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Effect of vitamin A on intestinal mucosal injury in pediatric patients receiving hematopoietic stem cell transplantation and chemotherapy: a quasai-randomized trial

ABSTRACT: Objective Vitamin A is involved in maintenance of gut mucosal integrity and normal immune function. However, it is unclear whether these functions of vitamin A have any beneficial effects in patients undergoing hematopoietic stem cell transplantation (HSCT). In this study, we aimed to examine the potential protective effect of vitamin A supplementation on gastrointestinal (GI) mucosal integrity in HSCT recipients using plasma citrulline as a surrogate marker of intestinal integrity. Results We performed a quasi-randomized trial in 30 pediatric patients undergoing HSCT. Half (n?=?15) of the patients received a single high dose of vitamin A (200,000 IU) before the conditioning regimen was given, and half (n?=?15) did not. Clinical data of patients who developed post-transplant complications were recorded for 60 days after HSCT. There were no significant differences in mean plasma citrulline levels on day 7 after HSCT between the treatment and control groups (5.8 vs. 5.9 µmol/L, respectively). The incidence of mucositis and other complications were not different between the two groups within 60 days of HSCT. Vitamin A supplementation prior to HSCT in pediatric patients had no clinical benefit in protecting GI mucosal integrity.

SUBMITTER: Pattanakitsakul P

PROVIDER: S-EPMC7532573 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:The gastrointestinal tract is the predicted reservoir for most bloodstream infections (BSIs) after hematopoietic stem cell transplantation (HSCT). Whole-genome sequencing and comparative genomics have the potential to improve our understanding of the dynamics of gut colonization that precede BSI in HSCT recipients. Within a prospective cohort study of children (age <18 years) undergoing HSCT, 9 subjects met criteria for mucosal barrier injury BSI. We performed whole-genome sequencing of the blood culture isolate and weekly fecal samples preceding the BSI to compare the genetic similarity of BSI isolates to fecal strains. We evaluated temporal associations between antibiotic exposures and the abundances of BSI strains in the gut microbiota and correlated the detection of antibiotic resistance genes with the phenotypic antibiotic resistance of these strains. The median patient age was 2.6 years, and 78% were male. BSIs were caused by Escherichia coli (n = 5), Enterococcus faecium (n = 2), Enterobacter cloacae (n = 1), and Rothia mucilaginosa (n = 1). In the 6 BSI episodes with evaluable comparative genomics, the fecal strains were identical to the blood culture isolate (>99.99% genetic similarity). Gut domination by these strains preceded only 4 of 7 E. coli or E. faecium BSIs by a median of 17 days (range, 6 to 21 days). Increasing abundances of the resulting BSI strains in the gut microbiota were frequently associated with specific antibiotic exposures. E. cloacae and R. mucilaginosa were not highly abundant in fecal samples preceding BSIs caused by these species. The detection of antibiotic resistance genes for β-lactam antibiotics and vancomycin predicted phenotypic resistance in BSI strains. Bacterial strains causing mucosal barrier injury BSI in pediatric HSCT recipients were observed in the gut microbiota before BSI onset, and changes in the abundances of these strains within the gut preceded most BSI episodes. However, frequent sampling of the gut microbiota and sampling of other ecological niches is likely necessary to effectively predict BSI in HSCT recipients.

Project description:BackgroundMucosal-associated invariant T (MAIT) cells are innate-like T cells, some studies have reported that the number of circulating MAIT cells reduced in patients with acute graft-versus-host-disease (aGVHD) development. However, the role of donor MAIT cells on aGVHD development and subsequent functional change still remain unclear.MethodsThe study recruited 86 patients with hematological malignancies who underwent allogeneic hematopoietic cell transplantation (HCT) from May 1, 2018 to June 30, 2019. MAIT cells, their subset, and cytokine levels were measured by flow cytometry. Gray's test was used to assess the impact of graft MAIT cell proportion and number on aGVHD incidence. The Cox proportional hazard model was used in the multivariate analysis. The comparison for continuous variables was assessed using Mann-Whitney analysis. RNA-sequencing was performed to investigate the possible molecular pathway changes.ResultsOur study showed that the proportion of MAIT cells in grafts was not different from normal controls, but the CD4/8 subsets were altered. Taking the median of the proportion and number of MAIT cells in the graft as the threshold, the results showed that the incidence of grade B-D aGVHD in patients with MAIT cell proportion ≥ 3.03% was significantly higher than that in patients with MAIT cell proportion < 3.03% (56.3%, 95% CI 37.1-71.2 versus 23.1%, 95% CI 13.8-46.2; P = 0.038).The number of MAIT cells in the graft was not associated with aGVHD development (P = 0.173), however, when the graft contained more CD4 positive, CD8 positive, and CD4/CD8 double-positive MAIT cells, the incidence of aGVHD was significantly increased (P = 0.019, P = 0.035 and P = 0.027, respectively). Besides, reduced frequencies and counts of circulating MAIT cells were observed in patients with aGVHD when compared to patients without aGVHD, accompanied by enhanced production of Tumor necrosis factor-α, Interferon-γ and upregulated programmed death-1, CXC Chemokine Receptor-6 (CXCR6) and CD38 expression. Gene set enrichment analysis of MAIT cell RNA-seq data showed interferon-α response pathway upregulated in aGVHD patients when compared with patients without aGVHD and healthy controls.ConclusionsOur study shows that MAIT cells in grafts and peripheral blood are both closely related to the aGVHD development post allogeneic HCT. Interferon-α response pathway perhaps is a critical regulation mechanism for the MAIT cell involvement in aGVHD development.

Project description:Rapid and accurate pathogen identification is essential for timely and effective treatment of pneumonia. Here, we describe the use of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage (BALF) fluid to identify pathogens in patients with hematologic comorbid respiratory symptoms in a retrospective study with 84 patients. In the transplantation group, 8 cases (19.5%) and 47 cases (97.9%) were positive for BALF by conventional method detection and mNGS detection, respectively, and 6 cases (14.0%) and 41 cases (91.1%) in chemotherapy group, respectively. The detection rate of mNGS in both groups was significantly higher than that of conventional detection methods (all P<0.05). Pseudomonas aeruginosa and Streptococcus pneumoniae were the most common bacterial infections in the transplantation and chemotherapy groups, respectively. Aspergillus was the most common fungal infection in both groups. Human betaherpesvirus 5 (HHV-5), torque teno virus and human betaherpesvirus 7 (HHV-7) were the most common pathogen species in both groups. The most common type of infection in patients in the transplantation and chemotherapy groups was the mixed infection of bacteria-virus. Most patients in the transplantation group had mixed infections based on multiple viruses, with 42 cases of viral infections in the transplantation group and 30 cases of viral infections in the chemotherapy group, which were significantly higher in the transplantation group than in the chemotherapy group (χ2 = 5.766, P=0.016). and the mixed infection of virus-virus in the transplantation group was significantly higher than that in the chemotherapy group (27.1% vs 4.4%, P=0.003). The proportion of death due to pulmonary infection was significantly higher in the transplantation group than in the chemotherapy group (76.9% vs 16.7%, χ2 = 9.077, P=0.003). This study demonstrated the value of mNGS of BALF in improving the diagnosis and prognosis of hematologic comorbid pneumonia, helping patients to obtain timely and effective treatment, and giving guidance on the overall treatment plan for patients, with particular benefit for patients with hematologic chemotherapy comorbid pneumonia.

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Effect of vitamin A on intestinal mucosal injury in pediatric patients receiving hematopoietic stem cell transplantation and chemotherapy: a quasai-randomized trial

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