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Re-induction with modified CLAG regimen in relapsed or refractory acute myeloid leukemia in children bridging to allogeneic hematopoietic stem cell transplantation
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Na Zhang, Jing-Bo Shao, Hong Li, Jing-Wei Yang, Kai Chen, Jia-Shi Zhu, Hui Jiang |
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Background: The prognosis for relapsed or refractory acute myeloid leukemia (RR-AML) in children is poor, and the preferred salvage chemotherapy is unclear. One regimen is cladribine, cytarabine, and granulocyte-colony stimulating factor (CLAG), but little is known about its efficacy and safety in children with RR-AML.
Methods: We enrolled RR-AML patients aged 0-18 years who received modified CLAG regimen for re-induction between July 1, 2015 and April 1, 2018, or conventional induction between August 1, 2011 and April 1, 2018. Patients were followed up to March 31, 2019. Patients underwent allogeneic stem cell transplantation (allo-SCT) or chemotherapy after the induction of complete remission (CR). The CR rate, survival, and side effects were analyzed.
Results: The CR rate for induction was 66.7% after one cycle and 75.0% after two cycles of the CLAG regimen in 12 children. The nine children who received conventional chemotherapy had a CR rate of 22.2% after one cycle and 33.3% after two cycles (P = 0.087 vs. CLAG). The 3-year event-free survival (EFS) of the CLAG group and the conventional treatment group were 44.4 ¡À 15.7% and 22.2 ¡À 13.8% (P = 0.112). The 3-year overall survival of the two groups were 59.5 ¡À 16.2% and 22.2% ¡À 13.8% (P = 0.057). The 3-year EFS for allo-SCT and chemotherapy after CLAG regimen was 66.7 ¡À 19.2% and 25.0 ¡À 21.7% (P = 0.015). A single case of chemotherapy-related death was recorded. Conclusion: Our data suggest a promising CR rate using CLAG salvage treatment in childhood RR-AML. Allo-SCT after CR may improve the long-term outcome in these patients. |
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[Abstract] [Full Text] [PDF]
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Efficacy and safety of tacrolimus and low-dose prednisone in Chinese children with steroid-resistant nephrotic syndrome
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Hai-Xia Chen, Qia Cheng, Fang Li, Qing-Nan He, Yan Cao, Zhu-Wen Yi, Xiao-Chuan Wu |
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Background: Tacrolimus, a calcineurin inhibitor, is recommended by the recent guidelines from the Kidney Disease Improving Global Outcomes Group as the first-line treatment for steroid-resistant nephrotic syndrome (SRNS), but its clinical application in China is still limited. We investigated the efficacy and safety of tacrolimus combined with low-dose corticosteroids in a population of Chinese children with SRNS.
Methods: In this prospective non-randomized, non-controlled study, Chinese children with SRNS who failed the previous full-dose prednisone treatment were given tacrolimus (0.1 mg/kg/day) and low-dose prednisone (0.25-0.50 mg/kg/day). We compared the overall remission rate (ORR) and adverse events in the follow-up period with this therapeutic regimen.
Results: A total of 76 children were enrolled into the study with an average follow-up period of 18 ¡À 6 months (maximum 36 months). ORR achieved by the first, third, and sixth months was 94.7%, 94.7%, and 96.0%, respectively. All patients who attained an initial tacrolimus trough concentration (FK506C 0 ) > 6 ng/mL (60.3%) achieved remission. The relative risk of relapse at FK506C 0 < 3 ng/mL compared to 3-6 ng/mL, 6-9 ng/mL, and 9-12 ng/mL was 2.3, 3.2, and 16.9, respectively. During the follow-up period, adverse effects that had been previously reported were rare. Conclusions: Combination of tacrolimus and low-dose prednisone was safe and effective for the treatment of children with SRNS, with high remission rates observed as early as the fi rst month. Relapses were infrequent, but tended to increase significantly with decreases in FK506C0. |
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[Abstract] [Full Text] [PDF]
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Intestinal microbiome analysis demonstrates azithromycin
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Elpiniki Nikolaou, Elena Kamilari, Dragana Savkov, Artemy Sergeev, Irina Zakharova, Paris Vogazianos, Marios Tomazou, Athos Antoniades, Christos Shammas |
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Background: Next-generation sequencing has revolutionized our perspective on the gut microbiome composition, revealing the true extent of the adverse effects of antibiotics. The impact of antibiotic treatment on gut microbiota must be considered and researched to provide grounds for establishing new treatment strategies that are less devastating on commensal bacteria. This study investigates the impact on gut microbiome when a commonly used antibiotic, azithromycin is administered, as well as uncovers the benefits induced when it is used in combination with lactulose, a prebiotic known to enhance the proliferation of commensal microbes.
Methods: 16S rRNA gene sequencing analysis of stool samples obtained from 87 children treated with azithromycin in combination with or without lactulose have been determined. Children¡¯s gut microbial profile was established at the pre- and post-treatment stage.
Results: Azithromycin caused an increase in the relative abundance of opportunistic pathogens such as Streptococcus that was evident 60 days after treatment. While few days after treatment, children who also received lactulose started to show a higher relative abundance of saccharolytic bacteria such as Lactobacillus, Enterococcus, Anaerostipes, Blautia and Roseburia, providing a protective role against opportunistic pathogens. In addition, azithromycin-prebiotic combination was able to provide a phylogenetic profile more similar to the pre-treatment stage. Conclusion: It is suggested that during azithromycin treatment, lactulose is able to reinstate the microbiome equilibrium much faster as it promotes saccharolytic microbes and provides a homeostatic effect that minimizes the opportunistic pathogen colonization. |
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[Abstract] [Full Text] [PDF]
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Fever of unknown origin: a retrospective review of pediatric patients from an urban, tertiary care center in Washington, DC
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Ann Marie Szymanski, Hugo Clifford, Tova Ronis |
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Background: Fever of unknown origin (FUO) continues to challenge clinicians to determine an etiology and the need for treatment. This study explored the most common etiologies, characteristics, and average cost of hospitalization for FUO in a pediatric population at an urban, tertiary care hospital in Washington, DC.
Methods: Records from patients admitted to Children¡¯s National Health System between September 2008 and April 2014 with an admission ICD-9 code for fever (780.6) were reviewed. The charts of patients 2-18 years of age with no underlying diagnosis and a temperature greater than 38.3 oC for 7 days or more at time of hospitalization were included. Final diagnoses, features of admission, and total hospital charges were abstracted.
Results: 110 patients qualified for this study. The majority of patients (n = 42, 38.2%) were discharged without a diagnosis. This was followed closely by infection, accounting for 37.2% (n = 41) of patients. Rheumatologic disease was next (n = 16, 14.5%), followed by miscellaneous (n = 6, 5.4%) and oncologic diagnoses (n = 5, 4.5%). The average cost of hospitalization was 40,295 US dollars. Conclusions: This study aligns with some of the most recent publications which report undiagnosed cases as the most common outcome in patients hospitalized with FUO. Understanding that, often no diagnosis is found may reassure patients, families, and clinicians. The cost associated with hospitalization for FUO may cause clinicians to reconsider inpatient admission for diagnostic work-up of fever, particularly given the evidence demonstrating that many patients are discharged without a diagnosis. |
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[Abstract] [Full Text] [PDF]
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Clinical characteristics, molecular epidemiology and antimicrobial susceptibility of pertussis among children in southern China
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Jiao-Sheng Zhang, Hong-Mei Wang, Kai-Hu Yao, Ying Liu, Yan-Ling Lei, Ji-Kui Deng, Yong-Hong Yang |
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Background: Increasing numbers of pertussis cases have been reported in recent years. The reported cases from Shenzhen Children¡¯s Hospital were close to one tenth of all cases in China. The epidemiology of antigenic genotype and antibiotic resistance of circulating strains in children have been unknown in Shenzhen, southern China. The aim of this study was to describe the clinical features and explore the genotypes and antimicrobial susceptibility of circulating Bordetella pertussis among children in Shenzhen.
Methods: Data of hospitalized children with pertussis in Shenzhen Children¡¯s Hospital from August 2015 to April 2017 were collected. The genetic variability of isolates was investigated and Etest was performed for phenotypic susceptibility to erythromycin, azithromycin, clarithromycin, clindamycin, and trimethoprim/sulfamethoxazole.
Results: 469 children with pertussis confirmed by real-time quantitative polymerase chain reaction were hospitalized and strains were isolated from 105 patients. White blood cell count ¡Ý 20 ¡Á 109/L and lymphocyte proportion ¡Ý 60% were observed in 39.29% of infants younger than 3 months. The two predominant profiles of virulence-associated allelic genes were ptxA1/ptxC1/ptxP1/prn1 (48.6%) and ptxA1/ptxC2/ptxP3/prn2 (44.8%). Among the isolates, 48.6% (51/105) were found resistant to macrolides. Conclusions: These findings indicate that leukocytosis is not a sensitive indicator of pertussis. Isolates with the gene profile ptxP3/prn2 were highly circulating in Shenzhen and less resistant to macrolides, different from patterns observed in other parts of China. |
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[Abstract] [Full Text] [PDF]
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The neuroprotective effect of mesenchymal stem cells is mediated through inhibition of apoptosis in hypoxic ischemic injury
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Fang Li, Kun Zhang, Hua Liu, Tan Yang, Dong-Jie Xiao, Yun-Shan Wang |
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Background: Neonatal hypoxia ischemia causes severe brain damage. Stem cell therapy is a promising method for treating neuronal diseases. Clinical translation of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for the recovery of neurons after hypoxic ischemic encephalopathy (HIE) may represent an effective therapy.
Methods: Primary neurons were exposed to oxygen-glucose deprivation (OGD) and subsequently cocultured with UC-MSCs. Apoptosis was examined by Annexin V-FITC-PI. Genes related to apoptosis were detected using RT-PCR and western-blot analyses. Using an in vivo model, HIE was induced in postnatal day 7 mice, and UC-MSCs were transplanted via the intraventricular route. UC-MSC migration was investigated by immunofluorescence, and lesion volumes were measured by TTC staining. Apoptosis in injured brain cells was detected by the TUNEL assay. RT-PCR and ELISA were used to detect the expression of inflammatory factors in cells and animal tissues.
Results: Flow cytometry analysis revealed that apoptosis in injured neurons was inhibited by UC-MSCs. The RT-PCR and western blot results indicated that coculture inhibited the expression of proapoptotic genes and upregulated expression of antiapoptotic genes. In the animal model, transplanted UC-MSCs migrated toward the cerebral lesion site and decreased the lesion extent in HIE. TUNEL staining showed that the MSC group exhibited significantly reduced numbers of TUNEL-positive cells. RT-PCR and ELISA showed that UC-MSCs inhibited the upregulation of TNF-¦Á and IL-1¦Â in response to hypoxic ischemic injury. Conclusion: These results indicate that UC-MSCs exert neuroprotective effects against hypoxic ischemic injury by inhibiting apoptosis, and the mechanism appears to be through alleviating the inflammatory response. |
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[Abstract] [Full Text] [PDF]
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MiR-29b expression is altered in crescent formation of HSPN and accelerates Ang II-induced mesangial cell activation
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Shan Cheng, Chun-Hua Zhu, Ai-Hua Zhang, Song-Ming Huang |
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Background: MicroRNA-29b (miR-29b) has been suggested to possess pro-inflammatory activity, which can partially be explained by the repression of tumor necrosis factor alpha protein three antibody (TNFAIP3). Meanwhile, it also promotes thyroid cell proliferation via Smad signaling pathways. The present study aimed to elucidate the role of miR-29b in Henoch Schonlein purpura nephritis (HSPN) and its underlying molecular mechanism in angiotensin II (Ang II)-induced human glomerular mesangial cell (HGMC) activation.
Methods: We evaluated miR-29b expression in 35 HSPN renal tissues based on crescent formation, glomerular sclerosis, interstitial fibrosis, thrombosis formation and capillary loop necrosis. Meanwhile, HGMCs were cultured, treated with Ang II and then transfected with LV-hsa-miR-29b-1 to induce miR-29b overexpression or LV-hsa-miR-29b-3p-inhibition to inhibit miR-29b expression. Finally, we examined the effects of miR-29b on cell proliferation and release of inflammatory mediators.
Results: We observed that miR-29b expression was significantly higher in the crescent group than in the no crescent group. MiR-29b overexpression induced the release of intercellular adhesion molecule-1, interleukin-1¦Â (IL-1¦Â), IL-6, IL-8, the increase of CyclinA2, CyclinD1, and cell proliferation. It also could inhibit the expressions of TNFAIP3 and NF-kappa-B-repressing factor (NKRF). Correspondingly, miR-29b inhibition produced the opposite effects and increased the expression of TNFAIP3 and NKRF. Conclusion: MiR-29b expression is altered in crescent formation of HSPN and accelerates Ang II-induced mesangial cell proliferation and release of inflammatory mediators. |
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[Abstract] [Full Text] [PDF]
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