NewYork-Presbyterian Columbia ORthopaedics February 2013

Development of Computer-Modeling Software Predicts Glenoid Erosion After Total Shoulder

ariances in the degree of glenoid erosion from patient to patient arguably present surgeons performing total Vshoulder replacement surgery with their most significant clinical challenge. These variances also play an important role with regard to the long-term outcomes associated with the procedure. However, researchers at the Center for Shoulder, Elbow and Sports Medicine and the Center for Orthopaedic Research’s Biomechanics Laboratory at NewYork-Presbyterian Hospital/Columbia University Medical Center are working jointly to develop computer-modeling software that will Computer modeling technology under development ultimately make this difficult procedure “easier and more at the Center for Shoulder, Elbow and Sports repeatable while improving outcomes,” according to Medicine and the Center for Orthopaedic Research’s Christopher S. Ahmad, MD, Director, Biomechanics Laboratory; Biomechanics Laboratory at NewYork-Presbyterian/ Director, Center for Pediatric and Adolescent Sports Medicine Columbia University Medical Center is able to simulate at NewYork-Presbyterian/Morgan Stanley Children’s Hospital; surgical procedures and provide surgeons with a and Associate Professor of Orthopaedic Surgery at Columbia roadmap they can use as a guide in total shoulder replacement surgery. The models also can be used as University College of Physicians and Surgeons. Dr. Ahmad a predictive tool, as they can recreate the workload a believes the new technology will become a routine part of replacement joint will face over its life span. preoperative preparation in total shoulder replacement at the Hospital within the next 2 to 3 years, which is significant given that it is the fastest-growing orthopaedic joint replacement glenoid erosion. Even with the latest in scanning technology, procedure (in terms of numbers) in the United States. surgeons still had difficulty selecting the right component “That’s the goal,” he said. “We have a long history here to repair the joint. Although failure rates with total shoulder when it comes to shoulder replacement surgery. This is just replacement have not been well studied and/or defined— the next phase of the evolution for us in terms of leading the primarily because failures may take years to occur—Dr. Ahmad way in innovation for the procedure.” said it is well known within the field that most failures are the NewYork-Presbyterian/Columbia was the Hospital where result of cracks due to pressure at the cement interface, where Charles S. Neer, MD, practiced, widely known as the “father of the replacement component is fastened to the joint. shoulder replacement” surgery, Dr. Ahmad noted. Dr. Neer’s Dr. Ahmad and his team, which includes mechanical techniques have been passed down through generations at engineers—specifically, Charlie Yongpravat, ME (a doctoral the Hospital, from Louis U. Bigliani, MD, who is Chief, Shoulder candidate in the Mechanical Engineering Department at Service, Center of Shoulder, Elbow and Sports Medicine at Columbia University) and Thomas R. Gardner, ME, of the the Hospital and Frank E. Stinchfield Professor and Chairman, Department of Orthopaedic Surgery—sought to develop Department of Orthopaedic Surgery, Columbia University a model that could map the effects of glenoid erosion and College of Physicians and Surgeons, and now to Dr. Ahmad. replicate the stress the replacement joint would be exposed Even the brilliant Dr. Neer, however, could never have to over the course of 10 to 20 years. The model used individual envisioned this latest development in the procedure, which patient data obtained from computed tomography and Dr. Ahmad believes will “give more orthopaedic surgeons the magnetic resonance imaging scans. Dr. Ahmad is mentoring confidence to perform total shoulder replacement.” the work of the 2 engineering students as they conduct their The idea for the project stemmed from Dr. Ahmad’s research and pursue their advanced degrees. undergraduate training at Columbia University, where he “Rather than experimenting on cadavers, which is majored in mechanical engineering. As an orthopaedic common practice in orthopaedics research, we started surgeon, Dr. Ahmad recognized the problems presented by See Technology, page 4 Genetics Research Across Medical Specialties Now Yielding Secrets and Improving the Practice of Medicine

The decoding of the human genome and subsequent concerted efforts by 1,983 individuals aged 66 to 101 years. physician-scientists to decipher the relationships between specific genes and These patients were followed for an the diseases they influence have already yielded tremendous advancements average of 8 years. After adjusting in medicine. This work is fostering important strides in understanding and for age and education, among other factors, researchers found that those caring for people with diseases affecting all health systems, and much of the individuals with shorter telomeres laboratory and translational studies, as well as clinical research, are being had higher rates of both dementia and done at Columbia University College of Physicians and Surgeons, Weill Cornell mortality. The researchers must now Medical College, and NewYork-Presbyterian Hospital. examine whether shorter telomeres directly increase the risk for dementia esearch abounds in every field. clinical factors such as Helicobacter and death, or if the telomeres are being Perhaps no area of medicine has pylori infection and use of nonsteroidal influenced by some other factor that is Rbeen as affected by research into the anti-inflammatory drugs; and genetic both shortening telomere length while genetic foundations of disease as factors including immune regulatory at the same time increasing dementia much as oncology. Examples of genetic single-nucleotide polymorphisms. A and mortality risk. discoveries in oncology are plentiful. second type, diffuse gastric cancer, Within psychiatry, schizophrenia An important recent discovery is is associated with CDH1 mutation has long been known to be genetic the revelation that certain cases of and family history and has no known in origin, but the networks of genes glioblastoma are caused by the fusion environmental or clinical factors. The involved in this disability have not of 2 genes.1 Researchers, led by Antonio third type, proximal gastric cancer, is been well characterized. A recent paper Iavarone, MD, Professor of Pathology caused by tobacco and alcohol use; published in Nature Neuroscience and Neurology at Columbia’s Institute has no known genetic link; and is found a link between schizophrenia for Cancer Genetics at the Herbert associated with obesity, high body mass and autism.4 Columbia researchers Irving Comprehensive Cancer Center index, and gastroesophageal reflux examined a collection of mutations at NewYork-Presbyterian/Columbia, disease. Dr. Shah’s work has alerted associated with schizophrenia and conducted genetic analyses of patients those performing drug clinical trials found occult interrelations among with glioblastomas, searching for that testing should be based on these genes that had previously been thought evidence of gene fusions. They found subtypes and not on gastric cancer to be unrelated. The researchers found them, with the most common being as a whole. Because of the genetic that most of the mutated schizophrenia fusions involving the fibroblast growth differences in subtypes, the effects of genes were related to 2 main gene factor receptor (FGFR1 or FGFR3) and drug therapy may vary significantly networks, which together affect key transforming acidic coiled-coil (TACC1 between groups. processes, including axon guidance, or TACC3) genes. The protein produced The field of geriatrics was intrigued synapse function, neuron mobility, and by the fusion of FGFR-TACC disrupts the by a study led by Columbia University chromosomal modification. mitotic spindle, causing aneuploidy, researcher Lawrence S. Honig, MD, The research, which was led by and from there tumorigenesis. The PhD, Professor of Clinical Neurology Dennis Vitkup, PhD, Associate Professor finding is important because it provides in the Taub Institute, an Alzheimer’s in the Department of Biomedical researchers with a protein target for disease research center funded by the Informatics at Columbia’s Center pharmaceutical research for a cancer National Institute on Aging.3 Dr. Honig’s for Computational Biology and that is especially difficult to treat. research found that telomere length Bioinformatics, also looked at genes Gastroenterologists have been relates both to the likelihood of the mutated in patients with autism and interested in recent work performed patient developing dementia and found the similarities were surprisingly by Manish Shah, MD, Director of his or her overall remaining life span. robust. Noting that the genetic Gastrointestinal Oncology at Weill This research could lead to the use networks for autism and schizophrenia Cornell Medical College, who with his of telomere length as an accurate are closely intertwined, the researchers colleagues elucidated the heterogeneity biomarker of aging in people, as well postulated that many other psychiatric of gastric cancer, dividing it into 3 as an early warning sign for future disorders also might share the same types.2 The first type, noncardia gastric dementia. genetic networks and interrelated cancer, is linked to environmental The researchers examined molecular processes. factors such as high dietary salt, telomere lengths from DNA samples Significant research on the tobacco use, and increasing age; of white blood cells obtained from genetics behind psychological illness

2 columbiaortho.org An important recent is being undertaken at Weill Cornell or a mental illness that will occur later discovery is the revelation Medical College. As just one example, in life. Francis S.Y. Lee, MD, PhD, Professor A co-author of this study that certain cases of and Vice Chair for Research in the was Wendy Chung, MD, PhD, the glioblastoma are caused Department of Psychiatry and Professor Director of Clinical Genetics at in the Department of Pharmacology, NewYork-Presbyterian Morgan by the fusion of 2 genes. who is also an Attending Psychiatrist at Stanley Children’s Hospital. Her Researchers, led by the Hospital, directs efforts focused on research interests span multiple areas, using genetic models to define the role including the molecular genetics Antonio Iavarone, MD, of growth factors, such as brain-derived of obesity and diabetes; congenital Professor of Pathology and neurotrophic factor, and their affect on heart disease; the genetic foundations the pathophysiology and treatment of of cardiomyopathies, arrhythmias, Neurology at Columbia’s affective disorders.5 long QT syndrome, and pulmonary Institute for Cancer Pulmonology has begun to hypertension; congenital diaphragmatic explore the use of gene-based vaccines hernias; mental retardation; inherited Genetics at the Herbert targeted against pulmonary infectious metabolic conditions; and susceptibility organisms. At Weill Cornell Medical to breast and pancreatic cancers. Irving Comprehensive College, a team led by Stefan Worgall, She is Director of the Pediatric Heart Cancer Center at MD, PhD, Division Chief of the Pediatrics Network Genetic Core, the Pediatric Pulmonology, Allergy and Immunology Neuromuscular Network Molecular NewYork-Presbyterian/ Division, has developed capsid-modified Core, the New York Obesity Center Columbia, conducted adenovirus vectors6,7 to heighten Molecular Genetics Core, and the immune responses from genetic Diabetes and Endocrine Research genetic analyses of vaccines against both Pseudomonas Center Molecular Genetics Core. She patients with glioblastomas, aeruginosa and respiratory syncytial also serves as Director of the Clinical virus. In research on the pathogenesis Cancer Genetics Program and the searching for evidence of of cystic fibrosis, Dr. Worgall is Fellowship Program in Cytogenetics and investigating the interaction of alveolar Molecular Genetics. gene fusions. macrophages with P. aeruginosa. The field of clinical genetics is Nephrologists and psychiatrists, rapidly changing and improving the meanwhile, were interested in the practice of medicine. As the field of results of a large multinational study genetics continues to grow so too 4. Gilman SR, Chang J, Xu B, et al. Diverse types of genetic variation converge in which Columbia University played the physician-scientists at Columbia on functional gene networks involved an important role.8 The study, led by University College of Physicians and in schizophrenia. Nat Neurosci. Ali Gharavi, MD, Associate Director Surgeons, Weill Cornell Medical College, 2012;15(12):1723-1728. of the Division of Nephrology at and NewYork-Presbyterian Hospital NewYork-Presbyterian/Columbia, is the will continue to be at the forefront of 5. Soliman F, Glatt CE, Bath KG, et al. A first to link congenital kidney disease, integrating genetics into all specialties. genetic variant BDNF polymorphism which together with urinary tract alters extinction learning in defects accounts for about one-fourth References both mouse and human. Science. 2010;327(5967):863-866. of all birth defects in the United States, 1. Singh D, Chan JM, Zoppoli P, et al. with neurodevelopmental disorders. Transforming fusions of FGFR and 6. Halbreiner M, Pagovich O, Finnin E, The study found that 10% of children TACC genes in human glioblastoma. et al. Disrupted adenovirus-based born with kidney defects have genomic Science. 2012;337(6099):1231-1235. vaccines against small addictive molecules circumvent anti-adenovirus alterations that have been linked 2. Shah MA, Kelsen DP. Gastric cancer: immunity. Human Gene Ther. 2012 Nov with neurodevelopmental delay and a primer on the epidemiology and 9. [Epub ahead of print] mental illness. The finding is important biology of the disease and an overview because it paves the way for identifying of the medical management of 7. Krause A, Worgall S. Delivery subgroups of patients with kidney advanced disease. J Natl Compr Canc of antigens by viral vectors for defects whose treatment will be guided Netw. 2010;8(4):437-447. vaccination. Ther Deliv. 2011;2(1):51-70. by specific genetic information. The 3. Honig LS, Kang MS, Schupf N, et al. 8. Sanna-Cherchi S, Kiryluk K, Burgess finding also alerts physicians who care Association of shorter leukocyte KE, et al. Copy-number disorders are a for children with congenital kidney telomere repeat length with common cause of congenital kidney disorders that there may be a genetic dementia and mortality. Arch Neurol. malformations. Am J Hum Genetics. basis for a neurodevelopmental delay 2012;69(10):1332-1339. 2012;91(6):987-997.

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Continued from Technology, page 1 of different objects to see how a said. “In fact, using the software, we’ve modeling glenoid socket deformity replacement component—and the even been able to track the different using computers, inputting actual cement sealant—manages stress, tendencies of individual surgeons. patient data,” Dr. Ahmad explained. according to Dr. Ahmad. With this However, at this point, the software “We can now create a virtual model approach, the team has been able is still more of a research tool than a of the patient’s shoulder and reshape to pinpoint the amount of use a clinical tool.” the glenoid on the computer. We can component and placement will be able That will change in the near future measure the erosion and, by trial and to withstand before the cement will if Dr. Ahmad has his way and if the error, select the replacement component start to crack. results continue to be positive. At this and the placement of that component To date, Dr. Ahmad and his point, he and his team are continuing that will give us the ideal result. We can team have used the computer- to refine the technology to, hopefully, also tell the program to replicate the modeling program in 5 total shoulder improve its predictive capabilities. load the shoulder will bear—the use, the replacement cases at the Hospital. At “We continue to change it for our rotation, the weight—over a simulated this point, it is too soon to tell what the research needs and we keep asking 20-year period, which is the ideal life clinical benefits of the technology will more questions,” Dr. Ahmad said. “When span of a replacement, to essentially be—given that all of these surgeries a shoulder replacement fails, it typically tell us which component will last the have been performed within the past does not fail immediately or even a longest. In that sense, the technology is year—but Dr. Ahmad said it has already few months after the procedure; it may not only a powerful surgical tool but a “influenced intraoperative decision fail 10 years later. But as surgeons we predictive model as well.” making.” cannot wait 10 years to find out the Indeed, using the system’s “Our surgeons have placed answer. With this technology we no animation technology, the team is able components based on the results of longer have to, and because of that to load the shoulder repeatedly and the computer modeling, and done we know for sure that one day our “push the ball against the socket” to things a little bit differently than they approach will be beneficial in clinical simulate the lifting or even throwing might have in the past,” Dr. Ahmad practice.”

NewYork-Presbyterian Columbia ORthopaedics

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