Yale team implants new prosthetic ankle

A tailor-made prosthetic joint restores function while reducing side effects and amputation risk.

The ankle’s position in the hierarchy of artificial joints corresponds roughly to its location at the bottom of the human body; however, a new Yale team—armed with prostheses that better mimic the ankle’s structure—aims to raise its stature.

The development of a prosthetic hip in the early 1960s set the modern standard for arthroplasty, followed by advances in other manmade joints. “We know a ton about the knee. We know a ton about the hip,” said John S. Reach Jr., M.D., assistant professor of orthopaedics and the new director of the reconstituted Yale Foot and Ankle Service. “The foot, in medicine, hasn’t been looked at much at all. It just hasn’t gotten enough respect. The hand is sexier. A hip is easy to put in; it’s a ball and socket,” Reach said. “An ankle is pretty complex. It’s small. It’s fussy.”

Prosthetic ankles have “lagged behind, but not for lack of trying,” Reach said. They have come a long way from 19th-century efforts to fashion a ball and stem from elephant tusks. The first modern synthetic ankle, developed in the 1970s, was “a basic hinge,” but doctors learned quickly that the human body isn’t that simple. The latest generation of prosthetic ankles more closely follows the joint’s anatomy. “Now they look more like what God gave you,” Reach said.

The components of the new implant could easily be mistaken for parts that hold a dishwasher together. The implant—made of titanium, chromium and plastic—replaces the top of the talus and base of the tibia. Because the prosthesis is modular, each part is tailored to the patient. In November, Reach performed Connecticut’s first total ankle replacement with the new device, called the Inbone, on a 38-yearold man whose life was upended in a bizarre auto accident one Sunday in 1994.

The patient, Damian Diaz, who lives in the Fair Haven neighborhood in New Haven, lost an eye, a shoulder and his lower left leg in the crash when the wheel came off the axle and burst through the floorboard. He had had 30 surgeries, and though he felt lucky to be alive, the pain in his right ankle limited his walking to no more than a few steps at a time. “My bone was disappearing,” Diaz said. “I could not live with the hurt every day.”

Diaz was a good candidate for total ankle replacement. Trauma patients often develop severe arthritis in the ankle, and though it’s less common than hip or knee arthritis, Reach expects the incidence of post-traumatic arthritis to rise—partly because advances in medicine and safety enable younger people to survive these traumas. Airbags protect the upper body, but “people are left with horribly mangled feet,” he said. “When you have pain in the joints, it’s bad. It’s bone against bone.”

The first lines of treatment for ankle arthritis are painkillers and braces. Another established option is fusing the ankle bones, but that can leave patients with a permanent limp. It can also lead to further arthritis and, perhaps, amputation. A recent review of the literature found that 1 percent of patients who had a total ankle replacement needed an amputation, compared to 5 percent of the fusion patients. Reach expects 85 percent of the new prosthetic ankles to last at least eight years.

Diaz said that so far he’s happy with the prosthetic ankle. “I’m waiting to get used to it, but I’m walking,” he said. “It doesn’t hurt anymore.”

—John Dillon

Scientists report link between high levels of a protein and severe asthma

Late last year two Yale researchers reported a link between severe asthma and a certain protein, YKL-40, which appeared in elevated levels in patients who used rescue inhalers and oral corticosteroids most frequently and required hospitalization for severe attacks.

Now, in findings published in the New England Journal of Medicine in April, Geoffrey L. Chupp, M.D., associate professor of medicine (pulmonary and critical care), and Jack A. Elias, M.D., Waldemar Von Zedtwitz Professor and chair of the Department of Internal Medicine, with colleagues at the University of Chicago and the University of Wisconsin-Madison, describe a single nucleotide polymorphism (SNP)—a one-letter change in the genetic code—that correlates with asthma and its severity. The SNP is located in the chitinase 3-like 1 gene (CHI3L1), the gene that encodes YKL-40.

“The first study demonstrated that YKL-40 was increased and that levels in the blood correlated with levels in the lungs. ... But it was possible that it was just a bystander and not part of the asthmatic pathway,” said Chupp. “This study strongly suggests that YKL-40 plays a significant role in the development of asthma.”

YKL-40 belongs to the family of chitinases and chitinase-like proteins. Chitinases bind to, chew up and digest chitin, a tough natural polymer found in the cell walls of fungi and the bodies and eggs of parasitic worms. Chitinaselike proteins, however, can’t digest chitin. YKL-40 and its role in asthma came to light several years ago when Elias and his colleagues found that chitinase and chitinase-like proteins were overexpressed in the lungs of mice with asthma-like diseases. The surprise discovery supported the idea that asthma is an antiparasitic response in a setting where parasites cannot be detected.

Unpublished studies suggest that YKL-40 controls inflammation in the asthmatic airway. “When YKL-40 is there, it keeps inflammatory cells alive longer, and when it is not, they die quickly,” said Elias.

In the future, YKL-40 could help doctors treat asthma by serving as a biomarker, notifying them of patients who are likely to have severe asthma. Pharmaceutical companies might also develop a drug that targets YKL-40 and use serum measurements of YKL-40 to help predict who will respond to these new therapies. “Ultimately,” said Chupp, “blocking the effects of YKL-40 may prove to be a novel and effective way to treat asthma.”

—Hannah Hoag

A podcast of Geoffrey Chupp speaking on this subject can be found on the Yale page on iTunes U. Visit itunes.yale.edu or launch iTunes, then select Yale from the offerings under iTunes U. The podcast is included under “Yale Health & Medicine.”

et cetera

Technique promotes new bone

A novel technique—removing bone marrow and injecting a hormone—promotes rapid formation of new bone in rats, Yale researchers reported in February in the journal Tissue Engineering.

“This could radically change the way patients are currently treated for weakened or fractured hips, vertebrae and acute traumatic long-bone fractures,” said senior author Agnès M. Vignery, D.D.S., Ph.D., associate professor of orthopaedics and rehabilitation. Existing therapy, which involves surgery and artificial materials, often leads to unsatisfactory outcomes.

Researchers removed bone marrow from thigh bones in mice and then gave them daily injections of bone anabolic agents like parathyroid hormone (PTH). The procedure creates new bone tissue that appears structurally and biologically normal, and endows the targeted bone with improved biomechanical properties at a rate that can’t be achieved by injecting hormones alone, Vignery said.

—J.D.

Colon screening questioned

Colorectal cancer screenings for the severely ill may do more harm than good, according to a Yale study published in the Archives of Internal Medicine in November.

This finding resulted from a new method of evaluating medical tests that gauges “payoff time”—how long it takes for a test’s benefits to outweigh complications and side effects. Researchers led by R. Scott Braithwaite, M.D., assistant professor of medicine, studied 50-year-old men with HIV and 60-year-old women with severe congestive heart failure.

The payoff time for the screenings was up to five years for the men and 2.9 years for the women. But patients with severe congestive heart failure were less likely to benefit—they have a life expectancy of less than 2.9 years. Patients with HIV, however, have a life expectancy of more than five years.

“This issue is becoming increasingly important as pay-for-performance and physician ‘report cards’ encourage clinicians to offer screening to everyone, regardless of individual benefit,” said Braithwaite.

—John Curtis


			Originally published in Yale Medicine, Spring 2008. Copyright © 2008 Yale University School of Medicine. All rights reserved.