Culture

CHICAGO (July 2, 2020): Postoperative pain can pose a number of challenges for surgical patients and their care providers. A common method to treat pain has been to administer opioids. However, opioids come with a number of different, often intolerable, side effects, and surgeons have been actively looking for other, safer, pain-relieving options. To address postoperative muscle pain in patients undergoing abdominal surgery, researchers from Yonsei University College of Medicine, Seoul, South Korea, developed a new method of effective pain control called needle electrical twitch obtaining intramuscular stimulation (NETOIMS). The research team's findings appear as an "article in press" on the website of the Journal of the American College of Surgeons ahead of print.

According to study authors, surgical manipulation, such as retraction and suture, shortens skeletal muscle fibers, contributing to postoperative pain. The NETOIMS method effectively alleviates this pain by inserting a needle in the muscle and electrically eliciting twitch responses. NETOIMS targets the deep motor endplate zones of the skeletal muscles, targeting strained muscle fibers. This technique results in the stretching of the shortened muscle fiber and improving circulation, relaxing the muscle and alleviating postoperative pain.

The researchers said their study is one of the first to investigate the effects of NETOIMS on postoperative pain, functional indicators, and postoperative complications after open abdominal surgery.

"The major goal of postoperative care is to reduce the postoperative complication and to restore function as soon as possible," said corresponding study author Joon Seong Park, MD, PhD, FACS, of the pancreatobiliary cancer clinic, department of surgery, Gangnam Severance Hospital, Yonsei University. "NETOIMS not only reduced postoperative muscular pain, but also reduced the time it takes for gait speed and peak cough flow to recover to the preoperative state."

To study the NETOIMS method, a double-blind, randomized controlled clinical trial was developed that included 44 patients scheduled for open pylorus-preserving pancreaticoduodenectomy (PPPD), a surgical procedure performed to remove pancreatic tumors where a portion of the duodenum is removed and the pylorus--the part of the stomach that connects to the duodenum--is kept.* The patients were randomly allocated to the NETOIMS group or the control group.

Once the operating surgeon left the operating room after completing the procedure, another surgeon who did not participate in the operation conducted the NETOIMS procedure. The treatment site was covered and markings on the NETOIMS sites were erased, making it impossible to identify the patients who received NETOIMS.

Pain was measured using a visual analog scale (VAS) that utilizes a measure on a scale from 1-10 of how much pain a patient is experiencing. Patients in the NETOIMS group returned to a VAS score of 2--a very tolerable level of pain--in an average of 2.6 fewer days after surgery than the control group. Further, on the third day after surgery, the VAS score of the NETOIMS group was 20 percent lower than that of the control group.

"Not only was the reduction in pain intensity greater, but the rate of pain relief was also faster in the NETOIMS group," study authors write. "Patients are unlikely to require hospitalization for pain management. Thus, NETOIMS is expected to reduce the length of hospital stay after surgery."

Dr. Park said that NETOIMS is a convenient and safe intervention that can be implemented in other medical centers. "Any experienced professional can safely perform the procedure without an image guide such as ultrasound while monitoring the tissue resistance felt at the fingertip during needle insertion and monitoring the regular twitching responses obtained by the intramuscular stimulation," he said.

The researchers report that in this study, NETOIMS was performed only once after the operation. Future studies will address whether there is cumulative effect of this type of treatment.

"NETOIMS helps in rapid reduction of somatic pain resulting from open abdominal surgery," the researchers concluded. "We suggest that NETOIMS is an effective new treatment modality for postoperative pain control and rapid functional restoration following open abdominal surgery such as PPPD."

What The Study Did: This observational study compares the rate of ischemic stroke among patients with COVID-19 compared with influenza in two New York hospitals.

Authors: Babak B. Navi, M.D., M.S., of Weill Cornell Medicine 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/jamaneurol.2020.2730)

Editor's Note: The article includes conflicts 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.

The Earth's crust is under constant stress. Every now and then this stress is discharged in heavy earthquakes, mostly caused by the slow movement of Earth's crustal plates. There is, however, another influencing factor that has received little attention so far: intensive erosion can temporarily change the earthquake activity (seismicity) of a region significantly. This has now been shown for Taiwan by researchers from the GFZ German Research Centre for Geosciences in cooperation with international colleagues. They report on this in the journal Scientific Reports.

The island in the western Pacific Ocean is anyway one of the most tectonically active regions in the world, as the Philippine Sea Plate collides with the edge of the Asian continent. 11 years ago, Typhoon Morakot reached the coast of Taiwan. This tropical cyclone is considered the one of the worst in Taiwan's recorded history.

Within only three days in August 2009, three thousand litres of rain fell per square metre. As a comparison, Berlin and Brandenburg receive an average of around 550 liters per square meter in one year. The water masses caused catastrophic flooding and widespread landsliding. More than 600 people died and the immediate economic damage amounted to the equivalent of around 3 billion euros.

The international team led by Philippe Steer of the University of Rennes, France, evaluated the earthquakes following this erosion event statistically. They showed that there were significantly more small-magnitude and shallow earthquakes during the 2.5 years after typhoon Morakot than before, and that this change occurred only in the area showing extensive erosion. GFZ researcher and senior author Niels Hovius says: "We explain this change in seismicity by an increase in crustal stresses at shallow depth, less than 15 kilometres, in conjunction with surface erosion". The numerous landslides have moved enormous loads, rivers transported the material from the devastated regions. "The progressive removal of these loads changes the state of the stress in the upper part of the Earth's crust to such an extent that there are more earthquakes on thrust faults," explains Hovius.

So-called active mountain ranges, such as those found in Taiwan, are characterized by "thrust faults" in the underground, where one unit of rocks moves up and over another unit. The rock breaks when the stress becomes too great. Usually it is the continuous pressure of the moving and interlocking crustal plates that causes faults to move. The resulting earthquakes in turn often cause landslides and massively increased erosion. The work of the GFZ researchers and their colleagues now shows for the first time that the reverse is also possible: massive erosion influences seismicity - and does so in a geological instant. Niels Hovius: "Surface processes and tectonics are connected in the blink of an eye." The researcher continues: "Earthquakes are among the most dangerous and destructive natural hazards. Better understanding earthquake triggering by tectonics and by external processes is crucial for a more realistic assessment of earthquake hazards, especially in densely populated regions."

The environmental benefits of taller, shrubbier tundra plants in the Arctic may be overstated, according to new research involving the University of Stirling.

Current ecosystem and climate models suggest that, as the Arctic warms, tundra ecosystems are becoming more productive, with greater photosynthesis resulting in more carbon being removed, or sequestered, from the atmosphere.

However, most models do not consider the transfer and fate of this carbon below-ground, and how this can interact with soil carbon through the activities of soil microorganisms. This is critically important because the vast majority of carbon in Arctic ecosystems is found in soil and 'permafrost' (permanently frozen soil or sediment) in the form of organic matter produced by the incomplete decay of dead plants, animals and soil organisms in cold conditions.

The new research considered the impact of a shrubbier Arctic on soil carbon stocks and the overall carbon sequestration potential of these ecosystems. Significantly, it found that some tall shrub communities stimulate recycling of carbon in soils, releasing it back into the atmosphere as carbon dioxide - meaning that more productive shrubs might not always result in greater carbon sequestration.

Professor Philip Wookey of the Faculty of Natural Sciences at the University of Stirling led the Natural Environment Research Council (NERC) funded research programme of which this study was a part. Stirling colleague Dr Jens-Arne Subke was also involved in this work.

Professor Wookey said: "While previous studies suggest that a warmer, greener Arctic may increase the rate that carbon dioxide is removed from the atmosphere, our research identified an acceleration in the rate of loss of carbon from soils, back into the atmosphere.

"This may more than offset carbon sequestration and would, unexpectedly, turn these ecosystems into a net source of carbon dioxide to the atmosphere. Significantly, current ecosystem and climate models do not account for this conundrum, which means we may be underestimating future climate feedbacks from Arctic ecosystems."

The study was led by Dr Lorna Street, of the University of Edinburgh's School of GeoSciences, and also involved scientists from the NERC Radiocarbon Facility in East Kilbride, and the Universities of Durham and Liverpool. Further support was received from the Aurora Research Institute, Wilfrid Laurier University, and the University of Montreal, all in Canada.

The fieldwork - looking at how carbon is cycling in plants and soils over the past 50 years - was conducted in 2013 and 2014 in the Mackenzie Uplands of Northwest Territories, Canada.

The team found evidence that birch shrubs in Arctic tundra are strongly linked to the release of old carbon - fixed by photosynthesis more than 50 years ago and stored in soil organic matter. However, this was not true of alder, another type of Arctic shrub.

Dr Street said: "We think this is because, in birch, the products of photosynthesis are transferred to the soil through fungal symbionts, which stimulate the decomposition of soil organic material as a means of releasing the nutrients, like nitrogen, that the birch shrubs require to grow.

"By contrast, in alder, photosynthesis products are mostly retained in plant tissues because alder often has the help of microorganisms in the roots, which are capable of 'fixing' nitrogen directly from the atmosphere.

"These findings indicate that, if - as evidence has suggested - shrub birch proliferates in tundra ecosystems over the next decades, this might directly stimulate the loss, through accelerated decomposition, of pre-existing soil carbon as carbon dioxide."

Uncertainty surrounds the level of potential carbon release from high latitude permafrost systems - with predictions ranging between 0 and 200 gigatons. For context, 200 Gt represents approximately 20 years of current total global carbon emissions, due to human activity, to the atmosphere.

Dr Street added: "If our results apply across permafrost tundra regions, this suggests there is a previously unaccounted for process which could push the system towards the upper end of those predictions. This is hugely important as it means we may need to do more than currently expected, in terms of carbon dioxide emissions reductions, to meet our climate targets."

Researchers from the Moscow Institute of Physics and Technology, Kazan Federal University, and George Washington University have proposed an algorithm for producing patient-specific mathematical models describing the electrical excitation of human heart cells. Published in PLOS One, the study looks at two possible approaches - one using experimental records of electrical activity and the other based on gene expression profiles.

Each heart contraction is caused by a preceding electrical excitation, the so-called action potential. The latter results from electrical currents through ion channels. The number of such channels forming ion currents varies with both pathological conditions and the individual properties of heart tissue in healthy patients. When the balance between various types of ion currents gets disrupted, this may lead to dangerous arrhythmias and death.

Since many factors are involved in excitation propagation, the studies investigating the basic principles underlying arrhythmia have relied on mathematical models over the past 50 years. Despite the effort behind developing these models, they are so far rarely used in the clinical practice, mainly because they describe a hypothesized average patient. The research reported in this story addresses the challenging task of applying such models to real individual patients.

The first approach discussed in the paper relies on experimental recordings of action potential and subsequent model optimization using dedicated computer algorithms. They employ evolutionary principles to find the parameters that make the model reproduce the experiment. Randomly generated models are subjected to selection, crossover, and mutation. Prior research by a number of scientific groups has identified the key challenge faced by this approach. Namely, it is hard to find the unique solution, because of the numerous distinct combinations of parameters that result in the same action potential waveform.

Study co-author Andrey Pikunov from the MIPT Laboratory of Human Physiology commented: "We have closely examined and optimized the algorithm's pipeline at every stage. For instance, previously, model parameters were subjected to mutation independently from each other, whereas we used 'vector mutation,' affecting all parameters at once. This makes the search for the right model parameters considerably more efficient. Along with other modifications we have developed an algorithm that determines the conductivities of the main ion channels with a high degree of precision."

The second approach discussed in the article uses the gene expression data, which determine how the genetic information is converted into RNAs and proteins. Each ion channel in the cell membrane is made of protein subunits incorporated into the membrane following translation from the matrix RNA. The amount of such expressed RNA can be measured, but it has so far been impossible to use these data to predict the electrophysiological features specific to a certain patient. The researchers calibrated the model on one actual patient, using the algorithms mentioned above. Then the differences between gene expression profiles were used to create mathematical models successfully predicting the action potential for other patients based on their individual gene expression profiles.

The head of the MIPT Laboratory of Human Physiology, study co-author Roman Syunyaev added: "Aside from the fundamental interest, this research has far-reaching practical applications, from using patient-specific models in the clinical practice to drug design. Many medications act on ion channels, and our algorithms can provide insights into how certain drugs affect the heart cells' electrophysiology. This information can be extracted from measurements of the action potential."

TORONTO, ON (June 30, 2020) -- A collaboration between the University of Toronto's Faculty of Dentistry and the National Jewish Health in Denver -- the top-ranked respiratory research hospital in the U.S. -- has yielded a new drug discovery that could be useful to combat inflammation of all varieties and shows promise in fighting acute respiratory illnesses such as COVID-19.

Called TAT CARMIL1, the "drug" is actually a combination of two naturally occurring peptides that, when combined, work together to penetrate a cell's membrane in order to dampen an acute inflammatory response.

In this first ex vivo study, the peptide reduced collagen degradation by up to 43 per cent. If deployed early enough, the researchers say, the peptide could allay some of the worst damage caused by acute inflammatory responses.

DOUSING CYTOKINE STORMS

Acute infections can cause inflammatory responses known as "cytokine storms," a term that has gained in popularity during the COVID-19 pandemic.

This storm is a natural defense response to an acute infection. Cytokines are a type of immune response cell, but when the body becomes overwhelmed by infections such as those caused by influenza, H1N1 or COVID-19, it can release an unregulated flood of cytokines into the body.

In those instances, infection-busting cytokines can cause severe damage in the body -- everything from holes in the lung tissue to vascular damage and blot clots, with the most acute cases causing death.

TARTGETED PATHWAYS, PRECISION MEDICINE

Dr. Greg Downey, pulmonologist, professor and executive vice president, academic affairs in the Department of Medicine at the National Jewish Hospital, who co-authored the study, calls the peptide discovery "exciting."

Here's how it works: the peptide combines a segment of a naturally occurring protein, CARMIL1, with a peptide "vehicle," TAT, that brings the CARMIL1 directly into the cell. That enables the CARMIL1 to calm the inflammatory storm. The CARMIL peptide effectively blocks a family of cytokines, called interleukin1, from signalling and reproducing in vast quantities.

"There are a lot of people looking at these areas, but this study gives the first indication of how these CARMIL proteins are involved with this pathway," Downey adds.

But what makes the discovery so unique is how precise it is. The TAT CARMIL1 peptide targets two receptors, sticking to both the cell's surface and its cell substrate, where it adheres to other cells.

"The two receptors necessary for it to work supplies an unusual level of specificity," explains Chris McCulloch, professor at the Faculty of Dentistry and a co-lead of the study. "We think the unusual nature of this pathway might restrict its side effects."

That could make the peptide an unusually strong candidate as a potential drug. Drugs designed to work in conjunction with this peptide would need to target cells at both receptors, narrowing the potential field of candidates from tens of thousands to hundreds.

"This is a precise pathway to deal with a precise issue," says Downey.

THE FUTURE IS CARMIL

Next, the team hope to track the peptide's success in in vitro models. Given the broad applicability of the peptide, which can be combined with other drugs, such as cancer or arthritis drugs, the discovery could one day become a useful ally in the fight against all types of inflammation.

Still, Downey cautions, more work needs to be done. The initial study shows that the storm- stopping peptide is most effective when it is applied as an early intervention. That, says Downey, is impractical: "In the clinical world the reality is that you don't have that luxury."

A new pilot study by the University of Chicago Medicine and the Stanford University School of Medicine team from the VA Palo Alto Health Care System (principal investigators Carolyn Rodriguez, MD, PhD, and

David Clark, MD, PhD) provides an early glimpse of how veterans suffering from posttraumatic stress disorder (PTSD) may benefit from one simple, inexpensive treatment involving nitrous oxide, commonly known as laughing gas.

For military veterans suffering from PTSD, symptoms such as anxiety, anger and depression can have a devastating impact on their health, daily routine, relationships and overall quality of life.

“Effective treatments for PTSD are limited,” said anesthesiologist Peter Nagele, MD, chair of the Department of Anesthesia & Critical Care at UChicago Medicine and co-author of the paper. “While small in scale, this study shows the early promise of using nitrous oxide to quickly relieve symptoms of PTSD.”

The findings, based on a study of three military veterans suffering from PTSD and published June 30 in the Journal of Clinical Psychiatry, could lead to improved treatments for a psychiatric disorder that has affected thousands of current and former members of the U.S. military.

For this new study, three veterans with PTSD were asked to inhale a single one-hour dose of 50% nitrous oxide and 50% oxygen through a face mask. Within hours after breathing nitrous oxide, two of the patients reported a marked improvement in their PTSD symptoms. This improvement lasted one week for one of the patients, while the other patient’s symptoms gradually returned over the week. The third patient reported an improvement two hours after his treatment but went back to experiencing symptoms the next day.

“Like many other treatments, nitrous oxide appears to be effective for some patients but not for others,” explained Nagele, who is himself a veteran of the Austrian Army and grateful to have identified an opportunity to help other veterans. “Often drugs work only on a subset of patients, while others do not respond. It’s our role to determine who may benefit from this treatment, and who won’t.”

The next step for the team is to determine whether nitrous oxide effects are replicated in a larger sample under randomized, controlled conditions and whether the effects benefit specific PTSD domains (http://ClinicalTrials.gov ID: NCT04378426). If these findings are replicated in independent samples, it may be feasible that nitrous oxide can be implemented to achieve rapid symptom reduction while longer-term PTSD treatments like psychotherapy or pharmacology are allowed to take effect over a longer time course.

Nagele is a pioneer in the field of using nitrous oxide to treat depression. Most commonly known for its use by dentists, nitrous oxide is a low-cost, easy-to-use medication. Although some patients may experience side effects like nausea or vomiting while receiving nitrous oxide, the reactions are temporary.

Exactly how and why nitrous oxide relieves symptoms of depression in some people has yet to be fully understood. Most traditional antidepressants work through a brain chemical called serotonin. Nitrous oxide, like ketamine, an anesthetic that recently received FDA-approval in a nasal spray form to treat major depression, works through a different mechanism, by blocking N-methyl-D-aspartate (NMDA) receptors.

A 2015 landmark study by Nagele found that two-thirds of patients with treatment-resistant depression experienced an improvement in symptoms after receiving nitrous oxide.

For his next study, Nagele is researching the ideal dose of nitrous oxide to treat intractable depression. Study participants with treatment-resistant depression received different doses of nitrous oxide so that Nagele and his team could compare each dose’s effectiveness and side effects. The study is being funded by the Brain & Behavior Research Foundation.

Several interacting exoplanets have already been spotted by satellites. But a new breakthrough has been achieved with, for the first time, the detection directly from the ground of an extrasolar system of this type. An international collaboration including CNRS researchers* has discovered an unusual planetary system, dubbed WASP-148, using the French instrument SOPHIE at the Observatoire de Haute-Provence (CNRS/Aix-Marseille Université;). The scientists analysed the star's motion and concluded that it hosted two planets, WASP-148b and WASP-148c. The observations showed that the two planets were strongly interacting, which was confirmed from other data**. Whereas the first planet, WASP-148b, orbits its star in nearly nine days, the second one, WASP-148c, takes four times longer. This ratio between the orbital periods implies that the WASP-148 system is close to resonance, meaning that there is enhanced gravitational interaction between the two planets. And it turns out that the astronomers did indeed detect variations in the orbital periods of the planets. While a single planet, uninfluenced by a second one, would move with a constant period, WASP-148b and WASP-148c undergo acceleration and deceleration that provides evidence of their interaction. Their study will shortly be published in the journal Astronomy & Astrophysics.

ITHACA, N.Y. - Although studies have shown that women are more likely than men to enter and complete college in U.S. higher education, women are less likely to earn degrees in science, technology, engineering and math fields.

In new research, Kim Weeden, the Jan Rock Zubrow '77 Professor of the Social Sciences in the College of Arts and Sciences at Cornell University, traces the discrepancy in college majors back to gender differences that emerge early in high school.

Weeden is corresponding author of "Pipeline Dreams: Occupational Plans and Gender Differences in STEM Major Persistence and Completion," published in Sociology of Education. Co-authors are Dafna Gelbgiser of Tel Aviv University and Stephen L. Morgan of Johns Hopkins University.

The researchers found that gender differences in high school students' occupational plans - where they see themselves at age 30 - have a large effect on gender differences in STEM outcomes in college, whereas gender differences in high school grades, math test scores, taking advanced math and science courses, self-assessed math ability, and attitudes toward family and work account for only a small percentage of the gap between female and male STEM major graduates.

"Gender differences in academic achievement in high school and in work-family orientation are 'zombie explanations': They refuse to die, no matter how weak the empirical evidence for them," said Weeden, director of the Center for the Study of Inequality.

Gender differences in plans emerge very early in students' academic careers, Weeden added, "even among students who do well in math and science and have similar orientation to work and family."

The researchers analyzed data from the Educational Longitudinal Surveys (ELS), a data set collected by the U.S. Department of Education that tracked students who were high school sophomores in 2002 through 2012.

"The ELS cohort is one of the first to complete its schooling after women's college completion rates began to exceed men's and when the gender composition of the STEM workforce became a significant focus of policy and discussions about higher education," the researchers wrote.

The gender differences in occupational plans are substantial. Among high school senior boys, 26% planned to enter STEM or biomed occupations, compared with 13% of girls, while 15% of girls planned to enter nursing or similar health occupations compared with 4% of boys.

At the college level, gender disparities show up not only among those completing a STEM major, but also among those who persist in STEM after declaring a STEM major as a college sophomore. Among all college entrants, 18% of men compared with 8% of women completed STEM/biomedical majors. Among college sophomores who declared STEM majors, 42.5% of women went on to complete a STEM baccalaureate degree, compared with 58.2% of men.

The results suggest that efforts to reduce gender differences in STEM outcomes need to begin much earlier in students' educational careers. This is hard to do, Weeden said, because of persistent cultural messages and a gender-segregated adult workforce that reinforce young men's and women's beliefs - whether accurate or not - about the types of occupations where they will be welcome and rewarded fairly.

"University-based programs to support students in STEM are worthwhile," Weeden said, "but they can't really be expected to reverse all the social and cultural influences on the plans that young men and young women form well before college."

Alexandria, Va., USA -- As the global battle to understand and eliminate the coronavirus continues, a new study published in the Journal of Dental Research demonstrates that testing of oropharyngeal secretions (OS) may reduce the number of false negative results from nasal swab testing of patients who have seemingly recovered from the disease.

In the study, led by Jingzhi Ma, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Department of Stomatology, Wuhan, China, a small number of patients that had tested negative through nasopharyngeal swabs were found to be positive through the testing of oropharyngeal secretions.

The first prospective study of its kind included 75 ready-for-discharge COVID-19 patients who tested negative using two consecutive nucleic acid amplification testing (NAAT) of viral samples retrieved with nasopharyngeal swabs (NPS).

Because of detection of potential false-negatives in that cohort, NAAT results of paired OS and NPS samples collected from 50 additional COVID-19 recruits during their recovery stage were used in a second prospective study to compare the diagnostic values of the two viral RNA sampling methods.

Oropharyngeal secretions obtained from 2 of the 75 subjects in the first study yielded positive results for SARS-CoV-2 nucleic acid. In the second study, OS samples were significantly more sensitive for detection of the virus that NPS samples and missed only 14% of positive cases compared with 59% for the NPS samples.

Sampling of OS is a simple procedure that can be performed in any quarantine setting and minimizes contact between healthcare workers and patients, thereby reducing the risk of virus transmission.

"The NPS test has a risk of sending home more patients who still have the infection while the OS test will make such errors in fewer patients. Although OS sampling improves the accuracy of SARS-CoV-2 nucleic acid testing, it must be emphasized that this conclusion is based on a very small sample size," stated Ma.

There's considerable controversy over whether "COVID toes"--red sores or lesions on the feet and hands in children and young adults--are truly caused by COVID-19. A new study published in the British Journal of Dermatology provides evidence in support of the link.

In most cases, affected individuals test negative with traditional COVID-19 tests involving throat swabs and measurements of circulating antibodies, but this study's investigators found that the SARS-CoV-2 virus that causes COVID-19 was present in skin biopsies in children with symptoms of COVID toes, despite negative results from traditional tests.

Analyses detected the virus in skin's blood vessel endothelial cells, as well as in the sweat glands. Electron microscopy in one biopsy also found evidence of viral particles within endothelial cells.

"Our findings support a causal relation of SARS-CoV-2 with COVID toes. Endothelial damage induced by the virus could be the key mechanism causing these lesions," said lead author Isabel Colmenero, MD, of Hospital Infantil Universitario Niño Jesús, in Spain. "Furthermore, vascular damage could also explain some clinical features seen in patients with severe COVID-19."

Repeated measurements of the biomarker FIB-4 in the blood every few years can predict the risk of developing severe liver disease, according to a new study from Karolinska Institutet in Sweden published in the Journal of Hepatology. The risk of liver cirrhosis increases if the levels of this biomarker rise between two testing occasions.

Fat accumulation in the liver is common and is often seen in people with obesity or diabetes. In the worst case, fatty liver can lead to cirrhosis or liver cancer. It is unusual for this to occur but in those affected, symptoms often only occur at a late stage when there is no available treatment.

"It is difficult to predict the risk of cirrhosis, although you can get some guidance in using regular blood tests that measure liver damage," says lead author Hannes Hagstrom, hepatologist at the Karolinska University Hospital and docent at Karolinska Institutet. "Therefore, we wanted to investigate whether what is known as the FIB-4 score can increase the accuracy of the identification of people at high risk, in particular with information from repeated measurements."

The new study shows that repeated sampling and measurements of the FIB-4 score, rather than measuring FIB-4 on one sole occasion, can increase the prediction of future liver cirrhosis. The researchers used the AMORIS cohort that contains laboratory test data in a very large population, surveyed between 1985 and 1996. More than 40,000 people had blood test data for FIB-4 from several sampling occasions. They were followed in national registers to identify those who developed cirrhosis after up to 27 years.

The main finding was that the risk increases in people where the FIB-4 score rises between two testing occasions and decreases when it falls. In this way, almost half of those who were later affected by cirrhosis could be identified. One problem, however, was that the accuracy was relatively low, with a risk of false positive tests.

The study also established that it took a long time to develop cirrhosis, and that it may be enough to recalculate the FIB-4 score at intervals of several years.

"We show that this biomarker is useful for identifying people in primary care with an increased risk of cirrhosis who may need to be more carefully investigated and to exclude people who do not need this," says Dr Hagstrom. "But the method needs to be further developed to reduce the risk of false positive findings, which can lead to unnecessary examinations in healthy people."

Patients with low income have a higher risk of death following surgery for lung cancer compared with patients with high income. The association remains even after taking prevalence of common comorbidities, and other factors that are known to influence the risk of death, into account. This is according to a study published in the journal Thorax by researchers at Karolinska Institutet in Sweden.

There are known survival differences in the general population that are related to differences in socioeconomic status. Moreover, the gap in life expectancy seems to be increasing and can to a large part be explained by differences in deaths from cardiovascular disease and cancers.

Swedish population-based studies have previously shown a link between educational level and lung cancer survival and a strong correlation between income and survival after cardiac surgery. This prompted the research group in this study to investigate a possible association between household disposable income and survival after surgery for lung cancer.

"Sweden has a tax-funded universal health care system granting citizens equal access to care, therefore, we hypothesized that household disposable income would not be associated with long-term survival following lung cancer surgery," says Erik Sachs, PhD student at the Department of Molecular Medicine and Surgery at Karolinska Institutet, and resident in cardiothoracic surgery at the Karolinska University Hospital.

The researchers performed a population-based register study that included 5,500 patients who underwent surgery for lung cancer between 2008 and 2017. During a mean follow-up time of 3.2 years, 1,736 patients died.

After adjusting for a range of factors known to increase the risk of death, including old age, smoking and common comorbidities such as cardiovascular disease, the researchers found that patients in the highest income quintile had a 23 percent lower risk of death compared with patients in the lowest income quintile.

"Contrary to our hypothesis, the analysis showed that patients with low household disposable income had significantly worse long-term survival compared with patients with high household disposable income," says Erik Sachs, one of the study's authors. "We don't know what causes this association. To answer this question, studies investigating the underlying mechanisms of the association are needed."

The researchers note that they did not have access to information on diet, physical activity and social support, factors that have previously been associated with socioeconomic status and could potentially influence life expectancy.

"It is reasonable to assume that there are a number of factors that negatively affect lung cancer survival and whose effects would be possible to modify," says co-author Veronica Jackson, researcher at the Department of Molecular Medicine and Surgery at Karolinska Institutet and a cardiothoracic surgeon. "Our findings are important as they suggest that, with proper measures, it would likely be possible to improve the prognosis for patients with low household disposable income. But firstly, we have to identify which measures that are the "right" measures."

An analysis of patient records in Canada provides important new insights into changing patterns of inpatient healthcare utilization. Between 2007 and 2016, standardized hospitalization rates declined for coronary artery and vascular disease, heart rhythm disorders, stroke, and heart failure but increased for some important conditions: acquired valvular heart disease; vascular cognitive impairment; and congenital heart disease. The study appears in the Canadian Journal of Cardiology, published by Elsevier.

“Recent data on hospitalizations in Canada for a comprehensive set of cardiovascular diseases, stroke, and vascular cognitive impairment were lacking,” explained lead investigator Cindy Y.Y. Yip, PhD, Heart and Stroke Foundation of Canada, Toronto, ONT, Canada. “This is a unique study that reports recent Canadian hospitalization data for a comprehensive set of heart and stroke diseases and also reports how hospitalization trends differ between provinces/territories, age groups, and males and females.”

Investigators tracked more than 2.6 million hospital records from 2007 to 2016 from the Canadian Institute for Health Information (CIHI) Discharge Abstract Database for patients up to 105 years old. They analyzed the records for diseases that align with the Heart and Stroke Foundation of Canada’s six focus areas. These are the six disease groups that together represent the greatest burden on the health of people in Canada, on the economy, and on society: coronary artery and vascular disease; heart failure; heart rhythm disorders; structural heart disease (including congenital heart disease and acquired valvular heart disease); stroke; and vascular cognitive impairment. Data were available for all provinces and territories except Quebec.

Between 2007 and 2016, standardized hospitalization rates in Canada declined for coronary artery and vascular disease (27.4 percent) and heart rhythm disorders (16.8 percent), with relatively small decreases for stroke and heart failure. Contributing factors included increased multidisciplinary outpatient management such as specialized outpatient clinics for heart failure and atrial fibrillation and stroke prevention clinics; improvements in treatment and reductions in some medical risk factors such as hypertension and cholesterol levels; and better management of lifestyle risk factors such as smoking, poor diet, and physical inactivity.

However, there were notable increases for acquired valvular heart disease (31.1 percent), congenital heart disease (7.2 percent), and vascular cognitive impairment (23.4 percent). Contributing factors to these increases included the impact of an aging population, increased prevalence of dementia, and increases in the survival of congenital heart disease patients to adulthood due to treatment advances.

“The decrease in standardized hospitalization rates for some conditions suggests increased adoption of multidisciplinary outpatient management of these conditions,” noted first author Leigh C.P. Botly, PhD, Heart and Stroke Foundation of Canada, Toronto, ONT, Canada. “This highlights the importance of an integrated care approach to disease management and the need to assess how these conditions are being managed at the community level by primary healthcare providers and specialized clinics.”

This study also reports how hospitalization trends differ between age groups and sex. Heart failure, acquired valvular heart disease, and stroke are impacting people in Canada at earlier life stages than 10 years ago, especially for women. For example, heart failure hospitalization rates increased by 56 percent for men and 25 percent for women age 20-39 years. Hospitalization rates for stroke increased 25 percent for women aged 20-39 years, likely reflecting the increase in stroke risk during pregnancy. This was not true for males in the same age group. The increase in hospitalization rates for acquired valvular heart disease was much more pronounced for females (+65.7 percent) than males (+15.9 percent) aged 20-39 years.

“To improve the care for the people we serve, we must understand the pattern of change rather than static snapshots,” commented Dr. Yip. “Ultimately we want fewer people to be diagnosed with these conditions. For those who do experience them, we hope they can use their energy to focus more on their own recovery and experience a better quality of life rather than having to navigate a fragmented healthcare system.”

“This report describes the pattern of change from the past decade and is a first step in developing baseline data to inform healthcare policy, prevention strategy, and system planning. In the current landscape, these trends may be essential to help us understand the impact of COVID-19 on our healthcare system,” Dr. Yip continued.

“This study provides important insights on the changing epidemiology of cardiovascular disease in Canada,” commented Daniel G. Hackam, MD, PhD, Division of Clinical Pharmacology, Departments of Medicine, Clinical Neurological Sciences and Epidemiology and Biostatistics, Western University, London, ONT, Canada, in an accompanying editorial. “A renewed emphasis on treating and preventing major risk factors in younger age groups is needed to reverse disturbing trends in cardiovascular disease hospitalizations in young and middle-aged adults. Similarly, increased rates of vascular cognitive impairment also suggest that more attention needs to be paid to midlife antecedent risk factors such as hypertension and diabetes, if the coming epidemic of dementia is to be prevented.”

---

Notes for editors The article is “Recent Trends in Hospitalizations for Cardiovascular Disease, Stroke and Vascular Cognitive Impairment in Canada,” by Leigh C.P. Botly, PhD, M. Patrice Lindsay, RN, PhD, Sharon L. Mulvagh, MD, Michael D. Hill, MD, MSc, Cristina Goia, MSc, Michelle Martin-Rhee, PhD, Leanne K. Casaubon, MD, MSc, and Cindy Y.Y. Yip, PhD (https://doi.org/10.1016/j.cjca.2020.03.007 ).

The editorial is “The Changing Epidemiology of Cardiovascular Disease: Two Steps Forward, One Step Back,” by Daniel G Hackam, MD, PhD (https://doi.org/10.1016/j.cjca.2020.03.010). They appear in the Canadian Journal of Cardiology, volume 36, issue 7 (July 2020) published by Elsevier and are openly available.

The authors thank the Canadian Institute for Health Information (CIHI) for the use of their database in this study and also acknowledge the generosity of Heart and Stroke donors and volunteers.

Full text of the articles is available to credentialed journalists upon request. Contact Eileen Leahy at +1 732 238 3628or cjcmedia@elsevier.com to obtain copies. Journalists wishing to speak to the study’s authors should contact Megan Radford, Heart & Stroke, Canada, at +1 416 938 9483 or megan.radford@heartandstroke.ca. To reach the editorial’s author for comment, please contact Daniel G. Hackam at +1 519 663 3340 or dhackam@uwo.ca.

About the Canadian Journal of Cardiology The Canadian Journal of Cardiology is the official journal of the Canadian Cardiovascular Society. It is a vehicle for the international dissemination of new knowledge in cardiology and cardiovascular science, particularly serving as a major venue for the results of Canadian cardiovascular research and Society guidelines. The journal publishes original reports of clinical and basic research relevant to cardiovascular medicine as well as editorials, review articles, case reports, and papers on health outcomes, policy research, ethics, medical history, and political issues affecting practice. www.onlinecjc.ca

About the Editor-in-Chief Editor-in-Chief Stanley Nattel, MD, is Paul-David Chair in Cardiovascular Electrophysiology and Professor of Medicine at the University of Montreal and Director of the Electrophysiology Research Program at the Montreal Heart Institute Research Center.

LA JOLLA--Flashback to mid-March: the novel coronavirus had reached San Diego, California. Few people could get tested, and even less was known about how the virus mutated as it spread from person to person.

Scientists now know that two variants of the novel coronavirus (SARS-CoV-2) were circulating at that time. The variants, called G614 and D614, had just a small difference in their "spike" protein--the viral machinery that coronaviruses use to enter host cells.

In a new study, an international team of scientists show that the G version of the virus has come to dominate cases around the world. They report that this mutation does not make the virus more deadly, but it does help the virus copy itself, resulting in a higher viral load, or "titer," in patients.

The new study, led by scientists at Duke University, Los Alamos National Laboratory and La Jolla Institute (LJI) was published July 2, 2020 in Cell.

"We are focused on the human immune response because LJI is the headquarters for the Coronavirus Immunotherapy Consortium (CoVIC), a global collaboration to understand and advance antibody treatments against the virus," says LJI Professor Erica Ollmann Saphire, Ph.D., who leads the Gates Foundation-supported CoVIC.

Saphire explains that viruses regularly acquire mutations to help them "escape" antibodies made by the human immune system. When a virus acquires many of these individual changes, it "drifts" away from the original virus. Researchers call this phenomenon "antigenic drift." Antigenic drift is part of the reason you need a new flu shot each year.

It is extremely important for researchers to track antigenic drift as they design vaccines and therapeutics for COVID-19.

For the study, Saphire collaborated with Bette Korber, Ph.D., a fellow at Los Alamos National Laboratory (LANL), who serves as senior author of the study. Korber and her colleagues at LANL have developed tools to track mutations around the world. In the new study, their tracking showed that while the G and D viruses both spread widely around the world, the G virus was "fixed" as the dominant variant by mid-March.

Meanwhile, Saphire and co-author David Montefiore, Ph.D., of Duke University Medical Center, led research into the immune response to these variants. They determined that viruses carrying spike with the G mutation grew two to three times more efficiently, leading to a higher titer.

Saphire and her colleagues then used samples from six San Diego residents to test how human antibodies neutralized the D and G viruses. Would the fast-growing G virus be harder to fight?

Their experiments showed that the human immune response could neutralize the new G virus as well or better than the original D virus. This meant the immune system didn't need to produce more antibodies or better antibodies against the G virus, even though this variant was more successful at spreading. This finding was in line with what doctors saw in COVID-19 patients.

"The clinical data in this paper from the University of Sheffield showed that even though patients with the new G virus carried more copies of the virus than patients infected with D, there wasn't a corresponding increase in the severity of illness," says Saphire.

Korber adds, "These findings suggest that the newer form of the virus may be even more readily transmitted than the original form--whether or not that conclusion is ultimately confirmed, it highlights the value of what were already good ideas: to wear masks and to maintain social distancing."

Saphire says the novel coronavirus could be successful precisely because many patients do only get a mild version, or no symptoms at all.

"The virus doesn't 'want' to be more lethal. It 'wants' to be more transmissible," Saphire explains. "A virus 'wants' you to help it spread copies of itself. It 'wants' you to go to work and school and social gatherings and transmit it to new hosts. Of course, a virus is inanimate--it doesn't 'want' anything. But a surviving virus is one that disseminates further and more efficiently. A virus that kills its host rapidly doesn't go as far--think of cases of Ebola. A virus that lets its host go about their business will disseminate better--like with the common cold."

So while the G mutation doesn't make cases more severe, a different mutation might. "We'll be keeping an eye on it," says Saphire.