Faculty Peer Reviewed
News about the devastating tornado that flattened Joplin, MO had begun to fall from the headlines until reports of a relatively rare fungal infection in a surprisingly large number of people emerged this week. Mucormycosis is generally spread via puncture wounds or through the air, not person-to-person. It mainly inflicts its woes on those with impaired immune systems. More troubling was the recent E. coli outbreak in Germany which caused 31 deaths and sickened thousands.  Health officials finally found the potential source, contaminated bean sprouts. Pictures of meals snapped with camera phones helped solved the mystery. Women appear to have developed much more severe disease than men when infected with this lethal strain of E. coli. 
With some nods to findings supportive of women’s health, let’s take a look at a few noteworthy medical news items this week. A multinational multicenter study published in the NEJM this week demonstrated benefits of the aromatase inhibitor, exemestane, compared with placebo in preventing the development of invasive breast cancer and pre-cancerous lesions.  The researchers studied women with increased risk as assessed by the Gail risk score and other criteria.  While earlier studies with tamoxifen and reloxifene, selective estrogen receptor modulators (SERMs), have shown reductions in cancer incidence, these trials failed to show a mortality benefit, and these drugs also exhibited toxic side effects. In this new study, there was a 65% reduction in incidence of invasive cancer at 3 years compared with placebo, with an even greater reduction at 5 years. Quality of life measures were similar between the two groups and there was a lack of significant adverse toxic events, such as fractures and myocardial infarction, as had been suggested before in head-to-head comparisons with tamoxifen. The downside is that the number needed to treat is much higher at 3 years than at 5 years, which proved difficult to achieve given the side effect profile.
A not-terribly-surprising, albeit strong, study came out of Boston this week which demonstrated that smoking was a significant risk factor for symptomatic peripheral artery disease in women.  Smoking is known to lead to cardiac disease and strokes, and it had been naturally assumed to lead to peripheral artery disease and intermittent claudication. This new study looked at participants in the Women’s Health Study and evaluated the relationship between smoking tobacco and claudication symptoms and surgical and catheter-based procedures to treat PAD. The researchers also examined inflammatory markers, including hsCRP and sICAM-1, and traditional markers for cardiovascular disease risk. Interestingly for clinicians is that smoking cessation reduces the risk of PAD, similar to that of cardiovascular disease. However, unlike in heart disease where risk levels fall to baseline after roughly 20 years of tobacco abstinence, risk for PAD does not. This underscores the importance of primary prevention, especially in younger, less educated, pre-menopausal participants. Education, whether at a university or in a clinician’s office, is an incredibly valuable tool to prevent disease.
Speaking of cardiac disease, our colleagues in England looked at the effects of simvastatin and ezetimibe in preventing major atherosclerotic events in patients with advanced kidney disease (serum creatinine greater than 1.7 in men and 1.3 in women, regardless of dialysis status) in the SHARP trial (Study of Heart And Renal Protection) . The mechanism of cardiac disease seems to change from mostly atherosclerosis in patients with relatively good renal function to a multifactorial etiology (calcification, structural cardiac changes and sympathetic overactivity) in patients with poor renal function. The authors wanted to see if reducing LDL with lower statin doses would be beneficial to cardiovascular health, since patients with renal disease are more likely to develop myopathy at higher doses. And with the news this week that high dose simvastatin has an increased risk of muscle damage, this article is especially timely. 
Low-dose statin (simvastatin 20mg) was paired with a cholesterol-absorption inhibitor (ezetimibe 10mg). The reduction of 17% in atherosclerotic events was similar to results from other studies assessing risk in patients without advanced renal disease. Non-significant reductions in non-fatal myocardial infarction were seen, but the study was not powered effectively to look at finer components of cardiovascular risk. One standout is the 25% reduction in ischemic strokes. What will be interesting to learn is whether renal patients with known cardiovascular disease, who were excluded, would benefit as well.
Our colleagues uptown at Columbia published a study in the NEJM this week evaluating the non-inferiority of transcatheter aortic-valve replacement in high risk patients as compared with surgical replacement.  Patients with severe aortic stenosis and NYHA Class II pump function or worse who were not too sick by their criteria to undergo surgical repair were randomized to either the transcatheter (transfemoral or transapical) or surgical arm. More surgical patients fell out of the study than in the transcatheter arm, so both intention-to-treat and per-protocol analyses were presented for the primary outcome of death from any cause. There was a significant reduction in mortality at 30 days in the transfemoral approach in the intention-to-treat analysis, but there was no significance in any of the other analyses, either at 30 days or 1 year. The transcatheter approach performed equally well as the traditional method.
And there were some other benefits in the transcatheter arm, including shorter ICU and hospital stay and improved aortic gradient (albeit with an occasionally worse perivalvular regurgitation). Not surprisingly, the transcatheter procedure had a disturbingly higher rate of stroke but without increased mortality, regardless of approach. The authors report equipment design changes are likely needed. And the patients who were treated with the less invasive procedure were ambulatory more reliably at 30 days than those who went under the knife. But at one year, the surgical group appeared to fare just as well in pump function and exercise tolerance as their friends in the catheter group.
As if the glitazones didn’t have enough to bad press already. New reports have emerged regarding Actos and the increased risk of bladder cancer in the men who take this drug.  The German and French equivalents of the FDA have suspended sales in their respective countries. Stay tuned for the FDA’s official recommendation.
And now for the men. As if internists didn’t have enough of a challenge sorting out whether to recommend prostate cancer screening to begin with, the FDA has a sneaking suspicion that the 5-alpha-reductase inhibitors (think finasteride) may lead to high-grade (Gleason 8-10) prostate cancer, and recommend screening before starting these meds. 
And that’s a full lid. Remember, Father’s Day is this Sunday.
Dr. Christopher Schultz is a 3rd year resident at NYU Langone Medical Center
Peer reviewed by Ishmeal Bradley, Section Editor, Clinical Correlations
Image courtesy of Wikimedia Commons
1. Williams T. Rare Infection Strikes Victims of a Tornado in Missouri [Internet]. 10 June 2011. http://www.nytimes.com/2011/06/11/us/11fungus.html?hp
2. Kupferschmidt K. Restaurant Photos Help Nail Sprouts in German Outbreak [Internet]. 10 June 2011. http://news.sciencemag.org/scienceinsider/2011/06/restaurant-photos-help-nail-bean.html?ref=hp
3. Neuman W. Sprouts, Poster Plant of Health Food, Can Pack Risks [Internet]. 10 June 2011. http://www.nytimes.com/2011/06/11/business/11sprouts.html?ref=science
4. Goss PE et al. Exemestane for Breast-Cancer Prevention in Postmenopausal Women [Internet]. NEJM 2011. E-pub ahead of print, 4 June 2011. http://www.nejm.org/doi/full/10.1056/NEJMoa1103507
5. National Cancer Institute/U.S. National Institutes of Health. Breast Cancer Risk Assessment Tool [Internet]. Last updated: 16 May 2011. http://www.cancer.gov/bcrisktool/about-tool.aspx.
6. Conen D, et al. Smoking, Smoking Status, and Risk for Symptomatic Peripheral Artery Disease in Women: A Cohort Study [Internet]. Ann Int Med. 6 June 2011; 154 (11): 719-726. http://www.annals.org/content/154/11/719.abstract
7. Baigent C et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial [Internet]. Lancet 2011. E-pub ahead of print, 9 June 2011. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60739-3/fulltext
8. Hensley S. FDA: High Dose of Popular Cholesterol Medicine May Damage Muscles [Internet]. 8 June 2011. http://www.npr.org/blogs/health/2011/06/08/137063562/fda-high-dose-of-popular-cholesterol-medicine-may-damage-muscles?sc=nl&cc=es-20110612
9. Smith CR, et al. Transcatheter versus Surgical Aortic-Valve Replacement in High-Risk Patients [Internet]. NEJM 9 June 2011; 364(23): 2187-2198. http://www.nejm.org/doi/full/10.1056/NEJMoa1103510
10. Dow Jones for The Wall Street Journal. Update: France, Germany Suspend Takeda’s Actos On Bladder Cancer Risk [Internet]. 10 June 2011. http://online.wsj.com/article/BT-CO-20110610-700058.html
11. Stein R. FDA Issues Warning On Prostate Drugs [Internet]. 9 June 2011. http://www.washingtonpost.com/blogs/the-checkup/post/fda-issues-warning-on-prostate-drugs/2011/06/09/AG0IHfNH_blog.html