Body

PHILADELPHIA - Patients with obesity are at higher risk of developing heart failure. And yet, many obese patients face obstacles to getting heart transplants, as recovery is considered to be more challenging and risky in individuals with high body mass. Some physicians have attempted to pair bariatric surgery, which has shown to effectively reduce body mass in some patients, with LVAD surgery - considered a bridge to heart transplantation. However, the studies in general were too small to assess whether the approach was generalizable. New research from Jefferson pooled and analyzed data from multiple studies in a meta-analysis to assess the real-life impact of pairing the bridge-to-transplant LVAD surgery with a sleeve gastrectomy, a bariatric procedure for morbidly obese patients performed for weight reduction.

"Despite being at higher risk for heart disease, when patients with obesity develop heart failure, their road to transplant can be frustrating," says cardiac surgeon and senior author of the study, Vakhtang Tchantchaleishvili, MD, assistant professor of surgery at Thomas Jefferson University. "Our study shows that weight reduction surgery can help patients both lose weight, and qualify for heart transplant for which they were previously not eligible due to excessive weight." The research was published in Obesity Surgery.

The study also aimed to compare two variations of the paired approach: LVAD surgery and bariatric surgery at the same time, versus a staged approach, where bariatric surgery was performed as a separate operation on average two years after LVAD. Researchers included a total of eight studies in the meta-analysis, making up a total of 58 patients who underwent dual-surgeries for LVAD and bariatric surgery. Of these 22 had simultaneous surgeries and 37 had staged.

"The goal of the study was really to see if these two surgeries could improve a patient's chance of eligibility for heart transplant, which is the best long-term treatment for heart failure," says Dr. Tchantchaleishvili.

The researchers found that during the average follow-up of one year, 66% of these previously ineligible patients met listing requirement for heart transplant, and 33% got actually transplanted. Both simultaneous and staged approaches were comparable in terms of outcomes, including significantly reducing the body weight.

"Many people don't realize that heart failure can be a multi-year disease," says co-author Todd Massey, MD, the surgical director of the heart transplant program at Jefferson Health. "Our results show that we can improve a patients chances of successfully being put on a transplant list by pairing these surgeries."

Approximately four in five people living with hepatitis B and three out of four people with hepatitis C infection across the European Union and European Economic Area (EU/EEA) and the UK have not yet been diagnosed. This is a major obstacle on the way towards the Sustainable Development Goal (SDG) for health in 2030 as highlighted by ECDC on occasion of World Hepatitis Day.

ECDC is working in close collaboration with the World Health Organization to monitor the progress towards the elimination of hepatitis B (HBV) and C (HCV) across the EU/EEA. The first progress report highlights major gaps in prevention programmes in the region with suboptimal HBV vaccination coverage and insufficient levels of harm reduction targeting people who inject drugs.

The report shows that robust data for the so-called continuum of care looking at the numbers of diagnosed people and those in treatment and care are lacking in most countries. However, available data suggest that a high proportion of people living with hepatitis B and C infections appear to be undiagnosed and that many of those who have been diagnosed with hepatitis B and C infection are not receiving life-saving treatment. Available evidence also indicates that those at high risk of infection, including people who inject drugs and people in prison, are not being effectively targeted for testing.

In addition, mortality related to viral hepatitis is high across the region and there is very little evidence of progress towards the 2030 elimination target of a 65% reduction in mortality against the 2015 baseline.

"Looking at the latest monitoring results and surveillance data in 2020, we have to conclude that we are not on track to reach the 2030 target. To get there, Europe needs to massively scale up efforts to reduce the number of people who have never been tested for hepatitis B and C, especially among people at most risk of infection", highlights ECDC Director Andrea Ammon on occasion of World Hepatitis Day on 28 July. "Safe and effective vaccines are the main pillar for hepatitis B prevention. In addition, effective hepatitis treatment exists and improves the health of those who receive it. Treatment also helps preventing further transmission. It is as simple as that: people need to know their hepatitis status if we are to make progress towards eliminating these diseases by 2030."

European surveillance data show on-going transmission of hepatitis B and, despite a recent slight decline, high annual levels of hepatitis C diagnoses.

But according to recent ECDC findings, only a few countries across the EU/EEA have met the 2020 target of the European Action Plan to diagnose 50% of people with chronic hepatitis.

The ECDC testing guidance provides an overview of effective strategies to identify those with undiagnosed infection and highlights the importance of community testing and the integration of testing services (e.g. HIV and hepatitis) to enable synergies and efficiency in times of resource constraints.

Early diagnosis and linkage to care bring strong individual and public health benefits: effective viral hepatitis treatment either eliminates or suppresses the viruses significantly which in turn means that those on treatment interrupt existing transmission chains, preventing further infections.

The European Test Finder makes it easy to locate testing sites for HIV, hepatitis and sexually transmitted infections across Europe.

DALLAS - June 22, 2020 - For decades, high-density lipoprotein (HDL) cholesterol has been dubbed "good cholesterol" because of its role in moving fats and other cholesterol molecules out of artery walls. People with higher HDL cholesterol levels tend to have lower rates of cardiovascular disease, studies have shown.

Now, UT Southwestern scientists have analyzed data on more than 15,000 people to better understand the association between HDL cholesterol, heart attacks, and strokes in diverse populations. They found that the number of HDL particles, a little-used measurement of HDL, is a more reliable predictor of heart attack and stroke risk than the standard HDL cholesterol metric. Moreover, they found that among black people, neither HDL measurement was significantly associated with heart attack.

"Previous studies have looked at HDL levels in the population as a whole," says Anand Rohatgi, M.D., an associate professor of internal medicine at UTSW. "But we know that sometimes biology differs by gender and race, so we thought it was important to separately tease apart what's happening in those populations, as well as how HDL is associated with stroke, which has been understudied."

According to the Centers for Disease Control and Prevention, heart disease is the leading cause of death in the U.S. More than 12 percent of adults in the U.S. have high total cholesterol levels, and more than 18 percent have what's currently considered low levels of HDL cholesterol.

Cholesterol is a waxy substance that is used by the body to make hormones and keep cells functioning properly. But when low-density lipoprotein (LDL) cholesterol levels are too high, cholesterol can accumulate inside blood vessels, forming deposits called plaques. These plaques can eventually lead to blood vessel blockages that cause heart attacks or strokes. HDL cholesterol helps remove cholesterol from blood vessels. But recent studies have come to mixed conclusions about the association between HDL cholesterol levels and health outcomes.

For the new paper, published in the journal Circulation, Rohatgi and his colleagues pooled together information on people who had participated in four large, nationwide studies - the Dallas Heart Study, Atherosclerosis Risk in Communities study, Multi-Ethnic Study of Atherosclerosis, and the Prevention of Renal and Vascular Endstage Disease study. In all, the studies included 15,784 people followed over an average of 8 to 12 years. Of the participants, 54 percent were male, 22 percent were black, and their average age was 56 years.

"By combining all these large existing cohorts, we had enough numbers to look at these populations that had been understudied in the past," says Kavisha Singh, M.D., a research fellow in cardiology at UTSW and first author of the new study.

In addition, the data included two different measurements of HDL: HDL-P levels tally how many particles of HDL are circulating in the blood. HDL-C levels, the standard test, instead quantify how much total HDL cholesterol is inside those particles. Since the number of HDL particles may vary with regards to how much cholesterol they contain, the two measurements can be quite different and are only moderately correlated.

In the study, people with the highest HDL-P levels, above 37 mmol/L, had a 37 percent lower risk of heart attack and a 34 percent lower risk of stroke than those who had the lowest HDL-P levels. In women, this association was stronger - those with the highest HDL-P levels had a 49 percent reduction in heart attacks and 46 percent reduction in stroke. While HDL-C predicted heart attack risk in the overall pool of people as well as in women, it was not associated with stroke.

When the researchers homed in on black participants, the results were different - neither HDL-C nor HDL-P was linked to a black person's risk of heart attack.

"If you're white, low HDL cholesterol is still a powerful predictor of heart attack and stroke risk, and that has not changed," says Rohatgi. "But if you're not white, it's not that straightforward."

A better understanding of how HDL can help predict disease, and how that association varies among populations, is vital to lowering rates of cardiovascular disease, the researchers say.

"These risk markers are really relevant in everyday primary care and cardiology," says Singh. "Doctors use cholesterol levels to make decisions like whether a patient goes on medication or not."

The team is planning future studies on the functionality of HDL particles among black people, how HDL-P may be used clinically, and whether HDL-P might be associated with specific subtypes of strokes.

BOSTON – In a paper published in the Journal of the American Medical Association Internal Medicine today, researchers showed how analysis of data from the multigenerational Framingham Osteoporosis Study may in part explain why the incidence of hip fracture in the U.S. has declined during the last two decades. Douglas P. Kiel, M.D., M.P.H., and Marian T. Hannan, D.Sc., M.P.H., are among the authors. Dr. Kiel is Director, and Dr. Hannan is Co-Director, of the Musculoskeletal Research Center in the Hinda and Arthur Marcus Institute for Aging Research at Hebrew SeniorLife.

Led by Dr. Kiel, the Framingham Osteoporosis Study is an ancillary study of the Framingham Heart Study, which enrolled its first cohort of participants in 1948 and now includes a third generation of participants.  Initially launched to understand the epidemiology of cardiovascular disease, the study has become a treasure trove of data for epidemiologists searching for factors that contribute to many conditions that impact public health, including hip fractures. An estimated 150,000 hip fractures occur each year in the U.S., with estimated costs of care between $10.3 billion and $15.2 billion.

The cause of the decrease in the incidence of hip fracture is unknown, but has been attributed to the treatment of osteoporosis – a disease that causes bones to become weak and brittle. However, in this study, researchers looked at factors beyond osteoporosis treatment that could better explain the dramatic decline in hip fracture in recent decades. For example, Framingham Osteoporosis Study data showed that in persons aged 85 to 89 years, the incidence of hip fracture was 759 per 100,000 person-years in the offspring group compared with 2,018 per 100,000 person-years in the original cohort. The decrease in fracture was too significant to be explained by osteoporosis treatment alone, especially since the decreases were occurring before the availability of effective treatments for osteoporosis.

Study researchers carefully looked at decades of hip fracture data, which allowed statistical differentiation of changes in the incidence of hip fractures arising from the year of birth, aging, and the time period in which the data was collected. They found that a reduction in smoking and excessive alcohol consumption explained some of the declines in rates, emphasizing that ongoing public health considerations help to prevent fractures.

As a result of this study, Dr. Kiel cautioned, “While there is still a need to treat patients with osteoporosis, health care providers should continue to encourage public health interventions, specifically smoking cessation and preventing heavy drinking of alcohol.”

Dr. Hannan added, “There is a need to continue public health approaches along with treating osteoporosis to decrease fracture risk.”

This study was funded by the National Institute of Health’s National Institute of Arthritis and Musculoskeletal and Skin Diseases.

About the Hinda and Arthur Marcus Institute for Aging ResearchScientists at the Hinda and Arthur Marcus Institute seek to transform the human experience of aging by conducting research that will ensure a life of health, dignity, and productivity into advanced age. The Marcus Institute carries out rigorous studies that discover the mechanisms of age-related disease and disability; lead to the prevention, treatment, and cure of disease; advance the standard of care for older people; and inform public decision-making. For further information on the Hinda and Arthur Marcus Institute for Aging Research at Hebrew SeniorLife, please visit https://www.marcusinstituteforaging.org/.

About Hebrew SeniorLifeHebrew SeniorLife, an affiliate of Harvard Medical School, is a national senior services leader uniquely dedicated to rethinking, researching, and redefining the possibilities of aging. Based in Boston, the nonprofit organization has provided communities and health care for seniors, research into aging, and education for geriatric care providers since 1903. For more information about Hebrew SeniorLife, visit http://www.hebrewseniorlife.org and our blog, or follow us on Facebook, Instagram, Twitter, and LinkedIn.

Journal

JAMA Internal Medicine

People who received at least one flu vaccination were 17% less likely to get Alzheimer's disease over the course of a lifetime, according to researchers at The University of Texas Health Science Center at Houston (UTHealth).

First author Albert Amran, a fourth-year medical student at McGovern Medical School at UTHealth, presented the findings at the 2020 Alzheimer's Association International Conference July 27-31. The conference was held virtually due to COVID-19. Senior author of the study was Paul E. Schulz, MD, Rick McCord Professor in Neurology and Umphrey Family Professor in Neurodegenerative Diseases at UTHealth.

"Because there are no treatments for Alzheimer's disease, it is crucial that we find ways to prevent it and delay its onset," Amran said. "About 5.8 million people in the United States have this disease, so even a small reduction in risk can make a dramatic difference. We began our study by looking for ways we could reduce this risk."

Amran and Schulz teamed up with a group of researchers at UTHealth School of Biomedical Informatics, led by Xiaoqian Jiang, PhD, associate professor, to pinpoint potential factors that could reduce risk.

"Our role was to sort through enormous amounts of de-identified patient data in the Cerner Health Facts database to see whether there are drugs that could be repurposed to reduce the risk of Alzheimer's disease," Jiang said. "Once we identified the flu vaccine as a candidate, we used machine learning to analyze more than 310,000 health records to study the relationship between flu vaccination and Alzheimer's disease."

Cerner Health Facts® is a database of privacy law-compliant electronic health records from over 600 participating Cerner client hospitals and clinics that is hosted by the School of Biomedical Informatics.

Amran and the research team also found that more frequent flu vaccination and receiving vaccination at younger ages were associated with even greater decreases in risk.

"One of our theories of how the flu vaccine may work is that some of the proteins in the flu virus may train the body's immune response to better protect against Alzheimer's disease," Amran said. "Providing people with a flu vaccine may be a safe way to introduce those proteins that could help prepare the body to fight off the disease. Additional studies in large clinical trials are needed to explore whether the flu shot could serve as a valid public health strategy in the fight against this disease."

Amran also notes that more research is needed to investigate why and how the flu vaccine works in the body to help prevent Alzheimer's disease.

COLUMBUS, Ohio -- Though same-day access to IUDs increases the likelihood a woman will get the reproductive health care she wants and decreases the chance she'll become pregnant when she doesn't plan to, most providers in Ohio don't offer the service, a new study has found.

Researchers from The Ohio State University examined access to same-day implantation of the long-acting contraceptive option by calling 396 randomly selected ob-gyn offices and posing as would-be patients.

Almost 95% of practices offered IUD placement. Of those, 92% required multiple appointments.

The study appears in the journal Contraception.

"The need to make -- and keep -- multiple appointments presents significant barriers to reproductive care, particularly for those women with the fewest resources," said Jaclyn Serpico, who led the research as a graduate student in health behavior and health promotion and in women's, gender and sexuality studies.

"The challenges are likely greatest for people who can't take a lot of time off work, young people, people of color and people who live in rural areas," she said.

Following a script, callers determined whether single-visit IUD insertion was available, and whether office staff willingness to schedule an IUD insertion appointment varied by the caller's perceived age, childbearing history or race.

Office staff frequently said they required more than one visit because of a need to verify insurance coverage or order the device directly through the patient's insurance company. Even when callers said they had already checked with their insurance, office staff responded that they needed to verify benefits, the researchers found.

"Insurance coverage seemed to be the biggest perceived barrier, over and over again. That's troubling because these devices should be almost universally covered under the Affordable Care Act," Serpico said.

Women who told the office staff that they had previously given birth were more likely to be told that they could get an IUD placement the same day, the study found.

The study doesn't answer why, but possibilities include a perception that those women are more likely to be sure of what they want and better able to manage the discomfort of the procedure, said study senior author Maria Gallo, interim chair and professor of epidemiology in Ohio State's College of Public Health.

The researchers found no significant differences based on age and race in this study, but those are questions that should be explored in future research, Serpico said, particularly if the study allows for in-person interactions with office staff or clinicians.

"It's really good that we didn't see evidence of racial discrimination at the office-staff level in this study, but that doesn't mean it doesn't exist," she said.

Serpico and Gallo said this study and other work analyzing whether insurance policies are complying with the Affordable Care Act could point to a need for additional policies to ensure women are able to access IUDs, ideally in one appointment.

And there may also be opportunities for medical practices to explore operational changes that ease the way for same-day access, Gallo said.

"It could be that even just training your front desk staff to listen to the woman and what she wants and not present a barrier would make a difference. Our callers were talking to office staff, not providers. It's possible that providers might be surprised by these findings," she said.

National public health and medical organizations strongly recommend IUDs and other long-acting forms of birth control, emphasizing that most women, including those who have not had babies, are good candidates.

"IUDs are one of the most effective methods of contraception. We've seen significant drops in unintended pregnancies and a lot of this has been driven by increasing use of long-acting contraceptives," Serpico said. "Once it's inserted you just go about your life and it's working, and you don't have to do anything until you have it taken out."

COLUMBIA, Mo. - As the coronavirus pandemic continues to put a strain on health care systems, nursing homes have become overburdened with the challenge of keeping both patients and staff safe and healthy. Older residents in long-term care facilities are especially vulnerable to the effects of a respiratory illness like COVID-19, and nursing homes are not appropriately designed nor staffed to handle large numbers of infectious residents.

In response, two MU Sinclair School of Nursing support teams - the Quality Improvement Program for Missouri and the Missouri Quality Initiative - are working with the Missouri Department of Health and Senior Services to provide assistance to more than 500 nursing homes across the state.

"The main goal of our response efforts is to make sure nursing home residents are staying as safe as possible during this very traumatic and challenging experience," said Lori Popejoy, associate professor in the MU Sinclair School of Nursing. "At the beginning of the pandemic, access to personal protective equipment (PPE) was a big concern for nursing home staff. We were able to collaborate with various community organizations to distribute more than 3,000 face shields to nursing homes throughout the state."

In addition to securing and distributing PPE, other efforts include offering recommendations, guidance and support to nursing home staff and administrators as they navigate and implement the ever-changing COVID-19 infection control practices. As the Centers for Disease Control and Prevention and Missouri Department of Health and Senior Services continue to update their recommendations for mitigating the spread of COVID-19, the support teams are synthesizing, summarizing and organizing this information to help nursing homes establish and modify protocols for isolating sick patients, use PPE properly and notify the family members of infected patients.

"Now that the nursing homes are isolating residents in individual rooms, the residents are no longer dining in groups, attending group activities or inviting outside visitors into the facilities," said Amy Vogelsmeier, associate professor in the MU Sinclair School of Nursing. "In order to continue providing support to these individuals, nursing homes have adopted creative practices, such as video chatting with family members so residents can see their loved ones, or assigning staff members to check in daily with residents who may be struggling to cope with the effects of social isolation."

Given the shortage of nurses in Missouri, the pandemic has highlighted the importance of advanced practice registered nurses, who play a key role in identifying and managing illness in nursing homes to prevent avoidable hospitalizations.

"This is a time where the public is really becoming aware of the value registered nurses bring to the health care industry," Popejoy said. "It has been inspiring to see the impact they have had to mitigate the effects of this public health crisis."

With advances in genome sequencing, cancer treatments have increasingly sought to leverage the idea of "synthetic lethality," exploiting cancer-specific genetic defects to identify targets that are uniquely essential to the survival of cancer cells.

Synthetic lethality results when non-lethal mutations in different genes become deadly when combined in cells. In a new paper published online July 27, 2020 in the Proceedings of the National Academy of Sciences (PNAS), researchers at the San Diego branch of Ludwig Institute for Cancer Research and University of California San Diego School of Medicine report that inhibiting a key enzyme caused human cancer cells associated with two major types of breast and ovarian cancer to die and in mouse studies reduced tumor growth.

The research team, led by senior study author Richard D. Kolodner, PhD, Distinguished Professor of Medicine and Cellular and Molecular Medicine and member of the Ludwig Institute for Cancer Research San Diego Branch, studied Saccharomyces cerevisiae, a species of yeast used in basic research, to search for synthetic lethal relationships.

They zeroed in on Flap Endonuclease 1 (FEN1), a DNA structure-specific endonuclease involved in DNA replication and repair. Turning their attention to cancer cells, they found that when they blocked functions of FEN1 using either a small molecule inhibitor or genetic ablation, BRCA1 and BRCA2 mutant cancer cell lines were preferentially killed. Notably, normal cells were able to recover from FEN1 inhibition.

BRCA1 and BRCA2 genes normally act to prevent breast and ovarian cancer as well as other cancers, but when mutated, may cause a person to be more likely to develop breast or ovarian cancer or develop cancer at a younger age. Less than 10 percent of women diagnosed with breast cancer have a BRCA mutation, but it's estimated that 55 to 65 percent of women with the BRCA1 mutation will develop breast cancer before age 70 while approximately 45 percent of women with a BRCA2 mutation will develop breast cancer by age 70, according to the National Breast Cancer Foundation.

Similarly, women with inherited BRCA mutations have an increased risk of developing ovarian cancer and men with inherited BRCA mutations have increased risk of developing breast and prostate cancer.

Breast cancer is the most common type of cancer in the United States, with approximately 276,000 new cases per year, according to the National Cancer Institute. Prostate cancer is the fourth most common, with 191,930 new cases and ovarian is 17th, with an estimated 21,750 new cases annually, according to the National Cancer Institute.
Kolodner and colleagues then tested the approach in an immune-compromised mouse xenograft model, and found that FEN1 inhibition significantly reduced tumor growth.

The researchers say their findings are significant in two ways: They underscore the value of using S. cerevisiae yeast as a genetics tool for discovering synthetic lethality relationships and identify FEN1 inhibitors as a possible therapeutic agent to further develop for treating certain cancers with targeted vulnerabilities.

Announcing a new article publication for BIO Integration journal. In this case report the authors Zijun Zhao, Zhanghai He, Hongyan Huang, Jiewen Chen, Shishi He, Ailifeire Yilihamu and Yan Nie from Sun Yat-sen University, Guangzhou, China consider drug-induced interstitial lung disease in breast cancer patients.

Taxanes represented by paclitaxel and targeted therapy including trastuzumab are two common agents for human epidermal growth factor receptor-2 (HER-2)-positive breast cancer patients.

Effectiveness, however, usually comes at the cost of many side effects, some of which are even fatal. Drug-induced interstitial lung diseases (DILDs) comprise a group of drug-induced pulmonary injuries usually caused by using these medications. For DILDs, systemic therapy can be harmful to lung tissues and rapidly threaten the lives of some breast cancer patients.

Through case studies, and reference to related studies in medical databases, the authors discuss how multi-disciplinary integration of clinical practice and pharmacological mechanisms can make anti-cancer agents less harmful, and reduce the incidence of DILD in breast cancer patients during systemic therapy.

Yale School of Medicine and the biopharmaceutical firm AI Therapeutics have launched a multi-institutional clinical trial of a drug for treating COVID-19.

Known as LAM-002A (apilimod), the drug has a proven safety record. Preliminary research has shown it can block cellular entry and trafficking of the SARS-CoV-2 virus, the cause of COVID-19.

Previous trials involving more than 700 patients have shown LAM-002A to be safe for the treatment for autoimmune diseases and follicular lymphoma. The drug has received Fast Track Status and Orphan Drug Designation from the Food & Drug Administration for treatment of lymphoma.

The Yale Center for Clinical Investigation is now enrolling patients in a Phase II trial for the drug's use as a COVID-19 treatment. The study is expected to enroll 142 newly diagnosed patients to test the safety and efficacy of the drug in reducing virus levels in infected individuals.

AI Therapeutics, a Guilford, Conn.-based biopharmaceutical company formed by Yale alumnus Jonathan Rothberg, owns intellectual property rights to the drug.

A multi-institutional study published in Nature, which screened more than 13,000 existing drugs against two strains of the live SARS-CoV-2 virus, found LAM-002A to be the most effective in combatting the virus, including in lung cells infected with the virus. In another study in the journal Cell, another group of researchers independently showed that LAM-002A could combat SARS-CoV-2 infections in human lung cells.

AI Therapeutics' unpublished data along with data recently published by the Scripps Research Institute suggest that LAM-002A administered with remdesivir, already approved for treating COVID-19, can boost the effectiveness of the antiviral agent.

"LAM-002A holds promise to be a powerful new therapy for COVID-19 patients to prevent progression of disease, hopefully avoiding the need for hospitalization" said Yale's Murat Gunel, professor of neurosurgery and professor of genetics and neuroscience. Gunel serves as the chief scientific adviser to AI Therapeutics and has a financial interest in the company.

Gunel noted that if LAM-002A shows effectiveness in this phase, the trial could be expanded to assess whether it would help prevent the development of disease after exposure, particularly in high-risk populations, such as the elderly in nursing homes, health care and frontline workers, or people in underserved communities.

Charles S. Dela Cruz, associate professor of medicine and microbial pathogenesis and director of the Center for Pulmonary Infection Research at Yale University, will lead the study. Institutions in other areas of the country are expected to enroll patients soon.

"We are delighted to be partnering with AI Therapeutics to see if LAM-002A can help ameliorate the devastating impact of this coronavirus pandemic on our society," Dela Cruz said.

Understanding any similarities between SARS and COVID-19 inflammation could help in a clinical setting. A protein in the viruses causing COVID-19 and SARS is almost identical. Researchers propose testing if targeting COVID-19 with FDA-approved drugs, already tested in mice infected with SARS, could improve the outcomes for COVID-19 patients experiencing severe respiratory symptoms.

The finding was a collaborative effort from teams at KAUST following a comparison of Betacoronavirus genomes. "We have long-standing expertise in analyzing genomic data at KAUST's Computational Bioscience Research Center," says molecular biologist, Takashi Gojobori.

Gojobori, Carlos M. Duarte and a team of scientists compared the genomes of 24 Betacoronaviruses, including four SARS-CoV-2 viruses, which causes COVID-19. Two of the four were sequenced in the United States, while the other two were sequenced in China.

"SARS-CoV-2 appears to have recently evolved from other related Betacoronaviruses, such as the ones causing SARS and Middle East respiratory syndrome (MERS)," explains Intikhab Alam, first author of the study. "We wanted to understand the genetic make up of SARS-CoV-2. Seeing what has changed might help find ways to detect the virus and understand its rapid spread. Seeing what remains conserved between these viruses might help predict if therapeutic approaches developed for other Betacoronaviruses could work on SARS-CoV-2," he says.

Their genomic comparisons followed by structural analyses found that a small protein that extends across the viral membrane, called envelope protein E, is almost identical in SARS-CoV-2 and the SARS virus (called SARS-CoV-1).

A molecular component of this protein in the SARS virus helps trigger the release of inflammation-causing substances in its host. This inflammatory reaction causes fluids to accumulate in the lungs resulting in breathing difficulties, a condition called acute respiratory distress syndrome. Scientists studying the SARS virus have found that this reaction can be inhibited in mice by FDA-approved drugs. "Drugs that inhibit the envelope protein E of previous SARS viruses should also block the protein in COVID-19," says Alam. "Even though these drugs won't stop the virus from spreading, we hope they could attenuate or prevent acute respiratory distress syndrome and help save lives."

A group of researchers led by Osaka University established a new pathological grading system to evaluate the therapeutic effect of neoadjuvant chemotherapy (NAC) for metastatic lymph nodes (LNs) removed in esophageal cancer (EC) surgery, demonstrating that the system predicts recurrence and prognosis in EC patients better than conventional systems. Their research results were published in Annals of Surgery.

The majority of patients with progressive EC have LN metastases. Such patients usually receive NAC before surgery. Since patients who showed good response to NAC are known to have a favorable prognosis, it is important to accurately evaluate the therapeutic effect of NAC.

Routine pathological evaluation of NAC is conducted for the therapeutic effect on the primary tumor (PT). PT regression grade is determined by calculating the proportion of viable tumor area within the whole tumor bed area. Evaluations are classified into four categories according to the proportion. A high grade shows a high therapeutic effect of NAC. This tumor regression grade classification is a good indicator for predicting recurrence and prognosis.

Because metastatic status of LN, which is known to be associated with systemic micrometastases, serves as a more reliable indicator of patient survival compared with PT progression in EC patients, this group hypothesized that, in patients who have undergone NAC for EC, the pathological LN response might be a better prognostic factor than the pathological PT response.

Among 371 eligible patients, 52 had negative LNs with no evidence of regression. The researchers evaluated the therapeutic effect of NAC for the remaining 319 patients by grading pathological tumor regression into four categories according to residual tumor per tumor bed.

For all metastatic LNs, the researchers generated a total LN regression grade according to the proportion of the summed viable tumor area relative to the summed tumor bed area (Figure 1I). 153 patients (48.0%) exhibited better response and 191 (59.9%) showed a difference in response between the PT and LN regression grades. Specifically:

- Prognosis varied depending on the total LN regression grade (Figure 2A) and the recurrence-free survival (RFS) rate among responders was significantly better than that of non-responders.

- Although the therapeutic effect was significantly correlated with survival in both PT (Figure 2B) and LN (Figure 2C), the survival difference was more prominent in LN than PT.

- LN regression grade was an independent prognostic factor of the duration of survival.

- The rates of hematogenous recurrences and lymphatic recurrences were significantly lower in responder compared with non-responder in both PT and LN. However, these differences were more remarkable in LN response.

These findings show that pathological assessment of all metastatic LNs is excellent in predicting prognosis and disease recurrence in patients who undergo NAC for EC.

Lead author Professor Tomoki Makino says, "We've found that it is possible to predict disease recurrence and prognosis by performing pathological assessment of all metastatic LNs. Moving forward, this will enable 'tailor-made' treatment according to the pathological assessment of all metastatic LNs, eventually improving treatment performance of EC."

New modelling of Typhus infections in the Warsaw Ghetto during WWII reveals how public health interventions eradicated the disease.

Through state-of-the-art mathematical modelling and historical documents, the study points to community health programs and social distancing practices as the most likely explanations for the epidemic's sudden and mysterious collapse, which was hailed by survivors at the time as a miracle.

The historical analysis underscores the critical importance of the cooperation and active recruitment of communities in efforts to defeat epidemics and pandemics such as COVID-19, rather than relying too heavily on government regulation.

Mathematician and disease modeller Professor Lewi Stone from RMIT University and Tel Aviv University led the study published in Science Advances, with collaborators from Hong Kong, Amsterdam and Berlin.

In 1941, the Nazi forces in Poland crammed more than 450,000 inmates into a confined 3.4 km2 area known as the Warsaw Ghetto.

"With poor conditions, rampant starvation and a population density 5 to 10 times higher than any city in the world today, the Warsaw Ghetto presented the perfect breeding ground for bacteria to spread Typhus and it ripped through the mainly Jewish population there like a wild fire. Of course, the Nazis were well aware this would happen," Stone says.

As many as 120,000 ghetto inmates were infected by Typhus, with up to 30,000 dying directly from it and many more from starvation or a combination of both.

Stone says it was a historically documented case of disease being used as a weapon of war and as a pretext for genocide.

"Then, in October 1941, as a harsh winter was beginning and just as Typhus rates would be expected to skyrocket, the epidemic curve suddenly and unexpectedly nose-dived to extinction," he says.

"It was inexplicable at the time and many thought it was a miracle or irrational."

The team's mathematical modelling designed with theoretical ecologist Dr Yael Artzy-Randrup (University of Amsterdam) together with modelling and statistical analysis carried out by Dr Daihai He (Hong Kong Polytechnic University), shows the epidemic was in fact on track to become 2 to 3 times larger and peak in the middle of winter, just before it disappeared.

So, what happened?

-How the Ghetto beat Typhus-

Stone says the steady decline in disease transmission rates most likely reflects the success of behavioural interventions.

"Fortunately, many of the anti-epidemic activities and interventions are documented and it turns out that Warsaw Ghetto had many experienced doctors and specialists," he says.

"To learn more, I spent many, many hours in libraries around the world seeking rare documents or publications to find details about the interventions employed and the actual size of the epidemic itself, which was also poorly recorded."

Stone found evidence of well organised training courses covering public hygiene and infectious diseases, hundreds of public lectures on the fight against Typhus and an underground medical university for young students.

General hygiene and apartment cleanliness were encouraged and sometimes enforced. Social distancing was considered basic common sense, and home quarantining was not uncommon. Many volunteer soup kitchens were opened up in the period before the epidemic's decline.

"In the end, it appears that the prolonged determined efforts of the ghetto doctors and anti-epidemic efforts of community workers paid off," Stone says.

"There is no other way we can find to explain the data."

Holocaust historian Stephan Lenstaedt from Touro College in Berlin assessed the team's modelling in relation to archival material.

It tallied with primary sources including respected historian, Israel Gutman, who wrote "while almost 100,000 ghetto residents died mostly from starvation and disease in the period up until July 1942, a similar or greater number were saved thanks to the dedicated relief workers and self-help relief agencies operating".

"The tragedy, of course," says Stone, "is that almost all of those lives saved through these sacrifices, discipline and community programs would soon end in extermination at the Nazi death camps."

Typhus - a bacterial disease spread by lice - had pandemic status in Europe. It is less contagious but deadlier than COVID-19. While the two diseases spread and behave differently, the team says there are still parallels and lessons to be learnt.

"Today, more than ever, society needs to grasp how the damage caused by a tiny virus or bacteria can create utter havoc, dragging humankind to the terminal point of evil as witnessed over the Holocaust," Stone says.

"As those in the Warsaw Ghetto demonstrated, however," Artzy-Randrup explains, "the actions of individuals in practicing hygiene, social distancing and self-isolating when sick, can make a huge difference within the community to reduce the spread."

"It is the cooperation and active recruitment of communities that beat epidemics and pandemics, not government regulations alone."

"Only recently have we witnessed at close view how essential community engagement has been in containing and defeating the deadly and horrifying spread of Ebola outbreaks across African countries."

"This study is a unique instance where quantitative and qualitative methods could be used for revealing hidden historical processes at the interface of infectious diseases and society, that are directly relevant to the present COVID-19 crisis."

"Unquestionably, there are invaluable lessons for us to learn from the past," says Lehnstaedt.

The study 'Extraordinary curtailment of massive typhus epidemic in the Warsaw Ghetto' is published in Science Advances.

The ongoing disruptive changes from efforts to reduce the spread of COVID-19 are having a substantial negative impact on the physical and mental well-being of parents and their children across the country, according to a new national survey published today in Pediatrics.

Families are particularly affected by stressors stemming from changes in work, school and day care schedules that are impacting finances and access to community support networks, according to the five-day survey of parents across the U.S. run June 5-June 10 run by Monroe Carell Jr. Children's Hospital at Vanderbilt and Ann & Robert H. Lurie Children's Hospital of Chicago.

Top line results showed:

27% of parents reported worsening mental health for themselves

14% reported worsening behavioral health for their children

24% of parents reported a loss of regular child care

The impact of abrupt, systemic changes to employment and strain from having access to a limited social network is disrupting the core of families across the country. Worsening physical and mental health were similar no matter the person's race, ethnicity, income, education status or location. However, larger declines in mental well-being were reported by women and unmarried parents.

"COVID-19 and measures to control its spread have had a substantial effect on the nation's children," said Stephen Patrick, MD, MPH, director of the Vanderbilt Center for Child Health Policy and a neonatologist at Children's Hospital in Nashville. "Today an increasing number of the nation's children are going hungry, losing insurance employer-sponsored insurance and their regular child care. The situation is urgent and requires immediate attention from federal and state policymakers."

Parents with children under age 18 were surveyed to measure changes in their health, insurance status, food security, use of public food assistance resources, child care and use of health care services since the COVID-19 pandemic began.

Since March, more families are reporting food insecurity, and more reliance on food banks, and delaying children's visits to health care providers. With COVID-19 cases and deaths on the rise around the country, families may continue to experience higher levels of need and disruption.

The proportion of families with moderate or severe food insecurity increased from 6% to 8% from March to June.

Children covered by parents' employer-sponsored insurance coverage decreased from 63% to 60%.

Strikingly, families with young children report worse mental health than those with older children, pointing to the central role that child care arrangements play in the day-to-day functioning of the family.

"The loss of regular child care related to COVID-19 has been a major shock to many families," says Matthew M. Davis, MD, MAPP, interim chair of the Department of Pediatrics at Northwestern University Feinberg School of Medicine and senior vice-president and chief of Community Health Transformation at Ann & Robert H. Lurie Children's Hospital of Chicago. "In almost half of all cases where parents said that their own mental health had worsened and that their children's behavior had worsened during the pandemic, they had lost their usual child care arrangements. We need to be aware of these types of stressors for families, which extend far beyond COVID-19 as an infection or an illness."

(Boston, MA)-- In the first study to examine the association between high out-of-pocket costs and adverse cardiovascular events, research led by the Harvard Pilgrim Health Care Institute finds that individuals with cardiovascular disease risk factors who switched to high-deductible health plans (HDHPs) did not experience increased risk of heart attack or stroke. The study, "Association Between Switching to a High-deductible Health Plan and Major Cardiovascular Outcomes" appears in JAMA Network Open on July 24.

Cardiovascular disease kills more people in the U.S. than any other condition, accounting for 30% of deaths in 2017. Improvements in cardiovascular mortality began slowing a decade ago and major adverse cardiovascular events such as stroke and myocardial infarction began increasing among adults under age 65. Reasons for these trends are unclear, but experts have proposed causes such as the earlier onset of cardiovascular risk factors, stagnation of preventive care, and a change in health insurance coverage in the U.S. Concerns about the contribution of health insurance to these trends are based on the rapid expansion of HDHPs and previous research about health effects of high out-of-pocket costs.

The study team examined the effects of a transition to a HDHP on the risk of major adverse cardiovascular outcomes such as myocardial infarction and stroke. The study population, drawn from a large national health insurance plan, included individuals with risk factors for cardiovascular disease who were continuously enrolled in low-deductible (

Study findings show that HDHP members did not experience an increase in major adverse cardiovascular events compared with individuals in low-deductible plans. "Based on previous high-deductible health plan research, we had hypothesized that those with risk factors for cardiovascular disease would experience increases in major adverse cardiovascular events after a switch to high-deductible health plans, but this did not turn out to be the case," said Frank Wharam, lead author and Associate Professor of Population Medicine at the Harvard Pilgrim Health Care Institute and Harvard Medical School. Dr. Wharam adds, "HDHPs typically include features such as low or no out-of-pocket costs for medications and preventive services. Our study detected small changes in cardiovascular medication use and preventive services which may have protected HDHP members from increased adverse cardiovascular events.

These findings provide a measure of reassurance that HDHP enrollment was not associated with an appreciable increased risk of major adverse cardiovascular outcomes. But researchers caution that policymakers and employers should remain careful in promoting HDHPs among low-income and other vulnerable patients given the potential for adverse financial and health outcomes that this study did not address. Research should also extend follow up time to better assess long-term outcomes and should examine whether people with HDHPs ultimately require more intensive workups and more advanced treatments for cardiovascular events.