X-Ray Visions: What is your radiation risk?

January 29, 2009

xraylogo.jpgCommentary by Michael Hanley MD PGY-3 and James D. Koonce MD PGY-3, Department of Radiology, Medical University of South Carolina – A Free Online Calculator that Estimates an Individual’s Additional Risk of Cancer as a Result of Medical Imaging

An estimated 62 million CT scans are obtained in the United States each year.(1) While debated, a recent study suggests that radiation exposure from medical imaging may be responsible for 1-3% of cancers worldwide.(2) With recent media coverage focusing on the risk of cancer from medical imaging, patients and physicians have become more concerned about the increased use of CT scans and x-rays. Patients are asking their primary care providers and emergency room physicians for information about their personal risk. In 2004, Lee et al concluded that “patients are not given information about the risks, benefits and radiation dose for a CT scan”. Additionally, this study found that both patients and physicians were “unable to provide accurate estimates of CT doses”.(3)

While the need for education in this area has clearly been established, there are no widely available resources that provide information to both patients and health care providers about the increased risk of cancer from medical imaging. is a free educational website that caclulates this risk. The site is specifically designed for both patients and health care providers. One of the site’s main features is a web-based calculator that allows users to track their imaging history and estimate their personal risk. The site also provides basic information about radiation in the form of ‘Frequently Asked Questions’.

There are no published studies that prove the direct causality between medical imaging and cancer, however there is enough data to warrant precaution. Current data on radiation exposure and cancer risk is based on data from survivors of atomic bombs, nuclear accidents and the early use of x-rays. The assumed risk of cancer from medical imaging (primarily CT scans) is based on individuals exposed to atomic bombs and nuclear accidents. The theory that the increased risk of cancer holds true at these lower doses is called the linear no threshold model and is generally accepted in the scientific community.

From the Home Page of, the user can select the ‘Calculate Your Risk’ icon. Next, the user enters his or her gender and age. There is an extensive list of different plain films (x-rays), CT scans, nuclear medicine studies, as well as fluoroscopic and interventional procedures. The user’s radiation dose, age and sex are used to calculate the additional risk of cancer based on that study. After a user builds their complete imaging history, they have the option to print, e-mail or save their report. The user can also log-in (optional) and save their report to revisit and update with subsequent studies.

Exposure data for the website was compiled from the National Academy of Sciences report on the Health Risks From Exposure to Low Levels of Ionizing Radiation in 2006, specifically the Biological Effects of Ionizing Radiation (BEIR) VII Phase 2 Report.(4) Average doses from common imaging studies were used, which were adapted from Mettler et al.(5) If exact dose is known, the user can convert their Dose Length Product (mGy • cm) to Effective Dose (mSv), then calculate additional cancer risk using conversion factors adapted from Huda, et al.(6) The website is also designed to assist in radiation exposure research and clinical record keeping.

Great effort has been made throughout the medical community to ensure patient safety while providing quality diagnostic images. It is important to realize that in a properly performed individual exam, the potential health benefits almost always outweigh the potential risks of radiation exposure. However, patients are expecting their physicians to address these risks. provides accurate information for patients and health care providers to facilitate well-informed discussions about the increased risk of cancer from medical imaging.

1. Brenner DJ, Hall EJ. Computed Tomography – An Increasing Source of Radiation Exposure. NEJM 357: 2277-84, 2007. 2. Berrington de Gonzalez A, Darby S. Risk of cancer from diagnostic x-rays: estimates for the UK and 14 other countries. Lancet 363:345-51, 2004.
3. Lee CI, Haims AH, Monico EP, et al. Diagnostic CT Scans: Assessment of Patient, Physician, and Radiologist Awareness of Radiation Dose and Possible Risks. Radiology 231 (2): 393-398, 2004.
4. National Research Council. Health risks from exposure to low levels of ionizing radiation. BEIR VII Phase 2. Washington, DC: National Academies Press, 2006.
5. Mettler FA, Huda W, Yoshizumi TT, Mahesh M: Effective Doses in Radiology and Diagnostic Nuclear Medicine: A Catalog. Radiology 248: 254-263, 2008.
6. Huda W, Ogden KM, Khorasani MR: Converting Dose-Length Product to Effective Dose at CT. Radiology 248:995-1003, 2008.

Should All Patients with Cellulitis Be Treated for Community-Acquired Methicillin-Resistant Staphylococcus Aureus?

January 22, 2009

120px-mrsa_sem_9994_lores.jpgCommentary by Melanie Maslow, MD, FACP, Associate Professor of Medicine, NYUSOM, Chief, Infectious Diseases, New York Harbor Healthcare System, NY

Faculty Peer Reviewed

Cellulitis is an acute spreading infection of the skin extending to the deep subcutaneous tissue characterized by pain, swelling, erythema and warmth. Cellulitis in the non-neutropenic patient, in the absence of bite wounds, salt or fresh water exposure, and coexisting ulcers is usually caused by Gram-positive pathogens, the most common being the beta-hemolytic streptococci and S .aureus, including methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) strains. Empiric therapy for management of cellulitis has traditionally included antibiotics with activity against beta-hemolytic streptococci and MSSA such as penicillinase-resistant penicillins or first generation cephalosporins, unless the patient was known to have a previous MRSA infection or in cases of severe systemic toxicity.

Over the past decade there has been a steady rise in the incidence of community-acquired methicillin-resistant S. aureus (CA-MRSA). A recent study [1] documented a nearly three-fold increase in the incidence of skin and soft tissue infections (SSTIs) presenting to Emergency Departments in this country concurrent with the emergence of CA-MRSA. A study published in 2006 from the Grady Health System found that 72% of community-acquired S. aureus skin and STI were caused by MRSA [2].

The USA 300 clone of CA-MRSA predominates in this country and differs from hospital acquired MRSA in several important ways. CA-MRSA is found in patients without the traditional risk factors for MRSA, is usually more susceptible to different antibiotic classes, has a unique chromosomal cassette containing a smaller resistance gene thought to result in more efficient transmission, and usually contains a virulence factor, Panton-Valentine leukocidin (PVL) [3]. PVL produces cytotoxins, causing tissue necrosis and leukocyte destruction, which can result in serious infections such as necrotizing fasciitis and pyomyositis. However, most CA-MRSA associated infections are purulent or pustular skin lesions and SSTIs.
Outbreaks of CA-MRSA have been documented in inmates of correctional facilities, athletes, military personnel, intravenous drug abusers, homosexual men, homeless persons, in healthy children, and in specific populations including Alaskan Natives, Native Americans and Pacific Islanders. The current epidemic extends to populations not traditionally infected with MRSA such patients with diabetes, HIV-infection, ESRD on hemodialysis, those receiving prior antibiotics, and in recently hospitalized and/or nursing home patients [3]. A recent prospective study of patients hospitalized with MRSA found that there were no clinical or epidemiological risk factors that could reliably distinguish between community-acquired MRSA and MSSA [4].

Given the increasing incidence of CA-MRSA SSTIs and the inability to reliably identify CA-MRSA, alternative regimens have been recommended for the treatment of suspected and/or confirmed CA-MRSA infection. In the outpatient setting, these include sulfamethoxazole-trimethoprim, clindamycin, doxycycline, and linezolid. Clindamycin has the potential advantage of also decreasing production of staphylococcal toxins, but increasing resistance to clindamycin has been documented and the microbiology lab should test for inducible resistance using the double-disk D-test. Increasing resistance to doxycycline in CA-MRSA has also been reported [5]. For hospitalized patients, recommended parenteral agents for the treatment of suspected CA-MRSA cellulitis include vancomycin, linezolid, daptomycin and tigecycline. Although vancomycin remains the gold standard, increasing resistance to vancomycin has been documented and strains with heteroresistance to vancomycin may also develop resistance to daptomycin. Linezolid, like clindamycin, has the ability to impair toxin production in more serious SSTI and limited resistance to linezolid has been documented to date [5]. Several promising investigational agents include dalbavancin and telavancin (lipoglycopeptides), oritavacin (a semisynthetic glycopeptides), and ceftobiprole, a broad-spectrum third generation cephalosporin [6].

Given the current epidemic of CA-MRSA skin and soft tissue infections and the inability to distinguish MRSA from MSSA by risk factors and/or clinical presentation, the clinician should initiate treatment for MRSA with one of the recommended oral or parenteral antibiotics. It is also important to attempt confirmation of the etiologic agent of cellulitis, which is not usually done secondary to the low yield of cultures. All abscesses and pustules should be aspirated and sent for culture. Bullae should be unroofed and the base swabbed and sent for culture. Establishing the susceptibility of S. aureus isolates in even a small proportion of patients will enable the provider to switch to a narrower spectrum agent if CA-MRSA is ruled out, decreasing the resistance pressure that is driving this current epidemic.


Reviewed by Howard Leaf MD, Assistant Professor, NYU Division of Infectious Diseases and Immunology


1. Pallin DJ, Egan DJ et al. Increased US Emergency Department Visits for Skin and Soft Tissue Infections, and Changes in Antibiotic Choices During the Emergence of Community-Associated Methicillin-Resistant Staphylococcus aureus. Ann Emerg Med 2008;51(3):291-298
2. King MD, Humphrey, BJ et al. Emergence of Community-Acquired Methicillin-Resistant Staphylococcus aureus USA 300 clone as the Predominant Cause of Skin and Soft-Tissue Infections. Ann Intern Med 2006;144(5):309-317
3. Weber, JT. Community-Associated Methicillin-Resistant Staphylococcus aureus. Clin Infect Dis 2005;41:(suppl 4):S269-279.
4. Miller, LG, Perdreau-Remington, F. et al. Clinical and Epidemiologic Characteristics Cannot Distinguish Community-Associated Methicillin-Resistant Staphylococcus aureus from Methicillin-Susceptible Staphylococcus aureus Infection: A Prospective Investigation. Clin Infect Dis 2007;44:471-82.
5. Moellering, Robert C. Jr. Current Treatment Options for Community-Acquired Methicillin-Resistant Staphylococcus aureus Infection. Clin Infect Dis 2008;46:1032-7.
6. Stryjewski, ME and Chambers, HF. Skin and Soft-Tissue Infections Caused by Community-Acquired Methicillin-Resistant Staphylococcus aureus. Clin Infect Dis 2008:46(Suppl 5);S368-377.

Image courtesy of Wikimedia Commons

Grand Rounds: “VEGF and Renal Thrombotic Microangiopathy”

January 21, 2009

Grand Rounds Image

Commentary by Ilana Bragin, MD, PGY-3

Please also see the clinical vignette presented before last week’s grand rounds.

Last week’s Medical Grand Rounds was given by guest speaker Dr. Sue Quaggin, Associate Professor of Medicine at the University of Toronto, who shared with the audience her knowledge and passion of the role of Vascular Endothelial Growth Factor (VEGF) in kidney function.  VEGF is a critical family of signaling proteins that is involved in vasculogenesis and angiogenesis. While the discovery of VEGF could be applied to many aspects of medicine, it has become especially relevant to the realm of cancer therapy. Tumors are often highly vascular entities and require VEGF to create their own vasculature. If a rapidly growing tumor cannot create its own blood supply, the tumor will be unable to propagate. Agents that target VEGF have proliferated, revolutionizing cancer care in general, and particularly impacting the treatment of solid tumors with treatments like bevacizumab (Avastin), ranibizumab (Lucentis), sunitinib (Sutent), and sorafenib (Nexavar), with several more in clinical trials.

However, like all medications, researchers and clinicians are learning that anti-VEGF agents can have some adverse effects on non-tumor tissue as well.  This is where Sue Quaggin’s research plays a tremendous role. Dr. Quaggin’s lab focuses on the effect of VEGF on the kidney. She noted that some of the most common adverse affects of bevacizumab, an anti-VEGF agent, include hypertension (3-36% of patients) and proteinuria (in 21-64% of patients). More serious side effects include several cases of kidney failure due to thrombotic microangiopathy. Dr. Quaggin set about to define the role of VEGF in the development and maintenance of the glomerulus, thus possibly explaining the disease processes that occur when VEGF is inhibited.

Using mouse models, Dr. Quaggin explored how VEGF works on the podocytes of the glomerulus. Podocytes require VEGF production in order to create the glomerular endothelium, as done in embryonic development, but they also require VEGF throughout life in order to maintain the health of the adjacent glomerular endothelium.

When VEGF production is disrupted, by medications such as bevacizumab, there is a characteristic pattern of renal damage—mesangiolysis, endothelial swelling, and effacement of the foot processes—all characteristic of thrombotic microangiopathy. She suggests that the reason VEGF inhibition in the glomerulus is particularly significant compared to the minimal known effect on other vasculature in the body, lies in the delicate nature of the glomerulus. She proposes that this is because glomerular endothelial cells contain fenestrations that are responsible for the unique permeability of the glomerulus, and VEGF is vital to the formation of these fenestrations. A loss of healthy glomerular endothelial cells, along with their fenestrations, leads to microvascular injury and thrombotic microangiopathy.

Although it has been argued that the kidney disease associated with VEGF inhibition may be secondary to the HTN also seen due to these medications, Dr. Quaggin postulates that the HTN is seen after glomerular changes, and may also somehow be linked to the lack of VEGF.

This research has particular clinical relevance, given the impressive therapeutic use of these medications in oncology and the expectation that their use will increase. Perhaps, for example, further studies will lead to a difference in the type of monitoring of kidney function in patients who are on anti-VEGF medications.
With more patients surviving their cancer, understanding the side affects of the medication regimens involved in treatment is becoming more and more important.

Mystery Quiz- The Answer

January 16, 2009

Posted by Daniel Frenkel MD PGY-3 and Jeffrey Lorin MD, Assistant Professor, NYU Division of Cardiology

Edited by Vivian Hayashi MD and Robert Smith MD, Mystery Quiz Section Editors 

The answer to last week’s mystery quiz is accelerated idioventricular rhythm (AIVR) [a.k.a. accelerated ventricular rhythm or slow ventricular tachycardia]

AIVR is an ectopic ventricular rhythm with intermediate rates between an escape rhythm (<40 bpm) and ventricular tachycardia (>100-120 bpm). It has the usual features of ventricular arrhythmias including AV dissociation, fusion complexes, and capture complexes. However, the underlying mechanism of this arrhythmia is automaticity rather than reentry. Given the slower rate of this rhythm, the ventricles are more likely to be activated by a supraventricular source which results in more frequent fusion and capture complexes and more readily succumb to overdrive pacing. The AIVR emerges when the sinus node slows and the fastest pacemaker in the heart at the time takes over (i.e. the focus of ventricular automaticity). At the initiation of the AIVR, both the sinus node rate and AIVR rate are similar so that depolarization can occur simultaneously from a sinus origin down the normal conduction pathway and from the focus of ventricular automaticity resulting in a hybrid QRS complex known as a fusion complex. These complexes often initiate or terminate AIVR. Similary, if the focus of automaticity slows down transiently, a native beat can be conducted down the native pathway resulting in a capture complex (normal narrow QRS). This is noted in our patient’s EKG at beat 14.

AIVR can occur in numerous conditions including myocardial disease (ischemic cardiomyopathy, dilated cardiomyopathy, congenital, hypertensive disease), rheumatic heart disease, myocarditis, digitalis toxicity, acute coronary syndrome, and reperfusion injury. It occurs in 8 to 46% of acute MI’s and in as many as 90% of patients within the first 24 hours after reperfusion (frequency highest early on and decreasing after 8 to 12 hours).

Accelerated idioventricular rhythm is usually benign and transient (lasting from seconds to hours). It does not impact hemodynamics, progress to more serious ventricular arrhythmias, nor increase mortality. Of note, the coordinated contraction between the atria and ventricles is disrupted, impeding ventricular filling, and in certain patients this can lead to vague symptoms of weakness and unsteadiness. This arrhythmia rarely warrants any treatment and will self-resolve in a matter of hours. If there is hemodynamic compromise in the presence of AIVR, atrial overdrive pacing or atropine can be tried in order to reestablish AV synchrony.

In our patient’s EKG, there is an accelerated idioventricular rhythm at a slow rate (90-120 bpm) with normal sinus conduction at beat 14 (capture beat). There are retrograde p waves representing ventricular to atrial conduction; but interestingly, there is no retrograde p wave in beat 11. In order to decipher beat 11, look further down the EKG strip. The distance between the retrograde p wave in beat 13 to the sinus p wave in beat 14 likely represents sinus recovery time. If this distance is measured out from the retrograde p wave in beat 10, there is likely a sinus p wave superimposed on beat 11 (not visualized), marking the interval that would be expected from the presumed sinus node recovery time. This sinus p wave is not conducted to the ventricle due to ventricular refractoriness. However, the impulse likely goes through the AV node, rendering the AV node refractory to retrograde V-A conduction. Thus, no retrograde p wave is visible after beat 11. This phenomenon has been termed concealed conduction of the AV node. Taking all of these features into account, the complete rhythm diagnosis is AIVR with retrograde excitation of the atria and a competing sinus rhythm with capture and concealed AV conduction.

EKG with labels

(click to enlarge)


Rho RW, Page RL. Chapter 39. Ventricular Arrhythmias. In: Fuster V, O’Rourke RA, Walsh RA, Poole-Wilson P, Eds. King SB, Roberts R, Nash IS, Prystowsky EN, Assoc. Eds. Hurst’s The Heart. 12th ed. McGraw-Hill; 2008. Accessed October 10, 2008.

Surawicz, B, Knilans TK. Chou’s Electrocardiography in Clinical Practice. 5th ed. Pennsylvania: Saunders, 2001:408-411.

Wagner GS. Marriott’s Practical Electrocardiography. 10th ed. Philadelphia, PA: Lippincott Williams and Wilkins, 2001:295-296.

Coronary Artery Disease in South Asians

January 14, 2009

southasia.jpgCommentary by Muhammad Ghumman MD, PGY-3

Faculty Peer Reviewed

South Asia (India, Pakistan, Bangladesh, Sri Lanka, and Nepal) comprises 25% of the global population yet contributes nearly 60% of the global cardiovascular disease burden. There are over 3 million South Asians living in North America (2 million in United States and nearly a quarter million in New York City alone). It is important to recognize that South Asians develop coronary artery disease (CAD) at a younger age, die from CAD at younger ages, and have higher overall CAD-associated mortality.(1-6)

Numerous studies have demonstrated higher CAD rates amongst South Asians at all ages. Prevalence of CAD in rural South Asia is 3-4%, while the CAD prevalence amongst urban South Asians and South Asian immigrants to the western world approaches 10%. (2,7,8) The Coronary Artery Disease in Indians (CADI) study demonstrated a CAD prevalence of 10% amongst first generation South Asian immigrants to the United States, compared to a 2.5% CAD prevalence among the general population in the Framingham study.(2) The higher prevalence is further magnified in younger South Asians. United Kingdom mortality data demonstrates 3 times higher CAD prevalence for South Asians younger than 40 years and 1.5 times higher CAD prevalence for South Asians older than 60 years. Contribution of the younger age group to overall CAD-associated mortality is significantly higher in South Asians. A 1990 World Health Organization showed that the proportion of cardiovascular deaths occurring before 70 years of age was 26% in developing countries but 52% in India.

Despite the increased prevalence of CAD, rates of many traditional CAD risk factors such as smoking, hypertension, and obesity are not higher among South Asians. Smoking is actually lower amongst South Asians and virtually nonexistent among South Asian females.(7,12,17) Diabetes Mellitus (DM) however is significantly more common among South Asians, having a 2% prevalence in rural South Asia but approaching a 20% prevalence in urban South Asia and amongst immigrant South Asians.(7,11,12,13) While total cholesterol and LDL levels may be similar to other ethnic groups, South Asians have characteristic lipid profiles increasing their risk for CAD: higher triglyceride levels, higher lipoprotein(a) levels, increased ratio of apolipoprotein B to apolipoprotein A-1 (apoB/apoA-1), smaller HDL and LDL particle size, and lower levels of HDL.(14,15,16,25) These factors are rarely screened for or targeted by most physicians. Lipoprotein(a) is an emerging independent and compounding risk factor for the development of CAD and, unlike other lipids, its levels are almost entirely determined by genetics. South Asians have the second highest levels of lipoprotein(a) after African Americans and this may explain some of the increased CAD risk in these ethnic groups. Lipoprotein(a) is proposed to be an independent CAD risk factor and also thought to multiply the effect of traditional CAD risk factors (low HDL, high LDL, DM). Screening for lipoprotein(a) is most important in younger South Asians since the lipoprotein(a)-associated CAD risk is highest between 45-55 years of age and declines in old age. (24,25) Because of the multiplicative effect of lipoprotein(a) on other CAD risk factors, South Asians have a higher CAD risk at any given level of LDL and total cholesterol. Physicians should be aware that this leads to a significant underestimation of CAD risk in South Asians by the Framingham risk score.

Most of the increased CAD risk in South Asians can be explained by a higher prevalence of traditional risk factors, especially at a younger age. INTERHEART study (9) (an international case-control study examining risk factors for initial MI in 52 countries, including 12,000 cases of initial MI and 14,000 controls) demonstrated that over 90% of global MI risk can be attributed to 9 modifiable risk factors (smoking, DM, lipids, central obesity, hypertension, diet, physical activity, alcohol consumption, and psychosocial factors). This was true for all populations including South Asians. However, South Asians presented with initial MI at earlier ages (53 yrs vs. 58 yrs) and this can be explained by the presence of more risk factors at an earlier age. Protective factors (moderate daily alcohol consumption, regular physical activity, daily intake of fruits and vegetables) were significantly lower among South Asians. Harmful factors were significantly higher in South Asians (DM and elevated apoB/apoA-1 ratio). When compared to other risk factors, elevated apoB/apoA-1 ratio had the single highest attributable risk in South Asians. When compared to other ethnic groups, certain risk factors had higher attributable risk in South Asians: apoB/apoA-1 ratio, low daily consumption of fruits and vegetables, lack of regular exercise, and high waist hip ratios (marker of central obesity which predisposes to insulin resistance).

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Mystery Quiz

January 8, 2009

Posted by Daniel Frenkel MD PGY-3 and Jeffrey Lorin MD, Assistant Professor, NYU Division of Cardiology

Edited by Vivian Hayashi MD and Robert Smith MD, Mystery Quiz Section Editors 

The patient is a 68 year old man with history of smoking, hypertension, hyperlipidemia, and stable exertional angina who presented with an acute posterior wall myocardial infarction. He was found to have a totally occluded left circumflex artery requiring bare metal stent placement. Several hours after stent placement, the nurse calls stating that the patient had an arrhythmia and the following ECG was obtained. The patient is without any acute complaints and his vital signs are stable.

Current EKG:


 (click to enlarge)


Baseline EKG (post-cath, several hours prior to event):


(click to enlarge)

What is the arrhythmia?

View Results

Grand Rounds: “The Cardiovascular Molecular Basis of CPVT and other arrythmias”

January 7, 2009

Grand Rounds Image

Commentary by Anjali Grover MD, PGY-2 

Please also see the clinical vignette presented before December 17th’s grand rounds.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is classified as an inherited disorder which manifests itself as an adrenergically driven polymorphic ventricular tachyarrythmias.  The molecular etiology of this arrythmogenic disorder stems from a disruption in the calcium channels found in the sarcoplasmic reticulum.   This type of arrhythmia is an important cause of syncope and sudden cardiac death in those individuals with structurally normal hearts.  Genetic studies have elucidated two variants of the disease: an autosomal dominant variant with mutations in the cardiac ryanodine receptor (RyR2), and a recessive variant with mutations calsequestrin gene (CASQ2). 

            This disease clinically presents usually as a bi-directional polymorphic ventricular tachycardia induced by exercise or any events activating the sympathetic nervous system inducing a catecholaminergic state. It is often seen as sudden syncope during physical activity or acute emotional stress. Given this, the diagnosis can be made during an exercise stress test.  The resting EKG is usually normal, but during exercise, premature ventricular contractions that occur serve as a substrate for further development and propagation of bi-directional ventricular tachycardia.  This being said, beta blockers are the appropriate medical therapy for this adrenergically driven arrhythmia.

            The current hypothesis on the molecular abnormalities leading to arrythmias in CPVT patients is centered around two well studied mutations.  The first being that of the ryanodine receptor-a modulator of intracellular calcium through the sarcoplasmic reticulum.  Under normal physiologic conditions, the ryanodine receptor, located in the membrane of the sarcoplasmic reticulum, allows the release of calcium from the sarcoplasmic reticulum in the cytoplasm of the cell, allowing for cardiac muscle contraction.

            However, with the RyR2 gene mutation, in high-adrenergic states, the normally regulated intracellular calcium channels leak out calcium, leading to a depolarizing current and subsequently higher rates ventricular arrythmias.  Calsequestrin (CASQ2) is another protein involved in the regulation of intracellular calcium.  It is a calcium binding protein located within the sarcoplasmic reticulum, whose role is to essentially increase the storage of calcium in the cell.  A mutation in the CASQ2 gene leads to a decrease in the calcium binding capacity and the resulting build-up of calcium, in the presence of a high adrenergic state is thought to contribute to the ventricular arrythmias.  In sum, these proteins are responsible for the management of intracellular calcium, and these mutations alter the normal release of calcium from the sarcoplasmic reticulum, thus electrophysiologically predisposing cells to degenerate into a ventricular arrhythmia.

Class Act: AGE-RAGE: What we know about the pathophysiology of diabetic neuropathy.

December 26, 2008

neuropathy.jpgCommentary by Regina Mysliwiec, NYU Medical Student

Faculty Peer Reviewed

G.L. is a 62 year-old African-American male with a six year history of Type 2 Diabetes with variable glucose control and a progressive one year history of burning pain in a unilateral T10 distribution. The pain began at his right abdomen, then spread first to his umbilicus and finally ventrodorsally to his spine. His most recent HgbA1c is 8.0.

One does not have to be a medical student in New York City for very long to find a patient with tingling and numbness that started in the toes, spread up both legs, and is sometimes accompanied by sharp or burning pain. Distal symmetric polyneuropathy is common in diabetes, and diabetes is common in NYC. The patient described above may be an example of the less common diabetic thoracic radiculopathy. What he has in common with his stocking-and-gloved counterparts is poor glucose control. Several long-term clinical trials focusing on the effects of glycemic control have illustrated the correlation between hyperglycemia and what are now commonly known as the microvascular complications of diabetes – including neuropathy. We know that nerve damage happens. What remains somewhat unclear is how it is accomplished.

There appear to be three main mechanisms of nerve damage in diabetics. First, excess glucose causes endothelial injury. Second, there are changes in activation of various cellular pathways that alter cell function without immediately causing cell death. And third, AGE meets RAGE; time and the accumulation of altered molecules wreak additional havoc on patients’ tissues. Endothelial damage is evidenced by the increased presence of thrombomodulin, a marker of microangiopathy in animal models of diabetes. It is assumed that microangiopathy caused by glucose will have sequelae similar to microangiopathy of various other causes: impaired blood flow to nerves, tissue hypoxia, and oxidative stress. In the ‘90s, there was evidence suggesting that inflammatory responses in microvasculature of neurons led to additional ischemic damage to nerves.

Serum glucose does not affect only blood vessels. The more sugar there is in the blood, the longer it spends degrading without being used or filtered and the more it finds its way into tissues. Fructosamines and sorbitol produced by this degradation of sugar interfere with the protein kinase C and the Na/K ATPase of nerve cells. This injury alone is enough to reduce nerve function, but it does not occur alone. Degraded sugar molecules bind to N-terminal and lysyl side chain aspects of protein, nucleotide, and lipid molecules; this is glycosylation that occurs without the involvement of an enzyme. It is called glycation and it renders the molecules in question more stable than their original, non-glycated states.

Being more stable, glycated end products last longer. They are difficult to clear from the body. They accumulate. They deposit themselves on molecules with long lifespans, such as myelin. They are recognized by special cell receptors – receptors for advanced glycated end products, or RAGE – that, when activated by AGEs, trigger various cellular processes involving TNF-α, VEGF, nitric oxide, and other potentially damaging mediators. In molecular studies, AGEs have been found within the perineurium, endothelial cells, and basement membranes of both myelinated and unmyelinated nerve fibers of diabetic patients with neuropathic symptoms.

OK, this is where our knowledge of the mechanism of diabetic neuropathy gets a little fuzzy. Studies show many possible points of injury. AGEs have been shown to modify neurofilament and tubulin. These changes may impair axonal transport, leading to atrophy of the nerve fibers. This could explain the fibrillation (nerve degeneration) found in EMG studies of human patients with diabetic neuropathy. In vitro, AGE accumulation has also caused neuronal and Schwann cell death – processes that, if occurring in vivo, would certainly lead to the demyelination and atrophy of nerve fibers. These processes, and others yet undiscovered, stand between us and a full understanding of the pathophysiology of diabetic neuropathy. They stand between the clinician and the diabetic neuropaths who may not understand why the medicine we ask them to take will treat their pain, but not stop the process that is causing it.

I asked myself what I knew about this physiology for a reason: I wanted to know what could be done about G.L.’s T10 strip of burning, hypersensitive skin. The major clinical implication of finally elucidating a pathophysiological process is development of new therapies. Considering how difficult it is to treat diabetic neuropathy, a successful approach would be welcome. We use antidepressants, anticonvulsants, and other drugs which, by unknown mechanisms, may or may not bring relief*. It has been demonstrated that better glucose control reduces the amount of glycation damage in diabetic nerves. However, there is no evidence that reducing or stopping glycation can reverse the symptoms caused by hyperglycemic damage, such as the sensory loss that remains a painful diabetic neuropathy resolves. Therefore it cannot yet be said that drugs targeting the molecules and mechanisms responsible for glycation will have a beneficial clinical effect. An example of this is aldose reductase inhibitors, which have been shown to reduce the levels of AGEs in diabetic patients (thereby reducing damage) without affecting symptoms believed to be caused by those AGEs. For now, this may mean that G.L.’s pain and hyperesthesia will be treated symptomatically with gabapentin until they eventually give way to anesthesia. But I hope that, for future diabetics, AGE and RAGE don’t have the final word.

*Please also refer to Bedside Rounds: How Do You Diagnose and Treat Diabetic Neuropathy, by Judith Brenner, MD

Commentary by Robert Staudinger MD, Associate Professor, NYU Department of Neurology

Diabetic neuropathy is the most common complication of diabetes, affecting 50% of patients. Diabetes can cause a variety of neuropathies. Most common and well known to all clinicians is a distal symmetric, slowly progressive painful neuropathy. Perhaps less know to the internist is the disabling diabetic radiculoplexopathy (“diabetic amyotrophy”), usually seen in patients with weight loss who develop subacute progressive leg weakness and pain, followed by spontaneous improvement. Diabetic radiculopathy is not limited to the lumbar area, but may also, rarely, involve thoracic segments and then present with abdominal pain. In contrast to cervical or lumbar radiculopathy, a thoracic radiculopathy is often not recognized and a patient may undergo extensive testing including invasive procedures, before the correct diagnosis is made.

The treatment of diabetic neuropathic pain is symptomatic and remains limited. Regina Mysliwiec nicely summarizes our still incomplete understanding of the pathophysiology of diabetic neuropathies. She describes the recent exciting co-localization of AGE and RAGE in diabetic peripheral nerves. Agents that inhibit the ACE-RAGE oxidative stress system could have therapeutic implications in vascular complications in diabetes


R. Brewer. Diabetic thoracic radiculopathy: an unusual cause of post-thoracotomy pain. Pain. 2003 May;103(1-2):221-3.

The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993 Sep 30;329(14):977-86.

D.G. Kikta, A.C. Breuer, et al. Thoracic Root Pain in Diabetes: The Spectrum of Clinical and Electromyographic Findings. Ann Neurol. 1982 Jan;11(1):80-5.

P.C. Johnson, S.C. Doll, et al. Pathogenesis of diabetic neuropathy. Ann Neurol 1986 May;19(5):450-7.

G.F. Longstreth. Diabetic thoracic polyradiculopathy. Best Pract Res Clin Gastroenterol. 2005 Apr;19(2):275-81.

K. Sugimoto, M. Yasujima, et al. Role of Advanced Glycation End Products in Diabetic Neuropathy. Current Pharmaceutical Design. Schiphol: Apr 2008. Vol. 14, Iss. 10; pg. 953.

P.J. Thornalley. Glycation in diabetic neuropathy: characteristics, consequences, causes, and therapeutic options. Int Rev Neurobiol. 2002;50:37-57.

C. Toth, L.L. Rong, et al. Receptor for Advanced Glycation End Products (RAGEs) and Experimental Diabetic Neuropathy. Diabetes 2008;57:1002–1017.

R. Wada and S. Yagihashi. Role of Advanced Glycation End Products and Their Receptors in Development of Diabetic Neuropathy. Ann N Y Acad Sci. 2005 Jun;1043:598-604.

Cardiac MRI: Assessing Myocardial Viability

December 18, 2008

Commentary by Muhammad Ghumman MD, PGY-3

Faculty Peer Reviewed

Clinical Case:

A 65 year old male with hypertension, iron deficiency anemia, and atrial fibrillation (not anticoagulated due to prior gastrointestinal bleed,) presents with new onset lower extremity edema, dyspnea on exertion, orthopnea, and profound fatigue. Physical exam is significant for jugular venous distention to 17 cm, bilateral basilar crackles on lung exam, 3+ pitting edema in the lower extremities to mid thighs, and guaiac positive brown stool. Labs are significant for hemoglobin of 5.4, normal kidney function, and mildly elevated troponin. Patient denies chest pain and is hemodynamically stable with normal vitals. Electrocardiogram shows new ST depressions in lateral leads. Transthoracic echocardiogram shows new segmental wall motion abnormalities along with a newly reduced ejection fraction of 30%.   Capsule endoscopy shows non-bleeding angioectasias in the jejunum.  The patient is started on medical therapy for congestive heart failure and presumed coronary artery disease (ACE-I, Beta blocker, diuretic) and transfused to hemoglobin goal of 10 with improvement in his symptoms of dyspnea and fatigue. Echocardiogram strongly suggests ischemic cardiomyopathy due to the presence of regional wall motion abnormalities and an assessment of the patient’s coronary anatomy is warranted. However, the medical team and cardiology consult are reluctant to perform cardiac catheterization due to the risk of bleeding in a severely anemic patient who may require coronary artery stenting and subsequent long term anticoagulation. What other modalities are available for assessing this patient’s new cardiomyopathy and coronary anatomy?


Cardiac magnetic resonance imaging (CMR) is a rapidly evolving field which provides high contrast and high resolution 3-dimensional images of the heart, coronary vessels, and the great vessels without subjecting the patient to ionizing radiation. CMR is often considered a “one-stop shop” as it can provide a comprehensive assessment of the heart including myocardial wall motion, cavity size, ventricular ejection fraction, wall thickness, valvular function, infarct area, proximal coronary artery lesions, aortic disease including aneurysm and dissection, pericardial disease, congenital heart defects, and myocardial viability.

Myocardial viability: 

Currently, the most important and common clinical use of CMR is assessing myocardial viability. Dysfunctional myocardium is deemed viable if it can regain function (contractility) after regional blood supply is improved via revascularization. Nonviable myocardium is dead or scar tissue which has permanently lost its function irrespective of its regional blood supply. Viability testing guides clinical practice in patients with left ventricular (LV) dysfunction as revascularization of nonviable myocardium would not improve myocardial contractility, ejection fraction, or mortality and may even increase morbidity and mortality by subjecting the patient to an unnecessary interventional procedure.

CMR is excellent at determining myocardial viability using late gadolinium enhancement (LGE or hyperenhancement). When gadolinium is “taken up” by nonviable or scarred myocardium, it is not washed out as quickly as healthy myocardium due to poor blood flow, and thus images taken > 10 minutes after gadolinium injection will exhibit hyperenhancement or late gadolinium enhancement (regions where gadolinium is retained). The transmural extent of LGE signifies the thickness of nonviable or scar tissue and this correlates well to areas that are less viable and are partially or completely damaged in an irreversible manner. Conversely, absence of LGE corresponds to areas of viable myocardium.(1,2,3 ) A study of 50 patients with ventricular dysfunction undergoing revascularization showed that CMR accurately identified viable myocardium before revascularization. Absence of late gadolinium enhancement correlated well with segments which improved function after revascularization (78% of segments without LGE had improved function). Presence of late gadolinium enhancement correlated accurately with segments which had no improvement after revascularization (less than 2% of segments with LGE had improved function). The probability of improvement in segmental function significantly decreased as the extent of transmural LGE (thickness of scar) increased (see Figure 1).(3 )

Figure 1: Relation between the Transmural Extent of Hyperenhancement before Revascularization and the Likelihood of Increased Contractility after Revascularization.  804 dysfunctional segments were identified by CMR in 50 patients who were scheduled to undergo revascularization. As the transmural extent of late gadolinium enhancement increased, the likelihood of post-revascularization improvement in contractility significantly decreased. (adapted from Kim et al.)(3)


Figure 2: Cardiac MRI displaying late gadolinium enhancement


Traditionally, radionuclide myocardial perfusion imaging (using thallium, technetium-sestamibi, or positron emission tomography) and dobutamine echocardiography have been utilized to assess myocardial viability. CMR compares very favorably to these modalities and is even superior in some respects. In a study of 208 patients with suspected coronary artery disease referred for revascularization, dobutamine stress MRI had a 86% sensitivity and 74% specificity in terms of predicting viability when compared to dobutamine stress echocardiography which had a 85% sensitivity and 69% specificity.(4) When compared to positron emission tomography with F- 18 deoxyglucose (FDG-PET), CMR had similar sensitivity and specificity (94% and 84% respectively).(5) In comparison to resting thallium-201 perfusion imaging, CMR performs as well in terms of detecting transmural infarctions but is more accurate in detecting subendocardial infarctions.(6) Several studies have suggested that CMR may be more sensitive in detecting viability in regions of severely dysfunctional myocardium, which are often deemed non-viable by traditional techniques. CMR and conventional modalities are both poor at detecting viability in regions of intermediate residual viability but have similar performance in regions with high and low residual viability.

Clinical case applications:

Cardiac MRI can be used to assess for myocardial viability in our patient and thus guide future therapy (revascularization or optimal medical therapy). Furthermore, CMR can accurately determine ejection fraction and extent of proximal coronary artery atherosclerotic lesions, thus risk stratifying this patient. Left main or triple vessel disease may necessitate a surgical intervention in this patient. However, medical therapy or single vessel PCI may be more appropriate than CABG despite multivessel CAD if there is limited or no viability in multiple infarct areas.

In our patient, cardiac MRI/MRA showed mildly dilated LV with moderately reduced LV ejection fraction, hypokinetic myocardium without scar in LAD territory, hypokinetic myocardium with mild scar in RCA territory, and hypokinetic but viable myocardium in LCX territory. Coronary artery origins were incompletely visualized due to motion but there was patent origin of RCA, LAD, and LCX (L main couldn’t be visualized). Patient was discharged home on medical therapy and planned to return for coronary angiogram and possible revascularization as his coronary anatomy was not completely delineated by the Cardiac MRI.




1.         Kim, RJ, Fieno, DS, Parrish, TB, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 1999; 100:1992.

2.         Fieno, DS, Kim, RJ, Chen, EL, et al. Contrast-enhanced magnetic resonance imaging of myocardium at risk: distinction between reversible and irreversible injury throughout infarct healing. J Am Coll Cardiol 2000; 36:1985.

3.         Kim RJ, Wu E, Rafael A, et al. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 2000; 343:1445-1453.

4.         Nagel, E, Lehmkuhl, HB, Bocksch, W, et al. Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography. Circulation 1999; 99:763.

5.         Kuhl HP, Beek AM, van der Weerdt AP, et al. Myocardial viability in chronic ischemic heart disease: comparison of contrast-enhanced magnetic resonance imaging with (18)F-fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol 2003;41:1341-8.

6.         Bellenger NG, Burgess MI, Ray SG, et al. Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance. Are they interchangeable? Eur Heart J 2000;21:1387-96.

Reviewed by Robert Donnino MD, NYU Division of Cardiology:

The case report and discussion provided by Dr. Ghumman highlights some of the important uses of CMR in patients with ischemic cardiomyopathies.  In this case the CMR provided several important pieces of information relevant to this patient’s care. First, by the distribution of myocardial scar (seen as LGE on CMR) we can confirm with high confidence that this patient’s cardiomyopathy is ischemic in etiology.  In addition, the presence of only mild scar (as opposed to transmural or near-transmural scar) indicates that this patient is very likely to have a significant improvement in left ventricular function after revascularization in all three major coronary vessel distributions.  As mentioned, this assessment of viability using CMR has been proven to be very reliable and is being used with increasing frequency in patients undergoing coronary revascularization (particularly in those being considered for bypass surgery). While it was not possible in this patient due to motion artifact, CMR can also provide an assessment of coronary stenosis, particularly of the proximal and larger vessels. Although there is continuing progress, CMR remains somewhat inferior to CT angiography and invasive x-ray angiography for detection of coronary stenosis, particularly of distal arteries and smaller caliber vessels.  Finally, CMR is considered the gold standard for measurements of left ventricular ejection fraction and chamber volume.  This may further assist the clinician in determining therapies such as biventricular pacemakers or cardiac defibrillators, particularly in those patients with technically challenging echocardiograms.

Meeting Perspectives: American Heart Association Scientific Sessions 2008- Report from the cardiology fellows

December 16, 2008

heart.jpgCommentary by Steven Sedlis, MD Associate Professor of Medicine, Chief, Division of Cardiology Manhattan Veterans Administration Medical Center

The annual scientific session of the American Heart Association was held in New Orleans on November 8-12 2008, the second major cardiology meeting in New Orleans since Katrina. The city has obviously not recovered. The crowds on the streets are sparser and the lines at restaurants considerably shorter than they were before the hurricane. Charity Hospital is closed and a large sign for LSU Interim Hospital is a stark reminder that the health care system is also nowhere near back to normal.

It was hard to feel gloomy however under the blue skies with the temperature in the 70s. The cardiology fellows certainly enjoyed themselves a great deal. The fellows stayed at the JW Marriott on Canal Street, halfway between the convention center and the heart of Bourbon Street. Either way, they were at the heart. I can attest to that, having seen them at the meetings and having heard about all the fine dinners they enjoyed in the French Quarter. This posting will include accounts of the studies that the cardiology fellows thought were particularly interesting or important.

The big news from AHA was the JUPITER trial presented as a late breaking trial on Sunday and simultaneously published online in the New England Journal of Medicine. Eldad Einav presented the trial to our cardiology division and Tatyana Danilov presented the paper at journal club . JUPITER, a randomized trial of rosuvastatin in the prevention of cardiovascular events among 17,802 apparently healthy men and women with elevated levels of C – reactive protein (hsCRP) was an investigator initiated trial funded by Astra- Zeneca that compared outcomes in men over the age of 50 and women over the age of 60 with LDL cholesterol levels < 130 and hsCRP > 2 mg/dl randomized to rosuvastatin 20 mg or placebo. The study was stopped prematurely by the data safety monitoring board after a mean follow-up of less than 2 years because the pre-specified endpoint of first major cardiovascular event or death from any cause was met. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval 0.46 to 0.69; P<0.00001). As Paul Ridker, the principal investigator, pointed out in his late breaking trial presentation these data suggest that the number of patients needed to treat with rosuvastatin for 5 years to prevent one event is as low as 25.

JUPITER has sparked considerable controversy. Many have pointed out that Paul Ridker and Harvard hold a patent for the hsCRP assay. Does this financial incentive bias Ridker’s interpretation of the data? Others have pointed out that by stopping the trial early the data safety monitoring board may have overestimated the degree of benefit. On the other hand, many others (particularly in the field of prevention) say they would have prescribed statins to patients such as the ones enrolled in JUPITER irrespective of the hsCRP. So will JUPITER change practice? Will it change yours? A not particularly scientific survey of nearly 2500 physicians who responded to a poll in the New England Journal of Medicine indicated that the medical community is split nearly down the middle with 50% of respondents saying that the trial indicates that the approach to laboratory screening should be changed. Another 48% of voters responding to a second question thought that the trial provides a basis for a change in the therapeutic use of stains.

My own view is that JUPITER is an important study because it shows that 20 mg of rosuvastatin is a well tolerated and safe dose of a potent statin that will benefit many individuals at risk for atherothrombosis. There was no difference in the side effect profile of rosuvastatin and placebo except for a slight difference in glycemic control favoring placebo. My own bias is that difference is not clinically significant, but obviously some will differ. The importance of statin dose was underscored by a negative study presented at the AHA. The SEARCH trial randomized 12,000 patients with prior myocardial infarction to either 20 mg or 80 mg of simvastatin and found a non significant 6% reduction in vascular events with the higher dose at the cost of significantly more cases of myopathy (53 versus 3). In my view this was a predictable, but instructive finding. The Heart Protection Study showed that 40 mg of simvastatin was a safe and effective dose so I am sure that many patients in SEARCH randomized to the low dose ended up on 40 mg when they or their physicians noted suboptimal control of LDL. On the other hand, 80 mg of simvastatin is not a well tolerated dose and is associated with significant side effects. What this means to practitioners is that for most patients 40 mg of generic simvastatin is cost-effective treatment with 20 mg of rosuvastin or 80 mg of atorvastatin available for patients who do not reach goal with simvastatin and 40 mg of rosuvastatin reserved for patients who require the most potent statin. JUPITER did not address the higher dose of rosuvastatin, but taken together with other trials notably PROVE-IT, TNT, IDEAL and A to Z there is a growing body of evidence to suggest that intensive LDL lowering with statins is beneficial and now JUPITER confirms that 20 mg of rosuvastatin is a safe and effective means of achieving this goal.

Alex Natanson presented the findings of TIMACS (Timing of Intervention in Patients with Acute Coronary Syndromes). This was probably my favorite study from AHA because the findings mean that when I get a call about an ACS admission at night I can with a clear conscience and a happy heart go back to bed for a nice long snooze before I come to the hospital in the morning and take the patient to the cath lab. Now I am, and I hope you are too, a confirmed believer in an early invasive approach for most patients with ACS. The question is what does “early” mean? The TIMACS investigators randomized 3031 patients admitted with ACS to early angiography (within 24 hours) versus delayed angiography (greater than 36 hours) following hospital admission. The median time to cath was 14 hours for the early group and 50 hours for the delayed group. There was no significant difference in the primary endpoint of death, MI or stroke. Not surprisingly, there was a difference in the secondary endpoint of refractory ischemia requiring urgent cath. Clearly patients in the delayed group had more time when they were at risk for refractory ischemia than the early group that had undergone cath and revascularization. TIMACS did show benefit to early cath in their very high risk subgroup with ongoing ischemia or hemodynamic instability, but these are patients who most practitioners would take for early cath. A very important conclusion of TIMACS is that there is no benefit to waiting. There is no need to “cool down” patients – the same finding as in ISAR-COOL which showed no benefit and even harm from a strategy of intensive antiplatelet therapy for 72-120 hours prior to cath and intervention. So the moral is: don’t rush, but don’t delay – get your patient to the cath lab by the end of the day.

Read more »

Breaking News: FDA Advisory Committee Calls For Ban on Long Acting Beta Agonists in Asthma

December 12, 2008

foradil.jpgCommentary by Denise Pate MD, PGY-1 

The FDA released a 460 page document regarding the safety of long acting beta agonists (LABA) for the use of asthma, in addition to a two day advisory committee meeting this week on the call to ban LABA when used alone and not in combination with an inhaled steroid. The FDA found through a meta-analysis of 110 trials studying 4 drugs—2 LABAs, Foradil and Serevent, and 2 LABA/ICS (Inhaled Corticosteroids) Advair and Symbicort. The study found that there was an increased risk of hospitalization and asthma related deaths from LABAs alone ,with 20 asthma related deaths of which 16 came from those of patients strictly taking LABA. Prior to the implementation of LABAs in asthma these drugs were used in COPD with good results. Therefore, although the FDA is calling for their ban in the use of asthma they will most likely not be pulled from the market for the use of COPD.

Despite the FDAs forceful stance against the use of LABAs, the NY Times reports that many medical associations, including the American Academy of Pediatrics, American Thoracic Society, American Academy of Allergy Asthma and Immunology, and American College of Allergy Asthma and Immunology still support the continued use of the medications.

The FDA’s role is to protect patients. However some of the officials may be detached from clinical practice where we often see the benefits of LABAs. The major contention lies between the use of LABAs alone versus LABAs with ICS, however the FDA is considering continuing studies on the safety of Advair and Symbicort, particularly in children. As the NY Times explains, LABAs may cause an increased risk in death because such agents immediately relieve symptoms, thereby potentially making patients less likely to use an inhaled steroid concurrently.Some anecdotal evidence that was published in the NEJM in the early 90s stated that two elderly patients were found dead holding their Serevent inhalers. While this is tragic, maybe the onus lies on us to properly educate our patients as to how and when to utilize their medications and simultaneously teaching them to be as vigilant as possible by taking cues from their symptoms.

Tackling Cancer Control Worldwide: Report From the 2008 World Cancer Congress

December 11, 2008

logo-world-cancer-congress.gifCommentary by Antonella Surbone MD PhD FACP, NYU Department of Medicine and Clinical Correlations Ethics Section Editor

On Tuesday December 9th 2008, leading global cancer organizations met in Atlanta to discuss the 2008 WHO World Cancer Report predicting that cancer will overtake heart disease as the world’s top killer by 2010, and that global cancer cases and deaths will more than double by 2030. They called on governments to act, by ratifying an international tobacco control treaty and by asking the US to also invest in cancer vaccines and research. A “global health diplomacy” approach, making good use of past US experiences in the field of cancer control and advocacy, was suggested also for developing countries.

The 2008 World Cancer Congress was hosted in Geneva from Thursday August 27th to Sunday August 31st by the International Union Against Cancer (UICC), a leading international non-governmental organization dedicated to the global control of cancer. This event was unique due to its comprehensive approach to all dimensions of cancer control, from medical to social and political. The thrust of the 2008 Congress is especially significant due to the rapidly increasing number of cancer patients and survivors in developed and developing countries and the existence of major health care disparities worldwide. In order to adequately represent the global situation and to foster cancer advocacy on the global political scene, UICC funded the participation of 250 delegates from poorer countries. Read more »