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Researchers at Lawson Health Research Institute (Lawson) are developing a hand-held photoacoustic imaging probe to be used during breast conserving surgery to quickly and accurately verify if all cancerous tissue has been removed.

Surgeons currently do not have real-time technology to guide tumour removal during surgery.

Using current tools, there is a 20 per cent chance that cancerous cells will be left behind, risking recurrence and repeat surgery.

Breast cancer represents 25 per cent of all new cancer diagnoses in women and 13 per cent of all cancer related deaths in women. Treatment for breast cancer often requires either complete breast removal in severe cases, or surgical removal of the cancerous tumour in combination with other therapies. Removing only the tumour is called breast conserving surgery.

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Photoacoustic Screening

The new device is an extension of the photoacoustic screening (iPAS) technology developed in the laboratory of Dr. Jeffrey Carson, Principal Investigator and Lawson Scientist. The technique uses light and sound to capture 3D images of surgically removed breast tissue. Their studies show that iPAS can catch up to 75 per cent of missed tumour cells, decreasing the odds of failed surgery to five per cent.

Dr. Muriel Brackstone, Associate Scientist at Lawson, Head of the Breast Care Clinic at St. Joseph’s Hospital London, and Surgical Oncologist at London Health Sciences Centre, brings her clinical expertise to the project.

“With the first generation iPAS technology, we would remove the tumour, take it to the lab for imaging and wait to see if there was a rim of normal tissue around the removed tumour so we knew it was removed completely. The wait was anywhere from 20 minutes to an hour. During that time, the patient is under anesthesia, the surgical team is idle and precious OR time is being used,” explains Dr. Brackstone.

A hand-held tool that surgeons can use

Creation of a hand-held probe to be used in the operating room is the next step in the advancement of this new technology. Elina Rascevska, biomedical engineering student at Western University, recently joined the Lawson team to convert lab-based iPAS technology into a hand-held device.

“We have developed a prototype of the iPAS probe, and once we can verify the quality of the images it produces, we will give it to Dr. Brackstone to test in the OR,” says Rascevska.

The iPAS probe does not need a trained operator and would be used by the surgical team. Instead of imaging the removed tissue, it scans the surgical cavity in real time to give the team a faster and more accurate indication as to whether the cancerous tissue has been removed.

“If we can progress this technology to a point where physicians can use it as part of standard protocols, we will have reduced the amount of time each patient needs to spend in the OR, the amount of call-backs and repeat surgeries, and ultimately improve quality of life for patients with breast cancer,” adds Dr. Carson.

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A team from Lawson Health Research Institute are being funded by the Government of Ontario’s COVID-19 Rapid Research Fund to study whether inhaled sedatives can replace those that are delivered intravenously in COVID-19 patients requiring ventilation. The multi-centre clinical trial aims to address a global shortage of intravenous (IV) sedatives while improving patient outcomes. 

“When COVID-19 patients develop severe respiratory failure and need to be ventilated, they require sedation. While IV sedatives are currently used, there is concern about global drug shortages, particularly if there’s a second wave of COVID-19 in the fall,” explains Dr. Marat Slessarev, Scientist at Lawson and Critical Care Physician at London Health Sciences Centre (LHSC). “Even if we have enough ventilators, we won’t be able to ventilate patients without sedatives.”

The clinical trial, being co-led by Dr. Slessarev and Dr. Angela Jerath at Sunnybrook Health Sciences Centre, will study the replacement of IV sedatives with inhaled sedatives. Inhaled sedatives, also called volatiles, are widely available due to their use in operating rooms to sedate patients during surgery. While they have not been routinely used to sedate patients needing ventilation, early studies suggest they could be safe and even more effective than IV sedatives. 

“Preliminary studies in non-COVID patients with severe respiratory failure suggest that inhaled sedatives can reduce lung inflammation, shorten the duration of ventilation and potentially improve survival. Inhaled sedatives could therefore reduce the pandemic’s strain on ventilator capacity while improving patient outcomes,” says Dr. Slessarev. “Since these drugs are safe, cheap and readily available, they can easily be used to address IV sedative shortages if found effective.”

The researchers will recruit approximately 800 patients from across Canada and the United States including patients from LHSC. Each patient will be randomized to receive either IV sedatives or inhaled sedatives. Patient outcomes such as survival and length of ventilation will be compared between the two groups to determine which method of sedation is most effective. 

“This is the largest trial of its kind. If inhaled sedatives can shorten the length of ventilation or improve survival in patients with serve respiratory failure, this could cause a paradigm shift in the way we sedate patients in intensive care units (ICUs) around the world,” notes Dr. Slessarev. 

Given many survivors of critical illness experience cognitive impairment for months or even years after an intensive care unit (ICU) stay, the team is also planning a sub-study to assess whether one method of sedation results in better cognitive outcomes after treatment. 

In addition to funding from the Government of Ontario, the study is being supported with funding from the Canadian Institutes of Health Research (CIHR), London Health Sciences Foundation and Sunnybrook Health Sciences Centre.

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Dr. Marat Slessarev, Scientist at Lawson and Critical Care Physician at LHSC

As we continue to live with a COVID-19 pandemic, patients will need good treatment options.

Hospital researchers in London, Ontario, through Lawson Health Research Institute, are testing treatment options for patients who have been hospitalized from a COVID-19 infection, often for severe symptoms.

During the peaks of the COVID-19 pandemic, there were concerns of a global drug shortage when it came to IV sedatives for patients needing ventilation. Through funding from the Government of Ontario’s COVID-19 Rapid Research Fund, a team of Ontario researchers studied whether inhaled sedatives could replace those that are delivered through IV.

“In addition to easing the burden on IV stocks, the inhaled sedatives have additional benefits,” says Dr. Marat Slessarev, a Critical Care Physician at LHSC. “They may reduce inflammation in the lungs and shorten the duration of sedation because they are eliminated from the body faster than IV sedatives.”

Dr. Slessarev, also a Scientist at Lawson, adds that using inhaled sedatives could also be safer for severe COVID-19 patients, who in many cases are on a ventilator for a long time. “When using IV sedatives, they can accumulate and metabolize with accumulation. This can leave the patient with the potential of developing kidney issues because it is hard to dispel them quickly.” 

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Dr. Marat Slessarev, Critical Care Physican at LHSC and Lawson Scientist

To date, around 800 patients across ten hospital sites have been enrolled in this trial, with the hopes of getting more hospital sites on board as the clinical trials continue.

• Read more about this multi-centre clinical trial.

A majority of people with severe COVID-19 infections in critical care end up developing sepsis, which is a potentially life-threatening condition that occurs when the body's response to an infection damages its own tissues. 

“An inflammatory response is what the body uses to fight an infection, but sometimes it is more than necessary and it causes damage to the organs and the body,” explains Dr. Claudio Martin, a Physician in the Intensive Care Unit (ICU) at London Health Sciences Centre (LHSC). “This is why a patient with a severe COVID-19 infection caused by a virus can get sepsis.”

Dr. Martin, who is also an Associate Scientist at Lawson, began studying the use of a human protein called Annexin A5 as a potential treatment for COVID-19 patients with sepsis. “It can work in two ways. The annexin may coat injured cells and reduce the inflammatory response. Or, the injured cells and exposed proteins trigger the clotting mechanism in the body. Those with COVID-19 could get blood clots in the brain and the lungs, and using annexin may improve their outcomes.”

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Dr. Claudio Martin, Critical Care Physician at LHSC and Lawson Scientist

Currently, a clinical trial using Annexin A5 on severe COVID-19 patients is underway at LHSC to look at the efficacy of using this human protein.

• Read more about this clinical trial.
   

The COVID-19 virus is also known to cause respiratory failure, prompting Dr. Jim Lewis, Respirologist at St. Joseph’s Health Care London and Scientist at Lawson, to investigate the use of pulmonary surfactant as a potential treatment for these patients.

Bovine Lipid Extract Surfactant Suspension (BLES) is a pulmonary surfactant manufactured in London, Ontario. It’s currently used worldwide to help improve lung function in premature babies. Now, it is being studied with COVID-19 patients experiencing respiratory failure.

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Dr. Jim Lewis, Repirologist at St. Joseph's Health Care London and Lawson Scientist 

“We know that patients who have injury to their lung and require ventilation have inflammation in the airways of their lungs. Surfactant is a homogeneous layer of lipids and proteins that line the lungs to allow us to breath with minimal effort,” explains Dr. Lewis. “If we gave these patients surfactant as soon as possible after they were put on a mechanical ventilator, it may have some benefit in improving their outcome and getting them off the ventilator sooner.”

Dr. Lewis and his team conducted a clinical trial using pulmonary surfactant with ten critically ill COVID-19 patients and initial results have shown patient safety and efficacy.

• Read more about the BLES study.
   

Another team of hospital researchers turned to using modified dialysis machines to offer treatment options to those with severe COVID-19 symptoms. Nephrologist at LHSC, Dr. Chris McIntyre, was the first in the world to modify a dialysis device to treat a patient with COVID-19.  The device gently removes a patient’s blood, modifies white blood cells, and returns them to fight hyperinflammation.

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Dr. Chris McIntyre, Nephrologist at LHSC and Lawson Scientist

“It was quick.  We went from the initial idea to the approvals, creating the device and appointing the first patient within 40 days,” says Dr. McIntyre who is also a Scientist at Lawson. “After the first 12 patients, we found that those treated with the device needed significantly less drugs to maintain their blood pressure. We were able to deliver the treatment for all the patients – none of the treatments failed and we had no safety issues.”

Dr. McIntyre is now looking into using this form of therapy for chronic dialysis patients to help modify organ injury.

• Read more about his COVID-19 research with modified dialysis machines.