A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism (
ABSTRACTIncreasing attention has focused on the role of free radicals derived from oxygen in the pathophysiology of a wide variety of disorders. One of the well-recognized targets of free radical-induced iWury is peroxidation of lipids. Using a variety of approaches, we have found that a series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase mechanism involving free radicalcatalyzed peroxidation of arachidonic acid. Levels of these compounds in normal human plasma and urine range from 5 to 40 pg/ml and 500 to 4000 pg/mg of creatinine, respectively.
Background and objectives The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients.Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Results Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups.
ConclusionsIn the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.
Soluble urokinase plasminogen activator receptor (suPAR) is a circulating form of a physiological and pathophysiological important cell surface receptor, implicated in inflammation. Recent studies showed that suPAR is a promising biomarker, useful for diagnosis, assessment and prognosis of several diseases. This review summarises the majority of preliminary studies and analyses the significance and the clinical application of suPAR in various clinical conditions. SuPAR seems to have a significant value in the diagnosis as well as prognosis of many diseases; nonetheless, it merits large-scale studies to set cut-off values that help physicians in following up their patients and accordingly tailor their treatment plans.
Goals and Background:
We aimed to develop a novel 1-year mortality risk-scoring system that includes use of antithrombotic (AT) drugs and to validate it against other scoring systems in patients with acute gastrointestinal bleeding (GIB).
Study:
We developed a risk-scoring system from prospectively collected data on patients admitted with GIB between January 2013 and August 2020, who had at least 1- year of follow-up. Independent predictors of 1-year mortality were determined after adjusting for the following confounders: the age-adjusted Charlson Comorbidity Index (CCI) (divided into 4 groups: CCI-0=0, CCI-1=1 to 3, CCI-2=4 to 6, CCI-3 ≥7), need for blood transfusion, GIB severity, need for endoscopic therapy, and type of AT. The risk score was based on independent predictors.
Results:
Five hundred seventy-six patients were included and 123 (21%) died at 1-year follow-up. Our risk -score was based on the following: CCI-2 (2 points), CCI-3 (4 points), need for blood transfusion (1 point), and no use of aspirin (1 point), as aspirin use was protective (maximum score=6). Patients with higher risk scores had higher mortality. The model had a better predictive accuracy [AUC=0.82, 95% confidence interval (0.78-0.86), P<0.0001] than the Rockall score for upper GIB (Area Under the Curve (AUC)=0.68, P<<0.0001), the Oakland score for lower GIB (AUC=0.69, p=0.004), or the Shock Index for all (AUC=0.54, P<0.0001).
Conclusion:
A simple and novel score that includes use of AT upon admission accurately predicts 1-year mortality in patients with GIB. This scoring system may help guide follow-up decisions and inform the prognosis of patients with GIB.
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