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NEW YORK - October 15, 2020 - The MITHRAS randomized clinical trial found that interventional closure of an iatrogenic atrial septal defect (iASD) driven by transcatheter mitral valve repair (TMVR) was not superior to conservative medical treatment with regard to the primary endpoint of change in six-minute walking distance.

Findings were reported today at TCT Connect, the 32nd annual scientific symposium of the Cardiovascular Research Foundation (CRF). TCT is the world's premier educational meeting specializing in interventional cardiovascular medicine. The study was also published simultaneously in Circulation.

TMVR requires transseptal access to the left atrium, which creates an iASD that remains with detectable shunting across the intra-atrial septum. While the induction of an iASD has been linked to improved hemodynamics in specific heart failure populations and is currently being investigated in large-scale clinical trials in patients with heart failure, the presence of a persistent iASD is also associated with increased long-term mortality and morbidity following TMVR.

The MITHRAS trial investigated whether the closure of a TMVR induced iASD is superior to medical therapy alone. In this prospective, randomized, single-center trial, patients with a persistent iASD one month following TMVR and relevant left-to-right shunting (Qp:Qs ?1.3) were randomly assigned in a 1:1 ratio to standard medical therapy alone or closure of the iASD using the Occlutech ASD occluder. The primary endpoint was change in 6-minute walk distance five months after iASD occlusion. Secondary endpoints included all-cause mortality and rate of heart failure hospitalization at one year.

Between January 2016 and October 2019, a total of 80 patients were enrolled. All patients underwent TMVR with 95% using the MitraClip device one month prior to enrollment and were diagnosed with an iASD with relevant left-to-right shunting on transesophageal echocardiography. Overall, 40 patients were randomized into the iASD closure group and 40 patients into the medical therapy only group. There were no differences observed in change in the primary endpoint of six-minute walking distance or any of the prespecified secondary endpoints at five months between groups.

"Interventional closure of iASD one-month post transcatheter mitral valve repair was not superior to conservative treatment with regard to the primary endpoint six-minute walking distance," said Philipp Lurz, MD, PhD, Deputy Head of the Cardiology Department at Heart Center Leipzig at the University of Leipzig, Germany. "The results are corroborated by no difference in secondary endpoints such as heart failure symptoms or hospitalization and survival. The presence of an iASD is associated with a higher rate of HF hospitalization irrespective of its management when compared to patients without relevant iASD following TMVR. The presence of an iASD following transcatheter mitral valve interventions might be a prognostically relevant surrogate, but not necessarily causative for inferior outcomes."

LA JOLLA, Calif. (October 15, 2020) -- Cannabidiol (CBD) is a chemical found in hemp or marijuana plants that does not make users high. Despite CBD only being approved by the US Food and Drug Administration (FDA) to treat rare forms of childhood epilepsy, CBD has been widely marketed as a cure-all under the auspices of wellness. These claims have coincided with an explosion in CBD's popularity raising the troubling question: Are patients using CBD to treat medical conditions that could otherwise be improved or cured by established treatments with verifiable efficacy?

A new study lead by the Qualcomm Institute's Center for Data Driven Health at the University of California San Diego, published in JAMA Network Open, reviewed CBD user testimonials to discover why they take CBD, finding the vast majority used CBD to treat diagnosable medical conditions, including for psychiatric, orthopedic, and sleep conditions while fewer took CBD for wellness.

Mining Public Testimonials to Understand Why Patients Use CBD

"The reasons consumers take CBD had not been previously studied because experts lacked access data where large groups of users discussed in detail why they take CBD," said Dr. Eric Leas, Co-Founder of the Center for Data Driven Health, Assistant Professor in the Herbert Wertheim School of Public Health and Longevity Science at UC San Diego, and lead author.

To fill this gap the team turned to Reddit, a social media website with 330 million active users. Reddit is organized into communities focused on specific topics, many of which deal exclusively with health. The team monitored all r/CBD (http://www.reddit.com/r/CBD/) posts, where users can find anything and everything CBD related, from its inception in January 2014 through February 2019.

A random sample of posts was drawn and analyzed by the team who labeled them according to if the poster testified to using CBD to treat a diagnosable medical condition or using CBD for non-specific wellness benefits. "On r/CBD users tell us in their own words why they take CBD," added Dr. John W. Ayers, also with the Center for Data Driven Health and Vice Chief of Innovation in the Division of Infectious Disease and Global Public Health who co-authored the study. "

Most CBD Users Take CBD to Treat Medical Conditions

90 percent of testimonials on r/CBD cited using CBD to treat diagnosable medical conditions. For example, many testimonials recounted experiences such as, "after using CBD for 2 months, my autism symptoms have improved. My family has noticed great improvements and I have finally been able to attend important social events."

Through a process of labeling the posts, the team grouped this subset of testimonials into 11 categories corresponding to medical subspecialties. Psychiatric conditions (e.g., "autism" or "depression") were the most frequently cited sub-category, mentioned in 64 percent of testimonials, followed by orthopedic (26 percent), sleep (15 percent), and neurological (7 percent) conditions. There were also testimonials that claimed CBD treated addiction, cardiological, dermatological, gastroenterological, ophthalmological, oral health, and sexual health conditions, ranging from 1 to 4 percent of all posts [as detailed in the accompanying study materials].

"The public appears to believe CBD is medicine," added Dr. Davey Smith, Chief of Infectious Diseases and Global Public Health and study coauthor. "Who would have predicted that the public might ever think CBD is a cardiology medication?"

By contrast, just 30 percent of testimonies cited using CBD for wellness benefits, the vast majority citing mental wellness, e.g., "quieting my mind", and about 1 percent citing any physical wellness benefit, e.g., "exercise performance."

"CBD retailers attempt to evade FDA regulation by framing their product as a wellness aid, rather than a therapeutic," said Dr. Alicia Nobles, with the Center for Data Driven Health and Assistant Professor in the Division of Infectious Disease and Global Public Health. "But when users explain why they take CBD in absence of any prompts they will commonly cite they are using it for medicinal purposes like to treat acne."

The Need for Enhanced Regulation of the CBD Marketplace

"At this time there are no known medical uses for over-the-counter CBD," said Dr. Leas. "CBD is this generation's snake oil as millions believing to have discovered a new medical breakthrough are actually taking a product without evidence of a benefit."

"The obvious harm is that some patients might forgo seeing a physician or taking medications with known, tested and approved therapeutic benefits in favor of CBD and thereby become sicker or succumb to their illness," added Mr. Rory Todd, study co-author and research associate in the Center for Data Driven Health.

While many think that using CBD poses few risks to consumers trying CBD out, the team notes that taking CBD can harm patients in other ways that warrant cautious use. "There are several documented cases of CBD products leading to mass poisons, because unlike FDA approved medications there are no uniform safety standards governing the manufacture or distribution of CBD," said Mr. Erik Hendrickson, study co-author and research associate with the Center for Data Driven Health. "CBD can also interact with patients' prescribed medications, including resulting in rare but dangerous side effects such as liver damage and male reproductive toxicity," added Dr. Smith who is also a practicing physician.

The lack of regulation governing the CBD marketplace may drive misperceptions of CBD the team notes. "The public isn't spontaneously coming to the conclusion that CBD is medicine. Instead this is a natural response to the largely unchecked marketing claims of CBD retailers," added Dr. Ayers. "A lack of regulation puts the onus on physicians who must raise concerns about CBD with patients one-on-one instead of focussing on evidence-based treatments. For instance, since the COVID-19 outbreak claims that CBD prevents or treats COVID-19 are now commonplace."

"Now is the time to act," concluded Dr. Leas. "Government regulators must step up to the plate and give CBD the same level of scrutiny as other proven medications. Moreover, anyone considering taking CBD should instead consult a physician to identify a proven medication."

Findings by Monash Biomedicine Discovery Institute (BDI) researchers have pointed to a new combination of treatments that may help breast cancer patients with certain gene mutations.

The study, published in Molecular Cell and led by Dr Antonella Papa, identified potential new treatments for patients who lacked PTEN, a gene that suppresses tumours, and/or have mutations in the cancer gene PI3K.

The researchers demonstrated using animal models, organoids and proteomic screening, that the loss of PTEN synergises with mutant PI3K gene in forming tumours in mammary glands. They then found that inhibiting the protein AKT suppressed the growth of PTEN and PI3K mutant mammary organoids.

In a surprising finding, the team also discovered that loss of PTEN function increased levels of the glucocorticoid receptor (GR) and made the tumour cells more prone to death.

The researchers found that combining a treatment called dexamethasone (an anti-inflammatory medication currently available), which activates GR, with an AKT inhibitor, better suppressed growth of PTEN/PI3K mutant cancer cells than treatment with a single compound.

The scientists are now testing the efficacy of their combination therapy in pre-clinical animal models with a view to future testing in clinical trials for breast cancer treatment.

PTEN gives instructions for making an enzyme found in most tissues in the body and functions by stopping cells from growing and dividing too rapidly or too uncontrollably. In contrast, PI3K is an enzyme that promotes cell growth and sustains proliferation in cancer when mutated.

Mutations in either PTEN or PI3K alone occur in almost 50 per cent of breast cancer patients. In addition, 10 per cent of breast cancer patients have combined genetic alterations in these two genes.

"These patients could benefit from our findings," Dr Papa said.

"The finding that GR sensitises PTEN mutant cells to death is absolutely new; it was the opposite of what you would expect," Dr Papa said.

Dr Papa said while the research had concentrated on breast cancer, the two genes could cause tumours to form in many of the body's cells.

Researchers at Linköping University, Sweden, have developed a unique method to predict influenza epidemics by combining several sources of data. The forecasts can be used, for example, when planning healthcare provision, such that resources can be redistributed in the best possible manner and give everyone the best possible care during an epidemic.

"Our method predicts influenza epidemics by using data from real episodes of care and consultations about influenza symptoms with the Swedish Healthcare Direct (1177). The various sources of data are used to forecast different phases of an epidemic, which makes our study unique", says Armin Spreco, doctor of medicine at the Department of Health, Medicine and Caring Sciences at Linköping University, and specialist in epidemiology and statistics at Region Östergötland. He is principal author of the article in which the study is presented.

The study has been published in Emerging Infectious Diseases, and focusses on upper respiratory tract infections, comparing three large medical care regions: Stockholm, West Gothia, and Scania, for the ten-year-period from January 2008 to February 2019. The method developed by the researchers gave accurate forecasts and satisfactory results for all influenza seasons, under stable conditions.

It would have been essentially impossible to predict, for example, the peak of an influenza epidemic, if the researchers had looked only at admissions or visits to primary care. Such a forecast has now been made possible by including extra sources of data that precede the peak by several weeks. Calls made by county residents to the Swedish Healthcare Direct, for example, have proved to be useful to predict when a peak in influenza infections will occur.

Another conclusion of the study is that care should be taken when using forecasting in periods of social unrest. When the population behaves or moves around in unusual patterns, infection can spread in unexpected directions, which can have a negative impact on the forecasts.

The research group started its research on forecasting for different types of virus epidemics and pandemics as early as 2005, during the outbreak of avian influenza. Swedish legislation specifies that it must be able to reconfigure the public sphere, such as, for example, the medical care system, for emergency tasks. The regions have a responsibility in this respect.

"During the second decade of the new millennium, we started to prepare the information systems used in our medical care region, such that routine data can be used for this type of analysis. We have been able to use our experiences from working with skilled statisticians and technical experts at Region Östergötland and in this way ensure that other databases in Sweden have prepared for the analyses needed for emergency purposes", says Toomas Timpka, professor in the Department of Health, Medicine and Caring Sciences at Linköping University, and consulting physician in Region Östergötland. He has led the study now being presented.

This is one of the reasons that Armin Spreco has been able to spend the past ten years analysing data from these databases. The data harvesting does not disturb either the care systems or the healthcare personnel, since it takes place in the administrative part of the databases, and the data extracted are completely anonymous, which is one of the strengths of the study.

In addition to being useful during influenza epidemics, the method can be extremely useful during the ongoing corona pandemic, which is a typical example of social unrest. The method has been used during the first wave of the pandemic in several Swedish regions and will be used in the event of a second wave.

A research team led by Professor Hongzhe SUN, Norman & Cecilia Yip Professor in Bioinorganic Chemistry, Department of Chemistry, Faculty of Science, and Professor Kwok Yung YUEN, Henry Fok Professor in Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine of the University of Hong Kong (HKU), has discovered a novel antiviral strategy for treatment of COVID-19.

They discovered that a class of metallodrugs currently used in the treatment of other infectious diseases is showing efficacy to potently suppress SARS-CoV-2 replication and relieve viral-associated symptoms in an animal model.

The findings provide a new and readily available therapeutic option with high clinical potential for infection with SARS-CoV-2. This ground-breaking work has been published online in a top-class scientific journal Nature Microbiology. A related patent has been filed in the US.

Background

SARS-CoV-2 is an emerging coronavirus that has caused over 30 million laboratory-confirmed cases and more than 1 million deaths globally of COVID-19 since December 2019. As the process of developing an effective vaccine is still ongoing, another approach for prevention and treatment of the disease is to identify anti-COVID-19 agents from existing virus-specific antiviral drugs to repurpose their uses to target the new virus. Remdesivir, a broad-spectrum antiviral drug, has been reported to show efficacy towards SARS-CoV-2. However, global shortage of the drug, its relatively high price and lack of significant clinical benefits in severe cases, are factors that have limited its wider applications. Clinical trials on a series of antiviral agents are still ongoing which have yet to demonstrate therapeutic efficacies. Therefore, greater efforts are needed to extend the evaluation to cover a wider spectrum of clinically approved drugs, which hopefully could open the way to alternative treatment strategies against the disease through some readily available channels.

Study method and findings

Generally, metal compounds are used as anti-microbial agents; their antiviral activities have rarely been explored. After screening a series of metallodrugs and related compounds, the research team identified ranitidine bismuth citrate (RBC), a commonly used anti-ulcer drug which contains the metal Bismuth for treatment of Helicobacter pylori-associated infection, as a potent anti-SARS-CoV-2 agent, both in vitro and in vivo.

RBC targets the vital non-structural protein 13 (Nsp13), a viral helicase essential for SARS-CoV-2 to replicate, by displacing the crucial zinc(II) ions in the zinc-binding with Bismuth-ions, to potently suppress the activity of the helicase.

RBC has been demonstrated to greatly reduce viral loads by over 1,000-folds in SARS-CoV-2-infected cells. In particular, in a golden Syrian hamster model, RBC suppresses SARS-CoV-2 replications to reduce viral loads by ~100 folds in both the upper and lower respiratory tracts, and mitigates virus-associated pneumonia. RBC remarkably diminishes the level of prognostic markers and other major pro-inflammatory cytokines and chemokines in severe COVID-19 cases of infected hamsters, compared to the Remdesivir-treated group and control group.

RBC exhibits a low cytotoxicity with a high selectivity index at 975 (the larger the number the safer the drug), as compared to Remdesivir which has a low selectivity index at 129. The finding indicates a wide window between the drug's cytotoxicity and antiviral activity, which allows a great flexibility in adjusting its dosages for treatment.

The team investigated the mechanisms of RBC on SARS-CoV-2 and revealed for the first time the vital Nsp13 helicase as a druggable target by RBC. It irreversibly kicks out the crucial zinc(II) ions in the zinc-binding domain to change it to bismuth-bound via a distinct metal displacement route. RBC and its Bi(III) compounds dysfuntionalised the Nsp13 helicase and potently inhibited both the ATPase (IC50=0.69 μM) and DNA-unwinding (IC50=0.70 μM) activities of this enzyme.

The research findings highlight viral helicases as a druggable target, and the high clinical potential of bismuth(III) drugs and other metallodrugs for treatment of SARS-CoV-2 infections. Hopefully, following this important breakthrough, more antiviral agents from readily available clinically approved drugs could be identified for potential treatment of COVID-19 infections. They can be in the form of combination regimens (cocktails) with drugs that exhibit anti-SARS-CoV-2 activities including RBC, dexamethasone and interferon-β1b.

TAMPA, Fla. -- The development of cancer is a highly complicated process, involving multiple genes and signaling pathways that become upregulated or downregulated throughout different stages of tumor growth and spread. Two of the most commonly altered genes in cancer are p53 and AKT. In a new article published in the journal Nature Communications, Moffitt Cancer Center researchers describe how the protein TAp63 controls levels of RNA molecules, which subsequently connects the activities of p53 and AKT to promote disease progression.

P53 is one of the most highly mutated genes in cancer. Mutations in p53 can impact a downstream protein named TAp63 and block its anti-cancer activity, resulting in tumor development. Likewise, AKT is an important mediator of cancer progression that controls proliferation, migration, invasion and survival.

Moffitt researchers previously showed that TAp63 functions as a tumor suppressor gene and that loss of its activity can lead to tumor development and spread. In follow-up studies, they wanted to determine the mechanism of how loss of TAp63 activity can lead to cancer in an effort to hijack these pathways to overcome p53 mutation in a therapeutic setting. Their investigations led them to make a connection between TAp63 and a type of RNA molecule called long noncoding RNA (lncRNA).

RNA is considered an intermediary molecule; DNA codes for RNA, which is turn codes for protein. However, scientists are now aware that some RNA molecules do not code for proteins, rather they are noncoding RNA molecules with a variety of functions that control normal physiological processes, and altered expression or activity of these lncRNAs can lead to the development and progression of disease. The Flores Lab at Moffitt Cancer Center, in collaboration with colleagues at MD Anderson Cancer Center, Baylor College of Medicine, University of Houston and University of Nottingham, performed a variety of laboratory and mouse studies to show that TAp63 regulates the expression of lncRNA.

Elsa Flores, Ph.D., chair of the Department of Molecular Oncology and leader of the Cancer Biology and Evolution Program at Moffitt, and colleagues wanted to determine the relevance and function of these lncRNAs. They demonstrated that the lncRNAs stimulated cell migration and invasion, and high expression of two of the lncRNAs named TROLL-2 and TROLL-3 was associated with breast cancer progression. Importantly, downregulation of TROLL-2 and TROLL-3 inhibited the formation of several tumor types in mice including breast, melanoma and lung cancer. Additionally, the researchers found that TROLL-2 and TROLL-3 are highly expressed in a variety of metastatic human cancers, suggesting that these lncRNAs may be potential prognostic markers for tumor progression and targets for anti-cancer therapies. The researchers also demonstrated that the tumor-promoting properties of the lncRNAs are dependent on the proteins WDR26 and NOLC1, which allow for shuttling in and out of the cell nucleus and regulation of cellular processes critical for cell survival. In cancer cells that lack TAp63 activity, TROLL-2 and TROLL-3 bind to WDR26 in the nucleus of the cell, preventing its interaction with NOLC1 and causing WDR26 to be shuttled out of the nucleus into the cytoplasm. In the cytoplasm, WDR26 stimulates the AKT signaling pathway, leading to increased cell migration and invasion and the promotion of tumor development.

The discovery of this complicated interplay between multiple proteins and lncRNAs highlights several key points throughout the signaling pathway that may be viable prognostic markers for tumor progression and therapeutic targets for cancer, including TROLL-2, TROLL-3, WDR26 or the interaction between these molecules and AKT.

"Our findings identify a crucial mechanism for the activation of the AKT pathway through TAp63-regulated lncRNAs (TROLLs) and pave the way for more effective diagnostic tools for cancer progression and therapies against metastatic cancers with alterations in TP53 and hyperactivation of the PI3K/AKT pathway," Flores said.

New parents who receive attentive, supportive nursing care during labor and immediately after childbirth are more likely to exclusively breastfeed their newborn when leaving the hospital, finds a study published in MCN: The American Journal of Maternal/Child Nursing.

"Nurses make substantial, often unrecognized, contributions to public health during pregnancy, and during and following birth. Our research provides a great example of how supportive nursing care can have longer term effects on maternal and infant health," said study author Audrey Lyndon, PhD, RN, FAAN, professor of nursing and assistant dean for clinical research at NYU Rory Meyers College of Nursing.

Breast milk is a complete nutritional source for babies and helps strengthen their immune systems. Because of these benefits, exclusive breastfeeding during hospitalization--where breast milk is the only source of nutrition for newborns--is considered a national quality indicator of maternity care in hospitals.

"Breastfeeding is proven to have a range of health benefits for both the mother and child and should be supported by health systems," said Lyndon.

Nurses play a central role supporting families with their feeding goals after childbirth, which often includes breastfeeding, although some parents are not able to breastfeed or choose not to. To assist with breastfeeding, nurses provide education and encouragement, promote skin-to-skin contact immediately after birth, make referrals to lactation consultants as needed, and keep healthy birth parents and babies together.

Having adequate nursing staff is critical for nurses to be able to fully perform these essential aspects of care--likewise, too few nurses may hurt their ability to give each patient enough attention, or provide the care in a timely fashion, a concept researchers refer to as "missed nursing care." The Association of Women's Health, Obstetric and Neonatal Nurses' (AWHONN) guidelines on nurse staffing levels for maternity units call for one nurse to one birthing person during many parts of labor, two nurses at birth, one nurse for each mother-newborn pair during the first few hours after birth, and one nurse for every three pairs of mothers and babies following birth.

In their study of nursing care and breastfeeding rates, researchers from Mercy Hospital St. Louis, NYU Rory Meyers College of Nursing, the University of California, San Francisco, and Trinity Health surveyed 512 labor nurses from 36 hospitals in three states. The nurses answered a series of questions about their ability to complete essential aspects of nursing care during labor and birth and how often care was missed by nurses on their units. The researchers also evaluated each hospital's rate of exclusive breastfeeding, measured as infants who are exclusively fed breast milk during their birth hospitalization. The rate excludes infants likely to have barriers to breastfeeding, including those who are born preterm, admitted to a neonatal ICU, or have a hospital stay of more than 120 days.

The researchers found that hospitals with higher rates of exclusive breastfeeding had less missed nursing care, with nurses more consistently providing important care such as assisting with breastfeeding within an hour of birth and facilitating skin-to-skin contact. Exclusive breastfeeding was also associated with hospitals adhering to AWHONN's nurse staffing guidelines during labor and for immediate postpartum care.

The nurses surveyed reported that some facets of nursing care during childbirth were occasionally delayed, unfinished, or completely missed. They attributed these lapses or delays to communication problems and inadequate staffing.

"We suspect that multiple structural factors affect nurses' capacity to provide sufficient and appropriate support for successful exclusive breastfeeding. Hospital and maternity unit culture, policies, communication, availability of resources, including adequate nurse staffing, and promotion of effective practices for initiation and sustainment of human milk feeding are all important," said Kathleen Rice Simpson, PhD, RNC, CNS-BC, FAAN, a perinatal clinical nurse specialist in St. Louis, MO, and the study's lead author.

The researchers recommend that maternity units focus on improving nurse staffing in order to avoid missed nursing care. Beyond AWHONN's guidelines, they cite research demonstrating that having one nurse continuously at a new parent's bedside during the two hours immediately after delivery can support safe skin-to-skin positioning and breastfeeding.

DALLAS - Oct.15, 2020 - When a child has a rare blood disorder, clinicians can struggle to find the best diagnostic and treatment methods. New research led by UT Southwestern shows the effectiveness of a treatment for aplastic anemia and reveals the range of diagnosis and treatment options used by hospitals around the country for a related disease - myelodysplastic syndrome (MDS).

Two studies, published recently in Pediatric Blood & Cancer and conducted as part of the North American Pediatric Aplastic Anemia Consortium (NAPAAC), show the benefit of collaboration in studying childhood blood disorders.

"At UT Southwestern, we're trying to push forward the diagnostic approach and treatment options for these rare blood disorders," says Kathryn E. Dickerson, M.D., M.S., an assistant professor of pediatric hematology-oncology at UTSW, pediatric hematologist and oncologist at Children's Health and a lead author of the two papers. "But with these kinds of rare diseases, you really have to be willing to come together with institutions around the country and work as a group to make progress."

Aplastic anemia occurs when the body's immune system attacks the stem cells in the bone marrow that usually produce blood cells. This results in the bone marrow making too few red blood cells that carry oxygen through the body, white blood cells that help fight infections, and platelets that aid in blood clotting. Children with aplastic anemia are often tired, pale, unable to tolerate their normal activities, and get frequent infections and bruises. Only two treatments have been shown to work: a bone marrow transplant or immune system suppression therapy.

Typically, bone marrow transplants are only carried out in children with aplastic anemia if they have a sibling who is a match or if they've failed immune suppression therapies and doctors can find an unrelated donor. That's because receiving bone marrow cells from an unrelated donor is more likely to lead to complications. But in recent years, approaches to minimize these complications have improved. So Dickerson and her NAPAAC collaborators wanted to know whether bone marrow transplants from unrelated donors is now a more viable treatment option - even for children who haven't tried immune suppression yet.

For the study, Dickerson and her collaborators randomized 21 children under the age of 26 with newly diagnosed severe aplastic anemia to receive either a bone marrow transplant from an unrelated donor or the typical standard-of-care immune-suppressive therapy. The patients, who were located at nine different hospitals around the country, were then followed for an average of 18 months.

Ten of the 12 patients randomized to receive a bone marrow transplant were able to find a matched, unrelated donor within eight weeks. Four months after treatment, there was no statistical difference in the number of patients from each treatment group who had recovered from aplastic anemia; seven of 11 patients treated with immune suppression had healthy levels of blood cells and six of the 10 patients who had received transplants had fully recovered. On average, patients treated with immune suppression recovered in 82.5 days and patients who received a transplant recovered in 62 days.

"What we showed in this pilot study is that we're certainly not putting patients at any increased harm by proceeding to a transplant instead of immune suppression," says Dickerson, also clinical program director of bone marrow failure and leukemia predisposition at Children's Health. "That finding lets us now start planning a larger, randomized phase 3 trial to try to show that a transplant would be a superior first-line treatment option to immune suppression."

In a second paper, Dickerson and another group of NAPAAC collaborators surveyed North American medical centers about their approaches to diagnosing, treating, and managing MDS.

In MDS, similar to aplastic anemia, the body has a shortage of mature blood cells. However, there is no shortage of bone marrow stem cells; instead, these stem cells fail to mature normally. In the past, MDS was sometimes called "pre-leukemia" since children with MDS are more likely to go on to develop leukemia.

Currently, there's no standardized approach to how clinicians in North America diagnose and treat MDS, Dickerson says. Patients often go undiagnosed for months as their doctors struggle to pin down exactly what they have. To be treated, patients typically must visit a major medical center with pediatric cancer specialists and specially trained pathologists.

The survey carried out by Dickerson and her collaborators was a step toward developing widespread standards on MDS to help guide doctors in diagnosing the rare disease and assist large medical centers to collaborate on similar guidelines.

The team sent a survey to all 35 NAPAAC institutions known to treat MDS; 28 completed the survey. While diagnostic criteria were fairly standard among institutions, the survey revealed a wide range of treatment standards used to manage MDS.

"We have a goal of a national patient registry and collaborative studies where we can look at treatment for MDS in a standardized way," says Dickerson. "But right now, our survey showed that people are really doing different one-off combinations of things without any infrastructure."

The survey results, Dickerson hopes, will help the NAPAAC MDS working group move toward its goal of clinical guidelines to treat patients with MDS more quickly and effectively.

Researchers from North Carolina State University and the University of North Carolina have developed a technique that uses ultrasound to provide non-invasive assessments of pulmonary fibrosis and pulmonary edema. The technique has been shown to both quantify lung scarring and detect lung fluid in rats. A study on pulmonary edema in humans is under way.

The new ultrasound technique is significant because it would allow healthcare providers to determine how effective medical interventions are at reducing lung scarring (pulmonary fibrosis) or fluid in the lungs (pulmonary edema).

"Assessing the extent of fibrosis in the lung currently requires computerized tomography (CT) scans, and sophisticated pulmonary function tests," says Marie Muller, co-senior author of the study and an associate professor of mechanical and aerospace engineering at NC State. "Both aspects of the assessment present challenges.

"CT scans use radiation, so you want to limit their use. They are also expensive, and require a trained radiologist. For all of these reasons, they are not suitable for frequent monitoring. Ultrasound is a good solution because it does not pose a cancer risk, it's portable, it's relatively inexpensive, and our technique effectively gives users a quantitative assessment of the fibrosis."

"One of the pulmonary function tests is called a DLCO test," says Dr. Tom Egan, co-senior author on the study and a professor of surgery at UNC. "The DLCO test measures the amount of gas exchange surface in the lung, and it requires specialized equipment that you won't find outside of hospitals and some large pulmonary clinics. The specialized technology means that this testing can be expensive - particularly now, due to heightened decontamination procedures associated with the COVID-19 pandemic. If this new ultrasound technology can reduce our reliance on DLCO tests, that would likely reduce costs for patients."

"Being able to monitor pulmonary edema in patients with heart failure would also be very useful," Muller says. "This is often done by assessing fluctuations in a patient's body weight in order to estimate how much fluid has collected in the patient's lungs - which is not as specific as we'd like it to be.

"We've recently received a grant from NIH to investigate if our novel ultrasound technique can quantify pulmonary edema in heart failure patients."

"Pulmonary fibrosis is a major public health problem," Egan says. "The most common form of pulmonary fibrosis affects 200,000 Americans, with 50,000 new cases diagnosed each year.

"Pulmonary edema is another common condition. It can be caused by a number of health conditions, but affects more than 75% of patients with heart failure."

The new technique makes use of the multiple transducer elements on conventional ultrasound probes to direct multiple ultrasound waves at lung tissue. As the ultrasound waves bounce back to the transducer, the data is collected and fed into a computational model that determines the density of healthy alveoli in the lung. This can be used to provide a quantitative assessment of the amount of fibrosis in the lung tissue. Researchers are testing whether it can also quantify the amount of water in the lung.

The current paper demonstrates the efficacy of the technique in assessing pulmonary fibrosis and edema in rats, and distinguishing between the two lung abnormalities.

"The automated quantitative assessment would allow the technology to be used by personnel with minimal training, and would allow healthcare providers to compare data across time," Muller says. "For example, caregivers would be able to tell if a patient's edema is getting better or worse."

"Because this is ultrasound, people have a hard time grasping this concept: there are no images; the output is a number," Egan says.

"The quantitative element of this work is particularly important, given that previous approaches to assessing lung health with ultrasound could really only provide qualitative assessments," Muller says. "They could say that lung health was bad or good, but couldn't give you measurable gradients between the two."

The researchers have received funding for a study focused on using the technique to assess pulmonary edema in human patients, and are applying for funding to pursue the work in patients with pulmonary fibrosis.

"We've seen new treatments come online in recent years for pulmonary fibrosis patients," Egan says. "It would be valuable to determine how effective they are, and what factors may contribute to their effectiveness."

In an age when many people get their news from social media, ensuring health information is communicated accurately and understood clearly is critical, especially during infectious disease outbreaks.

When the San Diego region experienced a Hepatitis A outbreak in 2017 that spread rapidly through its homeless population, eventually sickening nearly 600 people and claiming 20 lives, it fell to public health officials to contain it. It took almost two years before the outbreak was officially declared over, and stories about workers sanitizing public transit surfaces, educating the homeless about hygiene and vaccinating them, and installing hand-washing stations made national news.

On Twitter, while public health agencies issued updates on the city's efforts to stem the outbreak and make downtown safe, people were tweeting about how they were scared to go downtown, and expressing doubts about the protection from vaccinations.

This disconnect between the public and government agencies, and how information is communicated on social media during an outbreak was the focus of a study by San Diego State University researchers. They found key lessons that can be applied to the COVID-19 pandemic, which could stem the tide of misinformation currently happening.

"The country and world have been rife with misinformation during the pandemic. What to do, what not to do, when should you wear a mask, what medication to take, is socially distancing necessary, will a vaccine be safe," said Eyal Oren, an infectious disease epidemiologist with the SDSU School of Public Health and one of the lead authors.

The 2017 experience, he said, shows how public health officials can counter misinformation and boost vaccination rates among those at risk.

Tweet more often

Published in October in the American Journal of Public Health, the study was led by public health and communication researchers and students, and found that while government agencies had a social media presence, they could be more active and meet the public where they're at on Twitter, Instagram and other channels.

Secondly, inconsistent information between government agencies and the public can emerge during an outbreak. Thirdly, misinformation about vaccines can also start to spread on social media during outbreaks.

"Confusion from these inconsistencies can be reduced with greater dialogue between government agencies and members of the public," said Lourdes Martinez, associate professor with the SDSU School of Communication and the other lead author of the study. "Agencies could also craft responses that empower and reassure concerned communities about vaccine safety."

Her expertise is in how people communicate health related information, so Martinez collaborated with Oren to look at how people communicated during the Hepatitis A outbreak.The study predates the pandemic, and they found both similarities and differences.

At that time, there was a vaccine available for Hepatitis A and it was deployed quickly among eligible individuals. But COVID-19 is caused by the novel coronavirus for which a vaccine is still under development. The scale of the pandemic is colossal and worldwide, while the Hepatitis A outbreak was limited to the city. But both are serious diseases with profound impacts on people.

Address the confusion

"We came across the issue of vaccine shortage during the Hepatitis A outbreak which was in alignment with what public health agencies said," Martinez said. "But we also came across tweets that said "I just got vaccinated but I'm still scared to go downtown" which suggests they had doubts about its effectiveness."

While officials were caught unaware in 2017 by the outbreak and the initial response time was slow, the city ramped up comprehensive efforts to target sanitation, containment and vaccination. Yet, months later, people were still tweeting that the city had not done enough.

To analyze some 750 tweets during the fall of 2017 when the outbreak was at its peak, the researchers used a social media analytics research tool (SMART) developed by the SDSU Center for Human Dynamics in the Mobile Age, headed by geographer Ming-Hsiang Tsou.

Oren and Martinez are now analyzing tweets related to COVID-19 and finding many parallels between the two outbreaks in terms of misinformation. They suggest proactive measures could help reverse the rampant misinformation currently circulating.

"We continue to find a disconnect which is now compounded by contradictory statements, partly because information is evolving with COVID-19 and because agencies like the CDC (U.S. Centers for Disease Control and Prevention) have backtracked on earlier statements such as not needing masks," Oren said. "So people have decided to use their own discretion on what to do."

Use celebrities to spread awareness

To better engage the public on social media, they recommend seeking some star power to share vital information. To a 20-year old, Oren said, a rock star or an athlete like LeBron James will "have many more followers and hold more sway" than someone in a lab coat.

Aside from this, if social media companies such as Facebook and Twitter actively scrutinized posts for misinformation and took down false information, that would make a big difference.

"If the companies were vigilant and government agencies communicate the way they should, we would be in a completely different place right now," Oren said. "But it's not too late. Even if we started today, we could still improve our situation and people might change their behaviors in response to trusted evidence-based information, which would help bring the spread of this coronavirus down to manageable levels."

NEW YORK - October 14, 2020 - New data from PROSPECT ABSORB, a pilot randomized trial of percutaneous coronary intervention (PCI) of non-flow-limiting vulnerable plaques in native coronary arteries, found that PCI was safe, substantially enlarged follow-up lumen areas, and was associated with favorable long-term clinical outcomes.

Findings were reported today at TCT Connect, the 32nd annual scientific symposium of the Cardiovascular Research Foundation (CRF). TCT is the world's premier educational meeting specializing in interventional cardiovascular medicine. The study was also published simultaneously in the Journal of the American College of Cardiology.

Acute coronary syndromes (ACS) commonly arise from plaque rupture and thrombosis of coronary artery lesions that angiographically appear mild but pathologically contain large plaque burden (PB) with an organized lipid-rich necrotic core that is separated from the lumen by a thin fibrous cap. Known as vulnerable plaques, these thin-cap fibroatheromas place patients at risk for future adverse events, including acute myocardial infarction (MI) and cardiac death. Vulnerable plaques may be identified by several noninvasive and invasive imaging techniques.

PROSPECT ABSORB was an investigator-sponsored, multicenter, single-blinded, active-treatment-controlled randomized trial that was embedded into the PROSPECT II natural history study. Between June 10, 2014 and December 20, 2017, 902 patients at 16 sites were enrolled in PROSPECT II.

Three-vessel imaging was performed with a combination intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) catheter after successful PCI of all flow-limiting coronary lesions in 898 patients presenting with MI. Among these, 182 patients at 15 centers with an angiographically non-obstructive stenosis not intended for PCI but with IVUS plaque burden ?65% were randomized to treatment of the lesion with a bioresorbable vascular scaffold (BVS) plus guideline-directed medical therapy (GDMT) (n=93) vs. GDMT alone (n=89).

The primary effectiveness endpoint was the IVUS-derived minimum lumen area (MLA) at protocol-driven 25-month follow-up. The primary (non-powered) safety endpoint was target lesion failure (TLF; composite of cardiac death, target vessel-related MI or clinically driven target lesion revascularization) at 24 months. Angiographic follow-up at 25 months was completed in 167 patients (91.8%), and median clinical follow-up was 4.1 years.

The follow-up MLA in BVS-treated lesions was 6.9±2.6 mm2 compared with 3.0±1.0 mm2 in GDMT alone-treated lesions (least square means difference 3.9 mm2, 95% CI 3.3-4.5, P

"The results from PROSPECT ABSORB indicate that PCI of vulnerable plaques may safely enlarge the lumen and change the structure of the lesion, theoretically reducing its propensity for thrombosis and progression," said Gregg W. Stone, MD. Dr. Stone is Director of Academic Affairs, Mount Sinai Heart Health System and Professor of Medicine at The Zena and Michael A. Wiener Cardiovascular Institute of the Icahn School of Medicine at Mount Sinai. Dr. Stone and Dr. David Erlinge served as study co-chairs.

"The favorable randomized lesion-related MACE rates observed after BVS treatment compared with medical therapy alone warrants the performance of an adequately powered randomized trial to determine whether PCI treatment of vulnerable plaques improves patient outcomes."

NEW YORK - October 14, 2020 - Data from COMBINE (OCT-FFR) found that the use of FFR combined with OCT imaging can help improve the accuracy of high-risk lesion identification in patients with diabetes.

Findings were reported today at TCT Connect, the 32nd annual scientific symposium of the Cardiovascular Research Foundation (CRF). TCT is the world's premier educational meeting specializing in interventional cardiovascular medicine.

Fractional flow reserve (FFR) is widely used to guide the revascularization strategy in the catheterization lab. The FAME I and FAME II trials have shown that stable ischemic heart disease lesions with FFR >0.80 can be safely treated medically, while PCI of lesions with FFR

However, recent evidence has shown that in some patient subgroups such as diabetes mellitus (DM) and/or acute coronary syndrome (ACS), lesions with FFR>0.80 can have worse outcomes than in patients without DM or ACS, most likely due to plaque instability or rapid progression of atherosclerotic plaque.

Previous studies have shown that lipid-rich plaques with a thin cap fibroatheroma (TCFA) have unfavorable clinical outcomes compared to non-TCFA lesions particularly in DM patients. Optical coherence tomography (OCT) can accurately identify lipid-rich and TCFA lesions. Whether OCT can identify lesions with future unfavorable clinical events despite lack of ischemia has not been studied previously.

The COMBINE (OCT-FFR) trial was a prospective international, natural history study. Patients with DM and with stable or acute coronary syndromes who had one or more non-culprit target lesion(s), with a 40-80% diameter stenosis, underwent FFR assessment. FFR-negative patients underwent OCT assessment and were further medically treated. Depending on the presence or absence of TCFA, patients were divided in two groups: TCFA negative (group A) and TCFA positive (group B). Patients with target lesions with FFR

The primary endpoint was the incidence of target lesion related MACE defined as cardiac death, target vessel myocardial infarction (MI), clinically-driven target lesion revascularization (TLR), or hospitalization due to unstable or progressive angina at 18 months in the medically treated patients with FFR>0.80 and TCFA patients (Group B) compared with medically treated patients with FFR>0.80 and no-TCFA (Group A). The secondary endpoint was the incidence of MACE between patients with FFR>0.80 and TCFA (Group B) vs. revascularized lesions that had FFR

The primary endpoint occurred in 13.3% of Group B compared with 3.1% of Group A [HR 4.7 95%CI (2.0-10.9) P=0.0004], suggesting that the presence of TCFA even in the absence of an abnormal FFR was predictive of future events. This rate of adverse events was even higher than the rate of events among the revascularized lesions with abnormal FFR at baseline (Group C) [HR 1.25 95%CI (0.28-5.59) P=0.77].

"In patients with diabetes, COMBINE (OCT-FFR) showed that the presence of a high-risk plaque (TCFA) is a strong predictor of future MACE, despite lack of ischemia," said Elvin Kedhi, MD, PhD. Dr. Kedhi is Professor of Cardiology, working in ULB (Liberal University Brussel) Hopital Erasme and Silesian Medical University, Katowice, Poland

"Additionally, patients with high-risk plaques (TCFAs) have a significant increase in target-lesion related MACE and MI compared to patients without TCFA at 18 months. These findings indicate that combining FFR and OCT can improve the accuracy of high-risk lesion and patient identification and should be adopted in practice."

Various genetic diseases caused by point mutations have no established therapeutic approaches. Prof. Tsukahara and colleagues (Japan Advanced Institute of Science and Technology) are studying a therapeutic method using artificial RNA editing. It was announced that this year's Nobel Prize in Chemistry will be given to the two scientists who discovered CRISPR/Cas9 for genome editing. Although genome editing is drawing attention as a gene repair technology, genome editing such as CRISPR/Cas9 may result in permanent alterations in genomic DNAs, potentially affecting multiple loci. Currently, it is very difficult to perform accurate genome editing in all targeted cells in vivo. So, it is possible to edit the genome in a fertilized egg, embryo, or cells, however, it is not suitable for gene therapy in humans. Moreover, genome editing raises ethical concerns. Therefore, we believe that genome editing is a suitable method for "ex vivo" techniques, or for use in fertilized eggs, but not throughout a patient's body. In contrary, changes resulting from the RNA editing are not permanent because they do not affect the genome sequence, and can be done in sequence-specific manner. Therefore, for the purpose of therapeutic treatments, RNA editing is preferable to genome editing, says Prof. Tsukahara. Artificial site-directed RNA editing is an important technique for modifying genes and ultimately regulating protein function. We are trying to modify the genetic code of transcripts (RNA) by artificial RNA editing for the treatment of genetic disorders.

RNA editing is a physiological process and widespread in living organisms to produce various proteins with different functions from a single gene. In mammals, C or A of the RNA chain is base sequence-specifically hydrolytically deaminating, whereby C is replaced by U and A by I (inosine). These base conversions occur as a result of deamination of A or C, which has been found to be catalyzed by ADAR and APOBEC family enzymes, and then change genetic codes in RNAs. In this paper, we succeeded for the first time in the world in artificial C-to-U conversion of mutated RNA using APOBEC1.

Many genetic diseases are caused by T-to-C point mutations. Hence, editing of mutated genes represents a promising strategy for treating these disorders. We engineered an artificial RNA editase by combining the deaminase domain of APOBEC1 (apolipoprotein B mRNA editing catalytic polypeptide 1) with a guideRNA (gRNA) that is complementary to the target messenger RNA (mRNA). In this artificial enzyme system, the gRNA is bound to a MS2 stem-loop, a deaminase domain is fused to the MS2 coat protein and has the ability to convert mutated target nucleotides from C-to-U. As a target RNA, we used RNA encoding blue fluorescent protein (BFP) that was derived from the gene encoding GFP by a 199T > C mutation. Upon transient expression of both components (deaminase and gRNA), we observed GFP by confocal microscopy, indicating that mutated 199C in BFP had been converted to U, restoring the original sequence of GFP. This result was confirmed by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) and Sanger's sequencing using cDNA from transfected cells, revealing an editing efficiency of approximately 21%. Deep RNA sequencing result showed that off-target editing was sufficiently low in this system. We successfully developed of an artificial RNA editing system using artificial deaminase (APOBEC1) in combination with the MS2 system that could lead to therapies that treat genetic diseases by restoring wild-type sequences at the mRNA level.

Corresponding Author: Aaron Baum, PhD, Assistant Professor, Health System Design and Global Health, Icahn School of Medicine at Mount Sinai, New York, and other coauthors.

Bottom Line: 60% of American adults have a chronic condition, but adults in Mississippi are 50% more likely to have one than adults in Colorado. In Denver, rates of chronic conditions vary 3-fold across zip codes. What is the reason the United States has such large geographic health disparities?

One explanation is that people who live in Mississippi are different in many ways from people in Colorado, and those differences--such as economic status or demographics including age and gender--may cause the health disparity. Another possibility is that the place where a person lives actually affects their health.

A new study disentangles these explanations by examining millions of people who moved to new neighborhoods, counties, and states, and then traced how their health changed after the move.

The study found that a person's risk of an uncontrolled chronic condition increased after moving to a place where the uncontrolled chronic condition was more common. For example, moving from a 10th-ranked zip code to 90th-ranked zip code for a given chronic condition was associated with a significantly increased prevalence of uncontrolled blood pressure of 7 percentage points, uncontrolled diabetes of 1 percentage point, obesity of 2 percentage points, and depressive symptoms of 3 percentage points among movers.

Results: The researchers found that a persons' place of residence substantially influences their risk of uncontrolled chronic disease. Place mattered the most to a patient's risk of high blood pressure and depression, and to a smaller extent, uncontrolled diabetes and obesity.

Why the Research Is Interesting: Unlike prior research, this study evaluated changes in health outcomes over time within the same individual before and after the person moved to a new environment. The findings could have important implications for the design of public policies that target the underlying sources of increasing health disparities in the United States.

Who: About 5 million adults treated at Veterans Health Administration (VHA) facilities in the United States, including 1 million adults who moved zip codes and 4 million adults who did not move.

When: Patients treated at all VHA facilities in the United States from 2008-2018.

What: The study examined how much a person's place of residence contributed to their health outcomes by comparing their risk from common chronic conditions before and after they moved.

How: Researchers studied electronic medical records of all patients treated at VHA facilities from 2008-2018 who moved at least once or did not move at all. They identified who moved based on their zip code of residence, and tracked movers' health outcomes including blood pressure, diabetes, symptoms of depression and obesity before and after the move. Using statistical models that adjusted for the person's characteristics, the time since they moved, and national trends, the researchers evaluated how much a person's health outcome changed after moving to a new zip code where the health outcome was more (or less) common than in their origin zip code.

Study Conclusions: In this retrospective study of patients treated at VHA facilities, the researchers found that the place where a person lived substantially affected their likelihood of having poorly controlled blood pressure or experiencing symptoms of depression. They also found that where a person lived somewhat affected their likelihood of having poorly controlled diabetes or obesity.

Said Mount Sinai's Dr. Aaron Baum of the research:
This study confirms something Americans are currently acutely aware of: where you live affects your health. By evaluating medical records of millions of adults before and after they moved to a new neighborhood, we showed that where a person moved to affected their risk of having a poorly controlled chronic condition. In addition to individual behaviors like healthy eating and exercise, our findings suggest that local and regional factors substantially influence the health of the 60% of American adults who have a chronic condition.

View the full study here. To schedule an interview with Dr. Baum, please contact the Mount Sinai Press Office at stacy.anderson@mountsinai.org or at 347-346-3390.

In a time already full of challenges and changes, some pregnant and postpartum women will also experience a rare but dangerous heart complication: an aortic dissection.

For a new investigation published in JAMA Cardiology, researchers studied the experiences of 29 participants in an international registry who were unexpectedly hospitalized for a dissection while pregnant. Most already had an underlying heart condition, although it was often not yet diagnosed.

Aortic dissections only affect 3 in 100,000 people per year. They cause the layers of the aorta to tear, and blood to pool or leak instead of flowing normally. A patient needs a timely diagnosis and then urgent, life-saving medical attention.

Aortic diseases and conditions like Marfan syndrome or Loeys-Dietz syndrome are usually culprits in women who have a dissection while pregnant, the researchers say, although an association to high blood pressure, the most common risk factor in the general population, may exist, too.

Pregnancy increases risk of dissection

Notably, the researchers found 19% of aortic dissections in women younger than 35 years old were associated with pregnancy. That means a woman already predisposed to have a dissection is more likely to have one during pregnancy, possibly due to hormones and changes to the body during pregnancy and postpartum.

Women in the cohort experienced dissections in all three trimesters of pregnancy in addition to within three months postpartum, although more cases occurred in the latter part of pregnancy and immediately following.

All of the participants who had a Type A aortic dissection, the most dangerous, underwent surgery to repair the dissection. Eighty-five percent of those women with a Type A dissection went into their pregnancies with a known diagnosis such as Marfan syndrome (the most common).

The participants who had a type B dissection were more likely to be given medication, although some received an open or minimally invasive heart surgery.

IRAD's unique opportunity

Given that aortic dissection is already rare, the ability to study a cohort of people who had the condition while pregnant provides an important opportunity, says senior author Kim Eagle, M.D., a director of the Michigan Medicine Frankel Cardiovascular Center and a professor of internal medicine.

"It's important to understand what these women experienced, including their risk factors, underlying medical conditions and ultimate outcomes, in order to learn how best to care for others and to prevent future aortic dissections in this population," he says. Eagle started the International Registry of Acute Aortic Dissection, housed at Michigan Medicine, in 1996. Members include 57 active centers in 13 countries.

Twenty-eight of the 29 patients in the IRAD registry who had a dissection during pregnancy survived the hospitalization. The dissections studied in this publication occurred between 1998 and 2018 and the 29 women represent 1% of all women in the registry.

This is the 100th publication to come out of IRAD.

"Twenty years ago, the seminal IRAD paper was published, aptly also in JAMA, detailing the first 454 patients," Eagle says. "Over 10,000 patients and 24 years since data collection began, IRAD continues to influence our understanding and treatment of acute aortic dissection."

"IRAD has been instrumental in characterizing the presentation of aortic dissection, along with better understanding its natural history and the impacts of different therapeutic approaches in the treatment of this very deadly disease," says Himanshu Patel, M.D., a cardiac surgeon and professor at Michigan Medicine. Patel leads adult cardiac surgery at the Frankel CVC, and co-leads the international cohort in IRAD.

The rise of cardio-obstetrics

Although aortic dissection is most often seen in older men, this cohort study underscores the importance of careful monitoring of cardiac conditions during pregnancy, researchers say.

Co-author Melinda Davis, M.D., a cardio-obstetrics expert at Michigan Medicine with appointments in both cardiology and obstetrics and gynecology, says pre-pregnancy care for a woman with known aortic disease would include evaluation of maternal and fetal risk, counseling and possible genetic testing, followed by ongoing monitoring and testing.