About one third of cancer patients die because of cachexia – an involuntary weight loss, characterized primarily by muscle wasting and metabolic changes, which cannot be addressed or treated solely with increased food intake. A study by researchers at the McGill University Health Centre (MUHC) aims to save patient lives by giving doctors a practical tool to easily diagnose cachexia before it becomes irreversible.

Cachexia is a serious health condition that goes beyond simple weight loss. Clinicians and scientists have been trying to better understand and treat this condition for many years. It is often associated with poor responses to oncological treatments, increased hospitalizations, and has been shown to be a major burden to family caregivers. It is still largely overlooked and untreated in many oncology centres. Patients with this condition eventually experience a decline of their overall health to a point where it cannot be reversed by eating more or taking nutritional supplements. Despite recent advancements in research, cachexia remains very difficult to alleviate or treat.

‘We are losing many cancer patients, not because of their cancer, but because their bodies have undergone important metabolic changes. In other words, they have simply stopped functioning correctly. In severe stages of cachexia, weight loss becomes very important and nutrients can no longer be absorbed or used properly by cancer patients,’ explains Dr. Antonio Vigano, lead author of the paper and Director of the Cancer Rehabilitation Program and Cachexia Clinic of the MUHC. ‘Cachexia gets worse with time and the longer we wait to address it, the harder it is to treat. Effectively diagnosing cachexia when still in its early stages can make an enormous difference for a cancer patient’s prognosis and quality of life. In order to save more lives, we need practical and accessible tools that can be effectively used by clinicians in their routine practice to identify patients with cachexia.’

The tool developed to diagnose cachexia is composed of five routinely available clinical measures and laboratory tests, which could be available to doctors within the next few years or sooner. The researchers also hope the tool can be applied to other patients who are losing weight from chronic diseases, such as acquired immunodeficiency syndrome (AIDS), chronic obstructive pulmonary disease, multiple sclerosis, chronic heart failure, tuberculosis and many more.

Dr. Vigano’s team at the McGill Nutrition and Performance Laboratory (MNUPAL) is also participating in studies aiming at developing treatments for cachexia. However, he insists, these treatments will only be useful if doctors can diagnose cachexia and understand the severity of each case. ‘Research is still needed to understand all the causes of cachexia. Unless we can talk the same language in terms of what type of patients we are treating and the severity of their condition, it is often very difficult to make substantial progress,’ he states.

McGill University Health Centre muhc.ca/newsroom/news/race-against-time-diagnose-deadly-weight-loss-cancer-patients

The brain is the most temperature-sensitive organ in the body. Even small deviations in brain temperature are capable of producing profound effects-including behavioural changes, cell toxicity, and neuronal cell death. The problem faced by researchers and clinicians is how to measure and understand
these changes in the brain and how they are influenced by complex biochemical and physiological pathways that may be altered by disease, brain injury or drug abuse.
In a new paper Stefan Musolino of the University of Adelaide and the ARC Centre of Excellence for Nanoscale BioPhotonics, Australia, and his colleagues describe a new optical fibre-based probe capable of making pinpoint brain temperature measurements in moving lab animals.
‘Within our centre we house physicists, chemists, and medical researchers and one of the interests of our centre’s Origin of Sensation’ theme is temperature change in the central nervous system,’ Musolino said. ‘It is only recently that more studies in my area of research- drug-induced hyperthermia- have started looking at changes in brain temperature in addition to changes in core body temperature within drug-treated animals.
We wanted to further investigate these drug-induced brain temperature changes using centre-developed probes in order to develop a better understanding of the mechanisms driving them.’
The probe developed by Musolino and his colleagues consists of an optical fibre, sheathed within a protective sleeve and encased within a 4-millimeter-long 25-gauge needle. The end-face of the approximately 2-mm-long probe tip is dipped into molten glass made of tellurite, doped with a small amount of the rareearth oxide erbium. When inserted into the brain, the colour of the light emitted from the erbium ions will vary depending on the temperature of the surrounding tissue; the temperature of that tissue can thus be determined by monitoring the light of these colour changes. This method allows for measurements to be performed with a precision of a fraction of a degree (0.1degree CelsiusC).
‘The area that can measure temperature is less than 125 micrometers in size,’ said study co-author Erik Schartner ‘making it highly spatially precise and able to isolate temperature readings from very small brain areas.’ The researchers say it is possible to make the temperature-sensing area of the probe tip smaller still – as small as a few microns across – by modifying the probe’s design.
The probe’s immediate application will be to investigate changes in brain temperature within moving lab animals exposed to certain drugs of abuse, such as MDMA (or ecstasy’). ‘We will also look at the possible therapeutic properties of the tetracycline antibiotic minocycline and its ability to attenuate the changes in temperature caused by the administration of MDMA,’ said Musolino. ‘In the future we will also be looking into combining this probe with other optical sensors in the hopes of developing new optical fibre-based sensing techniques for use in medical science labs that are examining real-word medical problems.’
Eventually, a fully developed probe could be used in human brain temperature monitoring after traumatic brain injury, stroke or hemorrhage – times when the brain is extremely sensitive and small deviations in temperature can lead to additional brain injury.
‘Continuous monitoring of brain temperature after brain injury would allow for the effects of hyperthermia management techniques such as anti-pyretics – drugs that reduces fever – and hypothermia to be observed and evaluated by clinicians in real time,’ Musolino said. ‘These new tools and this deeper understanding will ultimately give us better understanding of the brain and how to more quickly react to brain injury.’

The Optical Society http://tinyurl.com/hkrqo9w

Researchers investigating a novel device to repair the mitral heart valve report 100 percent procedural success in a safety and performance study, the first such study done in humans. The image-guided device, based on technology developed at the University of Maryland School of Medicine, is deployed through a tiny opening in a beating heart, avoids open-heart surgery, automates a key part of the valve repair process, simplifies the procedure and reduces operating room time.
Traditional mitral valve repair is performed during open heart surgery, a lengthy operation in which the patient’s chest is opened, the heart is stopped and circulation is maintained with a heart-lung bypass machine. Recovery can take months, and patients face significant risks. As a result, there is considerable interest in finding less invasive mitral valve treatment options.
‘We think this is a safer approach than open heart surgery,’ says principal investigator James S. Gammie, MD, professor and chief of cardiac surgery at the University of Maryland School of Medicine. ‘We think the safety profile is going to be better and, ultimately, people will be able to go home from the hospital the next day.’
The device, known as the Harpoon TSD-5, made by Harpoon Medical Inc. of Baltimore, is an investigational device. At the present time, the US Food and Drug Administration has not approved the device for use in patients in the United States. It is designed to treat degenerative mitral regurgitation (MR), the most common type of heart valve disorder. In MR, a leaky valve lets blood travel in the wrong direction on the left side of the heart, causing shortness of breath, fluid retention, irregular heartbeats and fatigue. MR develops when the small fibrous cords that open and close the valve’s flaps, known as leaflets, are broken or stretched, preventing them from closing tightly and causing the leaflets to bulge or prolapse upward toward the left atrium. The natural cords connect the valve flaps to muscles inside the heart that contract to close the mitral valve, which gets its name because its two flaps resemble a bishop’s mitre.
The TSD-5 anchors artificial cords on the flaps to take the place of the natural cords. The artificial cords are made of expanded polytetrafluoroethylene (ePTFE), a polymer commonly used as sutures in cardiac surgery.
Surgeons insert the device into the beating heart through a tiny opening in the ribcage and, using echocardiographic imaging, guide it to the surface of the defective mitral flaps. When the surgeon determines the optimal placement for an artificial cord, the device is actuated and a specially designed needle wrapped with 50 coils of ePTFE makes a tiny hole and sends the cord material through the flap. An automated process makes a knot to hold the cord in place. The other end of the cord is adjusted for optimum length and tied to the outside layer of the heart, the epicardium. Three or four cords are required for most cases.
Gammie says the ability to make adjustments to the artificial cords while the heart is beating is a key advantage over open heart surgery: ‘The heart’s fully loaded and beating and we can just adjust the length of the cords to optimize the result, and only when we’re really happy do we tie it off.’

University of Maryland School of Medicine http://tinyurl.com/j5m9lmp

A team of Mayo Clinic researchers has, for the first time, successfully mapped patterns of prostate cancer recurrence, following surgery. Using C-11 choline PET imaging and multi-parametric MRI, researchers found an anatomically diverse pattern of recurrence, which may help optimize treatment of patients whose prostate cancer returns after surgery.
‘This study has important implications for men who have a rising prostate-specific antigen (PSA) test, also known as biochemical recurrence, after radical prostatectomy for prostate cancer,’ says Jeffrey Karnes, M.D., a urological surgeon at Mayo Clinic. ‘In men with biochemical recurrence, determining where the disease has recurred is quite challenging, especially when the PSA level is low.’
According to Dr. Karnes, in the U.S., approximately 30 percent of patients who have had an initial prostate cancer surgically excised will suffer a recurrence and seek treatment. ‘Current imaging tests like conventional bone and CT scans are not sensitive enough to identify sites of recurrence, especially when the PSA value is lower than 10,’ he says.
Dr. Karnes says the combination of C-11 choline PET scanning and multiparametric MRI, helps physicians accurately identify sites of recurrence at an average PSA of 2. More importantly, he says, ‘This type of staging allows us to identify sites of recurrent disease that can be potentially treated either surgically or with radiation.’
Dr. Karnes and his team also were able to describe patterns of prostate cancer recurrence. They found that nearly two-thirds of men in the study had recurrence limited to the pelvis, which potentially can be targeted for radiation therapy.

Mayo Clinic http://tinyurl.com/h9ot93x

Computer algorithms can automatically interpret echocardiographic images and distinguish between pathological hypertrophic cardiomyopathy (HCM) and physiological changes in athletes’ hearts, according to research from the Icahn School of Medicine at Mount Sinai (ISMMS).

HCM is a disease in which a portion of the myocardium enlarges, creating functional impairment of the heart. It is the leading cause of sudden death in young athletes. Diagnosing HCM is challenging since athletes can present with physiological hypertrophy, in which their hearts appear large, but do not feature the pathological abnormality of HCM. The current standard of care requires precise phenotyping of the two similar conditions by a highly trained cardiologist.

‘Our research has demonstrated for the first time that machine-learning algorithms can assist in the discrimination of physiological versus pathological hypertrophic remodeling, thus enabling easier and more accurate diagnoses of HCM,’ said senior study author Partho P. Sengupta, MD, Director of Cardiac Ultrasound Research and Professor of Medicine in Cardiology at the Icahn School of Medicine at Mount Sinai. ‘This is a major milestone for echocardiography, and represents a critical step toward the development of a real-time, machine-learning-based system for automated interpretation of echocardiographic images. This could help novice echo readers with limited experience, making the diagnosis rapid and more widely available.’

Using data from an existing cohort of 139 male subjects who underwent echocardiographic imaging at ISMMS (77 verified athlete cases and 62 verified HCM cases), the researchers analyzed the images with tissue tracking software and identified variable sets to incorporate in the machine-learning models. They then developed a collective machine-learning model with three different algorithms to differentiate the two conditions. The model demonstrated superior diagnostic ability comparable to conventional 2D echocardiographic and Doppler-derived parameters used in clinical practice.

‘Our approach shows a promising trend in using automated algorithms as precision medicine techniques to augment physician-guided diagnosis,’ said study author Joel Dudley, PhD, Director of the Institute for Next Generation Healthcare and Director of the Center for Biomedical Informatics at ISMMS. ‘This demonstrates how machine-learning models and other smart interpretation systems could help to efficiently analyse and process large volumes of cardiac ultrasound data, and with the growth of telemedicine, it could enable cardiac diagnoses even in the most resource-burdened areas.’

Mount Sinai Health System www.mountsinai.org/about-us/newsroom/press-releases/mount-sinai-researchers-demonstrate-ability-of-machine-learning-algorithms-in-echocardiographic-interpretation-and-diagnosis-of-hcm