Imagine if doctors could determine, many years in advance, who is likely to develop dementia. Such prognostic capabilities would give patients and their families time to plan and manage treatment and care. Thanks to artificial intelligence research conducted at McGill University, this kind of predictive power could soon be available to clinicians everywhere.
Scientists from the Douglas Mental Health University Institute’s Translational Neuroimaging Laboratory at McGill used artificial intelligence techniques and big data to develop an algorithm capable of recognizing the signatures of dementia two years before its onset, using a single amyloid PET scan of the brain of patients at risk of developing Alzheimer’s disease.
Dr. Pedro Rosa-Neto, co-lead author of the study and Associate Professor in McGill’s departments of Neurology & Neurosurgery and Psychiatry, expects that this technology will change the way physicians manage patients and greatly accelerate treatment research into Alzheimer’s disease.
“By using this tool, clinical trials could focus only on individuals with a higher likelihood of progressing to dementia within the time frame of the study. This will greatly reduce the cost and the time necessary to conduct these studies,” adds Dr. Serge Gauthier, co-lead author and Professor of Neurology & Neurosurgery and Psychiatry at McGill.
Scientists have long known that a protein known as amyloid accumulates in the brain of patients with mild cognitive impairment (MCI), a condition that often leads to dementia. Though the accumulation of amyloid begins decades before the symptoms of dementia occur, this protein couldn’t be used reliably as a predictive biomarker because not all MCI patients develop Alzheimer’s disease.
To conduct their study, the McGill researchers drew on data available through the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a global research effort in which participating patients agree to complete a variety of imaging and clinical assessments.
Sulantha Mathotaarachchi, a computer scientist from Rosa-Neto’s and Gauthier’s team, used hundreds of amyloid PET scans of MCI patients from the ADNI database to train the team’s algorithm to identify which patients would develop dementia, with an accuracy of 84%, before symptom onset. Research is ongoing to find other biomarkers for dementia that could be incorporated into the algorithm in order to improve the software’s prediction capabilities.
“This is an example how big data and open science brings tangible benefits to patient care,” says Dr. Rosa-Neto, who is also director of the McGill University Research Centre for Studies in Aging.
While new software has been made available online to scientists and students, physicians won’t be able to use this tool in clinical practice before certification by health authorities. To that end, the McGill team is currently conducting further testing to validate the algorithm in different patient cohorts, particularly those with concurrent conditions such as small strokes.

McGill Universityhttp://tinyurl.com/y8dd4zda

Researchers at the University of Cincinnati (UC) College of Medicine have shown that a new targeted treatment could benefit patients with certain pancreatic tumours by preventing spread of the cancer and protecting their heart from damage—a direct result of the tumour. Higher levels of serotonin among other tumour secretions can cause injury to the valves of the heart over time, leading to cardiac impairment—a condition referred to as cardiac carcinoid disease—in these patients.
These findings could lead to another targeted treatment for patients and prevent the onset of additional complications from their cancer.
"Pancreatic neuroendocrine tumours—pancreatic NETs, pNETs or islet cell tumours—are tumours that form from the abnormal growth of neuroendocrine cells in the pancreas,” says lead author Hala Elnakat Thomas, PhD, research assistant professor in the Division of Hematology and Oncology, Department of Internal Medicine, and member of the Cincinnati Cancer Consortium and UC Cancer Institute’s Pancreatic Cancer Center. "Most pancreatic NETs are functional, meaning they produce hormones. The overproduction of certain hormones results in a number of symptoms termed carcinoid disease which may impact the patients’ quality of life if not managed appropriately.”
She says mutations in key players of the mTOR pathway, a molecular pathway present and active in several types of cancer, have been identified in pNETs.
"Inhibiting mTOR signalling using everolimus, a targeted therapy, known as a rapalog, for patients with lung and gastroenteropancreatic NETs, has been approved by the FDA. A rapalog inhibits the mTOR protein by preventing it from activating some signals,” she says. "However, patients eventually experience progression of cancer on this treatment, highlighting the need for additional therapies. In this study, we focused on pancreatic NETs (pNETs) and thought that treatment of these tumours upon progression on rapalog therapy, with an mTOR kinase inhibitor (mTORKi), could overcome a number of resistance mechanisms in tumours and delay cardiac carcinoid disease.”
Elnakat Thomas’ team and colleagues including Jack Rubinstein, MD, a member of the Heart, Lung and Vascular Institute and an associate professor within the UC College of Medicine, performed preclinical studies using human pNET cells injected into animal models to determine tumour progression and cardiac function in those treated with a rapalog alone or switched to the mTORKi (CC-223) when cancer progression was noticed.
"Our results showed that in the majority of pNETs that progress on rapalog therapy, it is possible to reduce disease progression when switching instead to an mTORKi, such as CC-223,” Elnakat Thomas says. "The mTORKi also may lead to additional cardiac benefit by decreasing valvular fibrosis (damage) when compared with placebo or just the rapalog. The mTORKi also inhibit mTOR but they do it differently than rapalogs, and they are stronger inhibitors of signals, so the inhibition is more complete with an mTORKi than a rapalog. This data warrants further testing of the long-term cardioprotective benefit of an mTORKi in neuroendocrine tumour patients prone to carcinoid syndrome. Altogether, these results are timely as an mTORKi therapy called sapanisertib is currently in phase II clinical trial testing in pNET patients with metastatic cancer or tumours that are not reacting to treatment and cannot be surgically removed.”
University of Cincinnati
healthnews.uc.edu/news/?/29597/

A research team led by investigators from Massachusetts General Hospital (MGH) and collaborators has shown, for the first time, that it may be possible to non-surgically treat or even prevent the damage to a major heart valve that often occurs after a heart attack. In their report the investigators – including co-senior authors at Boston Children’s Hospital and Brigham and Women’s Hospital – describe how treatment with the antihypertension drug losartan reduced mitral valve damage in an animal model of heart attack.
“Our study supports a new concept transforming how we think about heart valves,” says Robert Levine, MD, of the Heart Valve Program and the Cardiac Ultrasound Laboratory in the Corrigan Minehan Heart Center at MGH, co-senior author of the report. “They are not just passive tissue flaps, as previously thought, but are biological battlegrounds where medicines can be used to help patients. Patients with heart valve disease are currently treated with interventions – surgery or implanted devices – late in their illness when the heart is failing. We aim to prevent disease progression at an early stage and keep our patients’ hearts healthy.”
When blockage to a coronary artery causes the death of heart muscle, the body responds by sending immune cells and other inflammatory factors to the site of the damage. Co-lead author Jacob Dal-Bianco, MD, also of the MGH Heart Valve Program, explains, “A heart attack is like a fire in the heart;  inflammation triggered by damage to the heart muscle attracts cells to clear up the damage and form a healed scar. The mitral valve can be caught up as an innocent bystander in this process and become inflamed and scarred, eventually becoming shorter, stiffer and less able to close effectively.”
Located between the left atrium, which receives oxygenated blood from the lungs, and the left ventricle, from which blood is pumped out to the body, a healthy mitral valve keeps blood flowing in the right direction. But if the valve tissues called leaflets don’t close properly after the heart beats, blood can leak back towards the lungs – a process called mitral valve regurgitation – reducing the efficiency of the heart and placing additional stress on the already-damaged organ. While it had been thought that post-heart-attack damage to the mitral valve was caused only by physical forces exerted by the scarring and stretching of damaged heart muscle, recent research by MGH team members found that the valve itself becomes thicker and stiffer, further reducing its ability to close.
Among the factors released by immune cells in an attempt to heal damaged heart muscle is transforming growth factor (TGF)-beta. While it is an important regulator of processes involved in growth, development and the immune response, excess levels of TGF-beta can overactivate other cells, leading to further scarring and stiffening of the mitral valve. Surgical repair of a damaged mitral valve fails within two years in 60 percent of patients, leading to shortness of breath and eventual heart failure.
The hypertension drug losartan is known to inhibit the effects of TGF-beta, and the current study was designed to see whether it could reduce post-heart-attack mitral valve damage in an animal model. For two months, daily doses of the drug were given to sheep in which a heart attack had been surgically induced. A control group of animals that did not receive the drug had surgical mesh sutured to their left ventricular walls to restrict the stretching that typically follows a heart attack and keep the size of the ventricle the same as in the drug-treated animals. At the end of the study period, significantly less inflammation, thickening and scarring had developed in the mitral valves of the losartan-treated animals, compared with the control group. Another study by the same group is investigating whether losartan treatment actually can reduce mitral valve regurgitation.

Massachusetts General Hospital
www.massgeneral.org/about/pressrelease.aspx?id=2141

No single solution exists for alleviating crowding in emergency rooms, but a new study identifies four key strategies that have reduced the problem.
The study concludes that engaged executive leadership can alleviate the problem when combined with a data-driven approach and coordination across the hospital from housekeepers to the CEO. Crowding in emergency rooms has been associated with decreased patient satisfaction and even death.
“Emergency department crowding can be dangerous for patients,” said senior author Benjamin Sun, M.D., a professor of emergency medicine in the OHSU School of Medicine. “We know, for example, that emergency department crowding can lead to delays in pain medications for patients with broken bones, as well as delays in antibiotics for patients with pneumonia. We know the risk of death is higher when the emergency department is more crowded than when it’s less crowded.”
The study identified groups of hospitals categorized as low, high or highest-improving in terms of lengths of stay and boarding times (the length of time an admitted patient must wait for an inpatient bed), as measured through statistics provided by 2,619 U.S. hospitals to the Centers for Medicare and Medicaid Services. The authors picked a representative sample of four hospitals in each of the three categories of performance, then systematically interviewed a broad range of stakeholders.
The researchers talked to 60 people at the 12 hospitals. Interviewees included nursing staff, emergency department directors, directors of inpatient services, chief medical officers and other executive officers.
The study identified four key strategies:
1) Involvement of executive leadership: The study noted that executive leaders in highperforming hospitals identified hospital crowding as a top priority complete with clear goals and resources to achieve those goals.
“In contrast, low performing hospital executive leadership did not prioritize crowding initiatives, despite acknowledging the causes,” the authors wrote. “Emergency department leadership often felt isolated in their struggle with significant boarding and lengths of stay.”
2) Hospital-wide coordinated strategies: High-performing hospitals performed as a cohesive system across departments to alleviate crowding, in contrast to low-performing hospitals that operated in silos. For example, one executive at a high-performing hospital developed strategies for improving bed turnaround times on inpatient rooms.
“Instead of waiting for the room to go from dirty to clean and then to book transportation for a patient to come, we started doing things in parallel so that we would cut down on waiting time,” the executive said in the report.
3) Data-driven management: High-performing hospitals gathered and used data to adjust operations in real time, provided immediate feedback to key personnel, and predicted patterns of flow in the emergency department and hospital, matching resources to meet expected demand.
“In contrast, at low-performing hospitals, data were most often available only retrospectively, and, if the data were used, they were discussed by executive leadership at monthly or quarterly meetings,” the authors wrote.
4) Performance accountability: High-performing hospitals held staff accountable and problems were addressed immediately to reduce crowding.
Sun described a typical scenario in one high-performing hospital: “If boarding in the ED exceeded the acceptable limit, the chief medical officer would physically get out of the office, go onto the ward floors, and start reviewing charts and asking, ‘What can we do to fix the problem?’” he said.
OHSU School of Medicine
http://tinyurl.com/y8bq3gvg

Human rhinovirus (HRV), the culprit behind most colds, is the leading cause of hospitalization for premature babies. However, in very preterm children, exactly how HRV causes severe respiratory disease — and which patients may need more intensive observation and treatment — is less well understood.
A new study led by Children’s National Health System research clinicians showed that in children who were born severely premature, HRV infections seem to trigger an airway hyper-reactivity (AHR) type of disease, which leads to wheezing and air-trapping (hyperinflation) and more severe respiratory disease. This, in turn, increases the risk for hospitalization.
The study found that other signs of respiratory distress, such as low arterial blood oxygen or rapid shallow breathing, were no more common in severely premature children (less than 32 weeks of gestational age) than in kids born preterm or full-term. The findings have implications for administering supportive care sooner or more intensively for severely premature children than for other infants.
“When it comes to how they respond to such infections, severely premature children are quite different,” says Geovanny Perez, M.D., a specialist in pulmonary medicine at Children’s National and lead study author. “We’ve known they are more susceptible to human rhinovirus infection and have more severe disease. However, our study findings suggest that severely premature kids have an ‘asthma’ type of clinical picture and perhaps should be treated differently.”
The study team sought to identify clinical phenotypes of HRV infections in young children hospitalized for such infections. The team theorized that severely premature babies would respond differently to these infections and that their response might resemble symptoms experienced by patients with asthma.
“For a number of years, our team has studied responses to viruses and prematurity, especially HRV and asthma,” Dr. Perez says. “We know that premature babies have an immune response to HRV from the epithelial cells, similar to that seen in older patients with asthma. But we wanted to address a gap in the research to better understand which children may need closer monitoring and more supportive care during their first HRV infection.”
In a retrospective cross-sectional analysis, the study looked at 205 children aged 3 years or younger who were hospitalized at Children’s National in 2014 with confirmed HRV infections. Of these, 71 percent were born full-term (more than 37 gestational weeks), 10 percent were preterm (32 to 37 gestational weeks) and 19 percent were severely premature (less than 32 gestational weeks).
Dr. Perez and his team developed a special respiratory distress scoring system based on physical findings in the children’s electronic medical records to assess the degree of lower-airway obstruction or AHR (as occurs in asthma) and of parenchymal lung disease. The physical findings included:

• Wheezing;
• Subcostal retraction (a sign of air-trapping/hyperinflation of the lungs), as can occur in pneumonia;
• Reduced oxygen levels (hypoxemia); and
• Increased respiratory rate (tachypnea).

The research team assigned each case an overall score. The severely premature children had worse overall scores — and significantly worse scores for AHR and hyperinflated lungs relative to children born late preterm or full-term.
“What surprised us, though, in this study was that the phenotypical characterization using individual parameters for parenchymal lung disease, such as hypoxemia or tachypnea, were not different in severe preterm children and preterm or full term,” says Dr. Perez. “On the other hand, our study found that severely preterm children had a lower airway obstruction phenotype associated with retractions and wheezing. Moreover there was a ‘dose effect’ of prematurity: children who were born more premature had a higher risk of wheezing and retractions.”
Among the implications of this study, Dr. Perez sees the potential to use phenotypical (clinical markers, such as retractions and wheezing) and biological biomarkers to better personalize patients’ treatments. Dr. Perez and his team have identified biological biomarkers in nasal secretions of children with rhinovirus infection that they plan to combine with clinical biomarkers to identify which patients with viral infections will benefit from early supportive care, chronic treatments or long-term monitoring.
ScienceDailyhttps://tinyurl.com/yd3mz3eu