Top 10 Medical Innovations: 2013

Top 10 Medical Innovations: 2013

The Selection Process

Bringing Medical Innovation from Bench to Bedside

Top 10 Medical Innovations for 2013

Where Are They Now?

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Top 10 Medical Innovations: 2013 | 1

Top 10 Medical Innovations: 2013

The Selection Process

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

Top 10 Medical Innovations: 2013 | 3

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, stubbornness, persistence, flexibility, and unwillingness to give up on the part of the innovator(s) in order to yield an FDA approval 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, its back to the drawing board. Linus Pauling, the American chemist and the only winner of two unshared 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 patients 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.

Top 10 Medical Innovations: 2013 | 5

Healthcare Programs with

Monetary Incentives
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. Its 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 dont 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 programs budget goes towards preventive health
strategies. In 2011, nearly 2.3 million seniors in the Medicare

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 programs second and third years. All of these monetary incentives will come
entirely from savings generated by seniors becoming healthy and utilizing fewer healthcare services.

Top 10 Medical Innovations: 2013 | 7

Breast Tomosynthesis
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 structuresincluding milk ducts, blood vessels, and ligamentslocated at
various levels within it. When scanned and viewed as a flat, two-dimensional image,
the mammography scan can be confusing to interpret and doesnt 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 twodimensional 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.

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.
Its 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.

Top 10 Medical Innovations: 2013 | 9

Modular Device for Treating

Complex Aneurysms
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 patients 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

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.

Top 10 Medical Innovations: 2013 | 11

Ex Vivo Lung Perfusion

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 lungs 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 vivooutside the bodylung perfusion. This novel lung washing
procedure can reverse lung injury in many donor organs deemed unsuitable and allow
for transplantation.

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 multicenter 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.

Top 10 Medical Innovations: 2013 | 13

Femtosecond Laser
Cataract Surgery
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.

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.

Top 10 Medical Innovations: 2013 | 15

Handheld Optical
Scan for Melanoma
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. Its 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 lifethreatening 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 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 devicewhich uses imaging technology created by the military for guided
missile navigationis 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 skins 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.

Top 10 Medical Innovations: 2013 | 17

Novel Medications for

Advanced Prostate Cancer
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. Its 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

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 antihormone 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 thats successfully managed with a routine of daily medication, lifestyle modification, and
regular checkups.

Top 10 Medical Innovations: 2013 | 19

Mass Spectrometry for

Bacterial Identification
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 whats 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.

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 instruments 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 yearas well as some acquired
by patients already under medical carequick 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 daysis a major advance in treating infections.

Top 10 Medical Innovations: 2013 | 21

Neuromodulation Therapy for

Cluster and Migraine Headaches
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.

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 asneeded 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.

Top 10 Medical Innovations: 2013 | 23

Bariatric Surgery for

Control of Diabetes
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 disruptedmost often because of obesityType 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 persons 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

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 bloodsugar-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 diabetesand not as a last resort.

Top 10 Medical Innovations: 2013 | 25

Where Are They Now?

To 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

#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 threedimensional 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.
w h e r e

a r e

t h e y

n o w ?

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,

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 sportsand 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.
w h e r e

a r e

t h e y

n o w ?

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 athletes 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 todayand
its right at their fingertips.

Top 10 Medical Innovations: 2013 | 27

w h e r e

a r e

t h e y

n o w ?

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 marketwith its apps, devices, and servicesnow
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 persons genome. Leading geneticists envision
a day soon when everyones genome will be sequenced and included as a routine part of their medical records. Nextgeneration sequencing machines can help achieve this goal in the near future with the wider dissemination of faster
and affordable sequencing machines.
w h e r e

a r e

t h e y

n o w ?

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

Where Are They Now?

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.
w h e r e

a r e

t h e y

n o w ?

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.
w h e r e

a r e

t h e y

n o w ?

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 users legs for themit 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.

Top 10 Medical Innovations: 2013 | 29

#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.
w h e r e

a r e

t h e y

n o w ?

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.

Where Are They Now?

w h e r e

a r e

t h e y

n o w ?

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.
w h e r e

a r e

t h e y

n o w ?

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 diseasecausing 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.

Thank You
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, PhD

Director
Nursing Research & Innovation

Vinod Labhasetwar, PhD

Staff
Biomedical Engineering

Rishi Singh, MD
Staff
Ophthalmology

Stacy Brethauer, MD
Staff
Bariatric & Metabolic Institute

Richard Lang, MD
Chair
Preventative Medicine

Edward Soltesz, MD
Staff
Thoracic & Cardiovascular Surgery

Thomas Daly, MD
Section Head
Clinical Pathology

Andre Machado, MD, PhD

Director
Center for Neurological
Restoration

Anthony Stallion, MD
Staff
Pediatric Surgery

Joseph Foss, MD
Director
Clinical Research for General
Anesthesiology
Leonard Golding, MD
Staff
Biomedical Engineering
Brian Griffin, MD
Section Head
Cardiovascular Imaging
Joseph Iannotti, MD, PhD
Chair
Orthopaedic & Rheumatologic
Institute

Roger Macklis, MD
Staff
Radiation Oncology
Kandice Marchant, MD, PhD
Chair
Pathology & Laboratory
Medicine Institute
Gordon McLennan, MD
Staff
Diagnostic Radiology
James Merlino, MD
Chief Experience Officer
Patient Experience Office

Jihad Kaouk, MD
Staff
Glickman Urological & Kidney
Institute

Francis Papay, MD
Chair
Dermatology & Plastic Surgery
Institute

Irene Katzan, MD
Staff
Neurological Institute

Michael Roizen, MD
Chair
Wellness Institute

Eric Klein, MD
Chair
Glickman Urological & Kidney
Institute

Ellen Rome, MD
Section Head
General Pediatrics

Eric Kodish, MD
Chair
Center for Ethics, Humanities &
Spiritual Care

Jonathan Schaffer, MD
Staff
Orthopaedic Surgery
Philip Schauer, MD
Director
Bariatric & Metabolic Institute

Wolf Stapelfeldt, MD
Chair
General Anesthesiology
John Suh, MD
Chair
Radiation Oncology
Joe Turk
Information Technology Director
e-Cleveland Clinic
Geoffrey Vince, PhD
Chair
Biomedical Engineering
Michael Vogelbaum, MD, PhD
Associate Director
Brain Tumor and Neuro-Oncology
Center
Marianela Zytkowski, RN
Director
Nursing Informatics
We would also like to give thanks
to the team who tirelessly worked
to produce the Top 10 book and
video especially:
Susan Bernat
Gerald Secor Couzens
Additional support provided
by Jason Ospina, Ph.D and
Kimberley Woods.

Cleveland Clinic Innovations is ranked Top 4 in the world in

healthcare corporate venturing by Global Corporate Venturing

Cleveland Clinic Innovations

Christopher M. Coburn, Executive Director
coburnc@ccf.org
9500 Euclid Avenue / GCIC 10

Cleveland, Ohio 44195

www.clevelandclinic.org/innovations

Tel. 216.444.5757