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ANCA-associated vasculitis (AAV) is an autoimmune disease involving vascular inflammation and the formation of autoantibodies (anti-neutrophil cytoplasmic antibodies - ANCA). AAV diseases include a variety of conditions accompanied by the involvement of different organs. The kidneys, lungs and upper respiratory tract are most frequently affected, as are the heart, skin and nervous system. Severe, potentially life-threatening courses of disease are feared. Therapy is with immunosuppressants; conjunctive therapy with glucocorticoids and rituximab (RTX, a monoclonal anti-CD20 antibody) is frequently used for initial remission induction. Recurrent episodes of AAV are not uncommon, especially if relapses have occurred in the past. As the effect of RTX is not persistent, maintenance therapy is required.

The international, multi-center RITAZAREM study was a randomized, controlled (open label) trial of two strategies for preventing relapse in AAV patients after remission induction with RTX and glucocorticoids. The efficacy of fixed interval repeated RTX doses was compared with daily oral azathioprine. If remission was achieved after four months, participants were randomized equally and received either 1000 mg of RTX (every four months, five times in total) or daily doses of azathioprine (2 mg/kg). The follow-up was at least 36 months. At four months, 170 patients were randomized (85 RTX; 85 azathioprine). All patients were followed up for at least 24 months. Median age was 59 (19-89) years, and the duration of the disease was 5.3 years (0.4-38.5). The results showed that rituximab was superior to azathioprine (preliminary HR 0.36; p

Among the RTX group, only 2/11 relapses (18%) were severe "major relapses", compared to 12/32 (38%) among the azathioprine group. Severe adverse events occurred in 19/85 patients (22%) on RTX, and in 31/85 patients (36%) on azathioprine. As a recognised side effect of RTX, 25/85 patients (29%) developed hypogammaglobulinemia (low immunoglobulin levels as a sign of immunosuppression) and 42/85 patients (49%) had infections (but not severe). Hypogammaglobulinaemia was seen in 25% of the azathioprine group and non-severe infections in 48%.

"AAV is a disease that can be life-threatening and/or lead to kidney failure requiring dialysis, so for that reason it is so important to prevent relapses", explains the study's first author, Dr. Rona Smith, Cambridge, UK. "The study results clearly showed the superiority of RTX over azathioprine during the treatment period, without our finding any evidence that the substance has a worse risk profile - on the contrary."

"The RITAZAREM study is of groundbreaking importance because RTX, as a remission-sustaining therapy, is not recommended for all AAV patients, so it is essential, therefore, to refine the guidelines in future so as to indicate which patient groups benefit most from the therapy," adds ERA-EDTA Press Officer Professor Ron Gansevoort. "This seems to apply especially to maintenance therapy after an early relapse, but possibly also for elderly, frail subjects after a first presentation. Further large-scale studies also need to clarify the optimal RTX dose, the necessary duration of RTX maintenance therapy and other unanswered questions, so that more precise statements can be made in this regard when the guidelines are next revised."

Empagliflozin (EMPA), a selective inhibitor of sodium/glucose cotransporter 2 (SGLT2 inhibitors, "gliflozines"), reduces CKD progression in type 2 diabetics (T2D) with cardiovascular disease, presumably by lowering intraglomerular pressure. Positive effects of the drug on the cardiovascular risk of patients have also been observed.

However, uncertainty has been generated by the initial reduction in glomerular filtration rate after introducing an SGLT2 inhibitor. The increase in tubular flow rate caused by the reduced reabsorption of glucose and sodium from the glomerular filtrate under EMPA triggers the tubuloglomerular feedback mechanism in the kidney. The increased rate of tubular filtration causes the release of vasoactive hormones at the afferent arterioles of the glomerulus and thus to constriction of the afferent arterioles, as a result of which the glomerular filtration rate (GFR) decreases. But when administration of the drug is stopped, this feedback mechanism is terminated and the GFR increases again.

A study presented at the ERA-EDTA Congress today as a "Late Breaking Clinical Trial" investigated whether this effect of the initial 'GFR dip' after EMPA initiation was influenced by baseline characteristics and/or might have an impact on the EMPA-induced risk reduction in kidney outcomes. The study analyzed data of the EMPA-REG OUTCOME trial, in which patients with T2D and established cardiovascular disease had been treated treated (1:1:1) with EMPA 10 mg, 25 mg or placebo. The new analysis presented by Bettina J. Kraus, University Hospital Würzburg, Germany, searched for patients who had experienced an initial 'eGFR dip' of >10% from baseline at Week 4 after treatment initiation. Twenty-eight percent of participants on empagliflozin experienced an 'eGFR dip' >10%. Diuretic use and/or higher KDIGO risk category at baseline were predictive of an initial 'eGFR dip' of >10% in empagliflozin compared to placebo treatment. However, rates of kidney adverse events were consistent across subgroups based on these predictive factors. Also, an 'eGFR dip' >10% had no major impact on the risk reduction with EMPA for the composite kidney outcome.

"These data show that around one in four patients treated with EMPA experiences an initial 'eGFR dip'. This was more likely in those taking diuretics and/or in more advanced stages of chronic kidney disease, but EMPA was safe and effective even in those. For such high-risk patients, especially, any intervention is welcome that slows the progression of kidney disease and allows the need for dialysis to be postponed as long as possible", commented Professor Christoph Wanner, Würzburg, Germany, President-Elect of the ERA-EDTA.

LA JOLLA--Every year, more than 68,000 people end up with a clinical case of Japanese encephalitis. One in four of these patients will die. The mosquito-borne virus, which is most common in Southeast Asia, also causes severe neurological damage and psychiatric disorders.

There is no cure for Japanese encephalitis, but there are effective vaccines against Japanese encephalitis virus (JEV). The problem is that JEV's range is spreading, and more and more people at risk of the disease also live in areas where viruses like Zika are prevalent.

In a new study, published June 5, 2020, in the Journal of Experimental Medicine, scientists at La Jolla Institute for Immunology (LJI) shows that antibodies against JEV are "cross-reactive" and can also recognize Zika virus. Unfortunately, these antibodies can actually make Zika cases more severe. The research, conducted in mice, is the first to show that T cells can counteract this dangerous phenomenon.

"This means we probably need to be developing a vaccine against both viruses that can elicit a good balance of antibodies and T cells," says Associate Professor Sujan Shresta, Ph.D., who co-led the study in collaboration with Jinsheng Wen, Ph.D., of Ningbo University and Wenzhou Medical University, and Yanjun Zhang, Ph.D., of Zhejiang Provincial Center for Disease Control and Prevention.

Shresta has spent much of her career studying flaviruses, a family of viruses which includes Zika, JEV, dengue, West Nile virus and yellow fever. These diseases have spread in recent years as more people around the world have moved to cities and climate change has allowed the mosquitoes that carry these diseases to expand their habitat. People in many countries now live at risk of encountering multiple harmful flaviviruses in their lives.

"The immune responses to these viruses are very cross-reactive," says Shresta. "The problem is that the immune response can be both good and bad."

In some cases, antibodies against one flavivirus can make a future flavivirus infection even worse by allowing the virus to enter host cells. Shresta and investigators worldwide have shown this process, called antibody-dependent enhancement (ADE), during Zika and dengue infections in animal models that recapitulate severe dengue or Zika disease in individuals with prior exposure to dengue or Zika virus. However, ADE of Zika disease in cases of previous JEV exposure, and the interplay between antibodies and infection-fighting immune cells called CD8+ T cells, had not been studied before.

For the new study, Shresta and her colleagues took antibodies from JEV-infected mice or JEV-vaccinated people and injected them into healthy mice. The healthy mice were then exposed to Zika virus. These mice experienced ADE and had far more severe cases of Zika fever than mice with no antibodies against JEV.

Shresta and her colleagues next focused their attention on CD8+ T cells from JEV-infected mice. They found that CD8+ T cells primed to fight JEV could counteract the harmful effects of cross-reactive antibodies. "These JEV-elicited T cells were indeed able to recognize and get rid of the Zika virus infection," says Shresta.

In short, the mouse survival rate went up and their viral load went down, thanks to the CD8+ T cells. A future JEV vaccine would need to prompt a similar response from CD8+ T cells to help a person avoid ADE of Zika infection.

Shresta says this work can help shed light on how to fight the whole family of flaviviruses, which includes over 70 different species, and many countries are increasingly dealing with cocirculation of multiple flaviviruses. "Any of these viruses could cause a major, major outbreak," says Shresta. "We need to look at deploying a combination Zika/JEV vaccine, and we may need to tailor vaccines to particular locations where we know both JEV and Zika pose a threat."

Shresta adds that research into cross-reactive antibodies and T cell responses is especially important today as scientists investigate whether exposure to common cold coronaviruses can leave a person with any immunity against SARS-CoV-2, the novel coronavirus.

"This provides us with a really good model to learn about immune response," Shresta says.

Rochester, MN, June 5, 2020 - "On a scale of 1 - 10, how much do you exercise (0-none, 10-always)." Adding this simple question when assessing elderly patients undergoing coronary artery calcium (CAC) scans can help clinicians better understand and treat patients, report scientists in Mayo Clinic Proceedings: Innovations, Quality & Outcomes, published by Elsevier. Elderly patients with high levels of atherosclerosis detected by CAC scans, who reported very frequent exercise, had a lower mortality rate than patients who reported getting little or no exercise and a mortality rate similar to patients with low levels of atherosclerosis who exercised rarely or never.

"Our study is the first to assess - and show - that this assessment of exercise activity in the elderly strongly influences the risk of death when significant atherosclerosis is detected on CAC scanning," explained lead investigator Alan Rozanski, MD, Professor of Medicine (Cardiology) at the Icahn School of Medicine at Mount Sinai, and Director of Nuclear Cardiology and Cardiac Stress Testing and Chief Academic Officer for the Department of Cardiology at Mount Sinai Morningside, New York, NY, USA. "A notable aspect was that the use of just a single, self-reported question regarding exercise served to risk stratify older patients if they had elevated coronary artery calcium scores."

Cardiovascular diseases increase markedly with age and constitute a leading cause of death and disability in older adults. One underlying cause is advancing atherosclerosis, which can be evaluated by measuring the extent of CAC. There is growing interest in using CAC scanning as a simple and inexpensive means to determine which older patients are most at risk, and then assessing which interventions might modify that risk. Studies in middle-aged patients suggest that high levels of physical activity are associated with lower mortality and cardiac death rates among patients with atherosclerosis, but studies in elderly patients have been scarce.

The scientists identified 2,318 patients between the ages of 65 and 84 years who were referred for CAC screening between August 1998 and November 2016, and who died more than one year after the scan. The patients completed a questionnaire at the time of their scan, which asked about chest pain symptoms, cardiac risk factors, medication use, and physical activity. Patients self-reported their physical activity on a scale from 0-none to 10-always. Resting heart rate, blood pressure, height, and weight were recorded. Medical history of dyslipidemia, diabetes, hypertension, and smoking was identified.

The patients were followed for an average of 10.6 years to assess rates of death. During this time, 23 percent had died. For the entire cohort, the annualized mortality rate was 2.3 percent per year, with the highest mortality occurring among patients reporting low physical activity (2.9 percent per year) and the lowest mortality occurring among patients reporting high physical activity (1.7 percent per year).

Among patients with low CAC scores (0-99), survival was similar for each level of physical activity. In contrast, in patients with moderate CAC scores (100-399), the risk for all-cause mortality increased 2.07-fold among patients with low physical activity compared with patients with high physical activity. In patients with CAC scores over 400, all-cause mortality increased 2.35-fold for patients with low versus high activity.

Among all clinical parameters, age and the magnitude of CAC score were the most potent predictors of mortality. Notably, among all other variables, including chest pain symptoms, smoking, and obesity, physical activity was the next most potent predictor.

Dr. Rozanski and colleagues noted that there are several factors that could explain the observations of this study. For example, patients who reported high physical activity had better health profiles, with lower frequency of hypertension, smoking, and diabetes. Of patients reporting high physical activity, only 7.7 percent were obese, while more than 25 percent of patients reporting low physical activity were obese.

"Our results indicate that a simple assessment of self-reported daily-life physical activity can substantially improve the effectiveness of CAC scanning for risk stratifying older adults and is strongly encouraged," said Dr. Rozanski. "This is consistent with recent suggestions to make assessment of physical activity a 'fifth vital sign' that should be entered into patient electronic medical records, along with body temperature, pulse rate, respiration rate, and blood pressure."

Researchers at Baylor College of Medicine are recommending that all COVID-19 patients admitted to the ICU undergo a thromboelastography (TEG) to test for the risk of forming blood clots. This recommendation comes after they found that more than half of the patients tested under these same conditions developed clinically significant blood clots that went undetected using routine screenings.

The findings appear in in the latest edition of JAMA Network Open.

"As the surgical critical care team at Baylor St. Luke's Medical Center was discussing their work in the ICU a few weeks ago, I was amazed to hear them express that one of their greatest challenges was that the central intravenous and arterial lines and the dialysis catheters kept unexpectedly clotting in COVID-19 patients in the ICU," said Dr. Todd Rosengart, chair and professor of the Michael E. DeBakey Department of Surgery at Baylor and senior author of the paper. "I'd never seen or heard anything like this in my 30 years as a surgeon, even in our sickest patients."

This prompted Rosengart and colleagues to look at what types of tests could be performed to identify these otherwise undetected blood clots.

Researchers observed 21 patients with confirmed COVID-19 infection admitted to the Baylor St. Luke's Medical Center ICU between March 15 and April 9. They found that the standard clotting profile or screening of the patients was fairly normal. They were then moved to the next level of more specific clotting tests, which included analyzing a patient's fibrinogen and D dimer levels. Fibrinogen is the protein that makes up the clot and D dimer levels are used to indicate the rate at which a patient's clots are being broken down, which would usually suggest that the body is "chewing up" all of the clotting factors.

For the COVID-19 patients in the ICU, researchers found that the levels of fibrinogen were more than three times the normal range, indicating that the body was churning out this protein. Looking at these two results together, there was no clear indication that these patients were at increased risk for forming blood clots.

At this point, the researchers looked to a third tier of tests that is not a regularly used process in most ICU patients, the thromboelastography test. This test looks at how quickly a clot forms, its strength and stability. It is used mostly for open heart surgery patients who often have abnormal clot function and also is commonly used for trauma patients.

This test showed the researchers two things: the patients who they found were clotting their central intravenous and arterial lines and dialysis catheters had abnormally high clotting function compared to the patients who did not have clotting issues, and the clot breakdown function was significantly higher in the patients who were clotting less than others.

Among the 21 patients studied, 13 of them, or 62%, developed 46 blood clots that could only be detected through the TEG test.

For patients who are at a higher risk of blood clots as indicated by the TEG test, the researchers recommend administering additional blood thinners.

"The TEG test should be performed on all COVID-19 ICU patients immediately to find those who are at a higher risk of clotting," Rosengart said. "At the point where physicians discover that their central line and catheter is clotting, the horse is out of the barn."

The researchers are now looking at whether these undetected blood clots could be related to the unexplained deaths they are seeing in COVID-19 patients.

A current Swedish study came to the result that among patients with high disease activity, one in one hundred will develop venous thromboembolism within one year, a more than twofold increase compared to patients in remission (1). Data of the German RABBIT1 register (2) published by the European League against Rheumatism (EULAR) show that this increased risk of thrombosis can be reduced by treatment with biological disease-modifying antirheutmatic drugs (bDMARD). This is important information, especially at this time during the COVID-19 pandemic, since thrombosis and pulmonary embolism also play a major role in COVID-19 infection. Vigilance for thrombosis during the treatment of people with arthritis is particularly recommended. Moreover, maintaining therapies to keep disease activity under control is vital.

Thrombosis is a significant medical problem. In the case of venous thromboembolism (VTE), clotting occurs inside a blood vessel and can affect the blood flow. Quick diagnosis and treatment are important as untreated deep vein thrombosis (DVT) in the leg can lead to potentially life-threatening pulmonary embolism: Parts of the thrombus tear off and enter a pulmonary vessel through the blood stream. In up to 30 percent of cases, patients die within 30 days after diagnosis from deep vein thrombosis in the leg or pulmonary embolism (3).

Due to chronic inflammation in patients suffering from rheumatoid arthritis, the risk of dangerous deep vein and pulmonary thrombosis is two to three times as high (3). "In the case of autoimmune diseases such as rheumatoid arthritis (RA), the immune system turns against the body and causes inflammation in a number of places. Inflammation may have a disruptive effect on coagulation," explains EULAR President Professor Dr. med. Iain B. McInnes from The University of Glasgow, UK. In people who are suffering from rheumatoid arthritis, the risk of thrombosis must always be taken into account.

The factors promoting thrombosis in patients suffering from rheumatoid arthritis and the medication that potentially reduces the risk have now been examined in two current studies.

One in one hundred patients with RA increased disease activity will suffer from thrombosis:

A Swedish cohort study tried to find an answer to the question of whether the degree of disease activity has an impact on the thrombosis risk (1). The team around Viktor Molander, PhD student at the Karolinska Institutet in Stockholm analysed the data of 46,311 patients suffering from RA taken from the Swedish Rheumatology Quality Register (SRQ) over a period of 12 years. For the measurement of disease activity the "Disease Activity Score 28" (DAS28) was used. The DAS28 assesses the disease activity of rheumatoid arthritis based on the assessment of 28 defined joints.

The study indicates a close connection between the clinical disease activity of RA measured by DAS28 and the risk of VTE: Molander came to the result that "among patients with high disease activity, one in one hundred is going to develop VTE within the following year, a more than twofold increase compared to patients in remission."

"Having regular check-ups by a rheumatologist can be inconvenient. However, it is an important measure to monitor the development of the condition and whether treatment has to be adjusted accordingly," explains EULAR Scientific Chair Professor Dr. John Isaacs from The University of Newcastle, UK.

Biologics can reduce the risk of thrombosis:

The risk of thrombosis is also influenced by the medication used in rheumatoid arthritis cases. Conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) such as Methotrexate, Sulfasalazine and Leflunomide are part of the basic treatment of RA. A next step are biologics (bDMARD), which also include tumour necrosis factor (TNF) inhibitors like Adalimumab, Certolizumab Pegol, Etanercept, Golimumab and Infliximab.

The question of whether the risk of thrombosis is reduced by application of bDMARDs such as TNF inhibitors in comparison to csDMARDs was addressed in a scientific study including the lead author Dr. rer. nat. Martin Schäfer from the programme area of Epidemiology at the German Rheumatism Research Center, Berlin, Germany. For this purpose, the team has analysed the data of more than 11,000 RA patients in the German RABBIT1 register, who were treated either with another csDMARD after at least one csDMARD failure, or whose treatment was switched to bDMARD.

The result: "By treatment with TNF inhibitors, the risk of major VTE events is reduced by almost half in comparison to csDMARDs," explains Schäfer. According to the RABBIT data, an increase in inflammatory activity was also associated with a significant increase in the risk of VTE: The risk was approximately twice as high as a CRP value of at least 5 mg/l. "For patients with an increased risk of thrombosis, alternative treatment with TNF inhibitors, and possibly other biologic drugs, should be considered instead of standard csDMARD treatment," concludes PD Dr. med. Anja Strangfeld, study manager at RABBIT register in Berlin and co-author of the study. "Reducing the inflammatory activity is also an important factor to reduce the risk of VTE."

What The Study Did: This pharmacokinetic simulation study estimates appropriate pediatric-specific dosing regimens for hydroxychloroquine and remdesivir in the treatment of pediatric patients with COVID-19.

Authors: Michael Cohen-Wolkowiez, M.D., Ph.D., of the Duke University School of Medicine in Durham, North Carolina, is the corresponding author.

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

(doi:10.1001/jamapediatrics.2020.2422)

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

To reduce the number of traumatic brain injuries in children, a team of health care professionals at the Johns Hopkins University School of Medicine and the Johns Hopkins Bloomberg School of Public Health is urging emergency room physicians to help ensure that youngsters are thoroughly educated on the proper use of bike helmets, especially in urban environments where most severe head injuries occur.

One way, they suggest, is through the use of a new educational program -- including support materials and a video made with the ideas and insight of Baltimore, Maryland, youth -- that the Johns Hopkins team pilot tested in 2017. The successful outcome of that trial is reported in the May 17, 2020, issue of Health Promotion Practice.

"For families in low income and minority communities, programs that inform about helmet safety measures is crucial," says lead study author Leticia Ryan, M.D., M.P.H., associate professor of pediatrics and director of research in pediatric emergency medicine at the Johns Hopkins University School of Medicine. "Our youth-oriented and culturally tailored approach could be explored as a strategy to achieve that goal."

In the United States, 26,000 of the 325,000 children treated each year in emergency rooms for bicycle-related injuries experienced a traumatic brain injury. The Johns Hopkins researchers say prevention programs are needed but that they must be designed to reach all groups, regardless of socioeconomic status.

For example, they recommend providing helmets to disadvantaged families during information sessions about their proper use. The team says another way to overcome social barriers to prevention is to use educational materials -- such as the Baltimore video -- developed with input from the target audience of young bicycle riders.

In their study conducted between September and December 2017, the researchers worked with 20 urban Baltimore parents and their children, ages 8 to 15 (average age of 9), who had ridden a bicycle within the previous six months. To start, the children completed a pre-intervention survey and watched the "You Make the Call" video where urban youth discuss the importance of wearing a helmet. The intervention program also included a free helmet, fitting instructions and a parent guidance document. The study ended with the children completing a post-intervention survey.

Prior research had shown that the highest injury rate from bicycle use without a helmet occurs in the 10- to 15-year age range, and that most bicyclist deaths occur in urban areas. In the Johns Hopkins study, 13 (65%) of the participants reported in the pre-intervention survey that they rode their bikes on a weekly basis; however, 16 (80%) said that they did not own a helmet or never wore a helmet.

In the post-intervention survey after one month, five out of the 20 children (25%) reported riding their bikes during the study period, and all said that they used a helmet. All 20 children reported that they intended to use a helmet as a result of the intervention program.

Based on the findings of their study, the researchers say there is a need to tailor specific bike-helmet safety interventions to the most impacted groups, including low-income families and minorities.

WASHINGTON--The COVID-19 pandemic presents new challenges for clinicians caring for infected patients with diabetes, according to new guidance published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Hospitalized patients with COVID-19 and diabetes need to receive glucose-lowering therapy in addition to other complex medical management as a way of minimizing risk for complications and death. However, appropriate glycemic management--including bedside glucose monitoring and insulin administration--requires intensive patient interactions and puts clinicians at risk.

"This manuscript provides guidance for healthcare providers caring for patients hospitalized for COVID-19 who also have a prior history of diabetes or who have high blood sugar levels at the time of hospitalization," said lead author Mary T. Korytkowski, M.D., of the University of Pittsburgh School of Medicine in Pittsburgh, Pa. "These healthcare providers are at risk for contracting COVID-19, and while glycemic management in the hospital improves patient outcomes, it also intensifies the amount of time with direct patient contact."

Clinicians may limit their risk of exposure by minimizing the use of IV insulin infusions and using remote glucose monitoring devices and non-insulin therapies when possible. Diabetes self-management by selected patients who are knowledgeable and capable of this in the hospital also can be considered as a way of limiting direct patient interactions. Clinicians should be aware that some medications used in treating COVID-19 patients, including glucocorticoids and hydroxychloroquine, can affect blood glucose levels.

Experience throughout the world, including in Europe, shows that advanced age is the most important risk factor for death in COVID-19: people aged over 70 years are over 10 times more likely to die compared to those aged below 50. Other factors increasing the risk of death include male sex and comorbidities, including obesity, hypertension, cardiovascular disease, diabetes, chronic lung disease and cancer.

Until now, data on COVID-19 in kidney transplant patients have been limited. In response to the pandemic, ERACODA was established as a European database to investigate COVID-19 outcomes in patients with kidney failure. ERACODA is now the largest international database with detailed follow-up, and unlike some other databases, contains data on kidney transplant as well as dialysis patients.

"There are several reasons why kidney transplant patients could be at higher risk. Not only do they often have known risk factors for severe COVID-19, but they also take daily immunosuppressive drugs that impair their immune response," said Professor Luuk Hilbrands. "At the same time, these patients know that they are vulnerable, and must protect themselves from infection and seek medical help for fever or other symptoms. Immunosuppressive drugs may also reduce the hyperinflammatory response in severe COVID-19, and some immunosuppressants (for example, cyclosporine) inhibit corona virus replication in the laboratory." Professor Hilbrands was speaking at the press conference held during the run-up to the ERA-EDTA Congress.

By June 1st, a total of 1073 patients with COVID-19 and complete 28-day follow-up had been entered on to the ERACODA database by 197 physicians from 98 centres in 26 countries, mainly in Europe. Of patients included on the database, 305 (28%) were kidney transplant recipients. By 28 days, 21% of these patients had died--a case fatality rate only slightly lower than the 25% case fatality rate seen in dialysis patients. In patients managed outside the hospital, mortality was low at 3% of kidney transplant patients compared to 5% of dialysis patients. Following admission to hospital, 24% of transplant patients died compared to 33% of dialysis patients. Of those treated in the intensive care unit (ICU), 45% of kidney transplant patients died compared with 53% of dialysis patients.

As in the general population, age over 75 years was the most important risk factor for death in kidney transplant patients, but male sex, diabetes and cardiovascular disease were not associated with mortality risk. There was also no evidence of benefit from treatment with antiviral drugs, or reduction or withdrawal of immunosuppressive therapy.

Professor Hilbrands commented: "With longer-term follow-up, we will be able to evaluate the consequences of COVID-19 for long-term kidney graft function. In the meantime, younger, relatively healthy kidney transplant patients do not seem to be at particular risk of death as long as they strictly follow social distancing and hygiene rules. However, risk is individual, and I strongly advise all patients to talk to their physicians before making decisions about work, social life or travel."

This ERACODA database was established in March 2020 and is endorsed by the European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA. Participating physicians submit data voluntarily on all consecutive adult (?18 years) kidney transplant and dialysis patients treated at their centre for COVID-19, either as outpatients or in hospital. A further expansion of the database with more patient data and longer follow-up will allow additional analyses to support clinical decision-making.

DALLAS, June 5, 2020 -- Analysis of Seattle emergency medical services (EMS) and hospital data from January 1 to April 15, 2020, indicates bystander CPR is a lifesaving endeavor whose benefits outweigh the risks of COVID-19 infection, according to a new article published yesterday in the American Heart Association's flagship journal Circulation.

Resuscitation of patients in out-of-hospital cardiac arrest (OHCA) depends on rapid, coordinated efforts involving laypersons, telecommunicators, prehospital professionals and hospital providers. However, during the pandemic, experts have questioned whether chest compressions are a high-risk "aerosolizing" procedure that could increase the risk of COVID-19 infection, especially since bystander CPR is typically provided for only a few minutes.

In a Research Letter titled Prevalence of COVID-19 in Out-of-Hospital Cardiac Arrest: Implications for Bystander CPR, University of Washington EMS physicians and researchers in Seattle and King County, Washington, analyzed EMS and hospital treatment data, and death certificates of all OHCAs to estimate the frequency of COVID-19 infection among the total out-of-hospital cardiac arrest population served.

From January 1 to April 15, EMS responded to 1,067 out-of-hospital cardiac arrests of which 478 were treated by EMS with CPR. During the active period of COVID-19 (February 26-April 15), EMS responded to 537 (50.3%) out-of-hospital cardiac arrests, of which 230 (48.1%) were EMS treated with CPR.

The researchers note, as of April 15:

The community had 15 deaths per 100,000 population from COVID-19, higher than 42 other states at that time.

COVID-19 was diagnosed in less than 10% of out-of-hospital cardiac arrests.

Assuming the risk of transmission to bystanders performing hands-only CPR without PPE [personal protective equipment] is 10%, treating 100 patients could result in 1 bystander infection (10% with COVID-19 x 10% transmission).

Given a 1% mortality for COVID-19, approximately 1 rescuer might die in 10,000 bystander CPR events.

By comparison, bystander CPR saves more than 300 additional lives among 10,000 patients with out-of-hospital cardiac arrest.

"We believe the current findings support telecommunicators and bystanders maintaining the most efficient approach that prioritizes rapid identification of cardiac arrest and immediately proceeds to chest compressions and use of a defibrillator," the authors write. "Delaying bystander CPR to [put on personal protective equipment] should only be considered when the prevalence of COVID-19 infection is substantially increased."

As communities across the U.S. have struggled to cope with the effects of the COVID-19 pandemic, many have focused on the lack of widespread testing as a major barrier to safely reopening the country. As progress has been made on this front, concern has shifted to testing accuracy, predominantly with antibody tests, which are designed to identify prior infection.

But according to a new Dartmouth-led paper published in the New England Journal of Medicine, more emphasis should be placed on addressing the inaccuracy of diagnostic tests, which play a key role in containing the pandemic.

"Diagnostic tests, typically involving a nasopharyngeal swab, can be inaccurate in two ways," explains lead author Steven Woloshin, MD, MS, a professor of medicine and community and family medicine at Dartmouth's Geisel School of Medicine, and of The Dartmouth Institute for Health Policy and Clinical Practice. "A false-positive result mistakenly labels a person infected, with consequences including unnecessary quarantine and contact tracing. False-negative results are far more consequential because infected persons who might be asymptomatic may not be isolated and can infect others."

In their paper, Woloshin and his colleagues discuss factors contributing to the current limitations of diagnostic tests--including variability in test sensitivity and the lack of a standard process for validating test accuracy--and also cite several large studies whose frequent false-negative results are cause for concern.

The researchers draw several conclusions from their work. "Diagnostic testing will help to safely open the country, but only if the tests are highly sensitive and validated against a clinically meaningful reference standard--otherwise we cannot confidently declare people uninfected," says Woloshin.

The FDA should also ensure that test manufacturers provide details of their tests' clinical sensitivity and specificity at the time of market authorization. Tests without such information will have less relevance to patient care.

"Measuring the sensitivity of tests in asymptomatic people is an urgent priority," says Woloshin. "A negative result on even a highly sensitive test cannot rule out infection if the pretest probability--an estimate before testing of a person's chance of being infected--is high, so clinicians shouldn't trust unexpected negative results."

This estimate might depend on how common COVID-19 is where a person lives, their exposure history, and symptoms, he says.

Disrupted nightly sleep and clogged arteries tend to sneak up on us as we age. And while both disorders may seem unrelated, a new study from the University of California, Berkeley, helps explain why they are, in fact, pathologically intertwined.

UC Berkeley sleep scientists have begun to reveal what it is about fragmented nightly sleep that leads to the fatty arterial plaque buildup known as atherosclerosis that can result in fatal heart disease.

"We've discovered that fragmented sleep is associated with a unique pathway -- chronic circulating inflammation throughout the blood stream -- which, in turn, is linked to higher amounts of plaques in coronary arteries," said study senior author Matthew Walker, a UC Berkeley professor of psychology and neuroscience.

The findings, published June 4 in the journal PLOS Biology, adds poor sleep as a key risk factor for cardiovascular disease, which ranks as the top killer of Americans, with some 12,000 deaths each week -- although COVID-19, which has killed, on average, 1,000 a day during the pandemic in the U.S., comes close.

"To the best of our knowledge, these data are the first to associate sleep fragmentation, inflammation and atherosclerosis in humans," said study lead author Raphael Vallat, a postdoctoral researcher in Walker's Center for Human Sleep Science at UC Berkeley.

Established risk factors for cardiovascular disease in humans include poor diet, lack of exercise, obesity, high blood pressure and smoking.

Using statistical modeling, the researchers analyzed the diagnostic data of more than 1,600 middle-aged and older adults using a national dataset known as the Multi-Ethnic Study of Atherosclerosis.

To isolate the effect of sleep quality on heart health, the study controlled for age, ethnicity, gender, body mass index, sleep disorders, blood pressure and high-risk behaviors such as smoking.

The researchers then tracked the results of the study participants, analyzing their blood tests, their calcium scores that can gauge plaque buildup, as well as several different measures of sleep, including wristwatch-assessed sleep across a week and a night in a sleep laboratory that measured electrical brainwave signals.

The final outcome clearly linked disrupted sleep patterns to higher concentrations of circulating inflammatory factors and, specifically, of white blood cells known as monocytes and neutrophils, which are key players in atherosclerosis.

"In revealing this link with chronic inflammation, the findings suggest a missing middleman that is brokering the bad deal between fragmented sleep and the hardening of blood vessels," Walker said.

"Indeed, these associational results in humans mirror recent data in which experimentally manipulated sleep disruption in mice led to higher levels of circulating inflammation that caused atherosclerotic lesions in the rodents," added Vallat.

The findings linking poor sleep to atherosclerosis via chronic inflammation have major public health implications, researchers said.

For example, atherosclerosis often begins in early adulthood. "Unfortunately, this process goes largely unnoticed until the plaque buildup, in middle or old age, suddenly blocks arterial blood flow to the heart, lungs, brain and/or other organs, hence its moniker, 'silent killer,'" said Vallat.

"The insidious nature of the disease requires that we pay attention to our sleep hygiene, even starting in early to midlife," said study co-lead author Vyoma Shah, a doctoral student in Walker's lab.

To more accurately gauge one's sleep quality, the researchers recommend the use of clinical grade sleep trackers, because the study found that people's subjective assessments of their sleep were not reliable.

"If you track your sleep patterns using objective measures, the same way you track your weight, blood pressure or cholesterol, you can make modifications to your sleep habits, which could make a tangible difference to later life health outcomes," said Shah.

With chronic inflammation shaping up to be a bridge connecting poor sleep to cardiovascular disease, it's worth exploring its role in a plethora of other diseases where inflammation is known to be a possible factor, the researchers said.

"This link between fragmented sleep and chronic inflammation may not be limited to heart disease, but could include mental health and neurological disorders, such as major depression and Alzheimer's disease," Walker said. "These are new avenues we must now explore."

Memphis, Tenn. (June 5, 2020) - A team of University of Tennessee Health Science Center (UTHSC) researchers in the College of Medicine recently received a National Institutes of Health (NIH) award to study how genetic differences may explain why some people are more susceptible to opioid addiction than others.

Hao Chen, PhD, associate professor in the Department of Pharmacology, Addiction Science, and Toxicology, and Megan Mulligan, PhD, assistant professor in the Department of Genetics, Genomics, and Informatics, received $1.7 million for their project titled, "Reduced complexity mapping of oxycodone self-administration and stress responsiveness in rats."

"Prescription opioid use and abuse results in millions of people addicted to opioids, and we know that genetic and environmental factors, such as stress, can interact to increase addiction vulnerability," Dr. Mulligan explained. "Unfortunately, we do not have a strong or complete understanding of how genetic differences contribute to risk of opioid addiction or contribute to stress-induced vulnerability."

To identify genetic differences in stress response, oxycodone consumption, and stress-induced drug seeking, the team will compare voluntary oxycodone intake between two strains of rats that differ in their vulnerability to stress.

"What makes this model unique is that the two strains demonstrate large differences in addiction-relevant behavior, and they are genetically similar," Dr. Mulligan said. "This makes it easier to identify the gene variants that cause differences in stress response, opioid intake, and stress-induced opioid intake."

"We can swap genetic material between the strains and study if this replacement causes changes in drug intake and seeking behavior. We can even do this in specific types of cells in a certain part of the brain," said Dr. Chen. Dr. Mulligan added, "The findings from our study have great potential to translate to the human condition of opioid addiction."

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

Historical Insights on Coronavirus Disease 2019 (COVID-19), the 1918 Influenza Pandemic, and Racial Disparities: Illuminating a Path Forward

The COVID-19 pandemic is exacting a disproportionate toll on ethnic minority communities and magnifying existing disparities in health care access and treatment. To help understand the current crisis, the authors from the Johns Hopkins University School of Medicine look to history for insights, especially the 1918 influenza pandemic. The authors frame a discussion of racial health disparities through a resilience approach rather than a deficit approach and offer a blueprint for approaching the COVID-19 crisis through the lens of health equity. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-2223.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author, Lakshmi Krishnan, MD, PhD, can be reached through Michael Newman at mnewma25@jhmi.edu or 240-602-5365.