Body

Hennigsdorf/Berlin, Germany, May 14, 2020 - Diagnostics company SphingoTec GmbH ("sphingotec") and 4TEEN4 Pharmaceuticals GmbH ("4TEEN4") announced today the publication of new data showing that high blood levels of Dipeptidyl Peptidase 3 (DPP3) are indicating upcoming multiple organ failure and mortality risk in burn patients. DPP3 is a proprietary biomarker of 4TEEN4 for hemodynamic instability and cardiac depression. sphingotec has in-licensed global rights to develop and commercialize in vitro diagnostic (IVD) tests for the DPP3 biomarker from 4TEEN4 and made it available on its proprietary Nexus IB10 point-of-care platform.

The results from the recent study1 provide evidence that DPP3 blood concentrations in severely ill burn patients are indicating fatal outcomes. The data also shows that high DPP3 concentration in the blood is linked to circulatory failure, cardiac depression, and acute kidney injury. Decreasing DPP3 levels in the blood, on the other hand, indicate a substantially reduced risk of mortality.

According to a newly identified disease mechanism, the release of the cardiac depressant factor DPP3 into the bloodstream is a major cause of short-term organ failure: DPP3 is an enzyme that is present in many cell types and normally plays an important role in the recycling of cellular proteins. When massive uncontrolled cell death occurs, like in the case of burn patients, DPP3 is released into the bloodstream where it degrades angiotensin II, a peptide hormone controlling the heart function. Unphysiologically low levels of angiotensin II rapidly lead to cardiac depression and ultimately organ failure. Previously published data2,3 provided evidence that poor outcome of patients with severe heart failure or cardiogenic shock are caused by DPP3. Furthermore, the causal role of DPP3 in cardiac depression could be reproduced in several model systems.

"The new data adds to the growing body of evidence that places the cardiac depressant factor DPP3 in strong connection with short-term organ failure and high mortality in critical care settings. We have already started a collaboration with the critical care community to provide our fully automated DPP3 point-of-care test to support the management of acute care patients," said Dr. Andreas Bergmann, CEO and founder of sphingotec.

The IVD test for DPP3 is commercialized under the brand name IB10 sphingotest® DPP3 and is designed and validated for use in conjunction with sphingotec's fully automated Nexus IB10 whole blood point-of-care platform, delivering results within 20 minutes. This new test complements a wide-range of assays for acute care settings that are already available on this widely used point-of-care platform that can be flexibly deployed in laboratory as well as near-patient settings such as emergency departments and intensive care units.

A small study in Greece found that the clinically approved anti-inflammatory drug anakinra, used to treat rheumatoid arthritis, improved respiratory function in patients with severe coronavirus disease 2019 (COVID-19). The eight patients also had a condition called secondary hemophagocytic lymphohistiocytosis (sHLH), which is characterized by overactivation of the immune system and organ failure. One patient, who did not require mechanical ventilation, improved rapidly after starting treatment with the drug and was discharged from the hospital 9 days later. But the therapy did not prevent three out of seven patients on ventilators from dying, and it's not yet clear whether it improves mortality rates. The report appears May 14 in the journal Cell Host & Microbe.

"These data argue that the administration of anakinra may be a viable treatment in severe COVID-19 with sHLH, supporting larger clinical studies to validate this concept," says senior author Evangelos J. Giamarellos-Bourboulis, a professor of internal medicine at the Medical School of the National and Kapodistrian University of Athens.

The death rate in patients with severe COVID-19 admitted to intensive care units (ICUs) is estimated to be between 50% and 65%. Severe complications of COVID-19 are thought to be driven by inflammatory responses, particularly through signaling molecules called interleukin 1β (IL-1β) and interleukin 6 (IL-6). The overproduction of IL-1β by immune cells called macrophages can cause sHLH, also known as macrophage activation syndrome, which is characterized by low counts of blood cells, excessive blood clotting, kidney injury, and liver dysfunction. Anakinra inhibits IL-1β signaling and has been shown to reduce the mortality of patients with signs of sHLH by 30%.

In the new study, the researchers tested whether anakinra could effectively treat severely ill COVID-19 patients with pneumonia and sHLH. Seven of the eight patients were males who had respiratory failure, were on ventilators in ICUs in Greece, and had serious underlying conditions such as heart disease and high blood pressure. They were treated with anakinra intravenously 200 mg every 8 hours for 7 days. They also received treatment with the antimalarial drug hydroxychloroquine and broad-spectrum antibiotics. The researchers monitored their outcomes over the course of 4 weeks.

Anakinra treatment improved the majority of laboratory findings and decreased signs of sHLH in the ICU patients. All of them showed improved respiratory function, as indicated by a 15% to 117% increase in the ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO2/FiO2), which compares the oxygen level in the blood to the oxygen concentration that is breathed. Moreover, six patients needed a lower dose of drugs that increase blood pressure. Although three of the ICU patients died, previous studies have shown that sHLH can lead to death rates as high as 67%.

The non-ICU patient was a 71-year-old woman who was hospitalized in the Netherlands for COVID-19 2 weeks after the third cycle of chemotherapy. This patient was also on hydroxychloroquine for rheumatoid arthritis. She received anakinra treatment 300 mg once daily intravenously for 4 days, followed by 100 mg once daily for an additional 5 days. She improved within the first day of anakinra treatment, showing a reduced need for oxygen and a decrease in signs of sHLH, and was discharged 9 days after starting treatment. According to the authors, these results suggest that anakinra may prevent the progression of respiratory failure and the need for mechanical ventilation in COVID-19 patients with sHLH.

"We believe that anakinra has the potential to improve outcomes in patients with severe COVID-19," says first author George Dimopoulos of the National and Kapodistrian University of Athens. "Larger clinical trials are warranted to validate these results and demonstrate the usefulness of anti-IL-1 therapy when COVID-19 is complicated by sHLH."

TAMPA, Fla. -- Prostate cancer is the most common cancer in men. One in nine men will be diagnosed during their lifetime. While most men will not die from prostate cancer, there is a small subset of patients whose disease is so aggressive at the time of diagnosis that surgery and radiation are not able to control their cancer. Researchers in the Center of Excellence for Evolutionary Therapy at Moffitt Cancer Center want to better understand what is happening in the tumor microenvironment to drive prostate cancer to become aggressive and grow rapidly. In a new article published in Nature Ecology & Evolution, the research team provides a closer look at a multiscale mathematical model they developed to analyze integrated biologic and pathologic data to determine tumor aggressiveness.

The prostate is made up of epithelial tissue surrounded by supporting stroma. While prostate cancer begins in the epithelial tissue, the surrounding stroma contributes to cancer growth and progression. The Moffitt researchers wanted to learn how the stromal ecology, which can be inhibitory, highly reactive or nonreactive, shapes prostate cancer tumor evolution.

"Our previous models show that reactive stroma has a role in prostate cancer progression, but this new model allowed us to look more closely at how the stromal ecology alters tumor evolution, growth and invasiveness," said Alexander R.A. Anderson, Ph.D., director of the Center of Excellence for Evolutionary Therapy and chair of the Integrated Mathematical Oncology Department at Moffitt. He led the Moffitt team with collaborators from the University of Texas Health Science Center and NorthShore University.

To do this, the researchers developed an eco-evolutionary mathematical model that mimics how prostate cancers grow and simulated tumors growing in different stromal ecologies. The model predicted larger tumors with highly reactive stroma and smaller tumors in nonreactive stroma. Surprisingly, it also predicted that these tumors evolved differently, with the smaller tumors driven by nonreactive stroma being far more aggressive.

This result was validated in animal models and quantified in patients. Anderson and his team analyzed pathology data from prostate cancer patients guided by the mathematical model. They used patients' Gleason scores, a standard grading for prostate cancer diagnosis, along with reactive stroma grading, a measurement based on the amount of reactive stroma in the prostate, to create a new integrated cancer biomarker capable of more accurately scoring a patient's prostate cancer. That integrated cancer biomarker was then cross validated in a large cohort of prostate cancer samples and was able to accurately stratify all Gleason scores.

"Our results demonstrate that traditional metrics like the Gleason score, which are often tumor-cell centric, could be improved with ecological metrics," said David Basanta, Ph.D., co-author and associate member of Moffitt's Integrated Mathematical Oncology Department.

The mathematical models and patient samples all agreed and showed that stromal ecology can explain prostate cancer growth dynamics. Importantly, they also showed that the stroma is a major driver of the aggressiveness of prostate cancer cells.

"This suggests that aggressive, environmentally independent prostate cancer may be a result of poor stromal ecology, supporting the concept that incorporating markers of stromal ecology into prostate cancer scoring could improve a patient's prognosis," said Anderson.

A new report authored by Pool Re and Cranfield University's Andrew Silke, Professor of Terrorism, Risk and Resilience, reveals how the COVID-19 pandemic is already having a significant impact on terrorism around the world.

The report, 'COVID-19 and terrorism: assessing the short-and long-term impact' reveals:

There is a mixed picture on the level of attacks in the short-term - lockdown measures will tend to inhibit attacks but terrorist propaganda calling for attacks (while authorities are distracted, etc.) will incite some incidents.

Much propaganda - and particularly that connected to far-right extremism - is focusing on conspiracy theories connected to COVID-19 and this has already inspired plots and attacks.

Islamist extremist propaganda is focusing more on the vulnerability of government opponents distracted by the pandemic and the opportunity this presents for attacks.

There is a significant current increase in online extremist activity, raising the risk of increasing short-to-medium term radicalisation.

There are strong long-term concerns that states weakened by the serious economic consequences of the pandemic will be more vulnerable to the emergence/resurgence of terrorist groups in many parts of the world.

Launching the report, Andrew Silke Pool Re and Cranfield University's Professor of Terrorism, Risk and Resilience, said: "The pandemic is likely to have a mixed impact on terrorism trends in the short term. While lockdown measures may represent obstacles to terrorists to carry out real-world attacks, many terrorist groups have also flagged that the pandemic has left government and security resources being severely stretched.

"As a result, the ability of government, intelligence and law enforcement agencies to focus on traditional priorities such as counterterrorism has been undermined."

Commenting on CBRN weapons, Professor Silke continues: "One genuine concern is that COVID-19 may lead to a resurgence in interest among terrorists for using chemical, biological, radiological and nuclear weapons. Historically, a range of terrorist movements have been interested in bioterrorism though there have been very few successful attacks by terrorists using biological weapons. While serious obstacles certainly remain, the huge impact of COVID-19 may re-ignite some interest in biological weapons."

Pool Re's Chief Resilience Officer, Ed Butler said: "This report is very timely and worth digesting at a time when we are quite rightly focussed on the near-term issues and human and economic devastation being caused by this global pandemic. However, Pool Re's core purpose remains the provision of terrorism reinsurance and we need to continue to understand the contemporary terrorist threats as well as horizon scan the future landscape. Pool Re's strategic relationship with Cranfield University underpins the importance we attach to collaborating with academia in understanding and mitigating against catastrophic perils."

Researchers from Russia and Italy have proposed a compact sensor system that can implement the functionality of the electronic nose and developed a reproducible technology for its manufacture. This device is designed as flexible electronics that can analyze exhaled air, as well as identify pathologies of the respiratory tract and organs.

During the experiments, the device demonstrated high accuracy in determining patients with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the respiratory tract, which increases the risk of complications when infected with COVID-19.

Chronic obstructive pulmonary disease (COPD) develops in the bronchial mucosa in response to pathogenic external factors and leads to a negative change in the functions of the respiratory tract. A person with COPD cannot receive the necessary oxygen, because the inhaled air flow is limited. COPD is commonly caused by gases and volatile particles, such as dust, tobacco, cadmium and silicon particles, and others. The methods for detecting this disease are complex and time consuming, which is inextricably linked to a threat to the patient's health. Conventional methods for breath analysis, such as gas chromatography and mass spectroscopy, are expensive and time-consuming, so new approaches are required that are notable for their low cost and speed of testing. COPD is an urgent problem, as the disease may lead to the limitation of physical performance and disability of patients. It is important to note that people with COPD are most at risk for complications if they become infected with COVID-19.

"Malfunctioning of human organs causes a change in a number of processes in the metabolism, which affects the composition of exhaled air. Its analysis can be used to identify diseases of the respiratory system as well as other internal organs, such as the stomach," explains Ivan Bobrinetskiy, Doctor of Science, project manager for the Russian Science Foundation grant, leading research associate of the National Research University of Electronic Technology. "The proposed concept of the electronic nose allows for operational monitoring and preliminary detection of diseases in just a few minutes. At the same time, the sensors are reusable, and the basic data and the identification of possible pathologies of organs are transferred from the device to digital mode using methods of statistical data analysis, including the capabilities of artificial intelligence. "

The system is based on modified carbon nanotubes (CNTs), which allows the electronic nose to combine various desired properties. For example, flexible conductive films can be made from carbon nanotubes. Such films are needed in order to provide the system with a layer with a given electronic structure, which will be responsible for the operation of the device. "CNTs were synthesized by aerosol chemical vapor deposition and deposited in the form of thin transparent and conductive films. This technology is highly reproducible, easily scalable and allows applying films of nanotubes to any surface," said Albert Nasibulin, professor at the Skolkovo Institute of Science and Technology, professor of the Russian Academy of Sciences. The development of the CNT manufacturing technology for the sensor system is also supported by a grant from the Russian Science Foundation.

The study of the effectiveness of the new system involved 12 patients with COPD and 9 healthy individuals in accordance with the rules of clinical trials. Breath sampling was carried out in disposable polytetrafluoroethylene (PTFE) plastic bags - made of a very inert material - containing a sensor matrix. The subjects inhaled and inflated the bag as much as possible through a plastic straw. When the straw was removed, the packages were sealed. The sensor matrix inside the bag was in contact with exhaled air for about three minutes, so that all sensors could fully work and interact with the gas molecules that characterize the pathology. Then the system was cleaned with dry air for the next study. Samples were collected from each participant with an interval of one hour.

Since the system detected all people with COPD, it can be argued that the device is effective. In the exhaled air, an increased concentration of nitrogen dioxide was detected. It should be noted that the gas content is less than one molecule per million molecules of the exhaled air, which indicates high sensitivity of the developed sensors.

Researchers have also successfully tested their system on gases that can characterize other diseases. The volatiles selected for this study (ammonia, nitrogen dioxide, sodium hypochlorite, water, benzene, hydrogen sulfide, acetone, ethanol and 2-propanol) are associated with specific diseases and can potentially be considered as their biomarkers. Thus, the content of 2-propanol, benzene, ethanol and acetone in exhaled air is increased in people with lung cancer, while acetone is found in patients with diabetes. A high concentration of ammonia in human breath is associated with liver or kidney diseases, and hydrogen sulfide has been proposed as a biomarker of asthma. It is shown that the concentration of sodium hypochlorite is an increased content in exhaled air in children with bronchial asthma and cystic fibrosis.

The studies were carried out together with colleagues from the Catholic University of the Sacred Heart (Italy), Aalto University (Finland), Biosense Institute in University of Novi Sad (Serbia).

INDIANANAPOLIS--As COVID-19 continues its sweep around the globe, dialysis units have continued to be hotspots for the virus' spread. Researchers at Indiana University School of Medicine hope to combat that threat, through a novel study published May 14, 2020 in JAMA. The study, conducted by members of the Pediatric Nephrology Dialysis Unit at Riley Hospital for Children at IU Health, used antibody testing on patients, doctors, nurses and staff within the unit to track symptomatic and asymptomatic spread in a confined space, such as a dialysis unit.

"There are unique exposure challenges in dialysis units that limit social distancing efforts, including open bay formats and rotating nursing assignments," said David Hains, MD, lead investigator on the study. "Dialysis units find threat among many infectious diseases and COVID-19 is dangerous to patients receiving dialysis."

Studies from Wuhan, China show the spread of COVID-19 among dialysis units, but this study is the first of its kind in a pediatric setting, as well as being one that used antibody status as a determining factor.

"Our study also highlights the importance of distancing and PPE," said Hains, division chief of pediatric nephrology in the Department of Pediatrics. "We saw a dramatic decrease in 'new' cases as we implemented more aggressive measures to protect our patients and staff. More studies to examine this are underway by a number of people here on campus."

The group's study tracked 13 patients, 11 nurses, four staff and 10 physicians. By day 21 of the study, 11 health care workers and three patients had positive COVID-19 antibodies. No participants developed symptoms between days seven and 21.

"This study found a high occurrence of COVID-19 antibodies in individuals interacting in a pediatric dialysis unit. This high rate of occurrence suggests that more health care workers may be antibody-positive than would otherwise be expected," Hains said. "Testing for the presence of these antibodies can allow for strategically staffing the care of patients who have COVID-19, or who are suspected to be positive, with nurses and physicians who also have tested positive for these antibodies."

Hains said that a nurse who was participating in the study did not exhibit any of the symptoms of the virus and had a positive antibody test. She subsequently had a COVID-19 PCR test, which came back positive. Because of that test, Hains said, his group was able to react quickly to the situation.

"When she had a COVID-19 test, she was positive. That allowed us to rapidly quarantine her, which may have helped prevent the spread in our unit," Hains said. "I can see this being utilized in other healthcare settings or arenas where distancing is not easily done."

As social distancing regulations begin to loosen across the state, Hains and his team, including Department of Pediatrics faculty Andrew Schwaderer, MD, Aaron Carroll, MD, Amy Wilson, MD, and Michelle Starr, MD, plan to continue this study to see the impact these changes have on their numbers. Hains is working with the Richard L. Roudebush Indianapolis VA Medical Center to replicate their study in an adult unit.

WASHINGTON - The Society for Cardiovascular Angiography and Interventions (SCAI) has published a position statement addressing optimal percutaneous coronary intervention (PCI) treatment of patients with complex coronary artery disease (CAD).

The position statement was presented today during the SCAI 2020 Scientific Sessions Virtual Conference and published in SCAI's official journal, Catheterization and Cardiovascular Interventions.

While complex PCI has not yet been fully defined, this patient group presents both complex anatomic lesions and clinical parameters including advanced age, frailty, comorbidities, compromised hemodynamic status, depressed ventricular function and concomitant valvular disease. These factors increase both the procedural complexity of percutaneous coronary intervention (PCI) and the risk of adverse patient outcomes.

"Over the last several years, there has been an increase in the anatomic and physiologic complexity of patients presenting to the catheterization lab. During that time, a multitude of tools have been developed to aid defining and treating this group when percutaneous revascularization is indicated," said Robert F. Riley, MD, FSCAI, member of the document writing group, and research and medical director, Complex Coronary Therapeutics Program at The Christ Hospital. "However, this population has been incompletely defined up to this point and there is a need to provide a contemporary evidence-based document that specifically addresses aspects of complex PCI in this patient group."

In the position statement, a multidisciplinary group of experts provide a state-of-the art update addressing evidence regarding PCI in patients with complex clinical and anatomical features and provide procedural guidance to achieve optimal outcomes for this challenging patient group. The document examines pre-procedural assessment of coronary anatomical complexity and higher-risk clinical features and interventional treatment of complex CAD.

"This document further complements the concomitantly published SCAI statement on the performance of PCI in ambulatory surgical centers. Together, we hope these documents will provide guidance on best practices and the performance settings for PCI across the spectrum of clinical and anatomical complexity," Riley concludes.

WASHINGTON - The Society for Cardiovascular Angiography and Interventions (SCAI) today issued a position statement on the performance of percutaneous coronary intervention (PCI) in ambulatory surgical centers (ASCs). The document was published in SCAI's official journal, Catheterization and Cardiovascular Interventions.

Earlier this year, The Centers for Medicare & Medicaid Services (CMS) began reimbursement for PCI performed in ASCs in response to data on patient outcomes from observational studies and randomized controlled trials supporting same-day discharge (SDD) after PCI.

"One of the biggest stories in interventional cardiology this past year was the initiation of payment by CMS for PCI performed in ambulatory surgical centers or ASC," said Lyndon Box, MD, FSCAI, chair of the writing group and interventional cardiologist at West Valley Cardiology Services in Idaho. "SCAI recognized the potential for this new rule to decrease cost, improve patient satisfaction and increase physician autonomy."

The position statement makes recommendations for facility and equipment standards, procedural and periprocedural standards, transfer protocols, and operator standards based on an examination of the evidence for potential benefits and harms. The statement also provides an overview for operators on regulatory considerations.

When defining appropriate treatment in the ASC, the writing groups suggests that diagnostic procedures (ie. left and right heart catheterization, coronary and graft angiography) are appropriate for ASCs. Invasive diagnostic testing that involves intravascular imaging (IVUS and/or OCT) or functional evaluation (FFR and/or resting indices) and coronary angioplasty and stenting were also deemed appropriate.

Notably, the document advises that only patients who are considered appropriate for SDD should be considered for intervention in an ASC. The 2018 SCAI Expert Consensus Document on Length of Stay Following PCI provides guidance on patient suitability for SDD. Additionally, the writing groups suggests that not all patients that might be suitable for SDD in the hospital setting are appropriate for ASC-based PCI, stating that the ASC setting does not provide the option of easily converting a patient to overnight observation. PCI in patients with high-risk clinical features should be avoided in the ASC setting.

The document concludes that the decision to perform PCI in an ASC should be made in the context of the local healthcare environment, while initiation of an ASC PCI program should require transparent adherence to state and federal regulations and operational standards.

"It is crucial that patients in the ASC receive the same quality of care as those in the hospital setting. The paper covers regulatory issues, standards, protocols, quality assurance and ethics. This paper is a 'must-read' for anyone involved with PCI in an ASC," said Box.

WASHINGTON - The Society for Cardiovascular Angiography and Interventions (SCAI) has released an expert consensus statement describing recommendations for the management of patients with out-of-hospital cardiac arrest (OHCA). The statement, published today in Catheterization and Cardiovascular Interventions, was presented during the SCAI 2020 Scientific Sessions Virtual Conference.

OHCA continues to present as significant public health problem due to high mortality and morbidity. Coronary artery disease is often the cause for cardiac arrest in patients with a presenting rhythm of ventricular fibrillation or pulseless ventricular tachycardia.

"Interventional cardiologists are often consulted to assess patients with out of hospital cardiac arrest for emergent invasive evaluation," said Amir Lotfi, MD, FSCAI, chair of the writing group and interventional cardiologist at Baystate Cardiology in Springfield, MA. "We created a document based on evidence-based and patient oriented management to assess and treat patients with out of hospital cardiac arrest."

"We emphasized that out of hospital cardiac arrest treatment is a continuum from pre-hospital, hospital, and post-hospital care which requires a multidisciplinary approach to enhance both survival and return to a good quality of life," Lotfi continued. "With this document our goal is to increase standardized language and decrease variation in care in order to improve outcome."

An international team of scientists, led by University of Helsinki reported that vitamin B3, niacin, has therapeutic effect in progressive muscle disease. Niacin delayed disease progression in patients with mitochondrial myopathy, a progressive disease with no previous curative treatments.

Vitamin B3 forms have recently emerged as potent boosters of energy metabolism in rodents. These vitamins are precursors for NAD+, a molecular switch of metabolism between fasting and growth modes.

As fasting has been shown promote health and longevity in for example mice, a variety of "NAD boosters" are being developed. However, whether actual NAD+ deficiency exists in human disease, and whether NAD+ boosters could have curative effects in patients with degenerative diseases, has remained elusive.

In the current publication, a collaborative team of investigators led by academy professor Anu Suomalainen-Wartiovaara and academy research fellow Eija Pirinen report lowered NAD+ levels in both blood and muscle of mitochondrial myopathy patients.

"The disease is characterized by progressive muscle weakness, exercise intolerance and cramps. Currently, no treatments that would slow down disease progression exist", says Suomalainen-Wartiovaara.

Niacin - a promising treatment option

Pirinen and colleagues report that niacin treatment efficiently increased blood NAD+ both in patients and healthy subjects. Niacin restored NAD+ in the muscle of the patients to the normal level and improved strength of large muscles and mitochondrial oxidative capacity. Overall metabolism shifted towards that of normal subjects.

The results of this open pilot study revealed that niacin is a promising treatment option for mitochondrial myopathy. The authors emphasize, however, that niacin and NAD+ are efficient metabolic modifiers and niacin treatment should be cautiously applied only, when NAD deficiency is detected for example in the patient's blood.

"Our results are a proof-of-principle that NAD+ deficiency exists in humans and that NAD+ boosters can delay progression of mitochondrial muscle disease", Suomalainen-Wartiovaara comments.

"The study is a significant leap in the development of targeted therapy options for energy metabolic diseases", Suomalainen-Wartiovaara continues.

CHICAGO (May 14, 2020) -- Heart and lung surgeons are fully aware of the difficulties that exist in the intensely demanding and competitive specialty of cardiothoracic surgery; even still, they report being extremely satisfied with their jobs--more so than ever before, according to a survey published online today in The Annals of Thoracic Surgery.

"Despite numerous external pressures, the practice of cardiothoracic surgery remains strong," said John S. Ikonomidis, MD, PhD, from the University of North Carolina at Chapel Hill. "It is a vibrant and multidimensional specialty that continues to be practiced at a very high level by an outstanding group of caring, hard-working, and highly intelligent individuals."

Administered by The Society of Thoracic Surgeons approximately every 5 years since the early 1970s, the cardiothoracic surgery workforce survey helps establish a current, detailed profile of the specialty, including surgical practice trends and attitudes in the United States. For the most recent survey, 70 questions were shared with 3,834 members; 1,069 surgeons participated, resulting in a 27.9% response rate.

Cardiothoracic surgery has existed for more than 100 years, and throughout that time, extraordinary progress and remarkable achievements have occurred in every aspect of the specialty. Few career paths offer the same personal and professional satisfaction as that of a cardiothoracic surgeon, according to Dr. Ikonomidis. This is where "medicine best embodies the interface between humanity and science," he said, making cardiothoracic surgery "one of the most rewarding specialties to choose."

The survey results show that an increasing number of cardiothoracic surgeons agree, with 83.1% reporting that they are either satisfied, very satisfied, or extremely satisfied with their current career, compared with 72.8% in 2014.

"Cardiothoracic surgery remains an exciting and stimulating career considering the scope of standard surgical procedures performed and new developing technologies, which are exponentially expanding," said Kevin D. Accola, MD, from AdventHealth Medical Group in Orlando, FL. "I believe the overall rise in surgeon satisfaction can be partially attributed to these new technologies and procedures, as well as the ability to attract students and young surgeons into our specialty."

In addition, half of practicing surgeons would recommend that their children or grandchildren pursue a career in cardiothoracic surgery, while only 47.5% and 37.1% reported feeling that way in 2014 and 2009, respectively. Some surgeons are even postponing retirement because they have a "high level of career satisfaction."

"When a surgeon heals a patient through a carefully thought-out and expertly performed procedure followed by compassionate and comprehensive postoperative care, a deeply satisfied feeling ensues, which never dulls with time or age," said Dr. Ikonomidis.

The two leading causes of death in the US are heart disease and lung cancer, and the most common birth defect is a congenital cardiac anomaly--all diseases treated by cardiothoracic surgeons. This puts the specialty in a position to have the greatest impact in terms of the number of people affected.

Also important, patients are living longer, with life expectancy more than doubling during the past century. A separate study showed that the anticipated cardiothoracic surgery case load will increase from approximately 530,000 cases in 2010 to more than 850,000 cases by 2035, translating into a 121% increase in case load per surgeon. As a result, the demand for cardiothoracic surgery is not expected to decrease any time soon.

"Cardiothoracic surgery is busy and exhaustive at times," said Dr. Ikonomidis. "Patients are usually pretty sick, and their lives often depend on the outcome of the operation about to be performed. The surgeons, who are the 'captains of the ship' in the operating room, have developed the stamina and focus that enables them to get through long and stressful days and operations and still be able to come back for more."

Despite the increasing need for surgeons and continuing advances in the specialty, these still are trying times for cardiothoracic surgery.

The educational debt accumulated by many surgeons is staggering, with 17.8% having $150,000 or more at the time they began active surgical practice. Though jobs are sometimes more difficult to find, the current survey showed that 59.2% of practices are looking to hire a new surgeon within the next 2 years, up from 52.3% in 2014.

Gender disparity also still exists in cardiothoracic surgery. Although more women make up the cardiothoracic workforce than previously reported, they are still underrepresented in the specialty. The current survey reported that 8.4% of respondents were female, whereas that number was only 6.9% in 2014.

Another challenge is the aging cardiothoracic surgeon workforce. The current survey showed an increase in the average age of practicing surgeons by 2 years compared with the 2014 survey (56 years vs. 54 years, respectively). As a retirement surge nears, so does the expected decline in the workforce--from 4,000 surgeons in 2010 to less than 2,900 by 2035, as calculated by another study.

Also with the workforce aging, concern about overall surgeon performance will increase, especially since cardiothoracic surgery is considered one of the most technically, cognitively, and physically demanding fields. The survey revealed that 85.3% of cardiothoracic surgeons worked in institutions that did not conduct cognitive and psychomotor performance testing for surgeons who are 65 years or older. This issue, especially with more institutions expected to offer testing programs in the coming years, could potentially contribute to the diminishing cardiothoracic surgery workforce.

Perhaps one of the biggest challenges, though, is the risk of depression and burnout within the specialty. More than 55% of surgeons reported symptoms of burnout and/or depression related to their jobs over the past year, which is 10% to 20% higher than that observed in other specialties.

"Cardiothoracic surgery--as a 'frontline' surgical specialty--is at great risk for burnout and depression because of high stress and long working hours," said Dr. Ikonomidis. "Surgeons must be honest with themselves regarding symptoms and take steps to prevent burnout and depression."

This survey did not track specific elements contributing to these symptoms, but Dr. Ikonomidis explained that the "time-consuming, often counter-intuitive, and frustrating" implementation of electronic medical records, as well as increased scrutiny on surgeon productivity and outcomes, are among the factors that have likely impacted the personal well-being and emotional health of cardiothoracic surgeons.

Several techniques and strategies have been found to significantly lower the risk of distress. According to Dr. Ikonomidis, surgeons should actively focus on both their personal and professional lives, stressing a positive work/life balance. They should place greater emphasis on finding meaning in their daily work, focusing on what is important in life and maintaining a positive outlook. Other methods such as celebrating small victories, practicing mindfulness techniques, and receiving guidance and mentorship also may help. And the sooner the better, as symptoms of burnout and depression and their associated behaviors can start as early as medical school, he added.

"People become surgeons for many reasons," said Dr. Ikonomidis. "The specialty combines the use of clinical knowledge and technical skills, as well as affords opportunities to develop new treatments with research, train the surgeons of tomorrow, and care for a variety of patients on a daily basis. Even though this profession is associated with a lot of stress and is not the most lifestyle-friendly, cardiothoracic surgery is not only challenging and satisfying, but fun."

What The Study Did: The association between 26 common medical conditions including diabetes and high blood pressure and levels of use of alcohol was investigated with data from electronic health records of 2.7 million primary care patients.

Authors: Stacy A. Sterling, Dr.P.H., M.S.W., of Kaiser Permanente Northern California in Oakland, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.4687)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

What The Viewpoint Says: The effectiveness of school closure as a preventive measure during the COVID-19 pandemic is discussed.

Authors: Susanna Esposito, M.D., of the University of Parma in Italy, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamapediatrics.2020.1892)

Editor's Note:  Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

What The Study Did: This report assesses the risk associated with COVID-19 for pediatric patients with cancer.

Authors: Andrew L. Kung, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center in New York, is the corresponding author.

 To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamaoncol.2020.2028)

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Patients repeatedly express their concern that anti-rheumatic drugs could promote the development of breast cancer. In an autoimmune inflammatory disease such as rheumatoid arthritis (RA), the immune system attacks the body's own structures. This can be prevented by taking immunosuppressive drugs, which inhibit parts of the body's own immune defense. The potential disadvantage: weakening the body's immune system might make it less prone to fight emergent cancers. Earlier studies therefore reported an increased risk of some cancer types in rheumatic diseases.

However, this does not apply to all types of cancer: "Studies from the past show an intriguing reduced breast cancer risk in women with diagnosed RA," explains EULAR President Professor Dr. Iain B. McInnes from Glasgow, Scotland, UK.

Previous studies have shown that anti-hormonal therapy with tamoxifen or aromatase inhibitors used in women with breast cancer is associated with a more frequent occurrence of joint pain, but whether they may also lead to RA has remained debated.

In a nationwide Swedish cohort study, scientists have now investigated the connection between breast cancer, anti-hormonal therapy, and rheumatoid arthritis. Hjalmar Wadström, PhD student in the team at Karolinska Institutet Stockholm, identified 15,921 women who were diagnosed with RA between 2006 and 2016. These data were linked to breast cancer risk factors and the risk of breast cancer in women with RA and the risk of RA in women with breast cancer was investigated. These were then compared with a control group of the same age and sex. The result: the risk of breast cancer in women with rheumatoid arthritis was lower than in women with healthy joints, and no association between anti-hormonal breast cancer prophylaxis and later RA was found.

"Our investigations show that although the risk of breast cancer in women with rheumatoid arthritis is reduced, this correlation cannot be easily explained by conventional risk factors for breast cancer," said Wadström summarizing the results of the cohort study. "Even the use of anti-hormonal therapy for breast cancer does not seem to increase the risk of RA," adds Wadström, concluding that in clinical practice, among women with RA who develop breast cancer, the RA disease likely has had limited impact on this cancer development.

"We now know that breast cancer is less common in patients with RA and that tamoxifen and aromatase inhibitors appear to be safe in terms of the risk of future RA at least in the observed first few years - this is important information for patient counseling," says EULAR Scientific Chair Professor Dr. John Isaacs from Newcastle University, UK. "Nevertheless, all patients with a symptomatic rheumatoid disease should regularly attend tumor screening with a frequency appropriate to their age."

In many countries, about one in ten women develops breast cancer, making breast cancer the most common form of cancer in women. About one percent of all people worldwide suffer from rheumatoid arthritis, in Europe alone about 120 million people are affected by a rheumatic or musculoskeletal disease according to figures published by EULAR in the run-up to its annual congress (2).