PrimeCuts: This Week in the Journals

October 12, 2009

nobelMichael Tees, MD, MPH

While the news was dominated by President Barack Obama winning the Nobel Peace Prize, other American Nobel Laureates should not be forgotten. After all, Elizabeth Blackburn, Carol Greider and Jack Szostak waited over 20 years for theirs. These American scientists shared the Nobel Prize in Physiology or Medicine this week “for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase”[1]. American scientists this year are also sharing the Nobel Prize in the field of Chemistry as well as Physics. While we thank our scientists (and politician) for all their amazing accomplishments, unfortunately, none were recipients of a PrimeCuts Prize this week. These highly selective PrimeCuts Prizes were born on the concept that all recipients must have published newsworthy, scientific information in the preceding week. Further, it must have been interesting. So without further adieu, here are the winners of this week’s PrimeCuts Prizes.

This week, Vincent Lombardi and colleagues are the recipients of the PrimeCuts Prize in Virology after publishing findings in Science that a gammaretrovirus was identified in peripheral mononuclear cells of 67% of patients with chronic fatigue syndrome[2]. Comparatively, the xenotropic murine leukemia virus-related virus (XMRV) was found in only 3.7% of the healthy control group. While repeating the name of the virus may cause an episode of fatigue, the estimated 17 million suffering from this ailment will welcome this news. A systematic review in 2005 showed only a 39.5% (range 8-63%) improvement in symptoms; worse, a median full recovery rate was 5% (0%-31%)[3]. To some, the XMRV may sound familiar. This retrovirus’s DNA was discovered three years ago, not in blood cells, but in prostate cancer cells. Less than a month ago, several pathologists from Columbia published a study in the Proceedings of the National Academy of Sciences showing XMRV proteins were expressed in 23% of prostate cancers, especially the higher-grade tumors[4]. This is strong evidence that the virus itself may be tumorigenic. Ironically, research in the oncology field suggests XMRV is responsive to interferon therapy[5]. In HCV therapy, side effects with interferon include muscle aches, headaches, and fevers in 80% of patients and rates of depression in 20-40% of those on therapy[6]. If further research shows that XMRV is actually the cause of chronic fatigue syndrome, we may find ourselves in a clinical predicament. Regardless, the study by Lombardi will likely create an explosion of further studies on chronic fatigue syndrome.

The PrimeCuts Prize in Cardiology goes to Garhard Steinbeck and 14 of his colleagues of the Immediate Risk-Stratification Improves Survival (IRIS) trial. These investigators demonstrated that, in fact, immediate risk-stratification does not improve survival[7]. Sudden cardiac death, often from tachyarrhythmias, is highest in the weeks surrounding an acute MI, and several prior studies had demonstrated a survival benefit of placing implantable cardioverter-defibrillator s (ICD) soon after a cardiac event. However, this study published in the New England Journal of Medicine showed overall mortality over 37 months was not reduced in those receiving an ICD compared to medical therapy alone. Competing this week for the Prize in Cardiology were Pawel E. Buszman and colleagues who published a study in the Journal of the American College of Cardiology assessing stent placement in “unprotected” left main coronary artery disease[8]. “Unprotected” left main coronary arteries (ULMCA) are those that have not had a bypass graft. This study showed that in ULMCA patients who were stented, the risk of major adverse cardiac and cerebral events as well as death was significantly lower in those receiving a drug-eluting stent (DES) compared to a bare-metal stent (BMS). This study did not match those receiving a stent to those receiving a bypass graft, and therefore does not significantly change our current management. However, it adds to the increasing scrutiny of bypass being the only option in left main coronary artery disease.

The PrimeCuts Prize in Cancer this week is awarded to Werner Schroth and 21 co-authors who published in JAMA this week that that women with breast cancer receiving tamoxifen responded differently to the drug depending on the activity of a cytochrome P450 2D6[9]. The anti-proliferative activity of the cancer drug tamoxifen lies in the metabolites formed after breakdown. Those with increased activity of cytochrome P450 2D6, the “extensive metabolizers”, were associated with a significantly decreased rate of breast cancer recurrence compared to intermediate and poor metabolizers. The poor and intermediate metabolizers also had a worse event-free survival and disease-free survival compared to the extensive metabolizers.

Researchers from NYU Division of Pulmonary and Critical Care published findings in Chest this week shedding light on the lung disease seen in NYC firefighters exposed to World Trade Center dust of the September 11, 2001 attacks. Researchers have previously have a decrease in lung function among the those exposed to the attacks, but this study combined data from several modalities using information from pre- 9/11 and post- 9/11. Authors discovered that for the vast majority of patients, the particulate matter and pollutants from the collapse appears to have caused obstructive airways disease rather than interstitial disease. These researchers share the PrimeCuts Prize in Pulmonology for their devotion to the treatment of the FDNY first responders and results that have potential implications for all acute pollutant exposures[10].

Nayer Khazeni and colleagues of Stanford University Medical Center are the recipients of the PrimeCuts Prize in Epidemiology this week. In the Annals of Internal Medicine, the researchers published findings on the effectiveness and cost-effectiveness of vaccination against H1N1/09 using epidemic models and different scenarios[11]. In the model, a hypothetical city of 8.3 million people received the H1N1 vaccine in mid-October or mid-November. Listen up healthcare providers in New York City; the model was built upon demographics and initial pandemic data from NYC. The model showed that, assuming a 40% vaccination of the population, a mid-October vaccination would avert 2051 deaths and save $469 million compared with no vaccination. But a vaccination of 40% of the population in mid-November would avert 1468 deaths and save $302 million compared with no vaccination. Results were then adjusted since there will be not enough vaccines available for the mid-October estimate. Unfortunately, a feat to vaccinate 40% of the city by October 15 will be impossible. Until more are vaccinated and herd immunity develops, clinicians must continue to emphasize hand washing and, of course, vaccinations.

Flu.gov, sponsored by the U.S. Dept of Health and Human Services (USHHS), did not receive the PrimeCuts Prize for Public Health this week. This website, also known as pandemicflu.gov, is designed to provide influenza information to the public. One section of the site is tackling major myths about the flu, including such rampant ideas as “you can get the flu from drinking water or swimming pools”[12]. Thankfully, we may still drink pool water safely, but the USHHS still has much work ahead to decrease the public fear. An Associated Press poll this week found that 1/3 of parents oppose the flu vaccine [13]. Not surprisingly, a Google search on “flu vaccine dangers” produced sites that erroneously presented how the vaccine can cause Alzheimer’s disease and, of course, autism. The first website on the query offers a list of alternatives, namely avoiding refined sugars, exercising regularly (#1 and #2), and washing your hands (#6). The real PrimeCuts Prize in Pubic Health should be given to all the researchers, epidemiologists, infectious disease specialists, universities, and departments of public health who have performed an amazing feat. In less than 6 months, a new viral strain was identified, tracked, and decoded, leading to a vaccine currently being massed produced and distributed across the country and world. Not everyone can be acknowledged with a Nobel Prize or a PrimeCuts Prize, but everyone wins by the discoveries made by the scientific community. Every day brings new scientific advances, and every week brings you a new edition of PrimeCuts. And that is a prize to share with all.

Dr. Tees is a 2nd year internal medicine resident at NYU Medical Center.

Faculty peer reviewed by Cara Litvin MD, Executive Editor, Clinical Correlations

1. http://nobelprize.org/nobel_prizes/medicine/laureates/2009/index.html
2.  Lombardi V, Ruscetti F, Das Gupta J, et al. Detection of an infectious retrovirus, XMRV, in bloodcells of patients with chronic fatigue syndrome. Sci. Published online 8 Oct 2009; 10.1126/science.1179052. (http://www.sciencemag.org/cgi/content/abstract/1179052)
3. Cairns R, Hotopf. A systematic review describing the prognosis of chronic fatigue syndrome. Occup Med-C. 2005 Jan;55(1):20-31.
4. Schlaberg R, Choe D, Thaker H, Singh I. XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors. P Natl Acad Sci USA. 2009 Sep;106(38):16351-6. (http://www.pnas.org/content/106/38/16351.abstract)
5. Dong B, Kim S, Hong S, et al. An infectious retrovirus suspectible to an IFN antiviral pathway from human porstate tumors. P Natl Acad Sci USA. 2007 Jan;104(5):1655-60. (http://www.pnas.org/content/104/5/1655.abstract)
6. http://www.uptodate.com/online/content/topic.do?topicKey=heptitis/19139#8
7. Steinbeck G, Andresen D, Seidl K, et al. Defibrillator implantation early after myocardial infarction. New Engl J Med. 2009 Oct;361(15):1427-36. (http://content.nejm.org/cgi/content/short/361/15/1427)
8. Buszman P, Buszman P, Kiesz S, et al. Early and long-term results of unprotected left main coronary artery stenting. J Am Coll Cardiol. 2009 Oct;54(16):1500-11. (http://content.onlinejacc.org/cgi/content/abstract/54/16/1500)
9. Schroth W, Goetz M, Hamann U, et al. Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA. 2009 Oct;302(13):1429-36. (http://jama.ama-assn.org/cgi/content/short/302/13/1429?home)
10. Weiden M, Ferrier N, Nolan A, et al. Obstructive airways disease with air trapping among firefighters exposed to world trade center dust. Chest. Published online 9 Oct 2009;10.1378/chest.09-1580. (http://chestjournal.chestpubs.org/content/early/2009/10/08/chest.09-1580.abstract)
11. Khazeni N, Hutton D, Garber A, et al. Effectiveness and cost-effectiveness of vaccination against pandemic influenza (H1N1) 2009. Ann Intern Med. 2009 Dec;151(12). Published online 6 Oct 2009. (http://www.annals.org/cgi/content/full/0000605-200912150-00157v1)
12. www.flu.gov/myths/index.html
13. http://news.yahoo.com/s/ap/20091007/ap_on_he_me/us_med_swine_flu_vaccine_fears

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