Repairing a Damaged Immune System:

Researchers Test World’s First Stem-Cell Therapy for Septic Shock

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Through a minimally invasive procedure, Jim Graves expected to have routine day surgery when he had his gall bladder removed. Instead, less than two days after the surgery, bile produced by the liver leaked into his system, causing a dangerous infection. Graves’s lungs collapsed and he was put on a ventilator to help him breathe.

By the time he was rushed to The Ottawa Hospital from where he was being treated, Graves’s condition was already dire. Bacteria had invaded his blood, and his heart, lungs and kidneys were shutting down.

Graves was sliding into septic shock, an avalanche of immune responses triggered by the infection in his bloodstream. With his body gripped by runaway inflammation and organ failure, Graves was fighting for his life in the intensive-care unit.

“I was in a coma for 19 days,” he says. “I lost about a month of my life, which was a mystery to me. In total, I spent nearly three months in hospital. My entire body shut down during that time so I have to learn to do everything all over again, like walking.”

It’s not acceptable that we have such limited ways to reduce death in patients with septic shock. There have to be better ways forward to help them in the future.

–Dr. Lauralyn McIntyre

Graves was fortunate to survive. Of the one in five patients admitted to ICUs with septic shock, nearly half die, making the condition a leading cause of death among critically ill patients in hospitals.

In treating septic shock, the challenge for physicians is recognizing an invasive infection early, before the cascading damage becomes unstoppable. Patients with septic shock require aggressive resuscitation measures, large doses of intravenous antibiotics and ventilators.

Yet because septic shock can at first look like less serious ailments and cause unpredictable complications, it is often deadly.

“Despite decades of research, medical experts haven’t made that much headway in developing new therapeutics to treat septic shock,” says Dr. Lauralyn McIntyre, a critical-care physician and researcher at The Ottawa Hospital.

In a world first, McIntyre and her collaborators at the Ottawa Hospital Research Institute are testing an experimental stem-cell therapy to treat septic shock.

Patients are injected with donated stem cells, grown and purified in a laboratory at the hospital, which have the potential to calm the body’s hyperactive immune response and reduce the cascade of inflammation that leads to organ failure.

“The neat thing about stem cells is that they can reduce inflammation in a number of ways,” McIntyre explains. “Instead of affecting just one pathway, they seem to affect many different inflammatory pathways. These cells seem to restore the natural balance of the body’s immune system. They seem to reduce organ failure, and they seem to reduce death.”

Stem cells can turn into a variety of specialized cells and tissues that have the potential to repair and regenerate damaged organs.

Early results from animal studies even raise the possibility that the stem cells, derived from the bone marrow of healthy donors, could eliminate the bacteria that causes septic shock, although their impact on humans is not yet known. That’s the focus of McIntyre’s clinical trial, which will start with a safety evaluation in up to 15 patients.

I don’t wish septic shock on anybody so I hope the researchers at the hospital are successful with their study.

–Jim Graves

While it’s theoretically possible to use a patient’s own stem cells to repair damaged tissue, septic shock is such a quick and overwhelming illness that there is simply no time to harvest cells from someone with the infection.

McIntyre credits her colleagues at the Ottawa Hospital Research Institute, some of whom are leading stem-cells experts, for nurturing the idea of the experimental therapy. “The people I work with are committed to answering the big questions that could help our patients. But they also care about doing research correctly.”

As with any research study, there are no guarantees that the lengthy testing will actually result in a beneficial treatment for patients. However, McIntyre remains optimistic. “That’s the nature of medical discovery. I feel passionate that we need to push the boundaries and explore new ways to help patients,” she says.

“It’s not acceptable that we have such limited ways to reduce death in patients with septic shock. There have to be better ways forward to help them in the future.”

Jim Graves is finally beginning the long road to recovery. With his wife, Frances, at his side, he has started learning to walk again.

“Getting my strength back has been very slow, but I’m grateful to be alive and I’m grateful for the excellent care that I got,” says Graves. “I don’t wish septic shock on anybody so I hope the researchers at the hospital are successful with their study.”

Research for Tomorrow: Rebuilding a Damaged Heart

To survive a heart attack is victory enough. To rebuild a heart once it has been damaged would be an extraordinary leap forward. Dr. Duncan Stewart, Chief Executive Officer of the Ottawa Hospital Researh Institute, is leading the world’s first clinical trial of a genetically enhanced stem-cell therapy for heart-attack survivors.

In a mid-phase study of up to 100 volunteers, Stewart and his team are testing the ability of a patient’s own stem cells, derived from blood, to repair damaged tissue caused by a heart attack. The key is genetically engineering the stem cells to have extra-strong healing powers. Previous studies have shown that while the human heart has the capacity to generate new muscle cells, that ability diminishes as people age, especially if they have suffered heart attacks.

“The stem cells that come from heart-attack survivors who are 60 or 70 years old don’t have the same youth and potency as those from young, healthy adults,” says Stewart. “Our strategy rejuvenates and restores the activity of these aging stem cells. We have shown that these ‘rejuvenated’ stem cells are better able to stimulate repair and can reduce scar tissue, which impairs the heart’s ability to pump blood efficiently.”

Rapid Diagnosis, Reduced Anxiety:

Innovative Program Offers Fast-Track Results for Women at the Highest Risk of Breast Cancer

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When a mammogram reveals a suspicious lump, women often find themselves in a maddening state of uncertainty. Waiting months for the results of a breast biopsy can be every bit as stressful as finding out about a cancer diagnosis.

Dr. Angel Arnaout, a surgical oncologist at The Ottawa Hospital, is concerned that the stress and anxiety of waiting can make life a whole lot worse for patients and their families.

Arnaout believes Eastern Ontario women deserve better.

Over the past two years, she and her collaborators at the hospital’s Women’s Breast Health Centre have worked tirelessly to drive down diagnostic and surgical wait times for patients who are at the highest risk of developing breast cancer.

The rapid diagnosis and treatment program established by Arnaout’s team has lowered wait times at every stage of the long, circuitous journey from diagnosis to surgery.

Of the 700 women treated at the centre every year, 200 have the type of abnormal mammogram that gives them at least a 90-per-cent risk of cancer. “These are the women who have the most urgent need for speedy diagnosis and treatment,” says Arnaout.

The hospital already leads Ontario’s 14 cancer centres in providing the fastest assessment and diagnosis for all women with abnormal mammograms. With Arnaout’s fast-track program, women in the highest risk group are getting diagnosed and treated even more quickly.

The faster access to care starts with a shorter wait for a diagnosis, which now takes an average of seven business days, a dramatic drop from 52 days in 2011. The second wait, from diagnosis to the first meeting with a surgeon, has fallen to an average of five days, down from 16. From there, the wait to surgery is now 24 days, down from an average of 31.

Cancer is my reality now. It’s the reality for a lot of women. So if we can find the safest, quickest, most efficient way of dealing with it and getting through it, I’m all for it.

–Cathy Crosthwait

Of all the wait times, perhaps the most vexing for a majority of women is the time to diagnosis, which can take up to three months. That’s because every woman with an abnormal mammogram must go through multiple tests to get a biopsy result.

Each step – diagnostic scans, biopsy, pathology – inevitably had its own waiting list, which has not traditionally been tracked. Only after all these tests are done do patients finally get a diagnosis – and an appointment with a surgeon to discuss treatment options.

The lengthy, seemingly haphazard journey can create efficiency gaps that contribute to longer wait times. It can also leave women feeling lost and neglected.

“During that whole time, somebody is waiting around, getting called back for another test, not knowing what’s going on. And all that time, they’re thinking that they’re going to die from breast cancer,” Arnaout explains. “That’s just not right. I want to change processes so that I can reduce the anxiety of patients who are waiting for their diagnosis.”

Cathy Crosthwait was referred to the rapid diagnosis and treatment program and given her breast-cancer diagnosis within a week. She also benefited from speedy access to surgery after meeting with Arnaout, her surgeon.

“The fast-track care made sure that I was not forgotten,” says Crosthwait. “Cancer is my reality now. It’s the reality for a lot of women. So if we can find the safest, quickest, most efficient way of dealing with it and getting through it, I’m all for it.”

Arnaout and her collaborators tackled the long wait times by creating a way of prioritizing appointments at every stage of the diagnostic journey. “Previously, we never triaged diagnostic tests,” says Arnaout. “Now, we’re moving the highest-risk women to the front of the line.”

Another game-changer has been the assignment of a nurse to help patients navigate the system and close any efficiency gaps. The nurse makes sure that high-risk patients get the first available appointments and the fastest pathology results possible. She also staffs a helpline to answer patients’ questions and provide them with information about what to expect at each of their appointments.

The counselling ensures that women are informed and prepared when they finally meet their surgeon, reducing the need for additional follow-up appointments.

Taken together, these deceptively simple interventions can shave weeks off the diagnostic journey. “We found that if the wait time for each was reduced somewhat, then the entire wait time was reduced dramatically,” says Arnaout.

Crosthwait, a mother of three grown children, said getting a speedy diagnosis has given her and her family a sense of confidence in the health-care system. It has also allowed her to get on with her life.

“I have a family history of breast cancer so when I got the diagnosis, I was not in shock,” says Crosthwait. “The main advantage is that I can reduce the anxiety of not knowing. And I can start doing other things before I have surgery, like spending time with my children and grandchild. Life doesn’t stop because something bad happens. You have to be able to take what life gives you and move forward.”

Research for Tomorrow: Can a Blood Thinner Also Fight Cancer?

The weeks before and after surgery can make cancer patients feel like they’re in medical limbo. No treatments are typically given out of concern that they could compromise a patient’s ability to heal.

Increasingly, however, researchers believe this hands-off period could actually be prime time to test new cancer therapies. Dr. Rebecca Auer, a surgical oncologist at The Ottawa Hospital, is testing treatments that could stimulate a patient’s immune system at a time when it is weakened, enabling cancer to grow and spread.

“The period around surgery is a golden opportunity for us to intervene and yet nothing is given,” says Auer, who’s also a scientist at the Ottawa Hospital Research Institute. “I think it’s really important that we target new cancer therapies to that peri-operative period.”

Auer and haematologist Dr. Marc Carrier have launched a “window-of-opportunity” study to test the tumour-fighting effects of low molecular-weight heparin, which has long been used as a blood thinner to prevent and treat blood clots. In animal studies, heparin has shown promising signs of preventing the spread of tumours by restoring balance to the body’s wound-healing mechanisms, which often get hijacked by cancer cells, leading to metastasis.

The study, which will enrol up to 1,000 colon-cancer patients from across the country, will test the effectiveness of heparin when it’s given as a preventive treatment in the weeks before and after cancer surgery.

Healthier Moms, Healthier Babies:

Lives are Transformed at a Unique Inner-City Clinic for Pregnant Teens

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At an age when most young women dream of going to the high-school prom, or getting their driver’s licence, Adysan Vincent is preparing to have a baby.

Vincent, 16, learned that she was pregnant on the day of a scheduled tonsil surgery. A pre-operative pregnancy test came out positive, catching Vincent and her mother by surprise. The father of her child was just as shocked.

“I didn’t know at the time that I was already two months pregnant,” Vincent admits. “It took me another three months to decide I wanted to keep the baby.”

At St. Mary’s, Vincent met Dr. Nathalie Fleming, an obstetrician and gynecologist at The Ottawa Hospital.

Fleming runs a perinatal clinic at St. Mary’s, making it the only one in Canada to be based, not at a hospital, but at a place where adolescent moms and moms-to-be gather. In effect, Fleming’s clinic is a little piece of The Ottawa Hospital in the neighbourhood of Vanier, where St. Mary’s Home is located.

Dr. Fleming’s clinic is the only one of its kind in Canada.

On the advice of a friend, she started taking prenatal classes at the Young Parent Outreach Centre at St. Mary’s Home, a refuge for pregnant teens as well as teen mothers and their newborns. The centre offers all kinds of wrap-around services under one roof, including parenting classes, a satellite high school and a shelter for pregnant teens who are homeless and need a safe place to stay.

We’re not waiting for them to come to us. We’re actually bringing the medical care to them.

–Dr. Nathalie Fleming

The location makes the clinic easy and comfortable for teens to visit. While taking high-school courses at St. Mary’s, provided by the Ottawa Catholic School Board, Vincent can take a short stroll down the hall for her appointments with Fleming.

“I don’t have to sit in a waiting room," says Vincent. "I just tell them to come and get me. That way, I can sit in class and do my work while I’m waiting.”

By simply basing her clinic out of a teen-friendly centre, Fleming has cultivated the loyalty and trust of her patients, who see her early and often, especially during the crucial first months of pregnancy.

In contrast, pregnant teens who must travel to hospitals or doctors’ offices often delay getting prenatal care.

By the time they see a doctor, many are well into their second or third trimester. The delay puts the women and their unborn children at higher risk of developing serious health complications.

The health risks can quickly add up given that many of these expectant mothers struggle with addictions, mental illness, violence, poverty, homelessness, or an unstable family life.

“We’re not waiting for them to come to us. We’re actually bringing the medical care to them,” says Fleming.

It now means we have healthier mothers and healthier children at birth, rather than children who need to be kept in a neonatal intensive care unit for a lengthy period of time.

–Nancy MacNider

“It’s very difficult to look after this population from a doctor’s office or hospital-based clinic. Many of these women simply can’t or won’t come. They may not have the money to take a bus. They may not have a family doctor. They may feel ashamed to go see a doctor. They may hide their pregnancy. They may not find out until very late that they’re actually pregnant. They’re looking for help, but society has judged them and they feel stigmatized.”

Vincent remembers feeling the sting of shame the first time she showed up at another doctor’s office for a prenatal visit.

“When I walked in, I was the youngest person pregnant. Everyone else stared at me. It made me feel awkward,” she says during an afternoon at St Mary’s. “Here, I don’t feel judged. Dr. Fleming takes the time to listen to what your issues are. She's somebody you can talk to.”

Since starting the clinic in 2006, Fleming has been able to show that providing perinatal care where pregnant teens gather can actually improve the health of the young mothers and their newborns.

Compared to pregnant teens who get their prenatal and post-partum care through hospital-based clinics or doctors’ offices, the women who go to Fleming’s clinic have fewer pre-term births. They have lower rates of caesarean sections. And they tend to deliver babies with higher birth weights, Fleming showed in a recently published study.

“The impact of having Nathalie's clinic here has been nothing short of profound," says Nancy MacNider, executive director of St. Mary’s Home. "It now means we have healthier mothers and healthier children at birth, rather than children who need to be kept in a neonatal intensive care unit for a lengthy period of time.”

MacNider praises Fleming for her vision and dedication. "It was her energy, enthusiasm and willingness to take risks that gave life to this clinic. It is first-rate health care provided by a medical specialist who, out of her own philosophy of care, is giving a very marginalized group of young people the very best that there is."

Fleming, a mother of two pre-teen girls, says she draws inspiration from many of her young patients.

"I have been a witness to so many success stories here at the clinic. It's fantastic to see some of these teens go from being in the street, using all sorts of drugs, to young women who come to St. Mary's, get plugged into the medical system and turn their lives around."

Vincent is one of those young women. Having initially dropped out of high school, she resolved to return after learning that she was pregnant. At St. Mary’s, she is taking Grade 10 classes run by Immaculata High School. And she has quit smoking, curbed her intake of junk food and started exercising.

"It's not about me anymore. It's about the baby," says Vincent. "I chose to go back to school because I realize I wasn't going to be able to support a baby without my education. I know I'm still going to struggle, but I'm keeping the baby mostly because I know that I have every single support system that I can get."