Title: NEJM This Week: Supplement to the New England Journal of Medicine, Vol. 359, No. 13.

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" Welcome to the New England Journal of medicine audio summary for the week of September 25 2008. I'm doctor Michael -- This week's issue features articles on from the lice is with -- took place three to four and a half hours after acute ischemic stroke. Drug eluding or bare metal stents for acute my party went -- action. Intensive lipid lowering with cinder Stanton and is at a mine in a nordic and doses. Analyses of cancer data from three is that in my trials. And cell therapies for muscular dystrophy. A review article on lung cancer. A case report of a woman with a mass in the breast and a solitary lesion in the spine. And perspective articles on the controversy surrounding Staten treatment in children and an update on campaign contributions. Lobbying. And the US health sector. From oasis with -- to place three to four and a half hours after acute ischemic stroke. By kvaerner pocket from the unit yes okay -- Germany. Intravenous from voices without -- place improves the outcomes after acute stroke. When out of place is given within three hours after the onset of symptoms. These investigators tested the efficacy and safety of out of place administered between three and four and a half hours after the onset of stroke. More patients had a favorable outcome with out of place -- with placebo. 52 point 4% versus 45 point 2%. Odds ratio one point 34. In the global analysis the outcome was also improved with out of place as compared with placebo odds ratio one point 28. The incidence of intra cranial hemorrhage was higher without replace -- with placebo. For any intra cranial hemorrhage 27%. Versus seventeen point 6%. For symptomatic intra cranial hemorrhage two point 4%. Versus zero point 2%. Mortality did not differ significantly between the out of place and placebo groups seven point 7% and eight point 4% respectively. As compared with placebo. Intravenous out of place administered between three and four and a half hours after the onset of symptoms. Significantly improved clinical outcomes in patients with acute ischemic stroke. How to place was more frequently associated with symptomatic. Intra cranial hemorrhage. Patrick -- and from the veterans affairs medical centers San Diego California. Rights and an editorial that neither of these results nor those of the previous pooled analysis suggests that the ideal window for -- therapy is four and a half hours after the onset of a stroke. Because we know that the potential for neurological rescue. Declines -- Conakry with every passing minute. From the moment the patient arrives at the door every minute counts. Drug eluding were bare metal stands for acute my party -- fortune. By Laura -- from Brigham and women's hospital Boston. In an analysis of patients undergoing coronary artery stent in for -- my party and fortune in Massachusetts. Recipients of drug eluding stents were compared with recipients of bare metal stance in propensity matched cohorts. The two year risk adjusted mortality rates were lower for drug eluding stents and prepare medal stands among all patients with my party and our action. Ten point 7% versus twelve point 8%. Among patients with my party on -- action with ST segment elevation. Eight point 5% versus eleven point 6%. And among patients with my party and -- action without ST segment elevation. Twelve point 8% versus fifteen point 6%. The two year risk adjusted rates of recurrent my -- in -- action. -- used in patients with my part of the fortune without ST segment elevation who were treated with drug eluding stents. And repeat we vascular his nation rates were significantly reduced with the use of drug eluding stents as compared with bare metal stance in all groups. In patients presenting with -- my partner in fortune. Treatment with drug eluding stents is associated with decreased two year mortality rates. And a reduction in the need for repeat -- vascular is nation procedures as compared with treatment with bare metal stents. Intensive lipid lowering which in the Staten and his at a mine in any or mixed analysis. By and Ross -- both from the university hospital Oslo Norway. Hyper with the Kenya has been suggested as a risk factor forced innocence of the aortic valve. But lipid lowering studies have had conflicting results. This trial studied the effects of long term intensive cholesterol lowering with daily use this in the Stanton and -- into mine on clinical and echo party graphic outcomes in patients with purity Faust in doses. The combination of cinder Stanton and his -- resulted in an average reduction in LDL cholesterol. Of at least 50%. As compared with placebo. Despite this favorable effect over a minimum period of four years. The primary outcome occurred in 35 point 3% of patients in this cinder Stanton is that in my group. And in 38 point 2% in the placebo group. You're valve replacement was performed in 28 point 3% of patients in this in the -- is that in my group. And in 29 point 9% in the placebo group. There was a reduction in the need for coronary bypass surgery in this in percent and his at my group. But unexpectedly. Active treatment was also associated with an increased incidence of cancer. 105. Versus seventy cases. Cinder Stanton and is that mine did not reduce the compass that outcome. Of combined aortic felt events and ischemic events. In patience with the -- denounces. In an editorial. -- Otto from the University of Washington Seattle. Writes that the results of this study are disappointing. -- intensive lipid lowering therapy is not the answer to the prevention of a -- denounce his progression. Where do we go from here. We need to explore other potential therapeutic targets especially the pathways that lead to tissue pacification. It is time to integrate and expand our understanding. Of the interactions among initiating factors genetic and clinical co factors. And the mechanisms of progression from an early inflammatory -- to -- to -- transformation. Of -- mile fiber blasts. And then to the end stage of severe -- house education. Analyses of cancer data from three is that in my trials. By Richard Quito from Oxford university in the United Kingdom. Five years of stand therapy. Lowers LDL cholesterol substantially end over a five year period results in reductions in the incidents of cardiovascular events. The trial by Ross a bow and colleagues involving the combination of his -- I've -- to stand in patients with -- critics denounces. Suggested an increased incidence of cancer associated with the use of active therapy. The current analysis of two other ongoing trials have is that in my -- and -- then does not support the suggestion of an increased incidence of cancer. But -- show increased cancer mortality. In the two other trials combined there was no overall excessive cancer. 313. Active treatment versus 326 control. Risk ratio of zero point 96. And no significant excess in any particular site. Among patients assigned to is that -- there were more albeit not significantly more deaths from cancer. 97 -- two in the control group. He equals zero point 7. But there were also fewer although not significantly fewer other cases of cancer 216. Versus 254. In the control group. 8. There was no evidence of a trend in the risk ratio for incidents of or death from cancer with increasing duration of follow. The available results from these three trials do not provide credible evidence of any adverse effect of his MI on rates of cancer. Follow up of longer duration will permit the balance of risks and benefits to be determined more reliably. In an editorial. Thomas -- from the University of Washington Seattle. Writes that three criteria stated in terms of questions. Should be considered in assessing the reliability of exploratory safety analyses. First is it statistically unlikely that such events can be explained by chance. Second is the safety risk biologically plausible and third. Can one identify Independent prospective -- obtained data to confirm the finding. Additional data are needed to adequately address the signal that cinder Stanton -- is associated with an increased risk of death from cancer. Such data should be provided by completed randomized trials that have been prospective we designed and conducted. To meet the performance standards for safety trials. Such confirmation. Is especially important in the case of agents such as is that in my. For which there are safety signals of major illness or death. And evidence of efficacy. That is limited to documented effects on a -- marker. In another editorial. And EJM editor Jeffrey brazen and colleagues write that when the cancer mortality data from the three trials were combined. There was an increase in cancer mortality risk in the combined is that in my groups 134 deaths as compared with 92 deaths in controls. Uncorrected -- equals zero point 7. Because this key value was obtained from one of several data driven analyses. Rather than from a test of a single pre specified hypothesis. He should be interpreted cautiously. The Oxford researchers believe that this finding is due entirely to the -- chance rather than to a true increasing cancer mortality. Although the Oxford group may ultimately proved to be correct. It is appropriate to raise a note of caution. As it -- interferes with the gastrointestinal. Absorption not only of cholesterol. But also other molecular entities that could conceivably affect the growth of cancer cells. The fact that the combined data from all three trials showed an increase in cancer mortality with a -- mind. Should not be assumed to be a chance finding until further data are -- The NE JM will continue to follow the matter and we are prepared to promptly publish new information that sheds further light on this unexpected finding. Physicians and patients are unfortunately left for now with uncertainty about the efficacy and safety of the drug. Lung cancer. Molecular margins of cancer article by Roy -- from the University of Texas MD Anderson cancer center Houston. Environmental factors such as tobacco smoke and genetic susceptibility interact to influence Carson -- Genesis. Actors that are unrelated to smoking including genetic hormonal and viral factors have been suggested. Tissue injury initially occurs in the form of genetic and anti genetic changes and global transcript on changes. These changes can persist long term and eventually lead to aberrant pathway activation in cellular function to produce pre malignant changes. Including this equation and clone little patches. Additional changes can result in angiogenesis. Invasion and early stage cancer and advanced cancer and metastasis. Pre malignant patches contain clones and so clones which can involve loss of hatteras I asked that he. Micro satellite instability and mutations. Lung cancers unrelated and related to smoking have strikingly different molecular profiles. Smoking related patches and primary cancers. Most often develop in the central airway. Most tumors that are not related to smoking are -- no carcinoma is and develop in the peripheral Airways. Molecular markers can signify risk prognosis. And sensitivity to treatment through predictive markers. Such stage specific markers can -- in the course of disease from its early stages through its late stages. They also can help to find mechanisms of resistance to therapy. A 47 year old woman with a mass in the breast and a solitary lesion in the spine. A case record of the Massachusetts General Hospital by William grant a -- and colleagues. -- 47 year old pre menopausal woman came to the hospital for treatment of breast cancer. A mask that measured five centimeters in diameter was present in the left breast. Needle biopsies showed infiltrating doctoral carcinoma. That was great to three hormone receptor positive her two new negative. A staging a valuation disclosed a solitary lesion in the peace expert people body which was asymptomatic. This clinical scenario. Is known as an intact primary tumor we -- metastatic disease. The physicians do not know whether political metastatic disease as seen in this patient. Represents the distinct biological entity with a different prognosis from that of cases with more widespread -- The key management question. Is whether this patient should be treated differently from any other patient with metastatic breast cancer. If the physicians consider that only go -- a static disease is not different from widely metastatic breast cancer. In the primary focus should be on selecting optimal systemic therapy with minimal side effects. And alternative approach for this patient. Would veto assumed that this or -- static breast cancer. Is biologically different from one with widespread in the past deceased so that it treatment approach aimed at long term. Disease free survival should be used including local as well as systemic therapy. Cell therapies for muscular dystrophy. A clinical implications of basic research article by Helen bile from Stanford university school of medicine California. -- muscular dystrophy is it devastating progressive. X linked muscle wasting disease. With an unsteady in early childhood. The disease progresses to final stages that are characterized by Carty a respiratory failure and death. Which usually occurs in the teenage years or early warnings. The disease affects straw I hated muscles of the leans diaphragm and heart in his associated with the progressive loss of muscle mass. Leading to impaired emulation in paralysis. No effective therapies available although a recent study demonstrates an interesting strategy in cell based therapy. Using a model of do -- muscular dystrophy involving the MDX mouse. The authors describe a sub population of freshly isolated satellite cells. Obtained with the use of a combination of molecular markers of which CE XCR for a receptive that responds to signals emitted by muscle damage may be key. Genetically mark skeletal muscle progenitor tours which express green fluorescent protein GFP. Can be recovered from the muscles to which they contribute. The investigators showed that the cells contributed not only to pre existing muscle fibers but also to newly formed fibers. Most remarkably this sub population of satellite cells contributed substantially. To the injected muscles. The authors observed in 90% of muscle fibers were composed themselves labeled with GF me. And led to an unprecedented increase in muscle force in the MDX mouse. Storm over standings. The controversy surrounding pharmacological treatment of children. A perspective article by -- different from Children's Hospital Boston. In July of this year the American academy of pediatrics a AP. Released revised recommendations for the management of hyper -- lenient in children. Within days after publication the new policy statement had elicited a firestorm of controversy including hundreds of print and broadcast news stories editorials in the New York Times in the Boston Globe. And thousands of Internet postings that took many members of the pediatric community by surprise. The AP. And the national cholesterol education program have advocated targeted screening and pharmacological treatment for nearly two decades. What sparked this sudden flurry of media attention. The most controversial change appears to -- in the inclusion of Staten us as potential first line pharmacological agents. The recommendation to you stands in childhood seems to have hit a collective nerve. Perhaps -- waking us to the fuller implications. Of the obesity epidemic. Regardless of how many additional children may receive stand treatment under these new guidelines. The broader more important question is whether we intend to treat pediatric obesity with an ever increasing array of powerful adult drugs. Beta blockers and diuretics for hypertension. Aspirin for coagulant apathy. Insulin sensitize -- for the metabolic syndrome and of course insulin for diabetes. Once this door has been opened the pharmaceutical industry will happily walk through it. Campaign contributions. Lobbying and the US health sector and update. A perspective article by Robert Stein broke a national correspondent for the and EJ and the 2008 US presidential election is already the most expensive ever. With overall fundraising surpassing that for the 2004 contest and the Democrats holding a large lead in the money race. As of the end of July all presidential candidates have reported receiving more than one billion dollars in total contributions. Senator Barack Obama of Illinois. Had reported 389. Point four million dollars. A record amount and more than twice the 174. Point two million reported by Senator John McCain of Arizona. As the election approaches. Health care has faded as the second most important issue for the US public after the war in Iraq. A position it held early in the campaign. In August. Health care was ranked third by Democrats behind the economy in Iraq and fifth by Republicans. Behind the economy Iraq. Gas prices and terrorism. Nonetheless health care reform continues to be passionately debated and the candidates have sharply different plans. As of July people affiliated with the health sector and political action committees associated with the sector. Had contributed about 29 million dollars to presidential candidates. Including eight point eight million dollars to Obama six point six million to Senator Hillary Clinton of New York the former democratic contender. And four point seven million to McCain according to the center for responsive politics. Although these contributions. Represent less than 3% of the funds raised by presidential candidates. It is remarkable that the health sector has reversed longstanding pattern of favoring Republican candidates. This week's images in clinical medicine features a 36 year old woman with mild mental retardation and facial and you'll find Romans. Who presented for valuation of recurrent seizures. Which you reported having had since childhood. Perry on wolf I've Romans were seen in the feet. These lesions usually seen in adults are typical of -- sclerosis. Which this patient had. In adolescence facial and you'll find dramas are often mistaken for acne. When in fact these lesions may be indicative of an underlying condition. Also featured in the images in clinical medicine. Is a 45 year old woman with a 27 pack your history of smoking. Who presented for valuation of progressive disco finger enlargement and -- our trousers. Physical examination revealed symmetric clubbing of the fingers. A chest X ray showed a seven centimeter rounded -- Cassidy in the right upper -- The patient underwent a right upper lumpectomy. At a six month follow up visit the patient was asymptomatic. And the clothing and bone pain had resolved. This concludes the summary of the September 25 issue of the New England Journal of medicine. We are interested in your feedback about our audio summaries and the comments or suggestions. May be sent to audio and any change and dot -- Thank you for listening."