Researchers say having a glass or two of champagne a day is good for the heart and blood circulation, according to The Guardian Observer.

According to University of Reading researchers, the fizz made with black grapes has the potential to reduce strokes and heart disease risk.

Dr. Jeremy Spencer of University of Reading said, “We have found that a couple of glasses a day has a beneficial effect on the walls of blood vessels ““ which suggests champagne has the potential to reduce strokes and heart disease. It is very exciting.”

Previous studies have shown two glasses a day of red wine helps ward off heart and circulation problems.

Most of that effect comes from chemicals called polyphenols, which affect circulation by slowing down the removal of nitric oxide from the blood. In turn, elevated levels of nitric oxide cause blood vessels to dilate, which lowers blood pressure and reduces risks of heart problems and strokes.

Polyphenols are also found in champagne, which is made from two varieties of black grape, pinot noir and pinot meunier, and one of white, chardonnay.

The team found that champagne had a far greater impact on nitric oxide levels in the blood than did a polyphenol-free alternative of alcohol and carbonated water.

In short, its polyphenols have the ability to improve blood pressure and reduce heart disease risks.

“Our data suggests that a daily moderate consumption of champagne wine may improve vascular performance via the delivery of phenolic constituents,” said the researchers.

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On the Net:

• University of Reading

In era of minimalist therapy, some mucinous carcinoma patients may need more, not less treatment

In a large review of breast cancer patients with mucinous carcinoma, researchers at The University of Texas M. D. Anderson Cancer Center have identified an association between this rare type of breast cancer long-associated with a favorable prognosis and multiple tumors undetected by mammography or ultrasound.

The study, presented today at the CTRC-AACR San Antonio Breast Cancer Symposium, is the first to observe this negative association and should caution those caring for mucinous breast cancer patients that more, not less, therapy, as well as additional screening may be needed for a select group of these patients, said George Perkins, M.D., associate professor in M. D. Anderson Department of Radiation Oncology and the study’s first author.

Mucinous breast cancer, also known as colloid carcinoma, is a rare type of invasive breast cancer formed by mucus-producing cancer cells. Perkins estimated that the disease accounts for approximately two percent of all breast cancers diagnosed. The prognosis for mucinous carcinoma is thought to be better than for the more common types of invasive breast cancers.

“While mucinous breast cancer is thought to be a disease with a favorable prognosis, our study is the first to identify it as one associated with significant multifocal presentation – a potentially unfavorable aspect with a subtype long thought to be extremely favorable,” said Perkins. “Our findings must caution those caring for these women that they may not only need more radiographic evaluation, such as MRI, but also intraoperative collaboration with radiology and pathology. These patients also may need standard radiation treatment, rather than the minimal effective therapy, which could include no post-surgery treatment at all.”

Researchers reviewed charts of 264 patients with mucinous carcinoma treated at M. D. Anderson between 1965 and 2005. The median age and follow-up was 57 years and 168 months respectively. Of the patients, 86 percent were stage T2 or less, and 80 percent had no lymph node involvement, 15 percent had 1-3 positive nodes and 5 percent had 4 or more.

Regarding treatment, 44 percent of the women received breast-conserving therapy, and the rest underwent a mastectomy; 51 percent had radiation.

However, while 10 percent of the women first presented with more than one tumor, after surgical resection and complete pathological review, the actual rate of multifocal disease was 38 percent. None of these tumors were detected by mammography and/or ultrasound.

“This actual rate of multifocal disease was a tremendous surprise and of true concern,” said Perkins. “We are also concerned that the age of disease presentation appears to be decreasing in this population. Combined with this trend of unfavorability, it’s imperative that we continue to research personalized treatment options for this subtype and that patients receive their treatment based on actual presentation rather than the assumption that this is always a favorable disease.”

The five, 10 and 15 year overall survival (OS), disease-free survival (DFMS), local-regional control (LRC) were: 95 percent, 88 percent, 83 percent; 97 percent, 95 percent, 92 percent and 97 percent, 94 percent and 85 percent, respectively. When analyzing surgical options, there was no statistically significant difference in overall OS, DFMS, or LRS. Likewise, there was no improvement in OS or DMFS in patients that received whole breast radiation. There was a trend, however, for improved LRC in patients who received radiation when comparing patients that underwent surgery without radiation.

As follow up, the researchers are evaluating a subtype of mucinous breast cancer thought to be exceedingly aggressive in hopes of establishing specific screening and treatment guidelines.

In addition to Perkins, other authors on the all-M. D. Anderson study include: Gildy Babiera, M.D., associate professor, Isabel Bedrosian, M.D., assistant professor, both of the Department of Surgical Oncology; Eric Strom, M.D., professor, Department of Radiation Oncology, Gary Whitman, M.D., professor, and Wei Yang, M.D., associate professor, both of the Department of Diagnostic Radiology; and Lavinina Middleton, M.D., associate professor, Department of Pathology.

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On the Net:

• University of Texas M. D. Anderson Cancer Center
• CTRC-AACR San Antonio Breast Cancer Symposium

But second study finds a subset of patients who may not benefit

Chemotherapy added to tamoxifen can improve outcomes for postmenopausal breast cancer patients, according to a landmark study by the Southwest Oncology Group.

But a related study presented today at the 2009 San Antonio Breast Cancer Symposium finds that a multigene test on tumors can identify a subset of patients who may not benefit from that chemotherapy.

Both studies were led by Dr. Kathy Albain, of Loyola University Health System. Both have just been published online, the first in the journal the Lancet, the second in the Lancet Oncology.

The studies report on a randomized phase III clinical trial of 1,477 postmenopausal women that was conducted at institutions across the U.S. and Canada by the University of Michigan-based Southwest Oncology Group (SWOG), one of the largest federally funded clinical trial networks. All of the women had estrogen receptor-positive (ER+) breast cancer that had spread to the lymph nodes under the arm, known as the axillary lymph nodes.

All women in the trial got daily tamoxifen for up to five years, long the standard therapy for treating ER+ breast cancer, the most common form of the disease. Estrogen latches on to receptors on these cancer cells and promotes tumor growth. Tamoxifen blocks those receptors, locking estrogen out.

Of the 1,477 women in the trial, 361 got only tamoxifen. The rest got tamoxifen plus a regimen of a three-drug chemotherapy treatment known as CAF (cyclophosphamide, Adriamycin®, and 5-fluorouracil).

Albain’s team reports in the Lancet paper that they saw long-term survival benefits for the women who received CAF chemotherapy. These women’s risk of dying or having a cancer recurrence was 24% lower than it was for women who had gotten tamoxifen alone. The team also found that those who got the chemotherapy before the tamoxifen did better than those who got both simultaneously.

The CAF group had higher overall survival rates as well. “Ten years after the start of their treatment, 68% of women who received chemotherapy followed by tamoxifen were still alive, while only 60% of women in the tamoxifen-only arm lived for at least ten years,” says William Barlow, Ph.D., of the SWOG Statistical Center in Seattle, who served as lead statistician on both studies.

Initial results from this trial presented at professional conferences in recent years have already changed the standard of practice to include several months of CAF chemotherapy before tamoxifen in treating postmenopausal women with ER+ breast cancer.

The second study, published in The Lancet Oncology, was conducted to determine if subsets of women in the SWOG trial could be identified who did not benefit from chemotherapy despite being at higher risk due to lymph node involvement. This study retrospectively analyzed tumor specimens from the trial using a genetic test called the 21-gene recurrence score assay (Oncotype DX®). The assay measures the expression or activity level of 21 specific genes within a tumor sample, and the score predicts risk of recurrence. Testing was conducted by Genomic Health, Inc, who were blinded to the study results.

The study found that women whose tumors scored low on the genetic test appeared to get little or no benefit from CAF chemotherapy added to tamoxifen, while those with higher scores seemed to derive major benefit from this addition.

The 21-gene recurrence score test is now routinely used on the tumors of many patients whose breast cancer has not spread to their lymph nodes ““ node-negative breast cancer. Doctors use the assay score to help them decide whether a patient is likely to benefit from a course of chemotherapy.

The researchers conclude that this test may similarly predict chemotherapy benefit in patients whose breast cancer has spread to their lymph nodes. These patients account for about one-fifth of newly diagnosed breast cancer cases in the U.S.

“There’s nothing magic about the biology being different in lymph node-negative versus lymph node-positive breast cancer,” says Albain. When it comes to predicting benefit from chemotherapy, “our data suggest that it doesn’t seem to matter whether the lymph nodes are involved or not, but the recurrence score on the genetic assay does matter. It identifies for us a group of patients who have a distinct tumor biology, for whom chemotherapy may not reduce the chances of recurrence even though their risk is high.”

Currently, several months of chemotherapy after surgery is the standard of care for a patient with node-positive breast cancer, regardless of the hormone receptor or other biomarker status in her tumor tissue. Indeed, chemotherapy in this setting has been credited in part for a marked decline in breast cancer mortality over the last 20 years. But if validated by later studies, the results reported by the SWOG investigators would mean that many of these patients are being treated needlessly, since they do not benefit from the chemotherapy.

The researchers stress that these results only pertain to patients with estrogen receptor-positive breast cancers, and that more work needs to be done to confirm the findings before doctors change clinical practice based on them.

“Many aspects of this retrospective study introduce uncertainty into our results and make our conclusions tentative,” says Dr. Daniel Hayes of the University of Michigan Medical School, who was senior author on the Lancet Oncology study. “Prospective studies with larger sample sizes are needed to determine who will benefit from chemotherapy added to hormonal therapy and who should avoid chemotherapy altogether.”

Hayes adds that the Southwest Oncology Group is now designing such a study.

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On the Net:

• University of Michigan Health System
• Lancet

According to a new guideline from the American Society for Gastrointestinal Endoscopy (ASGE) regarding the management of antithrombotic agents for endoscopy, aspirin and/or NSAIDs may be continued for all elective endoscopic procedures. When high-risk procedures are planned, clinicians may elect to discontinue aspirin and/or NSAIDs for five to seven days before the procedure, depending on the underlying indication for antiplatelet therapy. For patients on temporary anticoagulation therapy (e.g., warfarin for deep venous thrombosis), it is suggested that elective endoscopic procedures be deferred until antithrombotic therapy is completed. The guideline, “Management of antithrombotic agents for endoscopic procedures,” was developed by ASGE’s Standards of Practice Committee and appears in the December issue of GIE: Gastrointestinal Endoscopy, the monthly peer-reviewed scientific journal of the ASGE.

Antithrombotic agents include anticoagulants (e.g., warfarin, heparin, and low molecular weight heparin) and antiplatelet agents (e.g., aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), thienopyridines (e.g., clopidrogrel and ticlopidine), and glycoprotein IIb/IIIa receptor inhibitors. Antithrombotic therapy is used to reduce the risk of thromboembolic events (blocking of a blood vessel by a blood clot dislodged from its site of origin) in patients with certain cardiovascular conditions (e.g., atrial fibrillation and acute coronary syndrome), deep venous thrombosis (DVT), hypercoagulable states, and endoprostheses. The most common site of significant bleeding in patients receiving oral anticoagulation therapy is the gastrointestinal (GI) tract.

“Before performing endoscopic procedures on patients taking antithrombotic medications, one should consider the risks of stopping these medications versus the risk of a complication if the medications are continued. But one must also consider the urgency of the procedure,” said Jason A. Dominitz, MD, MHS, FASGE, chair of ASGE’s Standards of Practice Committee. “Alternative diagnostic studies for patient evaluation, such as video capsule endoscopy or radiologic studies, may be appropriate in some cases.”

Potential thromboembolic events that may occur with the withdrawal of medication can be devastating, whereas bleeding after high-risk procedures, although increased in frequency, is often not associated with any significant morbidity or mortality. Discussion with the patient and his or her prescribing physician before the procedure is invaluable to help determine whether antithrombotic agents should be stopped or adjusted in any particular patient. This guideline is an update of two previous ASGE guidelines and addresses the management of patients undergoing endoscopic procedures who are receiving antithrombotic therapy, providing recommendations and management algorithms.

RECOMMENDATIONS FROM THE ASGE STANDARDS OF PRACTICE COMMITTEE:

Elective Endoscopic Procedures

1. For patients on temporary anticoagulation therapy (e.g., warfarin for DVT), it is suggested that elective endoscopic procedures be deferred until antithrombotic therapy is completed.

2. It is recommended that aspirin and/or NSAIDs may be continued for all endoscopic procedures. When high-risk procedures are planned, clinicians may elect to discontinue aspirin and/or NSAIDs for five to seven days before the procedure, depending on the underlying indication for antiplatelet therapy.

3. It is recommended that elective procedures be deferred in patients with a recently placed vascular stent or acute coronary syndrome (ACS) until the patient has received antithrombotic therapy for the minimum recommended duration per current guidelines from relevant professional societies. Once this minimum period has elapsed, it is suggested that clopidogrel or ticlopidine be withheld for approximately seven to ten days before endoscopy and that aspirin be continued. For those patients not taking aspirin, the addition of aspirin during the time that clopidogrel or ticlopidine is withheld may reduce the risk of thromboembolic events. Clopidogrel or ticlopidine may be reinitiated as soon as deemed safe with consideration of the patient’s condition and any therapy performed at the time of endoscopy. Consultation with the patient’s cardiologist or other relevant provider may help determine the optimal management of these patients.

4. When clopidogrel and ticlopidine are used for other indications, it is suggested that these medications may be continued for low-risk procedures, but should be discontinued for approximately seven to ten days before higher-risk procedures. For those patients not taking aspirin, the addition of aspirin during the periendoscopic period may reduce the risk of thromboembolic events. Clopidogrel or ticlopidine may be reinitiated as soon as deemed safe with consideration of the patient’s condition and any therapy performed at the time of endoscopy.

5. It is suggested to discontinue anticoagulation (ie, warfarin) in patients with a low risk of thromboembolic events in whom it is safe to do so. It is suggested to continue the anticoagulation in patients at higher risk of thromboembolic complications, switching to low molecular weight heparin (LMWH) or unfractionated heparin (UFH) (ie, bridging therapy) around the time of endoscopy when indicated for known or expected therapeutic indications.

6. There is insufficient evidence to recommend for or against the prophylactic use of mechanical clips after polypectomy in patients on anticoagulation.

7. There is no consensus as to the optimal timing of reinitiation of anticoagulant therapy after endoscopic interventions, and decisions are likely to depend on procedure-specific circumstances as well as the indications for anticoagulation. It is suggested that the benefits of immediate anticoagulant therapy in preventing thromboembolic events be weighed against the risk of hemorrhage and determined in a case-by-case basis. In patients at high risk of thromboembolic events, it is suggested that UFH or LMWH (ie, bridging therapy) be restarted as soon as safely possible and that warfarin be restarted on the day of the procedure unless there is significant concern for bleeding. UFH may be restarted two to six hours after a therapeutic procedure. The optimal time to restart LMWH after endoscopy has not been determined. In patients with a low risk of thromboembolic events, it is suggested that warfarin be restarted on the evening after the endoscopy unless procedural circumstances suggest a high risk of postprocedure bleeding. Bridging therapy in patients with a low thromboembolic risk is not necessary.

8. In pregnant patients with mechanical heart valves needing endoscopic procedures, it is recommended that elective procedures be delayed until after delivery whenever possible, and when delay is not possible, that bridge therapy with LMWH or UFH be considered. Consultation with the patient’s cardiologist and/or obstetrician should be obtained.

Urgent and Emergent Endoscopic Procedures

1. It is suggested that patients with acute GI bleeding taking antiplatelet agents should have these medications withheld until hemostasis (stoppage of bleeding) is achieved. Administration of platelets may be appropriate for patients with life-threatening or serious bleeding. In situations of significant bleeding occurring in patients with a recently (less than one year) placed vascular stent and/or ACS, it is suggested that cardiology consultation be obtained before stopping antiplatelet agents.

2. It is recommended that patients with acute bleeding receiving anticoagulation therapy have these agents withheld until hemostasis is achieved. The decision to use fresh frozen plasma (FFP), prothrombin complex concentrate, and/or vitamin K should be individualized. It is suggested that protamine be reserved for patients with life-threatening bleeding on heparin because of the potential risks of anaphylaxis and severe hypotension. In situations of significant bleeding occurring in patients with a recently (less than one year) placed vascular stent and/or ACS, it is recommended that consultation with the prescribing service be obtained before stopping anticoagulants.

3. It is recommended that patients with acute GI bleeding taking warfarin with a supratherapeutic international normalized ratio (INR) undergo correction of anticoagulation, although the target level INR required for endoscopic therapy to be effective has not been determined.

4. The absolute risk of rebleeding after endoscopic hemostasis in patients who must resume anticoagulation is unknown, and the timing for resumption of anticoagulation should be individualized. It is suggested that in patients with high-risk stigmata for rebleeding (e.g., a visible vessel) intravenously administered UFH be used initially because of its relatively short half-life.

Endoscopy in the patient with a vascular stent or ACS taking antithrombotic drugs

Our understanding of the safety of endoscopy in patients with ACS and/or a recently placed vascular stent taking antithrombotic medications, including dual antiplatelet therapy (DAT) and glycoprotein IIb/IIIa inhibitors, is rapidly evolving and is likely to change as knowledge and experience are accumulated. For this reason, strong recommendations regarding the management of particular agents cannot be made at this time and clinicians are encouraged to seek the input of relevant consultants (e.g., cardiology and neurology) before discontinuing any antithrombotic agent for endoscopic procedures.

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On the Net:

• American Society for Gastrointestinal Endoscopy

Blood clotting, or coagulation, is an important process that prevents excessive bleeding when a blood vessel is injured. Sometimes, however, clots form on the inside of vessels without an obvious injury or do not dissolve naturally, a potentially life-threatening situation requiring treatment. Research presented today at the 51st Annual Meeting of the American Society of Hematology reveals that the practice of using the anticoagulants aspirin and heparin with the hope of preventing clots in placental blood vessels is ineffective for preventing unexplained, recurrent miscarriages. Two other studies look at treatments for venous thromboembolism, a common and sometimes deadly clotting disorder.

“Anticoagulants are one of the most common types of medications in use today and help prevent and treat a wide variety of health conditions,” said Bradford S. Schwartz, MD, moderator of the press conference highlighting this research and Professor of Medicine and Biochemistry, and Dean of the University of Illinois College of Medicine at Urbana-Champaign. “That’s why it’s so critical that studies examining both newer formulations and old standbys, like aspirin, provide practitioners with the most up-to-date evidence to ensure that they are being used appropriately and that the best option is chosen for each individual patient.”

This press conference will take place on Sunday, December 6, at 8:00 a.m.

Dabigatran Etexilate Versus Warfarin in the Treatment of Venous Thromboembolism [Abstract #1]

A new study provides welcome news for patients with a common clotting disorder known as venous thromboembolism (VTE). According to the Venous Disease Coalition, 1 million Americans experience VTE every year, which occurs when an abnormal clot forms in a vein and restricts the flow of blood, causing pain and swelling. In some cases, the clot may detach from its point of origin and travel through the heart to the lungs, causing a potentially fatal condition known as a pulmonary embolism.

Currently, patients with VTE are treated with a blood thinner known as warfarin, which has many burdensome interactions with other medications and foods and requires frequent monitoring of the dosage. However, this study shows that an oral drug called dabigatran etexilate, which does not have these disadvantages, is as safe and effective as warfarin for combating VTE.

To compare the two drugs, an international team of researchers conducted a randomized, double-blind trial of 2,539 patients with acute VTE. For six months, roughly half of the patients in the trial (1,274) were given a fixed dose of 150 mg of dabigatran etexilate twice daily, while the other half (1,265 patients) were given warfarin once daily in doses adjusted to an International Normalized Ratio (INR) of 2.0 to 3.0. INR is a blood test needed to monitor the effects of warfarin therapy to ensure an adequate, yet safe, dose is taken; in this study, the test was performed, on average, every 11 days.

The improvement seen in both groups from the treatments was similar. After six months of treatment, only 2.4 percent of the dabigatran etexilate group (30 patients) and 2.2 percent of the warfarin group (27 patients) experienced recurrent VTE. The safety of the two drugs was also comparable. In the dabigatran etexilate arm, 207 patients experienced bleeding (including 20 patients with major bleeding) versus 280 patients in the warfarin arm (including 24 with major bleeding). Other possible side effects, including death, acute coronary syndromes, and abnormalities in liver function tests, were infrequent in the two groups.

“We are excited by these findings and feel that they will change the standard of care for venous thromboembolism, which affects a large number of our patients,” said lead study author Sam Schulman, MD, Professor of Medicine, Thrombosis Service, McMaster Clinic and Hamilton General Hospital in Ontario, Canada. “This study found that dabigatran is a safe and effective anticoagulant that does not require the routine monitoring or dose adjustments that are necessary with warfarin. In other words, patients can receive the same results in a more convenient manner.”

Dr. Schulman will present this study during the Plenary Scientific Session on Sunday, December 6, at 2:00 p.m. in Hall F.

Aspirin and Aspirin Combined With Low-Molecular-Weight Heparin in Women with Unexplained Recurrent Miscarriage: A Randomized Controlled Multicenter Trial (ALIFE Study)
[Abstract #488]

Recurrent miscarriages are extremely traumatic and stressful for women, and, according to the American Society for Reproductive Medicine, the cause is unknown in more than 50 percent of cases (American Society for Reproductive Medicine. Patient’s Fact Sheet on Recurrent Pregnancy Loss. Available at: http://www.asrm.org/Patients/FactSheets/recurrent_preg_loss.pdf). Though treatments to avoid these tragedies remain elusive, some practitioners suspect that abnormal clots in the blood vessels that nourish the placenta are responsible for many recurrent miscarriages, and thus they have increasingly used aspirin and low-molecular-weight heparin to prevent further miscarriages, even though evidence to support their use is not available. Both medications are blood thinners and are used to prevent clots in the placenta that could cut off the supply of nutrients to a growing baby, or to decrease the risk of other pregnancy complications that might be causing the miscarriages.

To test the effectiveness of these controversial treatments, a team of researchers from the Netherlands conducted a multicenter, randomized clinical trial of 364 women between the ages of 18 and 42 who were attempting to conceive or were less than six weeks pregnant. The women had previously experienced at least two unexplained miscarriages by the 20th week of pregnancy. Because the researchers were focused on miscarriages with unexplained causes, women with previous venous or arterial thromboembolism (clotting disorders), endocrine disorders, or other indications for anticoagulant treatment during pregnancy were excluded from the study.

“The study clearly demonstrates that aspirin combined with heparin and aspirin alone do not prevent recurrent, unexplained miscarriages and that we should not needlessly put these women through the inconvenience and risks associated with these blood-thinning medications,” said lead study author Stef P. Kaandorp, MD, research fellow in the Department of Obstetrics and Gynecology at the Academic Medical Center in Amsterdam. “These results are extremely important because they will likely change the way some women at high risk for another miscarriage have been treated.”

During the study, three treatment groups were compared: aspirin and nadroparin (a low-molecular-weight heparin), aspirin alone, and placebo. Oral medication was administered once a day beginning on the day of inclusion in the study through 36 weeks of gestational age, or until miscarriage, ectopic pregnancy, or premature delivery. Patients on the oral regimens received either placebo pills or 100 mg of calcium carbasalate (a salt formulation of aspirin equivalent to 80 mg of aspirin). Women who were to receive low-molecular-weight heparin received subcutaneous injections once a day of 2,850 international units of nadroparin from six weeks of gestational age through 12 hours before delivery.

The intention-to-treat analysis of the study showed that the live birth rate did not differ significantly among the three treatment groups: 54.5 percent of those in the aspirin and nadroparin group had a live birth (67 women), compared with 50.8 percent in the aspirin group (61 women), and 57 percent of the placebo group (69 women). Side effects, most notably skin reactions, also occurred more often in women assigned to the aspirin and nadroparin group.

Dr. Kaandorp will present this study during an oral session on Monday, December 7, at 3:00 p.m. in Room 275-277.

Once-Daily Oral Rivaroxaban Versus Placebo in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism, the EINSTEIN-Extension Study [Abstract #LBA-2]

Venous thromboembolism (VTE), a condition in which a blood vessel is blocked by a clot, is a common and potentially life-threatening disorder. In the United States, there are more than 200,000 new cases of VTE that occur annually (American Heart Association. Venous Thromboembolism and Pulmonary Embolism ““ Statistics. Available at: http://www.americanheart.org/downloadable/heart/1200598191688FS29VTE08.pdf. Accessed November 24, 2009). Treatment for acute VTE typically consists of an anticoagulant, such as a vitamin K inhibitor, for a period of six to 12 months. Following this, the decision to continue the treatment to prevent future clots is controversial. Long-term use of vitamin K inhibitors carries the risk of serious side effects, such as major bleeding, and requires regular laboratory monitoring to optimize the dose while reducing these risks. As an alternative, the safety and efficacy of rivaroxaban, an oral anticoagulant that does not require continued monitoring and dose adjustment, was studied for long-term therapy and found to be safe and effective.

Researchers enrolled 1,197 patients in a double-blind trial involving 280 study sites in 28 countries. Prior to enrollment, the study participants had completed six to 12 months of anticoagulant treatment for acute VTE and were randomized to receive either 20 mg of rivaroxaban once daily (602 patients) or placebo (594 patients) for an additional six to 12 months.

Treatment with rivaroxaban was found to be both safe and effective. Only eight patients (1.3 percent) on rivaroxaban showed signs of recurrent VTE events, compared with 42 patients (7.1 percent) in the placebo arm. In the rivaroxaban arm, four patients (0.7 percent) experienced major bleeding, though none of these events were fatal or at a critical site. Non-major bleeding, such as a nose bleed, skin hematoma (a swelling of blood), or blood in the urine, occurred in 32 patients (5.4 percent) taking rivaroxaban. In the placebo arm, there were no incidences of major bleeding, though seven patients (1.2 percent) experienced non-major bleeding. After the study medication was stopped, six symptomatic recurrent VTE events occurred in each group during a one-month observational period.

“The results of this study are very compelling,” said lead study author Harry R. Bller, MD, PhD, Professor of Medicine in the Department of Vascular Medicine at the Academic Medical Center in Amsterdam. “For these patients in danger of having another VTE event, rivaroxaban lowered their risk by 82 percent without significantly increasing their risk of major bleeding. This once-daily pill provides the clinician with a simple option for patients in whom continued anticoagulant treatment is indicated.”

Dr. Bller will present this study in the Late-Breaking Abstracts Session on Tuesday, December 8, at 7:30 a.m. in Hall F.

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On the Net:

• American Society of Hematology

The World Health Organization announced Friday that H1N1 flu has peaked in the US and Canada.

A(H1N1) influenza is also peaking in western Europe, as the virus is moving east into central Europe and Asia.

“Disease activity has peaked and is declining in North America and has either recently peaked or is currently peaking in much of western and northern Europe,” WHO said.

“In the temperate zone of the northern hemisphere, the early arriving winter influenza season continues to intensify across central Europe and in parts of central, eastern, and southern Asia.”

The UN health agency still reported indications of a decline of flu activity in several European countries that were heavily affected, like Ukraine and Belarus.

As the H1N1 virus permeated 207 countries, the international death toll hit 8,768, with an increase of 942, a smaller amount than the large amount last week.

Since April, the flu has affected a 22 million Americans and 4,000 have died.

The swine flu pandemic has had two waves in the US: a spring movement, and a bigger wave that began late in the summer.

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On the Net:

• WHO

If the entrances and exits of freeways shut down, traffic all over the United States would come to a halt.

In a similar situation, injuries to the brain can make it impossible for neurons to determine information input from output and impedes the ability of the nervous system to operate.

In a recent report in The Journal of Neuroscience, researchers at Baylor College of Medicine and the University of Connecticut Health Center show that this is exactly what happens after nervous system injury.

Complexity of neurons

Neurons are structurally complex with specific parts of the cell responsible for information input, and other parts responsible for information output, said Dr. Matthew N. Rasband, associate professor of neuroscience at Baylor College of Medicine and senior author of the paper. When neurons cannot distinguish between the two activities, the nervous system stops working.

“This is a new way to think about nervous system injuries,” said Rasband. “We have found a new mechanism contributing to the inability of the nervous system to be repaired.”

Molecular fence

Previously, Rasband and his colleagues discovered that the protein ankyrinG builds a ‘molecular fence’ in neurons to maintain the distinction between dendrites (the parts of the cell responsible for information input) and axons (the part of the cell responsible for information output).

AnkyrinG is only found at the axon initial segment, the site where axons begin and dendrites end. Using genetic tricks, the researchers removed this molecular fence, and saw that proteins normally only found in dendrites moved into axons. In effect, they discovered that loss of ankyrinG converted axons (output) into dendrites (input).

Injury destroys protein

In the current study, they extend this previous work to show that nervous system injuries like stroke and nerve crush destroy ankyrinG, leading to neurons that cannot properly distinguish between their inputs and outputs. Although this damage is irreversible, Rasband’s group determined the events leading up to destruction of ankyrinG. They found that after injury, an enzyme gets activated and functions like molecular scissors, cutting ankyrinG into smaller, non-functional pieces. That discovery could be a window of opportunity to use inhibitors of the enzyme to stop the degradation, said Rasband.

“We were successful, but only if the enzyme was inhibited before it destroyed ankyrinG.”

Preservation may be key to treatment

Rasband suggested that their results point to the need for multifaceted treatments for brain injuries and stroke that focus not only on neuroprotection, but also to preserve the axon initial segment and maintain the distinction between axons and dendrites.

Another step forward will be to determine if degradation of ankyrinG is a common event in a variety of brain and spinal cord injuries. With a grant from the U.S. Department of Defense, Rasband’s group is currently studying traumatic brain injury to determine if blast injuries like those experienced by soldiers might also lead to damage of the axon initial segment.

Others who took part in the study include first author Dr. Dorothy P. Schafer, a former graduate student of Rasband and now with Harvard Medical School; Dr. Smita Jha, a postdoctoral fellow in Dr. Rasband’s laboratory in the department of neuroscience at BCM; Dr. Fudong Liu, Trupti Akella and Dr. Louise D. McCullough, all of the department of neuroscience at the University of Connecticut Health Center.

The research was supported by grants from the National Institutes of Health, the Department of Defense, the Dr. Miriam and Sheldon Adelson Medical Research Foundation and Mission Connect.

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On the Net:

• Baylor College of Medicine

The patient, age 76 years and diagnosed with a malignant tumor, was discharged 5 days after surgery

Barcelona, 30 November 2009. Performing surgical operations without leaving scars has ceased to be a chimera and has become a reality. This is demonstrated by the recent surgical advances made using NOTES (Natural Orifice Transluminal Endoscopy Surgery), an innovative surgical approach that allows surgical access using the body’s natural orifices. The results are all advantageous for the patient: lack of scars, shorter hospital stay and faster recovery. Currently, this type of minimally-invasive surgery is still in the research and development stage. Surgery through the mouth and vagina has been successfully used, but the transanal route (through the anus) is less utilized.

On November 9 2009, a team of surgeons carried out the first surgical removal of a rectal mass using the NOTES approach and TEM (Transanal Endoscopic Microsurgery) technique in the Hospital Clinic of Barcelona. The successful (deleted outcome) surgery was due to a collaboration between the Gastrointestinal Surgery team of the Hospital Clinic, headed by Dr. Antonio Mª de Lacy, and a team of surgeons from the Massachusetts General Hospital of Boston (Harvard University), headed by Dr. Patricia Sylla, Instructor of Surgery at the Harvard Medical School. This is the first time in the world that a rectal tumor has been excised using an approach through the anus.

The patient, a 76-year-old woman diagnosed with a malignant rectal tumor, was discharged home with no complications and excellent postoperative recovery on November 14 – only five days after surgery. During the operation, nearly all surgical instruments were introduced through the anus to avoid painful abdominal incisions. This new technique has been developed to achieve better results than laparoscopic surgery, and is a minimally-invasive technique with many advantages: less pain, shorter hospital stay and safe oncologic results. Thanks to the joint work of this international team of experts, surgery has taken a step forward, with a successful operation to excise a rectal mass without leaving surgical scars, whereas even laparoscopic surgery requires four or five minimal incisions.

Transanal Endoscopic Microsurgery (TEM) has many advantages

The transanal route presents many advantages. One essential point is that it can be used in both men and women, unlike the transvaginal route (through the vagina). Another advantage is the possibility of opening and closing the colon or rectum under direct vision. This is possible due to the use of techniques developed for the local treatment of rectal lesions, known as Transanal Endoscopic Microsurgery (TEM).

The TEM technique uses rectal endoscopy to introduce a specially-designed proctoscope connected to a CO2 insufflation system that dilates the rectum. This creates a working space that allows the instruments required to section and dissect the mass to be introduced. This route allows the dissection of the rectum and surrounding tissue until the abdominal cavity is reached, a wholly innovative technique.

The importance of international collaboration between hospitals

This landmark surgery, presented simultaneously today in the Hospital Clinic of Barcelona and Massachusetts General Hospital, was made possible due to the experience of the two surgical teams, who both specialize in minimally-invasive surgical approaches to treat diseases of the colon and rectum. Dr. Lacy has played a fundamental role in the widespread application of laparoscopic surgery, using small incisions in the abdomen, to treat colorectal cancer. Dr. Sylla has been developing techniques for application in colorectal surgery since 2007 in collaboration with Dr. David Rattner, Professor of Surgery at the Massachusetts General Hospital and Harvard Medical School, an authority on NOTES and co-founder of NOSCAR (Natural Orifice Surgery Consortium for Assessment and Research).

After demonstrating the safety and efficiency of the TEM technique in pigs, the two teams carried out studies on human cadavers. Unlike other NOTES procedures, which require incisions in order to access the surgical field, the transanal approach is the only route where the tissue perforated to gain access to the diseased area is part of the tissue that will ultimately be excised.

In the future, this new technique will be available to treat other diseases of the colon and rectum.

Dr. Lacy states: “We are convinced that this type of surgery will bring additional advantages to those already shown by laparoscopic surgery, reducing surgical invasiveness by eliminating abdominal incisions, and resulting in fewer postoperative complications and a speedier recovery”.

Dr. Sylla states: “Based on this first case, I am encouraged that in the near future we will be able to offer this type of procedure to more patients. This approach could have wide use for patients with colorectal cancer, diverticulitis, and other diseases of the colon and rectum.”

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On the Net:

• IDIBAPS – Institut d’Investigacions Biomdiques August Pi i Sunyer

Bacteria don’t have easy lives. In addition to mammalian immune systems that besiege the bugs, they have natural enemies called bacteriophages, viruses that kill half the bacteria on Earth every two days.

Still, bacteria and another class of microorganisms called archaea (first discovered in extreme environments such as deep-sea volcanic vents) manage just fine, thank you, in part because they have a built-in defense system that helps protect them from many viruses and other invaders.

A team of scientists led by researchers at the University of Georgia has now discovered how this bacterial defense system works, and it could lead to new classes of targeted antibiotics, new tools to study gene function in microorganisms and more stable bacterial cultures used by food and biotechnology industries to make products such as yogurt and cheese.

The research was published today in the journal Cell.

“Understanding how bacteria defend themselves gives us important information that can be used to weaken bacteria that are harmful and strengthen bacteria that are helpful,” said Michael Terns, a professor of biochemistry and molecular biology in UGA’s Franklin College of Arts and Sciences. “We also hope to exploit this knowledge to develop new tools to speed research on microorganisms.”

Other authors on the Cell paper include Rebecca Terns, a senior research scientist in biochemistry and molecular biology at UGA; Caryn Hale, a graduate student in the Terns lab at UGA; Lance Wells, an assistant professor of biochemistry and molecular biology and Georgia Cancer Coalition Scholar at UGA and his graduate student Peng Zhao; and research associate Sara Olson, assistant professor Michael Duff and associate professor Brenton Graveley of the University of Connecticut Health Center.

The system, whose mechanism of action was uncovered in the Terns lab (Michael and Rebecca Terns are a husband-wife team), involves a “dynamic duo” made up of a bacterial RNA that recognizes and physically attaches itself to a viral target molecule, and partner proteins that cut up the target, thereby “silencing” the would-be cell killer.

The invader surveillance component of the dynamic duo (an RNA with a viral recognition sequence) comes from sites in the genomes of bacteria and archaea, known technically as “clustered regularly interspaced short palindromic repeats” or more familiarly called CRISPRs. (A palindrome is a word or sentence that reads the same forward and backward.) CRISPR RNAs don’t work alone in fighting invaders, though.

Their partners in invader defense are Cas proteins that arise from a suite of genes called “CRISPR-associated” or Cas genes. Together, they form the “CRISPR-Cas system,” and the new paper describes this dynamic duo and how they protect bacteria from viruses.

“You can look at one as a police dog that tracks down and latches onto an invader, and the other as a police officer that follows along and `silences’ the offender,” said Rebecca Terns. “It functions like our own immune system, constantly watching for and neutralizing intruders. But the surveillance is done by tiny CRISPR RNAs rather than antibodies.”

What the team discovered was that a particular complex of CRISPR RNAs and a subset of the Cas proteins termed the RAMP module recognizes and destroys invader RNAs that it encounters.

“This work has uncovered intriguing parallels between the bacterial CRISPR-Cas system and the human immune system, suggesting a novel way to target disease-causing bacteria,” said Laurie Tompkins, Ph.D., who oversees genetic mechanisms grants at the National Institutes of Health’s National Institute of General Medical Sciences. “It may be possible to turn CRISPR-Cas into a suicide machine, killing pathogenic bacteria by an attack on their own molecules, similar to the self-destruction seen in human autoimmune diseases.”

Understanding how the system silences invaders opens up opportunities to exploit it. So far, CRISPRs have been found in about half of the bacterial genomes that have been mapped or sequenced and in nearly all sequenced archaeal genomes. Such pervasiveness indicates that an ability to manipulate the CRISPR-Cas system could yield a broad range of applications. For example, using the knowledge that they have obtained in this work, the Terns now envision being able to design new CRISPR RNAs that will take advantage of the system to selectively cleave target RNAs in bacterial cells.

“These could target viruses that wipe out cultures of bacteria used by industry to produce enzymes,” said Michael Terns, “or could target the gene products of the bacteria themselves. With this set of Cas proteins, we now know how to cut a target RNA at the site we choose.”

“Believe it or not, we have only recently recognized that these microorganisms have a heritable immune system [because it is so different from our own],” added Rebecca Terns.

Remarkably, scientists are already in a position to begin to capitalize on their rapidly growing knowledge of this bacterial immune system.

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On the Net:

• University of Georgia
• Cell

Cell fragments called platelets are essential to promote blood clotting. Virginia Tech faculty members and students have discovered novel molecular interactions at the surface of platelets that control blood clotting.

The Virginia Tech researchers describe how platelets perform this life-saving magic in the November 24 (8 p.m. Eastern U.S. Time) online issue of the journal PLoS ONE (Public Library of Science) in the article “Sulfatides Partition Disabled-2 in Response to Platelet Activation,” by Karen E. Drahos, biological sciences Master’s degree student from Roanoke, Va.; John D. Welsh, a biological sciences undergraduate student from Pennington, N.J.; and biological sciences Assistant Professors Carla V. Finkielstein and Daniel G. S. Capelluto.

Capelluto and Finkielstein study how proteins signal from biological membranes. One such membrane protein is the integrin receptor that resides on the surface of platelets. A protein that strongly promotes platelet activation through the integrin receptor is thrombin. When there is tissue injury, thrombin converts fibrinogen into fibrin to form a network that traps red blood cells and platelets, creating a clot.

However, the platelets may not remain trapped. They can break their bonds with the network and thin or remove a clot ““ a good thing if the clot is blocking an artery, as in thrombosis or stroke.

One part of the process is well known. When a platelet is stimulated, such as by thrombin, the protein Disabled-2 (Dab2) moves from where it is stored inside of the platelet to the surface, where it interacts with the integrin receptor. If this is the case, Dab2 inhibits blood clotting.

Experimentation and measurements by the Virginia Tech researchers revealed that Dab2 also binds to sulfatides, a lipid that also resides on the surface of platelets. Sulfatides sequester Dab2 proteins, preventing them from binding to the integrin receptor.

“That is, sulfatides partition Dab2 into two pools ““ one pool that is part of the clotting process and one pool that prevents coagulation,” said Capelluto.

When no longer on high alert to regulate clotting, the Dab2 proteins return to the interior of the platelet. “They are likely recycled for the next time they are needed,” said Capelluto.

The study was Drahos’ Master’s thesis research, conducted in both Capelluto’s and Finkielstein’s labs. The thesis received the 2009 William Preston Society Thesis Award in Life Sciences for the best original research with potential to benefit all people. Co-author John Welsh is now a graduate student in Finkielstein’s lab.

The PLoS ONE article stops with the definition of the chemistry of platelets’ two responses to thrombin. But research by Finkielstein and Capelluto is looking at the platelet aggregation inhibitor process as a target for intervention to control bleeding and clotting. “This promises a high impact at the clinical level,” said Capelluto. “The goal is a tool that could be used in surgery and could help people with bleeding or blood clotting disorders without drugs and side effects.”

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On the Net:

• Virginia Tech
• PLoS ONE

An editorial published online November 20 in the Journal of the National Cancer Institute discusses the exaggerated fears and hopes that often appear in news coverage of cancer research. The editorial provides guidance for both the media and journals to help alleviate the problem.

Lisa M. Schwartz, M.D., M.S., and Steven Woloshin, M.D., M.S., of Center for Medicine and the Media at the Dartmouth Institute for Health Policy and Clinical Practice in New Hampshire, and Barnett S. Kramer, M.D., editor-in-chief of the JNCI, use recent media coverage of two studies from the New England Journal of Medicine and the JNCI to demonstrate their point.

Coverage of trial results of the new anti-cancer drug olaparib, which appeared in the NEJM, exaggerated hope in many ways. One national news outlet claimed the drug “was the most important cancer breakthrough of the decade,” but failed to note that the study was uncontrolled (so there is no way to know if the drug accounted for the findings), and very preliminary (it is not known if the findings will ever translate into longer life).

The editorialists also point to coverage of a JNCI article on alcohol consumption and cancer risk among women, which may have caused unwarranted fear: “A drink a day raises women’s risk of cancer,” read one newspaper headline. Unfortunately, the coverage did not provide the magnitude of the risk. Comparing the highest level of drinking (â“°¥15 drinks a week) to the lowest (one to two drinks per week), the investigators observed a 0.6% absolute increase in the risk of breast cancer diagnosis: from 2% to 2.6% for more than 7 years.

Journalists are not the only ones to blame, though, according to the editorialists. Medical journals sometimes leave important elements out of studies. In many cases, absolute risks and study limitations are omitted from the abstracts and journal press releases.

To help journalists and medical journals, the editorialists include tip sheets with guidance on questions to ask study authors, the interpretation of common statistics, and ways to highlight study limitations.

The tip sheets are posted on a new JNCI Web site for science writers: http://www.oxfordjournals.org/our_journals/jnci/resource/reporting_on_cancer.html

“We hope that efforts””within medical journals and those directed toward journalists””will help foster healthy skepticism in the news,” the authors write. “Namely, setting a higher bar for covering very preliminary or inherently weak research, routinely providing data to support claims, and always highlighting study limitations.”

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On the Net:

• Journal of the National Cancer Institute

In a study published in an upcoming issue of The Journal of Child Psychology and Psychiatry researchers show that over reactive parenting, such as heavy criticism or yelling as a response to a child’s negative behavior, can produce higher levels of aggression or rule-breaking in a child who is normally introverted, non-benevolent, non-conscientious, or imaginative. Children who are extraverted, benevolent, conscientious, or not that imaginative by nature are least adversely affected by this parental response.

The research (taken from 586 families) shows that rule-breaking and aggressive behavior is influenced by the inherent personality traits of a child. The study also shows that aggression-related behavior generally decreases as the children grow but on average the rule-breaking behavior does not change, and both genders exhibit these behaviors between the ages six to fifteen. When examining both personality and gender boys and girls are not different affected by parenting methods.

This study is published in an upcoming issue of The Journal of Child Psychology and Psychiatry.

To view the abstract for this article, please click here.

Nutritional giant snails could address malnutrition

A nutritionist in Nigeria says that malnutrition and iron deficiency in schoolchildren could be reduced in her country by baking up snail pie. In a research paper to be published in the International Journal of Food Safety, Nutrition and Public Health, she explains snail is not only cheaper and more readily available than beef but contains more protein.

Ukpong Udofia of the Department of Home Economics, at the University of Uyo, has looked at the moisture levels, protein content, and iron composition of the flesh of the giant West African land snail and compared it to beef steak. Snail pie is much more nutritious than a beef pie, she says.

Udofia and her research team baked pies of both varieties and asked young mothers and their children to try the tasty meal. Most of them preferred the taste and texture of the pies baked with the snail Archachatina marginata to those made with beef. The kids and their mothers judged the snail pies to have a better appearance, texture, and flavor.

“Snail pie is recommended as a cheap source of protein and iron for school-age children and young mothers and could contribute in the fight against iron deficiency anemia,” Udofia says.

“The land snail is a readily available and affordable source of animal protein, inhabits a lot of the green forest and swamps of most developing countries including Nigeria,” Udofia adds, “It is also increasingly cultivated, although in the West it is more familiar as an unusual pet than a pie.

Iron deficiency and a lack of protein in the diet affect young mothers and their children in many developing countries including Nigeria, according to the World Health Organization leading to serious health problems. There is no quick fix for the problem of malnutrition in such countries, but alternative to high-cost meat products could help.

Snail meat contains protein, fat (mainly polyunsaturated fatty acid), iron, calcium, magnesium, phosphorus, copper, zinc, vitamins A, B6, B12, K and folate. It also contains the amino acids arginine and lysine at higher levels than in whole egg. It also contains healthy essential fatty acids such as linoleic and linolenic acids. The high-protein, low-fat content of snail meat makes it a healthy alternative food.

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On the Net:

• Inderscience Publishers
• International Journal of Food Safety

A landmark, 25-year review of cases in which surgeons had to remove the lower portion of the body from the waist down for severe pelvic bone infections shows the therapy can add years and quality of life to survivors, say researchers at UT Southwestern Medical Center.

The rarely performed surgery is called a hemicorporectomy or translumbar amputation, and involves removing the entire body below the waist, including legs, pelvic bone and urinary system.

“It is used as a last resort on patients with potentially fatal illnesses such as certain cancers or complications from ulcers in the pelvic region that cannot otherwise be contained,” said Dr. Jeffrey Janis, associate professor of plastic surgery at UT Southwestern and lead author of the study, which appears in the October issue of Plastic and Reconstructive Surgery. “We determined that it can be effective and a reasonable consideration in some of these extreme cases.”

Hemicorporectomy rarely has been performed because of the very limited indications for the procedure, said senior author Dr. Robert McClelland, professor emeritus of surgery at UT Southwestern.

“An increasing number of veterans of Iraq and Afghanistan conflicts are surviving very severe injuries that frequently lead to permanent paraplegia and are often complicated by severe bedsores and intractable bone infection, which is potential a source of fatal sepsis. Because of this, the frequency of indications for hemicorporectomy may soon increase significantly,” Dr. McClelland said.

Only 57 cases of translumbar amputations had been recorded in medical literature worldwide, although the researchers suspect more have occurred since the initial referencing in 1960. The authors added to their review nine UT Southwestern patients who had received the procedure as a result of terminal pelvic osteomyelitis, a type of bone infection.

About a third of the 66 patients survived at least nine years after having a hemicorporectomy. Of those who had the procedure for the bone infection, more than half survived at least nine years. Of the nine terminal pelvic osteomyelitis-driven patients treated at UT Southwestern, four remained alive after 25 years and the average survival was 11 years.

“Though it is impossible to know how the survival rate would compare had these patients not undergone the amputation, given the severe disease involved, it is reasonable to assume they survived longer than they would have without surgery. Most importantly, our survivors reported that they were satisfied with their decision to have the procedure,” said Dr. Janis, who is also chief of plastic surgery and wound care for Parkland Health & Hospital System, the primary teaching institution of UT Southwestern.

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On the Net:

• UT Southwestern Medical Center

Targeted postmortem testing to identify genetic mutations associated with sudden unexplained death (SUD) is an effective and less expensive way to determine risk to relatives than comprehensive cardiac testing of first degree relatives, according to research presented at the American Heart Association’s Scientific Sessions 2009.

Postmortem genetic testing can identify mutations that cause cellular dysfunctions leading to heart rhythm disturbances that can cause sudden cardiac death. Such inherited genetic defects occur in 25 to 30 percent of SUD victims, according to lead researcher Michael J. Ackerman, M.D., Ph.D., pediatric cardiologist and director of the Long QT Syndrome Clinic and the Windland Smith Rice Sudden Death Genomics Laboratory at the Mayo Clinic in Rochester, Minn.

Ackerman and senior research technologist David Tester, B.S., compared the yield and costs of postmortem genetic/molecular autopsy testing in 146 SUD cases. They found that 40 of the victims (26.7 percent) had either a catecholaminergic polymorphic ventricular tachycardia (CPVT) mutation (18) or a long QT syndrome mutation (22), both known contributors to sudden death.

Researchers estimated the costs of testing 160 relatives of victims who tested positive for mutations. The tests included genetic tests and either treadmill stress tests or electrocardiograms.

For the 424 relatives of the 106 victims who tested negative for mutations, researchers estimated the cost to do more extensive clinical cardiac testing.

Researchers estimated that the total cost of doing postmortem genetic testing, genetic confirmation testing of relatives of mutation-positive victims, followed by cardiac tests for both relatives of mutation-positive and mutation-negative SUD victims, was $6.78 million.

In contrast, the total cost associated with what is currently recommended “” comprehensive cardiac testing for all 584 relatives of the SUD victims, regardless of mutation status, followed by directed genetic testing “” would have exceeded $7.7 million.

The researchers’ primary endpoint, which they reached, was to see if the postmortem testing model would be less expensive and, if so, how great the savings might be.

“With less than 150 SUD cases, use of a cardiac channel molecular autopsy would be estimated to save almost $1 million dollars indicating a much less expensive way of evaluating those left behind,” Tester said. “If you identify a mutation in a sudden unexplained death victim, you can do a simple genetic test in first-degree relatives to assess their risk and perform a disorder-directed clinical evaluation rather than a full clinical evaluation. If a relative is negative for the causative mutation, they may not need to undergo further clinical evaluation at all, and that saves money.”

The researchers said that insurance companies pay for comprehensive cardiac testing for family members despite the fact that commercial molecular/genetic testing of the deceased can provide just as accurate a risk profile and in many cases minimize the need for clinical testing.

“We are reporting that there is data available to make such cardiac risk evaluations on both sides of the grave,” said Ackerman. “The real question is whether it is more prudent and effective to have sudden unexplained death surveillance in autopsy-negative cases. Some insurers cover postmortem gene testing, but it is the exception, not the rule.”

The prevalence of the mutations in the SUD autopsies and first-degree relatives was comparable to rates reported by European researchers.

“Clinical screening can be much more selective if there is postmortem gene testing for the defects that result in sodium and potassium channelopathies,” said Ackerman. “Currently, however, evaluations of the surviving family members are insurance-covered medical expenses whereas postmortem genetic testing has generally been denied.”

The study had limitations and needs to be corroborated by further research. “The cohort we studied was not a population-based collection of SUD cases but instead involved cases that were referred by coroner’s/medical examiner’s throughout North America so we don’t know what the true yield of postmortem genetic testing for autopsy negative SUD is at this time,” said Tester.

Coauthors include Argelia Medeiros-Domingo, M.D., Ph.D.; Carla M. Haglund, B.A.; and Jonathan N. Johnson, M.D.

The study was funded in part by an American Heart Association research grant.

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On the Net:

• American Heart Association
• Video Interview With Michael J. Ackerman, M.D., Ph.D.