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In myelodysplastic syndromes (MDS), anemia responds to recombinant human erythropoietin (rHuEPO) alone and in combination with recombinant human granulocyte-colony-stimulating factor (rHuG-CSF) in 10% to 20% and in 35% to 40% of patients, respectively. We randomly divided 60 patients with low-grade anemic MDS and serum EPO levels lower than 500 IU/L (500 mU/mL) into 2 groups: rHuEPO ؉ rHuG-CSF (arm A) and supportive care (arm B). After 12 weeks, those who had erythroid responses were given rHuEPO alone for 40 additional weeks.They were also given rHuG-CSF if they had relapses. A response was considered major if the hemoglobin (Hb) level was 115 g/L (11.5 g/dL) or higher and minor Hb increase was 15 g/L (1.5 g/dL) or more or if it remained stable without transfusion. Ten of 24 patients responded in arm A, and 0 of 26 responded in arm B (P ‫؍‬ .01). Eight patients in arm A continued rHuEPO therapy alone, and 6 had relapses. Responses were always restored when rHuG-CSF was reintroduced. IntroductionMyelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by ineffective hematopoiesis, peripheral cytopenia, and increased risk for acute myelogenous leukemia (AML). Approximately two thirds of patients with MDS have anemia at diagnosis, and it develops in nearly all the rest as the disease progresses. Many MDS patients require frequent transfusions, leading to secondary hemochromatosis and risk for viral infections. In low-risk MDS, anemia is often the major clinical problem. Anemia significantly affects quality of life and causes significant morbidity in older patients. Cardiovascular diseases are often aggravated. Treatment of anemia with recombinant human erythropoietin (rHuEPO) alone is effective only in a small percentage of MDS patients. A meta-analysis of 205 patients with MDS showed that 16% responded to rHuEPO alone. 1 Patients who responded to treatment had no or limited transfusion requirements. Granulocytecolony-stimulating factor (G-CSF) and granulocyte macrophagecolony-stimulating factor (GM-CSF) increase neutrophil counts, do not increase the risk for leukemia, and have no effect on survival. [2][3][4] When combined with myeloid cytokines, rHuEPO can have synergistic effects on erythropoiesis in vitro. 5,6 Some clinical studies have shown that the combination of rHuG-CSF and rHuEPO has a better response rate (40%-50%) than rHuEPO alone. [7][8][9][10][11][12] However, none of these clinical trials were randomized, and cost analyses and quality-of-life evaluations are lacking. In one randomized study, the response rate was similar with GM-CSF plus EPO and with placebo 4 In these studies, only a small proportion of subjects with baseline serum EPO concentrations exceeding 500 IU/L (500 mU/mL) responded to treatment. 9 Therefore, we designed a multicenter randomized trial comparing treatment with rHuEPO plus rHuG-CSF and supportive care in patients with MDS who had serum EPO concentrations lower than or equal to 500 IU/L (500 mU/mL) to determine the effect of this Patients, materials...

Transplant renal artery stenosis (TRAS) is a common complication of kidney transplantation but attempts to identify predisposing risk factors for TRAS have yielded conflicting results. In order to determine the predisposing factors for transplant (TRAS), we retrospectively reviewed the records of 29 renal allograft recipients with TRAS treated with percutaneous transluminal angioplasty (PTA). The TRAS group was compared with a case-control group of 58 patients. Predisposing factors for TRAS included CMV infection (41.4% vs. 12.1% p = 0.0018) and initial delayed graft function (DGF) (48.3% vs. 15.5% p = 0.0018), respectively in the TRAS and the control group. Acute rejection occurred more frequently in patients from the TRAS group (48.3%) compared with the control group (27.6%), although the difference was not significant (p = 0.06). In a multivariate analysis, only CMV infection (p = 0.005) and DGF (p = 0.009) appear to be significantly and independently associated with TRAS. The long-term graft survival was significantly higher in the control group, compared with the TRAS group (p = 0.03). Our study suggests that CMV infection and DGF are two reliable risk factors for TRAS. Despite treatment by PTA with primary successful results, TRAS significantly affects long-term graft outcome. † These authors contributed equally to this study.

Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide system may be central to SARS‐CoV‐2 infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe COVID‐19 in an observational multicenter study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID‐19, 277 (9.7%) were taking a FIASMA medication at the time of their hospital admission. The primary endpoint was a composite of intubation and/or death. We compared this endpoint between patients taking vs. not taking a FIASMA medication in time‐to‐event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow‐up of 9.2 days (SD=12.5), the primary endpoint occurred in 104 patients (37.5%) receiving a FIASMA medication, and 1,060 patients (41.4%) who did not. Despite being significantly and substantially associated with older age and greater medical severity, FIASMA medication use was significantly associated with reduced likelihood of intubation or death in both crude (HR=0.71; 95%CI=0.58‐0.87; p<0.001) and primary IPW (HR=0.58; 95%CI=0.46‐0.72; p<0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one particular FIASMA class or medication. These results show the potential importance of the ASM/ceramide system in COVID‐19 and support the continuation of FIASMA medications in these patients. Double‐blind controlled randomized clinical trials of these medications for COVID‐19 are needed.