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Credit: Vanderbilt University Medical Center Myrick “Ricky” Shinall Jr., MD, PhD, an assistant professor and general surgeon at Vanderbilt University Medical Center   Newswise — Even a minor surgery such as a laparoscopic gallbladder removal can prove to be a high-risk and even fatal procedure for frail patients, according to new research published in JAMA Surgery.  A team of researchers from leading U.S. academic medical centers and VA medical centers examined the records of 432,828 patients who underwent a non-cardiac surgical procedure. They found that patients who were classified as frail or very frail had substantially higher mortality rates after surgeries with low and moderate operative stress, with up to 43% dying after moderate stress procedures such as laparoscopic cholecystectomy (minimally invasive gallbladder removal).  “It’s been established that frailty is a strong predictor of complications and death related to surgery, but what we learned in this study is that frail patients have alarmingly high rates of postoperative death, no matter how minor the surgical procedure,” said lead author Myrick “Ricky” Shinall Jr., MD, PhD, an assistant professor and general surgeon at Vanderbilt University Medical Center (VUMC). “A laparoscopic cholecystectomy is one of the most common operations I do as a general surgeon, and this has really given me pause to think that for frail to very frail patients — about 10% of our sample — this is a big deal. Our data indicate that there are no ‘low-risk’ procedures among frail patients.”  In layman’s terms, frailty is a vulnerability to becoming sick from even minor stress when the body has lost the ability to recover, said Shinall. It is typically measured before surgery by a clinical tool known as the Risk Analysis Index (RAI). With the RAI, several symptoms are assessed such as unintentional weight loss, shortness of breath, weakness, and difficulties with daily activities like walking, eating or bathing.  The study’s investigators pulled patient medical records for a four-year period from the VA Surgical Quality Improvement Program (VASQIP) database, a representative sample of all surgeries conducted across the country in the Veterans Health Administration. Data included patient information for a minimum of one year following surgery, and the patients’ postoperative mortality was noted at 30, 90 and 180 days. Past research related to frail patients and surgery has largely focused on small groups undergoing high-risk procedures, but the current study had a large sample size and included a range of procedures grouped according to how much operative stress they cause. Because no tool to consistently measure operative stress existed, an Operative Stress Score (OSS) was created by the study investigators. Surgeries from the patients’ cases were then sorted into five categories of physiologic stress, ranging from the lowest (OSS1) to the highest (OSS5).  Of the study’s patient sample, 8.5% were classified as frail, and 2.1% were very frail. The 30-day mortality rates for frail patients undergoing the lowest stress operations and moderate stress operations were 1.55% and 5.13%, both exceeding the 1% mortality rate often used to define high-risk surgery. For very frail patients, 30-day mortality rates after the lowest and moderate-stress procedures was even higher at 10.34% and 18.74%. For frail and very frail patients, mortality continued to rise at 90 days and 180 days after surgery, reaching as high as 43% for very frail patients 180 days after moderate-stress operations.  “This leads us to recommend that pre-surgical frailty screenings should be done universally, even for procedures known to cause low to moderate physiological stress, and frail patients and their families should be counseled about the greater risk of undergoing even minor surgery,” said corresponding author Daniel Hall, MD, associate professor at the University of Pittsburgh, staff surgeon at the Veterans Affairs Pittsburgh Healthcare System, and core investigator at the VA Center for Health Equity Research and Promotion.  “The greatest volume of surgeries performed at hospitals are those that cause moderate operative stress, and it is expected that all procedures at ambulatory surgical centers are considered to be those with a low mortality risk, but clinicians spend little time considering whether or not their patients can actually endure the stress of surgery,” said Shinall. “It is worth pausing to assess every patient to determine whether they are frail, and if they are, taking steps to mitigate the factors contributing to their frailty before a procedure is ever scheduled or re-evaluating whether they should even undergo a procedure at all.”  The study was supported by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (I21 HX-002345 and XVA 72-909 [Hall] and CIN 13-413 [Massarweh]. Additional support was provided by NIH/NIA 5R03AG050930 [Arya], NIH/NCI K12CA090625 [Shinall] and U01 TR002393 [Hall and Shireman].
ORI, FAU Study First to Show Statistically Significant Links between Regular Use of Pain and/or Sleep Prescriptions and Frailty Risk in Older Adults 14-Nov-2019 9:00 AM EST   Credit: Oregon Research Institute   Newswise — Researchers from the Oregon Research Institute (ORI) and Florida Atlantic University (FAU) are the first to demonstrate statistically significant links between self-reported regular use of prescription drugs for pain and/or sleep, and longitudinal risk of frailty in adults ages 65 and older. Frailty consists of deficits in a variety of functional measures, and is a reliable predictor of loss of independence, increased use of health care resources, and mortality. The possible implications of current research findings are especially serious given that it is common for older Americans to use two or more prescription drugs at the same time and many of these prescription drugs are for pain and sleep, including analgesics and sedatives. Results, published online in the Journal of the American Geriatric Society, estimate long-term frailty risks and rank the long-term risks of two classes of prescription drugs. Researchers found over eight years of follow-up, those who self-reported regular use of prescription drugs for pain and sleep had a 95 percent increased risk of frailty compared to those who did not report regular use of these drugs. For regular prescription drug use for pain only or for sleep only, the increased risks were 58 percent and 35 percent, respectively. Co-authors Gulcan Cil, Ph.D., associate scientist, ORI, Juyoung Park, Ph.D., associate professor in FAU’s Phyllis and Harvey Sandler School of Social Work within the College for Design and Social Inquiry, and senior scientist Andrew Bergen, Ph.D., ORI, analyzed data from the Health & Retirement Study (HRS), a nationally representative longitudinal cohort of older Americans. For their analysis, they selected a large cohort (N=7,201) of community-living non-frail older adults (age 65 to 104, mean 72, median 70) from the HRS. Analyses were adjusted for demographics and other drug use. “Co-use of multiple prescription medications is a growing phenomenon, especially among older adults,” said Park.  “Geriatric medicine societies, including the American Geriatric Society, have developed guidelines to help prescribers avoid potentially inappropriate prescribing or PIP, which requires assessment of several types of PIP, including the benefits and risks associated with certain drug classes.”  “Our study shows that regular self-reported use and co‐use of prescription drugs for pain and for sleep are significantly associated with increased incidence of frailty,” said Bergen. “We recommend further research to estimate the frailty risk of pain and sleep measures and of prescription pain and sleep drugs.” The HRS dataset used by the researchers is sponsored by the National Institute on Aging (NIA) of the National Institutes of Health and the Social Security Administration (SSA) and is conducted by the University of Michigan. RAND HRS data products used in this study are produced by RAND Center for the Study of Aging with funding from the NIA and SSA. Park will present this work at the Gerontological Society of America Annual Scientific Meeting (geron.org/2019) on Nov. 16 in Austin, Texas.   About the Oregon Research Institute Founded in 1960, Oregon Research Institute (ORI) is a charitable 501(c) 3 research center, dedicated entirely to understanding human behavior and improving the quality of human life. Funded by research grants from the National Institutes of Health and by the United States Department of Education, ORI scientists study such topics as childhood obesity and behavioral problems, promoting health across the age span, preventing and treating teen substance use and abuse, and understanding and preventing eating disorders. Emerging areas include genetics, opioid addiction, Alzheimer's disease, and health economics. See www.ori.org.   About Florida Atlantic University: Florida Atlantic University, established in 1961, officially opened its doors in 1964 as the fifth public university in Florida. Today, the University, with an annual economic impact of $6.3 billion, serves more than 30,000 undergraduate and graduate students at sites throughout its six-county service region in southeast Florida. FAU’s world-class teaching and research faculty serves students through 10 colleges: the Dorothy F. Schmidt College of Arts and Letters, the College of Business, the College for Design and Social Inquiry, the College of Education, the College of Engineering and Computer Science, the Graduate College, the Harriet L. Wilkes Honors College, the Charles E. Schmidt College of Medicine, the Christine E. Lynn College of Nursing and the Charles E. Schmidt College of Science. FAU is ranked as a High Research Activity institution by the Carnegie Foundation for the Advancement of Teaching. The University is placing special focus on the rapid development of critical areas that form the basis of its strategic plan: Healthy aging, biotech, coastal and marine issues, neuroscience, regenerative medicine, informatics, lifespan and the environment. These areas provide opportunities for faculty and students to build upon FAU’s existing strengths in research and scholarship. For more information, visit www.fau.edu.
Newswise — LOS ANGELES (Nov. 11, 2019) -- A new study from researchers at the Smidt Heart Institute at Cedars-Sinai shows that electronic nicotine delivery systems, including devices such as e-cigarettes, may be just as harmful to the heart, if not more, than traditional cigarettes. The findings were presented today at the annual American Heart Association Scientific Sessions 2019.  "What makes e-cigarettes so harmful to the heart and lungs is not just nicotine," said senior author Florian Rader, MD, MSc, medical director of the Human Physiology Laboratory and assistant director of the Non-Invasive Laboratory at the Smidt Heart Institute. "It's the completely unknown bucket of manufactured products used to form vapors that is likely causing the most harm. This is what we believe is underlying the current public health problem."  These findings come at a crucial time, as reports of lung-related e-cigarette injuries are increasing, even while many distributors continue to claim that using e-cigarettes are safe and can help tobacco cigarette smokers kick the habit. A recent study by the Food and Drug Administration found that 27.5% of high school students used e-cigarettes in 2019, compared to 20.8% in 2018. The same study also estimates 3.62 million middle and high school students were e-cigarette users in 2018. In the Smidt Heart Institute study, the team of researchers compared healthy, young-adult smokers aged 18 to 38 who were regular users of e-cigarettes or tobacco cigarettes. The researchers then measured participants' blood flow to the heart muscle-focusing on a measure of coronary vascular function-before and after sessions of either e-cigarette use or cigarette smoking, while participants were at rest and also after they performed a handgrip exercise which simulates physiologic stress.  In smokers who used traditional cigarettes, blood flow increased modestly after traditional cigarette inhalation and then decreased with subsequent stress. However, in smokers who used e-cigarettes, blood flow decreased after both inhalation at rest and also after handgrip stress.  "Our results suggest that e-cigarette use is associated with coronary vascular dysfunction at rest, even in the absence of physiologic stress," said Susan Cheng, MD, MPH, MMsc, director of Public Health Research at the Smidt Heart Institute and director of Cardiovascular Population Sciences at the Barbra Streisand Women's Heart Center. "These findings indicate the opposite of what e-cigarette and vaping marketing is saying about their safety profile." The original concept and design of this study was initiated by the late Ronald G. Victor, MD, a foundational pioneer in cardiovascular physiology studies. "We have known for decades that smoking increases your risk for heart attack and dying from heart disease," said Christine Albert, MD, MPH, founding chair of the newly established Department of Cardiology at the Smidt Heart Institute. "Now, with this study, we have compelling evidence suggesting that newer methods of electronic nicotine delivery may be equally, or potentially more, harmful to your heart as traditional cigarettes." Given that e-cigarettes represent a relatively new product on the market, Albert cautions users that there may be a number of unforeseen health effects. To better understand the potentially dangerous consequences of e-cigarettes, Rader, Cheng and investigators in the Human Physiology Laboratory at the Smidt Heart Institute plan on studying the mechanisms underlying changes in heart and blood vessel flow seen in their work to-date, as well as the effects of e-cigarette use across a more diverse population of study participants including those with existing cardiovascular risk. "What we are learning from our own research, along with the work of others, is that use of any electronic nicotine delivery system should be considered with a high degree of caution until more data can be gathered," said Rader. URL : http://www.cedars-sinai.org/newsroom/study-e-cigarettes-may-be-more-harmful-to-heart-health-than-tobacco/
UNC School of Medicine researchers are the first to show in animal models that components of marijuana, including its cannabinoids THC and CBD, can cause brain and facial birth defects if used during the first trimester of pregnancy. Credit: UNC School of Medicine (Left) The brain of a control mouse. (Right) The brain of a mouse exposed to alcohol and a cannabinoid on the 8th day of pregnancy. Note the enlarged cerebral ventricle caused by the loss of the midline septal region (black arrow).     Newswise — CHAPEL HILL, NC – A new study published in Scientific Reports, a Nature Research journal, shows how a one-time exposure during early pregnancy to cannabinoids (CBs) – both synthetic and natural – can cause growth issues in a developing embryo. This is the first research to show such a connection in mammals.  The study was performed in mice, which are very accurate models for the development that occurs during early pregnancy, according to the study’s senior author, Scott Parnell, PhD, assistant professor of cell biology and physiology in the UNC School of Medicine. “The development of the embryo in this time period is very similar across all vertebrates,” said Parnell, a member of the UNC Bowles Center for Alcohol Studies. “In this study we also test a synthetic cannabinoid in zebrafish that yielded similar growth deformations as the natural CBs. Having the same results across animal models reinforces our findings.” In this study, the brain and facial developmental effects caused by one-time exposure to CBs – CBD and THC (the primary ingredients of marijuana) – are very similar to what is seen in fetal alcohol syndrome (FAS). Parnell and colleagues also found that when CBs and alcohol were used together, the likelihood of these birth defects more than doubled. They went on to show that these drugs may be causing defects by interacting on a basic cellular level and disrupting signaling between molecules and cells that control growth and development. “The interaction between alcohol and CBs we witnessed is very concerning,” said the study’s first author, Eric Fish, PhD, research associate in the UNC School of Medicine Bowles Center for Alcohol Studies. “Previous studies have shown that CBs and alcohol are frequently used together, and for pregnant women we’re learning that could be very dangerous to a developing child.” In the study CBs, and CBs with alcohol, were given in varying amounts on day eight of pregnancy, which is comparable to the third and fourth weeks of pregnancy in humans. This time period is when alcohol and CB exposure is especially damaging to a developing embryo, and is before some women know they are pregnant. The CBD amounts administered were within what is considered a therapeutic range for humans. The THC concentration administered was similar to levels reached by a person smoking marijuana. “It is concerning how little we know about the use of marijuana, its CBs, and products like CBD oil during pregnancy,” Parnell said. “We know that there is no safe period to drink alcohol during a pregnancy, and I think this research shows the same is likely true of marijuana use.” With the results of these one-time exposures, Parnell and Fish are planning to now test smaller, multiple exposures throughout a pregnancy that better mimics real-life usage in human pregnancy. This research was supported by grants U01-AA021651 and U54-AA019765 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health. This work was done, in part, with the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), which is funded by grants from NIAAA.
Newswise — Tuesday, Nov. 5, 2019, CLEVELAND: Patients struggling with type 2 diabetes and obesity are faced with the decision of whether to receive usual medical care or undergo weight-loss surgery. Now, a new risk calculator developed by Cleveland Clinic researchers can show these patients their risks of developing major health complications over the next 10 years depending on which course of treatment they choose. The research was presented today as one of the Top 10 studies at the ObesityWeek 2019 international conference in Las Vegas.  Research has shown that weight-loss surgery – also known as metabolic or bariatric surgery – can help people control their diabetes and improve cardiovascular health. In 2016, the world’s leading diabetes organizations recommended in a consensus report that metabolic surgery should be a treatment option for people with type 2 diabetes and obesity.  However, few eligible patients undergo the surgery.  To help patients and their physicians better predict the health benefits of usual care versus surgical treatment, Ali Aminian, M.D., a bariatric surgeon at Cleveland Clinic, and his research team developed a risk score calculator that provides personalized evidence-based information, based on a patient’s current health status.  “The calculator can be a useful tool for physicians and patients with type 2 diabetes and obesity. It shows a patient’s risk of heart disease, stroke, heart failure, diabetic kidney disease, and death over the next 10 years with usual care. It also shows how a patient’s risk of those adverse events could change after metabolic surgery,” said Dr. Aminian, who is also lead author of the study.  The calculator — 10-year Individualized Diabetes Complications Risk Scores — was developed in two phases over the course of about two years. In the first phase, an observational study looked at nearly 2,300 patients who underwent metabolic surgery and 11,500 matched patients with similar characteristics who received usual medical care.  The phase 1 results, published in the Journal of the American Medical Association (JAMA) in September, show that weight-loss surgery performed in patients with type 2 diabetes and obesity is associated with 40 percent lower risk of death and major adverse cardiovascular events than usual medical care. Surgical patients also lost more weight, had better diabetes control, and used fewer medications for treatment of their diabetes and cardiovascular disease than those undergoing usual medical care.  In phase 2, the researchers used the same group of patients to identify predictors for different health outcomes. Evidence-based models were built and integrated into a risk calculator to estimate the likelihood of coronary heart disease, stroke, heart failure, diabetic kidney disease, and mortality over the next 10 years in patients with type 2 diabetes and obesity with and without bariatric surgery  “Based on the advice of subject matter experts, our team was able to explore 26 risk factors for the different outcomes, including risk of dying, in that large group of patients,” said Michael Kattan, Ph.D., chairman of the Department of Quantitative Health Sciences in Cleveland Clinic’s Lerner Research Institute. “We then compared machine learning and traditional statistical techniques to identify the most accurate prediction models for each outcome and built those into the calculator.” Steven Nissen, M.D., Chief Academic Officer of the Heart & Vascular Institute at Cleveland Clinic, added, “Diabetes can be a devastating disease and combined with obesity, patients are at a high risk for cardiovascular complications. Metabolic surgery is an underutilized treatment for these patients. This calculator can help both physicians and patients quantify the risks and benefits of surgery and make the best decision for treatment.”  The calculator will be accessible on the Cleveland Clinic Risk Calculator Library website and as a smartphone application (BariatricCalc). The second version of the app with additional calculators will be released during ObesityWeek 2019.  This study was partially funded by an unrestricted grant from Medtronic. Medtronic had no role in the design, conduct of the study, or reporting of the results. About Cleveland Clinic Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation’s best hospitals in its annual “America’s Best Hospitals” survey. Among Cleveland Clinic’s 66,000 employees are more than 4,200 salaried physicians and researchers and 16,600 nurses, representing 140 medical specialties and subspecialties. Cleveland Clinic’s health system includes a 165-acre main campus near downtown Cleveland, 11 regional hospitals in northeast Ohio, more than 180 northern Ohio outpatient locations – including 18 full-service family health centers and three health and wellness centers – and locations in southeast Florida; Las Vegas, Nev.; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2018, there were 7.9 million total outpatient visits, 238,000 hospital admissions and observations, and 220,000 surgical cases throughout Cleveland Clinic’s health system. Patients came for treatment from every state and 185 countries. Visit us at clevelandclinic.org. Follow us at twitter.com/CCforMedia and twitter.com/ClevelandClinic. News and resources available at newsroom.clevelandclinic.org.
Newswise — (New York, NY – October 30, 2019) –A mother’s exposure to particulate air pollution during pregnancy is associated with reduced cardiac response to stress in six-month-old infants, according to Mount Sinai research published in Environmental Health Perspectives in October. This study is the first to find that particulate air pollution exposure in utero can affect heart rate variability, which is a known risk factor for health issues. Variability in how the heart rate responds to stressful experiences is essential for maintaining optimal functioning of the cardiovascular, respiratory, and digestive systems and also is central to emotional well-being and resilience to stress over one’s lifetime. Decreased heart rate variability, as observed in this study, is a known risk factor for mental and physical health problems in later life. Air pollution’s negative effect on heart rate variability has previously been found to lead to medical and psychological conditions such as heart disease, asthma, allergies, and mood or behavioral disorders in studies of older children, adolescents, and adults. Mount Sinai researchers studied 237 Boston-based mothers and their infants and used satellite data and air pollution monitors to determine the level of particulate air pollution the mothers were exposed to during pregnancy. The air pollution levels in this study were similar to levels experienced by the general U.S. population. By studying the babies’ heart rate and respiration at age six months, researchers found that the higher the level of the mother’s exposure to air pollution in pregnancy, the less variability in the infant’s heart rate in response to a stress challenge. “These findings, in combination with increasing worldwide exposure to particulate air pollution, highlight the importance of examining early-life exposure to air pollution in relation to negative medical, developmental, and psychological outcomes,” said senior author Rosalind Wright, MD, MPH, Dean for Translational Biomedical Research, and Professor of Pediatrics, Environmental Medicine and Public Health, and Medicine (Pulmonary, Critical Care and Sleep Medicine), at the Icahn School of Medicine at Mount Sinai. “A critical step in identifying children at risk for costly chronic disorders is identifying exposures that lead to early vulnerability.” “Identifying exposures that disrupt key processes such as heart rate response will lead to prevention strategies early in life when they can have the greatest impact. Specifically, these findings support individual-level and policy-level action to reduce exposure to particulate air pollution exposure during pregnancy,” said the study’s first author, Whitney Cowell, PhD, a postdoctoral fellow in Environmental Medicine and Public Health at the Icahn School of Medicine.    About the Mount Sinai Health System The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Geriatrics, Gynecology, Nephrology, Neurology/Neurosurgery, and Orthopedics in the 2019-2020 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 12th nationally for Ophthalmology, Mount Sinai St. Lukes and Mount Sinai West are ranked 23rd nationally for Nephrology and 25th for Diabetes/Endocrinology, and Mount Sinai South Nassau is ranked 35th nationally for Urology. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and Mount Sinai South Nassau are ranked regionally. For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.
Newswise — Global warming may increase undernutrition through the effects of heat exposure on people, according to a new study published this week in PLOS Medicine by Yuming Guo of Monash University, Australia, and colleagues. It has been well documented that global warming will indirectly result in more undernourished people through threatening crop production in the long term. In the new study, researchers analyzed daily hospitalization data that covers nearly 80% of the population of Brazil, spanning the years 2000 through 2015. They studied the link between daily mean temperatures and hospitalization for undernutrition.   For every 1°C increase in daily mean temperature during the hot season, there was a 2.5% increase in undernutrition hospitalization (OR=1.025, 95% CI 1.020–1.030, p<0.001). People under age 19 years or over age 80 years with undernutrition were the most vulnerable to heat exposure. Overall, heat exposure was estimated to be responsible for 15.6% (95% CI 9.0–21.4) of undernutrition hospitalization during the study period. That fraction increased from 14.1% to 17.5% over the study period, during which time the mean temperature increased by 1.1°C. “The possible pathways of this direct impact of heat might include reducing undernourished people’s food intake, impairing their digestion and absorption function, and causing fluid and electrolyte disturbances,” the authors say. “Global strategies addressing the syndemic of climate change and undernutrition should not only focus on food supply but also the prevention of heat exposure especially among the young and elderly people.”   Funding: RX was supported by China Scholarship Council [grant number 201806010405] (https://www.csc.edu.cn/chuguo/s/1267). QZ was supported by a Monash Graduate Scholarship and Monash International Postgraduate Research Scholarship (https://www.monash.edu/graduate-research). SL was supported by the Early Career Fellowship of the Australian National Health and Medical Research Council [grant number APP1109193] (https://www.nhmrc.gov.au/). YG was supported by the Career Development Fellowship of the Australian National Health and Medical Research Council [grant number APP1107107 & APP1163693] (https://www.nhmrc.gov.au/). The funding bodies did not play any role in the study design, data collection, data analyses, results interpretation and writing of this manuscript.   Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: YG is a member of the Editorial Board of PLOS Medicine. MA holds investigator-initiated grants from Pfizer and Boehringer-Ingelheim for unrelated research and an unrelated consultancy from Sanofi. The other authors declare no actual or potential competing financial interests.   Citation: Xu R, Zhao Q, Coelho MSZS, Saldiva PHN, Abramson MJ, Li S, et al. (2019) The association between heat exposure and hospitalization for undernutrition in Brazil during 2000−2015: A nationwide case-crossover study. PLoS Med 16(10): e1002950. https://doi.org/10.1371/journal.pmed.1002950
ROCHESTER, Minn. — Mayo Clinic physicians will present findings at the American College of Gastroenterologists Annual Scientific Meeting, Oct. 25–30 in San Antonio. Findings to be presented are: Patients with microscopic colitis do not have reduced risk of developing colon polyps Newswise — Cross-sectional studies have suggested that patients with microscopic colitis have a lower risk than the general population of developing colon polyps after diagnosis, but a 10-year, multicenter cohort study finds that there's no change in risk. Microscopic colitis is a common cause of chronic diarrhea, and previous studies have found that these patients have a lower incidence of colon polyps. The cohort study, which reviewed 1,128 cases of patients who underwent colonoscopy at Mayo Clinic and Columbia University Irving Medical Center in New York City, found that there was no significant association between microscopic colitis and risk of polyps, says Darrell Pardi, M.D., a Mayo Clinic gastroenterologist and the study's senior author. "Our data suggest that patients with microscopic colitis are at the same risk of developing polyps during follow-up examinations as the general population and therefore their need for surveillance colonoscopy is also the same," says Dr. Pardi. Anti-tumor necrosis factor (TNF) therapy linked to preeclampsia in women with inflammatory bowel disease Women with inflammatory bowel disease have an increased risk of adverse pregnancy outcomes, and some studies have suggested an association between the disease and preeclampsia, a pregnancy complication that results in high blood pressure, and possible damage to the liver, kidneys or other organs. Mayo Clinic researchers looked into whether anti-tumor necrosis factor therapy, which commonly is used to treat inflammatory bowel disease, reduced the risk of patients developing preeclampsia. The results of the small study, which involved nine women with preeclampsia and 18 controls, were surprising. "When we examined the risk for preeclampsia in those on anti-TNF therapy, it was actually higher than in the nonexposed group," says Sunanda Kane, M.D., a Mayo Clinic gastroenterologist and senior author. "We theorize that exposure to anti-TNF agents is a marker of more severe disease, and the amount of inflammation in the body is what drives the increased risk for preeclampsia." Positive polymerase chain reaction (PCR) test results may not predict recurrence of common infection Clostridioides difficile infection is the most common health care-associated infection in the U.S., and it sometimes recurs after initial treatment. Several tests are available for diagnosis, including polymerase chain reaction. This test provides quick results, but can produce a positive result, even after appropriate treatment of the infection. Mayo Clinic researchers wanted to determine whether a positive polymerase chain reaction result during or after treatment predicted infection recurrence. The study involved 50 patients with C. diffinfection who submitted stool samples for polymerase chain reaction testing. The infection recurred within 56 days for 28% of patients, but the study found that patients with a positive polymerase chain reaction after treatment completion did not have a higher risk of recurrence. "We were surprised that positive PCR results during or after treatment did not seem to predict recurrence," says Sahil Khanna, M.B.B.S., a Mayo Clinic gastroenterologist and the study's corresponding author. Though more research is needed, Dr. Khanna says patients with C. diff infection should not routinely undergo repeat polymerase chain reaction testing to predict recurrence. Study proposes new method, protocol to study stomach function after bariatric surgery Bariatric surgery reduces the size of the stomach and is intended to help patients lose weight by limiting how much they can eat. Some patients don't achieve significant weight loss, however, while some regain weight later. It's difficult to measure and assess the patient's stomach after surgery, which limits doctors' ability to develop treatment strategies. Mayo Clinic researchers set out to develop a new way to study stomach function after bariatric surgery. They also sought to develop a new protocol to evaluate stomach accommodation — how much the stomach increased in size after eating — and stomach emptying at the same time. Their study outlines values for the new test protocol. "Utilizing this new test, we will be able to have a better idea of how the stomach functions after bariatric surgery," says Xiao Jing Wang, M.D., a Mayo Clinic gastroenterology fellow and the study's lead author. "This protocol may lead to additional treatments, such as medications that delay stomach emptying, to restore the sensation of fullness after meals." About Mayo ClinicMayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news and An Inside Look at Mayo Clinic for more information about Mayo.
Credit: Allison Carter, Georgia Tech Graduate Student Chia-Heng Chu adjusts a 3D-printed cell trap in the laboratory of Assistant Professor A. Fatih Sarioglu at Georgia Tech. The trap captures white blood cells to isolate tumor cells from a blood sample.   Newswise — Finding a handful of cancer cells hiding among billions of blood cells in a patient sample can be like finding a needle in a haystack. In a new approach enabled by 3D-printed cell traps, researchers are removing the hay to expose the cancer cells. Trapping the white blood cells – which are about the size of cancer cells – and filtering out smaller red blood cells leaves behind the tumor cells, which could then be used to diagnose the disease, potentially provide early warning of recurrence and enable research into the cancer metastasis process. The work, led by researchers at the Georgia Institute of Technology, could advance the goal of personalized cancer treatment by allowing rapid and low-cost separation of tumor cells circulating in the bloodstream. “Isolating circulating tumor cells from whole blood samples has been a challenge because we are looking for a handful of cancer cells mixed with billions of normal red and white blood cells,” said A. Fatih Sarioglu, an assistant professor in Georgia Tech’s School of Electrical and Computer Engineering (ECE). “With this device, we can process a clinically-relevant volume of blood by capturing nearly all of the white blood cells and then filtering out the red blood cells by size. That leaves us with undamaged tumor cells that can be sequenced to determine the specific cancer type and the unique characteristics of each patient’s tumor.” The research was reported September 20 in the journal Lab on a Chip, and was supported by a seed grant from the Integrated Cancer Research Center at Georgia Tech. Other attempts to capture circulating tumor cells have attempted to extract them from the blood using microfluidic technology that recognizes specific surface markers on the cancer cells. But because the cancer can change over time, the malignant cells can’t be recognized with certainty. And even if they can be captured, the tumor cells must be removed from circuitous channels in the device and separated from the antigen without causing damage. Sarioglu and collaborators, including ECE graduate student and first author Chia-Heng Chu, decided to take a different approach, building 3D-printed traps lined with antigens to capture the white blood cells in a sample. The 3D printed traps allowed the researchers to greatly expand the surface area for capturing the white blood cells as they pass by in blood samples. Zig-zagging fluid channels, some as much as half a meter long, increase the likelihood that every white blood cell would come into contact with a channel wall. “Usual microfluidic devices have just a single layer with channel heights of 50 to 100 microns,” Sarioglu said. “They are thick, but most of it just empty plastic. Using 3D printing liberates us from the single channel and allows us to create many channels in three dimensions that better utilize the space.” While the 3D printing allowed an increase in channel density, that came with a significant challenge. Earlier microfluidic devices could be designed with etched channels to carry the blood. But with 3D printing processes that are fabricated layer-by-layer, channels had to be filled with wax to allow more channels to be built atop them. The torturous channel structure, designed to maximize cell-wall interaction, made it virtually impossible to get the wax out after fabrication. The solution was to design cell traps that fit into standard centrifuges designed to spin samples for separation. The traps were heated in the centrifuge and then spun to allow the melted wax to escape. After removing the liquid wax, the channels received the antigen coating. After the white blood cells are removed, the smaller red blood cells pass through a simple commercial filter that traps the cancer cells and any remaining white blood cells. The tumor cells can then be removed from the filter, which is integrated into the 3D printed device. Minimal processing of blood samples is a goal for the project to make the process available to clinics and hospitals without requiring specialized technician skills. Less processing also reduces the risk of damage to the tumor cells and minimizes other cellular changes that could skew the evaluation. As part of the proof of principle testing, the researchers coated the white blood cells with biotin to accelerate testing. Future cell traps will use antigens designed to attract the cells to the channel walls without the biotin processing step. The researchers tested their approach by adding cancer cells to blood taken from healthy people. Because they knew how many cells were added, they could tell how many they should extract, and the experiment showed the trap could capture around 90 percent of the tumor cells. Later testing of blood samples from prostate cancer patients isolated tumor cells from a 10-milliliter whole blood sample. Testing included cells from prostate, breast and ovarian cancer, but Sarioglu believes that the device will capture circulating tumor cells from any type of cancer because the removal mechanism targets blood cells rather than cancer cells. Next steps will be to narrow the channels in the device, test white blood cell removal without the use of biotin, boost the percentage of white cell extraction and connect cell traps to increase trapping capacity. “We expect that this will really be an enabling tool for clinicians,” Sarioglu said. “In our lab, the mindset is always toward translating our research by making the device simple enough to be used in hospitals, clinics and other facilities that will help diagnose disease in patients.” Other co-authors of the paper include Ruxiu Liu, Tevhide Ozkaya-Ahmadov, Mert Boya, Brandi E. Swain, Jacob M. Owens, Enerelt Burentugs, and John F. McDonald, all from Georgia Tech, and Mehmet Asim Bilen from Emory University. CITATION: Chia-Heng Chu, et al, “Hybrid Negative Enrichment of Circulating Tumor Cells from Whole Blood in a 3D-Printed Monolithic Device.” (Lab on a Chip, 2019) http://dx.doi.org/10.1039/C9LC00575G
Newswise — Bethesda, Md. – The effects of a traumatic brain injury (TBI) are pretty clear – problems with memory, headaches, and emotions – but what’s unclear is the underlying pathological causes for those symptoms. According to new research led by researchers at the National Institutes of Neurological Disorders and Stroke (NINDS), those underlying pathological causes may actually involve more extensive blood vessel damage than previously known. These findings could help target better treatment of these common injuries. The study, “Traumatic microbleeds and vascular injury,” was published Oct. 13 in the journal Brain, and was a collaborative effort between the Uniformed Services University of the Health Sciences (USU), the National Institutes of Health (NIH), the University of Maryland, and the Cold Spring Harbor Laboratory. TBI sustained in sports or on the battlefield can have fatal or lasting effects, but until now it’s been unclear how these symptoms develop pathologically. Therefore, the researchers sought to better understand the pathological mechanisms that cause these symptoms by examining the brains of hundreds of patients very soon after injury using high-resolution imaging techniques. They looked, specifically, at traumatic microbleeds – where trauma left a physical imprint on the brain that appeared as dark lesions on MRI scans, according to Dr. Lawrence Latour, the study's lead author and a researcher at NINDS. Of the study’s 439 patients with acute TBI (less than 48 hours after injury), about 30 percent had evidence of traumatic microbleeds (blood vessel injury). The traumatic microbleeds were also identified in 27 percent of mild, 47 percent of moderate, and 58 percent of severe TBI patients. They also found that traumatic microbleeds were seen in more than 25 percent of patients with mild TBI, suggesting that traumatic microbleeds are not exclusive to patients with moderate or severe TBI.  Overall, blood vessel damage was much more widespread than expected in patients with TBI. “These findings are also significant because the presence of traumatic microbleeds was an independent predictor of outcome,” according to Dr. Regina Armstrong, director of Translational Research in USU’s Center for Neuroscience and Regenerative Medicine (CNRM) who also collaborated on the study. The researchers also found patients who had traumatic microbleeds were more than twice as likely to have a disability as a result of their TBI upon follow-up at 30 and 90 days post injury.  “This study is important to the general public, and especially the military, to help detect TBI and provide treatments to those at risk of prolonged symptoms,” Armstrong said. “Future studies are needed to explore therapies targeting the effects of traumatic microbleeds in acute TBI, including TBIs that result from high-impact blast exposures.” The study was supported by USU’s CNRM, the NINDS, and the Intramural Research Programs at the NIH Clinical Center.