Body

A research group from Tel Aviv University (TAU) successfully reduced metastatic spread following tumor removal surgery in colorectal cancer patients. Using a short medication treatment around the time of the surgery, the researchers were able to reduce body stress responses and physiological inflammation during this critical period, preventing the development of metastases in the years following the surgery.

The study, which was published in the journal Cancer on June 13, was led by Prof. Shamgar Ben-Eliyahu from TAU's School of Psychological Sciences and Sagol School of Neuroscience and Prof. Oded Zmora from Shamir (Assaf Harofeh) Medical Center.

During the three-year-long study, researchers monitored 34 patients who received treatment surrounding a colorectal tumor removal surgery. During the pre- and post-surgical period, patients were administered two safe and known drugs: Propranolol (Deralin), an anti-anxiety and blood pressure reducing drug; and Etodolac (Etopan), an anti-inflammatory analgesic. The drugs were administered to the patients for 20 days -- from five days before surgery to two weeks after. Half of the patients received a placebo treatment as a control group.

The results were highly promising. While only 12.5% (2 out of 16) of patients receiving the drug treatment exhibited metastatic disease, the rate of metastases development was found to be 33% (6 out of 18 patients) in the control group, the known rate of metastasis for colorectal cancer patients. Prof. Ben-Eliyahu says that he is highly satisfied with these data, but also states that "despite the impressive results, this treatment must be examined again, in a much larger number of patients, in order to test whether it is, in fact, life-saving."

According to Prof. Ben-Eliyahu, the study of molecular markers in the cancerous tissue excised from the patients showed that the treatment with the medications led to a reduction in the metastatic potential of the tumor and potentially the residual cancer cells. In addition, the drugs triggered some beneficial alterations in the number and type of infiltrating tumor leukocytes (patients' white blood cells), markers that iindicate a reduced chance of disease recurrence.

"When the body is in a state of stress, whether physiological (from surgery) or psychological, this causes a release of high amounts of two types of hormones, prostaglandins and catecholamines," Prof. Ben-Eliyahu explains. "These hormones suppress the activity of the immune cells, indirectly promoting the development of cancer metastases. In addition, these hormones also directly promote the acquisition of metastatic traits in cancer tissue. Our study shows that inexpensive, accessible medication treatment could be used in order to reduce body stress responses and inflammation associated with surgery, which affects the tumor, significantly reducing the risk of metastases that might be detected months or years after surgery."

Following the success of the initial research, Prof. Ben-Eliyahu and Prof. Zmora are encouraging Israeli colorectal and pancreatic cancer patients to apply for participation in a large-scale clinical study now starting across Israel.

WASHINGTON - A brain imaging study of veterans with Gulf War illness (GWI) and patients with chronic fatigue syndrome (CFS) (sometimes called myalgic encephalomyelitis), has shown that the two illnesses produce distinctly different, abnormal patterns of brain activity after moderate exercise. The result of the Georgetown University Medical Center study suggests that GWI and CFS are distinct illnesses, an outcome that could affect the treatment of veterans with Gulf War illness.

The findings were published today in the journal Brain Communications.
While it is estimated that CFS affects 0.2-2% of the U.S. population, GWI is a multi-symptom illness that affects about 25% to 30% of the approximately 700,000 military personnel who participated in the 1990-1991 Persian Gulf War.

The two illnesses share many symptoms, including cognitive and memory problems (often described as "brain fog"), pain, and fatigue following mild to moderate exercise. Some medical institutions, including the U.S. Department of Veterans Affairs (the VA), list CFS as a symptom of GWI (called chronic multisymptom illness associated with service in the Gulf War by the VA).

"Our results strongly suggest that GWI and CFS represent two distinct disorders of the brain and therefore CFS is not a symptom of GWI," says Stuart Washington, PhD, a post-doctoral fellow and first author on the study. "Combining of two different disorders could lead to improper treatment of both." Washington works in the laboratory of James Baraniuk, MD, professor of medicine at Georgetown.

In the study, functional magnetic resonance imaging (fMRI) revealed that the brains of veterans with GWI and those of patients with CFS behaved differently when performing the same memory task after moderate exercise. Veterans with GWI showed a decrease in brain activity in the periaqueductal gray, a pain processing region within the brainstem, and in the cerebellum, a part of the brain responsible for fine motor control, cognition, pain, and emotion.

On the other hand, patients with CFS showed increased activity in the periaqueductal gray and in parts of the cerebral cortex related to maintaining vigilance and attention. In healthy subjects, these areas of the brain had no changes at all.

A previous study published by this same research group also suggested that the two illnesses are distinct. It showed that exercise causes different changes to the molecular makeup of cerebrospinal fluid in veterans with GWI and patients with CFS.

"Now that CFS and GWI have been shown to affect different regions of the brain, these regions can be more closely examined using neuroimaging and other techniques to further our understanding of the similarities and differences between the two illnesses," says Baraniuk. "Once this new information is adopted broadly, diagnoses and treatments for both disorders should improve."

This summer, children and teens will be spending more time outside. For some, this will include riding all-terrain vehicles (ATVs). Unfortunately, this activity comes with significant risks. A new study conducted by researchers at the Center for Injury Research and Policy and the Department of Otolaryngology-Head and Neck Surgery at Nationwide Children's Hospital analyzed data regarding ATV-related head and neck injuries treated in U.S. emergency departments from 1990 through 2014 involving patients younger than 18 years of age.

The study, published in Clinical Pediatrics, found an average of more than 11,000 children and teens treated for nonfatal ATV-related head and neck injuries annually in emergency departments - that's approximately 31 children and teens injured each day. The number of these injuries goes up during the warmer months of April through September, when they average 68 per day on the weekends. The number of injuries fluctuated over the course of the study, going up after the Consent Decree agreement between the ATV manufacturers and the government, which included numerous safety measures, ended in 1998. Injuries peaked in 2007.

"Although the number of nonfatal ATV-related head and neck injuries decreased during the latter part of the study period, they remain too frequent and can have long-term consequences," said Kris Jatana, MD, co-author of the study and pediatric otolaryngologist-head and neck surgeon at Nationwide Children's. "Most of these serious injuries can be prevented."

Being thrown off of an ATV was the most common mechanism of injury (30%), followed by crash (19%) and rollover (16%). Overall, broken bones and concussions/closed head injuries each accounted for approximately one-third of the injuries, but these proportions varied by age group. More than 15% of injured youth were admitted to a hospital. Riding on a roadway was especially dangerous. Children and teens who were injured on a street or highway were about 1.5 times more likely to be admitted to a hospital for their injury than those injured at other locations.

Children younger than 12 years of age accounted for almost half (46%) of injured youth in the study despite the recommendation by the American Academy of Pediatrics that children should be at least 16 years of age - old enough to drive a car - before they operate an ATV. Children younger than 12 years were more likely than teens to sustain broken bones and be injured when thrown off of an ATV, whereas teens were more likely than younger children to be diagnosed with concussions/closed head injuries and to be injured by an ATV rollover.

"ATVs are powerful machines designed strictly for off-road use that require mature judgement, coordination, strength, and moment-to-moment decision making. Adoption of the safety recommendations outlined by the American Academy of Pediatrics would go a long way in preventing many pediatric ATV-related head and neck injuries," said Gary Smith, MD, DrPH, senior author of the study and director of the Center for Injury Research and Policy at Nationwide Children's. "These recommendations include requiring children to be at least 16 years old before they operate an ATV, wearing a helmet designed for motorcycle use every time they ride, prohibiting passengers, and not riding on roadways."

A study of older mice with type 2 diabetes has yielded highly promising results for researchers investigating potential new vaccines for tuberculosis (TB).

A team of researchers from Australia, Bangladesh and France investigated a potential vaccine, BCG::RD1, and found it highly protective when administered directly into the lungs of diabetic mice, which were then exposed to TB.

According to the World Health Organisation, TB is one of the top 10 causes of death world-wide, and the leading cause from a single infectious agent. The only currently licensed vaccine, BCG, is not effective in adults.

"These findings are especially welcome because type 2 diabetes is not just a significant risk factor for TB, it's a risk factor that becomes more widespread every year in our aging population," said senior author Dr Andreas Kupz, a Senior Research Fellow at the Australian Institute of Tropical Health and Medicine (AITHM) at James Cook University.

Lead author and AITHM researcher Harindra Sathkumara said BCG::RD1 proved highly protective when administered to older, diabetic mice, acting not only on T cells but also on the other immune cell subsets, to mount a robust response against the TB-causing bacteria.

"We observed a remarkable level of protection against TB, with a significant increase in immune responses in the lungs of the diabetic mice," he said.

"By comparing the responses of older mice and younger mice, we have also gained insight into how type 2 diabetes increases the risk of TB.

"It appears that type 2 diabetes negatively impacts on how our immune system senses tuberculosis-causing bacteria in the lung and that vaccination with BCG::RD1 can overcome this defect.

"This makes BCG::RD1 a promising candidate for further investigation with a view to use as a vaccine for older people and those with type 2 diabetes."

In future studies the team aims to further investigate the specific immune pathways that are activated by vaccination with BCG::RD1.

Dr Kupz said multidrug-resistant TB remains a public health crisis, and makes work on new vaccines particularly important.

"That's why at AITHM we work with Australian and international collaborators to develop and test potential new vaccines, as well as to improve the effectiveness of existing treatments," he said.

Each week a woman consumes alcohol during the first five to 10 weeks of pregnancy is associated with an incremental 8% increase in risk of miscarriage, according to a study by Vanderbilt University Medical Center (VUMC) researchers.

The findings, published in the American Journal of Obstetrics and Gynecology, examine the timing, amount and type of alcohol use during pregnancy and how these factors relate to miscarriage risk before 20 weeks' gestation.

Impact of alcohol use rises through the ninth week of pregnancy, and risk accrues regardless of whether a woman reported having fewer than one drink or more than four drinks each week. Risk is also independent of the type of alcohol consumed and whether the woman had episodes of binge drinking.

Though most women change their alcohol use after a positive pregnancy test, consuming alcohol before recognizing a pregnancy is common among both those with a planned or unintended pregnancy. Half of the 5,353 women included in the analysis reported alcohol use around conception and during the first weeks of pregnancy.

The median gestational age for stopping alcohol use was 29 days. Although 41% of women who changed their use did so within three days of a positive pregnancy test, those who stopped consumption near their missed period had a 37% greater risk of miscarriage compared to women who did not use alcohol.

"Abstaining from alcohol around conception or during pregnancy has long been advised for many reasons, including preventing fetal alcohol syndrome. Nonetheless, modest levels of consumption are often seen as likely to be safe," said Katherine Hartmann, MD, PhD, vice president for Research Integration at VUMC and principal investigator for the Right from the Start cohort, from which participants were enrolled in the study.

"For this reason, our findings are alarming. Levels of use that women, and some care providers, may believe are responsible are harmful, and no amount can be suggested as safe regarding pregnancy loss."

According to the researchers, one in six recognized pregnancies ends in miscarriage, which brings great emotional cost and leaves unanswered questions about why the miscarriage occurred.

Biologically, little is known about how alcohol causes harm during early pregnancy, but it may increase miscarriage risk by modifying hormone patterns, altering the quality of implantation, increasing oxidative stress or impairing key pathways.

Because alcohol use is most common in the first weeks -- when the embryo develops most rapidly and lays down the pattern for organ development -- understanding how timing relates to risk matters.

Risk did not peak in patterns related to alcohol use in specific phases of embryonic development, and there was no evidence that a cumulative "dose" of alcohol contributed to level of risk.

The study recruited women planning a pregnancy or in early pregnancy from eight metropolitan areas in Tennessee, North Carolina and Texas. Participants were interviewed during the first trimester about their alcohol use in a four-month window.

"Combining the facts that the cohort is large, comes from diverse communities, captures data early in pregnancy and applies more advanced analytic techniques than prior studies, we're confident we've raised important concerns," said Alex Sundermann, MD, PhD, the study's first author and recent graduate of the Vanderbilt Medical Scientist Training Program.

To avoid increased risk of miscarriage, the researchers emphasize the importance of using home pregnancy tests, which can reliably detect pregnancy before a missed period, and ceasing alcohol use when planning a pregnancy or when pregnancy is possible.

NEW YORK, NY (Aug. 10) -- Only half of pregnant women worldwide who need a treatment developed over 50 years ago to prevent Rh disease--an often-fatal condition in fetuses and newborns that is now exceedingly rare in the United States and Western Europe--actually receive it, finds a study led by researchers at Vagelos College of Physicians and Surgeons (VP&S) at Columbia University Irving Medical Center.

A previous study estimated that complications of the disease may be linked to the deaths of at least 50,000 fetuses and 114,000 newborns worldwide annually.

Results of the study were published online in PLOS One.

"These findings are tragically surprising and disappointing," says Steven L. Spitalnik, MD, professor of pathology & cell biology at VP&S and senior author of the study. "This is a global crisis in which hundreds of thousands of fetuses and newborns are at risk for complications and death due to Rh disease because of a lack of awareness about, access to, and availability of effective measures to prevent this disease."

Roughly Half of Fetuses and Newborns with Rh Disease Die

Approximately 15% of women in the United States and 17% in Europe lack a protein on their red blood cells called the Rh factor. However, the estimated prevalence of women with the so-called Rh-negative blood type varies widely among different ethnic groups worldwide.

When such women become pregnant, red blood cells from an Rh-positive fetus can make their way into the mother's circulation during pregnancy or at delivery. This incompatibility prompts the mother's immune system to make antibodies and become "sensitized" to the fetus's red blood cells. During subsequent pregnancies, the mother's sensitized immune system is more likely to launch an attack against her fetus, leading to Rh disease.

More than half of fetuses or newborns with Rh disease die; those with severe disease who survive may have significant brain damage.

In the 1960s, physicians at VP&S developed an immunoprophylaxis therapy, Rh(D) immunoglobulin, that prevents the mother from becoming sensitized to her child's blood cells. Since then, Rh disease almost never occurs in the United States and other high-income countries.

"This treatment is the standard of care for preventing Rh disease, but we recognize that there remain significant obstacles to expanding access to this lifesaving therapy around the world," says Spitalnik, who has been working with an international team of physicians to increase access to therapy with Rh(D) immunoglobulin around the world.

Rh Disease Underrecognized, Undertreated in Poorer Countries

The burden of Rh disease in lower-income countries is not well known; the most recent estimates are based on reported rates of neonatal complications associated with Rh incompatibility.

For the current study, the researchers measured the gap between the women presumed to need Rh immunoprophylaxis and those who actually get it. First, they estimated the annual number of pregnancies worldwide involving an Rh-negative mother and an Rh-positive fetus, based on annual reported births and the most recent prevalence estimates of the Rh-negative blood type in each region. Next, they calculated the number of doses of Rh(D) immunoglobulin needed to treat these women and compared it with the actual number of doses administered globally.

The study found an annual worldwide gap of more than 2.5 million doses below the minimum recommended threshold for preventing Rh disease.

In particular, in 100 countries, fewer than 80% of pregnant women who required the therapy received a dose after delivery.

The biggest shortfalls occur in South Asia and Sub-Saharan Africa: Both regions have a high incidence of neonatal deaths due to complications of Rh disease, but virtually no Rh(D) immunoglobulin was dispensed.

The researchers found that none of the regions studied had acceptable levels of adherence to recommended guidelines for preventing Rh disease.

"A variety of factors, including lack of awareness of Rh incompatibility, limited availability of the therapy, and other health care priorities, play a role in hindering access to this life-saving therapy around the world," Spitalnik says. "Now that we have a better understanding of these gaps in treatment, we can begin to address them on a regional level."

To this end, Spitalnik and Brie Stotler, MD, associate professor of pathology & cell biology at VP&S and co-author of the study, along with an international group of collaborators in obstetrics & gynecology, midwifery, pediatrics, neonatology, epidemiology, and transfusion medicine, established Worldwide Initiative Rh Disease Eradication, a nonprofit organization dedicated to improving education about Rh disease and enhancing access to blood type testing and Rh(D) immunoglobulin.

New York, August 10, 2020 - "I went into the MRI bracing for the wave of panic I knew would come as soon as I was strapped down and inside the machine."

In "A Tale of Two MRIs" by patient Lelainia Lloyd, her experiences--good and bad--are shared as part of an upcoming special issue of the Journal of Medical Imaging and Radiation Sciences, published by Elsevier. This unique issue will feature stories about the interpersonal skills that medical radiation technologists must learn beyond the technical aspects to care for and guide patients through medical imaging and radiation therapy procedures. These skills--empathy, cultural competence, compassion--are not taught in a textbook. Rather they are gained through continuous learning on-the-job--and listening to patient voices is an essential part of that learning.

"I took the initial experience I had into every single MRI for years. Despite knowing that having the MRIs my neurologist ordered was important (not to mention hard to get), there were times when I would cancel because I just didn't have the capacity to cope. People who have chronic and/or serious illness often carry trauma related to medical treatment of their illnesses. With each successive stressful experience I had, that anxiety and panic grew. When I finally met with compassionate, patient-centered care, it transformed my experience."

The Journal of Medical Imaging and Radiation Sciences is the professional journal for medical radiation technologists--healthcare professionals that include radiological, nuclear medicine, and magnetic resonance imaging technologists and radiation therapists. This issue is special because it features the voices of patient authors.

Guest Editor Sue Robins, a patient and published author ("The Radiation Therapist and the Patient: Epiphanies, Stories, and Social Media") has curated this issue as a learning experience for technologists and therapists and patients alike. As Lelainia recounts, "How you choose to engage with patients matters. These experiences stick with patients and color future interactions with healthcare professionals. Done correctly, this can move the experience of healthcare being something done to a patient to something done with the patient. It shifts the balance of power from hierarchical to cooperative and honors the patient's right to autonomy."

Lelainia's eloquent story is a reminder to all healthcare professionals how crucial interpersonal skills are to patients.

A simple blood test that does not require overnight fasting has been found to be an accurate screening tool for identifying youth at risk for type 2 diabetes and heart disease risk later in life, according to a study from researchers at the Johns Hopkins Bloomberg School of Public Health.

The results suggest that the simple blood test, hemoglobin A1c (HbA1c), should be used more frequently to screen youth for diabetes and related health risks. The HbA1c test is accurate and easy to administer in younger patients.

For the study, published online August 10 in Pediatrics, the researchers analyzed national survey and medical exam data on more than 14,000 youth ages 10 to 19. One aim was to see how closely a positive result on different tests for high blood sugar (hyperglycemia) is related to risk factors for diabetes and heart disease such as obesity and high blood cholesterol.

The researchers found that hyperglycemia as defined by a blood test called HbA1c was strongly associated with these cardiometabolic risk factors, compared to hyperglycemia defined by the traditional fasting glucose test. Among youth with HbA1c-defined hyperglycemia, for example, 51 percent were obese, compared to just 29 percent of youth with hyperglycemia defined by the fasting glucose test.

The HbA1c test measures the degree to which sugar molecules have linked irreversibly to molecules in red blood cells in the previous few months. This makes it an accurate marker of chronic hyperglycemia. The HbA1c test, however, does not require compliance with overnight fasting before the test, and thus--compared to the fasting plasma glucose test--is less complicated to administer and can be less prone to error.

"Our study demonstrates that HbA1c is a useful non-fasting test for identifying high-risk youth who could benefit from lifestyle interventions to prevent diabetes and cardiovascular disease later in life," says study senior author Elizabeth Selvin, PhD, MPH, professor in the Bloomberg School's Department of Epidemiology.

The American Diabetes Association (ADA) has estimated that more than 34 million or roughly 10 percent of Americans have diabetes, and many of these cases are undiagnosed. Children and young people who develop diabetes more often develop the rarer form, type 1 diabetes, which is caused by an autoimmune reaction that destroys insulin-producing cells. However, the obesity-associated type 2 diabetes, which is far more common in adults, is rapidly becoming more prevalent in children, due to the rise in obesity, poor diet, and sedentary lifestyles. That trend has led researchers to emphasize early diabetes detection and lifestyle intervention in youth to reduce or even reverse hyperglycemia--thus helping prevent a lifetime of diabetes and associated medical complications, which can include heart disease, stroke, hypertension, and kidney disease.

In the study, Selvin and colleagues addressed some key questions about screening tools for diabetes and cardiometabolic risk by examining data on 14,119 youth aged 10 to 19 from the U.S. National Health and Nutrition Examination Surveys conducted between 1999 and 2016. The data included results of blood tests that are commonly used to detect hyperglycemia.

The ADA currently recommends such blood tests to screen for diabetes risk in youth who are at least 10 years old, are overweight or obese, and have at least one other risk factor such as a history of type 2 diabetes in close relatives, non-white race, or hypertension. One aim of the study was to evaluate how often the youth who are eligible for screening by these criteria actually have hyperglycemia--at least at the moderate level known as prediabetes.

The analysis suggested that the current screening criteria, despite covering about a quarter of U.S. children and adolescents, do not capture many youth with hyperglycemia. For example, only about one-third of the youth who had hyperglycemia as defined by a fasting glucose test would have been eligible for screening by the current ADA criteria.

"Current screening criteria miss a lot of children who are at high risk for diabetes," says study lead author Amelia Wallace, a PhD student in the Department of Epidemiology at the Bloomberg School.

The researchers also analyzed the dataset to see how closely different measures of hyperglycemia were linked to cardiometabolic risk factors. Here the HbA1c blood test was particularly useful as a screening tool, with stronger associations with the risk factors examined, compared to the fasting glucose test. For example, having hyperglycemia as defined by the HbA1c test was associated with a 4.1 times greater prevalence of obesity, whereas having hyperglycemia defined by the fasting glucose test was associated with an only 1.8 times greater prevalence of obesity.

"Some pediatricians have already been using HbA1c, but there hasn't been sufficient guidance from pediatric organizations," Selvin says. "I'm hoping that these results will help inform and guide the use of this important screening tool in clinical practice."

New Rochelle, NY, August 10, 2020--Gene therapy to the inner retina prevented blindness in a mouse model of the neuro-degenerative disorder CLN3 Batten disease. Adeno-associated viral (AAV)-mediated expression of the human CLN3 gene led to significant survival of bipolar cells and pre-served retinal function, as reported in the peer-reviewed journal Human Gene Therapy. Click here to read the full-text article free on the Human Gene Therapy website through September 10, 2020.

Batten disease is a group of fatal, inherited lysosomal storage disorders that predominantly affect children. The most prevalent form is CLN3 disease, for which there is no cure. Retinal degeneration and resulting vision loss is one of the symptoms.

Robin Ali, UCL Institute of Ophthalmology, London, and coauthors state that "Bipolar cell specific expression of human CLN3 rescues the retinal phenotype of Cln3-deficient mice." They show that the Cln3-deficient mice suffer a decline in inner retinal function resulting from the death of rod bipolar cells.

"In complex genetic diseases like Batten disease, the ultimate gene therapy solution may require parallel efforts between correction of the neurodevelopmental impairments and the vision loss," according to Editor-in-Chief of Human Gene Therapy Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School. "Thus, therapies aimed at correcting the retinal defect may prove to be very important in the care of these patients in the future."

Young adults and adolescents who are prescribed opioids for the first time may be at a slightly greater risk of developing a substance-related problem later in life, according to a new study co-authored by Indiana University researchers. However, the risk may not be as high as previously thought.

The study was published today in JAMA Pediatrics and co-authored by Patrick Quinn, an assistant professor at the IU School of Public Health-Bloomington.

The researchers looked at the health and other national records of Swedish individuals age 13 to 29, from 2007 to 2013, who were prescribed an opioid for the first time. Their goal was to further investigate whether prescribing opioids, such as codeine or oxycodone, during adolescence and young adulthood leads to a greater risk of substance-related problems.

They found that, compared with people who were not prescribed an opioid, 1 to 2 percent more of those prescribed an opioid for the first time developed a substance use disorder or other substance-related issue such an overdose or criminal conviction within five years of being prescribed.

"By using several rigorous research designs, we found that there was not a huge difference -- in fact, the difference was smaller than some previous research has found. But the study still shows that even a first opioid prescription may lead to some risk," Quinn said. "Our findings highlight the importance of screening for substance use disorders and other mental health conditions among patients with pain, including those receiving opioid therapy."

Quinn and his team used health data from Sweden because the country has nationwide records, which makes it easier to document people's prescriptions. They conducted a number of tests, including comparing youth and adolescents who were prescribed opioids with those whose pain was treated with a non-opioid pain medication. They also compared twins and other siblings of multiple births, one who was prescribed opioids and others who were not.

Across the board, the opioid recipients' risk was 1 to 2 percent greater than other people's risk. Quinn cautioned that further research is needed to determine how much of that risk is truly caused by opioid prescription and how much is caused by other factors, such as whether opioid recipients experienced more impairing pain.

The opioid epidemic in the U.S. has brought about welcome prescription policy changes, Quinn said, but it is important to have solid data that can help guide these decisions.

"Our goal is help patients and doctors understand the risks of opioid treatment for pain," he said. "We need to have a good understanding of what those risks might be in order for patients and doctors to make informed decisions."

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.

1. Initial weeks of pandemic saw a swift increase in virtual visits, sharp decrease in in-person visits at the VA

Compared to previous years, outpatient visits in 2020 decreased by 30 percent overall

Researchers from Icahn School of Medicine at Mount Sinai and the VA New York Harbor Healthcare System analyzed data from the VA Corporate Data Warehouse to describe changes in the number of in-person, telephone, and video visits during the initial 10 weeks of the COVID-19 pandemic, both overall and stratified by VA clinic. They found that there were more than 10 million fewer in-person visits to VA outpatient facilities during the initial 10 weeks of the COVID-19 pandemic compared to the preceding 10 weeks. They noted that the 56 percent decline in in-person visits was partly offset by a more than 2-fold increase in the number of telephone and video visits, but overall there was still a 30 percent decline in the number of outpatient visits. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-3026.

An accompanying editorial from the VA in Washington, DC says that these findings provide a starting point for understanding how to optimize the virtual visit experience. Optimizing telehealth visits is especially important for veterans, who are among the most at risk for COVID-19. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-5593.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author of the study, Aaron Baum, PhD, can be reached at aaron.baum@mssm.edu. The author of the editorial, Carolyn Clancy, MD can be reached at Carolyn.Clancy@va.gov.

2. Researchers report cases of myasthenia gravis associated with COVID-19 infection

Some patients with COVID-19 experience neurological symptoms. These symptoms could be caused by viral infection of nerve cells, but the possibility exists that these symptoms might be produced by autoimmune mechanisms. Researchers from Garibaldi Hospital; Catania, Italy describe three cases where patients without previous neurologic or autoimmune disorders were diagnosed with myasthenia gravis, an serious autoimmune disease that may cause weakness in the arm and leg muscles, double vision, and difficulties with speech and chewing, after the onset of COVID-19. Read the full text: https://www.acpjournals.org/doi/10.7326/L20-0845.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author of the study, Domenico A. Restivo, MD, PhS, can be reached at darestivo@libero.it.

Denver--(Embargoed for 7 a.m. EST August 8, 2020)--The interim analysis of ORIENT-11, a phase III double-blind randomized trial has shown a nearly two-fold increase in progression-free survival with addition of sintilimab to chemotherapy in patients with advanced or metastatic non-squamous non-small cell lung cancer without EGFR or ALK genomic aberrations, according to research data presented today at the International Association for the Study of Lung Cancer Virtual Presidential Symposium.

The research findings are also published simultaneously in the Journal of Thoracic Oncology, the journal of the International Association for the Study of Lung Cancer.

Previously, sintilimab in combination with pemetrexed and a platinum-based chemotherapy had shown promising activity for nonsquamous non small cell lung cancer in a phase 1b study, according to Li Zhang, M.D., of Sun Yat-sen University Cancer Center, Guangzhou, China.

Dr. Zhang and investigators from centers in China enrolled 397 patients in the study. Of these, 266 and 131 patients were randomly assigned to the sintilimab combination and to placebo combination, respectively. Patients with all ranges of PD-L1 expression (by tumor proportion score, TPS) were included. The median progression free survival per was significantly improved in sintilimab-combination group compared to placebo combination group (8.9 vs. 5.0 months)

Dr. Zhang reported that sintilimab-combination group showed a nominally significant improvement of overall survival The overall response rate also was improved for the sintilimab-combination group (51.9% versus 29%). The safety signal for the sintilimab combination was similar to that found in other studies, but rates of occurrence of grade > 3 adverse events were slightly higher in the sintilimab-combination group (61.7% versus 58.8%).

"This study demonstrated that the addition of sintilimab to chemotherapy significantly improved progression-free survival and a nominally improved overall survival, with an acceptable safety profile in [patients with] first-line non-squamous non small cell lung cancer," said Dr. Zhang. "In this study, we collected tumor samples at baseline of treatment. So, our next work will focus on biomarker exploration. By RNA sequencing of tumor samples, we look forward to searching a potential biomarker which can predict the survival benefit from PD-1 combination with chemotherapy."

PHILADELPHIA - After looking at the health records of over 10,000 patients with both HIV and multidrug resistant Tuberculosis (TB) in over 20 different countries, researchers at the Perelman School of Medicine at the University of Pennsylvania in collaboration with the Centers for Disease Control and Prevention, McGill University, and other institutions around the world, found that implementing antiretroviral therapy (ART) for HIV and newer tuberculosis medications decreased the risk of death for adults with drug-resistant TB. While the treatments associated with lower mortality risk are common in the United States and are recommended by the WHO as the best treatment for these patients, global accessibility varies widely. The findings, which were published today in The Lancet, suggest that every effort should be made to quickly bring these life-saving medications to those in need.

In the largest individual patient data meta-analysis study to assess mortality risk of people with both HIV and multi-drug resistant TB, scientists first compared the risk of death for HIV-positive people versus HIV-negative people, then examined how receiving ART and different types of TB drugs altered this risk. Because of the large sample size, associations of specific TB drugs with mortality were evaluated, focusing on the most effective drugs, categorized as "Group A" by the World Health Organization (WHO). Data from 52 studies and 37 different countries was used, and the investigators controlled for things like age, the wealth of the region in which the individuals lived, and severity of drug resistance. Researchers ultimately found that while patients with HIV infection were at higher risk of death, this risk was reduced substantially when Group A TB drugs and ART were used. As there are various types of Group A TB medications, the odds survival varied based on which Group A medication or combination was employed. When looking at only those with HIV, the risk of death was reduced by over 80% with use of specific TB drugs.

"Previous smaller studies had suggested these associations, but the large scale of this study solidifies the importance of using ART and the WHO Group A TB medications such as later-generation fluoroquinolones, bedaquiline, and linezolid to treat those who both have drug-resistant TB and are also HIV positive," said lead author Gregory Bisson, MD, MSCE, an Infectious Diseases specialist and an associate professor of Medicine at Penn. "In addition, using mortality as a measure of whether this treatment was effective offered clear answers as to just how valuable these medications are."

Having both tuberculosis and HIV is not uncommon. Multi-drug resistant TB affects roughly half a million people around the world every year according to the WHO. And of all those with TB, about 9 percent are also HIV positive. It is not surprising since HIV makes people more susceptible to all kinds of infections, like TB, as well as viral and fungal infections, Bisson said. But the reason patients in need don't often receive effective treatments for one or both of the conditions is mostly due to accessibility.

"The availability of ART and the most effective TB medications often depends on where patients live," Bisson said. "Previous studies have found that in some regions only a third of patients with drug-resistant TB access effective treatment. Given the associations with mortality we found in this study, there should be urgency in the medical community to find ways to make these medications more affordable and available."

While ART has been found to decrease risk of death when given during treatment of drug-sensitive TB, there has been less evidence indicating this is the case in the more complex case of highly-drug resistant TB disease, Bisson said. Hesitance to use ART when patients are on several drugs for drug-resistant TB may also come from the potential toxicity of ART medications. Negative effects from ART can range from neuropathy to a rash and central nervous system toxicity. While Bisson agrees that ART medications may have adverse effects, their benefits far outweigh their risks including in drug-resistant TB.

Bisson's research lays a foundation to further investigate the success of specific ARTs in conjunction with TB medications. It also allows the medical community to study methods that might bring these treatments to those who have trouble affording them or accessing them where they live.

FAIRFAX, Va. -- Endovascular treatment of vein of Galen aneurysmal malformation (VGAM) in babies with severe pulmonary hypertension can improve chances of survival, according to a study released today at the Society of NeuroInterventional Surgery's (SNIS) 17th Annual Meeting.

The study, Outcomes of Endovascular Treatment of Vein of Galen Aneurysmal Malformation in Neonates, evaluated data from 52 surgery patients with VGAMs at the Meshalkin National Medical Research Center. Eleven of these patients were younger than 10 days when surgery was performed.

Prior to surgery, all patients underwent cardiac ultrasonography to measure pulmonary artery pressure and neurosonography to measure the linear blood flow velocity in the vein of Galen and afferent vessels. All patients had pronounced pulmonary hypertension.

"This technique reduces the severity of pulmonary hypertension, thus lowering the risk for developing critical heart failure or multiple organ failure and allows babies to cross the critical line on their way to survival," said Dr. Kirill Orlov, lead author of the study. "These findings clearly indicate a new feasible treatment option for VGAM, marking a promising advancement of treatment in a case where there have been few paths forward to date."

What The Study Did: The increases and decreases in patient volume and associated changes in treatment experienced by individuals presenting with acute heart attack (myocardial infarction) before and immediately after the onset of the COVID-19 pandemic are examined in this observational study.

Authors: Ty J. Gluckman, M.D., of Providence St Joseph Health in Portland, Oregon, 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/jamacardio.2020.3629)

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