Medical Trends

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The Selection Process 1

Bringing Medical Innovation from Bench to Bedside 3

Top 10 Medical Innovations for 2013 5

Where Are They Now? 25

Top 10 Medical Innovations: 2013 ©

Top 10 Medical Innovations: 2013The Selection Process

Top 10 Medical Innovations: 2013 | 1

Which are the up-and-coming technologies and which will have the biggest impact on health care in 2013? Cleveland Clinic’s

culture of innovation naturally fosters a good deal of discussion about new “game changing” technologies and which ones will have

the greatest impact each year. The passion of our clinicians and researchers for getting the best care for patients drives a continuous

dialogue on what state-of-the art medical technologies are just over the horizon.

This book was developed to share outside Cleveland Clinic what our clinical leaders are saying to each other and what innovations

they feel will help shape health care over the next 12 months.

We used a rigorous process to gather the opinions of Cleveland Clinic physicians and researchers, create a field of nominated

innovative technologies for consideration, and develop a consensus perspective of what will be the Top 10 Medical Innovations

for 2013. Our team interviewed more than 110 Cleveland Clinic experts to elicit their nominations.

To receive consideration, nominated technologies had to meet the following criteria:

• The innovation had to have significant clinical impact and offer significant patient benefit in comparison to current practices. It must also have high user-related functionality that improves health care delivery.

• Nominated innovations had to have a high probability of commercial success.

• The innovation must be in or exiting clinical trials and be available on the market sometime in 2013.

• The innovation must have significant human interest in its application or benefits, and must have the ability to visualize human impact.

We probed the opinions of a broad cross-section of Cleveland Clinic staff from every major medical field. Our primary question

was, “What innovations are “game changers” in your field?” In all, these interviews yielded nearly 150 nominations of emerging

technologies.

These nominated innovations were screened to confirm threshold criteria and consolidate duplicates. Our team prepared research

on each technology and then presented a final list of over 55 up-and-coming technologies and their data profiles to two independent

panels of leading Cleveland Clinic physicians. In late August, each panel met to discuss, debate, and vote. The two panels then

voted on the combined lists and established our Top 10 Medical Innovations for 2013.

For this seventh annual event, Gerald Secor Couzens of MMC Worldwide conducted all of the interviews and assisted us in

navigating the detailed selection process. He and Susan Bernat, Director, Operations and Finance, ran all the mechanics of the

selection. Dr. Mike Roizen and Dr. Jim Merlino chaired the project and moderated the selections, respectively.

We hope you will find our selections interesting and will use them to stimulate your own thinking on future new trends and

technologies and maybe even spur some innovation of your own.

Risky Business: Bringing Medical Innovation from Bench To Bedside

At the turn of the 20th century, one in five American newborns died before the age of five. The average lifespan for a

male born in the United States in 1900 was 47. In a little over a century, almost 25 years has been added to that typical

lifetime. Today, thanks to medical innovation, an American male born in 2012 can look forward to living well into his 70s,

while his female counterpart is able to anticipate celebrating her 80th birthday.

Without question, it has been the extraordinary advances in medical technology that have been responsible for this

improved health and enhanced longevity. Between 1974 and 2010, U.S. patents on medical innovations increased by a

factor of six. Many of these medical breakthroughs became front-page news because the new therapies, medications, and

devices helped improve and save lives by providing innovative solutions for diagnosis, prevention and treatment of a variety

of ailments, including many that can disable, cripple, and kill. Doctors now have more than 6,000 drugs and well over

4,000 different medical procedures to choose from when managing the health of their patients.

“Creativity is thinking up new things. Innovation is doing new things.” — Theodore Levitt

Medical innovation does not just happen overnight. It takes a mixture of thoughtfulness, pluck, luck, serendipity, stub-

bornness, persistence, flexibility, and unwillingness to give up on the part of the innovator(s) in order to yield an FDA ap-

proval of a new drug for an ailment that had previously eluded effective therapy or 501(k) clearance for a medical device

that greatly improves a surgical procedure.

Large and small pharmaceutical companies invest research time and billions of dollars annually in efforts to create new

medications. While many look promising in Phase I and II human testing, nine out of ten ultimately fail in larger Phase III

studies. And so, it’s back to the drawing board. Linus Pauling, the American chemist and the only winner of two un-

shared Nobel Prizes once said, “The best way to have a good idea is to have a lot of ideas.” Add deep pockets to the list.

One Phase III drug trial today can cost $100 million, regardless of whether it succeeds or not.

“Innovation is the ability to see change as an opportunity – not a threat” — Steve Jobs


Making advances in medical science and technology is no simple undertaking. As you turn the pages of this

booklet, you will read about the medical breakthroughs that Cleveland Clinic experts believe are the game

changers that will transform the practice of medicine in 2013.

From altering the course of diabetes with weight-loss surgery to blocking the onset of a painful migraine headache

with a hand-held device, we owe thanks to the many talented and dedicated medical innovators who were willing

to endure all the challenges that it took to see their innovation move from initial idea at their work bench, all the

way to FDA approval and eventually the patient’s bedside.

Their work is extremely vital to the healthcare of millions worldwide and we salute them for their vision and

tireless efforts in improving the health and quality of life of so many. We support and encourage their continued

belief that innovation in the life sciences is good not only for the patient but for the economic ecosystem that

maintains it and helps it flourish.

Myopic Visionaries

1. Sir John Eric Ericksen, British Surgeon, 1873. “The abdomen, the chest, and the brain will forever be shut from the intrusion of the wise and humane surgeon.”

2. Lord Kelvin, President, Royal Society, 1895 “Heavier than air flying machines are impossible.”

3. Harry M. Warner, Warner Brothers Pictures, 1927 “Who the hell wants to hear actors talk?”

4. Tris Speaker, Hall of Fame baseball player, 1921 “Taking the best left-handed pitcher in baseball [Babe Ruth] and converting him into a right fielder is one of the dumbest things I ever heard.”

5. Robert Millikan, Nobel Prize in Physics, 1923 “There is no likelihood man can ever tap the power of the atom.”

6. Ken Olson, President, Chairman, Founder of Digital Equipment Corporation, 1977

“There is no reason anyone would want a computer in their home.”


Chronic diseases and infections coupled with

rising medical costs threaten both the health of

Americans and the economic wellbeing of the

United States. Almost half of all adult Americans

are living with a chronic illness, while 75% of

deaths each year are due to one of these chronic

diseases. It’s now estimated that by 2021 medical expenditures,

which have been growing 2% faster than the overall economy

each year, will total almost $5 trillion, or 20% of the national

gross domestic product.

In the last decade, healthcare costs doubled to $2.6 trillion

annually. If dollar bills were stacked atop one another, that

amount would stretch 170,000 miles into the atmosphere.

Healthcare costs today take almost 18 cents out of every dollar

spent by Americans, and this is severely straining personal,

state, and federal budgets. Sadly, these extraordinary medical

expenditures don’t always lead to less disability or enhanced

quality of life.

Personal health behaviors are a major cause of the unsustainable

medical costs and chronic illnesses that are overwhelming our

American healthcare system. Almost three-fourths of all medical

costs are for four chronic conditions: cardiovascular disease,

obesity, diabetes, and cancer. We know, however, that 60% to

90% of these ailments are preventable.

Approximately 96% of all Medicare dollars are used to care

for people with chronic illnesses, but as little as 3% to 5% of

the federal program’s budget goes towards preventive health

strategies. In 2011, nearly 2.3 million seniors in the Medicare

Healthcare Programs with Monetary Incentives

program went to their doctor for an annual wellness visit. Although Medicare spends $3.8 billion on these

exams annually, many patients leave without a formal game plan designed to improve their health.

With that in mind, the bipartisan Medicare Better Health Rewards Program Act of 2012 has been presented to

Congress as a way to improve healthcare and control costs for Medicare participants. The goal of the program is

to encourage people to take a more active role in their well being by developing and maintaining healthy habits.

The Better Health Rewards Program is part of a growing wellness revolution in American healthcare that is

designed to give everyone achievable health goals and a detailed plan to reach them, as well as financial

incentives to keep motivated and follow through with the various health strategies.

The three-year program uses the annual wellness visits Medicare already subsidizes to determine and measure

improvements in six key areas of health: body mass index, diabetes indicators, blood pressure, cholesterol,

vaccination status, and use of tobacco products.

In the first year, people will be assessed in each of these areas and then work with their doctor to develop a

plan to bring their indicators into a healthier range. Progress will be measured during subsequent wellness visits

in years two and three of the program.

By saving the Medicare program money, participants in the Better Health Rewards program will be given up

to $400 after checkups in the program’s second and third years. All of these monetary incentives will come

entirely from savings generated by seniors becoming healthy and utilizing fewer healthcare services.

After cancers of the skin, breast cancer is the most common cancer among women,

accounting for nearly one in four cancers diagnosed in American women today. Breast

cancer death rates are higher than those for any other cancer besides lung cancer. For

women ages 40 to 59, the main cause of death is cancer of the breast.

Although these statistics are sobering, breast cancer death rates have declined by

almost 20% over the past decade, in part due to increased screening for breast

cancer, which typically uncovers the disease at a time when the chance for successful

treatment is higher.

Several imaging techniques can detect breast lumps before a woman or her doctor can

feel them. Mammography, which allows doctors to uncover an abnormal breast mass

up to two years before it can be detected by touch, remains the gold standard imaging

technique for breast cancer.

Mammography relies on a two-dimensional x-ray image. However, this technology

has limitations because the female breast is three-dimensional and composed of

different structures—including milk ducts, blood vessels, and ligaments—located at

various levels within it. When scanned and viewed as a flat, two-dimensional image,

the mammography scan can be confusing to interpret and doesn’t always reveal every

cancer. This confusion is a major reason why normal tissue may appear abnormal and

why small breast cancers may be missed.

There is now a new imaging technology that is changing the way doctors screen

for breast cancer and it is improving the accuracy of diagnosis. Called breast

tomosynthesis or 3D mammography, the diagnostic technology was approved by

the FDA in 2011. Breast tomosynthesis does not currently replace traditional two-

dimensional mammography testing, but instead, it is performed along with the

conventional mammogram to provide a more accurate view of the breast.

During the tomosynthesis portion of the exam, the x-ray arm of the machine makes

a quick arc over the breast, taking dozens of images at a number of angles. Later

combined to make a three-dimensional rendering of the entire breast, the images can

be viewed by a radiologist at a computer workstation to check areas of concern.


Breast Tomosynthesis

If cancers are found when they are small, treatment options are generally less traumatic and the chance

for cure is greater. What 3D technology offers doctors and mammography technicians is a much greater

opportunity to discover small cancer cells obscured by surrounding tissue that may not be visible on standard

mammograms. This is particularly the case in women with dense breasts, in which tumors often escape

detection. Preliminary study results of 25,000 women reported a 47% increase in cancer detection when

tomosynthesis was used.

3D mammography also reduces the much-feared callbacks for women. Due to a lack of diagnostic clarity,

one in 10 women typically is asked to return for additional testing following a routine mammogram screening

that has raised concern. However, in a recent study of 7,500 women, the recall rate of women screened with

breast tomosynthesis and traditional mammography combined was 6.6% compared to 11.1% for traditional

mammography alone.

It’s for reasons like this and others that one day, in response to greater use and patient demand, experts

believe that breast tomosynthesis is expected to fully replace conventional mammography.

Aortic aneurysms pose a serious medical problem and when they rupture, the

results are catastrophic and deadly.

Aneurysm comes from the Greek word “aneurysma,” meaning, “a widening.” The

aorta is the largest artery in the body and is the primary artery that carries blood

from the heart and lungs to the head and rest of the body. Generally, about an inch

in diameter, the aorta is shaped like a candy cane, rises out of the heart, and then

rounds down towards the abdomen. Over the course of a lifetime, it transports

200 million liters of blood and has to withstand the pressure of three billion or so

heartbeats.

When someone has an aneurysm, there is a weak balloon-like bulge in the wall

of the aorta that causes the diameter to sometimes double in size over a period

of months or years. Abdominal aortic aneurysms, the most common, occur in the

section of the aorta that passes through the abdomen. Thoracic aortic aneurysms

occur in the portion of the aorta that passes through the chest. Aneurysms are

irreversible and the risk is that, as the aneurysm grows larger over time, it will

rupture, triggering massive internal bleeding, shock, and loss of consciousness.

Death is imminent in more than half of the cases, even for those who are able to

have emergency surgery. Aortic aneurysms are the 13th leading cause of death in

the United States, with over 15,000 fatalities annually. Most of these deaths could

have been avoided with proper monitoring and treatment.

Aneurysm treatment depends upon the size and location of the aneurysm and

the patient’s overall health. If the aneurysm is large (5.5 to 6 cm in diameter),

enlarging rapidly, or leaking, then minimally invasive endovascular repair is the

preferred treatment. This entails special tests to visualize the aneurysm followed by

selection of a stent graft to fit the body.

During the surgical procedure, a catheter is inserted through the femoral artery in


Modular Device for Treating Complex Aneurysms

the leg and snaked up to the aneurysm, where it is positioned to release the stent graft within the aorta. The

underlying metallic stent portion of the fabric graft immediately expands and holds it in place within the aorta,

reducing pressure on the aorta. Blood flows through the graft to arteries that go to the legs and, over time, the

aneurysm eventually shrinks.

Unfortunately, as many as 20 to 40% of people with aortic aneurysms have anatomies that are not suitable

for the grafts that are currently marketed, nor are they candidates for the more demanding open surgical repair

procedure.

However, thanks to a new innovative fenestrated stent graft system, surgeons can now treat patients with these

complex aneurysms without having to take detailed measurements and then wait for weeks, sometimes months,

for the customized endografts to be delivered.

The FDA recently approved a multi-center trial of the modular stent device for aneurysms that come close to the

renal artery. The device incorporates individual branches to both renal arteries and the superior mesenteric artery.

Taken “off-the-shelf” by a surgeon, it can be used for both elective and urgent cases involving the renal arteries.

The new modular stent graft system represents a giant leap forward from prior aortic aneurysm technologies. Not

only does it offer a significant reduction in morbidity and ICU stay, but more importantly, it allows an application

of life-saving technology to high-risk patients who never could have been treated for their aneurysms.

The respiratory system, consisting of the lungs and air passages, provides the body

with a continuous supply of oxygen as well as a means of removing carbon dioxide.

The life-sustaining oxygen that we inhale 17,000 times a day passes from the lungs

to the bloodstream, which distributes the oxygen to cells throughout the body.

Respiratory disorders serious enough to cause long-term breathing problems are

common in the United States and will increase in prevalence as the Baby Boom

population ages. Almost 400,000 Americans die of lung diseases every year, and

over 35 million are now living with chronic lung disease.

Fortunately, technological advances are producing opportunities to replace lungs

permanently damaged by end-stage diseases such as chronic obstructive pulmonary

disease, cystic fibrosis, pulmonary hypertension, or alpha-1 antitrypsin deficiency. As

a result, people with these disorders are living longer and better lives today than just

a decade ago.

Since the early 1990s, more than 25,000 lung transplants have been performed

at medical centers around the world. In the United States, more than 1,800 lung

transplants out of a pool of over 100,000 potential candidates are expected to be

completed in 2012. These patients had no other medical options and were expected

to die from lung disease within one to two years.

While lung transplantation is a lifesaver, donor lung shortage is a major limiting factor

to the number of transplants that can be performed annually. Lungs are harvested

from only 15 percent of donors due to the lung’s vulnerability to complications that

arise before and after donor brain deaths such as pneumonia, thoracic trauma,

ventilator associated lung injury, or pulmonary edema.

That is all about to change. Experts believe that as many as 40 percent of previously

rejected donor lungs may now be suitable for transplantation thanks to a new

approach called ex vivo—outside the body—lung perfusion. This novel “lung washing”

procedure can reverse lung injury in many donor organs deemed unsuitable and allow

for transplantation. 7Top 10 Medical Innovations: 2013 | 11

Ex Vivo Lung Perfusion

With scores of successful transplantation cases of ex vivo lungs that have been repaired and regenerated,

this is not science fiction. In this new pioneering procedure, the damaged lungs are removed from a donor,

placed in a bubble-like transparent chamber, and connected to a cardiopulmonary pump and a ventilator.

Over a four- to six-hour period, the lungs are then repaired and assessed. Special proprietary fluids are

forced through the blood vessels and nutrients are used to renourish the lungs as they inflate and deflate as

oxygen is pumped through. When necessary, targeted medications are introduced to clear infections. Once

determined as being viable, they are ready for immediate transplantation.

Ex vivo lung perfusion, which is approved in Europe and Canada, and is now undergoing a major multi-

center clinical trial in the United States, has the potential to significantly increase the number of available

lungs as the reconditioning process is adopted, refined, and improved at multiple transplant centers. This

increased availability of quality-tested donor lungs is going to make a huge difference to the 100,000

American patients with severe breathing problems who now wait on the lung transplant standby list.7

The eye is a complex organ that sends nerve impulses to the brain when stimulated

by reflected light rays. The brain can then process these impulses and create the

perception of vision.

The lens of the eye is a clear structure that stretches and contracts and allows us to

focus on objects at various distances. With aging, however, cataracts, one of the most

common eye ailments, can develop. These are dead cells that accumulate in the lens

capsule, causing the lens to gradually become cloudy. As these spots increase in size,

vision is no longer clear and sharp. The opaque areas on the lens make people feel as

if they are now seeing everything through a fog-covered window.

In the United States, 75% of people over age 60 have some sign of cataracts. In

most individuals any vision loss from cataracts can be corrected by surgery, which

is a common, safe, and effective way of replacing the clouded lens. In fact, cataract

surgery is the most commonly performed surgical procedure in the United States and

is considered by many doctors to be the most effective surgical procedure in all of

medicine. The American Academy of Ophthalmology estimates that 1.6 million cataract

operations are performed each year in the United States.

Cataract surgery, called phacoemulsification, involves removing all or part of the

damaged natural crystalline lens and replacing it with an intraocular lens implant to

provide vision correction, often eliminating the need for eyeglasses or contacts. Cataract

removal, which is done freehand with a surgical blade, will improve vision in more than

95% of cases if the eye is normal except for the cataract.

While surgical results have been outstanding, cataract surgery has now been

improved with the introduction of femtosecond laser technology. The device has

already been used successfully in ophthalmology, particularly for LASIK (Laser In-Situ

Keratomileusis) refractive surgery. 6Top 10 Medical Innovations: 2013 | 13

Femtosecond Laser Cataract Surgery

6 A femtosecond is one quadrillionth of a second. This is the super-fast amount of time that numerous laser

pulses of near infrared light are used by a surgeon in this new cataract procedure. The femtosecond laser

helps make a perfect circular hole in the lens capsule, splits the lens into sections, and then softens and

breaks up the cataract. The damaged lens is removed using ultrasound and an intraocular lens is then

implanted.

Unlike a surgical blade that cuts, a femtosecond laser separates tissue by ablating and cleaving it. The novel

FDA-approved bladeless cataract procedure is now revolutionizing surgery by making it more predictable and

accurate, allowing surgeons to make smaller, more precise incisions. It also requires less energy time inside

the eye, causes less inflammation, and offers more stability when implanting a new lens.

The combination of precision and simplification that is possible with femtosecond laser represents a major

advance for cataract surgery.

Skin cancer is the most common cancer in the United States, affecting millions each

year. One in five Americans will develop this cancer in their lifetime. According to the

National Cancer Institute, the incidence of melanoma, the least common but most

lethal type of skin cancer, has been increasing for at least 30 years, mainly due to UV

radiation from sunlight. More than 76,000 Americans develop melanoma annually

and 9,000 are expected to die from it this year.

The survival rate of patients diagnosed with early melanoma is almost 99%, while

survival for patients diagnosed with advanced stage cancer drops to about 15%.

Annual costs for treating skin cancer in the United States surpass $3 billion.

Therefore, early melanoma detection is critical and not just because it allows for more

effective treatment options and higher survival rates, but also because there are fewer

costly and invasive surgeries.

Melanoma can occur on any skin surface. It’s often found on the skin on the head,

neck, and between the shoulders and hips in men; in women, it typically appears on

the skin on the lower legs or between the shoulders and hips. When a dermatologist

makes a visual assessment of a mole that looks unusual or has grown or changed

color or shape recently, he or she will decide on doing a biopsy and removing a small

piece of the mole or the entire mole. A pathologist then looks at the sample under a

microscope to check for cancer cells.

The skin is the only organ entirely available to inspection and it can be looked at every

day. Dermatologists are experts at analyzing the surface of the skin but detecting life-

threatening melanomas with the human eye has its own set of challenges. Melanoma

in situ and invasive melanomas often mimic benign lookalikes. This is compounded

when a patient has many moles or suspicious spots on his or her body, which

sometimes adds to the difficulty in deciding what needs to be biopsied.

Additional facts for a dermatologist means that a more informed decision can be made

when having to decide whether to biopsy or not. There is now a new FDA-approved


Handheld Optical Scan for Melanoma

handheld office device for dermatologists that can provide that extra information needed to help these

specialists in the identification of skin lesions that have characteristics of melanoma.

Without cutting the skin, the device—which uses imaging technology created by the military for guided

missile navigation—is placed on the skin over the mole. Special lights of 10 specific wavelengths are

shined on the skin, and the computerized system rapidly visualizes the micro-vessel structure of the

lesion just below the skin’s surface. The device then uses sophisticated algorithms that objectively

analyze the lesion. Next, the device compares the image findings it has just developed to a database of

10,000 archived images of melanoma and other skin diseases. In less than a minute, an assessment of

the skin lesion is given and the dermatologist can then decide on possible next steps.

In a clinical trial of 1,300 patients, the largest study ever conducted in melanoma detection, the device

detected 98% of the melanomas, while missing fewer than 2% of these early cancers.

Prostate cancer is the most common cancer in men and the second leading cause of death

due to cancer in men. As many as 20 to 30 percent of men see their prostate-specific

antigen (PSA) levels rise again at some point after surgery or radiation treatment for prostate

cancer, a signal of the unrecognized spread of cancer beyond the prostate at diagnosis,

inadequate surgery, or resistance to radiation and/or androgen deprivation therapy. These

men are told that they have advanced cancer, and that they must now, with the counsel of

their doctors, decide what to do about it.

When further treatment is later deemed necessary because the cancer has spread to bone or

other body sites, withdrawal of androgens such as testosterone, which fuels cancer growth,

is the standard of care for metastatic prostate cancer.

Although this androgen deprivation therapy, or ADT, can result in long-term remissions of

metastatic prostate cancer, it is not curative. Cancer soon becomes resistant to this therapy

and continues to advance. More than 50,000 American men have castration-resistant

cancer, or cancer that no longer responds to ADT. It’s now believed that this cancer

thrives because the cancer cells manufacture their own androgens.

Scientists are searching for alternate methods to block abnormal cell

growth. Taxotere, approved by the FDA in 2004, was until recently the

only therapy available for castration-resistant prostate cancer. In the past

two years, however, five new drugs have been approved for advanced

prostate cancer: sipuleucel-T, denosumab, abiraterone, cabazitaxel, and

enzalutamide. A sixth, radium-223 dichloride, is expected to be approved

later this year.

Significant progress has been made in treating advanced prostate cancer,

not so much because survival is improved to a great extent, but rather

because these new medications are proving that innovative approaches to

treatment can be successful in halting the progress of this disease.

The FDA approved abiraterone in 2011. So successful was this drug in

Phase III testing that the monitoring committee recommended unblinding


Novel Medications for Advanced Prostate Cancer

the placebo-controlled group and having the patients switch to abiraterone.

Abiraterone blocks CYP17, a key driver of testosterone production, caused 90 percent of patients in

the clinical trial to have a dramatic reduction in PSA levels even though they had already taken anti-

hormone drugs. Most patients who use abiraterone also have significant shrinkage of tumors and for

those with bone pain due to metastases, many have improvement in pain levels.

Enzalutamide, approved in 2012, is the strongest inhibitor of testosterone receptors now available.

The drug blocks testosterone receptors at three separate points, preventing testosterone from traveling

into the nucleus of a cell and stimulating the genes that cause prostate cancer growth.

About 90 percent of men with advanced prostate cancer have bone metastases, a major cause of pain,

disability, and eventual death. Radium-223 dichloride, an injectable form of radiation therapy, targets

new bone growth caused by bone metastases and their tumor cells. The radiation kills these cells while

avoiding damage to healthy cells.

Many in the prostate cancer research community now believe that these drugs, and others coming from

the prostate cancer therapeutic pipeline, will one day help make advanced prostate cancer a chronic

disease that’s successfully managed with a routine of daily medication, lifestyle modification, and

regular checkups.

Clinical microbiology laboratories perform essential tests that allow physicians to

diagnose and treat bacterial infections. Specimens such as blood, cerebrospinal

fluid, or urine are collected from patients with a suspected infection and sent to the

laboratory for culture. The specimen is inoculated on an agar plate, incubated and

examined daily for growth. Each type of colony growing on the plate must be identified

and classified as normal flora or a possible pathogen responsible for the infection.

In this age of advanced medical technology, identification of bacteria growing in

culture can still require days or weeks.

However, clinical microbiology laboratories throughout the world are now

implementing new mass spectrometry technology to provide rapid organism

identification that is more accurate and less expensive than current biochemical

methods.

Mass spectrometry has been used for the past 50 years to ionize and then identify

molecules by determining their individual mass-to-charge ratio. However, early mass

spectrometry ionization methods were destructive and could not be used to analyze

large molecules such as proteins.

In 2002, the Nobel Prize was awarded for the development of a soft ionization

technique called matrix assisted laser desorption/ionization, or MALDI. The major

benefit of MALDI is that it does not fragment large molecules. A special matrix solution

protects large molecules from fragmentation by absorbing photonic energy from the

laser in a process that is known as “desorption.”

When used to determine the composition of a sample, for example, single charged

molecules are created and travel in a tube towards a detector. The time of flight (TOF)

of these molecules is directly proportional to mass and this is what’s used to calculate

a mass-to-charge ratio. Charting of the mass-to-charge ratios for individual ions

creates a series of peaks called a spectrum, which is then compared to a reference

database. Identifications generated using MALDI-TOF mass spectrometry have an

accuracy that is similar to molecular sequencing methods.


Mass Spectrometry for Bacterial Identification

Using one of the two MALDI-TOF mass spectrometry systems currently available in the United States is very

simple. A small amount of bacterial growth from a culture plate is applied to a target plate and covered with

a drop of matrix solution. The target is placed in the instrument where a laser shoots short pulses of light and

irradiates the sample to create ions inside the instrument’s vacuum chamber. The time of flight before detection

of these electrically charged particles is based on their particular masses and is used to create the spectrum or

“signature.”

Computer software compares the spectrum to a database and if there is a match, the identification is generated

within minutes of ionization. The cost for labor and reagent needed to generate this highly accurate identification

is approximately $.50.

Rapid organism identification now allows clinicians to prescribe the most appropriate treatment sooner and

de-escalate therapy from broad-spectrum agents that drive antimicrobial resistance. At a time when bacterial

infections account for a large proportion of people admitted to hospitals each year—as well as some acquired

by patients already under medical care—quick and accurate detection of these microorganisms help guide

appropriate patient treatment and improve outcomes is more critical than ever.

The use of MALDI-TOF mass spectrometry to provide more accurate identifications of bacteria in minutes—

rather than days—is a major advance in treating infections.

Headaches rank just after the common cold as the ailment that bothers most Americans,

and for 50 million of them the headaches are so severe that they consult a doctor.

Cluster headaches, which affect about three of every thousand American adults, are

the most painful of all. This headache gets its name because it comes without warning

in a cyclical pattern or cluster, typically occurring at the same time of day or night, and

continuing like clockwork day after day for weeks or months. There is no known cause

for these headaches or any effective therapy. Some people have been known to bang their

head against a wall to relieve the unremitting pain. Nicknamed the “suicide headache”

because doctors feared patients would take their lives, in order to end the torment, some

people resort to more drastic measures to get relief.

Tens of millions of Americans suffer from migraine headaches. The pain can range from

mild to severe, and last for just an hour to a day or two. By the time migraine pain reaches

higher levels, sufferers are unable to go about normal everyday activities. According to

the National Headache Foundation, migraine headaches affect approximately 28 million

adults in the United States, and American employers lose close to $13 billion annually due

to 113 million lost workdays because of migraine complaints. While there is no cure for

migraines, they can be managed with various medications.

The sphenopalatine ganglion (SPG) nerve bundle is located deep in the face, behind

the bridge of the nose. Since the application of cocaine or alcohol to the SPG was first

described in the medical journals more than 100 years ago as effective headache therapy,

the SPG bundle has been a specific target for the treatment of severe headache pain over

the years. When lidocaine and other medications are applied to the area, it creates a nerve

block. While headache relief is often good, it is short lived and repeat procedures are

needed. This is not easy, however, due to the location of the nerve bundle.

Rather than relying on a variety of preventive and abortive medications or other strategies

such as inhaling pure oxygen, the most common treatments for migraine and cluster

headaches, respectively, there is now a novel solution that can reduce their frequency and

severity without medication.


Neuromodulation Therapy for Cluster and Migraine Headaches

American researchers have invented an on-demand patient-controlled stimulator for the SPG nerve bundle. This

miniaturized implantable neurostimulator, the size of an almond, is placed through a minimally invasive surgical

incision in the upper gum above the second molar, and held in place there. The lead tip of the implant is placed

at the SPG nerve bundle on the side of the face where headache pain is typically experienced by the patient.

Whenever a patient feels a headache coming on, a remote control device is placed on the cheek and it delivers as-

needed stimulation to the SPG, blocking the headache pain in about five to ten minutes. Once the headache is treated,

the device is moved away from the cheek, which turns off the stimulation therapy.

In European testing, 68% of patients responded to neuromodulation therapy, achieving cluster attack pain relief,

reduction in attack frequency, or both. The therapy also improved headache disability in 64% and quality of life in

75% of the patients. Now already approved and available in Europe for the treatment of cluster headaches, the FDA

has granted investigational use of the neurostimulation system for cluster headaches for use in the United States.

International multi-center randomized clinical trials are currently ongoing for migraine treatment.

The pancreas normally makes enough insulin to keep the supply and use of glucose

in the body in balance. Glucose is used by cells for energy, but when the delicate

glucose balancing system is disrupted—most often because of obesity—Type 2

diabetes develops.

In the United States, the number of diabetes cases has tripled in the past 30 years to

more than 20 million, according to the Centers for Disease Control and Prevention,

and more than 90 percent of these people have Type 2 diabetes. As a person’s weight

increases, so does the risk and severity of this ailment. About 40% of people with

Type 2 diabetes need daily insulin injections to maintain safe levels of glucose.

70 percent of adults in the United States are either overweight or obese, and so are

one third of children and teens. Exercise and diet alone are not effective for treating

severe obesity or the Type 2 diabetes that develops. Once a person reaches 100

pounds or more above his or her ideal weight, losing the weight and keeping it off for

many years almost never happens.

While the medications we have for diabetes are good, about half of the people who

take them are not able to control their disease. This can often lead to heart attack,

blindness, stroke, and kidney failure.

Surgery for obesity, often called bariatric surgery, shrinks the stomach into a small

pouch and rearranges the digestive tract so that food enters the small intestine at a

later point than usual.

Over the years, many doctors performing weight-loss operations found that the

surgical procedure would rid patients of Type 2 diabetes, oftentimes before the patient

left the hospital.

To explore this diabetes treatment hypothesis, 150 patients with Type 2 diabetes and

obesity were enrolled in a study in 2007. 50 patients had gastric bypass surgery, a

procedure that reduces stomach volume from the size of an inflated football to golf 1Top 10 Medical Innovations: 2013 | 23

Bariatric Surgery for Control of Diabetes

ball size; 50 had a sleeve gastrectomy surgery, which reduces the stomach from the size of a football to that of

a banana; and 50 were offered counseling in nutrition and exercise while they continued taking their diabetes

medication.

By closing off most of the stomach to food, people who received bariatric surgery ate less and, therefore, lost

weight. Patients in the study lost about five times as much weight on average as those only taking blood-

sugar-lowering medications.

The study results, published in the New England Journal of Medicine in 2012, astounded the medical world.

Compared with patients taking diabetes medication and receiving lifestyle counseling, those who had

bariatric surgery were far more likely to be free of diabetes or to have reduced their dependence on diabetes

medications for at least two years. The weight-loss surgery also helped many to lower their blood pressure and

cholesterol. Most of the patients went from a dozen or more medications daily to none or just a few.

A cure for Type 2 diabetes? Perhaps. Larger randomized trials will eventually determine this.

In the meantime, many diabetes experts now believe that weight-loss surgery should be offered much earlier

as a reasonable treatment option for patients with poorly controlled diabetes—and not as a last resort. 1

#1 Catheter-Based Renal Denervation to Control Resistant Hypertension

o v e r v i e w

Renal denervation is a new 40-minute procedure performed in a hospital catheterization laboratory in which a

catheter-based probe is introduced through the femoral artery in the upper thigh and is threaded up into the renal

artery near each kidney. Once in place, the tip of the catheter delivers multiple two-minute treatments of low-power

radio-frequency energy to affect the surrounding sympathetic nerves.

w h e r e a r e t h e y n o w ?

For every drop of 20 mm Hg in systolic blood pressure, the risk of cardiovascular disease is cut in half. At the annual

European Society of Cardiology meeting in May 2012, multi-center study results of 46 patients with drug-resistant

hypertension experienced an average 22 mm Hg drop in blood pressure after undergoing renal denervation, and

another 6 mm Hg drop at the 30-day study milestone. Three months later, lowered blood pressure remained stable

for all study subjects. There are currently five companies manufacturing renal denervation devices, which are only

available in Europe. A study in the United States of the device and procedure is ongoing.

#2 CT Scans for Early Detection of Lung Cancer

o v e r v i e w

This high-tech scan generates a series of detailed cross-sectional images of the lungs that are used to create a three-

dimensional image. These scans not only identify tumors earlier, but also spot them when the tumors are smaller and

more treatable by surgery. Surgery is the best treatment for most types of lung cancer.


New guidelines published in May 2012 in the Journal of the American Medical Association recommend lung cancer

screening with low-dose CT scans. About 8 million Americans between the ages of 55 and 74 would be eligible

according to criteria endorsed by the American College of Chest Physicians, The American Society of Clinical Oncology,

Where Are They Now?Top 10 Medical Innovations: 2013 | 25

T o p 1 0 M e d i c a l I n n o v a t i o n s f o r 2 0 1 2

and the National Comprehensive Cancer Network. The new guidelines recommend that screening only be offered

in academic medical centers or other sites with specialized radiologists on staff. The scans, which are often

offered for as low as $100, are still not covered by insurance.

#3 Concussion Management System for Athletes

o v e r v i e w

The United States Centers for Disease Control and Prevention calculates that almost four million sports-

and recreation-related concussions occur each year-and they exact a heavy toll. There are about 235,000

hospitalizations and 50,000 deaths annually due to concussions. Estimates suggest that up to 40 percent

of football players experience a concussion annually, with the majority of these brain injuries going unreported,

unrecognized, and unmanaged. There is now a tool that objectively and accurately assesses cognitive and motor

function simultaneously.


Concussion worries loom large in the sports world. In the past year, more than 3,300 players have sued the

National Football League, charging that not enough was done to inform them of the dangers of concussions

in the past, or to take care of them today. On the grade school and high school level, there is a now a call for

school systems to have mandatory, science-based concussion management systems, developed in accordance

with national guidelines. A special concussion app is currently being tested with high school teams. The app

checks the athlete’s memory, reaction time and balance, then stores the information on an iPad. If a student

suffers a head injury, the data can be compared to see if there has been a concussion.

#4 Medical Apps for Mobile Devices

o v e r v i e w

Thanks to medical apps and mHealth, which is shorthand for mobile health, both doctor and consumer are

taking part in a technological revolution in the way healthcare information is accessed and delivered today—and

it’s right at their fingertips.


As mobile devices and applications have become more user-friendly, affordable and powerful, the appeal to healthcare

providers has grown exponentially. The mobile health technology market—with its apps, devices, and services—now

includes more than 40,000 mobile health apps, contributing to the $718 million global industry. The successful

apps are those that provide needed services, and make doctors and patients more efficient. The field is currently

unregulated but the FDA recently released a draft of guidelines requiring app creators that make medical claims to

apply for FDA approval just like any other medical device.

#5 Increasing Discovery with Next-Generation Gene Sequencing

o v e r v i e w

The best way to get to the root cause of serious illness is to sequence a person’s genome. Leading geneticists envision

a day soon when everyone’s genome will be sequenced and included as a routine part of their medical records. Next-

generation sequencing machines can help achieve this goal in the near future with the wider dissemination of faster

and affordable sequencing machines.


The field of next-gen sequencers is expanding rapidly and these devices have become go-to items in the

armamentarium of researchers. Pathology laboratories that utilize these silicon-based machines now offer clinicians

the ability to detect and characterize disease at earlier stages when cure is still possible. A benchtop device capable

of sequencing the human genome in one day for $1,000 is now available, while a newer palm-size device that can

sequence the genome in 15 minutes will be available in 2013.

#6 Implantable Device to Treat Complex Brain Aneurysms

o v e r v i e w

One in 15 people in the United States will develop a brain aneurysm in their lifetime. Aneurysms can occur in

people of all ages, but are most commonly detected in those ages 50 to 60. There is now a new minimally-invasive


procedure available that can safely and effectively manage large and difficult-to-treat aneurysms without

open surgery by implanting a new FDA-approved device directly into the artery.


The newly approved FDA device is proving to be superior to older forms of coiling and stenting because it forms

a fabric sleeve inside the blood vessel that allows blood to move away from the aneurysm, forming a new blood

vessel inside of the aneurysm. Over time, the aneurysm will heal around the stent and vanish. Over 90 percent

total obliteration rates at 12 months have been consistently confirmed in international studies. Because it helps

reconstruct blood vessels within the brain, experts feel that this device may one day replace traditional open

brain procedures.

#7 Active Bionic Prosthesis: Wearable Robotic Devices

o v e r v i e w

Estimates of the amputee population in the United States vary widely, from fewer than 400,000 to more than

1 million. Thanks to remarkable advances in prosthetics research in the last decade, space age plastics and

carbon fiber composites, which are much stronger, lighter and more durable, have been engineered to help restore

function. Now comes the computerized bionic leg with its microprocessors and computer chips that can rival the

functionality provided by biological limbs.


Technology in newer prosthetics is advancing rapidly. Users of a new 4.5-pound lower limb prosthetic report

less pain, more energy, an increase in daily activities, fewer pressures inside of the socket and more stability on

uneven terrain. Increasing scientific data now supports these many advantages. In addition, patients with more

severe mobility-inhibiting injuries now have a commercially-produced prosthetic exoskeleton to use instead of

wheelchairs. Delivery of the first $130,000 lower body exoskeleton was made in February. This high-tech medical

device supports the body while moving the user’s legs for them—it lets paraplegics walk again. At present, while

medical insurers will pay for basic prostheses, they typically do not pay for any of the innovative artificial limbs.

Where Are They Now?

#8 Harnessing Big Data to Improve Healthcare

o v e r v i e w

The amount of data collected each day dwarfs human comprehension and even brings most computing programs to

a quick standstill. Healthcare big data requires advanced technologies to efficiently process it with tolerable elapsed

time, so organizations can create, collect, search, and share data, while still ensuring privacy. In this way, analytics

can be applied to better hospital operations, track outcomes for clinical and surgical procedures, including length

of stay, readmission rates, infection rates, mortality, and comorbidity prevention. It can also be used to benchmark

effectiveness-to-cost models. Innovative companies are now answering the call to begin mining this mother lode of

untapped medical information.


Big data is becoming big business as more American hospitals digitize patient records and then analyze them to

discover particular patterns that can help improve care and outcomes. With a government push and financial incentive

to adopt electronic medical records, hospitals and researchers alike are using this information to find clues to the

initiation of various cancers and diseases like multiple sclerosis, and to look for possible links between particular

neighborhoods and the prevalence of certain medical conditions. By taking full advantage of big data accumulation,

all of the resulting number crunching is expected to lead to improved patient care, unexpected discoveries, and new

medical therapies.

#9 Novel Diabetes Therapy: SGLT2 Inhibitors

o v e r v i e w

There are many diabetes medications, and most work by affecting the supply or use of insulin, which helps move

glucose into the cells. But now there is a new class of drugs ready for prime time called sodium-glucose co-transporter

2 protein inhibitors, or SGLT2 inhibitors. These drugs represent a paradigm shift in diabetes treatment because they

reduce blood sugar in a totally new way: by causing it to be excreted during urination.



With concerns about side effects that included possible liver damage and a link with bladder and breast cancer,

the FDA issued a complete response letter in January for dapagliflozin and asked for additional data. In May 2012,

dapagliflozin received a positive opinion from the European Medicines Agency recommending approval of the drug.

At the May meeting of the American Diabetes Association, other pharmaceutical companies presented positive data

on their SGLT2 class of drugs, reporting efficacy in lowering A1C levels and overall tolerability. Information about

canagliflozin, a medication used in nine studies and over 10,000 patients, was recently presented to the FDA as part

of the approval process.

#10 Genetically Modified Mosquitoes to Reduce Disease Threat

o v e r v i e w

Mosquito control is one of the major health issues of the twenty-first century. Powerful insecticides, draining of

swamps, and mosquito nets have helped in some areas with prevention and control, but with no way to effectively

sustain these efforts, the mosquito breeding and eating habits remain unbroken. Researchers are now exploring new

avenues to fight mosquitoes-and it starts in the laboratory where scientists manipulate the DNA of the insects.


With the fear of dengue fever (nicknamed “break bone fever”) and its intense joint pain, cities in southern Florida

and also in Brasilia, Brazil, are considering the use of genetically modified mosquitoes to eliminate the disease-

causing pests. More than 400,000 cases of dengue have been registered in Brazil in 2012, while no cases have been

recorded in the Florida Keys in 2012. However, Florida authorities want to release the mosquitoes to eliminate the

threat of disease. The United States Department of Agriculture was asked to issue a federal permit for the release of

millions of the modified mosquitoes, but instead, due to public fears that eradicating mosquitoes could have negative

consequences to the food chain, the FDA is currently reviewing the project.

Where Are They Now?

Many thanks to the

Top 10 Selection Committee

members who chose the final

Top 10 Medical Innovations

for 2013.

We would like to especially

thank Michael Roizen, MD,

who for the fourth year in

a row has chaired the

selection committee and

panel and James Merlino,

MD, who moderated the

selection sessions.

Nancy Albert, PhDDirectorNursing Research & Innovation

Stacy Brethauer, MDStaff Bariatric & Metabolic Institute

Thomas Daly, MDSection HeadClinical Pathology

Joseph Foss, MDDirectorClinical Research for General Anesthesiology

Leonard Golding, MDStaffBiomedical Engineering

Brian Griffin, MDSection HeadCardiovascular Imaging

Joseph Iannotti, MD, PhDChairOrthopaedic & Rheumatologic Institute

Jihad Kaouk, MDStaffGlickman Urological & Kidney Institute

Irene Katzan, MDStaffNeurological Institute

Eric Klein, MDChairGlickman Urological & Kidney Institute

Eric Kodish, MDChairCenter for Ethics, Humanities & Spiritual Care

Vinod Labhasetwar, PhDStaffBiomedical Engineering

Richard Lang, MDChairPreventative Medicine

Andre Machado, MD, PhDDirectorCenter for Neurological Restoration

Roger Macklis, MDStaffRadiation Oncology

Kandice Marchant, MD, PhDChairPathology & Laboratory Medicine Institute

Gordon McLennan, MDStaffDiagnostic Radiology

James Merlino, MDChief Experience OfficerPatient Experience Office

Francis Papay, MDChairDermatology & Plastic Surgery Institute

Michael Roizen, MDChairWellness Institute

Ellen Rome, MDSection HeadGeneral Pediatrics

Jonathan Schaffer, MD StaffOrthopaedic Surgery

Philip Schauer, MDDirectorBariatric & Metabolic Institute

Rishi Singh, MDStaffOphthalmology

Edward Soltesz, MDStaffThoracic & Cardiovascular Surgery

Anthony Stallion, MDStaffPediatric Surgery

Wolf Stapelfeldt, MDChairGeneral Anesthesiology

John Suh, MDChairRadiation Oncology

Joe TurkInformation Technology Directore-Cleveland Clinic

Geoffrey Vince, PhDChairBiomedical Engineering

Michael Vogelbaum, MD, PhDAssociate DirectorBrain Tumor and Neuro-Oncology Center

Marianela Zytkowski, RNDirectorNursing Informatics

We would also like to give thanks to the team who tirelessly worked to produce the Top 10 book and video – especially:

Susan BernatGerald Secor Couzens

Additional support provided by Jason Ospina, Ph.D and Kimberley Woods.

Thank You

Cleveland Clinic Innovations

Christopher M. Coburn, Executive Director [email protected]

9500 Euclid Avenue / GCIC 10 Cleveland, Ohio 44195 Tel. 216.444.5757

www.clevelandclinic.org/innovations

Cleveland Clinic Innovations is ranked Top 4 in the world in healthcare corporate venturing by Global Corporate Venturing

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