Erythropoiesis-stimulating agents in the management of cancer patients with anemia: a meta-analysis

Background： Erythropoiesis-stimulating agents （ESAs） are widely used in the management of anemia in cancer patients. Despite their apparent effectiveness, recent studies have suggested that ESAs could result in serious adverse events and even higher mortality. The aim of the current study was to evaluate the benefits and risks of ESAs in the management of cancer patients with anemia using a recta-analysis. Methods： The initial literature search covered Medline, PubMed, Embase, and the Cochrane Center Register of Controlled Trials, and identified 1,569 articles. The final meta-analysis included eight randomized controlled trials （n=2,387） in cancer patients with 〈11 g/dL hemoglobin （Hb） at the baseline and target Hb （for stopping ESA treatment） at no more than 13 g/dL. The assessment measures included Hb response, blood transfusion rate and adverse events that included venous thromboemblism （VTE）, hypertension, and on-study mortality. The results are expressed as pooled odds ratio （OR）. Publication bias was assessed using funnel plot analysis. Results： ESAs significantly increased the Hb concentration [OR 7.85, 95% confidence interval （CI）： 5.85 to 10.53, P〈O.O01] and reduced the red blood cell （RBC） transfusion rate （OR 0.52, 95% CI： 0.42 to 0.65, P〈0.001）. ESAs did not increase the accumulated adverse events （OR 0.95, P=0.82）, or the on-study mortality （OR 1.09, P=0.47）. Conclusions： ESAs are not associated with increased frequency of severe adverse events in anemic cancer patients when the target Hb value is no more than 13 g/dL.

SA-IL-2锚定修饰治疗表浅膀胱癌的实验研究(英文)

Background and Objective:Intravesical administration of Bacillus Calmette-Guèrin(BCG) after transurethral resection is by far the most effective local therapy for superficial bladder cancer,the fifth most common cancer in the world.However,approximately one-third of patients fail to respond and most patients eventually relapse.In addition,there are pronounced side effects of BCG therapy,such as BCG sepsis and a high frequency of BCG-induced cystitis.This study established a novel immunotherapy through immobilization of streptavidin-tagged human IL-2(SA-hIL-2) on the biotinylated mucosal surface of bladder wall.Methods:A mouse orthotopic model of MB49 bladder cancer was established by perfusing MB49 cells into mouse bladders.The SA-hIL-2 fusion protein was immobilized on the biotinylated mucosal surface of the bladder wall.Treatment began on day 1 after MB49 implantation,once every 3 days for 6 times.Immunohistochemical assay was performed to assess the persistence of SA-hIL-2 immobilized on the biotinylated mucosal surface of the bladder wall.The mice were monitored for tumor growth and survival.On day 60 after MB49 implantation,the SA-hIL-2-cured mice,which were found to have no hematuria or palpable tumors,were challenged with wild-type MB49 cells implanted into the pretreated bladder and monitored for survival.Results:SA-hIL-2 could be immobilized efficiently and durably on the bladder mucosal surface as long as 7 days.On day 60 after MB49 implantation,9 out of 20 SA-hIL-2-treated mice survived,but all mice in PBS control group died.More importantly,5 out of 9 tumor-free mice in the SA-hIL-2 group were protected against a second intravesical wild-type MB49 tumor challenge.Conclusions:SA-hIL-2 fusion protein could significantly inhibit tumor growth and extend the survival time in the orthotopic model of MB49 bladder cancer.

Correlation between gut microbiota and glucagon-like peptide-1 in patients with gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)places both the mother and offspring at high risk of complications.Increasing evidence suggests that the gut microbiota plays a role in the pathogenesis of GDM.However,it is still unclear whether the gut microbiota is related to blood biochemical traits,particularly glucagon-like peptide-1(GLP-1),in GDM patients.AIM To explore the correlation between the gut microbiota and blood biochemical traits,particularly GLP-1,in GDM patients.METHODS The V4 region of the 16S ribosomal ribonucleic acid(rRNA)gene was sequenced based on the fecal samples of 35 pregnant women with GDM and was compared to that of 25 pregnant women with normal glucose tolerance(NGT).RESULTS The results showed that Ruminococcaceae_UCG-002,Ruminococcaceae_UCG-005,Clostridium_sensu_stricto_1,and Streptococcus were more abundant in the NGT group than in the GDM group.Bacteroides and Lachnoclostridium were more abundant in the GDM group than in the NGT group.Spearman’s correlation analysis was performed to identify the relationships between microbiota genera and blood biochemical traits.Paraprevotella,Roseburia,Faecalibacterium,and Ruminococcaceae_UCG-002 were significantly negatively correlated with glucose.Ruminococcaceae_UCG-002 was significantly negatively correlated with hemoglobin A1c.Bacteroides was significantly positively correlated with glucose.Sutterella,Oscillibacter,and Bifidobacterium were significantly positively correlated with GLP-1.A random forest model showed that 20 specific genera plus glucose provided the best discriminatory power,as indicated by the area under the receiver operating characteristic curve(0.94).CONCLUSION The results of this study reveal novel relationships between the gut microbiome,blood biochemical traits,particularly GLP-1,and GDM status.These findings suggest that some genera are crucial for controlling blood glucose-related indices and may be beneficial for GDM treatment.Alteration in the microbial composition of the gut may potentially serve as a marker for identifying individuals at risk of GDM.