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Posts Tagged ‘Boston Medical Center’


Call for the abandonment of the Off-pump CABG surgery (OPCAB) in the On-pump / Off-pump Debate, +100 Research Studies

Curator: Aviva Lev-Ari, PhD, RN

The curator shadowed Dr. J. Walker @MGH performing On-pump CABG in 1/2005 and On-pump CABG performed @Texas Heart Institute in 2/2005, and attended demos of ECMO at Vanderbilt Medical Center, Department of Surgery, Perfusion Program, 8/2005.

 

Public release date: 22-Jul-2013

Contact: Gina Orlando
gina.orlando@bmc.org
617-638-8490
Boston University Medical Center

BMC surgeon recommends off-pump coronary artery bypass grafting be abandoned

(Boston) – In a Special Report in the current issue of Circulation, Boston Medical Center cardiothoracic surgeon Harold Lazar, MD, has found that off-pump coronary artery bypass graft (OPCAB) surgery has failed to show any significant improvement in short-term morbidity or mortality as compared to the traditional on-pump coronary artery bypass graft (CABG) surgery. He recommends that the technique be abandoned, unless surgeons who perform off-pump surgery can show that their own results are as good as results reported with the traditional on-pump surgery.

During off-pump coronary artery bypass graft surgery, the heart is still beating while the graft attachments are made to bypass a blockage. While performing on-pump CABG surgery, the heart is stopped and a heart-lung machine takes over the work for the heart and lungs. This method has been an effective, safe and time-proven technique and is considered the gold standard with which all other surgical revascularization methods have been compared. However, performing coronary revascularization this way can result in myocardial ischemic injury, neurocognitive deficits, and strokes and activate inflammatory pathways that contribute to pulmonary, renal and hematologic complications.

In order to accurately compare the advantages and disadvantages of OPCAB and to determine what, if any, role it should have in the practice of surgical coronary artery revascularization, Lazar examined clinical data from numerous studies worldwide and found the OPCAB technique had failed to show any significant improvement in short-term morbidity or mortality.

According to Lazar a major impetus for performing OPCAB was to avoid the possible detrimental effects of cardiopulmonary bypass, which include activation of inflammatory pathways, changes in neurological and cognitive function and alterations in quality of life. “However, patients undergoing OPCAB have not shown any benefits in these areas,” said Lazar, a professor of surgery at Boston University School Medicine. “Even in those studies in which OPCAB has resulted in a small improvement in early postoperative outcomes, these improvements are no longer apparent on long-term follow-up,” he added.

In fact, several studies suggest that long-term survival may be significantly reduced in OPCAB patients compared with patients in whom on-pump techniques were used. Lazar explains that this may be attributable to the significant increase in incomplete revascularization seen in OPCAB patients and may be responsible for the increase in recurrent angina and need for revascularization procedures seen in OPCAB patients.

“Unless individual surgeons can demonstrate that they can achieve short- and long-term outcomes with OPCABG that are comparable to on-pump CABG results, they should abandon this technique,” said Lazar.

 

The debate over abandoning off-pump CABG surgery

JULY 29, 2013 

Boston, MA Off-pump coronary artery bypass graft (OPCAB) surgery is not as durable or as effective as coronary surgery performed with cardiopulmonary bypass (CPB) and should be abandoned in favor of conventional CABG surgery, according to one expert.

In the July 23, 2013 issue of CirculationDr Harold Lazar (Boston Medical Center, MA) argues that the primary focus of surgical coronary revascularization is complete revascularization and a technically perfect anastomosis that uses the best conduits with a minimal amount of hemodynamic instability. He adds that the procedure should be able to be performed “under all circumstances, on all patients, at all institutions, regardless of their cardiac volume.

“We must not forget that patients are sent for surgical revascularization because medical management has failed, their cardiologists believe that stents will not result in complete revascularization, and the goal is for optimal long-term survival and enhanced freedom from recurrent angina and the need for [repeat] revascularization,” writes Lazar. “These goals can be best achieved with on-pump CABG surgery.”

Dr Robbin Cohen (University of Southern California, LA), on the other hand, said that many physicians are routine off-pump CABG surgeons and the data suggest that results achieved by experienced operators are excellent. It is also a cheaper operation in experienced hands. He does not believe that OPCAB should be abandoned but acknowledged there is a need to better identify the ideal patient who would benefit from the procedure.

While there is yet no consensus and no studies have identified subgroups with better results, the ideal OPCAB candidate is one with a severely diseased descending aorta and those with single-vessel or two-vessel disease—in other words, a patient with favorable anatomy that doesn’t require moving the heart around too much, he said.

“I don’t doubt that I have treated some patients with off-pump surgery where if I had put them on the pump I would have killed them,” Cohen told heartwire.

Looking at the big picture

In his perspective, Lazar analyzes previously published retrospective studies and prospective, randomized controlled clinical trials, including the Randomized On/Off Bypass (ROOBY), Smart Management of Arterial Revascularization Therapy (SMART), and Coronary Artery Bypass Surgery Off- or On-Pump Revascularization (CORONARY) studies.

In ROOBY, the primary short-term end point of death and major cardiovascular events at 30 days was similar in the on-pump and off-pump treatment arms, while cardiac-related mortality and major adverse events were higher in the OPCAB arm at one year. The SMART trial also failed to show a mortality benefit with OPCAB. The CORONARY investigators reported no difference in the composite of death, nonfatal cerebrovascular accidents, nonfatal MIs, or new renal failure requiring dialysis between OPCAB and on-pump CABG surgery. In CORONARY, there was also no difference in quality-of-life scores and neurocognitive function at one year.

Importantly, Lazar says the data from published meta-analyses show that OPCAB patients tend to receive fewer grafts and have a higher incidence of incomplete revascularization. “Despite advances in stabilizers and other equipment, it may be difficult to graft inferior and posterolateral vessels because of right and left ventricular distension and hemodynamic changes,” he writes.

Abandoned? Not so fast, says another expert

So, will OPCAB be abandoned? Not likely, says Cohen. OPCAB is performed often in other countries, mainly because the procedure is quicker and has lower costs than conventional CABG surgery. Cohen had high praise for the systematic review by Lazar, however, noting that the OPCAB vs on-pump CABG debate is a complicated topic and nearly each month brings a new review, journal article, or other analysis in the medical journals.

“Early on, most of us assumed that the morbidity associated with cardiac surgery, that being stroke, renal failure, and so on, was the result of cardiopulmonary bypass,” said Cohen. “And when we started doing off-pump procedures, we assumed that the morbidity would be eliminated. That wasn’t the case. Some of the early studies showed an advantage with blood use and sometimes with the utilization of resources, but morbidity and mortality with the two surgeries were the same.”

Cohen addressed the criticism that OPCAB provides incomplete revascularization compared with on-pump CABG and that the anastomoses are not as good, saying these are all valid criticisms of the procedure. He agreed with Lazar’s point that if surgeons must cross over from OPCAB to conventional bypass, the outcomes are poor. To date, however, OPCAB “has been a moving target,” he added, noting that there has been a move toward addressing these shortcomings.

At one point, Cohen said his group was performing up to 90% of cardiac surgeries with OPCAB but now do just 10% of procedures off-pump. The reasons for decline in use include all of the previously cited reasons:

  • incomplete revascularization,
  • poorer anastomoses, and
  • no reduction in morbidity and mortality to show it is better than conventional CABG, as well the fact that
  • it is difficult to teach to residents.

For OPCAB to move forward, he said that research needs to provide evidence that the procedure is as least as effective and as durable as on-pump CABG. There is also a need to identify specific patient subgroups that would benefit from OPCAB, such as

  • older patients, those with
  • existing renal failure, or
  • patients who have previously had a stroke.
Source

  1. Lazar HL. Should off-pump coronary artery bypass grafting be abandoned? Circulation 2013; 128:406-413. 

 

Related links

Lazar and Cohen report no conflicts of interest. 

http://www.theheart.org/article/1564393.do?utm_medium=email&utm_source=20130731_heartwire&utm_campaign=newsletter

REVIEWS in

http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed_reviews&from_uid=23877063

Should off-pump coronary artery bypass grafting be abandoned?

Lazar HL.

Circulation. 2013 Jul 23;128(4):406-13. doi: 10.1161/CIRCULATIONAHA.113.003388. No abstract available.

PMID: 23877063 [PubMed – in process]

Related citations

 

Off-pump coronary artery bypass grafting: simple concept but potentially sublime scientific value.

Ngaage DL.

Med Sci Monit. 2004 Mar;10(3):RA47-54. Epub 2004 Mar 1. Review.

PMID: 14976442 [PubMed – indexed for MEDLINE]

Related citations

 

Coronary artery surgery: conventional coronary artery bypass grafting versus off-pump coronary artery bypass grafting.

Salzberg SP, Adams DH, Filsoufi F.

Curr Opin Cardiol. 2005 Nov;20(6):509-16. Review.

PMID: 16234622 [PubMed – indexed for MEDLINE]

Related citations

 

Outcomes of off-pump coronary artery bypass surgery: current best available evidence.

Raja SG, Berg GA.

Indian Heart J. 2007 Jan-Feb;59(1):15-27. Review.

PMID: 19098331 [PubMed – indexed for MEDLINE]

Related citations

 

Off-pump coronary artery bypass grafting through sternotomy: for whom?

Noora J, Puskas JD.

Curr Opin Cardiol. 2006 Nov;21(6):573-7. Review.

PMID: 17053406 [PubMed – indexed for MEDLINE]

Related citations

 

Reoperative off-pump coronary artery bypass grafting: current outcomes, concerns and controversies.

Raja SG, Amrani M.

Expert Rev Cardiovasc Ther. 2010 May;8(5):685-94. doi: 10.1586/erc.10.14. Review.

PMID: 20450302 [PubMed – indexed for MEDLINE]

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Off-pump versus on-pump coronary artery bypass grafting.

Halkos ME, Puskas JD.

Surg Clin North Am. 2009 Aug;89(4):913-22, ix. doi: 10.1016/j.suc.2009.06.015. Review.

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Myocardial revascularization for the elderly: current options, role of off-pump coronary artery bypass grafting and outcomes.

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Current status of off-pump coronary artery bypass surgery.

Raja SG, Dreyfus GD.

Asian Cardiovasc Thorac Ann. 2008 Apr;16(2):164-78. Review.

PMID: 18381881 [PubMed – indexed for MEDLINE]

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Cochrane Database Syst Rev. 2012 Mar 14;3:CD007224. doi: 10.1002/14651858.CD007224.pub2. Review.

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Should off-pump coronary artery bypass grafting be abandoned?

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Circulation. 2013 Jul 23;128(4):406-13. doi: 10.1161/CIRCULATIONAHA.113.003388. No abstract available.

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Curated by: Dr. Venkat S. Karra, Ph.D.

In our recent article we mentioned about the amyloidosis, most importantly the most common form of amlyodosis – Primary Amyloidosis (AL).

Primary amyloidosis (AL) is an acquired plasma cell disorder in which a monoclonal immunoglobulin light chain is produced in the bone marrow and usually found in the blood or urine. AL amyloidosis occasionally occurs with multiple myeloma. The amyloid fibrils in this type of amyloidosis are made up of immunoglobulin light chain proteins (kappa or lambda).

Amyloidosis can only be diagnosed by a positive biopsy (i.e., an identification of the amyloid deposits in a piece of tissue). Initial biopsies are most commonly obtained from the abdominal fat.

If amyloid is suspected in other organs, however, a biopsy may be needed from these specific areas. If amyloid is present in a tissue biopsy, further tests can be done to determine the type of the amyloid.

The Amyloid Treatment & Research Program (ATRP) at Boston Medical Center (BMC) is an international referral center that treats amyloidosis with stem cell transplantation.

Last week researchers at Mayo Clinic have used urinary exosomes as a non-invasive diagnostic tool that will offer a snapshot of what is occurring in kidney tissue.

Urinary exosomes are rapidly becoming a powerful tool in the study of renal disease.

English: Urinary system

Already proteomics studies are looking into ways of using urinary exosome to diagnose genetic diseases and characterize disease biomarkers.

The urinary exosomes are excreted from every renal epithelial cells (from the glomerular podocytes to the urinary epithelial cells lining the urinary drainage system) provides us with an opportunity to study proteins once were either difficult or impossible to reach.

With this understanding the researchers undertook this study to evaluate the possible differences among urinary exosomes from patients with different plasma cells dyscrasias. This study suggests that urinary exosomes may be an excellent non-invasive tool for identifying patients with AL amyloidosis because high molecular weight light chain oligomers were found only in patients with AL.

The oligomeric light chain species captured in the urinary exosomes may represent the initial steps of amyloidogenesis. The potential of urinary exosomes in AL is tremendous and deserves further studies. When combined with mass spectrometry and other proteomics techniques, urinary exosomes represent tremendous potential to increase our understanding of amyloidogenesis.

Authors believe that this is the first report of the use of urinary exosome in the study of patients with plasma cell dyscrasias, specifically patients with AL amyloidosis.

References:

1. Amyloidosis: https://pharmaceuticalintelligence.com/2012/06/04/amyloidosis/

2. Alzheimers Disease: https://pharmaceuticalintelligence.com/category/alzheimers-disease-2/

3. Prospects for urinary proteomics: exosomes as a source of urinary biomarkers

4. Source article: Differences in Immunoglobulin Light Chain Species Found in Urinary Exosomes in Light Chain Amyloidosis (AL)

5.  Exosomal Fetuin-A identified by proteomics: a novel urinary biomarker for detecting acute kidney injury.

 6. Characterization of PKD protein-positive exosome-like vesicles.

7. Large-scale proteomics and phosphoproteomics of urinary exosomes.

8. Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy.

Read Full Post »


β-amyloid fibrils.

β-amyloid fibrils. (Photo credit: Wikipedia)

Extracellular deposition of insoluble fibrillar proteins in tissues and organs lead to a condition known as amyloidosis which is thought to be caused by misfolding of proteins. There are several types of amyloidosis, but the unifying feature of the amyloidoses is that the deposits share a common ß-pleated sheet structural conformation that confers unique staining properties.

There are several types of amyloidosis and the most common form is the primary amyloidosis (AL) for amyloid of light chain composition. Symptoms can occur in any organ of the body and the organs most often involved include the heart, kidneys, nervous system, and gastrointestinal tract.

Amyloid deposits in these organs can cause

shortness of breath,

fatigue,

edema (swelling of ankles and legs),

dizziness upon standing,

a feeling of fullness in the stomach (especially after eating),

diarrhea,

weight loss,

enlarged tongue,

numbness of the legs and arms,

protein in the urine (proteinurea) and

enlarged liver (hepatomegaly).

Primary amyloidosis (AL) is an acquired plasma cell disorder in which a monoclonal immunoglobulin light chain is produced in the bone marrow and usually found in the blood or urine. AL amyloidosis occasionally occurs with multiple myeloma. The amyloid fibrils in this type of amyloidosis are made up of immunoglobulin light chain proteins (kappa or lambda).

Amyloidosis caused by infection or inflammation is known as Secondary Amyloidosis (also known as AA amyloidosis) in which elevation of an acute phase protein, SAA, a portion of which (AA protein) deposits as amyloid fibrils. AA amyloidosis usually begins as disease in the kidneys, but other organs can be affected, and may cause protein in the urine, edema, and fatigue.

Medical or surgical treatment of the underlying chronic infection or inflammatory disease can slow down or stop the progression of this type of amyloid where as in case of AL chemotherapy is the standard practice.

Other forms of amyloidosis are familial amyloidosis (ATTR) a most common form of inherited amyloidoses caused by a mutation in the transthyretin (TTR) gene that produces abnormal transthyretin protein which deposits as amyloid fibrils. Symptoms of disease are usually neuropathy (numbness and tingling in the arms and legs, dizziness upon standing, and diarrhea) and cardiomyopathy and occur in mid to late life. The standard treatment is liver transplantation since the transthyretin protein which causes familial amyloidosis is made in the liver, replacing this organ removes the source of mutant protein production. A new liver will make only normal transthyretin. Each family has its own pattern of organ involvement and associated symptoms and the mode of transmission is autosomal dominant.

Other rare forms of inherited amyloidosis include apolipoprotein A-I (AApoAI), apolipoprotein A-II (AApoAII) gelsolin (AGel), fibrinogen (AFib), and lysozyme (ALys).

Beta-2 microglobulin amyloidosis is caused by chronic renal failure and often occurs in patients who are on dialysis for many years. Amyloid deposits are made of the beta-2 microglobulin protein that accumulated in tissues, particularly around joints, when it cannot be excreted by the kidney because of renal failure.

There are many types of localized amyloidoses. The most common and best known is Alzheimer’s disease.

Localized amyloid deposits in the airway (trachea or bronchus), eye, or urinary bladder are made up of light chain proteins, similar to those in AL amyloidosis. However, in localized amyloidosis the abnormal plasma cells producing the amyloid light chains are in the tissues, not in the bone marrow. Other localized types of amyloidosis are associated with hormone proteins, aging, or specific areas of the body, and have not been found to develop into systemic amyloidosis

Diagnosis of this disease is sometimes difficult as many of the sysmptoms are general and can occur in other diseases. Symptoms in each patient depend on the type of amyloidosis and on the type of involved organ systems.

Amyloidosis can only be diagnosed by a positive biopsy (i.e., an identification of the amyloid deposits in a piece of tissue). Initial biopsies are most commonly obtained from the abdominal fat. image from BMCIf amyloid is suspected in other organs, however, a biopsy may be needed from these specific areas. Tissue biopsies must be stained properly with Congo red, a dye which will color the amyloid if it is present and cause it to have a unique appearance when viewed under a special microscope. If amyloid is present in a tissue biopsy, further tests can be done to determine the type of the amyloid.

The Amyloid Treatment & Research Program (ATRP) at Boston Medical Center (BMC) is an international referral center that treats amyloidosis with stem cell transplantation. The Program offers a multi-disciplinary approach to diagnosis and treatment of this multi-organ disorder. Amyloid doctors specializing in cardiology, pulmonary, nephrology, gastroenterology, neurology, and other systems participate in patient evaluation and care.

The ATRP at BMC studies the systemic types of amyloidoses defined under amyloid types. Other forms of amyloidosis include Alzheimer’s and other neurodegenerative diseases, prion diseases, serpinopathies, some of the cystic fibroses, and others.

They have developed Amyloid Light Chain Database, called ALBase, with the support of an NHLBI P01 award, HL68705. ALBase is a curated database and collection of analytical and graphical tools designed to facilitate the analysis of amyloidogenic immunoglobulin (Ig) light chains (LC) occurring in patients with AL amyloidosis. ALBase is designed to compile and analyze Ig LC sequences from patients with AL amyloidosis, to compare their predicted protein sequence and structure to non-amyloidogenic LC sequences from patients with multiple myeloma or health controls. The hypothesis underlying this is that the primary sequence of the LC is likely to be a major determinant of secondary structure and of propensity to unfold, oligomerize, and form fibrils.

“ALBase is available to the scientific community for research purposes. Please reference the site if you make use of it.”

Two patients of Dr. David Seldin are diagnosed with systemic amyloidosis and they shared their experiences from diagnosis to treatment and recovery (You can listen to an audio of this broadcast by clicking here: Rare Disease Feature (WAER 88.3 FM)).

Both patients credit their physicians for investigating abnormal tests and nonspecific symptoms, and for referring them to amyloid specialists early in the disease course.

http://www.bu.edu/amyloid/david-c-seldin-m-d-ph-d/

http://www.bu.edu/amyloid/2012/03/08/npr-interview/

http://www.bmc.org/amyloid.htm#2012gala

Curated by: Dr. Venkat S. Karra, Ph.D

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