Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, management of aGVHD is important for successful transplantation. Mucosal damage and alteration of the gut microbiota after allo-HSCT are key factors in the development of aGVHD. We conducted a prospective study to evaluate the ability of prebiotics, which can alleviate mucosal damage and manipulate the gut microbiota, to mitigate posttransplantation complications, including aGVHD. Resistant starch (RS) and a commercially available prebiotics mixture, GFO, were administered to allo-HSCT recipients from pretransplantation conditioning to day 28 after allo-HSCT. Prebiotic intake mitigated mucosal injury and reduced the incidence of all aGVHD grades combined and of aGVHD grades 2 to 4. The cumulative incidence of skin aGVHD was markedly decreased by prebiotics intake. Furthermore, the gut microbial diversity was well maintained and butyrate-producing bacterial population were preserved by prebiotics intake. In addition, the posttransplantation fecal butyrate concentration was maintained or increased more frequently in the prebiotics group. These observations indicate that prebiotic intake may be an effective strategy for preventing aGVHD in allo-HSCT, thereby improving treatment outcomes and the clinical utility of stem cell transplantation approaches. This study was registered on the University Hospital Medical Information Network (UMIN) clinical trials registry (https://www.umin.ac.jp/ctr/index.htm) as #UMIN000027563.
Post-transplant microbial diversity in the gastrointestinal tract is closely associated with clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the impact of the fecal microbiota before allo-HSCT. We analyzed fecal samples approximately 2 weeks before conditioning among 107 allo-HSCT recipients between 2013 and 2015. Microbial analysis was performed using 16S rRNA gene sequencing. Operational taxonomic unit-based microbial diversity was estimated by calculating the Shannon index. Patients were classified into three groups based on the diversity index: low (<2), intermediate (2, 3), and high (>3) diversity (18 (16.8%), 48 (44.9%), and 41 (38.3%) patients, respectively). There were no significant differences in the 20-month overall survival, cumulative incidence of relapse, and non-relapse mortality among three groups. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was similar among the three groups (low 55.6%; intermediate 35.4%; high 48.8%, p = 0.339, at day 100). Furthermore, we found no differences in the cumulative incidence of grade II to IV acute gastrointestinal GVHD among the three groups (low 38.9%; intermediate 21.3%; high 24.4%, p = 0.778, at day 100). Regarding the composition of microbiota before allo-HSCT, aGVHD patients showed a significantly higher abundance of phylum Firmicutes (p < 0.01) and a lower tendency for Bacteroidetes (p = 0.106) than non-aGVHD patients. Maintenance of Bacteroidetes throughout allo-HSCT may be a strategy to prevent aGVHD.
Background Refeeding syndrome is characterized by metabolic disturbance including hypophosphatemia and hypokalemia upon reinstitution of nutrition in severely malnourished patients. Objective The present study sought to identify the risk factors for the development of refeeding syndrome-like metabolic disturbance in very low birth weight infants. Methods The correlations of severe hypophosphatemia with the serum levels of potassium and ionized calcium, daily calorie and phosphate intake, and umbilical cord blood flow on ultrasonography were analyzed in 49 very low birth weight infants. Results Fifteen infants (36%) presented with hypophosphatemia during the first postnatal week. Hypophosphatemia was significantly associated with birth weight z score (odds ratio, 1.60; 95% confidence interval, 1.04–2.47; p = 0.034) and umbilical artery resistance index (odds ratio, 7.72E−04; 95% confidence interval, 1.14E−06–0.523; p = 0.031). Multiple regression analysis revealed that umbilical artery resistance index was independently associated with hypophosphatemia. Conclusions Umbilical artery resistance index may serve as a useful marker for future development of refeeding syndrome-like hypophosphatemia in very low birth weight infants. Close monitoring of serum phosphorus and potassium levels and early intervention are important for the management of very low birth weight infants with intrauterine growth restriction due to placental dysfunction.
A high-flow nasal cannula (HFNC) is a newly developed device that enables high-flow oxygen therapy for patients with serious cardiopulmonary problems, but there are few data regarding its use in patients with hematological disease. The efficacy and tolerability of HFNCs for patients who developed ARF during the treatment of various hematological diseases was evaluated. Fifty-six patients underwent HFNC therapy during the last 2 years, and the causes of ARF were mainly pneumonia (n = 37) or acute congestive heart failure (n = 7). Only 11 patients (20 %) showed a good response to HFNC therapy, and remaining 45 patients (80 %) failed to respond to the initial HFNC therapy and, therefore, underwent second-line therapy including endotracheal intubation with mechanical ventilation (n = 15), non-invasive positive pressure ventilation (n = 1), or narcotic palliation alone (n = 29). Thus, HFNC appear not to be a viable treatment option in 4 out of 5 patients in this cohort of patients with hematological disease, but it was well tolerated in most patients (96 %); no major complications except for nasal soreness (n = 2) were observed. Multivariate analysis showed that the cause of ARF (pneumonia, odds ratio 11.2, 95 % CI 1.76–71.5, p = 0.01) was the only risk factor for treatment failure.
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