Feeds:
Posts
Comments

Archive for the ‘Peripheral Arterial Disease & Peripheral Vascular Surgery’ Category


New method for performing Aortic Valve Replacement: Transmural catheter procedure developed at NIH, Minimally-invasive tissue-crossing – Transcaval access, abdominal aorta and the inferior vena cava

 

Reporter: Aviva Lev-Ari, PhD, RN

 

VIEW VIDEO

 

The new method was developed by researchers at the National, Heart, Lung and Blood Institute (NHLBI) and tested in a trial on 100 patients at 20 hospitals across the United States. Researchers said it proved successful in 99 of the patients.

“This is a seminal study,” said the lead author, cardiologist Adam B. Greenbaum, M.D., co-director of the Henry Ford Hospital Center for Structural Heart Disease, Detroit. “It challenged conventional wisdom, which objected to the idea of safe passage between the vena cava and the aorta. More important, it is the first of many non-surgical minimally-invasive tissue-crossing, or so-called transmural catheter procedures developed at NIH that can be applied to diverse fields of medicine.”

Robert J. Lederman, M.D., a senior investigator in NHLBI’s Division of Intramural Research who led the study, said researchers developed the method to address a specific clinical need, even though they knew it would be a challenging proposition for most surgeons and physicians to accept. The proposed and counterintuitive mechanism of action is that bleeding from the aorta spontaneously decompresses into a corresponding hole the physician makes in the vein, because the surrounding area behind the peritoneum has higher pressure than the vein.

The results of the research, which were independently confirmed by a committee of outside cardiologists, show the procedure not only has a high success rate, but also an acceptable rate of bleeding and vascular complications, particularly in the high risk patients studied. The study builds on the access technique that Lederman’s NHLBI team developed and first tested in animals in 2012 and first applied with Henry Ford physicians to help patients in 2013. NHLBI and its collaborators are now working to find ways to train more specialists to perform the procedure.

The study will also be presented on Monday, October 31 at the Transcatheter Cardiovascular Therapeutics conference in Washington, D.C. Co-authors include researchers from

  • Henry Ford Hospital;
  • Emory University, Atlanta;
  • Oklahoma Heart Institute, Tulsa;
  • Lexington Medical Center, West Columbia, South Carolina; and
  • Oschner Medical Center, New Orleans.

Researchers at the National Institutes of Health have developed a new, less invasive way to perform transcatheter aortic valve replacement (TAVR), a procedure widely used to treat aortic valve stenosis, a lethal heart condition. The new approach, called transcaval access, will make TAVR more available to high risk patients, especially women, whose femoral arteries are too small or diseased to withstand the standard procedure. The Journal of the American College of Cardiology published the findings.

Aortic valve stenosis involves the narrowing of the heart’s aortic valve which reduces blood flow through the heart. For about 85 percent of patients with this condition, doctors typically perform TAVR through the femoral artery in the leg. But for the other 15 percent, doctors must find a different access route. The most common alternative routes are through the chest, which requires surgery and are associated with significantly more complications.

Transcaval access, which can be performed in awake patients, involves electrifying a small wire so that it crosses between neighboring blood vessels in the abdomen. The technique calls for making large holes in both the abdominal aorta and the inferior vena cava, which physicians previously considered dangerous because of the risk of fatal bleeding.

SOURCE

https://www.nih.gov/news-events/news-releases/new-method-performing-aortic-valve-replacement-proves-successful-high-risk-patients

http://www.medscape.com/viewarticle/871196?nlid=110314_3866&src=WNL_mdplsfeat_161101_mscpedit_card&uac=93761AJ&spon=2&impID=1226378&faf=1

Read Full Post »


Robot-assisted coronary intervention program @MGH – The first CorPath Vascular Robotic System, lets Interventional Cardiologists position the right stent in the right place at reduces radiation exposure by 95%

Reporter: Aviva Lev-Ari, PhD, RN

 

Robot in the cath lab takes surgeons out of radiation’s way

October 3, 2016 By Abigail Esposito Leave a Comment

The system consists of a bedside unit and an interventional cockpit. Developer Corindus Vascular Robotics says the radiation-shielded cockpit features a control console with simple-to-use controls for the precise positioning of guidewires, balloons and stent catheters.

An interventional cardiologist loads the single use cassette and later manually introduces the guiding catheter into the coronaries. At that time, the physician can remove their lead covers and sit behind the Interventional Cockpit to perform the remainder of their procedure.

Harmful Exposures in the Cath Lab:

  • One study of self-reported brain tumors in interventionists showed that 86% of the tumors were left-brain—the side of the head most often exposed to radiation during procedures.
  • There’s also the risk of orthopedic injuries from wearing the heavy, leaded equipment used to block radiation (interventionists practicing over 21 years suffer a 60% incidence of spine issues) and
  • Cataracts, another effect of radiation exposure in interventionists. In a RELID study (Retrospective Evaluation of Lens Injuries and Dose), 50% of interventional cardiologists had posterior subcapsular lens changes (precursors to cataracts) caused by radiation exposure, versus less than 10% in the control group.

Benefits of CorPath Vascular Robotic System

One trial (Percutaneous Robotically-Enhanced Coronary Intervention Study) showed a

  • 95.2% reduction in radiation exposure for the primary operator,
  • 98.8% device success and
  • 97.6% clinical success with no device-related complications. What’s more, the trial saw a
  • 9% reduction in stent use as compared to historical data.

http://www.medicaldesignandoutsourcing.com/robot-in-the-cath-lab-takes-surgeons-out-of-radiations-way/?spMailingID=9704333&spUserID=MTU0MTAzNDg3OTA5S0&spJobID=1021334606&spReportId=MTAyMTMzNDYwNgS2

Read Full Post »


Inferior Vena Cava Filters: Device for Prevention of Pulmonary Embolism and Thrombosis

Reporter: Aviva Lev-Ari, PhD, RN

 

UPDATED on 7/18/2018

 

Original Investigation
Cardiology
July 13, 2018

Association of Inferior Vena Cava Filter Placement for Venous Thromboembolic Disease and a Contraindication to Anticoagulation With 30-Day Mortality

JAMA Network Open. 2018;1(3):e180452. doi:10.1001/jamanetworkopen.2018.0452
Key Points

Question  What is the association of inferior vena cava filter placement with 30-day mortality in patients with venous thromboembolic disease and a contraindication to anticoagulation?

Findings  In this cohort study, using 2 different statistical methods with adjustment for immortal time bias, inferior vena cava filter placement in patients with venous thromboembolic disease and a contraindication to anticoagulation was associated with an increased risk of 30-day mortality.

Meaning  Randomized clinical trials are needed to define the role of inferior vena cava filter placement in patients with venous thromboembolic disease and a contraindication to anticoagulation.

 

Abstract

Importance  Despite the absence of data from randomized clinical trials, professional societies recommend inferior vena cava (IVC) filters for patients with venous thromboembolic disease (VTE) and a contraindication to anticoagulation therapy. Prior observational studies of IVC filters have suggested a mortality benefit associated with IVC filter insertion but have often failed to adjust for immortal time bias, which is the time before IVC filter insertion, during which death can only occur in the control group.

Objective  To determine the association of IVC filter placement with 30-day mortality after adjustment for immortal time bias.

Design, Setting, and Participants  This comparative effectiveness, retrospective cohort study used a population-based sample of hospitalized patients with VTE and a contraindication to anticoagulation using the State Inpatient Database and the State Emergency Department Database, part of the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, from hospitals in California (January 1, 2005, to December 31, 2011), Florida (January 1, 2005, to December 31, 2013), and New York (January 1, 2005, to December 31, 2012). Data analysis was conducted from September 15, 2015, to March 14, 2018.

Exposure  Inferior vena cava filter placement.

Main Outcomes and Measures  Multivariable Cox proportional hazard models were constructed with IVC filters as a time-dependent variable that adjusts for immortal time bias. The Cox model was further adjusted using the propensity score as an adjustment variable.

Results  Of 126 030 patients with VTE, 61 281 (48.6%) were male and the mean (SD) age was 66.9 (16.6) years. In this cohort, 45 771 (36.3%) were treated with an IVC filter, whereas 80 259 (63.7%) did not receive a filter. In the Cox model with IVC filter status analyzed as a time-dependent variable to account for immortal time bias, IVC filter placement was associated with a significantly increased hazard ratio of 30-day mortality (1.18; 95% CI, 1.13-1.22; P < .001). When the propensity score was included in the Cox model, IVC filter placement remained associated with an increased hazard ratio of 30-day mortality (1.18; 95% CI, 1.13-1.22; P < .001).

Conclusions and Relevance  After adjustment for immortal time bias, IVC filter placement was associated with increased 30-day mortality in patients with VTE and a contraindication to anticoagulation. Randomized clinical trials are needed to determine the efficacy of IVC filter placement in patients with VTE and a contraindication to anticoagulation.

 

Requiem for Liberalizing Indications for Vena Caval Filters?

Samuel Z. Goldhaber

Guidelines

However, it is premature to hammer nails into the coffin and to gather as a medical community for a requiem that celebrates no indication for liberalizing indications for placing an IVC filter. Instead, we need to shift the focus of the questions that we investigate and pour resources into further randomized and observational trials of IVC filter insertion in special highrisk populations.

There remain important groups of patients who may benefit from IVC filters with reduction in PE and PE-associated mortality (Table 2). In some cases, tantalizing data suggest that these populations warrant filters. In other cases, we lack data to guide us. Patients with massive PE—accompanied by cardiogenic shock requiring vasopressors to support blood pressure—are desperately ill. They are clinically unstable. An additional PE under these circumstances can be the fatal blow. Data from the National Inpatient Sample and the International Cooperative PE Registry suggest that filters in these patients may be lifesaving.

Patients with severe PE who undergo acute surgical pulmonary embolectomy are vulnerable to recurrent PE, especially during the early postoperative period where full anticoagulation cannot be immediately implemented. I have had personal experience managing this type of patient where the embolectomy is successful but the patient dies of recurrent PE.19

Table 1. Generally Accepted Consensus Recommendations for IVC Filter Insertion in Patients With VTE

  • Major bleeding on full-dose anticoagulation
  • Major contraindication to full-dose anticoagulation
  • New-onset acute PE (especially recurrent PE) despite well-documented fulldose anticoagulation for an existing VTE

IVC indicates inferior vena caval; PE, pulmonary embolism; and VTE, venous thromboembolism.

 

Table 2. Special Populations Where Benefits of IVC Filter Insertion May Outweigh Risks

  • Massive PE or high-risk submassive PE
  • Surgical pulmonary embolectomy
  • Cancer patients with VTE or at high risk of VTE with concomitant high risk of bleeding if anticoagulated
  • Surgical patients (especially during preoperative evaluation) at high risk of VTE with concomitant high risk of bleeding if anticoagulated

IVC indicates inferior vena caval; PE, pulmonary embolism; and VTE, venous thromboembolism.

http://dx.doi.org/10.1161/CIRCULATIONAHA.116.022730

References

1. Stein PD, Matta F, Hull RD. Increasing use of vena cava filters for prevention of pulmonary embolism. Am J Med. 2011;124:655–661. doi:10.1016/j.amjmed.2011.02.021.

2. Jia Z, Wu A, Tam M, Spain J, McKinney JM, Wang W. Caval penetration by inferior vena cava filters: a systematic literature review of clinical significance and management. Circulation. 2015;132:944–952. doi: 10.1161/ CIRCULATIONAHA.115.016468

3. Owens CA, Bui JT, Knuttinen MG, Gaba RC, Carrillo TC, Hoefling N, Layden-Almer JE. Intracardiac migration of inferior vena cava filters: review of published data. Chest. 2009;136:877–887. doi: 10.1378/ chest.09-0153.

4. Nicholson W, Nicholson WJ, Tolerico P, Taylor B, Solomon S, Schryver T, McCullum K, Goldberg H, Mills J, Schuler B, Shears L, Siddoway L, Agarwal N, Tuohy C. Prevalence of fracture and fragment embolization of Bard retrievable vena cava filters and clinical implications including cardiac perforation and tamponade. Arch Intern Med. 2010;170:1827–1831. doi: 10.1001/archinternmed.2010.316.

5. Angel LF, Tapson V, Galgon RE, Restrepo MI, Kaufman J. Systematic review of the use of retrievable inferior vena cava filters. J Vasc Interv Radiol. 2011;22:1522–1530.e3. doi: 10.1016/j.jvir.2011.08.024.

19. Aklog L, Williams CS, Byrne JG, Goldhaber SZ. Acute pulmonary embolectomy: a contemporary approach. Circulation. 2002;105:1416–1419.

Other related articles published in this Open Access Online Scientific Journal include the follwoing:

 

Xarelto (Rivaroxaban): Anticoagulant Therapy gains FDA New Indications and Risk Reduction for: (DVT) and (PE), while in use for Atrial fibrillation increase in Gastrointestinal (GI) Bleeding Reported

https://pharmaceuticalintelligence.com/2012/11/04/xarelto-rivaroxaban-anticoagulant-therapy-gains-fda-new-indications-and-risk-reduction-for-dvt-and-pe-while-in-use-for-atrial-fibrillation-increase-in-gastrointestinal-gi-bleeding-reported/

Venous Thromboembolism (VTE): Blood Clots in Leg and Lungs – No. 3 Cardiovascular Killer Globally – Is Leading Cause of Premature Death and Disability in Hospitals

https://pharmaceuticalintelligence.com/2014/10/13/venous-thromboembolism-vte-blood-clots-in-leg-and-lungs-no-3-cardiovascular-killer-globally-is-leading-cause-of-premature-death-and-disability-in-hospitals/

The Relation between Coagulation and Cancer affects Supportive Treatments

https://pharmaceuticalintelligence.com/2015/10/19/the-relation-between-coagulation-and-cancer-affects-supportive-treatments/

Read Full Post »


Lysyl Oxidase (LOX) gene missense mutation causes Thoracic Aortic Aneurysm and Dissection (TAAD) in Humans because of inadequate cross-linking of collagen and elastin in the aortic wall

Mutation carriers may be predisposed to vascular diseases because of weakened vessel walls under stress conditions.

 

Reporter: Aviva Lev-Ari, PhD, RN

 

Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans

  1. Vivian S. Leea,
  2. Carmen M. Halabia,b,
  3. Erin P. Hoffmanc,1,
  4. Nikkola Carmichaelc,d,
  5. Ignaty Leshchinerc,d,
  6. Christine G. Liand,e,
  7. Andrew J. Bierhalsf,
  8. Dana Vuzmanc,d,
  9. Brigham Genomic Medicine2,
  10. Robert P. Mechama,
  11. Natasha Y. Frankc,d,g,3, and
  12. Nathan O. Stitzielh,i,j,3

Edited by J. G. Seidman, Harvard Medical School, Boston, MA, and approved June 7, 2016 (received for review January 27, 2016)

  • Author contributions: V.S.L., R.P.M., N.Y.F., and N.O.S. designed research; V.S.L., C.M.H., and N.O.S. performed research; E.P.H., N.C., C.G.L., D.V., B.G.M.P., R.P.M., and N.Y.F. contributed new reagents/analytic tools; V.S.L., C.M.

Significance

The mechanical integrity of the arterial wall is dependent on a properly structured ECM. Elastin and collagen are key structural components of the ECM, contributing to the stability and elasticity of normal arteries. Lysyl oxidase (LOX) normally cross-links collagen and elastin molecules in the process of forming proper collagen fibers and elastic lamellae. Here, using whole-genome sequencing in humans and genome engineering in mice, we show that a missense mutation in LOX causes aortic aneurysm and dissection because of insufficient elastin and collagen cross-linking in the aortic wall. These findings confirm mutations in LOX as a cause of aortic disease in humans and identify LOX as a diagnostic and potentially therapeutic target.

Abstract

Thoracic aortic aneurysms and dissections (TAAD) represent a substantial cause of morbidity and mortality worldwide. Many individuals presenting with an inherited form of TAAD do not have causal mutations in the set of genes known to underlie disease. Using whole-genome sequencing in two first cousins with TAAD, we identified a missense mutation in the lysyl oxidase (LOX) gene (c.893T > G encoding p.Met298Arg) that cosegregated with disease in the family. Using clustered regularly interspaced short palindromic repeats (CRISPR)/clustered regularly interspaced short palindromic repeats-associated protein-9 nuclease (Cas9) genome engineering tools, we introduced the human mutation into the homologous position in the mouse genome, creating mice that were heterozygous and homozygous for the human allele. Mutant mice that were heterozygous for the human allele displayed disorganized ultrastructural properties of the aortic wall characterized by fragmented elastic lamellae, whereas mice homozygous for the human allele died shortly after parturition from ascending aortic aneurysm and spontaneous hemorrhage. These data suggest that a missense mutation in LOX is associated with aortic disease in humans, likely through insufficient cross-linking of elastin and collagen in the aortic wall. Mutation carriers may be predisposed to vascular diseases because of weakened vessel walls under stress conditions. LOX sequencing for clinical TAAD may identify additional mutation carriers in the future. Additional studies using our mouse model of LOX-associated TAAD have the potential to clarify the mechanism of disease and identify novel therapeutics specific to this genetic cause.

SOURCE

http://www.pnas.org/content/early/2016/07/15/1601442113.abstract

Missense LOX Mutation Linked to Aortic Rupture, Aneurysm

NEW YORK (GenomeWeb) – Researchers from Washington University School of Medicine have linked a LOX gene variant with aortic rupture and aneurysm.

As they reported in the online early edition of the Proceedings of the National Academy of Sciences yesterday, the researchers sequenced two first cousins from a family with a history of aortic ruptures and aneurysms to uncover a missense mutation in the lysyl oxidase (LOX) gene, which encodes a protein that cross-links elastin and collagen. When they used CRISPR/Cas9 genome engineering to introduce the mutation into a mouse model, mice heterogeneous for the mutation had disorganized aortic walls, while mice homozygous for the mutation died shortly after birth of ascending aneurysm and spontaneous hemorrhage, suggesting that the LOX variant might be causal.

Read more @ the Source

SOURCE

https://www.genomeweb.com/sequencing/missense-lox-mutation-linked-aortic-rupture-aneurysm

Read Full Post »


Warfarin and Dabigatran, Similarities and Differences

Author and Curator: Danut Dragoi, PhD

 

What anticoagulants do?

An anticoagulant helps your body control how fast your blood clots; therefore, it prevents clots from forming inside your arteries, veins or heart during certain medical conditions.

If you have a blood clot, an anticoagulant may prevent the clot from getting larger. It also may prevent a piece of the clot from breaking off and traveling to your lungs, brain or heart. The anticoagulant medication does not dissolve the blood clot. With time, however, this clot may dissolve on its own.

Blood tests you will need

The blood tests for clotting time are called prothrombin time (Protime, PT) and international normalized ratio (INR). These tests help determine if your medication is working. The tests are performed at a laboratory, usually once a week to once a month, as directed by your doctor. Your doctor will help you decide which laboratory you will go to for these tests.

The test results help the doctor decide the dose of warfarin (Coumadin) that you should take to keep a balance between clotting and bleeding.

Important things to keep in mind regarding blood tests include:

  • Have your INR checked when scheduled.
  • Go to the same laboratory each time. (There can be a difference in results between laboratories).
  • If you are planning a trip, talk with your doctor about using another laboratory while traveling.
Dosage

The dose of medication usually ranges from 1 mg to 10 mg once daily. The doctor will prescribe one strength and change the dose as needed (your dose may be adjusted with each INR).

The tablet is scored and breaks in half easily. For example: if your doctor prescribes a 5 mg tablet and then changes the dose to 2.5 mg (2½ mg), which is half the strength, you should break one of the 5 mg tablets in half and take the half-tablet. If you have any questions about your dose, talk with your doctor or pharmacist.

What warfarin (Coumadin) tablets look like

Warfarin is made by several different drug manufacturers and is available in many different shapes. Each color represents a different strength, measured in milligrams (mg). Each tablet has the strength imprinted on one side, and is scored so you can break it in half easily to adjust your dose as your doctor instructed.

https://my.clevelandclinic.org/health/drugs_devices_supplements/hic_Understanding_Coumadin

Today, on the basis of 4 clinical trials involving over 9,000 patients, PRADAXA is approved to treat blood clots in the veins of your legs(deep vein thrombosis, or DVT) or lungs (pulmonary embolism, or PE)in patients who have been treated with blood thinner injections, and to reduce the risk of them occurring again.

In these trials, PRADAXA was compared to warfarin or to placebo (sugar pills) for the treatment of DVT and PE patients.

https://www.pradaxa.com/pradaxa-vs-warfarin?gclid=CMaRq7al9ssCFUxZhgodZuoC5w

Warfarin (NB-which goes by the brand name Coumadin, see link in here) reduces the risk of stroke in patients with atrial fibrillation (NB- atrial fibrillation (also called AFib or AF) is a quivering or irregular heartbeat (arrhythmia) that can lead to blood clots, stroke, heart failure and other heart-related complications. Some people refer to AF as a quivering heart, see link here) but increases the risk of hemorrhage and is difficult to use.

Dabigatran is a new oral direct thrombin inhibitor (NB-direct thrombin inhibitors are a class of medication that act as anticoagulants by directly inhibiting the enzyme thrombin). Some are in clinical use, while others are undergoing clinical development), see link in here.

Some international large clinical trials, see link in here,  show results for patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage.

Picture below shows a deep vein thrombosis which is a blood clot that forms inside a vein, usually deep within the leg. About half a million Americans every year get one, and up to 100,000 die because of it. The danger is that part of the clot can break off and travel through your bloodstream. It could get stuck in your lungs and block blood flow, causing organ damage or death, see link in here.

Blod Clot

Image SOURCE: http://www.webmd.com/heart-disease/guide/warfarin-other-blood-thinners

The behaviour of blood thinning drugs is dependent on their physico-chemical properties and since a significant proportion of drugs contain ionisable centers a knowledge of their pKa (NB-pKa was introduced as an index to express the acidity of weak acids, where pKa is defined as follows. For example, the Ka constant for acetic acid (CH3C00H) is 0.0000158 (= 10-4.8), but the pKa constant is 4.8, which is a simpler expression. In addition, the smaller the pKa value, the stronger the acid, see link in here ) is essential, see link in here. The pKa is defined as the negative log of the dissociation constant, see link in here:

pka=-log10(Ka)              (1)

where the dissociation constant is defined thus:

Ka=[A][H+]/[AH]

Most drugs have pKa in the range 0-12, and whilst it is possible to calculate pKa it is desirable to experimentally measure the value for representative examples. There are a number of instruments that are capable of measuring pKa utilising Sirius T3 instrument, see link in here .

Table 1 below shows the pka values for warfarin, see link in here  and dabigatran, see link in here.

Table 1

==========================

Anticoagulant           pka          

warfarin                     4.99

dabigatran                 4.24        11.51*

==========================

* dabigatran possess both acidic and basic functionality.

Both groups are at ionized at blood pH and exist as zwitterionic

structures, see link in here.

Adding physico-chemical features of anticoagulants utilized in “dissolving” blood clots is important for better understanding the de-blocking process within the veins utilizing anticoagulants.

SOURCE

http://theochem.chem.rug.nl/publications/PDF/ft683.pdf

http://www.rsc.org/chemical-sciences-repository/articles/article/dr000000003197?doi=10.1039/c5ra04680g

http://pubs.rsc.org/en/content/articlelanding/2015/ra/c5ra11623f#!divAbstract

http://www.cambridgemedchemconsulting.com/resources/physiochem/pka.html

http://www.webmd.com/heart-disease/guide/warfarin-other-blood-thinners

https://www.google.com/#q=define+atrial+fibrillation

https://www.researchgate.net/profile/Lars_Wallentin/publication/26777612_Dabigatran_versus_Warfarin_in_Patients_with_Atrial_Fibrillation/links/02bfe50c8c2fa639c0000000.pdf

http://www.webmd.com/heart-disease/guide/warfarin-other-blood-thinners

 

Other related articles published in this Open Access Online Scientific Journal, include the following:

Coagulation N=69

https://pharmaceuticalintelligence.com/?s=Coagulation

Peripheral Arterial Disease N=43

https://pharmaceuticalintelligence.com/?s=Peripheral

Antiarrhythmic drugs

https://pharmaceuticalintelligence.com/?s=Antiarrhythmic+drugs

A-Fib

https://pharmaceuticalintelligence.com/?s=a-fib

Electrophysiology N = 80

https://pharmaceuticalintelligence.com/?s=Electrophysiology

 

Read Full Post »


Endovascular procedures associated with lower mortality, LOS, cost vs. surgical bypass: Results of Critical Limb Ischemia National Study

Reporter: Aviva Lev-Ari, PhD, RN

 

SOURCE

https://consultqd.clevelandclinic.org/2016/03/critical-limb-ischemia-national-snapshot-management-holds-surprises/?utm_campaign=qd+tweets&utm_medium=social&utm_source=twitter&utm_content=160322+critical+limb+ischemia+management&dynid=twitter-_-qd+tweets-_-social-_-social-_-160322+critical+limb+ischemia+management

 

/

 

a new comprehensive analysis of a nationwide hospital sample of nearly 650,000 patients conducted from 2003 to 2011.

Mehdi Shishehbor

Mehdi Shishehbor, DO, MPH, PhD

“We found that rates of surgery for CLI are going down while rates of endovascular procedures are going up,” says Mehdi Shishehbor, DO, MPH, PhD, Director of Endovascular Services at Cleveland Clinic. “Meanwhile hospital admissions for CLI have remained constant even as rates of amputation and death from CLI have gone down. This suggests there’s something at work other than improved medical therapy for CLI.”

Dr. Shishehbor led the Cleveland Clinic-conducted analysis, which was just published in Journal of the American College of Cardiology and will also be presented at the 65th Annual Scientific Session of the American College of Cardiology (ACC.16) in Chicago in early April.

Key findings

The researchers’ key findings are reflected in the figure below and include the following:

Figure 1

Figure. Nationwide trends in CLI hospital admissions and outcomes over time, based on the analysis by Shishehbor and colleagues. Reprinted from Agarwal S, Sud K, Shishehbor MH, J Am Coll Cardiol. 2016 Mar 21 [Epub ahead of print], ©2016, with permission from the American College of Cardiology Foundation.

  • The annual rate of CLI admissions remained relatively constant (at ~150/100,000 population) throughout the 2003-2011 period despite a progressive increase in the rate of admissions for PAD. “The rise in PAD might be secondary to the rise in prevalence of cardiovascular risk factors, which we observed,” notes Dr. Shishehbor. “An increase in the rate of PAD-related admissions, with the constant rate of CLI-related admissions, might suggest early detection of PAD, leading to improved PAD management and the relative stabilization of CLI rates.”
  • The proportion of patients with CLI undergoing surgical revascularization declined significantly during the study period (from 13.9 percent in 2003 to 8.8 percent in 2011) while the proportion undergoing endovascular treatment rose significantly (from 5.1 percent to 11.0 percent).
  • There was a steady and significant decline in rates of in-hospital death and major amputation across the study period among patients with CLI as well as a significant overall decline in mean length of stay. Despite these improvements, mean hospitalization cost remained unchanged throughout the study period.
  • Compared with surgical revascularization, endovascular treatment of CLI was associated with significantly lower in-hospital mortality, mean LOS and mean hospitalization cost — even after adjustment for potential confounders — despite statistically comparable rates of major amputation.

SOURCE

https://consultqd.clevelandclinic.org/2016/03/critical-limb-ischemia-national-snapshot-management-holds-surprises/?utm_campaign=qd+tweets&utm_medium=social&utm_source=twitter&utm_content=160322+critical+limb+ischemia+management&dynid=twitter-_-qd+tweets-_-social-_-social-_-160322+critical+limb+ischemia+management

Read Full Post »


Outstanding Achievement in Pathology

Curator: Larry H Bernstein, MD, FCAP

 

Olympus America Honors Outstanding Pathologists During First Annual “Unsung Heroes” Awards

Melville, Ny—Tracey Corey Handy, M.D., Chief Medical Examiner of Kentucky, and Matthew Zarka, M.D., affiliated with the University of Vermont and the Fletcher Allen Health Center, were recognized as the 1999 winners of the “Unsung Heroes” Awards. The awards, sponsored by Olympus America Inc., a world leading manufacturer of microscopes, in cooperation with the College of American Pathologists (CAP), were presented at a ceremony during the Fall CAP Conference in New Orleans.

The awards are the first in the on-going “Unsung Heroes” program sponsored by Olympus for the purpose of increasing public awareness of the vital and often invisible role pathologists have in saving lives. In addition to their expertise with a microscope, pathologists are the doctors who ensure that clinical laboratory testing is reliable and that diseases are accurately diagnosed. They are on the front lines whenever the public is threatened with disease. Their role in forensic science is crucial in helping prevent people from falling prey to abuse or avoidable illness. As Dan Biondi, Olympus Senior Vice President, points out, “Olympus is committed to supporting the work of the world’s pathologists and to advocating an educated patient population.”

Dr. Tracey Corey Handy is recognized as an “Unsung Hero” for her role in upgrading the well-being of children as Kentucky’s Chief Medical Examiner. Along with several colleagues, Dr. Handy founded the state’s “Living Forensics” team in 1991. Since its inception, the team has consulted on more than 700 cases of suspected child abuse. This effort has led to an increased conviction rate of abuse perpetrators and helps to reduce further cases of child abuse. In addition, Dr. Handy has initiated a program of routine screening for metabolic defects apparent in victims of Sudden Infant Death Syndrome (SIDS), which has resulted in the correct diagnosis of conditions that would have otherwise been attributed to SIDS. Dr. Handy has also chaired the state’s first child mortality review group that has resulted in the initiation of prevention programs, particularly in the event of accidental child death. A frequent speaker and contributor of her expertise to organizations throughout the country, she also teaches forensic pathology and has been published in more than a dozen peer-reviewed journals and books.

Dr. Matthew Zarka is recognized as an “Unsung Hero” for his efforts in aiding the extremely poor Mexican-Indian population in the remote mountain regions of Oaxaca, Mexico. Over the last two years Dr. Zarka has volunteered his time and services to bring much needed medical care to these impoverished communities. He and his OB/GYN team have been setting up the very first clinics throughout the area, enjoining the coffee companies of Mexico to spread word of the clinics to the local population and to help transport patients to the clinics. After each female patient underwent a gynecological examination, Dr. Zarka stained and read her Pap test. When needed, more extensive evaluations, biopsies, treatment and counsel were provided. Overwhelmingly successful, Dr. Zarka’s outreaching medical mission has grown to include additional professional staff. By volunteering his time and expertise, Dr. Zarka provides the only real access most people of the region have to modern medical care. His contribution has undoubtedly saved lives that might otherwise have been lost.

Stanford University

Benjamin Pinsky, MD, PhD, Assistant Professor of Pathology and Medicine (Infectious Diseases) is the recipient of the 2014 Siemens Healhcare Diagnostics Young Investigator Award.  This award “honors outstanding laboratory research in clinical microbiology or antimicrobial agents and is intended to further the career development of a young clinical scientist and promote awareness of clinical microbiology as a career.”

Stephen J. Galli, MD, Chair of Pathology, Professor of Pathology and Microbiology and Immunology, and the Mary Hewitt Loveless, MD Professor, is the recipient of the 2014 ASIP (American Society of Investigative Pathology) Rouse Whipple Award.  This award is presented to a senior scientist with a distinguished career in research who has advanced the understanding of disease and has continued productivity at the time of this award.

Dr. Raffick Bowen, Clinical Associate Professor and Associate Medical Director of SHC’s Clinical Chemistry and Immunology Laboratory is the recipient of the American Association of Clinical Chemistry’s Outstanding Speaker Award for 2013. This award recognizes his achievement in earning a speaker evaluation rating of 4.5 or higher during a 2013 continuing education activity accredited by AACC. The title of Dr. Bowen’s presentation is “Implementation of Autoverification in a Clinical Chemistry Laboratory: Theory to Practice”

Richard Kempson, MD,

Emeritus Professor of Pathology, is the recipient of the 2014 United States and Canadian Academy of Pathology (USCAP) President’s Award. The USCAP President’s Award is given annually to recognize an individual for outstanding service to the field of pathology.

Dr. Kempson is richly deserving of this award. Dr. Kempson has not only contributed substantially to the surgical pathology literature, particularly in gynecologic and soft tissue pathology but also, with Dr. Ronald Dorfman, he trained a substantial percentage of this and the next generation’s academic and community leaders in surgical pathology.

Dr. Kempson’s affiliation with Stanford University began in 1968 when he and Dr. Ronald Dorfman were recruited to Stanford to develop a program in surgical pathology. In short order, they established an internationally recognized residency and clinical fellowship program which went on to train more than 275 pathologists in the art and science of diagnostic surgical pathology. Dr. Kempson developed a distinctive teaching style that emphasized precise diagnostic criteria, approaching diagnosis with a broad morphologic differential diagnosis, and most importantly, always highlighting the relevance to patient management of the morphologic distinctions being made.

Prior to his recruitment to Stanford, Dr. Kempson was an Assistant Professor of Pathology and Surgical Pathology at Washington University. Dr. Kempson served as an Associate Professor of Pathology at Stanford from 1968 to 1974 and a Professor of Pathology from 1974 to 2001. In addition to his academic duties, he served as Co-Director of Surgical Pathology from 1968 until 2001. He also has served as President of the Association of Directors of Surgical Pathology (1993-1995), the United States and Canadian Academy of Pathology (1996) and the Arthur Purdy Stout Society (1996) and the California Society of Pathologists. The Richard Kempson, MD, Professorship in Surgical Pathology was established by the Department of Pathology in 2002 to honor him and his remarkable contributions to surgical pathology.

University of California, San Diego

A new era in diagnostics has emerged within the concept of Personalized Medicine. Imagine selecting cancer chemotherapy drugs based on knowledge of the precise mutations in a cancer. Can we predict who may have an adverse response to a medication based on that individual’s genetic blueprint? At UCSD, we are dedicated to making these resources available to our patients in the very near future. This is why we recently established the Pathology Center for Personalized Medicine. The goal of the Center is to conduct leading research necessary to form the foundation for advanced personalized medicine diagnostic testing and then to make this testing available in the CALM. For more information on the Center for Personalized Medicine, click here.

The research enterprise in Pathology at UCSD has grown dramatically in the past five years, and we are now amongst the top 15 programs in the country. Basic and translational research laboratories in the UCSD Pathology Department tackle important problems concerning cancer development and progression, angiogenesis, stem cell biology, neurodegenerative diseases, peripheral neuropathy, inflammation, infectious diseases, and wound healing. Our laboratories provide excellent environments for learning cell biology, molecular genetics, biochemistry, and animal physiology. Our faculty includes many active participants in the Biomedical Sciences (BMS) Graduate Program. For more information on this program, click here. We also have excellent opportunities for postdoctoral researchers. Please click here to visit our web page on summarizing the Pathology Department research enterprise. Then visit individual web pages for each of our faculty member to view specific research interests.

The Department of Pathology is home to both an outstanding Comparative Pathology and Medicine Program (for more information, click here) and the UCSD Research Ethics Program. We provide major educational support to the School of Medicine and the Skaggs School of Pharmacy and Pharmaceutical Sciences. For further information on these training opportunities, click here.

The La Jolla/San Diego community is a fertile environment for research and the pharmaceutical industry. The Sanford Burnham Medical Research Institute, the Scripps Research Institute, the Sidney Kimmel Cancer Center, the Salk Institute for Biological Studies, and the La Jolla Institute for Allergy and Immunology house exciting scientific programs and provide for numerous scientific collaborations. We also boast a plethora of biotechnology companies, located nearby on the La Jolla mesa.

The overall theme and focus of the Department of Pathology is to elucidate the molecular basis and pathology of human disease.  The faculty is comprised of basic, translational and physician scientists that utilize the latest techniques in genomics, proteomics, cell biology, molecular biology and physiology to develop new diagnostic and therapeutic approaches for a wide range of diseases, including cancer, neurological disease, microbial infection, and inflammatory disease.

Steven L. Gonias, M.D., Ph.D.

Our laboratory is interested in identifying and characterizing novel pathways by which proteases and their cell-surface receptors regulate cell physiology. We are particularly interested in the function of proteases in cancer but also have active projects related to peripheral nerve injury, Alzheimer’s disease and cardiovascular biology. One focus involves urokinase-type plasminogen activator (uPA), a serine protease and plasminogen activator that binds with high affinity to a GPI-anchored receptor called uPAR. This event activates multiple cell-signaling pathways that affect cell migration, survival, and phenotype. We are actively working to elucidate mechanisms by which uPAR-initiated cell-signaling promotes cancer metastasis. We are particularly interested in breast cancer, but also work on prostate cancer and cancers of the central nervous system.

The complex of uPA with its inhibitor, PAI-1, is a ligand for a receptor called LRP-1. LRP-1 also is the receptor for other ligands, including extracellular matrix proteins, growth factors and foreign toxins. Our laboratory elucidated a pathway in which LRP-1 regulates cell-signaling indirectly, by regulating the cell-surface level of uPAR. However, recent studies suggest that LRP-1 also directly regulates cell-signaling by binding adaptor proteins, such as Shc and JIP. By this mechanism, LRP-1 regulates cell survival and gene transcription. Our current re­search is aimed at determining the role of LRP-1 in cancer and peripheral nerve injury, using in vitro and in vivomodel systems. Using proteomics approaches, we also are actively investigating the ability of LRP-1 to model the composition of the plasma membrane.

Our third area of focus concerns the plasma protease inhibitor, alpha2M. Our laboratory has demonstrated that this protein functions as a conformation-dependent carrier of growth factors. Alpha2M may also function in cell-signaling by binding to LRP-1. By site-directed mutagenesis, we have iso­lated and individually modified various functional sites in this multifunc­tional protein.

David Bailey, MD, PhD

David N. Bailey received his Bachelor of Science degree in Chemistry “with high distinction” from Indiana University and his Doctor of Medicine degree from Yale University.  He completed a National Institutes of Health postdoctoral fellowship in Laboratory Medicine and a residency in Clinical Pathology, both at Yale, serving as Chief Resident in his final year.  He is certified in Clinical Pathology and Chemical Pathology by the American Board of Pathology.

Dr. Bailey joined the University of California (UC) San Diego faculty in 1977 and served as Director of the Toxicology Laboratory of UC San Diego Medical Center (1977-2007), Head of the Division of Laboratory Medicine (1983-1989, 1994-1998), Acting Chair (1986-1988) and permanent Chair of the Department of Pathology (1988-2001),  Director of the Pathology Residency Program (1986-1999), Director of Clinical Laboratories of UCSD Medical Center (1982-1999), Interim Vice Chancellor for Health Sciences and Dean of the UC San Diego School of Medicine (1999-2000 and 2006-2007), Deputy Vice Chancellor for Health Sciences (2001-2007), and Dean for Faculty & Student Matters in UC San Diego School of Medicine (2003-2007).  From 2007 to 2009, he was Vice Chancellor for Health Affairs, Dean of the School of Medicine, and Professor of Pathology and Laboratory Medicine at the University of California, Irvine.

Dr. Bailey was recognized by the Institute of Scientific Information as one of the world’s ten most cited authors in forensic sciences (1981-93). He received the Gerald T. Evans Award from the Academy of Clinical Laboratory Physicians and Scientists in 1993 for his leadership and service to the Academy.  Dr. Bailey has served as President of the California Association of Toxicologists (1981-1982), President of the Academy of Clinical Laboratory Physicians and Scientists (1988-89), and Secretary-Treasurer of the Association of Pathology Chairs (1996-99).  He has also served on the Chemical Pathology Test Development and Advisory Committee of the American Board of Pathology; the Editorial Boards of Clinical Chemistry, the Journal of Analytical Toxicology, and the American Journal of Clinical Pathology; the Doris A. Howell Foundation for Women’s Health Research Board of Directors; the Board of Directors of the George G. Glenner Alzheimer’s Family Centers, Inc.; the Board of Directors of the Children’s Hospital of Orange County; the Board of Directors of Children’s Healthcare of California; the Board of Directors of the Rady Children’s Hospital of San Diego; the Board of Directors of the Veterans Medical Research Foundation (San Diego); and the Executive Committee and Governing Board of the California Institute of Telecommunications and Information Technology, among others.

David A. Herold, M.D., Ph.D.

My laboratory research interests are in the area of mass spectrometry application to clinical diagnostics. This includes prostaglandins, trace metal and steroids. Additionally, we has been involved in the development and validation of “classical” clinical chemistry diagnostic tests. The application of the mass spectrometry to determine the validity of endocrine tests, in particular testosterone, has been of particular interest. We have been using GC-MS, LC-MS, and MS-MS techniques for these investigations. At the present time, we are involved with the use of Accelerator Mass Spectrometry for the determination of calcium flux in serum and urine using 41Ca as a marker. The purpose of these studies is to better understand bone remodeling in normal and diseased patients. We have also investigated the use of microfluidics for the application to clinical diagnostics to measure selected proteins in a rapid and accurate manner.

 

David Cheresh, Ph.D.

Tumor growth, invasion, stem cells and drug resistance. Molecular regulation of tumor growth and angiogenesis. Drug development targeting molecular pathways involved in tumor growth metastasis and angiogenesis.

The Cheresh laboratory focuses on the discovery of molecular pathways involved in the progression of cancer. Cheresh’s earlier work identified integrin αυβ3 as a biomarker of tumor angiogenesis and tumor progression, and was involved in the discovery of a drug called cilentigide which targets integrins αυβ3 and αυβ5.

The Cheresh laboratory has identified a series of critical microRNAs that regulate the growth of blood vessels.  These microRNAs control the angiogenic switch that occurs during the earliest stages of tumor growth and neovascularization in the retina.  As such one of these microRNAs may have therapeutic application as it is capable of maintaining blood vessels in the quiescent state.

Cheresh and colleagues have identified integrin αυβ3 as a biomarker of tumor stem cells during intrinsic or acquired resistance of a wide range of tumors including: cancer of the lung, pancreas, breast, and colon.   Cheresh and his lab discovered that αυβ3 expression is both necessary and sufficient to account for tumor stemness and drug resistance based on its ability to drive a molecular pathway regulating these processes.  This has led to the development of new therapeutic strategies to resensitize patients to drugs such as erlotinib and lapatinib that target EGFR.

The Cheresh laboratory has identified RAF kinase as an important target involved in tumor growth and angiogenesis.  They have developed a new drug design strategy to target RAF and other relevant kinases by designing allosteric inhibitors of these targets.  This is based on the use of defined chemical scaffolds to dock into an allosteric pocket on these kinases to render them inactive.  The combined use of in silico and biological screening has yielded drugs with nM anti-tumor activity that produce strong anti-tumor growth in mouse models following once a day oral dosing.   This approach appears to yield drugs that target tumors that are resistant to ATP mimetic inhibitors of RAF, Kit or PDGFR

John Lowe

Senior Director, Pathology

I joined Genentech in 2008 as Senior Director of Pathology, after having spent more than 18 years as an HHMI Investigator at the University of Michigan and then 3 years as Chair of Pathology at Case Western Reserve University School of Medicine. The role of Senior Director of Pathology in Research at Genentech offered attractive opportunities to do research in an outstanding, disease-focused scientific environment, while also helping to lead the scientific and research support activities of the Pathology department. These latter efforts help Genentech continue to make a major positive difference to the health and well being of a large number of patients afflicted with cancer, autoimmune syndromes, neurodegenerative diseases and other illnesses for which therapies are unsatisfactory or nonexistent.

An exceptional team of pathologists, laboratory managers, scientific associates and administrative staff in the department collaborate with me in these efforts. Additional outstanding pathologists, scientists, and managers continue to be recruited to assist us in ensuring that the department performs at the highest level. Our task is made more straightforward by the environment at Genentech, which is characterized by exceptionally bright, motivated and collaborative colleagues at every level, spectacular facilities, and workplace philosophies that are conducive to the highest levels of achievement.

Postdoctoral Mentor

The opportunity to mentor postdoctoral fellows at Genentech has been a stimulating and gratifying experience for me. This derives in part from the freedom afforded by the program to pursue research directions that are deemed to be important and interesting, even if these have no immediate therapeutic relevance. The special mentoring experience also derives from extraordinary breadth and quality of the core laboratories at Genentech, and the spectacular intellectual environment. Together, these circumstances provide an unparalleled opportunity for postdoctoral fellows, and their mentors, to engage in biomedical discovery of the highest caliber.

Read Full Post »

« Newer Posts - Older Posts »