Investigators at Brigham and Women’s Hospital have developed a hydrogel patch that can adhere to tumours in a preclinical model of colon cancer, delivering a local, combination treatment as the elastic gel breaks down over time. The new technique may allow clinicians to someday use diagnostic colonoscopy equipment to immediately deliver treatment without the need for open surgery at a later date.
The researchers were able to deliver three therapeutic strategies in their mouse model of colon cancer: gene therapy, chemotherapy or thermal ablation or a combination of all three. The team used gold nanoparticles to deliver a gene therapy treatment that targets Kras, a known cancer gene, and used near-infrared radiation to release a chemotherapeutic and cause heat damage to the cancer cells. The local, triple-combination therapy not only shrank tumours but also had a sustained effect overtime, preventing tumour recurrence and significantly extending survival of mice.
The researchers examined the effects of the therapy both with and without resection (surgical removal of the tumour), which is the current standard treatment for colon cancer in humans. In human cases where resection is not possible, a neoadjuvant therapy, such as chemotherapy or radiation therapy, is often used to shrink tumours before clinicians attempt to remove them. Natalie Artzi, PhD senior author of the study and a principal investigator at BWH, and her colleagues anticipate that their hydrogel patch could someday be used to shrink tumours before resection or could eliminate the need for resection entirely. They plan to test the material in larger preclinical models and dive more deeply into the genetic changes resulting from therapy to pinpoint which genes are most critical to target.
Brigham and Women’s Hospital www.brighamandwomens.org/about_bwh/publicaffairs/news/pressreleases/PressRelease.aspx?PageID=2459
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Rice University students have created a prototype of a device to monitor the pulse and oxygen levels of a fetus undergoing endoscopic fetal surgery in a mother’s womb. The WombOx team of senior engineering students worked in close collaboration with the Texas Children’s Fetal Center to create their device, which miniaturizes the components found in a pulse oximeter commonly clipped to a patient’s finger in a doctor’s office. Pulse oximeters ‘see’ oxygen levels in the blood by comparing light from a source to the light that reaches a detector on the other side of the finger. The instrument can calculate oxygen saturation by how much light it senses is absorbed by the tissue. That kind of information hasn’t been available to doctors working to help fetuses suffering from congenital defects such as spina bifida, the incomplete closure of the backbone around the spinal cord. Texas Children’s Hospital is pioneering efforts to treat such conditions through the endoscopic procedure known as fetoscopic surgery. During surgery, doctors are able to monitor the health of a fetus through ultrasound, but that only gives them a basic heartbeat. Knowing oxygen levels in the blood is critical when doctors need to act quickly to help a fetus in distress, and the WombOx device shows potential for providing such data in real time. To build the prototype, the bioengineering students, Claudia Iriondo, Thomas Loughlin, Samir Saidi and Kathryn Wallace, worked closely with Dr. Magdalena Sanz Cortes, an associate professor of obstetrics and gynecology at Baylor College of Medicine and a clinician at the Texas Children’s Pavilion for Women, as well as their Rice faculty adviser, engineering lecturer Eric Richardson. It is the product of their capstone design project, required of most senior engineering students at Rice. A few weeks after winning the top Willy Revolution Award, a $5,000 prize presented at Rice’s annual Engineering Design Showcase for innovation in design, and days before commencement, the team spent a morning in a device-testing suite at the Pavilion for Women to watch their prototype in action. ‘This project was challenging because of the size of the instruments that we work with,’ Sanz Cortes said. ‘When we started talking about the whole project, we talked about the size of a pulse oximeter. Transforming that into the size of the device they have created is very challenging. ‘The other challenging part was the mechanics, how to design something that is safe enough for the baby and can be compatible with our surgeries. It’s not a trivial matter, and they did a great job,’ she said. At first glance, the device is a loop of wire on a hollow stick. But a closer look reveals that the wire is a special hybrid that expands to a predetermined shape at the correct temperature. It carries LEDs and a photodetector on miniature circuit boards that illuminate and sense the flow of blood through the tissue underneath. The loop is packaged in a retractable sheath that fits through the small incision made in fetoscopic surgeries. The WombOx device is used like all other endoscopic tools, with a miniature camera. The idea is to insert the tube into the mother’s womb and extend the loop. Once it expands, doctors use the video feed to guide the loop around a limb and gently tighten it, putting the sensors in place to monitor the fetus throughout the surgical procedure. ‘Our design, like other endoscopic tools, is intended for single use,’ Iriondo explained. The device is durable enough to withstand unsheathing, expansion in the womb, attachment to the fetus and resheathing during removal.’
Rice University http://tinyurl.com/z3p6dmc
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Paediatric researchers have devised an innovative, safe and minimally invasive procedure that helps relieve rare but potentially life-threatening airway blockages occurring in children who had surgery for congenital heart defects. The physician-researchers developed new imaging tools and used minimally invasive catheterization techniques to treat plastic bronchitis, a condition in which abnormal circulation causes lymphatic fluid to dry into solid casts that clog a child’s airways. The study, which describes the pathophysiological mechanism of plastic bronchitis and a treatment approach, arose from collaboration between Maxim Itkin, MD, an associate professor of Radiology in the Perelman School of Medicine at the University of Pennsylvania, and Yoav Dori, MD, a pediatric cardiologist in the Cardiac Center at The Children’s Hospital of Philadelphia (CHOP). They co-lead a specialized team dedicated to the care of lymphatic disorders as part of the Center for Lymphatic Imaging and Interventions at The Children’s Hospital of Philadelphia and the Hospital of the University of Pennsylvania. ‘This is a new treatment option for children with plastic bronchitis and has the potential to offer long-term improvement of this condition,’ said Dori. ‘This procedure may even provide cure and avoid the need for a heart transplant.’ The current study builds on the team’s 2014 article in Pediatrics, the first case report of the successful use of their technique in a patient with plastic bronchitis. ‘We have expanded on that study to report short-term outcomes in a larger group and to share insights into the development of plastic bronchitis, which has been poorly understood,’ said Itkin. In addition to heart patients, children and adults with idiopathic plastic bronchitis, in which the cause is unknown, have also been treated successfully using these techniques. Itkin and Dori discovered that the primary cause of plastic bronchitis is a lymphatic flow disorder, due to abnormal lymphatic flow into lung tissue. Because physical examinations and conventional imaging may not provide specific findings, lymphatic flow disorders often go undiagnosed. Over the past several years, Itkin and Dori developed a customized form of magnetic resonance imaging (MRI), called dynamic contrast enhanced MR lymphangiogram, to visualize the anatomy and flow pattern of a patient’s lymphatic system. This technique allows clinicians to locate the site at which lymph leaks into the airways. Plastic bronchitis may occur in children as a rare complication of early-childhood heart surgeries used for single-ventricle disease, in which one of the heart’s pumping chambers is severely underdeveloped. Approximately 5 percent of children surviving this surgery experience plastic bronchitis because the surgery alters venous and lymphatic pressure. The authors argue that this altered pressure may interact with pre-existing anatomical differences in the patients’ lymphatic vessels. The abnormal circulation causes lymph to ooze backward into a child’s airways, drying into a caulk-like cast formation that takes the shape of the airways. The first sign of plastic bronchitis may be when a child coughs out the cast. However, if unable to cough it up, a child may suffer fatal asphyxiation. After identifying the leakage site in a lymphatic vessel, the lymphatic team intervenes, using a technique called lymphatic embolization. Through small catheters, the team blocks the abnormal flow with a variety of tools: coils, iodized oil, and covered stents, based on an individual patient’s needs. In the current report, the team was able to perform lymphatic embolization in 17 of their 18 patients, ranging from age 2 to age 15 (median age 8.6 years). Fifteen of those 17 patients had significant improvements in cast formation, in some cases being cast-free longer than two years. Patients had transient side effects of abdominal pain and hypotension (low blood pressure), but the authors reported the procedure appeared safe in their patient group.
The Children’s Hospital of Philadelphia http://tinyurl.com/hjr4jps
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Computational modelling makes it possible to predict the onset and progression of knee osteoarthritis in overweight people, shows a new study from the University of Eastern Finland. A computational model based on the degradation of the collagen fibril network in the articular cartilage was able to predict the onset and progression of osteoarthritis in overweight people during a four-year follow-up. In normal-weight people, osteoarthritis did not develop within this time span.
The study also developed a model of the knee joint which makes it possible to evaluate the mechanical responses experienced by cartilage cells in healthy and osteoarthritic cartilage during daily activities such as walking. The model demonstrated that both menisectomy and osteoarthritic changes to the cartilage cause significant alterations in cartilage cell responses.
Osteoarthritis is a joint disease estimated to affect around 5% of the total world population. Osteoarthritis is the most common in the knee or hip joint and it often develops as a result of ageing, but it can also develop due to excessive loading or joint injury. In Europe, over 100 million people have arthritis, and in America, direct costs of arthritis were $51.1 billion in 2004. In addition, it has been predicted that the number of patients with knee osteoarthritis increases by 40% by the end of 2050.
Osteoarthritis proceeds gradually, weakening the articular cartilage and ultimately wearing it off completely from the ends of articulating bones. In these cases, the patient suffers from heavy joint pain and the joint becomes stiff, often leading to incapacity for work. Joint replacement surgery is the only effective treatment for osteoarthritis, which is why the prevention of osteoarthritis would be a cost-effective alternative both for the patient and society at large.
The study utilised a computational modelling method integrating the tissue and cellular levels of the articular cartilage in order to analyse the function of the articular cartilage during the onset and progression of osteoarthritis. The method simulated the effect of articular cartilage composition, structure and various loadings on the volume, shape and mechanical responses of cartilage cells.
Compared to healthy cartilage, the cell volume of osteoarthritic cartilage increased as a result of mechanical loading. The modelling indicated that the most important explanatory factors for the cell volume increase were the pericellular fixed charge density, i.e. the number of proteoglycan molecules, and the stiffness of the collagen fibril network.
The study also analysed the effect of menisectomy, a commonly used method in knee surgery, and simulated overweight on cell responses. Both menisectomy and simulated overweight substantially increased fluid pressures in the cell and cartilage tissue during walking, but they did not have an effect on the cell shape or volume in healthy cartilage. In osteoarthritic cartilage, however, cells were compressed and elongated more, probably due to altered cartilage integrity.
During standing, the strains were amplified more in the cell than in pericellullar tissue in healthy joint cartilages, but the opposite was observed in osteoarthritic joint cartilage. It is possible that the pericellular tissue’s function is to protect cartilage cells from sudden changes and to promote cartilage health.
The study also developed computational algorithms for the degradation of the collagen fibril network in the articular cartilage and its reorganisation in order to predict the development and progression of osteoarthritis caused by overweight and cartilage damage. The estimate obtained from the degradation algorithm was well in line with the clinically observed progression of osteoarthritis during a four-year follow-up. Furthermore, the collagen fibril network structure in the mechanically injured cartilage was observed to be disorganised in the vicinity of the injury, suggesting that a cartilage injury exposes cartilage to further damage.
In-depth understanding of the effects of abnormal loading, early osteoarthritis and mechanical injuries on cellular and tissue responses in cartilage makes it possible to develop new strategies for the recognition, prevention and slowing down the progression of the disease. The methods developed in the study may become widespread in specialised health care in the future. However, rigorous clinical validation will be necessary before they can be introduced to clinical use.
University of Eastern Finlandwww.uef.fi/-/computational-modelling-can-predict-onset-and-progression-of-knee-osteoarthritis-in-overweight-people
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Surgical teams from the UK-based charity Healing Little Hearts are using the NanoMaxx point-of-care ultrasound to help accelerate recoveries and improve outcomes for pediatric patients with congenital heart defects. Healing Little Hearts provides life-saving heart operations to babies and children across India who would not otherwise have access to treatment, as well as helping to develop local pediatric surgical programmes. Dr Sanaulla Syed, a pediatric cardiac anesthetist with the charity, commented: ‘Obtaining vascular access in small children can be difficult, and the availability of point of care ultrasound systems has revolutionized this practice. As the technology has improved, this has led to other applications, and we now use ultrasound for a range of diagnostic applications before, during and after cardiac surgery. Ultrasound-guided regional anesthesia – specifically bilateral paravertebral blocks – can also significantly reduce the amount of opiates required for surgery, considerably shortening post-operative recovery times and offering improved analgesia.’
www.sonosite.com
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There is a high rate of prescription pain reliever abuse in Europe, largely accounted by opioids, according to the first comparative study of prescription drug abuse in the European Union, which was conducted by researchers at RTI International.
The study investigated nonmedical prescription drug use in five European countries – Denmark, Germany, Spain, Sweden and the United Kingdom.
‘For certain classes of medications, like opioids, we found a significant rate of prescription pain reliever abuse in the EU,’ said Scott Novak, Ph.D., lead author of the study and senior development epidemiologist at RTI. ‘While the lifetime rates were not as high as in the U.S. – 20 percent for those aged 12 years and over, compared to between 7 percent and 13 percent in the EU – the past-year rates were only slightly lower. This suggests that the EU may be catching up to the United States for some substances.’
Nonmedical prescription drug use is typically defined as either the self-treatment of a medical condition using prescription medication that was not prescribed to the user, or as the use of prescription medication to achieve euphoric states. Nonmedical prescription drug use is among the leading public health issues in the United States and previous research has suggested that it is more widespread in the United States than in Europe, where prevalence and user characteristics remain largely unknown.
‘Previously, it was thought that the prescription drug epidemic was limited to the United States,’ Novak said, ‘but this study shows that the epidemic extends well beyond the U.S.’
Examining three different classes of subscription drugs – opioids, sedatives and stimulants – the researchers found that out of the five countries examined, Germany had the lowest levels of nonmedical prescription drug use, while the U.K., Spain and Sweden had the highest levels.
The most common sources of prescription drugs for nonmedical use were family and friends – 44 percent for opioids and 62 percent for sedatives. The next most common source was taking drugs from another person without their knowledge. Internet purchases were the least common source of prescription drugs.
Nonmedical prescription drug use was more common among men relative to women, among white relative to non-white people, and among those who were unemployed compared with other levels of employment. Young people aged 12 to 17 years were at lower risk of nonmedical prescription drug use than people aged 18 years or older.
Having been prescribed a pain reliever was associated with an eight times higher risk of subsequent nonmedical use of prescription pain relievers. The risk was ten times higher for sedatives and seven times higher for stimulants.
The researchers also found that about 52 percent of nonmedical stimulant users, 32 percent of nonmedical opioid users and 28percent of nonmedical sedative users also consumed illicit drugs – this is known as poly-drug use. Rates of poly-drug use involving either sedatives or opioids were highest in the U.K. – 48 percent for sedatives and 43 percent for opioids. Women were about half as likely to engage in poly-drug use as men. Suffering from serious psychological distress, having a sexually transmitted disease and having a history of childhood arrest were also associated with a higher risk of poly-drug use.
The study suggests that international collaborations across Europe are needed to monitor prescription drug abuse, identify its scope and develop targeted interventions.
Identification of the scope and prevalence of nonmedical prescription drug use in the EU is an important first step in building a worldwide system that can be used to monitor trends, track risk and protective factors and to develop targeted interventions aimed at reducing the risk of nonmedical prescription drug use, according to the researchers.
The authors caution that their findings should not be construed as recommendation against prescribing medications to treat legitimate conditions. The cross-sectional design of this study made it impossible to resolve the question if nonmedical prescription drug use serves as a gateway to other substances or if persons using illicit drugs are at higher risk for also using prescription drugs to self-treat or to achieve euphoria.
RTI International www.rti.org/news/prescription-drug-abuse-epidemic-extends-beyond-united-states
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When ketamine is used for general anesthesia, two connected parts of the cortex turn to ‘isolated cognitive islands.’ It’s a topic that has long captivated doctors, scientists and the public – what exactly happens in your brain when you’re oblivious on the operating table? Some anesthesia drugs work in a straightforward manner by dampening down neurons in the brain. The mechanism of one anesthetic, however, has proved elusive: ketamine. Certain doses of ketamine induce general anesthesia, though brain activity can still be robust, says Cynthia Chestek, Ph.D., co-senior author of a new study in neuroimage. Ketamine is used often in patient care and in laboratory settings. The new paper examines the neurological mechanisms at work during ketamine anesthesia. Co-senior authors Chestek and anesthesiologist George Mashour, M.D., Ph.D., led the research team, which took precise measurements down to the level of neurons in animal models. ‘We found that general anesthesia reflects a communication breakdown in the cortex, even though sensory information is getting processed,’ Mashour says. ‘But the processing appears to occur in isolated cognitive islands.’ Two adjacent parts of the brain that work together in the waking state simply stop talking to each other under general anaesthesia. When awake, communication between the primary somatosensory cortex and the primary motor cortex is critical to normal function. ‘This supports the idea that what anesthesia does to cause unconsciousness is interrupt communication between brain areas, stopping the processing of higher-level information,’ says first author Karen Schroeder, a doctoral candidate in the U-M Department of Biomedical Engineering. ‘This was the first time anyone directly observed the interruption between the two areas using individual neurons.’ Chestek’s biomedical engineering lab focuses on brain machine interfaces, recording activity of neurons and reading motor commands and sensory information in real time. So her team got on board to measure both areas of the brain, which kept firing during anesthesia. ‘As soon as we injected ketamine, the sensory information disappeared from the motor cortex. Normally these areas are tightly connected.’ The group plans to continue this work, turning next to investigate the level of anesthesia at which these changes in communication start to occur. They’re also looking into what the groups of neurons are doing under anesthesia when they are still active but no longer communicating with each other. ‘These insights could potentially improve our ability to monitor patients’ level of consciousness,’ Schroeder says.
University of Michiganhttp://tinyurl.com/z96b64d
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A survey finds that consumers are enthusiastic about the future of wearables, especially in health and wellness, but they’re still having issues staying motivated. Roughly one-third of those who bought smart clothing have admitted they aren’t using them as much anymore. The drop-off rate meanwhile, is 18 percent for fitness bands, 22 percent for smart watches and 16 percent for smartglasses. According to the survey, consumers say they lose their enthusiasm for wearables after a while, finding them ineffective, uncomfortable or unstylish, or finding that they can’t synch seamlessly with a smartphone or hold battery power. ‘For consumers to commit to wearables for the long term, a device should not only be attractive and comfortable, but should also reach beyond data delivery to provide knowledge and benefits unavailable elsewhere,’ states the report, titled ‘The Wearable Life 2.0: Connected Living in a Wearable Wiorld.’ While that news is discouraging, healthcare should take note of the rising numbers of consumers investing in wearables. Of those surveyed, 45 percent own a fitness band, 27 percent now own a smartwatch and 12 percent own sensor-embedded clothing. And while the percentage of people who see a bright future for wearable has jumped 16 percent since PwC’s 2014 survey, the number of respondents who have security or privacy concerns about wearables has dropped about 8 percent in those past two years. The survey also highlights a trust issue in healthcare. While the provider community hasn’t embraced consumer-facing wearables because they don’t think the data coming from them is reliable enough to use in clinical situations, consumers have their concerns as well. It’s a good news-bad news issue. According to the survey, some 65 percent of consumers are excited about the possibility of using a wearable provided or endorsed by their doctor’s office, while 62 percent feel that way about wearables coming from a hospital or their insurer. On the other hand, only 41 percent would trust a wearable coming from their doctor, while only 38 percent would trust a hospital-supplied wearable and only 34 percent would place their faith in a payer-supplied device. Farther down the list, 57 percent are excited about a wearable coming from their pharmacy, but only 29 percent would trust the device. And 25 percent of those surveyed said they wouldn’t trust their personal information to any branded wearable. So what motivates someone to use a wearable? According to the survey, more than half say they’d be motivated by a monetary reward, while 45 percent like gaming features that allow them to compete with others. Another 45 percent would use wearables if they provided information that they’d otherwise not have, and 36 percent want it to look good. They also want the device to synch with their smartphone – 78 percent said they’d use a wearable more frequently if it connected seamlessly to their smartphone, and 97 percent are happy with a smartphone application supporting the wearable.
mHealth Intelligence http://tinyurl.com/ht3q2r3
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New approach could aid in treatment of inflammatory bowel disease. Using ultrasound waves, researchers from MIT and Massachusetts General Hospital (MGH) have found a way to enable ultra-rapid delivery of drugs to the gastrointestinal (GI) tract. This approach could make it easier to deliver drugs to patients suffering from GI disorders such as inflammatory bowel disease, ulcerative colitis, and Crohn’s disease, the researchers say. Currently, such diseases are usually treated with drugs administered as an enema, which must be maintained in the colon for hours while the drug is absorbed. However, this can be difficult for patients who are suffering from diarrhea and incontinence. To overcome that, the researchers sought a way to stimulate more rapid drug absorption. ‘We’re not changing how you administer the drug. What we are changing is the amount of time that the formulation needs to be there, because we’re accelerating how the drug enters the tissue,’ says Giovanni Traverso, a research affiliate at MIT’s Koch Institute for Integrative Cancer Research, a gastroenterologist at MGH, and one of the senior authors of a paper describing the technique in the Oct. 21 issue of Science Translational Medicine. ‘With additional research, our technology could prove invaluable in both clinical and research settings, enabling improved therapies and expansion of research techniques applied to the GI tract. It demonstrates for the first time the active administration of drugs, including biologics, through the GI tract,’ says Daniel Blankschtein, the Hermann P. Meissner Professor in Chemical Engineering, who is also a senior author of the paper. Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, is also a senior author of the paper. The study’s lead author is Carl Schoellhammer, a graduate student in chemical engineering. Langer began exploring the possibility of using ultrasound to enhance drug delivery 30 years ago. ‘We’ve been working on ultrasound as a means to enhance transport through materials and skin since the mid-1980s, and I think the implications of this new approach have the potential to aid many patients,’ Langer says. Ultrasound improves drug delivery by a mechanism known as transient cavitation. When a fluid is exposed to sound waves, the waves induce the formation of tiny bubbles that implode and create microjets that can penetrate and push medication into tissue. In this study, the researchers first tested their new approach in the pig GI tract, where they found that applying ultrasound greatly increased absorption of both insulin, a large protein, and mesalamine, a smaller molecule often used to treat colitis. ‘Demonstrating delivery of molecules with a wide range of sizes, including active biologics, underscores the potentially broad areas in which this technology could be applied,’ says Schoellhammer, who won the $15,000 Lemelson-MIT ‘Cure it!’ Student Prize earlier this year for this research and for a micro-needle pill that delivers drugs directly into GI tissue. The team also reached the finals of the MIT $100K Entrepreneurship Competition.
MIT http://tinyurl.com/p8v9j2r
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A multicenter team of researchers led by Barbara Murphy, MD, of the Icahn School of Medicine at Mount Sinai has identified a panel of genes which can help predict whether a transplanted kidney will later develop fibrosis, an injury which can cause the organ to fail.
Researchers in the Genomics of Chronic Allograft Rejection (GoCAR) study obtained biopsy samples from transplanted kidneys three months and twelve months after transplantation. Using microarray, a method by which the expression levels of a large numbers of genes or proteins can be measured simultaneously, the researchers determined which genes were correlated with biopsy samples which had an increased Chronic Allograft Damage Index (CADI) score at the 12-month biopsy. The CADI score is a measure of the level of fibrosis in the transplanted kidney. The researchers then narrowed the genes down to a predictive gene set that identified patients at risk for decline in renal function and loss of the transplanted kidney beyond one year. The rate of correlation of the identified gene set with damage was greater than the clinico-pathological variables currently used in practice to identify kidney transplant recipients at risk of allograft damage and loss.
‘This is the first finding of its kind,’ said Barbara Murphy, System Chair of Medicine for the Mount Sinai Health System and Murray M. Rosenberg Professor of Medicine (Nephrology) at the Icahn School of Medicine at Mount Sinai, and the lead investigator on the study. ‘By helping us better understand the causes of damage to transplanted kidneys, this study has the potential to change how we monitor and manage all renal transplant patients.’
‘The study offers the potential to identify renal transplant recipients at risk for a loss of the new organ prior to the development of irreversible damage,’ said Dr. Murphy. ‘This would mean that doctors might eventually have the opportunity to change the therapeutic treatment approach in order to prevent fibrosis from progressing at all.’
Mount Sinai Health System www.mountsinai.org/about-us/newsroom/press-releases/mount-sinai-researchers-identify-way-to-predict-and-prevent-damage-in-donated-kidneys
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