Predictor Of Adverse Clinical Outcomes Research Articles

Clinical implications of switching from intensive to moderate statin therapy after acute coronary syndromes

Background and aimsIntensive statin therapy represents an effective option after acute coronary syndromes (ACS). Despite evidence, switching to less effective statins frequently occurs in practice. Aim of this observational study was to assess the impact of switching from intensive to moderate statin therapy on clinical outcomes after ACS. Methods and resultsA cohort of 1321 consecutive ACS patients (886 men, age 71±.8years) discharged on atorvastatin 80mg/d in a 6.5year period was followed for 12months after discharge. During follow-up, 557 patients (42%) were switched by primary care physicians to moderate statin therapy, either for side effects (56%) or for safety concerns (44%). No major adverse reaction was reported. Increasing age (HR 1.52 per 10-year increase, 95% CI 1.23–1.78, p=0.01), and female gender (HR 1.11, 95% CI 1.06–1.23, p=0.02) were associated with a higher probability of switch. Patients following a cardiac rehabilitation program (HR 0.64 95% CI 0.49–0.86, p=0.02) and diabetic subjects (HR 0.81, 95% CI 0.67–0.92, p=0.02) were more likely to continue atorvastatin 80mg/d. During follow-up, a major adverse clinical event occurred in 331 patients (one-year probability 0.25, 95% CI 0.22–0.27). Multivariate analysis with Cox proportional hazards method, including statin switching as a time-dependent covariate, demonstrated that, after adjustment for demographic and clinical variables, reduction from intensive to moderate statin therapy was an independent predictor of adverse clinical outcomes (HR 2.7, 95% CI 1.7–5.1, p=0.004). ConclusionSwitching from intensive to moderate statin therapy after ACS is associated with an increased incidence of adverse clinical events.

Recent advances in the rapidly evolving field of fibroblast growth factor 23 in chronic kidney disease

In recent years, there has been an increasing awareness of the central regulatory role of fibroblast growth factor 23 (FGF23) in mineral metabolism and its particular prominence in patients with chronic kidney disease (CKD). FGF23 is a powerful predictor of adverse clinical outcomes in CKD that appears to be superior to existing mineral metabolism markers such as serum phosphate and parathyroid hormone. Interesting new data suggest a central role of bone health in the regulation of FGF23 secretion, whereas another important new study reported that virtually all circulating FGF23 in advanced renal failure is biologically intact. Finally, new data demonstrate the ability to alter FGF23 levels using common CKD therapies such as phosphate binders, active vitamin D, and cinacalcet. Although FGF23 was originally discovered in studies of rare diseases, we expect that its primary utility in mainstream clinical practice will ultimately lie in the management of CKD. Emerging data highlight the potential of FGF23 as a novel diagnostic to identify CKD patients at the highest risk for disease progression, cardiovascular disease, and death, and those who might benefit from early phosphorus-related therapies before the onset of overt hyperphosphatemia.

Urinary Neutrophil Gelatinase-Associated Lipocalin: A Potential Biomarker for Predicting Rapid Progression of Drug-Induced Chronic Tubulointerstitial Nephritis

IntroductionThe role of urinary biomarkers of kidney injury in the prediction of adverse clinical outcomes in drug-induced chronic tubulointerstitial nephritis (D-CTIN) has not been well described. MethodsA total of 36 patients with D-CTIN were enrolled in the study. The baseline urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL), α1-microglobin (α1-MG), albumin (mAlb) and total protein were measured, and estimated glomerular filtration rate change rates within a period of 6 to 33 (mean: 24months) follow-up months were recorded. ResultsAreas under the receiver-operator characteristic curve of urinary NGAL, α1-MG, mAlb and total protein for predicting deterioration of estimated glomerular filtration rate were 0.707, 0.631, 0.685 and 0.678, respectively. The cutoff points that maximized the combined sensitivity and specificity for NGAL, α1-MG, mAlb and total protein were 37.71 ng/mL, 33.20μg/mL, 6.91mg/L and 60.00mg/L, respectively. At these thresholds, the sensitivity and specificity was 64.7% and 78.9% for NGAL, 66.7% and 50.0% for α1-MG, 80.0% and 50.0% for mAlb and 70.6% and 63.2% for total protein, respectively. The median renal survival time (years) of patients with urinary NGAL level exceeding 37.705 ng/mL was shorter than that of patients with urinary NGAL level below 37.705 ng/mL (1.59 ± 0.79 versus 2.09 ± 0.63, P=0.040, χ2=4.218). ConclusionsIncrease of baseline urinary NGAL was better than α1-MG, mAlb and total protein in predicting renal function deterioration in patients with D-CTIN. This noninvasive approach has potential to serve as a practical tool in D-CTIN prognosis.

AS-82: Admission HbA 1c is Not a Predictor of Adverse Clinical Outcome in Patients Without Diabetes Mellitus Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction

Data on admission HbA1c levels and long-term clinical outcomes in patients without diabetes mellitus undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) are limited. This study examined the value of admission HbA1c levels in clinical outcomes after PCI in patients without diabetes with AMI.

Postoperative infections are associated with adverse outcome after resection with curative intent for colorectal cancer

This study focused on the impact of post-operative infection on patient outcome after resection with curative intent for colorectal cancer. Postoperative surgical and medical complications have been implicated as a negative predictor of long-term outcome in various malignancies. We studied a population of 1083 patients who underwent resection with curative intent for colorectal cancer. These patients were divided into 2 groups based on the occurrence (65 patients, 6%) or absence (1018 patients, 94%) of postoperative complications due to infection. We investigated the demographic and clinicopathological features of each patient with and without postoperative infectious complications, as well as the impact of postoperative infection on long-term survival. Results showed that patients with postoperative infectious complications had diabetes mellitus more frequently and also had urgent surgery compared to those without infectious complications. In addition, patients with postoperative infectious complications had a significantly more unfavorable outcome compared with those without postoperative infection in cancer-specific, but not overall survival. Multivariate analysis demonstrated that age, rectal cancer and tumor stage correlated with overall survival, but not postoperative infectious complications. However, postoperative infections, as well as gender, were associated with the length of time until the patient succumbed from the recurrence of colorectal cancer after resection for curative intent. Thus, postoperative infectious complications are predictors of adverse clinical outcome in patients with colorectal cancer. However, further immunological study is necessary to confirm the biological significance of these findings.

Enterococcal peritonitis in Australian peritoneal dialysis patients: predictors, treatment and outcomes in 116 cases

Background. Enterococcal peritonitis is a serious complication of peritoneal dialysis (PD), although reports of this condition in the literature are exceedingly limited. Methods. The frequency, predictors, treatment and clinical outcomes of enterococcal peritonitis were investigated in all 4675 patients receiving PD in Australia between 1 October 2003 and 31 December 2006. Results. One hundred and sixteen episodes of enterococcal peritonitis occurred in 103 individuals. Enterococcal peritonitis tended to be associated with older age, Maori and Pacific Islander racial origin, renovascular disease and coronary artery disease. Polymicrobial peritonitis, defined as recovery of two or more organisms from dialysate effluent, was significantly more common when an Enterococcus species was isolated than when it was not (45% vs 5%, respectively, P < 0.001, odds ratio 13.4, 95% CI 9.45-19.0). Although international guidelines recommend intraperitoneal ampicillin therapy, only 8% of patients with pure enterococcal peritonitis were treated with this agent, whilst the majority (78%) received vancomycin monotherapy. Overall, 59 (51%) patients with enterococcal peritonitis were successfully treated with antibiotics without experiencing relapse, catheter removal or death. The sole independent predictor of adverse clinical outcomes was recovery of additional (non-Enterococcus) organisms. Polymicrobial enterococcal peritonitis was associated with very high rates of hospitalization (83%), catheter removal (52%), permanent haemodialysis transfer (50%) and death (5.8%). In contrast, clinical outcomes were broadly comparable for pure enterococcal and non-enterococcal peritonitis (hospitalization 75% vs 69%, respectively; catheter removal 25% vs 21%; permanent haemodialysis transfer 17% vs 17%; death 1.6% vs 2.2%) although worse than non-enterococcal Gram-positive peritonitis (63%, 12%, 3% and 0.6%, respectively). Removal of the PD catheter within 1 week of enterococcal peritonitis onset was associated with a lower probability of permanent haemodialysis transfer than later removal (74% vs 100%, P = 0.03). Enterococcal peritonitis is associated with an increased risk of catheter removal, permanent haemodialysis transfer and death, particularly when other organisms are isolated in the same episode.

Polymicrobial Peritonitis in Peritoneal Dialysis Patients in Australia: Predictors, Treatment, and Outcomes

The study aim was to examine the frequency, predictors, treatment, and clinical outcomes of peritoneal dialysis-associated polymicrobial peritonitis. Observational cohort study using ANZDATA (The Australia and New Zealand Dialysis and Transplant Registry) data. All Australian peritoneal dialysis patients between October 2003 and December 2006. Age, sex, race, body mass index, baseline renal function, late referral, kidney disease, smoking status, comorbidity, peritoneal permeability, center, state, organisms, and antibiotic regimen. Polymicrobial peritonitis occurrence, relapse, hospitalization, catheter removal, hemodialysis transfer, and death. 359 episodes of polymicrobial peritonitis occurred in 324 individuals, representing 10% of all peritonitis episodes during 6,002 patient-years. The organisms isolated included mixed Gram-positive and Gram-negative organisms (41%), pure Gram-negative organisms (22%), pure Gram-positive organisms (25%), and mixed bacteria and fungi (13%). There were no significant independent predictors of polymicrobial peritonitis except for the presence of chronic lung disease. Compared with single-organism infections, polymicrobial peritonitis was associated with higher rates of hospitalization (83% vs 68%; P < 0.001), catheter removal (43% vs 19%; P < 0.001), permanent hemodialysis transfer (38% vs 15%; P < 0.001), and death (4% vs 2%; P = 0.03). Isolation of fungus or Gram-negative bacteria was the primary predictor of adverse clinical outcomes. Pure Gram-positive peritonitis had the best clinical outcomes. Patients who had their catheters removed >1 week after polymicrobial peritonitis onset were significantly more likely to be permanently transferred to hemodialysis therapy than those who had earlier catheter removal (92% vs 81%; P = 0.05). Limited covariate adjustment. Residual confounding and coding bias could not be excluded. Polymicrobial peritonitis can be treated successfully using antibiotics alone without catheter removal in most cases, particularly when only Gram-positive organisms are isolated. Isolation of Gram-negative bacteria (with or without Gram-positive bacteria) or fungi carries a worse prognosis and generally should be treated with early catheter removal and appropriate antimicrobial therapy.

Preoperative lymphopenia is a predictor of postoperative adverse outcomes in children with congenital heart disease

Lymphopenia is a predictor of adverse clinical outcomes in adults with various systemic diseases. We hypothesized that preoperative absolute lymphopenia (absolute lymphocyte count of less than 3000 cells/microL) is associated with adverse postoperative outcomes in children with congenital heart disease undergoing corrective or palliative surgery on cardiopulmonary bypass during the first 2 years of life. A retrospective single center cohort study was performed. Categorical variables were analyzed with the chi(2) test. Preoperative variables were analyzed with logistic and linear regression analysis to determine whether they were associated with adverse outcomes. Analysis was performed on 280 patients, of whom 124 were female and 156 were male. Seventy-one patients were neonates (< or =30 days) at the time of the operation. Ninety patients had an absolute lymphocyte count of less than 3000 cells//microL before the operation. Regression models showed that RACHS-1 categories 5 and 6, age, and preoperative lymphopenia were significantly associated with postoperative mortality (P < .0006). Within RACHS-1 groups, lymphopenia remained a significant predictor of mortality for patients in RACHS categories 3 and 4. Lymphopenia and age were associated with longer length of stay and length of mechanical ventilation within RACHS categories 1 to 4 (P < .05). Preoperative lymphopenia was the only predictor of use of postoperative nitric oxide (P < .05). Preoperative lymphopenia is a predictor of adverse postoperative outcomes in children with congenital heart disease who undergo a corrective or palliative procedure with cardiopulmonary bypass during the first 2 years of life.

Current drugs and medical treatment algorithms in the management of acute decompensated heart failure

Background: Acute decompensated heart failure (ADHF) is associated with increased hospitalization rates and high in-hospital mortality, and has emerged as a major public health problem over the past decade. In recent years, several new drugs and therapeutic approaches have failed to reduce short- and long-term morbidity and mortality in ADHF patients. New agents and strategies are under investigation in order to effectively reduce the mortality and morbidity in these patients. Objective: To review the recent experimental and clinical evidence on existing therapeutic algorithms and investigational drugs used for the treatment of ADHF. Methods: A systematic search of peer-reviewed publications was performed on Medline and EMBASE from January 1995 to January 2009. The results of unpublished trials were obtained from presentations at national and international meetings. Results: Renal dysfunction and low systolic blood pressure (SBP) remain the main predictors of adverse clinical outcomes in ADHF patients. Thus, therapy should be tailored according to the level of SBP at admission, renal function and fluid retention. ADHF due to hypertensive disease should be treated with intravenous vasodilators and diuretics at low doses, while patients with low output syndrome need mainly inotropic support. However, few agents currently employed in the treatment of ADHF have been shown in large prospective randomized clinical trials to improve clinical outcomes. The calcium sensitizer levosimendan is superior than traditional inotropes in improving central hemodynamics and neurohormonal response in ADHF patients, without increasing their long-term survival. Vasopressin antagonists also seem to be promising and safe drugs in the treatment of ADHF patients, facilitating diuresis on top of standard-care therapy. Encouraging novel therapies include adenosine receptor antagonists, ularitide, istaroxime, cardiac myosin activators and relaxin. Conclusions: Clinical scenarios based on SBP are essential determinants of therapeutic approaches used for the management of ADHF. Traditional drugs (diuretics, dobutamine and milrinone) have several limitations in real clinical practice, and increase mortality rates. Investigational drugs targeting to novel pathophysiologic concepts are promising treatment approaches and ongoing trials will define their clinical efficacy and safety.

Clinical course of hepatitis B virus infection during pregnancy

For women with hepatitis B virus (HBV) infection, little is known about the natural progression of the disease during pregnancy or its impact on pregnancy outcomes. To investigate the natural progression of HBV infection during pregnancy or its impact on pregnancy outcomes. In this retrospective cohort study, we reviewed medical records of all patients who were pregnant and presented with HBsAg-positivity between 2000 and 2008 at a community gastroenterology practice and a university hepatology clinic. Maternal characteristics were analysed according to maternal and perinatal outcomes. A total of 29 cases with at least 2 measurements of either HBV DNA or alanine aminotransferase (ALT) levels were included. Older age was the only predictor of a trend towards higher risk of an adverse clinical outcome [OR = 1.21 (0.97-1.51), P = 0.089], defined as either a negative foetal outcome (premature delivery, spontaneous abortion), or a negative maternal outcomes (gestational diabetes mellitus, pre-eclampsia, hepatic flare, liver failure). This trend for age remained even after adjusting for baseline ALT. Baseline serum HBV DNA, ALT, hepatitis B e antigen status, gravida and parity were not significant predictors for adverse clinical outcomes. Four patients developed liver failure. Maternal and neonatal outcomes are highly variable in this clinic-based patient cohort. Severe complications due to HBV infection can occur during pregnancy in previously asymptomatic patients. It is unclear how generalizable the results observed in this cohort would be to the general population; therefore, further studies are needed to identify reliable predictors for significant adverse outcomes and until more data are available, pregnant patients with HBV infection should be monitored with periodic serum HBV DNA and ALT levels.

Impact of female gender and transradial coronary stenting with maximal antiplatelet therapy on bleeding and ischemic outcomes

Female gender has been associated with poorer outcomes after percutaneous coronary intervention (PCI) and femoral approach. However, no data are available on the impact of gender and transradial PCI with maximal antiplatelet therapy on bleeding and ischemic outcomes. In the EArly discharge after Stenting of coronarY arteries (EASY) trial, 1,348 patients with acute coronary syndrome underwent transradial PCI. All patients were pretreated with aspirin and clopidogrel. After sheath insertion, 70 U/kg heparin was administered and a bolus of abciximab was given before first balloon inflation. Major adverse cardiac events including death, myocardial infarction, and target vessel revascularization; major bleeding; and local hematomas were evaluated at 30 days, 6 months, and 12 months. Women (n = 298, 22%) were older, had more hypertension, more family history, and less previous PCI than men. Weight, baseline hemoglobin, and creatinine clearance were significantly lower in women. The number of dilated sites, complex lesions, and procedure duration was similar, but 5F sheath size was more frequent in women. Major adverse cardiac events remained similar at 30 days (3.4% vs 3.9%, P = .86), at 6 months (11.5% vs 7.8%, P = .06), and at 1 year (14.1% vs 12.6%) in both groups. There was no significant difference in the incidence of major bleeding between the 2 groups, but female gender was the only independent predictor of hematomas (odds ratio 4.40, 95% confidence interval 2.49-7.81, P < .0001). Despite more comorbidities, female gender was not a predictor of adverse clinical outcomes after transradial PCI with maximal antiplatelet therapy. Still, female gender remained associated with a higher risk of local hematomas. Efforts should continue to identify modifiable factors to reduce procedural bleeding in women, regardless of the access site.

Impact of Postoperative Infection on Long-Term Survival After Potentially Curative Resection for Gastric Cancer

We focused on the impact of postoperative infection on long-term survival after potentially curative resection for gastric cancer. Postoperative surgical and medical complications have been implicated as a negative predictor of long-term outcome in various malignancies. However, there have been no published reports assessing the impact of complications arising from postoperative infection on survival in gastric cancer. We studied a population of 1,332 patients who underwent curative resection for gastric cancer. These patients were divided into two groups based on the occurrence (141 patients, 10.6%) or absence (1,191 patients, 89.4%) of postoperative complications due to infection. We investigated the demographic and clinicopathological features of each patient with and without postoperative complications from infection, and thereby the impact of postoperative infection on long-term survival. Patients with postoperative infection had significantly higher frequency of males, upper side tumor location, and total gastrectomy as a surgical procedure, more advanced stage of gastric cancer, and greater age compared with those without postoperative infection. Patients with complications due to postoperative infection had significantly more unfavorable outcome compared with those patients without postoperative infection. Multivariate analysis demonstrated that age, preoperative comorbidity, blood transfusion, tumor depth, nodal involvement, and postoperative infection correlated with overall survival. We conclude that postoperative complications from infection are a predictor of adverse clinical outcome in patients with gastric cancer. However, further immunological study and prospective trials are necessary to confirm the biological significance of these findings.

Role of high-mobility group box 1 protein in post-infarction healing process and left ventricular remodelling

High-mobility group box 1 protein (HMGB1) is one of the recently defined damage-associated molecular pattern molecules derived from necrotic cells and activated macrophages. We investigated clinical implications of serum HMGB1 elevation in patients with acute myocardial infarction (MI). Then, we evaluated the effect of HMGB1 blockade on post-MI left ventricular (LV) remodelling in a rat MI model. Serum HMGB1 levels were examined in patients with ST-elevation MI (n = 35). A higher peak serum HMGB1 level was associated with pump failure, cardiac rupture, and in-hospital cardiac death. Then, an experimental MI model was induced in male Wistar rats. The mRNA and protein expression of HMGB1 were increased in the infarcted area compared with those values observed in sham-operated rats. We administered neutralizing anti-HMGB1 antibody (MI/anti-H) or control antibody (MI/C) to MI rats subcutaneously for 7 days. The mRNA levels of tumour necrosis factor-alpha and interleukin-1beta and the number of macrophages in the infarcted area were reduced on day 3 in MI/anti-H rats compared with MI/C rats. Interestingly, HMGB1 blockade resulted in thinning and expansion of the infarct scar and marked hypertrophy of the non-infarcted area on day 14. Elevated serum HMGB1 levels were associated with adverse clinical outcomes in patients with MI. However, HMGB1 blockade in a rat MI model aggravated LV remodelling, possibly through impairment of the infarct-healing process. HMGB1, a novel predictor of adverse clinical outcomes after MI, may have an essential role in the appropriate healing process after MI.

Abstract 2025: TIMI Major Bleeding Independently Predicts Mortality in an Unselected STEMI Population: Results from the AMI-Quebec Study

Major bleeding was recently identified as an independent predictor of adverse clinical outcomes in patients with acute coronary syndromes. We sought to determine the impact of major bleeding on in-hospital mortality in patients with ST-elevation myocardial infarction (STEMI) and the clinical characteristics associated with major bleeding. AMI-QUEBEC was a retrospective cohort study of consecutive STEMI patients admitted to 17 selected acute-care hospitals in the Province of Quebec (Canada) in 2003. Research coordinators identified major bleeding complications according to the Thrombolysis In Myocardial Infarction (TIMI) classification. The cohort included 1,655 patients. Thirty-eight percent (38%) of patients were treated with fibrinolysis, 51% with primary percutaneous coronary intervention (PCI) (65% femoral approach) and 12% received no reperfusion therapy. Twenty-eight percent (28%) of patients were females, mean age was 62.3 years, mean weight was 77.5 kg, 5.1% had prior stroke, and baseline serum creatinine was 104 μmol/L. Concomitant medications included clopidogrel loading in 32%, glycoprotein IIb/IIIa inhibitor 24%, unfractionated heparin 82% and low molecular weight heparin 9%. TIMI major bleeding occurred in 7.3% of patients. Overall in-hospital mortality was 11.6%. Independent predictors of mortality were major bleeding (OR 4.36 [2.48 –7.68]) and age (OR 1.06 [1.03–1.08] per year increase). Independent predictors of TIMI major bleeding were femoral approach (OR 11.2 [3.9 –32.1]) female gender (OR 2.8 [1.5–5.1]) and peak creatinine (OR1.02 [1.01–1.03] per 1μmol/L increase). Age, weight, blood pressure, mode of reperfusion, clopidogrel, aspirin, anticoagulant, clopidogrel load, glycoprotein IIb/IIIa inhibitors, PCI within 24 hours post-fibrinolysis were not independent predictors of major bleeding. TIMI major bleeding conferred a greater than four-fold increase in risk of short-term mortality in an unselected STEMI population. The use of the femoral approach for vascular access was the most powerful predictor of major bleeding in this patient population, highlighting the impact of vascular access site selection.

Innate immunity is a new therapeutic target for heart failure

Toll-like receptor (TLR) is expressed in a variety of tissues and recognizes pathogens such as bacteria, fungus and virus. Ligand binding to TLR leads to the activation of NF-kB and causes inflammatory response. On the other hand, pentraxin 3 (PTX3) is a soluble pattern recognition receptor produced by endothelial cells, smooth muscle cells and macrophages in response to primary inflammatory signals. PTX3 recognizes microbes, activates compliment and facilitates pathogen recognition. Therefore, TLR and PTX3 are thought to be responsible for cellular and humoral innate immunity, respectively. In TLR2 knockout (KO) mice, ventricular remodeling after myocardial infarction was suppressed, and cardiac function was preserved compared to wild-type littermate (WT) mice. Survival rate after myocardial infarction was higher in TLR2 KO mice than in WT mice. After doxorubicin administration, cardiomyocyte apoptosis and cardiac dysfunction were blocked in TLR2 KO mice compared to WT mice. In PTX3 KO mice, pressure overload-induced cardiac dysfunction was attenuated compared to WT mice. In human heart failure, plasma PTX3 levels increased with advancing NYHA functional class. The multivariate Cox proportional hazard analysis demonstrated that PTX3 was an independent predictor of adverse clinical outcomes in patients with heart failure. These data suggest that innate immunity plays an important role in heart failure and may be a potential novel therapeutic target to prevent heart failure.

Microvascular Obstruction and the No-Reflow Phenomenon After Percutaneous Coronary Intervention

C ase presentation A: A 50-year-old diabetic man presented to the hospital after 8 hours of continuous chest pain. Because of acute myocardial infarction of the anterior wall, he underwent direct stenting to an occlusion in the left anterior descending coronary artery. Despite revascularization, suboptimal coronary flow was achieved, and he subsequently developed heart failure. Case presentation B: A 77-year-old man underwent elective stenting of a significant stenosis in a degenerated saphenous vein coronary bypass graft. After the procedure, coronary flow in the graft was severely reduced, and he sustained a myocardial infarction in the subtended myocardial territory. The concept of “no reflow” refers to a state of myocardial tissue hypoperfusion in the presence of a patent epicardial coronary artery. The underlying cause of no reflow is microvascular obstruction, which may be produced by various mechanisms. No reflow can be classified according to the duration of the preceding myocardial ischemia (Figure 1). “Reperfusion no reflow” occurs after primary percutaneous coronary intervention (PCI) for reperfusion of an infarct artery in the setting of acute myocardial infarction (AMI) and may be asymptomatic or may present clinically with continued chest pain and ST-segment elevation. Reperfusion no reflow is preceded by ischemic cell injury, is confined to the irreversibly damaged necrotic zone, and may be exacerbated at the time of reperfusion. Reperfusion no reflow is an independent predictor of adverse clinical outcome after AMI regardless of infarct size and is associated with heart failure and increased mortality.1 Figure 1. Schematic illustrating the effect of duration of preceding myocardial ischemia on mechanism of no reflow (NR). “Interventional no reflow” follows noninfarct PCI and affects myocardium that was not subjected to prolonged ischemia before the procedure. Clinically recognized interventional no reflow that complicates PCI is typically sudden in onset, presenting as acute ischemia with chest …

Von Willebrand Factor in Cardiovascular Disease

von Willebrand factor (VWF) plays a pivotal role in platelet adhesion and aggregation at sites of high shear rates (eg, in coronary arteries that have stenotic or ruptured atherosclerotic plaque lesions). Numerous studies have investigated the relationship between VWF plasma levels and thromboembolic cardiovascular events. In contrast to the rather weak association in the general population, in patients with preexisting vascular disease, VWF is significantly predictive for adverse cardiac events, including death. Likewise, VWF typically rises during the course of acute coronary syndrome, and the extent of this VWF release is an independent predictor of adverse clinical outcome in these patients. Various lines of evidence indicate that VWF is not only a marker but also actually an important effector in the pathogenesis of myocardial infarction. This central role of VWF in thrombogenesis has made it a promising target for research into new antiplatelet therapies that specifically inhibit VWF. This review focuses on the role of VWF in acute coronary syndrome and further outlines the relevance of therapeutic interventions targeting VWF for acute coronary syndrome patients.

The predictive effect of insight on adverse clinical outcomes in bipolar I disorder: A two-year prospective study

Research has revealed that a lack of insight is associated with poorer clinical outcomes in schizophrenia; however, the predictive value of insight on adverse clinical outcomes among bipolar patients is quite understudied. The aim of this prospective study was to examine the impact of insight on adverse clinical outcomes among the patients with bipolar I disorder over a 2-year period. Sixty-five remitted bipolar I disorder patients received follow-up assessments at 3, 6, 9, 12, 18, and 24 months to detect the adverse clinical outcomes defined by the incidence of bipolar-related psychiatric hospitalization, emergency room visits, violent or suicidal behavior. The Schedule of Assessment of Insight was used to provide a baseline insight score. Cox regression analysis was used to examine the predictive value of insight on the adverse clinical outcomes. Impaired insight into treatment and a greater number of previous hospitalizations significantly increased the risk of adverse clinical outcomes with bipolar disorder in the 2-year period. However, insight into recognition of the illness and re-labeling of psychotic phenomena did not have any significant effect on adverse clinical outcomes. Bipolar patients' insight into treatment is an independent predictor of adverse clinical outcomes. Improving insight into treatment might be a promising target for a better outcome.

Urinary N-Acetyl-β-(D)-Glucosaminidase Activity and Kidney Injury Molecule-1 Level Are Associated with Adverse Outcomes in Acute Renal Failure

The role of urinary biomarkers of kidney injury in the prediction of adverse clinical outcomes in acute renal failure (ARF) has not been well described. The relationship between urinary N-acetyl-beta-(D)-glucosaminidase activity (NAG) and kidney injury molecule-1 (KIM-1) level and adverse clinical outcomes was evaluated prospectively in a cohort of 201 hospitalized patients with ARF. NAG was measured by spectrophotometry, and KIM-1 was measured by a microsphere-based Luminex technology. Mean Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score was 16, 43% had sepsis, 39% required dialysis, and hospital mortality was 24%. Urinary NAG and KIM-1 increased in tandem with APACHE II and Multiple Organ Failure scores. Compared with patients in the lowest quartile of NAG, the second, third, and fourth quartile groups had 3.0-fold (95% confidence interval [CI] 1.3 to 7.2), 3.7-fold (95% CI 1.6 to 8.8), and 9.1-fold (95% CI 3.7 to 22.7) higher odds, respectively, for dialysis requirement or hospital death (P < 0.001). This association persisted after adjustment for APACHE II, Multiple Organ Failure score, or the combined covariates cirrhosis, sepsis, oliguria, and mechanical ventilation. Compared with patients in the lowest quartile of KIM-1, the second, third, and fourth quartile groups had 1.4-fold (95% CI 0.6 to 3.0), 1.4-fold (95% CI 0.6 to 3.0), and 3.2-fold (95% CI 1.4 to 7.4) higher odds, respectively, for dialysis requirement or hospital death (P = 0.034). NAG or KIM-1 in combination with the covariates cirrhosis, sepsis, oliguria, and mechanical ventilation yielded an area under the receiver operator characteristic curve of 0.78 (95% CI 0.71 to 0.84) in predicting the composite outcome. Urinary markers of kidney injury such as NAG and KIM-1 can predict adverse clinical outcomes in patients with ARF.

Low triiodothyronine and survival in end-stage renal disease

Plasma triiodothyronine (fT3) is a strong predictor of adverse clinical outcomes in various clinical conditions. Since fT3 in patients with end-stage renal diseases (ESRD) is frequently reduced and is associated with inflammation and cardiovascular damage, we prospectively tested the hypothesis that it predicts death in a cohort of 200 hemodialysis patients. Plasma fT3 was lower in ESRD patients (P<0.001) than in healthy subjects and in clinically euthyroid patients with normal renal function. During the follow-up 102 patients died. Patients who died had significantly lower plasma fT3 than those who survived (P<0.001) and in a Kaplan-Meyer analysis plasma fT3 was associated with death (P<0.001). On multivariate Cox's regression analyses, adjusting for a series of traditional and emerging risk factors including inflammation markers, patients with relatively higher plasma fT3 (hazard ratio (HR) (1 pg/ml increase in fT3)) had a 50% reduction in the risk of death (HR=0.50, 95% CI: 0.35-0.72) as compared to those having relatively lower fT3 levels. Of note, plasma fT3 captured most of the predictive power of interleukin-6 (IL-6) because this latter variable emerged as a significant predictor of death only in a model excluding fT3. Low fT3 is an independent predictor of death in hemodialysis patients. These data lend support to the hypothesis that thyroid dysfunction is implicated in the high risk of the ESRD population.