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WASHINGTON, D.C., (April 28, 2021) - The latest, comprehensive data from The North American COVID-19 Myocardial Infarction (NACMI) Registry was presented today as late-breaking clinical research at the Society for Cardiovascular Angiography & Interventions (SCAI) 2021 Scientific Sessions. Results reveal in these series of STEMI activations during the COVID era, patients who tested positive for COVID-19 were less likely to receive diagnostic angiograms. Those with COVID-19 positive status had higher in-hospital mortality. The prospective, ongoing observational registry was created under the guidance of the SCAI, Canadian Association of Interventional Cardiology (CAIC) and American College of Cardiology (ACC). The initial results of the registry were published in the Journal for American College of Cardiology (JACC) on April 27, 2021.

According to the American Heart Association, more than 930,000 people suffer from heart attacks every year and more than a quarter of those patients suffer the more severe type of heart attack, an ST-elevated myocardial infarction, or STEMI caused by the sudden, total blockage of a coronary artery. Qualifying patients often undergo a (percutaneous coronary intervention (PCI), a nonsurgical, angiography procedure that improves blood flow to the heart. However, little is known on how the ongoing COVID-19 pandemic impacted the use of angiography procedures based on patient demographics and outcomes.

As of April 9, 2021, more than 1,600 patients were included in the NACMI (331 STEMI with were COVID-19, 645 suspected COVID-19 positive patients and 662 control - a group of age and sex matched STEMI patients treated pre-COVID-19). The primary outcome was a composite of in-hospital death, stroke, recurrent myocardial infarction or repeat unplanned revascularization. The overall goal of the registry is to understand demographic characteristics, management strategies and outcomes of COVID-19 patients with STEMI.

Findings show COVID-19 positive patients were more likely to be of minority ethnicity, have diabetes and undergo medical therapy as a first-line treatment rather than PCI (all p

"Leading clinicians and researchers have quickly and efficiently come together to understand the relationship between COVID-19 and heart attacks. This registry is an amazing feat of collaboration, speed and scale involving more than 60 sites, and three leading medical societies across the United States and Canada," said co-lead investigator Payam Dehghani, MD, FSCAI, Prairie Vascular Research Network, Canada. "We're seeing an alarming trend of the deadly impact of this pandemic on high-risk minority heart attack patients. This ongoing registry's goal is to help illuminate these disparity trends and inform future preventive and treatment strategies for this COVID-19 era."

The authors of the investigational registry are planning to conduct additional research to further understand the impact on specific minority and diabetic patient populations. In addition, investigators plan to follow up at one year to verify findings.

WASHINGTON, D.C, (April 28, 2021) - An analysis of the prospective Fuwai PCI Registry, confirms long-term dual antiplatelet therapy (DAPT) is an optimal treatment option for acute coronary syndrome patients (ACS) following a percutaneous coronary intervention (PCI). The study shows long-term DAPT reduces ischemic events without increasing bleeding or other complications as compared to short-term DAPT treatments. The study was presented today as late-breaking clinical research at the Society for Cardiovascular Angiography &Interventions (SCAI) 2021 Scientific Sessions.

Following ACS, patients have a high risk of ischemic events, which impacts chances of survival. Patients are predisposed for blood clots within an artery for years after an ischemic event, suggesting that the pathobiology of recurrent events post-ACS differs from that of stable coronary artery disease (CAD) patients who have not offered a previous ischemic event. Therefore, ACS patients may be more likely to benefit from long-term secondary prevention strategy, like extended-duration DAPT.

DAPT with aspirin and a P2Y12 inhibitor is the cornerstone of management after an ACS. Current practice guidelines recommend treatment of ACS patients include more aggressive risk factor modi?cation and prolonged antiplatelet therapy, as well as DAPT for a minimum of 12 months following an ACS, regardless of whether or not PCI is performed. In addition to protecting against stent thrombosis in the culprit lesion, an important objective of long-term DAPT in patients with ACS is the prevention of future coronary ischemic events from nonculprit lesions, as demonstrated in earlier trials. With the improvement of stent device technology, studies evaluating the safety and efficacy of shortening DAPT to less than 12-months in patients with ACS undergoing PCI reported conflicting results .

The study included 4,875 high-risk "TWILIGHT-like" patients undergoing PCI. The high-risk patients were defined by at least one clinical and one angiographic feature based on TWILIGHT trial selection criteria, with ACS who were event free at 12 months after PCI from the Fuwai PCI Registry. The primary outcome was the composite of all-cause death, MI or stroke at 30 months while the Bleeding Academic Research Consortium (BARC) type 2,3 or 5 bleeding was key secondary outcome.

Results showed that slightly more than two-third of ACS patients remained on DAPT beyond 12 months after PCI. Extended DAPT compared with shorter DAPT reduced the composite outcome of all-cause death, MI or stroke by 63%. BARC type 2, 3, or 5 bleeding rates did not differ significantly in patients treated with DAPT longer than 12-months versus those treated with DAPT less than 12-months. The effect of long-term DAPT on primary and key secondary outcome across the proportion of ACS patients with 1-3, 4-5, or 6-9 risk factors showed a consistent manner.

"Our findings suggested that prolonged DAPT in ACS patients who present with a particularly higher risk for thrombotic complications without excessive risk." said Haoyu Wang, M.D., Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, China. "Not only did we see long-term DAPT was associated with a lower risk of a major cardiovascular event without an increase in bleeding events, but it it could be considered an effective strategy to balance the risk for bleeding and ischemia in high-risk patients with ACS. Our results reinforce prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care."

Authors call for further analysis on high bleeding risk and ischemia patients and work to publish in additional publications across Asia.

The research team led by Prof. WENG Jianping from University of Science and Technology of China (USTC) of the Chinese Academy of Sciences has implemented a comprehensive preconception-to-pregnancy management plan, namely CARNATION study, for women with type1 diabetes (T1D), to reduce the risks of adverse pregnancy outcomes and improve the pregnancy care since 2015. The study was published in Diabetes Care.

The management plan, approved by the National Health and Family Planning Commission of the People's Republic of China, is made up of the checklist for the relevant health care providers (HCPs) covering 20 items of care in different stages from preconception care to postpartum care. These items include information on multidisciplinary cooperation and recommendations on diet, management of diabetes and its complications and other medical issues.

T1D commonly occurs among children and teenagers. However, pregnancy may speed up T1D complication, and T1D in turn is considered as a major factor in high-risk pregnancy.

To find out the key point for the pregnancy care management with pregestational T1D and how to make the information of pregnant women with T1D effectively pass through multidisciplinary fields, are questions need to be answered.

CARNATION study put prospective cohort study into priority. It provided T1D eugenic preconception counseling services and screening methods, and gave blood glucose treatment from pregnancy to postpartum stages as well as neonatal treatment.

Besides, this study proved that severe adverse pregnancy outcomes and several other adverse outcomes among pregnant women with T1D could be significantly lowered down.

Pregnant women with T1D take from a quadruple to ten times of higher risks of adverse pregnancy outcomes with fetal macrosomia, congenital malformation, intrauterine growth retardation, premature delivery as well as neonatal mortality. This study may help to change the situation.

ATLANTA--Processed diets, which are low in fiber, may initially reduce the incidence of foodborne infectious diseases such as E. coli infections, but might also increase the incidence of diseases characterized by low-grade chronic infection and inflammation such as diabetes, according to researchers in the Institute for Biomedical Sciences at Georgia State University.

This study used mice to investigate how changing from a grain-based diet to a highly processed, high-fat Western style diet impacts infection with the pathogen Citrobacter rodentium, which resembles Escherichia coli (E. coli) infections in humans. The findings are published in the journal PLOS Pathogens.

Gut microbiota, the microorganisms living in the intestine, provide a number of benefits, such as protecting a host from infection by bacterial pathogens. These microorganisms are influenced by a variety of environmental factors, especially diet, and rely heavily on complex carbohydrates such as fiber.

The Western-style diet, which contains high amounts of processed foods, red meat, high-fat dairy products, high-sugar foods and pre-packaged foods, lacks fiber, which is needed to support gut microbiota. Changes in dietary habits, especially a lack of fiber, are believed to have contributed to increased prevalence of chronic inflammatory diseases such as inflammatory bowel disease, metabolic syndrome and cancer.

In this study, the researchers found switching mice from a standard grain-based rodent chow to a high-fat, low-fiber Western-style diet resulted in a rapid reduction in the number of gut bacteria. Mice fed the Western-style diet were frequently unable to clear the pathogen Citrobacter rodentium from the colon. They were also prone to developing chronic infection when re-challenged by this pathogen.

The researchers conclude the Western-style diet reduces the numbers of gut bacteria and promotes encroachment of microbiota into the intestine, potentially influencing immune system readiness and the body's defense against pathogenic bacteria.

"We observed that feeding mice a Western-style diet, rather than standard rodent grain-based chow, altered the dynamics of Citrobacter infection, reducing initial colonization and inflammation, which was surprising. However, mice consuming the Western-style diet frequently developed persistent infection that was associated with low-grade inflammation and insulin resistance," said Dr. Andrew Gewirtz, senior co-author of the study and professor in the Institute for Biomedical Sciences. "These studies demonstrate potential of altering microbiota and their metabolites by diet to impact the course and consequence of infection following exposure to a gut pathogen."

"We speculate that reshaping gut microbiota by nutrients that promote beneficial bacteria that out-compete pathogens may be a means of broadly promoting health," said Dr. Jun Zou, senior co-author of the study and assistant professor in the Institute for Biomedical Sciences at Georgia State.

Children and young adults with compromised immune systems, such as those undergoing cancer treatment, may experience a prolonged period of infection with SARS-CoV-2, the virus that causes COVID-19, and the extended duration of infection may increase the incidence of mutations. This case study was conducted by investigators at Children's Hospital Los Angeles and is published in the journal EBioMedicine.

Most people are infectious for about 10 days after first showing COVID-19 symptoms. In this study, researchers describe two children and a young adult with acute lymphoblastic leukemia who tested positive for SARS-CoV-2 for months. This is the first report of prolonged infection in a pediatric or young adult population.

"It's significant that these patients continued to have active symptoms and active infections for such a long time," says lead author Jennifer Dien Bard, PhD, Director of the Clinical Microbiology and Virology Laboratory at Children's Hospital Los Angeles. "The large number of pediatric and adult patients receiving cancer therapy and being actively screened for the virus leads us to conclude that this is a rare occurrence but one that could have public health implications."

SARS-CoV-2 mutates about once or twice a month, according to Dr. Dien Bard. A long period of infection raises concerns about the development of viral mutations. When a virus replicates, it copies its genetic code, but sometimes the virus makes a mistake known as a mutation. Most mutations have no effect on how the virus behaves or on the disease it causes, but some may result in the virus acting differently. For example, the B.1.1.7 SARS-CoV-2 variant, which has 17 mutations, is thought to be more infectious than other virus variants.

Dr. Dien Bard notes there is some evidence to suggest the B.1.1.7 variant may have originated in a person who was immunocompromised and consistently infected with SARS-CoV-2. Yet even in immunocompromised patients, months-long infections are rare.

"We have had many other immunocompromised patients who have not experienced these prolonged infections, but it's something to be aware of, and hospitals may want to consider changing infection control policies to address this particular special population," says Dr. Dien Bard.

Dr. Dien Bard and other experts at Children's Hospital Los Angeles have been genetically sequencing SARS-CoV-2 samples since March of 2020. Learn more about their work here and here.

STUDY EXAMINES WHY SKIN LACERATIONS MAY BE SLOW TO HEAL, EVEN WITH TOPICAL ANTIBIOTICS

https://www.hopkinsmedicine.org/news/newsroom/news-releases/research-story-tip-study-examines-why-skin-lacerations-may-be-slow-to-heal-even-with-topical-antibiotics

Media Contact: Sheree-Monet Wisdom, swisdom1@jhmi.edu

When you get a cut, scrape or other minor skin laceration, doctors recommend that you take measures to ensure that the wound doesn't get infected and heals properly. Many people opt to use over-the-counter medications, such as topical antibiotic ointments and liquids, to aid the repair process -- and as commonly believed, promote healthy skin healing.

Aiming to put this theory to the test, Johns Hopkins Medicine researchers recently examined whether or not skin regeneration is affected when topical ointments are introduced to a wound site.

In their study -- which appeared April 1, 2021, in the journal Cell Host & Microbe -- the researchers suggest that such over-the-counter medications may not be the healers we believe them to be.

The natural environmental factors that enhance skin regeneration are largely unknown. Although our immune systems and the nonpathogenic microorganisms living within our bodies play critical roles in repairing and regenerating our skin's structure, the precise interaction between the two has been unclear.

In a small trial following six adults over a 10-month period, the researchers wanted to see if bacteria made a difference in wound healing. The participants either applied or didn't apply a topical broad-spectrum antibiotic following every skin wound they received. To the surprise of the researchers, the majority of the antibiotic users experienced slower healing. Furthermore, in a concurrent study in mice, the antibiotics prevented the regeneration of hair follicles after wounding.

"We tested many conditions where there were fewer or more bacteria present during wound healing, for example after antibiotic use. We found that generally speaking, normal levels of bacteria -- and even bacterial infections that the body could fight off -- would actually improve healing," says study senior author Luis Garza, M.D., Ph.D., associate professor of dermatology at the Johns Hopkins University School of Medicine.

"If further research confirms the finding of this study -- that common over-the-counter antibiotic treatments are slowing the healing process -- then perhaps people may need to reconsider their use of these products," Garza says.

Garza is available for interviews.

FOR DEPRESCRIBING MEDICATIONS, WHAT THE DOCTOR SAYS IS KEY

https://www.hopkinsmedicine.org/news/newsroom/news-releases/research-story-tip-for-deprescribing-medications-what-the-doctor-says-is-key

Media Contact: Waun'Shae Blount, wblount1@jhmi.edu

When an older patient no longer needs a medication or requires less dosage, doctors may consider "deprescribing" the medicine. Deprescribing enables clinicians to stop or reduce medications that are no longer beneficial or may even be harmful for a patient.

However, getting people to change their habits -- especially the regimens for taking medications -- may require doctors and other health care providers to think carefully about how they communicate deprescribing.

In a recent study, Johns Hopkins Medicine researchers examined the ways older patients prefer to get this communication, finding that "how it's said" can determine the success or failure of the process.

A report on the findings was published April 5, 2021, in JAMA Network Open.

"We tested targeted language that providers could use when suggesting patients stop potentially harmful medications," says study lead author and geriatrician Ariel Green M.D., M.P.H., Ph.D., assistant professor of geriatric medicine at the Johns Hopkins University School of Medicine.

Green and the research team say medicines that were helpful at one stage of life may be harmful or unnecessary at another stage of life. The language used by providers when reducing or stopping medications can help patients and their loved ones make better-informed decisions.

In the study, the researchers shared two scenarios with 835 adults age 65 and older related to medication regimens. One scenario involved a patient taking a statin or a cholesterol-lowering medication to prevent problems such as heart attacks or strokes, and the other scenario involved a sleeping pill being taken for the bothersome, but not life-threatening, symptom of insomnia.

The findings showed that patients were more likely to agree to stop taking the statin medication and the sleeping pill when doctors mentioned that the risk of side effects increased as a result of aging and co-existing health problems. In contrast, patients were less likely to agree to stop taking the statin when doctors used a phrase such as, "I think we should focus on how you feel now rather than thinking about things that might happen years down the road." They also were more hesitant to stopping the sleeping pill when told, "This medicine is unlikely to help you function better."

The study was conducted between March and April 2020. The average age of survey participants was 73 years old; 50% of participants were women; and 80% identified as white. Of the participants surveyed, 59% had personally taken a statin and 15% had taken a sleeping pill. Study participants were asked to choose from seven different phrases that a clinician could use to explain a recommendation for deprescribing.

The research team is currently developing and testing several interventions to improve prescribing -- and deprescribing -- medications for older adults in primary care, especially people living with memory problems or dementia. The current study shows that these interventions incorporate key language and rationales that improve the effectiveness of communication about medication use and deprescribing among older adults, their families and doctors.

Green is available for interviews.

WELL-CARE VISITS PROMOTE BETTER HEALTH DURING TRANSITION FROM CHILDHOOD TO ADOLESCENCE

https://www.hopkinsmedicine.org/news/newsroom/news-releases/research-story-tip-well-care-visits-promote-better-health-during-transition-from-childhood-to-adolescence

Media Contact: Waun'Shae Blount, wblount1@jhmi.edu

During well-care visits, children are seen by their primary care physician to address health needs. Maintaining these visits can have a positive impact on a child's current and future health. To determine how adolescents use well-care services over time, a research team at Johns Hopkins Medicine and the Kennedy Krieger Institute recently reviewed use patterns for nearly 7,000 adolescents based on their age and sex.

In their study -- one of the first to look at individual well-care use patterns throughout the transition from childhood to adolescence rather than just the cumulative number of visits over time -- the researchers discovered that well-care visits often declined during the transition, especially among boys, who were more likely to become disengaged after age 5 well-care visits.

A report on the team's findings was published in the May 2021 issue of the American Journal of Preventive Medicine (first posted online Feb. 27, 2021).

"We concluded how it is important to use a life course approach to understand which adolescents are getting or not getting well-care visits over time, since these type of visits are so important to promote positive health outcomes for children of all ages, including boys," says Arik Marcell, M.D., M.P.H., associate professor of pediatrics at the Johns Hopkins University School of Medicine and a physician at Johns Hopkins Children's Center.

The study assessed data from a survey of 6,872 children who were born between 1980 and 1997 and had at least one well-care visit between the ages of 5 (age reached during 1986-2000) and 17 (age reached during 1998-2015). The children were selected from the Child/Young Adult component of the 1979 National Longitudinal Survey of Youth.

Among the data factors for the children were race, ethnicity, mother's education and health insurance. Well-care use data were collected every two years from all study participants to assess the last time they were seen for a health checkup.

The study population was 50% female, 49% white, 30% Black and 21% Hispanic. More than three-quarters (78%) lived in an urban setting, 76% had a mother with at least a high school education and 89% had health insurance.

Participants were assessed on how engaged they were with their well-care visits over time -- specifically, from age 5 through age 17. Among girls, 37% were engaged in well care over the studied time frame, 39% were moderately engaged, 14% became gradually reengaged after initially dropping off after the age 5 visit (with visits resumed after age 7), and 10% became disengaged after the age 5 visit (with visits resumed after age 13).

For boys, 48% showed they were persistently disengaged from well care after their age 5 visit, 34% were engaged over the studied time frame, and 18% became gradually reengaged after initially dropping off at the age 5 visit (with visits resumed after age 7).

Well-care use for boys and girls decreased when the child transitioned into adolescence, with significantly greater drop-off for boys than girls. The researchers say this suggests health care providers should implement sex-specific measures to encourage more frequent well-care visits for both sexes during the middle childhood and adolescent years.

To continue their research, the Johns Hopkins Medicine and Kennedy Krieger investigators plan to examine the impact that regular well-care use has on establishing positive health promotion behavior and practices in children and adolescents over time.

Marcell is available for interviews.

GRANT FOCUSES ON PHYSICIAN USE OF PRESCRIPTION DRUG PRICING TOOLS DURING PATIENT CARE

https://www.hopkinsmedicine.org/news/newsroom/news-releases/research-story-tip-grant-focuses-on-physician-use-of-prescription-drug-pricing-tools-during-patient-car

Media Contact: Rachel Butch, rbutch1@jhmi.edu

Researchers at the Johns Hopkins University School of Medicine have received $400,000 from the Patrick and Catherine Weldon Donaghue Medical Research Foundation to analyze the use of real-time prescription pricing tools that automatically calculate the out-of-pocket cost of medications and appropriate alternatives for doctors to review with their patients during their visit.

"Our long-term goal is to facilitate the adoption of and measure the effectiveness of these real-time health benefit tools nationwide," says Fasika Woreta, M.D., M.P.H., assistant professor of ophthalmology at the Johns Hopkins University School of Medicine.

The Johns Hopkins Medicine researchers will use the grant to study how physicians use the real-time prescription benefit tools in their ambulatory clinic visits over a two-year period. The tools -- including the Surescripts Real-Time Prescription Benefit -- were integrated into electronic health records in 2019. They will now be evaluated at the Johns Hopkins Health System, Yale School of Medicine and the Froedtert & Medical College of Wisconsin health network.

The United States ranks higher in spending on prescription drugs than any other country in the world, with half of patients reporting that they have not taken a medication because it was too expensive. This year, the Centers for Medicare and Medicaid Services has mandated that providers seeing patients with Medicare Advantage and stand-alone Part D plans use real-time prescription benefit tools in electronic health records during every visit in which the provider orders a prescription in an effort to bring down these costs.

Because these pricing tools are so new, data are lacking on how they are used by health care providers. To help remedy this, the research team plans to study:

How and when providers are using the electronic system.

Whether this use is associated with prescribers choosing a different drug type or brand for their patients.

How the prescribing tool impacts patient spending at the pharmacy and decreases unused prescriptions.

How to identify barriers or facilitating factors that enable use of the tools among providers.

Preliminary work by Johns Hopkins investigators has confirmed that the real-time prescription benefit tools provide accurate drug pricing information.

"Our hope is that these tools will enable physicians and patients to engage in conversations regarding medication cost based on their individual prescription benefits at the point of prescribing," says Woreta. "We believe this will lead to selection of more affordable medications, and thus, increased medication adherence by patients."

The researchers will focus their analysis on some of the most commonly prescribed drugs in the U.S., including eye drops, statins and diabetes medications.

Woreta is available for interviews.

Philadelphia, April 28, 2021 - Researchers from the Center for Autism Research (CAR) at Children's Hospital of Philadelphia (CHOP) found that difficulties in diagnosing toddlers with autism spectrum disorder (ASD) might be due to the dynamic nature of the disorder during child development. Children with clinical characteristics that put them on the diagnostic border of autism have an increased susceptibility to gaining or losing that diagnosis at later ages. The findings were published online by The Journal of Child Psychology and Psychiatry.

While most children diagnosed with ASD at early ages retain their diagnosis, a significant number of children have more dynamic presentations of clinical features associated with autism and may show changes as they develop, particularly around the time they are between two and three years old. These changes may lead a minority of children to actually lose or gain their ASD diagnosis over time. Recent studies have introduced the notion that this change in diagnosis is the result of intermediate cases of ASD, where children are neither clearly affected nor clearly unaffected.

Although researchers have been aware of these intermediate cases and possible diagnostic shifts, no prior studies have quantitatively evaluated the transition region between these ASD and non-ASD cases. Using a data-driven approach, the study team wanted to explore the links between early diagnostic shifts in ASD and the "fuzzy nature" of the diagnostic boundary.

"This study is the first to really develop a quantitative understanding of how each person is unique and how some of their core attributes change in small ways over the third year of their life," said Robert T. Schultz, PhD, director of CAR and senior author of the study. "Past studies called attention to diagnostic instability at early ages without understanding why this was happening for each child and that these changes are gradual. Children grow in a continuous manner, and we now have a principled way to measure this steady growth and how it may push these children into and out of the diagnostic category of autism."

The researchers used a cohort of children with high risk of developing ASD, since all participants had an older sibling diagnosed with autism. The cohort included 222 participants assessed at 24 months of age and then at 36 months of age. Using machine learning, the team was able to empirically characterize the classification boundary between ASD and non-ASD participants by quantifying developmental and adaptive skills.

The study found that most children who switched diagnostic labels (dynamic group) - either from ASD to non-ASD or vice versa - had intermediate clinical feature profiles. They were, on average, closer to the classification boundary compared with children who had stable diagnoses, both at 24 and 36 months of age. The magnitude of the shift was similar for both the dynamic and stable diagnostic groups, suggesting that diagnostic shifts were not associated with a large change in clinical profiles.

However, when children were examined at an individual level, a few children in the dynamic group showed substantial change. There were also substantial improvements in some children with severe impairments, suggesting that not all diagnostic shifts are due to having an intermediate clinical profile. Diagnostic shifts could be due to a variety of factors, including different causes of ASD, varying timing of the onset of ASD, and different treatment histories.

"Our study clearly shows the inherently dynamic nature of early diagnoses of autism," said Birkan Tunç, PhD, a computational scientist with CAR and lead author of the study. "If we can identify predictive behavioral or neurobiological patterns of children who might have a change in their diagnosis, we may advance current clinical practices and better tailor individualized intervention strategies. Our findings call for more vigilant surveillance and faster initiation of intervention rather than waiting for a categorical diagnosis to begin treatment."

ROCHESTER, Minn. -- Difficult-to-treat, chronic wounds in preclinical models healed with normal scar-free skin after treatment with an acellular product discovered at Mayo Clinic. Derived from platelets, the purified exosomal product, known as PEP, was used to deliver healing messages into cells of preclinical animal models of ischemic wounds. The Mayo Clinic research team documented restoration of skin integrity, hair follicles, sweat glands, skin oils and normal hydration.

Ischemic wounds occur when arteries are clogged or blocked, preventing important nutrients and oxygen from reaching the skin to drive repair. This groundbreaking study titled, "TGF-β Donor Exosome Accelerates Ischemic Wound Healing," is published in Theranostics.

"This paper documents that PEP, an off-the-shelf, room-temperature-stable exosome, is capable of healing wounds that are depleted of adequate blood supply. Wounds healed with only a single application of exosome," says Steven Moran, M.D., a Mayo Clinic plastic surgeon and senior co-author on the study. "I was surprised that this product regenerated healthy skin with normal biomechanical properties -- not scar tissue. As this technology is now scaled and biomanufactured for clinical applications, it creates the potential for huge advancement in medical science and the field of plastic surgery."

This study has laid the foundation for Food and Drug Administration approval to begin a first-in-class clinical trial to test safety of using the purified exosomal product for wound healing in patients. This research is supported by Mayo Clinic's Center for Regenerative Medicine, which is a leader in advancing new, validated regenerative procedures from research into practice.

Chronic ischemic wounds are common in people with conditions such as diabetes, pressure ulcers, hardening of arteries, traumatic injury or side effects of radiation therapy. Standard treatments for these wounds include wound dressing, topical gels and surgery. Although these measures offer some relief, they often cannot fully close the wound. As a result, approximately 7 million people in the U.S. have wounds that don't close properly, and efforts to find solutions have grown to a multibillion dollar industry, according to National Institutes of Health-sponsored research. When the condition progresses, nonhealing wounds lead to limb amputation.

The purified exosomal product is an extracellular vesicle that delivers cargo from one cell to another, targeting exact tissues in need of repair. This technology is manufactured under strict quality control measures and formulated as a dry powder to enable long-term storage at room temperature. In the operating room or at the bedside, the powder is mixed with a hydrogel solution on-site and can be applied directly to the wound. Unlike cellular products, it does not have to be sent to an outside laboratory to be cultured and scaled.

"What we see with this technology is not just that the wound is closed, but also that the blood supply to the tissue is restored. Our effort culminating in the development of this exosomal technology was to create a therapy that can be offered to all patients in need through elimination of logistical limitations often seen with more traditional regenerative therapy," says Atta Behfar, M.D., Ph.D., deputy director of Translation, Mayo Clinic's Center for Regenerative Medicine and senior author. "Our research hopes to answer whether this can be a new healing solution for patients suffering with nonhealing chronic wounds." Dr. Behfar is director of the Mayo Clinic Van Cleve Cardiac Regenerative Medicine Program where the purified exosomal product was discovered.

The research

The research team replicated wounds with low blood supply in large animal models. They treated some of the wounds with the purified exosomal product and compared them to wounds that were treated with the hydrogel alone. They found wounds treated with the purified exosomal product were able to heal with skin restored to its normal architecture.

"We found that this exosome therapy has the ability to enhance regeneration of blood vessels in damaged tissues. Without treatment, chronic ischemic wounds grow larger and more problematic," says Ao Shi, Ph.D., a student in the Regenerative Sciences Training Program in Mayo Clinic Graduate School of Biomedical Sciences and first author.

NEW YORK, NY-- Diagnosing chronic kidney disease, which is often undetected until it causes irreversible damage, may soon become automated with a new algorithm that interprets data from electronic medical records.

The algorithm, developed by researchers at Columbia University Vagelos College of Physicians and Surgeons, automatically scours a patient's electronic medical record for results of blood and urine tests and, using a mix of established equations and machine learning to process the data, can alert physicians to patients in the earliest stages of chronic kidney disease.

A study of the algorithm was published in the journal npj Digital Medicine in April.

"Identifying kidney disease early is of paramount importance because we have treatments that can slow disease progression before the damage becomes irreversible," says study leader Krzysztof Kiryluk, MD, associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons. "Chronic kidney disease can cause multiple serious problems, including heart disease, anemia, or bone disease, and can lead to an early death, but its early stages are frequently under-recognized and undertreated."

Chronic Kidney Disease Progresses Silently

Approximately one in every eight American adults is believed to have chronic kidney disease, but only 10% of people in the disease's early stages are aware of their condition. Among those who already have severely reduced kidney function, only 40% are aware of their diagnosis.

The reasons for underdiagnosis are complex. People in the early stages of chronic kidney disease usually have no symptoms, and primary care physicians may prioritize more immediate patient complaints.

In addition, two tests, one that measures a kidney-filtered metabolite in blood and another that measures leakage of protein in urine, are needed to detect asymptomatic kidney disease. 

"The interpretation of these tests is not always straightforward," Kiryluk says. "Many patient characteristics, including age, sex, body mass, or nutritional status, need to be considered, and this is frequently under-appreciated by primary care physicians." 

Algorithm Automates Diagnosis

The new algorithm surmounts these obstacles by automatically scanning electronic medical records for test results, performing the calculations that indicate kidney function and damage, staging the patient's disease, and alerting physicians to the trouble.

The algorithm performs nearly as well as experienced nephrologists. When tested using electronic health records from 451 patients, the algorithm correctly diagnosed kidney disease in 95% of the kidney patients identified by two experienced nephrologists and correctly ruled out kidney disease in 97% of the healthy controls.

The algorithm can be used on different types of electronic health record systems, including those with millions of patients, and could easily be incorporated into a clinical decision support system that helps physicians by suggesting appropriate stage-specific medications. The algorithm can be easily updated if standards for diagnosing kidney disease are changed in the future and is freely available for use by other institutions.

Limitations

One drawback of the algorithm is that it depends on the availability of relevant blood and urine tests in the medical record. The blood test is fairly routine, but the urine test is underutilized in clinical practice, Kiryluk says. 

Despite these limitations, algorithmic diagnosis could enhance awareness of kidney disease, Kiryluk says, and, with earlier treatment, potentially reduce the number of people who lose kidney function.

Powerful Tool for Research

The algorithm has other important benefits for researchers. Because it can be applied to EHR datasets with millions of patients and identify all patients with chronic kidney disease, not just those diagnosed with the disease, the algorithm improves the power of many research studies. 

The researchers have already applied the algorithm to a database of millions of Columbia patients to find previously unrecognized associations between chronic kidney disease and other conditions. For example, depression, alcohol abuse, and other psychiatric conditions were considerably more common among patients with mild kidney disease compared to patients with normal kidney function, even after accounting for differences in age and sex. 

"Our analysis also confirmed that a mild degree of kidney dysfunction is often present in blood relatives of patients with kidney disease," says Ning Shang, PhD, associate research scientist in the Kiryluk lab and the lead author of the paper. "These findings support strong genetic determination of kidney disease, even in its mildest form."

In the future, Kiryluk says, the algorithm could be used to better understand the inherited risk of chronic kidney disease, because the algorithm empowers genetic analyses of millions of people to discover new kidney genes.

WINSTON-SALEM, NC - April 27, 2021 -- An intestinal bowel disease that affects up to 10 percent of premature infants at a very vulnerable and developmentally crucial time can lead to serious infection and death. Scientists at the Wake Forest Institute for Regenerative Medicine (WFIRM) are tackling the disease with a human placental-derived stem cell (hPSC) therapy strategy that is showing promising results.

Necrotizing enterocolitis is a life-threatening intestinal disease that is a leading cause of mortality in premature infants and treatment options remain elusive. The cause of the disease is unclear - it is a multi-faceted disease that results from the complex interaction of early bacterial colonization, an exaggerated inflammatory response, and immature intestinal tissue. It occurs when the wall of the intestine is invaded by bacteria which cause infection and inflammation. Developing treatment approaches for this disease would improve both the survival outcomes and the health of these children who have their entire lifetime to protect.

Based on recent cell therapy studies, WFIRM scientists investigated the effect of a human placental-derived stem cell therapy on intestinal damage in a pre-clinical animal model. In 2007, WFIRM scientists were the first to identify and characterize stem cells derived from amniotic fluid and placenta. Stem cells offer great promise for new medical treatments to treat disease and injury.

In the last decade, researchers have made significant advances in identifying important prevention strategies for reducing the risk of necrotizing enterocolitis onset. Unfortunately, few approaches have demonstrated the therapeutic ability to offset established damage. To address this gap, the researchers focused their study on the potential of human placental-derived stem cells for treatment.

"In our recent studies, we demonstrated that a promising placental stem cell therapy could induce repair of established damage caused by the disease. Interestingly, we saw that the predominate repair occurred in the barrier cells that line the intestine, which presents a potential new therapeutic target," said Victoria G. Weis, PhD, a lead author of the paper being published by the American Journal of Physiology's Gastrointestinal and Liver Physiology section. The American Physiological Society has also selected the paper to highlight in a special collection that showcases some of the best recently published articles in physiological research.

For the study, the pre-clinical model with induced intestinal damage received injections of either saline or the placental stem cell therapy at 32 and 56 hours following birth directly into the abdominal cavity. At four days, the induced damage was assessed. The researchers found that the placental stem cell therapy stopped disease progression and promoted healing of the intestinal damage at both the cellular and whole tissue levels.

One of the most prominent findings in the study is the significant improvement of the two critical cell populations that are important to the intestine's ability to continuously replenish and sustain the barrier. In necrotizing enterocolitis disease, these intestinal cell populations are significantly lost and the function of the intestinal barrier is drastically compromised. The placental stem cell treatment helped support the re-establishment of these cell populations to healthy levels which allow the intestine to properly form a functioning barrier against further bacterial infection.

"These findings open exciting new avenues for advanced therapeutic development that could hopefully one day contribute to the advancement of medical care for this disease and help set the foundation for a long and healthy life for these babies," Weis said.

Senior study author Anthony Atala, MD, and director of WFIRM, said that human placental-derived stem cells are a novel research tool that can be leveraged to identify ways to repair damage or combat disease altogether.

"Our results show that stem cell treatment can promote intestinal healing. In this disease model, utilizing them as an early intervention may be better tolerated in the infant and, further, may decrease disease progression to advanced stages that require surgery," Atala said.

The risk of developing atherosclerosis – a narrowing of the arteries as cholesterol plaque builds up, leading to obstruction of blood flow – is higher for people with autoimmune rheumatic diseases than for the general population. As a result, they are more likely to have heart attacks and other cardiovascular disorders. 

The good news, according to a new study published in Rheumatology, is that regular exercise is a powerful weapon against vascular dysfunction in these patients.

In the article, researchers working in Brazil and the United Kingdom report the results of a systematic review of the scientific literature on the subject. The review, which was supported by FAPESP, covered ten studies involving 355 volunteers with various diseases, such as rheumatoid arthritis, lupus, and spondyloarthritis (inflammation of the spine). The subjects took exercise programs such as walking in a park or on a treadmill, stationary cycling, high-intensity interval training, and muscle building. Most of the programs lasted 12 weeks.

“Our analysis of the results showed that exercise improved small and large vessel endothelial function to a clinically significant extent. Accordingly, we suggested that exercise can be considered ‘medication’ for these patients because of its potential to reduce the incidence of cardiovascular events,” said Tiago Peçanha, first author of the article. Peçanha is a postdoctoral fellow at the University of São Paulo’s Medical School (FM-USP) in Brazil.

These rheumatic diseases, he explained, are the result of an imbalance in the immune system that leads to the production of antibodies against the subject’s own organism, especially joints, muscles, ligaments and tendons. While there is no definitive cure for these diseases, they can be controlled by treatment with anti-inflammatory drugs, immunosuppressants, and biologics (drugs from living sources).

“Treatment doesn’t prevent patients from developing certain co-morbidities. Cardiovascular disease is the most worrisome,” Peçanha said. “The risk of heart attack is twice as high for people with rheumatoid arthritis as for healthy people. For people with lupus or psoriatic arthritis, the incidence of ischemic events [heart attack, angina and stroke] is between twice and five times as high.” 

Atherosclerosis develops rapidly in these patients owing to the chronic inflammation associated with rheumatic disease and continuous use of anti-inflammatory drugs. “It all begins with changes in blood vessel structure and function,” Peçanha said. “The arteries gradually harden and stop being able to dilate when necessary. Changes occur above all in the endothelium [the layer of cells lining the interior surface of blood vessels]. Alterations in vascular function, especially endothelial function, are considered initial markers of atherosclerosis for this reason.”

The systematic review showed that exercise improved small and large vessel vascular function in patients with autoimmune rheumatic diseases. However, the authors note that given the small number of studies reviewed the evidence is not sufficient to state categorically that exercise also promotes a structural recovery of damaged arteries.

“This area [physical activity in rheumatology] is still new, so more research is needed to identify the best exercise protocols and investigate such aspects as safety and adherence,” Peçanha said. “In any event, the data in our study underlines the importance of regular exercise to prevent and treat cardiovascular disease in these patients.”

For people with rheumatic disease, as indeed for everyone else, Peçanha recommends at least 150 minutes of moderate to vigorous exercise per week. Aerobic exercise should predominate and be complemented by activities that foster strength and balance.

Rockville, Md. (April 27, 2021)--Deep heat creams widely used by athletes to soothe sore muscles may also boost performance when applied before exercise, according to new research presented virtually this week at the American Physiological Society's (APS) annual meeting at Experimental Biology 2021.

Researchers at Nanyang Technological University in Singapore studied a small group of male volunteers to determine the effects of deep heat cream on exercise endurance. Each volunteer participated in two trials--one where he applied a thin layer of a commercially available deep heat cream to the muscles of his feet, calves, thighs and buttocks--and another where he applied a placebo cream before each trial workout. The over-the-counter product contained ingredients such as methyl salicylate, menthol, glyceryl stearate, eucalyptus and turpentine oils, lanolin and water. During each trial condition, the participants exercised on a stationary bicycle at 80% maximal effort until they were too tired to continue. The research team measured the volunteers' time-to-exhaustion in both conditions and found the men were able to exercise for an average of about two minutes longer when using the deep heat cream.

"Application of deep heat [cream] may help elite athletes, recreational and/or sports enthusiasts to improve their aerobic performance," said Govindasamy Balasekaran, PhD, first author of the study. "More studies are needed to explore the benefits of application of deep heat on exercise performance for both [sexes] and analyze the physiological mechanisms behind the improvement."

Rockville, Md. (April 27, 2021)--A new study by researchers at the VA Portland Health Care System in Oregon found that augmenting traditional treatment for traumatic brain injury (TBI) with morning bright light therapy (MBLT) improved physical and mental symptoms for participants. The team will present their work virtually at the American Physiological Society's (APS) annual meeting at Experimental Biology 2021.

According to the U.S. Department of Veterans Affairs (VA), over 185,000 veterans have been diagnosed with at least one TBI. TBI is both a common and complex injury. Because of the circumstances surrounding the brain injury, TBI frequently coincides with posttraumatic stress disorder (PTSD). Cognitive and memory impairments and poor sleep quality often result from these paired conditions. Unfortunately, the current treatment methods for TBI, which focus on improving the cognitive symptoms, have inconsistent results.

Noting the reciprocal relationship between sleep disruption and cognitive function, the research team focused on addressing the sleep quality in the experimental group. Over the course of eight weeks, one group received group cognitive therapy, while the other received cognitive therapy as well as 60 minutes of MBLT within two hours of waking each day.

The MBLT group reported improvements to cognitive function, sleep, depression and neuropsychiatric trauma symptoms. The traditional therapy group did not report improvements in any of these areas.

Jonathan Elliott, PhD, a member of the research team, said that the study "demonstrates a highly feasible mechanism to improve cognitive function and the efficacy of [current treatment] ... and ultimately overall quality of life in U.S. veterans."

New research conducted in rats suggests a compound that gives some cruciferous vegetables their pungent taste could help to reverse kidney problems associated with diabetes.

It is estimated that about one-quarter of people with diabetes will eventually develop diabetic nephropathy, a gradual loss of kidney function eventually requiring dialysis. The condition is a leading cause of chronic kidney disease in the U.S. and is also associated with a high risk of heart disease. There is currently no cure.

For the new study, researchers assessed the effects of phenethyl isothiocyanate (PEITC) in rats with diabetic nephropathy. PEITC is found in several types of vegetables but is most concentrated in watercress.

"Our study provides, for the first time, evidence that PEITC might be effective as a naturally occurring agent to reverse serious kidney damage in people with diabetes," said lead study author Mohamed El-Sherbiny, PhD, a postdoctoral fellow at AlMaarefa University in Riyadh, Saudi Arabia. "Our study introduces mechanistic evidence of how PEITC might manage kidney injury associated with diabetes by targeting multiple interconnected pathways involved in diabetic nephropathy, including inflammation, glycation and oxidative status."

El-Sherbiny will present the research at the American Association for Anatomy annual meeting during the Experimental Biology (EB) 2021 meeting, held virtually April 27-30.

Previous studies have suggested sulforaphane, a related compound in cruciferous vegetables, also helps reduce diabetes-associated kidney damage. The new study bolsters the evidence that eating more vegetables containing these compounds could help people with diabetes to stave off kidney problems.

"PEITC seems to manage one of the most serious and painful diabetic complications. Luckily, PEITC is naturally present in many dietary sources, importantly watercress, broccoli, turnips and radish," said El-Sherbiny.

Since the research was conducted in animal models, further studies will be needed to confirm the findings and understand how the results could translate to new treatments or dietary recommendations for people with diabetes.

El-Sherbiny will present this research from 3:45-4 p.m. Thursday, April 29 (abstract). Contact the media team for more information or to obtain a free press pass to access the virtual meeting.

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Researchers studying mice made a serendipitous discovery that could lead to a new dry mouth treatment. More than 10% of people experience dry mouth, which can be caused by medical conditions, radiation treatment, certain medications and aging.

Abigail Boyd, a doctoral candidate at the University of South Alabama, and colleagues made the new discovery while exploring the anti-inflammatory benefits of inhibiting phosphodiesterase-4 (PDE4) enzymes in a mouse model of bacterial lung infection. After noticing that mice treated with a PDE4 inhibitor were salivating, they decided to examine whether this observation could be translated into a dry mouth therapy. They also looked at the implications of the discovery for cystic fibrosis, which causes persistent lung infections and limits the ability to breathe over time.

"Saliva, while often taken for granted, is indispensable for oral health and overall well-being," said Boyd. "New ways to treat dry mouth are needed since treatment options are currently limited."

Boyd will present the new research at the American Society for Pharmacology and Experimental Therapeutics annual meeting during the virtual Experimental Biology (EB) 2021 meeting, to be held April 27-30.

The researchers were working with several distinct PDE4 inhibitors including roflumilast, a PDE4 inhibitor that is used clinically for the treatment of chronic obstructive pulmonary disease. Their analysis revealed that PDE4 inhibitors increase salivation by inhibiting PDE4 in the salivary glands and in the autonomic nervous system, which regulates involuntary body processes such as breathing.

"Although the causes of salivary gland dysfunction are varied, there is often an inflammatory component," said Boyd. "Thus, in addition to stimulating salivary secretions, PDE4 inhibition may also exert therapeutic benefits by alleviating the inflammatory responses that cause salivary gland dysfunction."

The researchers also studied the effects of PDE4 inhibition in a mouse model of cystic fibrosis. Cystic fibrosis occurs when the body doesn't make the cystic fibrosis transmembrane conductance regulator (CFTR) protein or doesn't make it correctly. This protein helps maintain the balance of salt and water on many surfaces in the body, including the lungs. In the new work, the researchers showed, for the first time that PDE4 controls CFTR-dependent salivation in mice. This finding suggests that PDE4 could have therapeutic potential for helping alleviate decreased CFTR function in patients with cystic fibrosis.

The researchers are continuing to study the mechanisms at work in PDE4 inhibition and plan to find out if their findings translate to people.

Abigail Boyd will present the findings in poster R154 (abstract). Contact the media team for more information or to obtain a free press pass to access the meeting.

Image available.