Using high-sensitivity troponin T: the importance of the proper gold standard.

OBJECTIVE: The study objective was to determine how best to use high-sensitivity cardiac troponin T (hscTnT) to diagnose myocardial infarction. METHODS: A total of 358 patients presenting with acute coronary syndromes sampled at admission and 2, 4, and 6 to 8 hours. Both contemporary cardiac troponin T (cTnT) and hscTnT were measured. Patients were classified with conventional cTnT values by independent investigators. Myocardial infarction required a cTnT value ≥99th reference percentile and a ≥20% change. RESULTS: Seventy-nine patients had non-ST-segment elevation myocardial infarction, 105 patients had unstable angina, and 174 patients had nonacute coronary syndromes. A cTnT cutoff at the 10% coefficient of variation value missed 14.5% of infarctions. hscTnT had a sensitivity at admission of 89.9%, but specificity was only 75.1% because of elevations in 45.3% and 25.3% of those with unstable angina and nonacute coronary syndromes, respectively. The optimal value for myocardial infarction diagnosis with hscTnT was 25 ng/L at admission and 30 ng/L during serial sampling. All infarctions were diagnosed within 4 hours, with a time saving of 11 and 68 minutes compared with a cTnT value at the 99th reference percentile value and a cTnT value at a coefficient of variation of 10%. By using the 99th percentile of hsTnT plus a ≥20% change, 25 additional infarctions were identified. With these included, the optimal cutoff decreased to 12 ng/L at admission and 13 ng/L over time, but time to diagnosis increased. CONCLUSIONS: The gold standard used to diagnose myocardial infarction makes a major difference in the results. When myocardial infarction is diagnosed using hscTnT 99th percentile values with a 20% change, more are identified, diagnosis is delayed, and the optimal value for use is reduced.

Transforming growth factor beta 1 as a biomarker of diabetic peripheral neuropathy: cross-sectional study.

BACKGROUND: Simple and efficient screening methods are lacking for diabetic peripheral neuropathy (DPN), the most common and most difficult to treat of the long-term diabetic complications. Increased levels of transforming growth factor beta 1 (TGFbeta1) in type 2 diabetic patients (T2DM) plays an immunomodulatory role in diabetic nephropathy and, possibly, in atherosclerotic evolution. Since preliminary interrelationships between experimental DPN and TGFbeta1 have been observed, we sought to assess whether TGFbeta1 could be a biomarker molecule for human DPN. MATERIALS AND METHODS: Cross-sectional cohort study focused on the assessment of the interrelationships between TGFbeta1 levels, cardiovascular disease (CVD), diabetic nephropathy (DNF), and neuropathy (DPN) in a group of T2DM patients (N=180; male 117, female 63) randomly selected from the North Catalonia Diabetes Study. DPN was diagnosed using clinical and neurophysiology evaluation. Incipient DNF was assessed by microalbuminuria (MAU). Total TGFbeta1 (without acidification) was measured by immunoassay by ELISA (Promega). RESULTS: DPN correlated with age, time of diabetes duration, MAU, CVD, and TGFbeta1 (P<.0001). Log-transformed TGFbeta1 (logTGbeta1) was significantly higher in patients with DPN than in those without (P<.0005). LogTGFbeta1 (OR=7.5; P=.006), age (OR=1.1; P<.0005), and logMAU (OR=2.0; P=.016) appear as significant estimators of the occurrence of DPN in our series. The integrated ROC curve evaluation with these three parameters expressed an important sensitivity (78.1%), specificity (76.0%), positive predictive value (79.2%), and negative predictive value (70.3%) in relation to DPN presence. DISCUSSION: TGFbeta1 stands as an important biomarker molecule for DFN and DPN screening in our series. Further prospective studies are warranted.

Development of an experimental model of induced bacterial peritonitis in cirrhotic rats with or without ascites.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe complication of cirrhotic patients associated with a high mortality. AIM: To develop an available experimental model of induced bacterial peritonitis in cirrhosis. MATERIAL AND METHODS: Sprague-Dawley rats with carbon-tetrachloride-induced cirrhosis with (N=22) or without (N=101) ascites were randomized to receive an intraperitoneal administration of different concentrations of Escherichia coli (E. coli) diluted in 1 mL of sterile water in ascitic rats and in different volumes in nonascitic rats. A subgroup of nonascitic animals received ceftriaxone 4 h after E. coli inoculation. Mortality of rats was evaluated 24 h after bacterial inoculation. RESULTS: None of the rats receiving sterile water alone and only one infected with 10(7) cfu of E. coli died. Ascitic rats showed a lower mortality rate than nonascitic rats infected with 10(8) or 10(9) cfu of E. coli (P<0.05). Mortality was higher with 10(9) cfu than with 10(8) cfu of E. coli in ascitic (P NS) and nonascitic (P<0.01) rats. A trend was noted to ward higher mortality in nonascitic rats inoculated with 10(8) cfu with increasing water volumes. A marked peritoneal polymorphonuclear cell response was observed 4 h after E. coli injection in both ascitic and nonascitic rats. Antibiotic therapy significantly reduced the mortality rate of rats infected with 10(8) cfu (P<0.01). CONCLUSIONS: This experimental model of induced bacterial peritonitis in cirrhosis with or without ascites may represent a useful tool for the study of pathogenic events postinfection and for the design of new therapeutic strategies to treat patients with SBP.