paper presents an experimental study on the local bond performance of rebar embedded in steel-polypropylene hybrid fiber reinforced concrete (HFRC). A total of 102 specimens under monotonic and cyclic loading are investigated by means of pull-out tests. The main variables include fiber volume fraction and aspect ratio, concrete strength and stirrup confinement. The results show that the introduction of hybrid fibers had a synergetic effect on improving the bond performance in terms of peak bond strength and corresponding slip, resulting in a more ductile bond behavior. The improvement becomes more pronounced as the fibers content and concrete strength increase. With respect to the energy dissipation capacity, the hybrid fibers also exhibit a great influence. Specimens with higher fibers content always demonstrate a better energy dissipation capacity, while the opposite is true for increasing the aspect ratio of both fibers. Furthermore, two phenomenological models were proposed to predict the monotonic and cyclic bond behavior of well-confined HFRC specimens, in which the benefits of hybrid fibers were taken into account. The models, as well as involved equations, were verified by independent experimental results.
Children with acute lymphoblastic leukemia (ALL) undergoing chemotherapy experience a relatively high risk of infection. And the disturbance of gut microbiota is generally believed to impair ...intestinal barrier function and may induce bacterial infections and inflammation. The study aimed to investigate the alterations in the gut microbiota and assess its relationship with chemotherapy-induced pneumonia in pediatric ALL patients.
We conducted a case-control study with 14 cases affected by pneumonia and 44 unaffected subjects and characterized the physiological parameters and gut microbiota by microarray-based technique.
There were significant differences in α- and β-diversity in the affected group compared with the control group. At species level, the LEfSe analysis revealed that Enterococcus malodoratus, Ochrobactrum anthropi and Actinomyces cardiffensis were significantly abundant in the affected subjects. A receiver operating characteristic (ROC) curve yielded the area under the curve (AUC) of 0.773 for classification between the two groups. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in the bacterial secretion system were more enriched in the affected group than in the control group.
Gut microbiota alteration was associated with chemotherapy-induced pneumonia in pediatric ALL patients, which provided a new perspective on the personalized clinical care of pediatric ALL.
Multiparameter flow cytometry (MFC)-based minimal residual disease has been a poor predictor of prognosis in children with acute myeloid leukemia (AML). This study aimed to evaluate the incremental ...value of serial monitoring by droplet digital PCR (ddPCR) in forecasting the outcome of AML. Twenty-four children with AML were enrolled and the relapse-free survival (RFS) rate was estimated using the Kaplan–Meier method. Survival estimates were compared using the log-rank test. Survival analysis showed that the RFS rate in the ddPCR ≥ 0.1% group was significantly lower than that in the < 0.1% group (35.7% ± 19.8% vs. 83.6% ± 10.8%,
P
= 0.003). Moreover, serial monitoring by ddPCR showed that some mutations remained positive in some patients even though other co-mutations were eliminated, and those patients were more prone to relapse, with a significantly poorer RFS compared to patients negative for mutation (22.0% ± 19.2% vs 83.3% ± 11.3%,
P
= 0.001). Consequently, ddPCR may assist in prognostic forecasting for pediatric AML.
T-cell acute lymphoblastic leukemia (T-ALL) is a rare hematological malignancy with a poor prognosis. The present study aims to identify the precise risk grouping of children with T-ALL.
We analyzed ...the outcomes for 105 consecutive patients treated using the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005706) between 2015 and 2020 in our center. Nine out of 21 clinical and biological indicators were selected for the new scoring system based on the analysis in this study.
The 5-year overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) rates for the 105 patients were 83.1 ± 4.8%, 72.4 ± 5.6%, and 78.4 ± 3.6%, respectively. Based on the new scoring system, 90 evaluable children were regrouped into low-risk (n=22), intermediate-risk (n=50), and high-risk (n=18) groups. The 5-year survival (OS, EFS, and RFS) rates for all patients in the low-risk group were 100%, significantly higher than the rates for those in the intermediate-risk group (91.2 ± 5.2%, 74.4 ± 8.6%, and 82.5 ± 6.2%, respectively) and high-risk group (59.0 ± 13.2%, 51.9 ± 12.4%, and 51.9 ± 12.4%, respectively) (all P values < 0.01).
The CCCG-ALL-2015 program significantly improved the treatment outcomes for childhood T-ALL as compared with the CCCG-ALL-2008 protocol. Our new refined risk grouping system showed better stratification among pediatric T-ALL patients and better potential in evaluating therapeutic efficacy.
Non-Down’s syndrome acute megakaryocytic leukemia (non-DS-AMKL) is a subtype of childhood acute myeloid leukemia (AML), whose prognosis, prognostic factors and treatment recommendations have not yet ...to be defined in children. We conducted a retrospective study with 65 newly diagnosed non-DS-AMKL children from August 2003 to June 2020 to investigate the clinical impact of factors and clinical outcome. Among all 65 patients, 47 of them were treated at our center who received three different regimens due to time point of admission (CAMS-another, CAMS-2009 and CAMS-2016 protocol), and the efficacy were compared. Patients with newly diagnosed non-DS-AMKL accounted for 7.4% of pediatric AML cases. The median age of the patients was 18 months at diagnosis, and over 90% of them were under three-years-old. The overall survival (OS) rates were 33.3% ± 1.7%, 66.7% ± 24.4% and 74.2% ± 4.0% for three groups (CAMS-another, CAMS-2009 and CAMS-2016 regimen), respectively. In CAMS-2016 group, the complete remission (CR) rate after induction was 67.7% (21/31), while the total CR rate after all phases of chemotherapy was 80.6% (25/31). The 2-year survival probability did not significantly improve in patients underwent HSCT when compared with non-HSCT group (75.0% ± 4.7% vs. 73.9% ± 4.6%,
p
=0.680). Those who had a “dry tap” during BM aspiration at admission had significantly worse OS than those without “dry tap” (33.3% ± 8.6% vs. 84.0% ± 3.6%,
p=
0.006). Moreover, the results also revealed that patients with CD34+ had significantly lower OS (50.0% ± 6.7% vs. 89.5% ± 3.5%,
p=
0.021), whereas patients with CD36+ had significantly higher OS than those who were negative (85.0% ± 4.0% vs. 54.5% ± 6.6%,
p
=0.048). In conclusion, intensive chemotherapy resulted in improved prognosis of non-DS-AMKL children and subclassification may base on “dry tap” and immunophenotypic. Although some progress has been made, outcomes of non-DS-AMKL children remain unsatisfactory, especially in HSCT group, when compared with other AML types.
This study retrospectively analyzed the clinical outcome of 172 children with newly diagnosed severe aplastic anemia (SAA) between January 2008 and April 2018, who received rabbit antithymocyte ...globulin (ATG) and cyclosporine (CsA) as first-line treatment. The median age at diagnosis was 5 years (range, 1–14). The overall response rates were 22.7%, 45.3%, and 61% at 40 days, 3 months, and 6 months, respectively, after rabbit ATG. In multivariate analysis, mild disease severity was the only predictor of favorable response at 6 months (
P
= 0.006). In the present study, median follow-up period was 63 months (range, 1–135). The 5-year overall survival (OS) and failure-free survival (FFS) rates were 90.5% and 70.4%. Multivariate analysis showed that erythroid burst-forming units (BFU-E) > 2/10
5
bone marrow mononuclear cell (BMMNC) (
P
= 0.037) and time interval before IST ≤ 30 days (
P
= 0.017) were independent positive predictors for OS, meanwhile BFU-E > 2/10
5
BMMNC (
P
= 0.029) was the only favorable prognostic factor for FFS.
Variation in normal blood cells during chemotherapy has not been recognised as a risk factor guiding chemotherapy in childhood acute lymphoblastic leukaemia (ALL). This study aims to explore whether ...variations in normal haematopoiesis determine prognosis as well as to improve risk-stratified treatment in childhood ALL. A retrospective study of 279 cases of ALL treated with the CCCG-ALL-2015 regimen in the Division of Pediatric Blood Diseases Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from May 2015 to January 2017 was performed to analyse the prognostic impact of blood cell levels on day 19 of induction therapy by Kaplan-Meier method. Patients with childhood ALL with absolute neutrophil count (ANC) ≤ 90 cells/μl, absolute monocyte count (AMC) ≤ 10 cells/μl or absolute lymphocyte count (ALC) ≤ 1000 cells/μl on day 19 of induction therapy had a lower event-free survival (EFS) rate than those with higher values (all
P
< 0.05). Multivariate analysis confirmed that ANC ≤ 90 cells/μl and ALC ≤ 1000 cells/μl were independent adverse prognostic factors (HR = 1.981 and 2.162, respectively, both
P
< 0.05). Among patients with minimal residual disease (MRD) < 1% on day 19 of induction therapy, those with ANC ≤ 90 cells/μl had lower EFS than those with ANC > 90 cells/μl (70.8 ± 6.1% vs 86.4 ± 3.1%,
P
= 0.001). In the subgroup with the BCR/ABL1 fusion gene, patients with ANC ≤ 90 cells/μl on day 19 of induction therapy also had lower EFS than those with ANC > 90 cells/μl (34.4 ± 25.2% vs 25.0 ± 21.7%,
P
= 0.041). ANC and ALC during induction therapy are independent prognostic factors for childhood ALL. ANC contributes to guiding the prognosis of patients with low-level MRD or the BCR/ABL1 fusion gene.
The aim of the study was to validate the diagnostic role of circulating tumor DNA (ctDNA) in genetics aberration on the basis of next-generation sequencing (NGS) in pediatric acute myeloid leukemia ...(AML).
Bone marrow (BM) and peripheral blood (PB) were collected from 20 AML children at the time of initial diagnosis, and a ctDNA sample was isolated from PB. Detection of mutation was performed on ctDNA, BM, and peripheral blood mononuclear cell (PBMC) by NGS based on a 185-gene panel.
Among 185 genes sequenced by the NGS platform, a total of 82 abnormal genes were identified in 20 patients. Among them, 61 genes (74.39%) were detected in ctDNA, PBMC, and BM samples, while 11 (13.41%) genes were found only in ctDNA and 4 (4.88%) were detected only in the BM sample, and 2 (2.44%) were detected only in PBMC. A total of 239 mutations were detected in three samples, while 209 in ctDNA, 180 in bone marrow, and 184 in PBMC. One hundred sixty-four mutations in ctDNA were shared by matched BM samples, and the median variant allelic frequency (VAF) of these mutations was 41.34% (range, 0.55% to 99.96%) and 44.36% (range, 0.56% to 99.98%) in bone marrow and ctDNA. It was found that 65.79% (75/114) of mutations with clinical significance were detected in three samples, with 9 mutations detected both in ctDNA and BM, and 2 mutations detected both in PBMC and BM. The consistency of mutations with clinical significance between ctDNA and BM was 77.06% (84/109). Among the 84 mutations with clinical significance detected in both sources, the concordance of VAF assessment by both methods was high (R
= 0.895).
This study demonstrates that ctDNA was a reliable sample in pediatric AML and can be used for mutation detection. Consistency analysis showed that ctDNA can mirror the genomic information from BM. In addition, a subset of mutations was exclusively detected in ctDNA. These data support the fact that monitoring ctDNA with next-generation sequencing-based assays can provide more information about gene mutations to guide precision treatment in pediatric AML.
Juvenile myelomonocytic leukemia (JMML) is a disorder characterized by the simultaneous presence of myeloproliferative and myelodysplastic features, primarily affecting infants and young children. ...Due to the heterogeneous genetic background among patients, the current clinical and laboratory prognostic features are insufficient for accurately predicting outcomes. Thus, there is a pressing need to identify novel prognostic indicators. Red cell distribution width (RDW) is a critical parameter reflecting the variability in erythrocyte size. Recent studies have emphasized that elevated RDW serves as a valuable predictive marker for unfavorable outcomes across various diseases. However, the prognostic role of RDW in JMML remains unclear. Patients with JMML from our single-center cohort between January 2008 and December 2019 were included. Overall, 77 patients were eligible. Multivariate Cox proportional hazard models showed that patients with red cell distribution width coefficient of variation (RDW-CV) >17.35% at diagnosis were susceptible to much worse overall survival rate (hazard ratio HR = 5.22, confidence interval CI = 1.50-18.21,
= .010). Besides, the combination of RDW elevation and protein phosphatase non-receptor type 11 (PTPN11) mutation was likely to predict a subgroup with the worst outcomes in our cohort. RDW is an independent prognostic variable in JMML subjects. RDW may be regarded as an inexpensive biomarker to predict the clinical outcome in patients with JMML.