Toronto General Research Institute

Acute Respiratory Distress Syndrome: Study Shows Long-Term Outcomes for Survivors
A recent study by UHN researchers Drs. Angela Cheung , Margaret Herridge and George Tomlinson established that most survivors of acute respiratory distress syndrome (ARDS) have a reduced health-related quality of life two years after being discharged from an intensive care facility. ARDS is a serious illness where fluid accumulates in the lungs, which causes oxygen levels in the blood to drop to dangerously low levels.

The researchers followed 109 ARDS survivors for two years to examine changes in the quality of life and associated healthcare costs. They found that all health-related quality of life domains, other than emotional and mental health, were diminished compared to those of the general population. However, most ARDS survivors adapted to their situation and could live independently and return to work.

"Our findings suggest that future research efforts should concentrate on early intensive rehabilitation programs for ARDS," says Dr. Cheung. "These types of programs could help improve the long term outcomes for ARDS survivors."

Am J Respir Crit Care Med. 2006 Sep 1; 174(5):538-44. Epub 2006 Jun 6. [ Abstract ]

Heart Attack: Bone Marrow Molecule Signals Repair "Troops"
UHN regenerative medicine researchers Drs. Shafie Fazel, Massimo Cimini, Liwen Chen, Shuhong Li, Denis Angoulvant, Paul Fedak, Richard Weisel, Armand Keating and Ren-Ke Li have identified the SOS distress signal that mobilizes specific repair cells to the heart after a heart attack.

C-kit, a molecule located on the surface of a subset of bone marrow cells, is turned on by the SOS signals sent by the damaged heart. C-kit binds to another molecule, activating c-kit to signal bone marrow cells to home in on the heart to help stimulate new blood vessel growth.

"Each year, 70,000 Canadians suffer from a heart attack and many of them are left with crushing disabilities, mainly because the heart muscle is not able to regenerate after a heart attack," says Dr. Li. "This study identifies how the body naturally repairs the heart and provides new potential therapies to stimulate cardiac regeneration and prevent heart failure in these patients."

J. Clin. Invest. 2006 Jul;116(7):1865-77. [ Abstract ]

Digestive System Diseases: Defining Treatment Criteria for Swallowing Disorder
Patients with the rare swallowing disorder achalasia are unable to relax the muscular ring that links the esophagus to the stomach. They experience difficulty swallowing and moving food from their mouth to their stomach through their esophagus-sometimes leading to pain, regurgitation and dangerous weight loss.

There are two common surgical treatments for achalasia; however, it is not clear which treatment is less likely to result in the need for subsequent interventions. To address the controversy, UHN health services researcher Dr. David Urbach performed a retrospective study using data records from 1461 achalasia patients in Ontario.

"Our study shows that although both methods commonly result in the need for subsequent intervention, less than 40% of patients treated with surgical dissection of the muscle had to be treated again compared to more than 60% of patients treated by enlarging the contracted opening using an air-filled balloon," says Dr. Urbach.

"Knowing that surgical dissection is slightly more efficient overall, we suggest that doctors consider the patient's attitude toward surgical procedures and the desire to avoid further treatments when making recommendations."

JAMA. 2006 Nov 8;296(18):2227-33. [ Abstract ]

Heart Failure: Knowing the Signs
A recent UHN-led study provides insight into the series of events involved in f heart failure, the fastest growing epidemic in cardiovascular disease, the number one killer of Canadians. Drs. Peter Liu , Thomas Parker and Rama Khokha have determined the importance of tumour necrosis factor alpha (TNFa)—usually involved in many cell processes such as growth and survival—in regulating cardiac repair and remodeling.

Using a mouse model, researchers compared the effects of pressure load on the left ventricle of the heart in the presence and absence of TNFa. In the presence of TNFa, pressure-overloaded cardiac cells are riddled with high levels of inflammatory proteins, leading to heart dilation, and the cells eventually succumb to TNF effects, contributing to cardiac dysfunction.

When TNFa was removed, adverse heart effects were reduced. "Based on this effect, TNFa could be used to alert physicians when heart repair processes threaten to deteriorate into heart failure," says Dr. Liu. "Even more exciting is its potential as a therapeutic tool in the treatment of patients. We stumbled upon this finding quite unexpectedly, and were surprised at its absolutely potent effect."

Circulation. 2007 Mar 20;115(11):1398-407. Epub 2007 Mar 12. [ Abstract ]

Liver Transplant: Showing the Benefits of Live Donation
TGH has been a world leader in liver transplants involving living donors, and a recent study has proven the beneficial effects of this treatment strategy. Living donation allows suitable recipients to avoid the long organ waiting list but may represent unknown immediate and long-term health risks given that recipients receive only part of a liver.

To compare the risks of being on the list to those of receiving a living donation, UHN researchers Drs. David Grant, Gary Levy, Paul Greig, Ian McGilvray, Leslie Lilly, Nigel Girgrah and Mark Cattral reviewed survival rates and mortality of patients in the liver transplant program.

They found that patients who received a right-lobe of a liver from a living donor had a higher survival rate post-transplant and reduced mortality on the waiting list than those who received a transplant from a deceased donor.

Says study leader Dr. Grant: "Live donor transplants significantly shorten wait times and reduce the chance of death for those patients who are on waiting lists. We have shown that we are able to help patients quicker and more effectively with live donation. Future studies will have longer follow-up times to more clearly understand the advantages and disadvantages of living donors."

Am. J. Transplant. 2007 Apr; 7: 998-1002. [ Abstract ]