Circulating trimethylamine N‐oxide (TMAO), a canonical metabolite from gut flora, has been related to the risk of cardiovascular disorders. However, the association between circulating TMAO and the risk of cardiovascular events has not been quantitatively evaluated. We performed a systematic review and meta‐analysis of all available cohort studies regarding the association between baseline circulating TMAO and subsequent cardiovascular events. Embase and PubMed databases were searched for relevant cohort studies. The overall hazard ratios for the developing of cardiovascular events (CVEs) and mortality were extracted. Heterogeneity among the included studies was evaluated with Cochran's Q Test and I 2 statistics. A random‐effect model or a fixed‐effect model was applied depending on the heterogeneity. Subgroup analysis and meta‐regression were used to evaluate the source of heterogeneity. Among the 11 eligible studies, three reported both CVE and mortality outcome, one reported only CVEs and the other seven provided mortality data only. Higher circulating TMAO was associated with a 23% higher risk of CVEs (HR = 1.23, 95% CI: 1.07–1.42, I 2 = 31.4%) and a 55% higher risk of all‐cause mortality (HR = 1.55, 95% CI: 1.19–2.02, I 2 = 80.8%). Notably, the latter association may be blunted by potential publication bias, although sensitivity analysis by omitting one study at a time did not significantly change the results. Further subgroup analysis and meta‐regression did not support that the location of the study, follow‐up duration, publication year, population characteristics or the samples of TMAO affect the results significantly. Higher circulating TMAO may independently predict the risk of subsequent cardiovascular events and mortality.

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Transplantation-associated thrombotic microangiopathy (TA-TMA) is an uncommon but severe complication in patients undergoing allogeneic stem cell transplantation (allo-SCT). However, the mechanism is unclear. From 2011 to 2014, 20 patients with TA-TMA, 20 patients without, and 54 patients with various other complications, including veno occlusive disease (VOD), graft-versus-host disease (GVHD), and infection, were recruited in the study. Plasma vWF antigen (vWFAg), vWF activity (vWFAc), and ADAMTS13 activity were determined in these patients by ELISAs and FRETS-vWF73 assay, respectively. Plasma C3b, sC5b-9, and CH50 were also determined by ELISAs. Plasma levels of C3b were significantly increased in patients with either TA-TMA (p < 0.0001) or GVHD (p < 0.01). Plasma sC5b-9 and CH50 levels in patients with TA-TMA were also significantly increased (p < 0.001). Plasma ADAMTS13 activity was lower in patients with VOD, but normal with other complications. Both plasma vWFAg and vWFAc levels were not elevated in patients with TA-TMA or VOD compared with those of other groups. Complement activation likely via an alternative pathway (increased C3b, sC5b-9, and CH50) may play a role in the pathogenesis of TA-TMA. ADAMTS13 activity is reduced in VOD, but the ADAMTS13/vWF axis appears to be unaffected in patients with TA-TMA.

Poor platelet graft function (PPGF) is a significant complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, no optimal treatment has been recommended. This study investigated aspects of platelet recovery after allo-HSCT, including prognostic value and the effect of recombinant human thrombopoietin (rhTPO). We retrospectively analyzed 275 patients who received allo-HSCT in our center. Of them, 135 (49.1%) patients had good platelet graft function (GPGF) and 140 (50.9%) had PPGF. The latter included 59 (21.5%) patients with primary PPGF and 81 (29.4%) with secondary PPGF. Multivariate analysis showed that male gender (P = .024), lower CD34 cell count (P = .04), and no use of rhTPO (P <.001) were associated with PPGF. The 3-year overall survival rate of patients with PPGF (58%) was significantly less than that of patients with GPGF (82%; P <.001). We further analyzed the effect of rhTPO on prognosis of patients after allo-HSCT. Although no advantage was apparent when analyzing the entire cohort, for patients with myelodysplastic syndromes and aplastic anemia, rhTPO was associated with a significant survival advantage (P = .014).

BackgroundTransplant-associated thrombotic microangiopathy (TA-TMA) is a dangerous and life-threatening complication in patients undergoing hematopoietic stem cell transplantation (HSCT). Eculizumab has been used in the treatment of TA-TMA, and several studies have confirmed the benefit of Eculizumab in patients with TA-TMA. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Eculizumab for TA-TMA.Materials and MethodsWe searched PubMed and Embase for studies on the efficacy and safety of Eculizumab in TA-TMA patients. Efficacy outcomes consisted of overall response rate (ORR), complete response rate (CRR), and survival rate at the last follow-up (SR). Safety outcomes were adverse events (AEs), including infection, sepsis, impaired liver function, infusion reactions, and death.ResultsA total of 116 patients from six studies were subjected to meta-analysis. The pooled estimates of ORR, CRR, and SR for TA-TMA patients were 71% (95% CI: 58–82%), 32% (95% CI: 11–56%), and 52% (95% CI: 40–65%), respectively. Only one patient presented with a severe rash, and infection was the most common AEs. The main causes of death were infection and GvHD.ConclusionCurrent evidence suggests that Eculizumab improves SR and ORR in patients with TA-TMA and that Eculizumab is well tolerated. However, the number of studies is limited, and the findings are based mainly on data from observational studies. Higher quality randomized controlled trials and more extensive prospective cohort studies are needed.

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Cytogenetic and genetic changes have prognostic significance in acute myelogenous leukemia (AML). In our study, we compared the cytogenetic changes and gene mutations (NPM1, CEBPA, DNMT3A, FLT3-ITD, FLT3-TKD, and C-KIT) with clinical outcomes in 1132 patients with AML enrolled at our center over a 10-year period. A total of 977 patients provided gene mutation data. There were subsets of patients who exhibited mutations in NPM1 (17.9%), CEBPA (16.4%), FLT3-ITD (18.5%), FLT3-TKD (3.9%), DNMT3A (8.6%), and C-KIT (8.8%). A total of 557 patients (49.2%) underwent hematopoietic stem cell transplantation (HSCT) as consolidation therapy. Multivariate analysis identified an adverse karyotype (hazard ratio [HR], 1.48; P = .001), the presence of FLT3-ITD (HR, 1.90; P < .001), and receipt of nonstandard first-line induction chemotherapy (HR, 1.45; P = .003) as significant risk factors for poor overall survival (OS), and the presence of CEBPA mut (HR, .42; P < .001) and receipt of HSCT (HR, .35; P < .001) as prognostic factors for favorable OS. In addition, the presence of FLT3-ITD mut (HR, 2.11; P < .001) was identified as an independent risk factor for poor disease-free survival (DFS), and receipt of HSCT was correlated with improved DFS (HR, .74; P = .046). Compared with chemotherapy as consolidation therapy, HSCT improved the prognosis and overcame the prognostic effect of karyotype from the initial diagnosis; however, the presence of FLT3-ITD or CEBPA mutation can predict prognosis in AML irrespective of HSCT.