Primecuts – This Week In The Journals

April 25, 2011

By Keri Herzog, MD

Faculty Peer Reviewed 

Amidst tornadoes in the southeast, wildfires in the southwest, and flooding in the northeast, it is often impossible to predict when or who may be affected by the weather that has been afflicting our nation. As we pick up the pieces, and take some control over our lives, it is comforting to know that this week the journals have focused on how we can best utilize our medical and scientific resources to be able to identify and change the future for those most at risk. 

 This week, The Annals of Internal Medicine set out to examine the characteristics and short term outcomes of those patients who are most at risk for perioperative myocardial infarctions (MI) [1]. In this cohort study encompassing 190 medical centers and 8351 patients, four cardiac markers/enzyme assays were measured within 3 days of non-cardiac surgery. 415 patients had a perioperative MI, 74.1% of those occurred within 48 hours of surgery, and 65.3% did not experience any ischemic symptoms. The 30-day mortality rate was 11.6% among patients who had a perioperative MI and 2.2 % among those who did not (P< 0.001). Among patients with a perioperative MI, mortality rates were elevated and similar between those with (9.7%; OR 4.76 [95% CI, 2.68 to 8.43]) and without (12.5%; OR, 4.00 [CI, 2.65 to 6.06]) ischemic symptoms. Overall this study is extremely notable because it demonstrated that most patients with perioperative MI will not experience ischemic symptoms.  Thus, it is imperative to continue routine monitoring of troponin levels in at-risk patients since they have a poor prognosis regardless of symptoms.

 The risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B was addressed in an prepublication online article in The Lancet Oncology. [2] While it is known that therapy targeting hepatitis B reduces the risk of progression to HCC, a simple scoring system to predict the risk of developing HCC in patients with hepatitis B would be very useful. Through a cohort study of 5089 patients, a Cox multivariate proportional hazards model predicting HCC risk at 3, 5, and 10 years was used. Variables such as age, gender, ALT, HBeAg status, and serum HBV DNA level were included to develop a 17-point risk score and the area under receiver operating curve (AUROC) was calculated and predicted HCC risk. The HCC risk ranged from 0% to 23.6% at 3 years, 0% to 47.4% at 5 years, and 0% to 81.6% at 10 years for patients with the lowest and highest HCC risk, respectively. This score thus estimated the risk of developing HCC at 3, 5, and 10 years in patients with chronic hepatitis B and might help guide management and screening decisions in these patients. 

 Highlighted in the Archives of Internal Medicine, a secondary analysis of 3 cohort studies was utilized to assess the validation of serial blood urea nitrogen (BUN) in predicting mortality in patients with acute pancreatitis (AP) [3]. There are several scoring indices we are familiar with that are used as predictors of survival such as Ranson criteria and the APACHE II, which calculate scores based on multiple measurements/parameters. This study set out to use just one parameter in predicting mortality. BUN was chosen for its role as a surrogate marker of intravascular volume as well as a marker of gi hemorrhage and renal function.  A total of 1043 AP cases were included in the analysis. A BUN level of 20 mg/dL or higher was associated with an OR of 4.6 (95% CI, 2.5-8.3) for mortality. Any rise in BUN level at 24 hours was associated with an OR of 4.3 (95% CI, 2.3-7.9) for death and accuracy of serial BUN measurement (AUC, 0.82-0.91) was comparable to that of the APACHE II score (AUC, 0.72-0.92) in each of the cohorts. Surprisingly, this study demonstrated the accuracy of BUN measurement alone as an early prediction of mortality in AP.  The authors also offered an algorithm that may assist us in decisions regarding early resuscitation efforts, and hopefully improve outcomes for our patients with AP.

 In a study published in the New England Journal of Medicine this week, genetic mutations were evaluated for their role in predicting/identifying those patients who have or may be at risk for developing pulmonary fibrosis [4]. The mutations that have been associated with pulmonary fibrosis previously have accounted for only a small proportion of the pulmonary fibrosis population. A common polymorphism in the promoter region of MUC5B (a 3.4-Mb region of chromosome 11p15) has been linked previously to idiopathic interstitial pneumonia and this study set out to evaluate genetic variation in this area and its expression in the lung. This was studied among 83 subjects with familial interstitial pneumonia, 492 subjects with idiopathic pulmonary fibrosis, and 322 controls. MUC5B expression in the lung was 14.1 times as high in subjects who had idiopathic pulmonary fibrosis as in those who did not (P<0.001). Therefore, a common polymorphism in the promoter of MUC5B is associated with familial interstitial pneumonia and idiopathic pulmonary fibrosis and that dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis. The implication that airway mucins are involved in the pathogenesis of pulmonary fibrosis will hopefully lead to  novel therapeutic agents that could take advantage of this finding.  The genetic predisposition could also lead to an  improvement in our ability to detect the disease at an earlier, more treatable stage.

Lastly, a triple-marker approach for chronic kidney disease (CKD) in predicting accuracy for all-cause mortality and end-stage renal disease was evaluated in a recent study in JAMA [5]. This study assessed whether combining creatinine, cystatin C, and urine albumin-to-creatinine ratio (ACR) would improve identification of risks associated with CKD (compared with just utilizing creatinine alone). We are all familiar with creatinine.  Cystatin c is a marker of kidney disease that is gaining popularity as it is less affected by age, race or muscle mass.  The use of ACR has been until now limited to diabetics.  26,643 were enrolled in this prospective cohort study and were categorized into 8 groups defined by GFR. Compared with those with CKD defined by creatinine alone, the hazard ratio for death was 3.3 (95% CI, 2.0-5.6) for participants with CKD defined by creatinine and ACR; 3.2 (95% CI, 2.2-4.7) for those with CKD defined by creatinine and cystatin C, and 5.6 (95% CI, 3.9-8.2) for those with CKD defined by all biomarkers. Risk of ESRD was higher among those with CKD defined by all markers (34.1 per 1000 person-years; 95% CI, 28.7-40.5) vs. those with CKD defined by creatinine alone (0.33 per 1000 person-years; 95% CI, 0.05-2.3). By adding cystatin C to the combination of creatinine and ACR in approaching CKD, the predictive accuracy for all-cause mortality and end-stage renal disease can be improved.

 While we cannot predict the future, this week we learned that in the medical world, we can utilize scientific advances such as triple-marker approaches, evaluation of genetic mutations, and laboratory values to prepare for the road ahead…even if our national weather may be constantly and forever unpredictable.

Dr. Herzog is a 2nd year resident at NYU Langone Medical Center

Peer reviewed by Neil Shapiro, Editor-In-Chief, Clinical Correlations

Image courtesy of Wikimedia Commons


1. Devereaux PJ, Xavier D, Pogue J, et al. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. April 19, 2011; 154: 523-528.

 2. Yang HI, Yuen MF, Chan HLY, et al. Risk estimation for hepatocellular carcinoma in chornic hepatitis B (REACH-B): development and validation of a predicative score. The Lancet April 15, 2011; 2045 (11) 70077-8.

 3. Wu BU, Bakker OJ, Papachristou, GI, et al. Blood urea nitrogen in the early assessment of acute pancreatitis. Arch Intern Med. 2011; 171 (&) 669-676.

 4. Seibold, MA, Wise, AL, Speer MC, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N England Journal of Medicine 2011; 364: 1503-1512.

 5. Peralta CA, Shlipak MG, Judd S, et al. Detection of chronic kidney disease with creatinine, cystatin c, and urine albumin-to-creatinine ration and association with progression to end-stage renal disease and mortality. JAMA. 2011; 305 (15):1545-1552.