Projected Clinical Benefits of Implementation of SGLT-2 Inhibitors Among Medicare Beneficiaries Hospitalized for Heart Failure

BackgroundThe sodium-glucose cotransporter-2 (SGLT-2) inhibitors form the latest pillar in the management of heart failure with reduced ejection fraction (HFrEF) and appear to be effective across a range of patient profiles. There is increasing interest in initiating SGLT-2 inhibitors during hospitalization, yet little is known about the putative benefits of this implementation strategy.MethodsWe evaluated Medicare beneficiaries with HFrEF (≤ 40%) hospitalized at 228 sites in the Get With The Guidelines-Heart Failure (GWTG-HF) registry in 2016 who had linked claims data for ≥ 1 year postdischarge. We identified those eligible for dapagliflozin under the latest U.S. Food and Drug Administration label (excluding estimated glomerular filtration rates < 25 mL/min per 1.73 m², dialysis and type 1 diabetes). We evaluated 1-year outcomes overall and among key subgroups (age ≥ 75 years, gender, race, hospital region, kidney function, diabetes status, triple therapy). We then projected the potential benefits of implementation of dapagliflozin based on the risk reductions observed in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial.ResultsAmong 7523 patients hospitalized for HFrEF, 6576 (87%) would be candidates for dapagliflozin (mean age 79 ± 8 years, 39% women, 11% Black). Among eligible candidates, discharge use of β-blockers, ACEi/ARB, MRA, ARNI, and triple therapy (ACEi/ARB/ARNI+β-blocker+MRA) was recorded in 88%, 64%, 29%, 3%, and 20%, respectively. Among treatment-eligible patients, the 1-year incidence (95% CI) of mortality was 37% (36-38%) and of HF readmission was 33% (32-34%), and each exceeded 25% across all key subgroups. Among 1333 beneficiaries eligible for dapagliflozin who were already on triple therapy, the 1-year incidence of mortality was 26% (24%–29%) and the 1-year readmission due to HF was 30% (27%–32%). Applying the relative risk reductions observed in DAPA-HF, absolute risk reductions with complete implementation of dapagliflozin among treatment-eligible Medicare beneficiaries are projected to be 5% (1%–9%) for mortality and 9% (5%–12%) for HF readmission by 1 year. The projected number of Medicare beneficiaries who would need to be treated for 1 year to prevent 1 death is 19 (11–114), and 12 (8–21) would need to be treated to prevent 1 readmission due to HF.ConclusionsMedicare beneficiaries with HFrEF who are eligible for dapagliflozin after hospitalization due to HF, including those well-treated with other disease-modifying therapies, face high risks of mortality and HF readmission by 1 year. If the benefits of reductions in death and hospitalizations due to HF observed in clinical trials can be fully realized, the absolute benefits of implementation of SGLT-2 inhibitors among treatment-eligible candidates are anticipated to be substantial in this high-risk postdischarge setting.     

Temporal Trends in Post Myocardial Infarction Heart Failure and Outcomes Among Older Adults

BackgroundWe sought to determine national trends and long term outcomes of post myocardial infarction (MI) heart failure. An MI can be complicated by heart failure; there are limited data describing the contemporary patterns and clinical implications of post-MI heart failure.Methods and ResultsWe studied patients with an MI aged 65 years or older from 2000 to 2013 in a Medicare database. New-onset heart failure after an MI was defined as either heart failure during the index MI admission or a hospitalization for heart failure within 1 year of the index MI event. A trend analysis of the incidence of heart failure was performed, and differences were examined by Gray tests. The 5-year mortality rates were evaluated and differences among heart failure cohorts were ascertained by Gray tests. There were a total of 1,531,638 patients with an MI and 565,291 patients had heart failure (36.0%). The rate of heart failure during index admission was 32.3% and the frequency of heart failure hospitalization within 1 year was 10.4%. Patients with heart failure were older (81 years vs 77 years). The temporal trend from 2001 to 2012 suggested a decrease in the incidence of heart failure during index admission (2001: 34.7%, 2012: 31.2%, P_trend < .01), as well as heart failure hospitalization within 1 year (2001: 11.3%, 2012: 8.7%, P_trend < .01). The 5-year mortality rate among patients without heart failure was 38.4% and for patients with any heart failure it was 68.7%.ConclusionsPost-MI heart failure in older adults occurs in 1 in 3 patients within 1 year; heart failure portends significantly higher long-term mortality.     

Inflammatory pathways in Alzheimer’s disease mediated by gut microbiota

In the past decade, numerous studies have demonstrated the close relationship between gut microbiota and the occurrence and development of Alzheimer’s disease (AD). However, the specific mechanism is still unclear. Both the neuroinflammation and systemic inflammation serve as the key hubs to accelerate the process of AD by promoting pathology and damaging neuron. What's more, the gut microbiota is also crucial for the regulation of inflammation. Therefore, this review focused on the role of gut microbiota in AD through inflammatory pathways. Firstly, this review summarized the relationship and interaction among gut microbiota, inflammation, and AD. Secondly, the direct and indirect regulatory effects of gut microbiota on AD through inflammatory pathways were described. These effects were mainly mediated by the component of the gut microbiota (lipopolysaccharides (LPS) and amyloid peptides), the metabolites of bacteria (short-chain fatty acids, branched amino acids, and neurotransmitters) and functional by-products (bile acids). In addition, potential treatments (fecal microbiota transplantation, antibiotics, probiotics, prebiotics, and dietary interventions) for AD were also discussed through these mechanisms. Finally, according to the current research status, the key problems to be solved in the future studies were proposed.     

全凭静脉麻醉下经内镜逆行胰胆管造影术后恶心呕吐的危险因素

目的筛选全凭静脉麻醉下经内镜逆行胰胆管造影术(endoscopic retrograde cholangio-pancreatography,ERCP)术后恶心呕吐(postoperative nausea and vomiting,PONV)的独立危险因素。方法选择上海瑞金医院2016年7月18日至8月31日全凭静脉麻醉下行ERCP的患者90例,男47例,女43例,年龄≥18岁,ASAⅠ~Ⅲ级。收集患者的一般资料和术中情况,随访术后24h内恶心呕吐的发生情况。采用Logistic回归分析全凭静脉麻醉下ERCP术后恶心呕吐的独立危险因素。结果有33例(36.7%)患者发生恶心。进一步Logistic回归分析结果显示,女性(OR=3.73,95%CI 1.36~10.27)、有PONV/晕动症史(OR=4.39,95%CI 1.40~13.76)、术后3h血淀粉酶3倍正常值(OR=5.22,95%CI 1.30~20.95)是全凭静脉麻醉下ERCP术后恶心呕吐的独立危险因素。结论女性、有PONV/晕动症史、术后3h血淀粉酶3倍正常值是全凭静脉麻醉下ERCP术后恶心呕吐的独立危险因素。     

Elevated serum IL-13 level is associated with increased Treg cells in tumor microenvironment and disease progression of diffuse large B-cell lymphoma

Diffuse large B cell lymphoma (DLBCL) is the most common aggressive lymphoid malignancy, with an immunosuppressive microenvironment affecting clinical outcome. Interleukin (IL)-13 overexpression is observed in multiple solid tumors and contributes to tumor progression. This study aims to investigate pretreatment serum IL-13 levels and their relationship with the prognosis of DLBCL patients. One hundred and sixty-six patients with newly diagnosed DLBCL from June 2015 to July 2017 were included. Patients with elevated pretreatment serum IL-13 levels (IL-13≥1.63 pg/ml) were classified into the high IL-13 group and they had significantly lower complete remission rate (60% vs. 74%, p = 0.0059), higher progression rate (43% vs. 23%, p = 0.0051), and poor progression-free survival (2-year PFS, 63% vs. 78%, p = 0.0078) and overall survival (2-year OS, 75% vs. 92%, p = 0.0027), when compared to those in the low IL-13 group (IL-13<1.63 pg/ml). Meanwhile, increased Treg cell ratio in peripheral blood (p = 0.0147) and elevated serum IL-2 levels (p = 0.0272) were observed in the high IL-13 group. Moreover, RNA sequencing data showed that patients in the high IL-13 group had significantly elevated expression of chemokines and chemokine receptors (CCR4, CCL19, CCL21, CXCL2) related to Treg activation and recruitment. Consistent with the chemokine profile, tumor immunophenotyping analysis revealed that higher Treg cells recruitment in the high IL-13 group than the low IL-13 group (p = 0.0116). In vitro, when lymphoma cells co-cultured with peripheral blood monocytes of healthy controls, metformin down-regulated both IL-13 level and Treg cell ratio, in consistent with the decreased serum IL-13 levels of patients after 6 months of metformin maintenance therapy in the high IL-13 group. Taken together, pretreatment serum IL-13 level is related to the immunosuppressive microenvironment and poor clinical outcome of DLBCL patients and could be targeted by metformin, thus providing a new therapeutic strategy in treating DLBCL with high serum IL-13 levels.