University of Maryland Rounds

FOR PHYSICIANS SPRING/SUMMER 2012

University of Maryland

Ro un ds

CLINICAL AND RESEARCH UPDATES FROM THE UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE AND THE UNIVERSITY OF MARYLAND MEDICAL CENTER

Living Liver Transplants: Full Steam Ahead In this Issue Rounding Out Care and Research

| p3

University of Maryland Completes Face Transplant | p4 Novel Lung Transplant Trial | p5 Advanced Fetal Care | p6

A 24-year-old woman’s liver unexpectedly shuts down, sending her to the University of Maryland Medical Center (UMMC) in acute liver failure. No one — including her father and uncle, who are both physicians — knows what caused the young woman’s condition to deteriorate so rapidly, but they do know she will die if she doesn’t receive a new organ quickly. Her boyfriend offered to donate part of his liver, and then they were both on the road to recovery within a few days.

Not all living liver donation stories are quite so dramatic, but this one was particularly poignant since it launched UMMC’s re-emergence into living liver transplants after a four-year hiatus.

With the addition of John LaMattina, M.D. — an assistant professor of surgery who was trained in livingdonor transplant surgery in Istanbul, Turkey — to the liver transplant team, UMMC’s program was recently recertified by the United Network of Organ Sharing (UNOS), which manages the nation’s organ transplant system under contract with the U.S. government. | cont’d p2

medicine on a mission | OneCall 1-800-373-4111 umm.edu

Living Liver Transplants: Full Steam Ahead | cont’d from p1

Offered by only a handful of medical centers around the United States, the living liver transplant program first began at UMMC in the late 1990s.

Dr. LaMattina and Benjamin Philosophe, M.D., Ph.D., head of the section of liver transplantation and hepatobiliary surgery and an associate professor of surgery, are donor surgeons, while Rolf Barth, M.D., an associate professor of surgery, and Sameh Fayek, M.D., an assistant professor of surgery, are recipient surgeons.

DRS. ROLF BARTH AND BENJAMIN PHILOSOPHE (L. TO R.)

“When I first started, the liver transplant program had two surgeons,” Dr. Philosophe says. “Now we have a team of four — two for donors and two for recipients — and all have experience with living donors, which is likely to yield the best possible outcomes.”

A MAGNET PROGRAM In 2009, 218 adult patients nationwide received a living-donor liver transplant according to UNOS, while more than 6,000 get transplants from deceased donors. But more living donations could help save greater numbers of the 17,500 U.S. patients waiting to receive a liver, Dr. Philosophe says — 1,700 of whom die each year while waiting. Indeed, one of the main advantages of living-donor transplants is the availability of an organ to a patient who might not otherwise be classified as “sick enough” for a cadaver liver by their MELD score. Deceased donor livers are allocated to patients with the highest MELD, or Model for End-Stage Liver Disease score within the blood group. MELD is based on blood tests and roughly reflects the severity of liver disease. However, for some patients MELD does not accurately indicate how clinically sick they are.

While they are desperately in need of a liver, they are unlikely to receive one because their MELD score is not high enough. Hence, in this context, a living donor liver transplant is truly life-saving.

“We want to create a magnet program,” Dr. Philosophe says. “Our strategy is for people to understand that certain patients may not have access to a deceased donor because they’re not high enough on the list.

For them, a living donor is their best option, if not their only option.”

Although it may be the ideal option for such patients, the process is still far from simple. Less than half of those who volunteer to give a portion of their liver — typically a relative, friend or co-worker of the patient — are actually eligible to do so after a battery of blood, imaging and other tests weed out those who

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cannot donate, Dr. Philosophe says. In addition to having a compatible blood type and being otherwise healthy, the donor must also be a similar size to the recipient to ensure that his or her liver is large enough to sustain the recipient. About 60% of the organ is taken, which will grow to full size in both people within a few weeks.

“If the donor is a five-foot-one lady and the recipient is a six-foot-two man, her liver may not be big enough,” he says.

LOW-RISK, BUT COMPLICATIONS CAN OCCUR Because liver transplantation involves a large organ and is still accomplished through open surgery — as opposed to kidneys, for example, which can be procured laparoscopically — complications for living liver donors and recipients are more likely. About one-third of both groups suffer some

EXPANDED

| CLINICAL SERVICES |

“More living donations could help save greater numbers of the 17,500 U.S. patients waiting for a liver.”

- Benjamin Philosophe, M.D.

kind of post-operative problem, such as blood clots or infections, which are generally treatable. The mortality rate for donors is exceedingly low though, at less than 0.5%, Dr. Philosophe notes. Still, the ever-present risks are always on physicians’ and recipients’ minds, even if donors are focused solely on saving their loved one’s life.

Fortunately, the vast majority of both donors and recipients go back to their normal lives after weeks of recovery, and those with new livers can expect to live a normal lifespan, Dr. Philosophe says. For the young woman whose transplant kicked off UMMC’s recertification, her operation represented not only a second chance at life, but a very generous gift from her boyfriend.

To learn more, call 410-328-3444 or visit www.umm.edu/livingliver.

Contact OneCall at 1-800-373-4111 at any time to arrange a physician consult or to transfer a patient.

ROUNDING OUT Care and Research ACUTE CARE EMERGENCY SURGERY SERVICES

The primary mission of the Acute Care Emergency Surgery (ACES) Service at the R Adams Cowley Shock Trauma Center is to provide timely surgical assessment, operative and/or non-operative management of the acutely ill, non-trauma surgical patient.

Under the leadership of Jose J. Diaz, Jr., M.D., professor of surgery, University of Maryland School of Medicine and chief of acute care surgery, R Adams Cowley Shock Trauma Center, ACES is staffed 24/7 by an experienced team versed in a wide spectrum of disease states, ranging from routine and complex presentations of appendicitis, cholecystitis, bowel obstruction with or without incarcerated hernia, to skin and soft tissue infections.

The ACES service is also capable of caring for the most complex surgical diseases, such as severe pancreatitis, perforated peptic ulcers, mesenteric ischemia, complicated diverticulitis, intestinal fistulas, complex ventral hernias, bowel perforation or infarction and the acute surgical abdomen. The ACES service is even equipped to accept patients directly from the operating room should the need arise. ACES is easily accessible through University of Maryland ExpressCare at 410-328-1234.

PEDIATRIC ECMO NOW AVAILABLE

The University of Maryland Children’s Hospital recently established a Pediatric ECMO Program. Within the

pediatric intensive care unit, young patients, from newborns to young adults, now have access to life-saving cardiopulmonary support for such reasons as pneumonia, infections, congenital heart disease and asthma. To arrange to have a patient transferred or to quickly speak with a member of the ECMO team, call University of Maryland ExpressCare for Kids at 410-328-1234 or 1-800-373-4111.

WOMEN’S CENTER FOR

CONTINENCE AND PELVIC HEALTH

Women with pelvic floor disorders have a clinic to call their own! The University of Maryland’s Women’s Center for Continence and Pelvic Health recently opened on the downtown campus. A physician team of urogynecologists and urologists work together, providing comprehensive diagnostic and treatment services, to care for women who suffer from a range of pelvic floor disorders, including urinary incontinence and pelvic organ prolapse. Appointments can be made by calling 1-855-289-1508.

CARDIAC SURGERY WEBCAST AVAILABLE ONLINE

Log on to umm.edu/webcasts and watch as Teng Lee, M.D., assistant professor of surgery at the University of Maryland School of Medicine, performs a hybrid arch debranching operation. Aortic arch aneurysms are traditionally treated with open surgery, which involves | cont’d p14

Spring/summer 2012 |3

University of Maryland Completes Most Extensive Face Transplant To Date A talented team at the R Adams Cowley Shock Trauma Center at the University of Maryland recently completed the most extensive full face transplant to date, including both jaws, teeth and tongue. The 36-hour operation occurred in mid-March and was led

by Eduardo D. Rodriguez, M.D., D.D.S., associate professor of surgery at the University of Maryland School of Medicine and chief of plastic, reconstructive and maxillofacial surgery at the Shock Trauma Center.

The actual surgery involved a multidisciplinary team of faculty physicians from the University of Maryland School of Medicine and a team of more than 150 nurses and professional staff.

“We utilized innovative surgical practices and computerized techniques to precisely transplant the mid-face, maxilla and mandible including teeth and a portion of the tongue. In addition, the transplant included all facial soft tissue from the scalp to the neck, including the underlying muscles to enable facial expression, and sensory and motor nerves to restore feeling and function,” explains Dr. Rodriguez. “Our goal is to restore function as well as have aesthetically pleasing results.”

“This accomplishment is the culmination of more than 10 years researching the immune system’s response to vascular composite allograft transplants,” says Stephen

T. Bartlett, M.D., Peter Angelos distinguished professor and chair of the department of surgery at the University of Maryland School of Medicine and surgeon-in-chief at the University of Maryland Medical Center. “Our solid organ transplant immunosuppressive protocol has led to excellent outcomes for our patients and will be part of the longterm care plan for the face transplant patient.” The scientific team that included Drs. Bartlett, Rolf Barth and Rodriguez focused on the anatomic and immunologic challenges to craniofacial transplantation.

Grant funding from the Office of Naval Research (ONR) in the Department of Defense to Dr. Bartlett has supported the University of Maryland basic and clinical research program in vascularized composite transplantation that can mean face, hand or limbs. The ONR funds medical research to support military operational medicine and clinical care of returning veterans.

This face transplant was part of a 72-hour marathon of transplant activity following one anonymous family’s decision to donate their loved one’s organs. Ultimately five lives were saved. Four of the transplants from this one donor, including a heart and a liver transplant, took place over the course of two days at the University of Maryland Medical Center.

AFTER | RICHARD RECEIVED A NEW FACE, TEETH, TONGUE AND JAW IN THE MOST EXTENSIVE FACE TRANSPLANT EVER PERFORMED.

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BEFORE | THE FACE TRANSPLANT RECIPIENT, 37-YEAR-OLD RICHARD LEE NORRIS OF HILLSVILLE, VA., WAS INJURED IN 1997 IN A GUN ACCIDENT.

INNOVATION

| IN TRANSPLANTATION |

Transplant Team Enrolls First U.S. Patient in Novel Lung Trial Visionary leadership and synchronized teamwork propelled the University of Maryland Medical Center to the forefront of transplantation once again when the lung transplant team became the first in the country to use an experimental ex vivo lung perfusion technique in a clinical trial to repair donor lungs prior to transplantation.

“We are excited about the prospect of what this ex vivo, out-of-the-body perfusion technique could mean for our many transplant candidates who often spend years waiting for lungs to become available,” says the principal investigator, Bartley P. Griffith, M.D., professor of surgery at the University of Maryland School of Medicine and chief of cardiothoracic surgery at the University of Maryland Medical Center.

“This research is part of our ongoing goal to develop innovative procedures and rapidly improve our patients’ quality of life.”

THE GOAL: MORE TRANSPLANTABLE LUNGS Currently, only 15 to 20% of donor lungs are transplantable; most do not meet transplant criteria. According to the United Network of Organ Sharing, nearly 30 people in Maryland are waiting for a lung transplant. This new technique, if approved by the FDA, could increase the donor lung pool significantly and provide more transplantable lungs to the more than 1,700 candidates on the waiting list.

“Our OR staff and clinical trial program managers have studied the variables of this case inside and out so that when the opportunity presented itself to use this new ex vivo technique, our team didn’t miss a beat. We were able to repair the lungs to meet our high transplant standards

For more information, please call OneCall 1-800-373-4111.

“This research is part of our ongoing goal to develop innovative procedures and rapidly improve our patients’ quality of life.”

- Bartley P. Griffith, M.D.

and give this patient an option where she otherwise might have had none,” says Dr. Griffith.

HOW THE PROCESS WORKS Lungs in this clinical trial are recovered using current donor lung retrieval techniques. Once brought to the study transplant center, the lungs are reassessed by the transplant team. The lungs are then physiologically assessed during ex vivo perfusion with STEEN SolutionTM over a period of three to four hours.

During this time, the transplant team evaluates abnormalities inside the lungs, oxygenation levels and overall health of the lungs. At the end of the process, the transplant team determines if the lungs meet the high standards necessary for transplantation.

“Studies from other sites outside the U.S. have demonstrated that the results after transplantation | cont’d p8

Spring/summer 2012 |5

Advanced Fetal Care Giving Families Hope for the Future Many fetal abnormalities that not long ago were untreatable and often dire are now routinely and successfully managed with the specialized clinical expertise, technical resources and comprehensive approach to care found at the University of Maryland Center for Advanced Fetal Care.

The Center’s team of specialized physicians, perinatal nurses, genetic counselors and perinatal sonographers boasts many pioneering efforts internationally and nationally.

They were the first in North America to insert fetal bladder shunts and to perform intravascular fetal transfusions. They were the first in the mid-Atlantic region to be certified to conduct first-trimester nuchal translucency screening and the first in Maryland to perform ultrasoundguided, intrauterine laser surgery for twin-to-twin transfusion syndrome.

In all, they have

SUCCESSFULLY

conducted MORE THAN

3,000

INTRAUTERINE FETAL PROCEDURES.

“In Maryland and beyond, our Center is recognized and valued for its unmatched expertise in the care of perinatal complications,” says Christopher Harman, M.D., professor and interim chair, obstetrics, gynecology and reproductive sciences at the University of Maryland School of Medicine. “Through continuing education conferences we sponsor and through our consulting work with community physicians, patients increasingly are being referred to us

before pregnancy reaches a crisis stage.”

The leading-edge nature of the Center’s work is typified in its accomplishments with twin pregnancies, in which numerous complications can occur.

Underscoring the importance of this focus, Ahmet Baschat, M.D., professor of obstetrics, gynecology and reproductive sciences and director of the Center’s Section of Fetal Therapy, points out, “In the past 10 years, the rate of twin pregnancies has soared more than 400%, and among identical twins, up to 30% can exhibit a complication such as twinto-twin transfusion syndrome (TTTS).

Careful screening is imperative to detect an abnormality before it causes problems. Our Center has the diagnostic capabilities to make an early diagnosis and to determine whether therapy will be needed.”

LASER ABLATION FOR TWINTO-TWIN TRANSFUSION SYNDROME Identical twins sometimes share the same placenta, though most have their own amniotic sac (monochorionic/diamniotic). Lying between the fetuses’ zones is the “equator,” in which placental blood vessels interconnect and the twins exchange blood. Usually the exchange is balanced. In some cases, though, one fetus (donor) may lose blood in the exchange while the other fetus (recipient) gains it. TTTS occurs in 20% or more of mono/di pregnancies and requires constant monitoring. The diagnosis is often suspected as early as 12 weeks gestation.

Early signs of TTTS. With mono/di twins, the Center’s team intensifies monitoring every two weeks to detect the earliest signs of TTTS before it

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becomes problematic and thereby to help families and their physicians make informed decisions. Ultrasound and Doppler flow analysis can identify discordance in amniotic fluid volume, differences in fetuses’ physical size and increasing thickness of blood.

In receiving the greater proportion of blood, the recipient has too much water and too many blood cells.

The recipient excretes more urine, increasing the volume of surrounding amniotic fluid. The recipient’s blood increases not only in volume but in thickness, causing the heart to work overtime and, absent intervention, to become hypertrophic and stiff. The donor, on the other hand, receives too little fluid and too little blood that is also thin, resulting in reduced amniotic fluid, malnutrition and anemia as evidenced by fetal growth restriction (FGR).

Staging TTTS. Stage 1 TTTS is characterized by polyhydramnios in the recipient and oligohydramnios in the donor. In Stage 2, one fetus excretes urine constantly, while the other excretes none at all and its bladder is no longer filling. Stage 3 involves cardiovascular challenges to one or both fetuses. Stage 4 is when one fetus, usually the recipient, exhibits heart failure. Abnormal flow of blood to and from the heart is evident on Doppler ultrasound. Stage 5 involves the death of one fetus, usually the donor. The recipient may be injured further at Stage 5 by losing blood into its dead twin, resulting in permanent brain, heart or other organ damage. When TTTS occurs earlier in pregnancy (as it often does) outcomes are usually poor.

Intervention. Increasing amniotic fluid around the recipient twin distends the uterus and can lead to preterm labor.

MATERNAL/

| FETAL CARE |

Until a few years ago, little could be done except to drain fluid in an attempt to delay premature delivery.

At times, this procedure paradoxically caused an even greater imbalance.

Today the optimal solution is laser coagulation used to interrupt the blood connections in the “equator” region and the proximal zones of shared circulation. Though some blood vessels can be identified with ultrasound, smaller ones may escape detection. However, a scope paired with the laser is just 2.2 mm in diameter (1.1 mm for early pregnancy), allowing for direct visualization of even the smallest vessels and areas of shared blood flow and mapping of the entire surface of the placenta.

Risk of ruptured membranes and other complications is also reduced with the use of such small-diameter instruments.

Circumstances likely to yield poor therapeutic results include TTTS that has reached Stage 4, or a donor whose size is 30% smaller than its co-twin. Options and prognoses are discussed thoroughly with parents. In extreme cases, eradicating the shared placental zone leads to the demise of the donor fetus. However, fetal discrepancies are seldom so extreme.

Outcomes have improved dramatically. The laser ablation technique is usually successful with the first attempt, creating a permanent separation in which there is little chance for the regrowth of small vessels. Close monitoring continues in the weeks following the procedure to observe for possible fluid imbalance. The donor usually recovers without residual damage and catches up with its twin. Cardiac sequelae in the recipient may heal before birth, but care after birth may also be needed. Today, at least one

DRS. AHMET BASCHAT AND CHRIS HARMAN (L. TO R.)

healthy baby survives in 80% to 90% of cases, and both babies do well in up to 70% of cases.

THE CENTER’S UNIQUE RESOURCES FOR FOLLOW-UP As delivery draws near, the Center coordinates ongoing care for infants with the Children Hospital’s Neonatal Intensive Care Unit and a team of neonatologists, pediatric cardiologists and pediatric surgeons. In contrast to centers that have pediatric-focused programs but lack full-range obstetric services, the Center for Advanced Fetal Care offers seamless care for both mother and child. It

is uniquely equipped to care for mothers throughout the perinatal and postpartum periods. With access to full maternal services, the Center has the infrastructure to successfully manage such issues as preterm labor, cervical shortening, ruptured membranes or maternal medical complications.

When there is any doubt about the well-being of a pregnancy, the Center for Advanced Fetal Care can help provide the best possible treatment.

To learn more, call 410-328-3865.

Spring/summer 2012 |7

University of Maryland Scientists Spearhead Stroke Drug Research University of Maryland School of Medicine scientists will be submitting a grant application to the National Institutes of Health to test a commonly used diabetes medication — which has shown great promise in preventing the often-fatal brain swelling accompanying large strokes — in a new nationwide clinical trial network.

In preliminary research led by Kevin Sheth, M.D., assistant professor of neurology, an intravenous version of the diabetes drug glyburide, which blocks a channel in the brain that can lead to devastating cerebral edema in the hours after a sizable stroke occurs, was given to patients at high risk for brain swelling.

The pilot study of IV glyburide, or RP-1127, was based on the discoveries of J. Marc Simard, M.D, Ph.D., a University of Maryland professor of neurosurgery, pathology and physiology. Dr. Simard’s research, published in leading journals such

as Nature Medicine and Stroke, has shed light on the fundamental understanding of edema formation after acute brain injury. His novel discoveries in molecular medicine form the basis for the Glyburide Advantage in Malignant Edema and Stroke (GAMES) pilot study, as well as parallel work in traumatic brain injury. Dr. Sheth’s clinical group, which includes University of Maryland Professor of Neurology Barney J. Stern, M.D., partnered with Massachusetts General Hospital in Boston, Rush Medical Center in Chicago, the University of Pittsburgh, the Medical University of South Carolina and Remedy Pharmaceuticals to test IV glyburide in 10 patients in the pilot study. Remedy Pharmaceuticals is the exclusive licensee of Dr. Simard’s inventions and has previously demonstrated safety in a phase I study in healthy volunteers.

NOVEL, SAFE AND EXCITING “We’re excited for a number of reasons: RP-1127 is a novel therapy, appears to be safe and the preliminary

results are very encouraging,” says Dr. Sheth, the research’s principal investigator, who also holds faculty appointments in neurosurgery and emergency medicine. “All of a sudden, in less than a decade, as a direct result of Dr. Simard’s work, we have a new target for which there has previously been no effective drug therapy — brain edema. This work is exciting because we are hoping to translate a novel basic science discovery to a group of patients who otherwise have a dismal outcome.”

Indeed, cerebral edema strikes approximately 10% to 12% of the 795,000 Americans afflicted by stroke every year — a complication, when severe, with a 60% to 80% mortality rate. Until now, the only effective therapy leading to improved survival in this population has been the surgical removal of a portion of the skull, which can relieve internal pressure but may leave patients neurologically disabled. Brain swelling can complicate many serious conditions, such as traumatic brain

Transplant Team Enrolls First U.S. Patient in Novel Lung Trial | cont’d from p5 using this ex vivo technique were at least as good as lungs that had not required perfusion,” says Griffith.

“These findings, plus the expertise from within our own center, give me great confidence in the future use of this ex vivo perfusion technique as an option to potentially increase our pool

of transplantable lungs and reduce long wait times for our transplant candidates.”

Other hospitals participating in the trial include Duke University, Columbia University Medical Center, Brigham and Women’s Hospital and the University

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of Colorado. For more information on lung transplantation, please contact Senior Thoracic Transplant Coordinator Janine Zoch at 410-328-2948 or jzoch@smail.umaryland.edu.

STROKE

| DRUG RESEARCH |

excited. But the study isn’t blinded and we have no comparison group.”

BIG TRIALS AHEAD

KEVIN SHETH, M.D.; MARC SIMARD, M.D.; KAREN YARBROUGH, M.S., A.C.N.P.; AND BARNEY STERN, M.D. (L. TO R.)

injury (TBI), encephalitis or cerebral hemorrhage, all of which may someday benefit from IV glyburide’s effects, Dr. Sheth says.

Glyburide receptors appear to be present on many cell types involved in stroke, including neurons, glia and endothelial cells, and the drug blocks a sodium channel in the brain that allows water to permeate brain cells and blood vessel linings. Preventing this swelling, which can compromise blood flow to surrounding tissues, increase clot damage and cause death, is far preferable to performing invasive procedures to relieve brain pressure after the fact, Dr. Sheth says.

THE GAMES PILOT In the GAMES pilot, Dr. Sheth and his team evaluated the safety and feasibility of a three-day infusion of IV glyburide on 10 patients under age 80 within 10 hours of stroke onset. Patients qualified if they presented with severe clinical deficits as measured by the NIH Stroke Scale and if an MRI calculated the size of their stroke infarct as 82 cubic centimeters or larger — patients considered at high risk for cerebral edema.

None of the patients developed low blood sugar from the diabetes drug — which could have been dangerous for brain function — and with one patient death, mortality has been lower than expected, Dr. Sheth says. Also, the majority of enrolled patients did not require surgical removal of the skull, ventilator assistance or the use of other anti-brain swelling medications.

Daily MRI studies during treatment showed that patients experienced less swelling, smaller stroke size and less brain bleeding when compared to prior patients with similarly large strokes.

Patients were not excluded from participating if they had received the clot-busting drug tPA (tissue plasminogen activator) — which increases the risk of brain hemorrhage — and Dr. Sheth says glyburide may actually enhance the safety of tPA since it may also reduce the incidence of cerebral bleeding.

“Then we’d be talking about a broad, major public health phenomenon,” he says. “Primarily (however), this study demonstrates feasibility and safety. Because the results are so dramatic to those of us who care for these critically ill patients, we’re very

With that cautionary note in mind, Dr. Sheth is enthusiastic about the drug’s prospects during the next phase of trials. It is the first proposed stroke and neuro-critical care study accepted by the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) new nationwide clinical trial network, NeuroNEXT, which aims to facilitate the rapid development and implementation of clinical studies in neurological disorders. Dr. Sheth and Dr. Stern will be co-principal investigators along with Gregory del Zoppo, M.D., of the University of Washington School of Medicine.

The randomized, double-blinded NeuroNEXT trial of glyburide will enroll approximately 170 patients in 25 to 30 research centers across the country and focus on signs of clinical and neuroimaging efficacy, Dr. Sheth says. “These are incredibly sick patients and it requires a multidisciplinary approach with neurosurgeons, neurologists and critical care specialists,” he says. “It makes it more satisfying to have everyone at the table working together.”

To learn more about the research, call 410-328-5803 or visit www.remedypharmaceuticals.com/ clinicaltrials.htm.

Website not belonging to this organization is provided for information only. No endorsement is implied.

Spring/summer 2012 |9

Changes within the MICU Mean Lives Saved The idea that tens of thousands of lives might be saved each year if intensive care units made the right investments has gained credence among critical care experts in recent years. Organizations like the American College of Critical Care Medicine and the Leapfrog Group, publishers of a national comparison of patient safety at various hospitals, had called for changes in facilities and staffing levels, but no unit had studied the impact of putting all of the new ideas into practice.

DRS. CARL SHANHOLTZ, JEFFREY HASDAY AND GIORA NETZER. (L. TO R.)

So when it came time to move into a new space to meet a growing regional need, the Medical Intensive Care Unit (MICU) at the University of Maryland Medical Center (UMMC) set out to achieve a best-in-field staffing model as it moved into a cutting-edge facility.

The MICU went from daytime-only physician staffing to 24/7 coverage by physicians specializing in critical care medicine (intensivists), daily coverage by dedicated clinical pharmacists and a lower ratio of respiratory therapists to patients. After the move, the team

saw that the changes were saving lives, and decided a formal study1 was needed to measure the combined worth of the interventions.

What they found when comparing the two years before and after the move was that mortality had dropped by an astounding 19%. The number is more remarkable considering that the “old” ICU was already a Leapfrog-compliant tertiary care unit with a high-intensity staffing model and best practices in place. According to the study authors, the adoption by all U.S. urban ICUs of both the Leapfrog criteria and added changes captured in the MICU study could potentially save 70,000 lives each year.

“In an ICU where people arrive severely ill for many reasons, it is terribly difficult to make changes that all at once increase survival across all patients,” says principal investigator Giora Netzer, M.D., a pulmonologist and critical care specialist at the University of Maryland Medical Center who is an assistant professor of medicine, epidemiology and preventive medicine at the School of Medicine. “Even the arrival of a powerful new drug does not always move the needle on mortality, so you can see why we are so excited.”

REAL WORLD IMPACT Published online in Critical Care Medicine in November 2010, the MICU study was a single-center, retrospective and observational study.

It compared the outcomes of 1,263 patients admitted to the medical center between April 19, 2004, and April 18, 2006, before the move to new quarters, to those of 2,424 patients admitted between Sept. 5, 2006, and Sept. 4, 2009, after the changes. There were no differences in patients admitted before and after the

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move in terms of gender, co-existing illnesses, risk factors or expected intensity of care.

In its new setting, the MICU supported 24-hour intensivist staffing and daily, bedside case review by multidisciplinary teams (intensivist, nurse manager, pharmacist and respiratory therapist). The joint teams worked to reduce sedation where possible and move patients off of respirators more quickly, both of which have been shown to reduce complications, infections and mortality. The nursing practice was expanded as well with the move to a larger facility, but because it was already among the best before the move — achieving Magnet status for nursing excellence — it was not highlighted in the study.

Along with a 19% relative reduction in MICU mortality, the authors found that the study interventions had decreased mortality by 16% hospital-wide during the study, arguing that the measures had a durable benefit (did not result from shifting mortality from one part of a patient’s hospital stay to another). Improved survival came with a 5% increase in ventilator-free days (VFDs) and a significant decrease in the use of sedative medications, both of which contributed to the improved outcomes.

The average length of stay for the MICU actually increased after the move, leading to speculation that, by living longer, patients spent more time on the unit. While the current study was not designed to determine which component in the multi-component package was most responsible for decreased mortality, some 20 studies had suggested that each individual intervention had some value.

MEDICAL

| INTENSIVE CARE |

“The study simply looked at whether driving staffing levels higher than the highest standard as we moved into a new facility could make a superior ICU better,” says Jeffrey D. Hasday, M.D., head of the division of pulmonary and critical care medicine at the Medical Center and professor of medicine at the School of Medicine. “What we found was that the study interventions achieved greater increases in survival even than previously estimated in studies of traditional, high-intensity physician staffing. We believe the study results should inspire a national conversation about targeted investments needed in ICUs to save more lives.”

Among the study’s limitations was that it had to be conducted as a before-and-after study rather than a randomized clinical trial. While the possibility that random case mix differences could have contributed to the drop in mortality cannot be completely eliminated, the team conducted a set of statistical analyses (e.g., Wilcoxon ranksum test, statistical regression), which confirmed that the observed reduction in mortality was not random.

The authors’ excitement about the results was also tempered by realization that they will not be applicable to every ICU. Some will not have the resources to change their physical plants and staffing levels. One solution may be to start by ensuring that each region has at least one center of excellence capable of delivering care at this level.

Another limit on the study’s potential impact on emergency medicine is a profound nationwide shortage of intensivists. According to the

A LARGER MOVEMENT

What they found when comparing the two years before and after the move was that mortality

had dropped by

an astounding

19%.

The number is more remarkable considering that the “old” ICU was already a Leapfrogcompliant tertiary care unit with a high-intensity staffing model and best practices in place.

Leapfrog Group, there are not enough to cover even every major urban ICU 24/7, let alone all ICUs, but the problem could be fixed in four years if their training became a national priority. UMMC seeks to do its part to address the problem with multiple training programs in place for medical, surgical and pulmonary care intensivists.

The MICU study serves as a case study for the value of larger patient safety efforts at UMMC, which is one of only two hospitals in the nation to be named to the Leapfrog Group’s list of top hospitals for patient safety and quality care for the sixth year in a row.

A growing culture of quality was coalescing at the Medical Center at the time of the move. The MICU leadership had already decided that it wanted to provide better compensation and training to address staffing shortages that were in place before a proposed expansion made them more urgent.

The team also decided to re-focus on professionalism, by shifting from temp workers to full-time staffing and by placing a premium on professional development. One measure of the success of this effort is the steady stream of journal publications now emanating from the medical center’s 11 ICUs. “There was a shared vision between the Medical Center and School of Medicine that we were going to do this right from the start with the new MICU,” says Associate Professor of Medicine Carl Shanholtz, M.D., study co-author and medical director of the MICU. “What started as an examination of staffing needs around an expansion became a determination to conduct an experiment in quality, to rethink staffing as a factor affecting quality of care.”

Netzer G, Liu X, Shanholtz C, Harris A, Verceles A, Iwashyna TJ. “Decreased mortality resulting from a multicomponent intervention in a tertiary care medical intensive care unit.”Critical Care Medicine. Published online ahead of print November, 2010. doi:10.1097/ CCM.0b013e3181ffdd2f.

1

Spring/summer 2012 |11

Congenital Heart Program The University of Maryland Children’s Heart Program provides a continuum of care for patients with congenital heart disease from birth through adulthood. This unique approach allows patients to be seen by a team of physicians in the same facility, providing exceptional care to infants, adolescents and adults.

Highly respected for its medical and surgical techniques, the Congenital Heart Program strives for excellent outcomes, reduced mortality and enhanced quality of life for its patients. The program’s cutting-edge technology and the vast expertise of its physicians — all of whom are University of Maryland School of

Medicine faculty members — make it a distinguished leader in congenital heart disease care.

Stacy Fisher, M.D., exemplifies the high level of expertise among Congenital Heart Program physicians. She is an assistant professor of medicine, specializing in women’s heart health, as well as adolescent and adult heart patients. Dr. Fisher’s clinical specialties include echocardiology, adult congenital heart disease, heart disease during pregnancy and pulmonary hypertension.

PROACTIVE APPROACH “The collaborative and expanding nature of the program, including pediatrics, cardiology, adult cardiology and cardiac surgery, sets

the Congenital Heart Program apart from other programs,” says Dr. Fisher.

“I’m proud of our multidisciplinary approach that provides better outcomes for our patients.”

ENHANCED SCREENING AND INTERVENTIONAL CARE There are many genetic causes of congenital heart disease, including Marfan syndrome, arrhythmia, hypertrophic cardiomyopathy and aneurysm. The Cardiogenetics Clinic allows increased diagnostic accuracy for possible patients and can thoughtfully guide genetic testing and screening for first-degree relatives of patients to detect potential problems. Using EKG, echocardiology, arrhythmia monitoring, cardiac CT or MRI, and/or genetic testing when appropriate, physicians look for associated problems in family members in an effort to reduce associated sudden death.

“Our multidisciplinary approach includes interventional catheter based care, arrhythmia management, electrical physiology assessment and care, imaging and genetics,” says Dr. Fisher. “We’re also proactive in screening and managing our pregnant patients who have known structural heart disease, arrhythmias or underlying clotting problems so we can anticipate problems before they occur.”

The Congenital Heart Program also offers congenital heart surgery from neonatal patients to adults.

Surgical procedures range from correcting heart physiology to heart transplantation.

DR. SUNJAY KAUSHAL TREATS A BABY WITH CONGENITAL HEART DISEASE.

|12 on a mission | OneCall 1-800-373-4111

“By correcting heart physiology, we can reduce the consequences and suffering from complications of congenital heart disease,” says pediatric cardiothoracic surgeon, Sunjay Kaushal, M.D., associate

| CARDIAC CARE | University of Maryland Children’s Hospital professor of surgery. “In the past 15 years we’ve moved into a new phase in caring for congenital heart disease patients by looking at long-term and quality of life outcomes.”

Dr. Kaushal, the only pediatric cardiac surgeon who is board certified in congenital heart surgery in Maryland, believes enhancing patients’ quality of life and ability to contribute to society is a huge change. This has been made possible, in part, by altering surgical methods and manipulating the cardiopulmonary bypass machine to improve clinical outcomes including the impact on intelligence and behavior issues.

PROMISING STEM CELL THERAPIES Hypoplastic left heart syndrome is a rare congenital heart defect in which the left ventricle is severely underdeveloped, and the right ventricle serves as the pumping chamber for systemic circulation.

Stem cells from the patient’s own heart can be used to improve right heart function in these patients.

Dr. Kaushal has been exploring novel therapies to treat underdeveloped cardiac chamber disease using resident cardiac stem cells to help patients regrow heart tissue. Early studies have shown the safety, feasibility and efficacy of this potentially breakthrough therapy.

Application of these stem cells hasn’t been explored in pediatric patients who exhibit different causes including myocardial ischemia and cardiomyopathy.

“I hope to obtain IRB and FDA approval to conduct Phase I clinical trials within three months,” says Dr. Kaushal. “We would be the first in the world to do this type of surgery, and it will make the University of Maryland very unique in the world for treating heart failure in children.”

The Children’s Heart Program at University of Maryland Children’s Hospital was designed with an emphasis on treating the entire range of cardiac disorders from the most common to the most severe conditions. The Children’s Heart Program offers a comprehensive spectrum of services, including clinics oriented to treat children with blood lipid abnormalities and hypertension, and a hybrid catheterization suite that allows complex treatments that can’t be performed in other institutions.

“We’ve recruited experts ranging from congenital heart surgeons to pediatric and interventional cardiologists who can work together to address the most complex needs of congenital heart patients,” says Geoffrey Rosenthal, M.D., professor of pediatrics and director of the Children’s Heart Program at the University of Maryland Children’s Hospital. “Our staff can perform the most cutting-edge surgical and catheter approaches in a hybrid surgical suite to achieve results that can’t be realized with one approach alone.”

According to Dr. Rosenthal, approximately 3% of the 4 million infants born in the United States each year have a birth defect. Congenital heart disease is the most common of these, occurring in about 1 in 110 births, affecting nearly 40,000 infants annually in the United States.1-4 Approximately 75% of all serious congenital heart disease is identified before birth.

Following a screening test, pregnant mothers are referred to the University of Maryland Medical Center’s Center for Advanced Fetal Care and/or the Children’s Hospital for diagnostic work to address structural heart abnormalities.

“I’m very proud of the way people at all levels of our institution and community have come together to meet the needs of these children,” says Dr. Rosenthal.

“We’ve achieved outstanding outcomes caring for children with the highest risk of complications and mortality. University of Maryland Children’s Hospital is operating at a level that far exceeds the national average.”

To learn more, call Physician OneCall at 1-800-373-4111 or visit www.umm.edu.

Sources: eller MD, Strickland MJ, Riehle-Colarusso T, Mahle WT, Correa A. “Prevalence of congenital heart R defects in metropolitan Atlanta, 1998-2005.” J Pediatr. 2008 Dec;153(6):807-13.

1

offman JI, Kaplan S. “The incidence of congenital heart disease.” J Am CollCardiol. 2002 Jun H 19;39(12):1890-900.

2

arin JA, Hamilton BE, Ventura SJ, Osterman M, Kirmeye S, Mathews TJ, et al. “Births: Final data for M 2009.” Atlanta, GA: National Center for Health Statistics, Centers for Disease Control and Prevention; 2011.

Available from: http://www.cdc.gov/nchs/fastats/births.htm.

3

oller JH, Taubert KA, Allen HD, Clark EB, Lauer RM. “Cardiovascular health and disease in children: M current status.” A Special Writing Group from the Task Force on Children and Youth, American Heart Association. Circulation. 1994 Feb;89(2):923-30.

4

For appointments with the Children’s Heart Program, please call 410-328-6749. For all other inquiries, call 410-328-4FIT (4348).

You may also email cardiology@peds.umaryland.edu.

Spring/summer 2012 |13

| MEDICAL RESEARCH |

Rounding Out Care and Research | cont’d from p3 putting the patient on a heart-lung machine, temporarily stopping blood flow to the head and body.

The hybrid arch debranching repair is less invasive than the traditional surgery and has a lower risk. In fact, the hybrid arch debranching approach has dramatically lowered the morbidity and risk of total arch replacement for aortic aneurysms.

During surgery, the aortic arch is ‘de-branched’ by sewing bypass grafts to the aortic arch blood vessels, and then an endograft is placed to seal off the aneurysm. With this operation, there is no need for the heart-lung machine and circulatory arrest.

The hybrid arch debranching procedure is ideal for a patient who has multiple medical issues (such as diabetes or high blood pressure) in addition to a thoracic aortic aneurysm and is considered too high-risk for a traditional operation. The hybrid arch debranching surgery allows patients to undergo a bypass and endograft in the same procedure, reducing their hospital stay and improving their chances at long-term success.

TURN DOWN THE VOLUME Serious injuries to pedestrians listening to headphones have more than tripled in the past six years, according to new research from the University of Maryland School of Medicine and the University of Maryland Medical Center. In many cases, cars or trains are sounding horns that pedestrians cannot hear, leading to fatalities in nearly threequarters of cases.

“Everybody is aware of the risk of cell phones and texting in automobiles, but I see more and more teens

distracted with the latest devices and headphones in their ears,” says lead author Richard Lichenstein, M.D., associate professor of pediatrics at the University of Maryland School of Medicine and director of pediatric emergency medicine at the University of Maryland Medical Center.

“Unfortunately, as we make more and more enticing devices, the risk of injury from distraction and blocking out other sounds increases.”

Dr. Lichenstein and his colleagues studied retrospective case reports from the National Electronic Injury Surveillance System, the U.S. Consumer Product Safety Commission, Google News Archives and Westlaw Campus Research databases for reports published between 2004 and 2011 of pedestrian injuries or fatalities from crashes involving trains or motor vehicles.

Cases involving headphone use were extracted and summarized. The research was published online on Jan. 16 in the journal Injury Prevention.

Researchers reviewed 116 accident cases from 2004 to 2011 in which injured pedestrians were documented to be using headphones. Seventy percent of the 116 accidents resulted in death to the pedestrian. More than two-thirds of victims were male (68%) and under the age of 30 (67%).

More than half of the moving vehicles involved in the accidents were trains (55%), and nearly a third (29%) of the vehicles reported sounding some type of warning horn prior to the crash.

The increased incidence of accidents over the years closely corresponds with the documented rising popularity of auditory technologies with headphones.

|14 on a mission | OneCall 1-800-373-4111

LISA SHULMAN, M.D.

PARKINSON’S PATIENTS AND EXERCISE Researchers from the University of Maryland School of Medicine and the Baltimore VA Medical Center found that Parkinson’s patients who walked on a treadmill at a comfortable speed for a longer duration (low-intensity exercise) improved their walking more than patients who walked for less time but at an increased speed and incline (high-intensity exercise). The investigators also found benefits for stretching and resistance exercises.

“Our study showed that lowintensity exercise performed for 50 minutes three times a week was the most beneficial in terms of helping participants improve their mobility.

Walking difficulty is the major cause of disability in Parkinson’s disease.

These results show that exercise in people with Parkinson’s disease can make a difference in their function.

Exercise may, in fact, delay disability and help to preserve independence,” says Lisa Shulman, M.D., principal investigator and professor of neurology at the University of Maryland School of Medicine. Appointments for movement disorders may be made by calling 410-328-4323.

New Leaders within University of Maryland University of Maryland School of Medicine Dean E. Albert Reece, M.D., Ph.D., M.B.A., has appointed Anthony F. Lehman, M.D., M.S.P.H., as the new senior associate dean for clinical affairs. In this new role, Dr. Lehman — professor and chair of the department of psychiatry — works closely with the University of Maryland Medical Center, the University of Maryland Medical System, the Baltimore VA Medical Center and the medical school’s faculty practice. Initially, he will continue serving as professor and chair of psychiatry, pending a national search for a new psychiatry chair.

In his new position, Dr. Lehman will lead the School of Medicine’s clinical initiatives and develop strategies for the clinical mission for both inpatient and outpatient services. He will explore new program developments and work to create new initiatives to enhance the School of Medicine’s clinical affairs effort. He will closely collaborate with partners to strengthen clinical care within the entire medical enterprise.

Dr. Lehman joined the University of Maryland School of Medicine as an associate professor of psychiatry in 1986 and became a professor of psychiatry in 1994. He was named acting chair of the department of psychiatry in 1998 and chair in 2000.

Dr. Lehman replaces Frank M. Calia, M.D., M.A.C.P., who retired after 42 years at the School of Medicine.

John A. Olson, Jr., M.D., Ph.D., has been appointed the new head of the division of general and oncologic surgery within

the University of Maryland Medical Center’s department of surgery.

Dr. Olson is also the Campbell and Jeanette Plugge Professor and vice chair of the department of surgery in the University of Maryland School of Medicine.

Dr. Olson is a nationally respected surgeon-scientist who specializes in endocrine and oncologic surgery with an emphasis on cancer of the parathyroid glands, thyroid and breast. His NIH-funded laboratory focuses on parathyroid disease, and he recently was awarded a NIH R01 grant to study molecular mechanisms of altered calcium sensing in human parathyroid disease.

His clinical research interests include development of biomarkers for breast cancer and the study of aromatase inhibitor therapy to improve surgical outcomes for post-menopausal women with breast cancer. Dr. Olson will continue to lead progressive research initiatives to address endocrine tumors and breast cancer in his new role.

Dr. Olson joins the University of Maryland from Duke University Medical Center, where he was chief of the section of endocrine, breast and oncologic surgery. He received his M.D. and Ph.D. in pharmacology and experimental therapeutics from the University of Florida. He received his general surgery training at Washington University in St. Louis and completed a surgical oncology fellowship at Memorial SloanKettering Cancer Center in New York.

Appointments with Dr. Olson may be scheduled at 410-328-1147. His academic office can be reached at 410-328-6187. Dr. Olson’s cell phone is 919-812-6148.

Patricia Shearer, M.D., is the new division head of pediatric hematology/ oncology at the University of Maryland Children’s Hospital and professor of pediatrics at the University of Maryland School of Medicine.

Dr. Shearer came to Baltimore from the University of Florida, Gainesville, where she was a faculty member and served as the director of the Cancer Survivor Program for Survivors of Childhood, Adolescent, and Adult Malignancies at the University of Florida Shands Cancer Center. Right now, Dr. Shearer is developing a cancer survivorship program at the University of Maryland.

With 80% of children expected to survive cancer, this program provides clinical care, education and research for pediatric and young adult survivors in accordance with evidence-based guidelines. It monitors late effects of cancer, such as vital organ function and hormonal issues, while keeping up with emotional and academic progress of young survivors.

Dr. Shearer received her medical degree from Louisiana State University School of Medicine. She completed her pediatric residency at Johns Hopkins and a fellowship at St. Jude Children’s Research Hospital in Memphis. She has published extensively on late effects of a variety of pediatric solid tumors, including Wilms tumor, thyroid carcinoma and acute myeloid leukemia. Her clinical interests include: sarcoma, germ cell tumors and neuroblastoma, as well as Wilms tumor.

To be in touch with Dr. Shearer or to schedule an appointment, please call 410-328-2808.

Spring/summer 2012 |15

Upcoming

CME Programs Offered by the University of Maryland School of Medicine in conjunction with University of Maryland Medical Center.

>> 4 TH ANNUAL GI CANCER

NON PROFIT US POSTAGE PAID University of Maryland Medical Center

22 South Greene St. Baltimore, MD 21201 OneCall 1-800-373-4111

SYMPOSIUM SEPT. 28

The 4th Annual GI Cancer Symposium will feature faculty from the University of Maryland School of Medicine who are distinguished in the fields of surgical oncology, medical oncology, radiation oncology, gastroenterology and interventional radiology. The series of lectures and discussion will focus on current issues of interest for physicians and other healthcare providers involved in the care of patients with various types of GI cancers.

>> F OCUS ON FETAL HEART OCT. 5 At the Center for Advanced Fetal Care at the University of Maryland Medical Center, there have been cases of complicated twin pregnancies referred nationally and internationally. This program will feature distinguished faculty from the University of Maryland School of Medicine who will provide an overview of the focused evaluation of monochorionic twins and the focus of the fetal heart. Diagnostic criteria, management options, and prenatal and postnatal outcomes will be discussed in live panel interaction with the audience.

>> 1 0TH ANNUAL BREAST

CANCER UPDATE OCT. 26

University of Maryland Rounds is a publication of the University of Maryland School of Medicine and the University of Maryland Medical Center.

E. ALBERT REECE, M.D., PH.D., M.B.A. Vice President for Medical Affairs University of Maryland John Z. and Akiko K. Bowers Distinguished Professor and Dean University of Maryland School of Medicine

JEFFREY A. RIVEST, F.A.C.H.E. President and Chief Executive Officer University of Maryland Medical Center

ADVISORY BOARD

STEPHEN T. BARTLETT, M.D.

The 10 Annual Breast Cancer Update will feature distinguished faculty from the University of Maryland School of Medicine. This group will present topics based on a multi-disciplinary focus that entails prevention, diagnosis and treatment that has led to significant strides in the reduction of breast cancer incidence and mortality.

It has become more evident that a multi-disciplinary team approach that involves a spectrum of breast experts is necessary to provide optimal care to patients.

Peter Angelos Distinguished Professor and Chairman, Department of Surgery University of Maryland School of Medicine Surgeon-in-Chief, University of Maryland Medical System

>> I BD SYMPOSIUM NOV. 9

Professor and Chair, Department of Pediatrics University of Maryland School of Medicine Physician-in-Chief, University of Maryland Children’s Hospital

th

Inflammatory bowel disease (IBD), comprised of ulcerative colitis and Crohn’s disease, affects approximately 1.4 million patients in the United States. This one-day symposium featuring faculty from University of Maryland School of Medicine, as well as expert panelists from visiting medical schools, will highlight the diagnosis and management of patients with these disorders.

All events will be held at the Southern Management Campus Center located at: 621 W. Lombard Street, Baltimore, MD 21201 All events offer CME credit. For details and registration, please visit: https://cmetracker.net/UMD/Catalog Approved for AMA PRA Category 1 Credits™. Sponsored by University of Maryland School of Medicine.

MAY H. BLANCHARD, M.D.

Associate Professor of Obstetrics, Gynecology and Reproductive Sciences University of Maryland School of Medicine

STEVEN J. CZINN, M.D., F.A.A.P., F.A.C.G., A.G.A.F.

STEPHEN N. DAVIS, M.B.B.S., F.R.C.P., F.A.C.P.

Theodore E. Woodward Professor of Medicine Professor of Physiology Chairman, Department of Medicine University of Maryland School of Medicine Physician-in-Chief, University of Maryland Medical Center

JANINE L. GOOD, M.D.

Associate Professor of Neurology University of Maryland School of Medicine Medical Director, Ambulatory Services University of Maryland Medical Center

JONATHAN GOTTLIEB, M.D.

Senior Vice President and Chief Medical Officer University of Maryland Medical Center Clinical Professor of Medicine University of Maryland School of Medicine

ANTHONY F. LEHMAN, M.D., M.S.P.H. Senior Associate Dean for Clinical Affairs Professor of Psychiatry University of Maryland School of Medicine

MOHAN SUNTHA, M.D.

Vice Chairman/Clinical Director Department of Radiation Oncology Professor, University of Maryland School of Medicine Associate Director of Clinical Affairs University of Maryland Marlene and Stewart Greenebaum Cancer Center

DEBORAH M. STEIN, M.D., M.P.H., F.A.C.S., F.C.C.M. Associate Professor of Surgery University of Maryland School of Medicine Medical Director, Neurotrauma Critical Care Chief, Section of Trauma Critical Care R Adams Cowley Shock Trauma Center

WILLIAM E. TUCKER, M.B.A., C.P.A.

Assistant Dean for Practice Plan Affairs University of Maryland School of Medicine Chief Corporate Officer, Faculty Physicians, Inc.

This publication does not constitute professional medical advice. Although it is intended to be accurate, neither the publisher nor any other party assumes liability for loss or damage due to reliance on this material. Images may be from one or more of these sources: ©Thinkstock, ©iStock, ©Fotolia. ©2012 The University of Maryland Medical Center.