Highlights Among hemodialysis patients admitted to the hospital, nearly a quarter of admissions were followed by an unplanned readmission within 30 days. Most readmissions were for a diagnosis different than the one for the initial hospitalization. A small proportion of patients accounted for a disproportionate number of readmissions. A new analysis found that nearly one-quarter of dialysis patients who are admitted to the hospital are readmitted soon after discharge, often for a diagnosis that is different than the one that led to the initial hospitalization. The analysis, which appears in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN), also identified certain patient characteristics linked to hospital readmissions. More than half a million people in the United States receive treatment for kidney failure, mostly through hemodialysis. On average, hemodialysis patients are admitted to the hospital nearly twice a year, and they have double the 30-day readmission rate as patients without kidney dysfunction. In 2017, the Centers for Medicare and Medicaid Services began penalizing outpatient dialysis units for excessive readmissions. Despite these efforts, there is a lack of information regarding characteristics and predictors of readmission. To investigate, a team led by Girish Nadkarni, MD, MPH and Lili Chan, MD, MS (Icahn School of Medicine at Mount Sinai) set out to determine the nationwide readmission rate in dialysis patients and to examine reasons for initial admissions and readmissions. When the researchers analyzed 2013 data from the Nationwide Readmission Database, they found 390,627 initial hospitalizations of hemodialysis patients, and 22% of these initial hospitalizations were followed by an unplanned readmission within 30 days. Readmission rates were similar across the top 10 initial admission diagnoses, and only 20% of readmissions were for the same diagnosis as the initial admission. “Regardless of what patients initially were admitted for, they had similar readmission rates. This along with the low concordance suggests that we need to focus on the patient as a whole rather than their admission diagnoses,” said Dr. Chan. The investigators also found that patient characteristics that were associated with a high likelihood of readmission included female gender, younger age, depression, liver disease, congestive heart failure, and drug abuse. Importantly, only a small proportion (2%) of all patients accounted for 20% of all readmissions. “To reduce readmissions in dialysis patients, perhaps a good starting place would be to institute interventions targeted at high utilizers and create a validated risk score incorporating likely risk factors,” said Dr. Nadkarni. In an accompanying editorial, Magdalene Assimon, PharmD, MS and Jennifer Flythe, MD, MPH (UNC School of Medicine) noted that there is surprisingly little published data evaluating interventions designed to reduce readmissions and stressed “the need for innovative, integrative data analytics in readmission risk modeling and a greater emphasis on testing and refining readmission prevention strategies.” They also quoted the American philosopher John Dewey, who said, “A problem well put, is half-solved.” “The problem of 30-day hospital readmissions among individuals receiving maintenance hemodialysis is increasingly ‘well put.’ The next step is to see that the problem is also well-solved,” they wrote. Study co-authors include Kinsuk Chauhan MD, Priti Poojary MD, Aparna Saha MD, Elizabeth Hammer, MD, Joseph Vassalotti, MD, Lindsay Jubelt, MD, Bart Ferket MD, PhD, and Steven Coca DO, MS. Disclosures: L.C. is supported in part by the National Institutes of Health. B.F is supported in part by American Heart Association. G.N. is supported in part by the National Institutes of Health. The article, entitled “National Estimates of Thirty Day Unplanned Readmissions of Patients on Maintenance Hemodialysis,” will appear online at http://cjasn.asnjournals.org/ on September 28, 2017, doi: 10.2215/CJN.02600317. The editorial, entitled “Thirty-Day Hospital Readmissions in the Hemodialysis Population: A Problem Well Put, But Half-Solved,” will appear online at http://cjasn.asnjournals.org/ on September 28, 2017. The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies. Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has nearly 17,000 members representing 112 countries. For more information, please visit www.asn-online.org or contact the society at 202-640-4660.
A novel psychological therapy that encourages addressing emotional experiences related to trauma, conflict and relationship problems has been found helpful for people with the chronic pain condition fibromyalgia. A research team led by Mark A. Lumley, Ph.D., professor of psychology in the College of Liberal Arts and Sciences at Wayne State University, in collaboration with a team from the University of Michigan Medical Center led by David A. Williams, Ph.D., professor of anesthesiology, has released the results of its research in the prestigious journal, PAIN. In the randomized clinical trial, 230 adults with fibromyalgia received one of three treatments, each of which was presented for eight weekly sessions to small groups of patients. The new therapy, which Lumley and co-developer Howard Schubiner, M.D., director of the Mind Body Medicine Program at Providence Hospital, call Emotional Awareness and Expression Therapy (EAET), helps patients view their pain and other symptoms as stemming from changeable neural pathways in the brain that are strongly influenced by emotions. EAET helps patients process emotional experiences, such as disclosing important struggles, learning how to adaptively express important feelings — especially anger and sadness but also gratitude, compassion, and forgiveness — and empowering people to be more honest and direct in relationships that have been conflicted or problematic. The EAET intervention was compared to both an educational intervention as well as the gold standard psychological approach in the field, cognitive behavioral therapy. Six months after treatments ended, patients were evaluated for the severity and extent of their pain and other problems that people with fibromyalgia often experience. Patients who received EAET had better outcomes — reduced widespread pain, physical impairment, attention and concentration problems, anxiety, and depression and more positive emotions and life satisfaction — than patients who received the education intervention. More than twice as many people in EAET (34.8 percent) reported that they were “much better” or “very much better” than before treatment, compared to 15.4 percent of education patients. An important additional finding was that the new emotion therapy also had greater benefits than cognitive behavior therapy in reducing widespread pain and in the number of patients who achieved at least 50 percent pain reduction. “Many people with fibromyalgia have experienced adversity in their lives, including victimization, family problems and internal conflicts, all of which create important emotions that are often suppressed or avoided. Emerging neuroscience research suggests that this can contribute strongly to pain and other physical symptoms,” Lumley said. “We developed and tested an approach that tries to help people overcome these emotional and relationship problems and reduce their symptoms, rather than just help people manage or accept their fibromyalgia. Although this treatment does not help all people with fibromyalgia, many patients found it to be very helpful, and some had dramatic improvements in their lives and their health.” More information about the research study, “Emotional awareness and expression therapy, cognitive behavioral therapy, and education for fibromyalgia: a cluster-randomized controlled trial,” can be found in PAIN, a journal published by the International Association for the Study of Pain (doi: 10.1097/j.pain.0000000000001036). About Wayne State University Wayne State University is one of the nation’s pre-eminent public research universities in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world. For more information about research at Wayne State University, visit research.wayne.edu. SEE ORIGINAL STUDY
NYU Langone Hospital – Brooklyn recently opened a new unit specializing in the diagnosis and treatment of epilepsy, the fourth most common neurological illness and one that is newly diagnosed in more than 2 million individuals annually in the U.S. “The need for epilepsy care in the community is immense. To facilitate access at NYU Langone Hospital – Brooklyn we have opened a dedicated epilepsy monitoring unit,” says Blanca Vazquez, MD, director of clinical trials in the Department of Neurology at NYU Langone Health and head of the epilepsy program in Brooklyn. Vazquez is an epileptologist, a neurologist who specializes in epilepsy. The epilepsy unit is equipped with state-of-the-art diagnostic and digital video monitoring technology and complements the hospital’s newly renovated neurology suite. Admission and procedures can be scheduled in advance, making it more convenient for patients and their families. “The various forms of epilepsy usually stem from uncontrolled electrical activity in the brain,” says Vazquez, who has been with NYU Langone Health for 26 years and in Brooklyn since 2010. “Many things can trigger seizures in an epilepsy patient, including fever, alcohol withdrawal, or sleep deprivation. Epilepsy can have a genetic component, and can result from malformations of development, brain trauma, tumors, infections, dementia, or stroke.” In addition to epileptologists, the unit team also includes neuropsychologists, psychiatrists, neurosurgeons, specially trained nurses and nurse practitioners, dieticians, physical, occupational and speech therapists, social workers, imaging technologists, and researchers. The team collaborates with colleagues at NYU Langone’s Comprehensive Epilepsy Center in Manhattan, where patients can be transferred if surgery or other more specialized procedures are necessary. “Epilepsy can severely impact a patient’s safety, quality of life, and work and school activities,” says Orrin Devinsky, MD, professor of psychiatry, neurosurgery and neurology at NYU Langone and director of the Comprehensive Epilepsy Center. “We recommend drugs that are easy to use with other medications and which minimally impact a patient’s activities of daily living.” Monitoring Effectiveness of Treatment If a patient does not achieve a desired seizure control after trying three different epileptic drugs on an outpatient basis, a hospital stay is usually recommended to monitor administration of a single drug or a combination of drugs. The unit’s video capabilities allow staff to closely monitor for evidence of seizure activity that can help pinpoint the precise type of seizure, and which part of the brain is involved. In addition, brain mapping on the unit helps determine the source of seizures and areas of the brain involving movement, speech, vision and memory that need to be protected. Uncontrolled shaking is the most common symptom with epilepsy – yet in many cases there are no overt signs. “These are the most challenging cases,” Vasquez says. “Patients can be misdiagnosed and treated inappropriately. Establishing a definitive diagnosis is critical to the successful management of epilepsy.” The opening of the new epilepsy unit continues a transformation initiative under way at NYU Langone Hospital – Brooklyn. “We are proud to reach another milestone with the opening of the neurology unit and now a specially equipped area for epilepsy,” says Bret J. Rudy, MD, executive hospital director and senior vice president, NYU Langone Hospital – Brooklyn. “Patients will benefit greatly being cared for by our outstanding team of experts in this brand new unit.” For more information about epilepsy and NYU Langone’s Comprehensive Epilepsy Center and the epilepsy program at NYU Langone Hospital – Brooklyn, please call 718-630-8600.
Outdoor air pollution has long been linked to major health conditions such as heart disease, stroke, cancer, asthma and chronic obstructive pulmonary disease. A new study now adds kidney disease to the list, according to researchers at Washington University School of Medicine in St. Louis and the Veterans Affairs (VA) St. Louis Health Care System. Pollution may increase the risk of chronic kidney disease and, ultimately, contribute to kidney failure, according to the researchers. The Washington University team, in collaboration with scientists at the Veterans Affairs’ Clinical Epidemiology Center, culled national VA databases to evaluate the effects of air pollution and kidney disease on nearly 2.5 million people over a period of 8.5 years, beginning in 2004. The scientists compared VA data on kidney function to air-quality levels collected by the Environmental Protection Agency (EPA) as well as the National Aeronautics and Space Administration (NASA). The EPA derived its data from land-based air-monitoring stations across the U.S. The findings suggest that 44,793 new cases of kidney disease and 2,438 new cases of kidney failure may be attributed to levels of air pollution that exceed the EPA’s threshold of 12 micrograms per cubic meter of air, which is the highest level of air pollution considered safe for the public, as set by the Clean Air Act of 1990 and updated in 2012. The study is published Sept. 21 in the Journal of the American Society of Nephrology. “Data on the relationship between air pollution and kidney disease in humans has been scarce,” said Ziyad Al-Aly, MD, the study’s senior author and an assistant professor of medicine at Washington University. “However, once we analyzed the data, the link between air pollution and the development of kidney disease was clear.” Fine particles can damage the kidneys in the same way they damage other organs such as the heart and lungs. Airborne and invisible, microscopic pieces of dust, dirt, smoke, soot and liquid droplets often become destructive when they invade the bloodstream. The kidneys filter the blood, and these harmful particles can disrupt normal kidney function. The study found that even low levels of particulate matter may adversely affect the kidneys. And those adverse effects increase as pollution levels increase. “The higher the levels of air pollution, the worse it is for the kidneys,” said Al-Aly, who is also the VA’s director of clinical epidemiology in St. Louis. “However, no level is completely safe. Even at relatively low levels, there was a relationship between particulate matter concentrations below the EPA thresholds and kidney disease.” Researchers also linked the VA data to space-borne sensors from NASA satellites. “NASA data and EPA data yielded consistent results,” Al-Aly said. “The beauty of using both EPA and NASA data is that the agencies used two distinct techniques for collecting data, yet the results were similar,” he said. “This constellation of findings suggests that chronic exposure to air pollution is a significant risk factor for the development and progression of kidney disease.” Study results placed Southern California and large regions in the South, Midwest and Northeast at the greatest risk for kidney decline attributed to air pollution. Over the years, unsafe levels of outdoor air pollution have decreased in the U.S. Still, more than half of the U.S. population lives in areas — from industrialized big cities to farming communities to coal-mining towns — with unhealthy levels of outdoor air pollution, according to a 2016 study by the American Lung Association. In many places across the globe, including China and India, outdoor air pollution is significantly worse than in the U.S. “In our analyses, the risk of chronic kidney disease and its progression was most pronounced at the highest levels of fine particulate matter concentration,” Al-Aly said. “This suggests further study is needed for a broader assessment of the global burden of kidney disease attributable to air pollution.”
Physical activity of any kind can prevent heart disease and death, says a large international study involving more than 130,000 people from 17 countries published this week in The Lancet. The Prospective Urban Rural Epidemiology (PURE) study, led by the Population Health Research Institute of McMaster University and Hamilton Health Sciences, shows any activity is good for people to meet the current guideline of 30 minutes of activity a day, or 150 minutes a week to raise the heart rate. Although previous research, from high income countries, shows leisure time activity helps prevent heart disease and death, the PURE study also includes people from low and middle-income countries where people don’t generally don’t participant in leisure-time physical activity. “By including low and middle-income countries in this study, we were able to determine the benefit of activities such as active commuting, having an active job or even doing housework,” said principal investigator Dr. Scott Lear. He added that one in four people worldwide do not meet the current activity guideline and that number is nearly three of four in Canada. Lear holds the Pfizer/Heart & Stroke Foundation Chair in Cardiovascular Prevention Research at St. Paul’s Hospital in Vancouver and is a professor of Simon Fraser University’s Faculty of Health Sciences. The PURE study showed that by meeting the activity guidelines, the risk for death from any cause was reduced by 28%, while heart disease was reduced by 20%, and it didn’t matter what type of physical activity the person did. The benefits also continued at very high levels with no indication of a ceiling effect; people getting more than 750 minutes of brisk walking per week had a 36% reduction in risk of death. However, less than 3% of participants achieved this level from leisure time activity while 38% of participants achieved this level from activities such as commuting, being active at work or doing household chores. Lear said that in order to realize the full benefits of physical activity, it needs to be incorporated into daily life. “Going to the gym is great, but we only have so much time we can spend there. If we can walk to work, or at lunch time, that will help too.” “For low and middle income countries where having heart disease can cause a severe financial burden, physical activity represents a low-cost approach that can be done throughout the world with potential large impact,” said Dr. Salim Yusuf, director of the Population Health Research Institute and the principal investigator of the overall PURE study. “If everyone was active for at least 150 minutes per week, over seven years a total of 8% of deaths could be prevented,” he added. The PURE study was led by the Population Health Research Institute and conducted in over 70 sites in 17 countries. It is funded from more than 50 sources, including the Population Health Research Institute at McMaster University and Hamilton Health Sciences, the Heart and Stroke Foundation of Ontario, the Canadian Institutes of Health Research, and the Ontario SPOR Support Unit. The Population Health Research Institute (PHRI) is a joint Research Institute of McMaster University and Hamilton Health Sciences Corporation. It is Canada’s premiere global health research institute and a world leader in large clinical trials and population studies. Originally formed with a focus on cardiovascular disease (CVD) and diabetes, PHRI’s research areas have broadened to include population genomics, perioperative medicine and surgery, stroke, thrombosis, renal disease, and obesity, with unparalleled expertise in epidemiology, population health and clinical trials. For more information, please visit www.phri.ca. Providence Health Care (PHC) is one of Canada's largest faith-based health care organizations, operating 16 health care facilities in Greater Vancouver. PHC operates one of two adult academic health science centres in the province – St. Paul’s Hospital – performs cutting-edge research in more than 30 clinical specialties, and focuses its services on six "populations of emphasis": cardio-pulmonary risks and illnesses, HIV/AIDS, mental health, renal risks and illness, specialized needs in aging and urban health and is home to the B.C. Centre for Excellence in HIV/AIDS. www.providencehealthcare.org. For interviews with Scott Lear contact: Elaine Yong | Senior Communications Specialist, Media Relations Providence Health Care T: 604.682.2344 ext. 66987| M: 604.837.6003 E: email@example.com For interviews with Dr. Salim Yusuf contact: Veronica McGuire, Media Relations McMaster University 905 525-9140, ext. 22169 firstname.lastname@example.org Veronica McGuire Media Relations, Faculty of Health Sciences, McMaster University (905) 525-9140, ext. 22169 email@example.com
Nisannne Ghonem, assistant professor at the University of Rhode Island’s College of Pharmacy, is a recipient of the 2017 Mentored Research Awards from Advance-CTR, a federally funded statewide effort to support clinical research that can be translated into approaches and policies to improve the health of Rhode Islanders. She is one of three researchers across the state to receive a two-year grant through the awards program, which aims to recruit and train early career health scientists representing diversity in background and discipline. Her research seeks to address a universal problem in kidney transplant surgery that can result in failure of the organ graft. The Advance-CTR (Clinical Translational Research) award covers 75 percent of the researcher’s salary, with additional funds for supplemental tuition or research needs as well as mentoring. “We are tremendously proud of our Mentored Research Awardees, who were selected from an extremely competitive batch of applications. Professor Ghonem shows highly promising research in the area of pharmacology and toxicology, and we look forward to supporting her career development through this award,” said Dr. Ira Wilson, director of the Professional Development Core of Advance-CTR based at Brown University, which runs the Mentored Research Awards program. Ghonem’s research will explore the use of a class of drugs known as prostacyclins to reduce ischemia-reperfusion injury to a transplanted kidney from a deceased patient that can result in failure of the organ graft. These injuries occur when blood flow to the donor organ is unavoidably interrupted (ischemia) and then resumes (reperfusion) upon transplantation. “This injury is inherent in the nature of the transplant surgery, and the problem remains unsolved,” Ghonem said. Prostacyclins, which act as anti-coagulants and vasodilators to improve blood flow, have shown promise in liver transplantation research, she said. Solving the ischemia-reperfusion problem could mean the difference between life and death for the 2 million people worldwide — and 650,000 in the United States — living with end-stage kidney disease and who are in need of organ transplants. “There is a great disparity in the number of patients waiting for transplants and organs available,” Ghonem said. “The discovery of a drug to treat this injury would allow acceptance of more kidney grafts, which could dramatically increase the number of organs available for transplant and improve patient outcomes and survival.” Ghonem’s mentor on the project is Fatemeh Akhlaghi, a URI pharmacy professor and the Ernest Mario Distinguished Chair in Pharmaceutics. The team also comprises two co-investigators and mentors: Dr. Reginald Gohh, associate professor at Brown University’s Alpert Medical School and surgeon and medical director of organ transplantation at Rhode Island Hospital; and Dr. Rujun Gong, associate professor and director of kidney research at the medical school. The researchers will assess the effects of prostacyclin on ischemia-reperfusion in laboratory rats. Such research is the foundation for supporting clinical trials involving adult patients undergoing kidney transplantation, Ghonem’s ultimate aim. Her research targets sub-optimal and extended criteria organ donors, which come from the deceased donor pool that makes up the majority of transplants. So far this year, Rhode Island Hospital — the only facility in the state that performs organ transplants — has conducted 35 kidney transplants, and only seven came from live donors, according to the United Network for Organ Sharing. Circumstances of death, storage/transportation time and other factors affecting how long the kidney is deprived of blood flow increase the chance and extent of injury, and ultimately, the outcome for the patient, Ghonem said. Advance-CTR (Award #U54GM115677) is a statewide program funded by the National Institute of General Medical Science/National Institutes of Health to support clinical and translational researchers in Rhode Island through funding, research resources and services, and professional development. It seeks to support research across the translational science spectrum, including basic science, clinical and public health.
Stony Brook Medicine kidney transplant specialist Frank Darras, MD, Clinical Porofessor of Uroogy and Medical Director of Transplantation Services, is avaiable to discuss kidney transplanation and Lupus patients. Accordng to Dr. Darras, Systemic lupus erythematosus (SLE) is an "autoimmune" disease that can harm your kidneys and other tissues, and may be fatal. SLE that affects the kidneys is called lupus nephritis. If the kidneys fail, lupus patients can be treated with dialysis or a kidney transplant. Many patients with lupus nephritis have received a kidney transplant. The drugs used to prevent rejection of the new kidney are the same or similar to those used to treat lupus. It is unusual for lupus to come back in the new kidney. Lupus patients with new kidneys do as well as any other patients with transplanted kidneys. More than 116,000 people are listed for an organ transplant nationwide. Many face a lengthy wait for an available organ. Yet only approximately 19,000 kidney transplants were performed in the U.S. in 2016, with about 5,600 kidney transplants by living donors. Living kidney donation is an important option for patients with end-stage renal disease (ESRD), and has improved life expectancy and quality for patients otherwise requiring maintenance dialysis. Studies have shown the outcome of a transplant from a living donor is better than that of a deceased donor. With a kidney from a living donor, there’s less waiting for a kidney than one from a deceased donor. A kidney from a living donor usually functions immediately, and for a longer period of time than a kidney from a deceased donor. Many living kidney donor transplants are done between family members. However, spouses, friends and even “strangers” can give the gift of life. While donating a kidney involves major surgery, it is usually performed Laparoscopically thru small incisions with less pain, less scarring and faster recovery to full activity than traditional open surgery. The risk of kidney failure is the same as for people who are not kidney donors, and living kidney donors tend to live longer than those who are not donors, because they have been screened so thoroughly. Donating a kidney is a major decision, but the gift of life is a noble act. The results are great, the downside is minimal. The need for kidney donors, both living and deceased, has never been greater than it is now. As transplantation continues to offer patients better outcomes, more patients are waiting for a kidney that matches their needs. Without an increase in donors, many more people will die before they have an opportunity to receive a life-saving transplant. If you are intent on becoming an organ donor, start by registering at the DMV. Have a discussion with your family and loved ones, so that they will know your wishes and can advocate for you when the time comes. If needed, Dr. Darras and all Stony Brook experts have access to a ReadyCam television studio system that provides remote access to television networks.
Highlights In individuals with chronic kidney disease, high sleep fragmentation was associated with an elevated risk of developing kidney failure. Higher sleep fragmentation and shorter sleep duration were each linked with steeper declines in kidney function over time. Subjectively measured daytime sleepiness was associated with an increased risk of early death from any cause. Sleep disturbances are common in individuals with kidney disease. Newswise — Washington, DC (September 14, 2017) — A new study reveals a potential link between disordered sleep and kidney function loss and early death among individuals with chronic kidney disease (CKD). The findings, which appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN), suggest that people with CKD may be especially vulnerable to the deleterious effects of impaired sleep. Increasing evidence suggests that sleep disorders are common in patients with CKD, but the influence of sleep duration and quality on their health is unknown. To investigate, Ana Ricardo, MD, MPH (University of Illinois at Chicago), Kristen Knutson, PhD (Northwestern University), and their colleagues evaluated sleep (using a wrist-worn accelerometer for 5-7 days) and clinical outcomes including worsening of kidney function over time and death from any cause in 431 individuals with mild-to-moderate CKD. Patients were assessed yearly for a median follow-up of 5 years. During follow-up, 70 patients developed kidney failure and 48 died. High sleep fragmentation was associated with an elevated risk of developing kidney failure. In addition, higher sleep fragmentation and shorter sleep duration were each linked with steeper declines in kidney function over time. Furthermore, subjectively measured daytime sleepiness was associated with an 11% increased risk of death from any cause. “These findings suggest that impaired sleep is an unrecognized and clinically significant risk factor for progression of CKD,” said Dr. Ricardo. “Future work is needed to evaluate interventions to improve sleep habits in patients with CKD and assess whether the observed relationship with CKD progression is causal.” Study co-authors include Jinsong Chen, PhD, Lawrence Appel, MD, Lydia Bazzano, MD, Eunice Carmona-Powell, Janet Cohan, MS, Manjula Kurella Tamura, MD, Susan Steigerwalt, MD, John Daryl Thornton, MD, Matthew Weir, MD, Nicolas Turek, BA, Mahboob Rahman, MD, Eve Van Cauter, PhD, and James Lash, MD. Disclosures: The authors reported no financial disclosures. The article, entitled “The Association of Sleep Duration and Quality with CKD Progression,” will appear online at http://jasn.asnjournals.org/ on September 14, 2017, doi: 10.1681/ASN.2016121288. The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies. Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has nearly 17,000 members representing 112 countries. For more information, please visit www.asn-online.org or contact the society at 202-640-4660.
The incidence of heart disease is on the rise, and new therapeutic strategies are needed. Approaches based on stem cells, which can potentially preserve or even regenerate heart muscle cells damaged by ischemia – a hallmark of heart disease – are especially promising. Now, thanks to an $11.6-Million Program Project Grant (PPG) from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) under award number P01HL134608, scientists at the Lewis Katz School of Medicine at Temple University (LKSOM) are poised to explore new possibilities in stem cell-based treatments for heart repair and regeneration. The project is aimed specifically at better understanding the regenerative capabilities of stem cell-derived microvesicles known as exosomes. The Principal Investigator on the new award is Raj Kishore, PhD, Professor of Pharmacology and Medicine and Director of the Stem Cell Therapy Program in the Center for Translational Medicine at LKSOM. According to Dr. Kishore, exosomes offer an exciting opportunity to develop a cell-free approach to stem cell-based therapy for heart disease. “Previous attempts at stem cell therapy for heart disease did not work as hoped,” Dr. Kishore said. “In many cases, the stem cells themselves were injured by inflammation in the heart following injection or were not functioning optimally, having been weakened from disease, such as diabetes, or age.” Exosomes differ from stem cells in that they are not actually cells. Rather, they are tiny packages, roughly 50-150 nanometers in diameter, which are secreted by stem cells and taken up by neighboring tissue cells. They carry stem cell-specific small RNAs, proteins, and other cargo that mimic stem cell functions once released inside cells, giving them beneficial properties. “In heart cells, the cargo inside exosomes can carry out stem cell activities necessary for cardiac repair,” Dr. Kishore explained. Many questions remain, however, about the function of stem cell-derived exosomes in the heart. It is unknown, for example, whether factors such as a patient's age or disease characteristics modify the ability of exosomes to repair or regenerate heart tissue. To answer those questions, Dr. Kishore and colleagues Walter Koch, PhD, the William Wikoff Smith Chair in Cardiovascular Medicine, Professor and Chair of the Department of Pharmacology, and Director of the Center for Translational Medicine at LKSOM, and Steven R. Houser, PhD, Senior Associate Dean for Research, Vera Goodfriend Professor of Cardiovascular Medicine, Chair of the Department of Physiology, and Director of the Cardiovascular Research Center at LKSOM, devised three collaborative projects. Each of the researchers leads a specific project as part of the new grant. In Dr. Kishore's laboratory, work is focused on understanding the function and content of exosomes from bone marrow stem cells in healthy versus diabetic animals and animals with severe inflammation. “We want to know whether diabetes, which is common in heart disease patients, and inflammation from heart damage change exosome function or affect their cargo, and if so, what changes occur,” he said. “Identifying specific disease-related alterations in exosome molecules will allow us to target and modify the molecules in ways that are beneficial therapeutically for the heart.” Dr. Koch's team is examining signaling pathways in cardiac stem cells involving G-coupled receptor kinase-2 (GRK2). GRK2 inhibition potentially facilitates heart repair through mechanisms that involve alterations to the cargo of secreted exosomes. The third project explores exosomes from cortical bone stem cells, originally discovered in Dr. Houser's laboratory, and their role in heart repair. “This research gives us the opportunity to explore the idea that cell-based exosomes can be used to enhance repair of the heart after a heart attack,” Dr. Houser explained. “Exosomes from cortical bone stem cells may contain factors that could reduce cardiac injury and enhance regeneration.” The new award also funds two scientific cores supporting all 3 projects – an exosome isolation and characterization core directed by Dr. Kishore, and an animal surgery and physiology core led by John Elrod, PhD, Assistant Professor of Pharmacology at the Center for Translational Medicine at LKSOM. “This NIH Award is a testament to what we have built here at Temple,” Dr. Koch said. “Dr. Kishore has shown great leadership in organizing this multi-component grant.” The outcomes of the various projects are expected to have important impacts on the basic scientific understanding of exosomes in the heart and on clinical aspects of heart disease. “The goal will be to translate our findings into novel therapies for patients with heart disease,” Dr. Houser added. Editor’s Note: The content above is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
FINDINGS In a two-year UCLA-led study, nearly two-thirds of people with advanced melanoma responded positively to a treatment that combines the immunotherapy drug pembrolizumab with a herpes virus called talimogene laherpareovec, or T-VEC. Researchers led by Dr. Antoni Ribas found that the treatment's side effects were manageable, and comparable to side effects for people who took either pembrolizumab or T-VEC as a standalone treatment. BACKGROUND UCLA scientists are testing the combination of pembrolizumab (marketed as Keytruda) and T-VEC (marketed as Imlygic) as a treatment option for people with advanced melanoma that doesn't fully respond to either treatment separately. T-VEC is a genetically modified version of the herpes simplex virus that causes cold sores, but is safe to use. T-VEC has already been approved for the treatment of melanoma and it works both by directly killing cancer cells and using a protein that attracts immune cells into the cancers. Pembrolizumab has become a standard-of-care treatment for advanced melanoma, and it is also being used to treat non-small-cell-lung cancer, cancers of the head, neck, kidney and bladder, and Hodgkin's disease. It works by taking the "brakes" off of the body's immune system, enabling it to attack cancer. According to Ribas, people whose melanoma does not respond to pembrolizumab often lack a type of T cell called CD8+ in their tumors; the lack of CD8+ cells seems to prevent immunotherapy drugs from working. But the researchers believe those people might benefit from a combination therapy, because T-VEC attracts CD8+ immune cells to the tumors and pembrolizumab allows them to attack the cancer cells. METHOD The phase 1 clinical trial evaluated 21 people with advanced melanoma. Researchers injected patients' melanoma tumors with T-VEC for six weeks and then gave them infusions of pembrolizumab. Sixty-two percent of the patients had a partial or complete response, meaning that their tumors either shrank or were no longer detectable. IMPACT The combination therapy could provide an alternative treatment for people with melanoma whose tumors don't respond to other therapies. It also being tested in people with head, neck and colon cancers. AUTHORS Ribas, the study's lead author, is director of the immunology program at UCLA's Jonsson Comprehensive Cancer Center, professor of hematology and oncology at the David Geffen School of Medicine at UCLA, and a member of the Parker Institute for Cancer Immunotherapy. JOURNAL The study is published online in the Cell. It is the first full report clinical trial to be published in the journal. FUNDING Funding was provided by Amgen and Merck. DISCLOSURES Ribas has received consulting fees from Amgen and Merck. VIDEO ABSTRACT A video abstract of the study is available for media use. YouTube link: https://youtu.be/pm46mQ7SeXU. For a broadcast-quality version, please contact Peter Bracke at PBracke@mednet.ucla.edu.