Body

SILVER SPRING, Md.--Vaccines such as Pfizer, Moderna, Johnson & Johnson and AstraZeneca are designed to prevent severe Coronavirus-19 Disease (COVID-19) due to acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and are highly efficacious. The efficacy is not different in people with and without obesity except for AstraZeneca which is not known, according to a new position statement from The Obesity Society (TOS), the leading scientific membership organization advancing the science-based understanding of the causes, consequences, prevention and treatment of obesity.

Trials have demonstrated high efficacy in individuals with and without obesity against COVID-19-associated hospitalization and death. Therefore, TOS encourages individuals with obesity to undergo vaccination with any of the available vaccines authorized for emergency use by the U.S. Food and Drug Administration as soon as they are able.

"Analysis of COVID-19 vaccine efficacy in certain disease sub-groups has been difficult because the number of trial participants with the disease was too small. This was not the case for obesity. Because the prevalence of obesity among trial participants was high, and because obesity is highly associated with hospital admission and death in COVID-19, the trial results were able to show that, contrary to concerns of reduced vaccine efficacy in people with obesity, that the vaccines were just as efficacious among persons with obesity compared with persons without obesity," said Alexandra M. Hajduk, PhD, MPH, an epidemiologist and associate research scientist in the Department of Internal Medicine (Geriatrics) at Yale School of Medicine in New Haven, Conn. Hajduk is one of the co-authors of the position statement.

The disease of obesity is a recognized risk factor for increased morbidity and mortality in persons with COVID-19 subsequent to infection with the SARS-CoV-2 virus. In addition, obesity is associated with conditions that are independent risk factors and predictors of mortality from COVID-19, including diabetes, cardiovascular, cerebrovascular and pulmonary diseases.

Due to the increased prevalence of severe disease, hospitalization, and death, the Centers for Disease Control and Prevention (CDC) identified obesity as body mass index (BMI) ≥30 kg/m2 as a high-risk medical condition in the COVID-19 pandemic. On Dec. 20, 2020, the CDC's Advisory Committee on Immunization Practices recommended that persons aged 16-64 years with obesity should be prioritized for vaccination in Phase 1c of the phased allocation to provide guidance for federal, state and local jurisdictions where vaccine supply was limited.

Authors of the position statement wrote the document in response to published literature, as well as inquiries made to the Society by patients, providers, Society members, policymakers and others regarding the efficacy of vaccines in persons with obesity against SARS-CoV-2.

“In addition to general misconceptions about the disease of obesity, speculation on the effectiveness of COVID-19 vaccines in obesity has certainly added to vaccine hesitancy in those individuals with obesity. I hope this position statement not only will encourage those with and without obesity to get vaccinated, but to continue the conversations on the existing weight bias in our current health policies and poor coverage and reimbursement of effective treatments for obesity,” said first author, W. Scott Butsch, MD, MSc, director of obesity medicine at the Bariatric and Metabolic Institute at the Cleveland Clinic in Ohio.

In their review, the authors found the following based on each of the vaccines:

Pfizer: In a sub-group analysis of the 13,218 participants with obesity (BMI ≥30 kg/m2, 31.5% of the study cohort), vaccine efficacy was 95.4 % among participants with obesity compared to 94.8% among participants without obesity. Further stratification by age revealed vaccine efficacy of younger adults (age 16-64) with obesity (94.9 %) and older adults (age ≥65) with obesity (100%).

Moderna: In a sub-group analysis among participants with severe obesity (BMI ≥40 kg/m2; 6.5% of cohort) demonstrated a vaccine efficacy of 91.2%, with only one case of severe COVID-19 illness identified among 901 participants with severe obesity, compared to 11 cases among 884 participants in the placebo group with severe obesity. Post hoc analysis reported a vaccine efficacy of 95.8% for participants with obesity (BMI ≥30 kg/m2; 34.5 percent of cohort), with 2 COVID-19 cases in the vaccine group and 46 in the placebo group.

Johnson & Johnson: There were 12,492 participants (28.5% of cohort) with obesity (BMI ≥30 kg/m2) in the trial. Vaccine efficacy 14 days after dose one was 66.8% and 65.9%, 28 days after dose one compared to placebo in participants with BMI ≥30 kg/m2. There were no deaths attributable to COVID-19 in the vaccine group, whereas 6 of the 7 fatalities due to COVID-19 in the placebo group were among participants with obesity.

AstraZeneca: Participants with obesity (BMI ≥30 kg/m2) comprised 19.4% and 20.3% of each trial cohort and was the most common comorbid condition. In an interim sub-group analysis of participants with one or more comorbidities, the vaccine efficacy was 73.4%, though, in the updated sub-group analysis, the vaccine efficacy was 62.7%. The specific vaccine efficacy and safety data in persons with obesity is not yet published.

The following recommendations are currently endorsed by TOS regarding vaccine efficacy in persons with obesity:

1. TOS has confidence in the FDA-approved vaccine trials and the CDC's Advisory Committee on Immunization Practices updated interim vaccine allocation recommendations in the indicated U.S. populations, including those individuals with obesity and severe obesity.
2. TOS recommends that persons with obesity be vaccinated for prevention of COVID-19, in agreement with CDC recommendations, as obesity is clearly associated with an increased risk of more severe course of COVID-19 disease and death.
3. There is no definitive way to determine which COVID vaccine is "best." Current FDA-approved COVID-19 vaccines from Pfizer, Moderna, and Johnson & Johnson were all highly efficacious against COVID-19--associated hospitalization and death in trials, and were found to be equally efficacious in persons with obesity compared to normal weight individuals. TOS advises persons with obesity to accept whichever available vaccination is offered.
4. Publication of long-term vaccine efficacy outcomes, stratified by obesity status, in peer-reviewed journals is needed and is strongly encouraged.
5. Currently, available peer-reviewed data do not support the hypothesis of impaired humoral responses to SARS-CoV2 vaccine in people with obesity.
6. TOS recommends that in the development of care plans for patients with COVID-19, obesity (BMI >30kg/m2) and severe obesity (BMI ≥40kg/m2) should be included as a significant risk of more severe course and outcome of COVID-19.
7. TOS strongly supports evidence-based weight management therapies which support a healthy BMI and the promotion of COVID-19 prevention strategies, including vaccine prioritization. TOS strongly supports policies which ensure access to such treatments, including adequate and equitable coverage for behavioral, medical, device and surgical treatments for obesity.

TOS plans to monitor emerging data on vaccine efficacy and will issue an updated evidence-based position statement at a future time.

"As new, more transmissible variants of SARS-CoV2 emerge, including the Delta variant, vaccination efforts are even more pressing to help limit the spread of disease. These vaccines work in individuals with and without obesity. We want to end this pandemic. Let's make it happen by getting vaccinated," said Catherine Kotz, PhD, FTOS; professor, University of Minnesota (Integrative Biology and Physiology), associate director of research, Geriatric Research, Education and Clinical Care, Minneapolis VA Health Care System; and president of The Obesity Society. Kotz is a co-author of the position statement.

"Accruing data on obesity and risk of COVID-19 severity are shocking, alarming and tragic. As individuals with obesity have a greater risk of severe COVID-19, in a sense they have even more to gain by getting vaccinated, preventing heart-breaking outcomes. By getting vaccinated, we are protecting ourselves and each other; let's get vaccinated!," said Ania M. Jastreboff, MD, PhD, associate professor, Yale University School of Medicine, an endocrinologist and obesity medicine physician-scientist and vice chair of TOS's Clinical Care Committee. Jastreboff is the senior author of the position statement.

In a new study on mice, Johns Hopkins Medicine researchers report that using MRI scans to measure blood volume in the brain can serve as a noninvasive way to potentially track the progress of gene editing therapies for early-stage Huntington's disease, a neurodegenerative disorder that attacks brain cells. The researchers say that by identifying and treating the mutation known to cause Huntington's disease with this type of gene therapy, before a patient starts showing symptoms, it may slow progression of the disease.

The findings of the study were published May 27 in the journal Brain.

"What's exciting about this study is the opportunity to identify a reliable biomarker that can track the potential success of genetic therapies before patients start manifesting symptoms," says Wenzhen Duan, M.D., Ph.D., director of the translational neurobiology laboratory and professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. "Such a biomarker could facilitate the development of new treatments, and help us determine the best time to begin them."

Huntington's disease is a rare genetic disorder caused by a single defective gene, dubbed "huntingtin," on human chromosome 4. The gene is passed on from parents to children -- if one parent has the mutation, each child has a 50% chance of inheriting it. Huntington's disease has no cure and can lead to emotional disturbances, loss of intellectual abilities and uncontrolled movements. Thanks to genetic testing, people can know if they have the disease long before symptoms arise, which typically happens in their 40s or 50s.

For the study, Duan and her team collaborated with colleagues from Kennedy Krieger Institute in Baltimore, Maryland, who developed a novel method to more precisely measure the blood volume in the brain by using advanced functional MRI scans. With the scans, they can map the trajectory of blood flow in small blood vessels called arterioles in the brains of mice engineered to carry the human huntingtin gene mutation that mirror the early stages of Huntington's disease in humans.

Duan notes that there are many known metabolic changes in the brains of people with Huntington's disease, and those changes initiate a brain blood volume response in the disease's early stages. Blood volume is a key marker for oxygen supply to brain cells, which in turn supplies energy for the neurons to function. But with Huntington's disease, the brain's arteriolar blood volume is dramatically diminished, which makes the neurons deteriorate because of lack of oxygen as the disease progresses.

In a series of experiments, the researchers suppressed the mutation in the huntingtin gene in mice, using a gene-editing technology known as CRISPR -- a tool for editing genomes that allows the alteration of a DNA sequence to modify gene function. Then, they used the MRI scanning technique and other tests to track the brain function over time both of mice with the huntingtin mutation, in which they edited out the faulty gene sequence, and a control group of mice in which the faulty gene was unedited.

The experiments assessed abnormalities in the trajectory of arteriolar blood volumes in mouse brains with the Huntington's disease mutation at 3, 6 and 9 months of age (pre-symptom stage, beginning of symptoms and post-symptom stage, respectively). The researchers looked at whether suppression of the mutant huntingtin gene in the neurons could normalize altered arteriolar blood volumes in the pre-symptom stage, and whether reduced expression of the huntingtin gene at the pre-symptom stage could delay or even prevent development of symptoms.

"Overall, our data suggest that the cerebral arteriolar blood volume measure may be a promising noninvasive biomarker for testing new therapies in patients with Huntington's who are yet to show symptoms of the disease," says Duan. "Introducing treatment in this early stage may have long-lasting benefits."

When the researchers mapped the trajectory of cerebral blood volume and conducted an assortment of brain and motor tests in the mice at 3 months of age, and compared the test to those of the control group, they observed no significant differences except in cerebral blood volumes. However, Huntington's symptoms in the mice with the huntingtin gene started at 6 months of age and progressively worsened at 9 months, suggesting that altered cerebral blood volume occurs before motor symptoms and atrophy of the brain cells -- typical traits of the disease.

The cerebral blood volume changes were also found to be similar to those observed in patients with Huntington's disease before they start manifesting symptoms, which declines with the start of symptoms and while the disease progresses over time.

The researchers also analyzed the structure of the arteriole blood vessels in the brains of mice with the mutant huntingtin gene at 3 and at 9 months of age and found no differences in the numbers of vessel segments in the pre-symptom stage. However, they observed that smaller blood vessels had an increased density and reduced diameter, which may be a vascular response to compensate for the impaired neuronal brain function. This might suggest, the researchers conclude, that impaired vascular structure leads to lowered arteriole blood volumes and possibly compromised ability to compensate for the loss in the symptom stage.

Considering that Huntington's disease symptoms depend not only on brain cell loss but also on how neurons deteriorate, the researchers set out to determine if suppressing the huntingtin gene during the pre-symptom stage in mice could delay or even prevent disease progression. To do that, the researchers introduced the altered huntingtin gene to the neurons in mice at 2 months of age and evaluated the outcomes at 3 months of age (when no atrophy or motor deficits were present).

Remarkably, the researchers say, the cerebral arteriolar blood volume in mice with the altered huntingtin gene was This suggests that the altered cerebral blood volume during the pre-symptom stage in mice is most likely due to neuronal changes in either activity or metabolism.

"Our findings demonstrate that significant changes in arteriolar cerebral blood volumes occur before neurons start to degenerate and symptoms begin, further supporting the idea that altered cerebrovascular function is an early stage symptom in Huntington's disease," says Duan. She explains that these changes also indicate there's a pre-symptom therapeutic window in which to test interventions. While no animal model replicates all the symptoms of human Huntington's disease, this research offers an alternative system to study functional changes in the pre-symptom stage, she says.

Further validation of these findings in human clinical trials would facilitate development of efficient therapeutic interventions for patients with Huntington's disease before they start developing symptoms. "The goal is to delay or even conceivably prevent the manifestation of Huntington's disease altogether," says Duan.

Along with Duan, other researchers who contributed to the work are Hongshuai Liu, Chuangchuang Zhang, Jing Jin, Liam Cheng, Qian Wu, Zhiliang Wei, Peiying Liu and Christopher Ross from Johns Hopkins, and Jiadi Xu, Xinyuan Miao, Hanzhang Lu, Peter van Zijl and Jun Hua from the Kennedy Krieger Institute and Johns Hopkins.

Nature has a vast store of medicinal substances. "Over 50 percent of all drugs today are inspired by nature," says Gisbert Schneider, Professor of Computer-Assisted Drug Design at ETH Zurich. Nevertheless, he is convinced that we have tapped only a fraction of the potential of natural products. Together with his team, he has successfully demonstrated how artificial intelligence (AI) methods can be used in a targeted manner to find new pharmaceutical applications for natural products. Furthermore, AI methods are capable of helping to find alternatives to these compounds that have the same effect but are much easier and therefore cheaper to manufacture.

Target molecules of natural substances are potential drug targets

And so the ETH researchers are paving the way for an important medical advance: we currently have only about 4,000 basically different medicines in total. In contrast, estimates of the number of human proteins reach up to 400,000, each of which could be a target for a drug. There are good reasons for Schneider's focus on nature in the search for new pharmaceutical agents. "Most natural products are by definition potential active ingredients that have been selected via evolutionary mechanisms," he says.

Whereas scientists used to trawl collections of natural products on the search for new drugs, Schneider and his team have flipped the script: first, they look for possible target molecules, typically proteins, of natural products so as to identify the pharmacologically relevant compounds. "The chances of finding medically meaningful pairs of active ingredient and target protein are much greater using this method than with conventional screening," Schneider says.

Tested with a bacterial molecule

The ETH chemists tested their concept with marinopyrrole A, a bacterial molecule that is known to have antibiotic, anti-inflammatory and anti-cancer properties. However, there had been limited research into which proteins in the human body the natural substance interacts with to produce these effects.

To find possible target proteins of marinopyrrole A, the researchers used an algorithm they developed themselves. Employing machine learning models, the algorithm compared the pharmacologically interesting parts of marinopyrrole A with the corresponding patterns of known drugs for which the target proteins to which they bind are known. Based on the pattern matches, the researchers were able to identify eight human receptors and enzymes to which the bacterial molecule could bind. These receptors and enzymes are involved, among other things, in inflammation and pain processes and in the immune system.

Laboratory experiments confirmed that marinopyrrole A did in fact generate measurable interactions with most of the predicted proteins. "Our AI method is able to narrow down the protein targets of natural products with a reliability often in excess of 50 percent, which simplifies the search for new pharmaceutically active agents," Schneider says.

So we have the effect: now to create a cheap alternative

But the work of Schneider's research group was not over. If the findings about the target proteins of marinopyrrole A are to result in a useful treatment in the future, it is necessary to find a molecule that is easy to manufacture. After all, marinopyrrole A - like many other natural substances - has a relatively complicated structure, which makes laboratory synthesis time-consuming and expensive.

To search for a simpler chemical compound with the same effect, the ETH researchers used yet another algorithm they designed themselves. This AI program was tasked with being a "virtual chemist" and finding molecules that have similar chemical functionalities to the natural model despite having a different structure. According to the constraints of the algorithm, it also had to be possible to make the molecules in a maximum of three synthesis steps, ensuring easy, low-cost production.

New chemical structures with the same effect

To define the synthesis path, the software had access to a catalogue of over 200 starting materials, 25,000 purchasable chemical building blocks and 58 established reaction schemes. After each reaction step, the program selected as the starting material for the next step the variants that matched marinopyrrole A most closely in terms of functionalities.

In total, the algorithm found 802 suitable molecules, based on 334 different scaffolds. The researchers synthesized the best four in the laboratory and discovered that they actually behaved very similarly to the natural model. They had a comparable effect on seven of the eight target proteins identified by the algorithm.

Subsequently, the researchers investigated the most promising molecule in detail. X-ray structure analyses showed that the compter-generated compound binds to the active centre of a target protein in much the same way as known inhibitors of this enzyme. Despite its different structure, then, the molecule found by AI works using the same mechanism.

Effects on pharmaceutical research

"Our work proves that AI algorithms can be employed in a targeted manner to design active ingredients with the same effects as natural substances, but with simpler structures," Schneider says, adding: "This helps not only to manufacture new drugs, but also places us on the cusp of a potentially fundamental change in medical-chemical research." That is to say, the ETH research group's methods make it possible to find drugs that do the same things as existing drugs but are based on different structures. This could make it easier in future to design new unpatented molecular structures. There is currently intense debate regarding both the extent to which AI could be used to systematically circumvent patent protection and the possible patenting of molecules designed by "creative" AI. In any case, the pharmaceutical industry will have to adapt its research approach to a new rulebook.

A recent study by scientists from Japanese universities has shown that the shape of cell-derived nanoparticles, known as "extracellular vesicles" (EVs), in body fluids could be a biomarker for identifying types of cancer. In the study, the scientists successfully measured the shape distributions of EVs derived from liver, breast, and colorectal cancer cells, showing that the shape distributions differ from one another. The findings were recently published in the journal Analytical Chemistry.

Early detection of cancerous tumors in the body is essential for effective treatments. However, it is difficult to detect all types of tumors at an early stage, because detection methods differ among types of cancer, and some of the methods require painful medical procedures. It is thus vital to find methods that are painless and can detect multiple types of cancer.

Extracellular vesicles (EVs) are biological particles with a diameter of about 100 nanometers (nm) that are secreted from various cells and exist in body fluids like blood and urine. Notably, EVs contain biological molecules that carry information about the cells of the secretion sources. In addition, genetic materials contained in EVs are involved in communications among cells. This suggests that analyzing biological molecules in EVs present in body fluids could help to detect and identify some kinds of cancerous tumors in the body.

Previous studies had observed images of various shapes of EVs with electron microscopes. However, no technology existed to investigate the shapes of EVs distributed in body fluids, mainly because of difficulties in measuring the shape of nanomaterials in solution. In this context, a team of researchers from Kyushu University, Nagoya University, Osaka University, and Tokyo Medical University tried to investigate the shape of individual EVs in a fluid using a device that they had developed, which can analyze the shape of single particles in solution by measuring the change of ionic current flowing through pores of 200 nm in diameter when particles pass through there.

Using the device, the team successfully measured the shape of EVs derived from cultured liver, breast, and colon cancer cells, as well as from cultured normal breast cells, and found that their shape distributions differ from each other. For example, EVs derived from liver cancer cells include a mix of spherical particles and oval (like rugby balls) particles, whereas EVs from breast cancer cells consist solely of spherical particles.

The team then compared shape distributions of EVs in blood samples from breast cancer patients and non-cancerous individuals. The results showed that the shape distributions of EVs from the two groups differ from each other, indicating that measuring shape distributions of EVs in blood could distinguish patients with breast cancer from non-cancerous individuals.

"In this study, we found that measuring shape distributions of EVs in body fluids could identify the type of cancer," said Associate Professor Takao Yasui at the Nagoya University Graduate School of Engineering, one of the authors of the study.

The researchers note that measuring a greater variety of types of EVs will provide them with a more accurate idea of potential EV shape distributions as an index for cancer detection, screening, and diagnosis.

An international research team has found that despite being the world's leading cause of pain, disability and healthcare expenditure, the prevention and management of musculoskeletal health, including conditions such as low back pain, fractures, arthritis and osteoporosis, is globally under-prioritised and have devised an action plan to address this gap.

Project lead, Professor Andrew Briggs from Curtin University said more than 1.5 billion people lived with a musculoskeletal condition in 2019, which was 84 per cent more than in 1990, and despite many 'calls to action' and an ever-increasing ageing population, health systems continue to under-prioritise these conditions and their rehabilitation requirements.

"One of the limiting factors to reform efforts is that no global-level strategic response to the burden of disability has been developed - until now. This novel data-driven initiative will be critical to guiding global-level work in health reform, such as that undertaken by the World Health Organization," Professor Briggs said.

"Addressing musculoskeletal health requires more than just healthcare reform - it requires inter-ministerial prioritisation and co-operation and collaboration with industry, transport and the built environment."

In response to a targeted call by the Global Alliance for Musculoskeletal Health (G-MUSC) headquartered at the University of Sydney, the international team of researchers mapped the current global landscape for the prevention and management of musculoskeletal health, identified current trends in national health policies and developed a blueprint to prioritise musculoskeletal health reform efforts in eight key areas.

Professor Lyn March from the University of Sydney said the blueprint was structured around critical areas for health systems reform, including community education; leadership and governance; health financing models; service delivery models that support integrated and person-centred care; equitable access to medicines and technologies; building capacity in the health workforce to deliver the right care at the right time; population health surveillance; and research and innovation.

"Each area is supported by detailed actions and priorities that countries may choose to adopt to build capacity in their health systems," Professor March said.

"Importantly, the blueprint is informed by people who work across all areas of health, and, critically, people with lived experience of musculoskeletal conditions.

"This blueprint is practical and can inform what a global strategic response might look like and how countries can respond to musculoskeletal health in order to arrest the increasing global burden of disability and cost."

Professor Helen Slater from Curtin University said the blueprint was developed with input from a panel of almost 700 stakeholders from 72 countries, representing 116 organisations.

"The research found global-level guidance, such as from the World Health Organization, is needed for country-level responses on musculoskeletal health and this blueprint provides that guidance which countries, including low and middle-income countries, can then adapt to suit local needs and priorities," Professor Slater said.

The work will now be considered by global agencies such as WHO and shared widely across countries, organisations and disciplines so that musculoskeletal health is integrated with other health reform initiatives in lifecourse and ageing, rehabilitation, non-communicable disease, and injury and trauma.

The project was funded by the Bone and Joint Decade Foundation, with additional funding provided by Curtin. The international team of researchers are from: Curtin University; Kolling Institute and University of Sydney; University of Toronto; Canadian Memorial Chiropractic College, Kathmandu University and the University of Southern Denmark.

Two research papers will be published in Global Health Research and Policy and BMJ Global Health and the resulting report 'Towards a global strategy to improve musculoskeletal health' will be published on the Global Alliance for Musculoskeletal Health website.

BOSTON - The numbers of cancer screening tests rebounded sharply in the last quarter of 2020, following a dramatic decline in the first months of the COVID-19 pandemic, at one large hospital system in the Northeastern United States. These findings were released in a study published in Cancer Cell. The research also found an increase in racial and socioeconomic disparities among users of some screening tests during the pandemic.

Study co-senior author Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, said following a dramatic decline during the first pandemic peak, there was a "substantial increase in screening procedures during the more recent periods with numbers exceeding those seen before the pandemic. However, racial disparities appear to differ between screening procedures, and are more marked in patients undergoing mammography."

"Early screening and diagnosis provide patients with the best chance for cancer cure--a widened racial gap in cancer screening due to COVID-19 will exacerbate existing racial disparities in cancer mortality," adds Quoc-Dien Trinh, MD, co-director of the Dana-Farber/Brigham and Women's Prostate Cancer Center, co-leader of the Mass General Brigham United Against Racism prostate cancer outreach clinic, and co-senior author on the study.

During September to December 2020, cancer screening rates for breast, prostate cervical, and lung cancer recovered and exceeded numbers seen before the pandemic, the study authors said. However, the recovery was not seen in colonoscopy screening to detect colorectal cancer.

"Colonoscopy did not get back to normal levels," said Chris Labaki, MD, of Dana-Farber, co-first author of the study. One reason may be that it is the most invasive of the tests, requiring hospital and anesthesia services, the authors suggested. The investigators also noted that some patients who would have undergone colonoscopies to screen for colorectal cancer may have opted for alternative, home-based methods such as tests for occult blood in stool.

In addition to the pandemic's temporary stifling of routine cancer screening, the researchers also found an increase in racial and socioeconomic disparities with some screening tests. Significant shifts in the racial distribution of patients undergoing mammography were revealed in the decreased numbers of Non-Hispanic Black and Hispanic patients having mammographies during the period September to December 2020 compared to the three months preceding the pandemic. This contrasted with an increase in mammography tests in the whole group of patients during the last quarter of 2020, according to the study. "These findings are concerning and suggest the pandemic may accentuate racial disparities related to cancer screening," the authors noted.

The racial proportions of patients undergoing screening during the pandemic remained stable for PSA, colonoscopy, Pap test, and CT scanning for lung cancer, compared to the pre-pandemic periods.

The study was based on records of the Mass General Brigham system, a large healthcare system in the Northeast -- a region that had experienced a sharp decline in screening during the early months of the pandemic. A decrease in numbers of screening tests during March to June 2020 and June to September 2020 ranged from minus 65% to minus 82% and minus 4% to minus 44%, respectively, depending on screening type.

The reduction in tests initially in 2020 and the resurgence in the last quarter of 2020 was accompanied by changes in diagnoses of cancer: only 1,985 positive tests were reported during the early pandemic (March-June 2020) compared to 3,476 positive tests in the September-December period.

Statisticians calculated that 1,187 diagnoses were "missed" from March to June 2020 because of reduced use of screening. Of those, 323 were "recovered" from September to December 2020, although the study did not note whether the cancers were found at later stages. For colonoscopy, no diagnoses were "recovered" and 38 positive diagnoses were "missed" across the three pandemic periods analyzed.

"The increase in screening tests that was identified from September to December 2020 helped to recover some of the "missed" cancer diagnoses from earlier time periods," Labaki added. "However, more efforts are still needed to ensure the implementation of large screening campaigns as a significant proportion of cancers remains undiagnosed." The delays in diagnosis are expected to cause adverse oncologic outcomes, the researchers say.

"We don't want to miss out on cancer screenings," Choueiri emphasized. "We would want patients to come back to discuss with us and their primary care providers and to embark on screening following the national COVID-19 pandemic guidelines."

Dutch-French research shows that Optical Genome Mapping (OGM) detects abnormalities in chromosomes and DNA very quickly, effectively and accurately. Sometimes even better than all existing techniques together, as they describe in two proof-of-concept studies published in the American Journal of Human Genetics. This new technique could radically change the existing workflow within cytogenetic laboratories.

Human hereditary material is stored in 46 chromosomes (23 pairs). Although those chromosomes are quite stable, changes in number or structure can still occur. A well-known example is Down syndrome, which is caused by an extra chromosome 21 (trisomy 21). An extra chromosome makes a big difference and is quite easy to visualize. But all kinds of other, smaller changes can occur as well in chromosomes. Sometimes pieces of DNA are lost (deletions), sometimes a piece is just repeated (duplication) or it is moved to another place (translocation). An existing piece can also be turned over (inversion) and sometimes new pieces are inserted (insertions). All these structural abnormalities in the chromosomes can cause disease, either congenital genetic diseases, which are present from birth, similar to Down syndrome, or acquired disorders, when the change occurs in a few cells during life which can lead to cancer, such as in leukemia.

Optical Genome Mapping

Cytogenetics is the genetic discipline that examines chromosomes for such abnormalities. To visualize both the large and small changes, several complementary techniques are needed, such as FISH, karyotyping and Copy Number Variant (CNV) microarrays. These are often laborious techniques that individually can only visualize a part of the above-mentioned abnormalities. Recently a new technique has become available - Optical Genome Mapping - which more or less brings together the previous techniques. But new techniques must prove themselves in practice. At Radboud University Medical Center (Radboudumc), Alexander Hoischen, associate professor of Genomics Technologies and Immuno-Genomics, researches new techniques for usability in clinical research and possibly later in patient care. It requires close cooperation between Radboudumc and the industry involved in building latest genomic technologies, in this case the America-based company Bionano Genomics.

Two advantages

Hoischen immediately mentions two major advantages of OGM: "We can now look at extremely long stretches of DNA, so there's fewer pieces needed to map the entire chromosome. It's faster and produces fewer errors. Furthermore, unlike the other techniques, we do not have to pre-process or manipulate the DNA, so we look at the real, 'natural' DNA. In short: what you see is what you get."

Automatic, objective, digital

Bionano has created a label that attaches to a specific piece of DNA that occurs very often, but irregularly. The ever-changing distances between the labels create a unique barcode so researchers always know exactly where they are situated in the DNA. This labeled DNA is pulled through thin long nanochannels, while a camera continuously takes pictures. Hoischen: "In this way we can automatically, objectively and digitally record DNA at a rapid pace, and at a resolution that is 10,000 times higher than in karyotyping. It's a kind of 'cytogenetics on steroids' because of its power and speed."

Hereditary disorders

But how well does the technology work? Two papers in the American Journal of Human Genetics give a positive answer. Dr. Laïla El Khattabi of the Université de Paris, Alexander Hoischen, and their colleagues, tested OGM on 85 samples from patients with a hereditary disorder that had previously been examined with the standard tests (karyotyping, FISH, CNV microarray). Remarkable and exceptional: OGM found them all. El Khattabi: "OGM can really revolutionize the detection of chromosomal aberrations. I think it could be the most significant technological breakthrough in the history of cytogenetics since the CNV microarray."

Early adapters

In the second paper, the team of Nijmegen researchers again compared the technique to the standard tests. This time they looked at the DNA of leukemia cells of 52 patients with leukemia, a hematological malignancy. Here too, OGM performed optimally by detecting all clinically known deviations. And even more than that. In a number of cases, the technique provided better and more accurate analyzes of chromosomal abnormalities. This is rather important, because the right treatment often depends on this. Hoischen: "We are early adapters of different genome technologies, often with the aim of quickly applying them routinely in the clinic. The very convincing data in these two proof-of-concept studies again place Radboudumc at the forefront of technical innovation for healthcare in human genetics. This 'Next Generation Cytogenetics' could replace decade old routine testing, vastly improving workflow and patient care." This is echoed by Dr. Marian Stevens-Kroef, Clinical Laboratory Geneticist for hematological malignancies: "OGM promises to greatly improve cytogenetic testing in patients with hematological malignancies."

Further roll out

Radboudumc researchers Dr. Kornelia Neveling and Dr. Tuomo Mantere, first authors in both studies, are also positive about the technique. Neveling: "It is a rather simple technology, for both the wet lab and data analysis, and we foresee great advantages for a use in a clinical setting. In addition, OGM has already helped to solve several medical mysteries, some of which have been waiting for answers for more than 20 years."

Tuomo Mantere, former postdoc in Alexander Hoischen's laboratory and now affiliated with Oulu University in Finland: "The easy implementation of this technique and the convincing concordance with the standard cytogenetic methods as presented in these two studies convinced me to set up OGM now in Finland as well."

Prostate cancer is the most diagnosed cancer and a leading cause of death by cancer in Australian men.

Early detection is key to successful treatment but men often dodge the doctor, avoiding diagnosis tests until it's too late.

Now an artificial intelligence (AI) program developed at RMIT University in Melbourne, Australia could catch the disease earlier, allowing for incidental detection through routine computed tomography (CT) scans.

The tech, developed in collaboration with clinicians at St Vincent's Hospital Melbourne, works by analysing CT scans for tell-tale signs of prostate cancer, something even a well-trained human eye struggles to do.

CT imaging is not suitable for regular cancer screening because of the high radiation doses involved, but the AI solution could be used to run a cancer check whenever men have their abdomen or pelvis scanned for other issues.

RMIT's Dr Ruwan Tennakoon said CT scans were great for detecting bone and joint problems but even radiologists struggled to spot prostate cancers on the images.

"We've trained our software to see what the human eye can't, with the aim of spotting prostate cancer through incidental detection," he said.

"It's like training a sniffer dog - we can teach the AI to see things that we can't with our own eyes, in the same way a dog can smell things human noses can't."

Prostate cancer is slow growing and is usually detected incidentally, so can go undiagnosed for years. In 2020, it was responsible for an estimated 12% of male cancer deaths in Australia.

*How it works*

For the study, published in Nature's Scientific Reports, researchers from RMIT and St Vincent's Hospital Melbourne studied CT scans of asymptomatic patients, with and without prostate cancer.

The team trained the AI software to look for features of disease in a variety of scans and where exactly to look for them, avoiding the need to manually crop the images.

The AI performed better than radiologists who viewed the same images, detecting cancerous growths in just seconds.

What's more, the AI improved with each scan, learning and adapting to read images from different machines to spot even the smallest irregularities.

RMIT's Head of Artificial Intelligence, Professor John Thangarajah, said the study demonstrated how AI can and should be used to create public good.

"Our health sector needs smarter solutions and AI can help, but we're only scratching the surface," he said.

"There's a lot of good that artificial intelligence can bring to the world, which is our focus at RMIT, and this study forms a big part of that."

Dr Mark Page, Head of CT in Diagnostic Imaging at St Vincent's Hospital Melbourne, said early intervention for prostate cancer was key to a better health outcome.

"Australia doesn't have a screening program for prostate cancer but armed with this technology, we hope to catch cases early in patients who are scanned for other reasons," he said.

"For example, emergency patients who have CT scans could be simultaneously screened for prostate cancer.

"If we can detect it earlier and refer them to specialist care faster, this could make a significant difference to their prognosis."

The technology can be applied at scale, potentially integrating with a variety of diagnostic imaging equipment like MRI and DEXA machines - pending further research.

"It was excellent to tap into the AI expertise at RMIT and we look forward to future possibilities for analysing more radiology scans," Page said.

The multi-disciplinary team, including researchers from RMIT's School of Engineering and School of Computing Technologies, is looking for interested commercial partners to develop software to further integrate the AI technology with hospital equipment for possible clinical trials.

July 7, 2021 - The murders of George Floyd and other Black Americans have prompted a national outcry against structural racism and police brutality. How are leading nursing organizations and schools of nursing defining their positions on racism? That's the topic of a special article in the July/August issue of The Journal of the Association of Nurses in AIDS Care (JANAC). The official journal of the Association of Nurses in AIDS Care, JANAC is published in the Lippincott portfolio by Wolters Kluwer.

Three major national nursing organizations and many top-ranked schools of nursing have issued position statements on racism in the past year, according to the report by Amelia Knopf, PhD, MPH, RN, FAAN, of Indiana University, Indianapolis, and colleagues. These statements "assert an organizational or institutional commitment to confronting racism and provide direction for nurses to engage in anti-racist actions," the researchers write.

'A unified response from the nursing profession'
Over a three-month period in 2020, Ahmaud Arbery, Breonna Taylor, and George Floyd - three unarmed Black Americans - were killed during responses to alleged criminal activity. These events spurred a massive series of anti-racism protests, a major social movement that has "shed a glaring light on the criminal justice system as a racist structure," according to the authors.

"This movement also provided a call to action to dismantle other racist structures, including those that permeate the health care system," Dr. Knopf and colleagues add. In the new paper, they analyze key ideas set out by position statements issued by three prominent national professional nursing organizations: the American Nurses Association (ANA), American Academy of Nursing (AAN), and American Association of Colleges of Nursing (AACN).

Thematic analysis revealed that "these national bodies responded in a timely and consistent manner...[providing] direction for a unified response from the nursing profession." The statements addressed six key themes:

Condemnation of police brutality: Sending "a clear message that injustice and racism will no longer be tolerated" (AACN)

Acknowledgement of the effects of racism on health: Recognizing racism as "a public health crisis that impacts the mental, spiritual, and physical health of all people" (ANA)

Calls to combat racism: Pledging to "oppose and address all forms of racism and discrimination" (ANA)

Calls to end systemic racism: Opposing the "institutional structures and processes that can block openness and prevent change" (AAN)

Calls to stand by or support those working against racism or discrimination: Calling for "action to change structures and policies that have enabled and permitted senseless violence to occur" (AAN)

Calls for respect for all persons: Speaking "with one strong voice as leaders and role models of compassion and empathy for our patients, families, communities and most importantly towards one another" (ANA)

The researchers then analyzed position statements by top-ranked US schools of nursing. Of 32 schools of nursing included in the review, 18 had issued statements on racism. Most were "well-aligned" with national statements, addressing at least two and up to six of the key themes.

However, the school of nursing position statements varied significantly. Although most addressed systemic racism, several avoided comments that might be considered "controversial" - such as references to White supremacy as the foundation of racism, support for protests and the Black Lives Matter movement, and calls for substantial policing reforms.

"[W]hile position statements are a viable approach to the public assertion of commitment to anti-racist reforms by schools of nursing, it remains unclear if and how such statements can promote meaningful and measurable changes," Dr. Knopf and colleagues conclude. "These calls must be accompanied by efforts that support lasting reform."

Click here to read "A Review of Nursing Position Statements on Racism Following the Murder of George Floyd and Other Black Americans."

DOI: 10.1097/JNC.0000000000000270

As the COVID-19 pandemic wanes in the U.S., a new study from the University of Maryland School of Medicine (UMSOM) and University of Maryland Medical Center (UMMC) finds that hospitals nationwide may not be adequately prepared for the next pandemic. A 10-year analysis of hospitals' preparedness for pandemics and other mass casualty events found only marginal improvements in a measurement to assess preparedness during the years leading up to the COVID-19 pandemic. The study was published last month in the Journal of Healthcare Management.

"Our work links objective healthcare data to a hospital score that assesses the ability to save lives in a disaster," said study lead author David Marcozzi, MD, Professor of Emergency Medicine at UMSOM and Chief Clinical Officer/Senior Vice President at UMMC. "It attempts to fill a glaring gap in the national conversation on the need for improved assessments of and the opportunity for better hospital planning to assure readiness."

To conduct the research, Dr. Marcozzi, who is also the COVID-19 Incident Commander for the University of Maryland Medical System, and his colleagues first developed and published a surge index tool that linked standard reported hospital information to healthcare preparedness elements.  The tool, called the Hospital Medical Surge Preparedness Index (HMSPI), used data from 2005 to 2014 to produce a score designed to predict how well a hospital can handle a sudden influx in patients due to a mass shooting or infectious disease outbreak.  Such data included the size of the medical staff, the number of hospital beds, and the amount of equipment and supplies.

Medical surge capacity is an important measure to assess a hospital's ability to expand quickly beyond normal services to meet an increased demand for healthcare. The Las Vegas mass shooting in 2017, for example, sent more than 500 concertgoers to local hospitals. During the early weeks of the COVID-19 pandemic, New York City hospitals were under siege with 4,000 patients hospitalized. To calculate the HMSPI, researchers input data from four important metrics.

Staff: Doctors, nurses, pharmacists, respiratory technicians and others

Supplies: Personal protective equipment, cardiac monitors, sterile bandages, and ventilators

Space: Total beds and number of beds that current staff can handle

Systems: Framework for enabling electronic sharing of files and information between departments and multiple hospitals

In the new study, Dr. Marcozzi and his colleagues used data from the American Hospital Association's annual surveys of more than 6,200 hospitals nationwide that were collected from 2005 to 2014. They also employed data from the U.S. Census Bureau to determine population estimates in cities and the Dartmouth Atlas Project to establish the geographic service area of each hospital. They combined the hospital metrics gleaned from the AHA's annual surveys with the geographic data to calculate HMSPI composite scores for hospitals in each state.

Their evaluation found varying levels of increases in HMSPI scores from 2005 to 2014 in every state, which could indicate that states are becoming better prepared to handle a medical surge. The scores also indicated that ideal readiness had not yet been achieved in any state before the COVID-19 pandemic.

"This is just the starting point. We need to better understand the ability of our nation's hospitals to save lives in times of crisis," said Dr. Marcozzi.  This information, and follow-up studies building from this work, will be key to better matching states' healthcare resources to their population to assure optimal care is delivered.  Dr. Marcozzi described one follow-up study that would be impactful would be to use data from the COVID-19 pandemic to see whether the index was predictive to indicate which hospitals were most prepared for the pandemic surge based on their patient outcomes.

"This pioneering work is a needed advancement that could allow for a transparent assessment of a hospital's ability to save lives in a large-scale emergency," Dr. Marcozzi said. "The COVID-19 pandemic demonstrated that there is still plenty of room for improvement in the ability of our nation's healthcare system to triage and manage multiple patients in a crisis and that translates into lives lost, unnecessarily. Our research is dedicated to those who lost their lives in this tragedy and other mass casualty events. We can do better."

National health leadership organizations, such as the U.S. Centers for Medicare and Medicaid Services, the Assistant Secretary for Preparedness and Response, the Joint Commission, and the American Medical Association, as well as state and local emergency planners, could all potentially benefit from the use of HMSPI scores, according to Dr. Marcozzi. The tool could be used to support data-driven policy development and resource allocation to close gaps and assure that individuals get the care they need, when then need it, during a crisis.

Ricardo Pietrobon, MD, PhD, MBA, Adjunct Associate Professor of Emergency Medicine at UMSOM, Nicole Baehr, Manager of Operations at UMMC, and Brian J. Browne, MD, Professor and Chair of the Department of Emergency Medicine, were co-authors on this study. Researchers from the University of Nebraska Medical Center, University of Miami, and the U.S. Department of Veterans Affairs also participated in this research. The study was funded by the Bipartisan Commission on Biodefense.

"The COVID-19 pandemic taught us that we need to be better prepared for the unexpected crisis," said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. "Having an important metric like the HMSPI could be a game changer that ultimately saves lives during a surge by helping hospitals identify and fix their vulnerabilities.

As more evidence emerges that opioid overdose deaths have increased dramatically since the onset of COVID-19, the Centre for Addiction and Mental Health (CAMH), in collaboration with subject matter experts and medical regulatory authorities across Canada, have now released updated national clinical guidelines for the treatment of opioid use disorder. Opioid Agonist Therapy: A Synthesis of Canadian Guidelines for Treating Opioid Use Disorder, harmonizes existing provincial and national guidelines, evidence-based practices, and expert opinions into one document aimed at providing consistent and high-quality care to people with opioid use disorder.

First-line treatment for those with opioid use disorder is opioid agonist therapy (OAT). This includes providing a medication that keeps the person out of withdrawal, reduces their cravings and prevents overdose deaths should they relapse. These medications are the most effective treatment option for opioid use disorder, and are scientifically proven to save lives, even when people use fentanyl. When combined with counselling and addressing the social causes and consequences of addiction, the person can make a full recovery and get back to living their lives. OAT is a long-term treatment and it can take some people a few tries before they get better completely.

"COVID has drastically changed the situation on the ground across Canada in regards to the opioid crisis and these need to be living guidelines that can be updated as circumstances change and new evidence evolves," said Dr. Peter Selby, Clinician Scientist, Addictions Division, and CAMH lead for this initiative. "For example, we wanted to change some of the old rules that were making it hard to provide person-centred care and help people stay in treatment. That is key because the longer people are in treatment the better they recover and the less likely they are to die from an opioid overdose."

The new guidelines are updated with the most up-to-date information and clinically-proven strategies to help patients overcome opioid addiction. These include updated medication delivery options, such as offering injectables, and expanding the list of medications for those who don't respond to traditional treatments. The guidelines also feature less regulatory restriction and new strategies to combat stigma to make treatment adherence easier.

"OAT, like any other substance use treatment, needs to meet every patient's individualized needs and goals," added Dr. Narges Beyraghi, CAMH Addictions Psychiatrist. "The recovery journey is different for every individual and they may connect to different components of care during this process. This updated guideline has tried to be inclusive to a patient's gender, age and other physical and mental health problems that could be a barrier to access to care or equitable care."

A CAMH study released in April found that a large number of people who were regular opioid users when the pandemic began reported heightened fears of dying from an overdose, in large part because of disruptions in the supply of street drugs that made drugs more expensive, harder to get and of unknown origin or potency. Lockdown measures across the country also increased the risk that people would use alone without anyone to help them in the event of an overdose. This risk was compounded by reduced access to harm reduction services like safe injection centres. All of these factors led experts to fear that the COVID pandemic would make the opioid crisis more deadly, and new numbers recently released by Ontario Public Heath confirmed those fears, with a 60 per cent increase in opioid deaths reported.

Dr. Marina Reinecke, Medical Consultant, Prescribing Practices Program, The College of Physicians & Surgeons of Manitoba, said: "Opioid use disorder affects a large and diverse group of Canadians. In Manitoba, our patients live in urban, rural and remote locations and have diverse care needs. These needs often collide with inequitable access to health care services. This compounds the tragedy associated with this very treatable disease. These guidelines provide evidence-based guidance and practical information for frontline clinicians in every care setting, empowering them to bring hope and health to Canadians where they live."

"However, guidelines alone don't change practice," added Dr. Beyraghi. "What does change practice is a combination of policy changes to address structural and societal stigma and education. We have several courses at CAMH that help providers acquire and improve their skills in treating people with opioid use disorder in a humane and respectful manner. We also have great resources for people who use opioids and their loved ones to make a science-based informed choice about treatment."

DALLAS, July 7, 2021 -- Myocarditis in children is a rare yet challenging condition to treat. Diagnosis and treatment includes multiple options, and many cases of myocarditis resolve on their own, according to a new scientific statement from the American Heart Association, "Diagnosis and Management of Myocarditis in Children," published today in Circulation, the Association's flagship journal. The scientific statement writing group reviewed the latest research to develop guidance in diagnosis and treatment for myocarditis in children.

Myocarditis is inflammation of the middle layer of the wall of the heart muscle, the myocardium, and it can temporarily or permanently weaken the heart muscle and the heart's electrical system, which keeps the heart pumping regularly. Approximately 10 to 20 per 100,000 people are diagnosed with myocarditis in the U.S. annually, and in children, the incidence is 1 to 2 per 100,000. Although many cases resolve on their own or with treatment, leading to a full recovery, severe myocarditis can lead to heart failure, abnormal heart rhythms, shock and sudden death. Signs and symptoms of myocarditis include fatigue, shortness of breath, fever, chest pain and palpitations .

"Myocarditis has distinct characteristics in children and a potential impact on their lifelong health," said Yuk M. Law, M.D., FAHA, chair of the scientific statement writing group, director of Cardiac Transplant and Heart Failure Service at Seattle Children's Hospital and professor of pediatrics at the University of Washington School of Medicine in Seattle. "We hope that this statement serves as an educational update as well as a unifying call for much needed research to better understand and treat this important pediatric condition. And, in light of the recently recognized occurrence of myocarditis after COVID-19 infection, as well as the emergence of cases of suspected myocarditis after COVID-19 vaccination, this statement is a resource for clinicians and health care professionals in caring for these patients."

Direct tissue examination from a biopsy is the standard for proving the presence of myocarditis, which can also identify if viruses are present. However, less invasive testing is widely available now. Additional screening tests for myocarditis may include blood tests to measure for elevated cardiac enzymes that would indicate heart inflammation or injury, including myoglobin, troponin and creatine kinase. Imaging tests include an echocardiogram or a cardiac magnetic resonance imaging (MRI) to determine if there is any visible injury to the heart or abnormalities in how the heart is functioning. Electrocardiography (ECG) screening can assess the heart rhythm and may show signs of injury to the heart as well as signs of pericarditis. Pericarditis is often related to myocarditis and involves swelling and inflammation of the pericardium, a thin, sac-like tissue structure that surrounds the heart to hold it in place and help it function properly.

Key guidance in the statement includes:

The incidence of myocarditis in children varies with age, being higher in infants and rising again in young adults.

Patients should not participate in competitive sports while active inflammation is present. In addition to normalization of inflammatory and myocardial injury markers, as well as ventricular function and heart failure, 24-hour Holter monitoring and exercise stress testing should be performed in athletes no sooner than 3 to 6 months after diagnosis and before they return to competition.

In children, myocarditis is most often the result of a viral infection, and it is most often acute or sudden-onset, rather than chronic myocarditis, which is seen more often in adults.

Symptoms in children can range from minimal to showing signs of heart failure, life-threatening arrhythmias or cardiogenic shock.

The most common symptoms of myocarditis in children include fatigue, shortness of breath, abdominal pain and fever. (Of note, the primary symptom reported in patients with COVID-19 vaccine-associated suspected myocarditis is chest pain.) However, it is important to consider alternative causes of these symptoms since none of them are specific to cardiovascular conditions including myocarditis.

Acute myocarditis can deteriorate rapidly, therefore, close monitoring in an inpatient setting should be considered.

The early phase of care should include monitoring for atrial or ventricular arrhythmias. The management of arrhythmia is addressed in the 2017 AHA/ACC/HRS Guideline for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death.

Acute myocarditis may lead to myocardial injury similar to a heart attack. Early intervention with mechanical circulatory support (MCS) should be considered for high-risk patients and can be lifesaving.

Treatment with antiviral and immunotherapies including intravenous immunoglobulin and corticosteroids is common; however, additional evidence-based research is needed to define these treatments more clearly for children.

Antiviral therapy should be considered if an active viral infection is found.

Myocarditis can also be seen secondary to systemic autoimmune diseases and is associated with rheumatic fever or Kawasaki disease. In these cases, it should be managed according to the guidance for the primary disease.

A new condition has emerged during the COVID-19 pandemic - multisystem inflammatory syndrome in children (MIS-C) - that involves the myocardium and coronary arteries in some infected patients. Therapy may consist of antiviral, IVIG (intravenous immunoglobulin), steroid and other anti-inflammatory medications used in atypical Kawasaki disease.

Regular cardiology follow-up including ECG, echocardiography and laboratory tests are recommended initially every 1 to 3 months after onset, then as needed.

"While our work on this scientific statement preceded the COVID-19 pandemic and the cases of suspected myocarditis after COVID-19 vaccination and after COVID-19 infection being reported in adolescents and young adults, the guidance detailed in this scientific statement can help to advise treatment for these patients as well," Law said.

Specific to the suspected cases of myocarditis after COVID-19 vaccination in teens and young adults recently reported and continuing to be monitored by the U.S. Centers for Disease Control and Prevention (CDC), the following statement reflects the views of the American Heart Association/American Stroke Association and its science leaders:

President Donald M. Lloyd-Jones, M.D., Sc.M., FAHA,

Immediate Past President Mitchell S.V. Elkind, M.D., M.S., FAHA, FAAN,

President-Elect Michelle A. Albert, M.D., M.P.H., FAHA,

Past President Robert A. Harrington, M.D., FAHA,

Chief Science and Medical Officer Mariell Jessup, M.D., FAHA,

Chief Medical Officer for Prevention Eduardo Sanchez, M.D, M.P.H., FAAFP, and

Chair of the Young Hearts Council Shelley Miyamoto, M.D., FAHA.

"The American Heart Association/American Stroke Association recommends all health care professionals be aware of rare adverse events that may be related to a COVID-19 vaccine including myocarditis. Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with symptoms related to cardiovascular conditions, as needed, in order to confirm the diagnosis and to provide appropriate treatment quickly. As indicated by the CDC, we agree that cardiologists should be consulted if myocarditis or any heart-related condition is suspected by a primary care clinician.

"This new scientific statement provides a thorough examination of the latest research on the diagnosis, treatment and follow-up for myocarditis in children prior to the COVID-19 era and confirms that myocarditis is a serious yet uncommon condition in children. The effects of COVID-19 infection include its potentially fatal consequences and the potential long-term health effects that are still revealing themselves, such as conditions affecting the heart including myocarditis, the brain, the vascular system and other organs.

"We remain steadfast in our recommendation for all adults and children ages 12 and older in the U.S. to receive a COVID-19 vaccine as soon as they can receive it, as authorized by the U.S. Food and Drug Administration and recommended by the CDC. Overwhelmingly, data continue to indicate that the benefits of COVID-19 vaccination - 91% effective at preventing complications of severe COVID-19 infection including hospitalization and death - far exceed the very rare risks of adverse events, including myocarditis."

Oncotarget published "Association between miRNA signatures in serum samples from epidermal growth factor inhibitor treated patients and skin toxicity" which reported that on average 70% of patients treated with EGFRIs suffer from skin toxicity.

Studies showed a correlation between overall survival and the appearance of a skin rash, which is used as a biomarker for therapy efficacy.

In this study, the authors searched for associations of miRNA expression profiles in serum, with the severity of skin rash, in order to identify tentative therapy predictive biomarkers.

In this cohort of patients treated with EGFR inhibiting monoclonal antibodies, miR-21 and miR-520e serum concentrations were negatively correlated with severity of skin rash whereas for miR-31, a positive correlation was observed.

This Oncotarget study suggests that miR-21, miR-31 and miR-520e expression might be a treatment dependent marker for EGFRI induced skin rash.

This Oncotarget study suggests that miR-21, miR-31 and miR-520e expression might be a treatment dependent marker for EGFRI induced skin rash.

Dr. Julia Carolin Stingl from The University Hospital of the RWTH Aachen said, "Epidermal growth factor receptor inhibitors (EGFRI) belong to the so called targeted cancer therapy and are used for the treatment of different cancer types like non-small-lung-cancer (NSLC), head-and-neck-cancer (head-and-neck-ca), colon-rectal-cancer (colon-ca) and pancreas-cancer (pancreatic -ca)"

But with all these possible treatments of EGFRI induced skin rash, its treatment predictive value might get lost and new biomarkers will be needed.

EGFR ligands like epiregulin, amphiregulin, and hepatocyte growth factor were investigated as biomarkers for skin rash and found to be inversely proportional to grades of skin toxicity.

Within the scope of this study, different aspects of the EGFRI-induced skin rash were investigated, all with the objective to better understand EGFRI induced skin rash and find predictive biomarkers.

However, so far most of the studies in cancer patients focused on miRNAs expressed in cancer cells or secreted into body fluids most likely by cancer cells, while miRNAs associated with the skin rash have not been investigated.

To elucidate the influence of miRNAs in the development of skin rash these authors previously investigated the miRNA expression in fibroblasts incubated with and without erlotinib.

The Stingl Research Team concluded in their Oncotarget Research Output that the biggest limitation might be that there are no serum samples from patients before they were treated with an EGFR inhibitor.

Hence, the authors cannot say if the effects we found are mostly due to the therapy with an EGFRI or if those effects can be seen in patients in general.

However, because of the heterogeneity of the cohort concerning the tumor type and cancer state, a treatment specific effect is possible.

Still these miRNAs give us a better understanding about the skin rash, which can be used for further investigations.

* Clinical trial at University of Warwick compares the familiar cast, traditionally signed in sympathy, to modern removable brace for immobilising broken ankles
* Cast was not more effective, with patients reporting similar levels of pain and functionality, suggesting that choice should be down to patient preference and cost effectiveness
* Some data suggested a patient preference for the removable brace - sometimes referred to as the 'Beckham boot' after David Beckham

Using a cast is not more effective than a brace for treating broken ankles, according to University of Warwick researchers - a conclusion that could hasten the decline of the tradition of signing a cast.

With little difference in the clinical effectiveness of either method, the researchers conclude that the choice of which to use should be down to cost and patient preference, with some evidence suggesting that the flexibility of the removable brace could prove more appealing to patients.

The research reports the results of the Ankle Injury Rehabilitation (AIR) Trial at Warwick Clinical Trials Unit at the University of Warwick, and is published today (6 July) in The BMJ. This four-year trial funded by the National Institute for Health Research (NIHR) aimed to compare cast to functional brace in the treatment of individuals with an ankle fracture.

Ankle fractures are very common and tend to occur when you land on your foot and twist it. They are most commonly related to sports, traffic accidents or falls in older people, though it is an injury that everyone is susceptible to. Not all ankle fractures will require surgery, but in all cases patients will need to keep their foot immobilised typically for a period of around 6 weeks to allow the bones to heal.

As part of the AIR trial, 669 patients were randomly given either a cast (334 patients) or removable brace (335 patients) to immobilise their foot following an ankle fracture. Those with the brace were given information advising them to take the boot off around three times a day and perform repetitions of ankle movement exercises. The cast group were not given specific ankle movement exercises from the trial as they were unable to remove their cast, nor move their ankle.

They were then followed up four months afterwards with a questionnaire that asked them if they had any pain or functional problems. Specifically, patients were asked about problems with pain when walking, stiffness, swelling, climbing stairs, running, jumping, squatting, use of supports and activities. Their answers were combined into a score called the Olerud Molander Ankle Score (OMAS), and these scores combined for each group and compared.

The research showed no statistically significant difference in the scores of those using a cast and those using a boot after four months. The results were also the same when comparing those who received surgery and those who didn't.

Lead author Professor Rebecca Kearney of Warwick Medical School at the University of Warwick said: "With cast not being better, it comes down to a decision on the cost of the interventions, patient preferences and if there's a difference in complications, which we did not find evidence of. Patients should discuss their preference with their clinician, who should take into account these factors.

"When people think of ankle fractures they think of the pain, swelling, and not being able to do things. But it has more far-reaching consequences than just the immediate physical limitations of a broken bone, which we're only just starting to appreciate."

Like many types of broken bone, ankle fractures have traditionally been treated by using the familiar cast that generations have signed their names on in sympathy. In more recent years, it has become just as common to use a removable brace - at one time referred to as the 'Beckham boot', after being popularised by former professional footballer David Beckham.

The brace is a plastic boot that comes in two halves with Velcro to wrap round and secure it. They're designed to be walked on and being removable allows patients to perform leg exercises and keep their leg clean.

Professor Kearney, who was supported by an NIHR Fellowship for this research, adds: "If you keep the ankle really still it allows the bones to heal up, but that's not great if all the joints around it stiffen up and all the muscles weaken. The idea behind the boot is that you can do movement exercises with the ankle and walk on it to encourage weight-bearing. In theory, that could result in decreased muscle wastage and joint stiffness. In practice though, it didn't result in better functional outcomes.

"It was also clear in the quantitative data that when patients swapped treatments, they swapped in predominantly one direction - from the cast to the brace."

An elegant new algorithm developed by Danish researchers can significantly reduce the resource consumption of the world's computer servers. Computer servers are as taxing on the climate as global air traffic combined, thereby making the green transition in IT an urgent matter. The researchers, from the University of Copenhagen, expect major IT companies to deploy the algorithm immediately.

One of the flipsides of our runaway internet usage is its impact on climate due to the massive amount of electricity consumed by computer servers. Current CO2 emissions from data centres are as high as from global air traffic combined - with emissions expected to double within just a few years.

Only a handful of years have passed since Professor Mikkel Thorup was among a group of researchers behind an algorithm that addressed part of this problem by producing a groundbreaking recipe to streamline computer server workflows. Their work saved energy and resources. Tech giants including Vimeo and Google enthusiastically implemented the algorithm in their systems, with online video platform Vimeo reporting that the algorithm had reduced their bandwidth usage by a factor of eight.

Now, Thorup and two fellow UCPH researchers have perfected the already clever algorithm, making it possible to address a fundamental problem in computer systems - the fact that some servers become overloaded while other servers have capacity left - many times faster than today.

"We have found an algorithm that removes one of the major causes of overloaded servers once and for all. Our initial algorithm was a huge improvement over the way industry had been doing things, but this version is many times better and reduces resource usage to the greatest extent possible. Furthermore, it is free to use for all," says Professor Thorup of the University of Copenhagen's Department of Computer Science, who developed the algorithm alongside department colleagues Anders Aamand and Jakob Bæk Tejs Knudsen.

Soaring internet traffic

The algorithm addresses the problem of servers becoming overloaded as they receive more requests from clients than they have the capacity to handle. This happens as users pile in to watch a certain Vimeo video or Netflix film. As a result, systems often need to shift clients around many times to achieve a balanced distribution among servers.

The mathematical calculation required to achieve this balancing act is extraordinarily difficult as up to a billion servers can be involved in the system. And, it is ever-volatile as new clients and servers join and leave. This leads to congestion and server breakdowns, as well as resource consumption that influences the overall climate impact.

"As internet traffic soars explosively, the problem will continue to grow. Therefore, we need a scalable solution that doesn't depend on the number of servers involved. Our algorithm provides exactly such a solution," explains Thorup.

According to the American IT firm Cisco, internet traffic is projected to triple between 2017 and 2022. Next year, online videos will make up 82 percent of all internet traffic.

From 100 steps to 10

The new algorithm ensures that clients are distributed as evenly as possible among servers, by moving them around as little as possible, and by retrieving content as locally as possible.

For example, to ensure that client distribution among servers balances so that no server is more than 10% more burdened than others, the old algorithm could deal with an update by moving a client one hundred times. The new algorithm reduces this to 10 moves, even when there are billions of clients and servers in the system. Mathematically stated: if the balance is to be kept within a factor of 1+1/X, the improvement in the number of moves from X2 to X is generally impossible to improve upon.

As many large IT firms have already implemented Professor Thorup's original algorithm, he believes that industry will adopt the new one immediately - and that it may already be in use.

About the study:

* The research article has just been presented at the prestigious STOC 2021 conference. A free version of the article can be read here: https://arxiv.org/abs/2104.05093

* Studies have demonstrated that global data centers consume more than 400 terawatt-hours of electricity annually. This accounts for approximately two percent of the world's total greenhouse gas emissions and currently equals all emissions from global air traffic. Data centre electricity consumption is expected to double by 2025.

* According to the Danish Council on Climate Change, a single large data centre consumes the equivalent of four percent of Denmark's total electricity consumption.

* Mikkel Thorup is head of the BARC research centre (Basic Algorithms Research Copenhagen) at the University of Copenhagen's Department of Computer Science. BARC has positioned Copenhagen as the world's fourth best place in basic research in the design and analysis of algorithms. BARC is funded by the VIILUM FOUNDATION.

* Read Vimeo Engineering Blog about the implentation of Mikkel Thorup's algorithm: https://medium.com/vimeo-engineering-blog/improving-load-balancing-with-a-new-consistent-hashing-algorithm-9f1bd75709ed