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Baskin Alison S. Dossett Lesly A. Harris Chelsea A. 《Annals of surgical oncology》2021,28(8):4088-4092
Annals of Surgical Oncology - Recognizing the need to raise awareness of core diversity, equity, and inclusion (DEI) issues in the healthcare system, our previously developed Cultural Complications... 相似文献
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Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis: data from a phase II clinical trial 总被引:1,自引:0,他引:1
Silverman MH Strand V Markovits D Nahir M Reitblat T Molad Y Rosner I Rozenbaum M Mader R Adawi M Caspi D Tishler M Langevitz P Rubinow A Friedman J Green L Tanay A Ochaion A Cohen S Kerns WD Cohn I Fishman-Furman S Farbstein M Yehuda SB Fishman P 《The Journal of rheumatology》2008,35(1):41-48
OBJECTIVE: Adenosine exerts antiinflammatory effects via activation of the A3 adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor, overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally bioavailable A3AR agonist. METHODS: This was a multicenter study, blinded to dose, designed to assess the clinical activity and safety of CF101 in active RA. Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC from 18 patients. RESULTS:. Maximal responses were observed with 1.0 mg bid, lower at 0.1 and 4.0 mg bid. At 12 weeks, 55.6%, 33.3%, and 11.5% of the patients receiving 1.0 mg CF101 achieved ACR20%, 50%, and 70% responses, respectively. CF101 was generally well tolerated, with mild headache (4.1%), nausea (2.7%), and rash (2.7%) being the most common treatment-related adverse events. Statistically significant correlations between A3AR overexpression at baseline and ACR50 and ACR70 responses were observed. CONCLUSION: CF101 administered bid for 12 weeks resulted in improvement in signs and symptoms of RA that did not achieve statistical significance, and was safe and well tolerated. The expression level of A3AR was directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic and therapeutic effects of this novel agent. These findings require confirmation in a double-blind randomized placebo-controlled trial, currently under way. 相似文献
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Multiple biomarker use for detection of adverse events in patients presenting with symptoms suggestive of acute coronary syndrome 总被引:2,自引:0,他引:2
BACKGROUND: We investigated multiple biomarkers of various pathophysiologic pathways to determine their relationships with adverse outcomes in patients presenting with symptoms of acute coronary syndrome. METHODS: We obtained plasma specimens from 457 patients on admission and measured 7 biomarkers: myeloperoxidase (MPO), soluble CD40 ligand (CD40L), placental growth factor (PlGF), metalloproteinase-9 (MMP-9), high-sensitivity C-reactive protein (hsCRP), cardiac troponin I (cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We used the Modification of Diet in Renal Disease formula to calculate the estimated glomerular filtration rate (eGFR). Endpoints were cardiac events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, cardiac death) and all-cause mortality. We estimated cumulative event rates over a 4-month period with the Kaplan-Meier method and relative risk (RR) with the Cox proportional hazards model. RESULTS: Patients with increased PlGF, NT-proBNP, hsCRP, or cTnI or decreased eGFR had 11% to 20% higher all-cause mortality rates than patients with concentrations within reference intervals: 20.4% (eGFR), 16.0% (PlGF), 15.8% (hsCRP), 12.7% (NT-proBNP), and 11.3% (cTnI; all P < or = 0.03). No differences in mortality rates were observed between those with increased vs normal concentrations of MPO, CD40L, or MMP-9. Decreased eGFR (RR 3.4, P = 0.004) and increased NT-proBNP (RR 7.9, P = 0.04) were independently predictive of mortality, and PlGF (RR 2.0, P = 0.08) approached significance. Patients with increased NT-proBNP (12.3%) or cTnI (33.8%) had higher cardiac event rates (each P <0.02), with increased MPO (11.1%) showing a trend (P = 0.09). Patients in whom both cTnI and MPO were increased had a cardiac event rate of 43%. CONCLUSION: Multiple biomarkers that are likely indicative of different underlying pathophysiologic mechanisms are independently predictive of increased risk for adverse events in patients with acute coronary syndrome. 相似文献
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Glucose control and the inflammatory response. 总被引:2,自引:0,他引:2
Bryan Collier Lesly A Dossett Addison K May Jose J Diaz 《Nutrition in clinical practice》2008,23(1):3-15
Though first introduced more than 130 years ago, the concept of stress diabetes or stress hyperglycemia has gained tremendous attention in recent years in view of the landmark article by van den Berghe and colleagues in 2001. As opposed to earlier work that suggested that hyperglycemia in the acute clinical setting may be beneficial, it now appears that lower glucose levels are associated with improved outcomes. The mechanisms behind the improved outcomes are numerous and seem to be tied to the inflammatory process. Both lower glucose values and insulin therapy seem to be anti-inflammatory, whereas hyperglycemia increases the proinflammatory process and negatively affects the innate immune system. Despite the numerous approaches to achieve normoglycemia described in the literature, only modest success has been achieved. Understanding the pathophysiology driving stress hyperglycemia--the stress response and modulation of the inflammatory process-seems to be the key to improving the care of the most critically ill and injured patients. 相似文献
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