Body

When clinical trials were conducted to determine the immunogenicity -- the ability to elicit an immune response -- for the first two vaccines marshaled against SARS-CoV-2the virus that causes COVID-19, one group was not among those included: people who have received solid organ transplants and others (such as those with autoimmune disorders) who are immunocompromised.

Now, Johns Hopkins Medicine researchers have tried to rectify that inequity, taking one of the first looks at how people who are immunocompromised respond to their first dose of one of the two mRNA vaccines -- Moderna and Pfizer-BioNTech -- currently being administered worldwide. Their findings, as published March 15, 2021, in a research letter in the Journal of the American Medical Association, disappointingly show that only 17% produced detectable antibodies against the SARS-CoV-2 virus.

"This is in stark contrast to people with healthy immune systems who are vaccinated, nearly all of whom mount a sufficient antibody defense against COVID-19," says study lead author Brian Boyarsky, M.D., a surgery resident at the Johns Hopkins University School of Medicine.

The study evaluated the vaccine immunogenic response for 436 transplant recipients, none of whom had a prior diagnosis of COVID-19 or tested positively for SARS-CoV-2 antibodies. The median age was 55.9 years and 61% were women. Fifty-two percent were administered a single dose of the Pfizer-BioNTech vaccine and 48% received one shot of the Moderna vaccine. The median time since transplant for the participants was 6.2 years.

At a median time of 20 days after the first dose of vaccine, the researchers report that only 76 of the 436 participants (17%) had detectable antibodies to the SARS-CoV-2 virus. The researchers also found that among the 76 transplant recipients, the most likely to develop an antibody response were those younger than age 60 who did not take anti-metabolites for immunosuppression and who received the Moderna vaccine.

"Given these observations, we feel that the U.S. Centers for Disease Control and Prevention should update their new guidelines for vaccinated individuals to warn immunocompromised people that they still may be susceptible to COVID-19 after vaccination," says study senior author Dorry Segev, M.D., Ph.D., the Marjory K. and Thomas Pozefsky Professor of Surgery and Epidemiology and director of the Epidemiology Research Group in Organ Transplantation at the Johns Hopkins University School of Medicine. "As the guidelines are currently written, people assume that vaccination means immunity."

Segev says that upcoming studies will define the immunogenic response of organ transplant recipients and other immunocompromised patients after a second vaccine dose. Other studies will look at the impact of more extensive immune system profiling -- including characterizing the immune cells that remember SARS-CoV-2 after vaccination and produce antibodies, or directly attack the virus in response to the presence of the virus -- to help guide vaccination strategies for this population.

Rural America is running short on physicians. This worries health experts who have linked limited access to primary care providers to major gaps in health outcomes for rural communities.

Addressing this issue is complicated, but new research from the University of Georgia suggests that understanding geographic trends in medical school applicants could help project where the future physician workforce is likely to practice.

Knowing a medical student's hometown is an important piece of the puzzle, said study author Donglan "Stacy" Zhang, because geography is known to predict where many new doctors choose to practice.

"More than 60% of doctors choose their practice location in their birth state, as well as where they attend medical schools or residency program training," said Zhang, an assistant professor of health policy and management in UGA's College of Public Health.

"Having a lower number of medical applicants from a lower-resourced region could mean fewer future doctors providing health care in these areas," she said.

Rural applications dropped

To find out if this prediction was accurate, she and colleagues in the College of Public Health and the Department of Geography in UGA's Franklin College of Arts and Sciences analyzed trends in medical school applications and matriculation between 2001 and 2015, tracking not only where applicants came from and how that changed over time, but what factors drove those changes. In addition, the team looked at the applicants' proximity to a medical school.

They found that applications have climbed steadily over time, but the number of applications coming from rural or remote areas has dropped.

"We also found that the number of counties without any applicants was increasing during the past 15 years, with the majority of these counties, between 60% and 70% being low-income or middle-low-income," said first co-author Gang Li, a doctoral student in the College of Public Health.

Reasons for the decrease

Zhang attributes this to multiple factors, all tied to socioeconomic status.

"Students from lower-resourced families and regions have fewer educational opportunities to begin with. For example, they have limited access to quality public schools or local colleges that likely hinder their pursuing higher education. Even when they show the potential to be successful in medical education, financial constraints significantly affect their decisions to attend medical school," said Zhang.

The researchers also found that applicants tended to live near a medical school, which makes sense given the consolidation of health care facilities, medical schools and higher income families to urban settings.

Potential solutions

There are some states and medical schools that have offered tuition waivers or invested in residency programs in underserved communities to attract physicians to practice in those communities, and this is a start, but Zhang emphasizes that addressing the underlying socioeconomic disparities is critical to ensuring future primary care options for rural areas.

"Some complementary and bold policies are necessary," said Zhang.

Investment in needs-based free tuition is one option, she said. In addition, primary care roles could be filled by international medical graduates, doctor of osteopathic medicine program graduates, nurse practitioners, and physician assistants - all programs that could be more accessible to a broader set of applicants.

ANN ARBOR, Mich., (March 23, 2021) Researchers are urging consumers to avoid using weight loss or sports supplements that list deterenol as an ingredient. Scientists at NSF International (NSF), Harvard Medical School and Cambridge Health Alliance recently tested 17 brands of supplements listing deterenol as an ingredient and found nine potentially harmful, experimental stimulants in the products.

Researchers at the Netherlands' National Institute for Public Health and the Environment (RIVM) and Belgium's Sciensano also participated in the study.

Supplements containing deterenol have not been approved for use in humans in the United States and have been linked to reports of adverse events, including nausea, vomiting, sweating, agitation, palpitations, chest pain and cardiac arrest. The research was published in the peer-reviewed journal Clinical Toxicology (DOI: 10.1080/15563650.2021.1894333).

"We're urging clinicians to remain alert to the possibility that patients may be inadvertently exposed to experimental stimulants when consuming weight loss and sports supplements," said Dr. Pieter Cohen, Associate Professor of Medicine at Harvard Medical School, Internist at Cambridge Health Alliance and a co-author of the study. "We're talking about active pharmaceutical stimulants that have not been approved by the U.S. FDA for oral use as either prescription medications or dietary supplements. These ingredients have no place in dietary supplements."

In some cases, the tested supplements contained as many as four experimental stimulants per product. Combinations of these ingredients may pose health risks to consumers, as their safety is poorly understood.

"These hidden stimulant cocktails have never been tested in humans and their safety is unknown," said John Travis, Senior Researcher at NSF International and co-author of the study. "You never want to find unlabeled ingredients in supplements, but it is especially concerning to find these strange brews of experimental stimulants in products that are readily available in the United States."

The research points to the need for independent testing and certification of dietary supplements, a public health service that NSF provides. NSF facilitated development of the only American National Standard for dietary supplements (NSF/ANSI 173), which became the foundation of NSF's accredited dietary supplement certification program in 2001 (ANSI-Accredited Product Certification Body - Accreditation #0216). To earn NSF certification, products are tested for product formulation, label claims and harmful levels of specific contaminants and potentially harmful ingredients. Additionally, NSF certified dietary supplements must be produced in a manufacturing facility that is inspected twice a year to comply with the U.S. FDA's Good Manufacturing Practice (GMP) requirements.

Products certified under NSF's Certified for Sport® program must meet additional requirements and are screened for 280 athletic banned substances. Many professional and elite sports associations and leagues recommend or require the use of Certified for Sport® products, including MLB, NHL, NFL, PGA, LPGA, CFL and the Canadian Centre for Ethics in Sport.

The study's co-authors in The Netherlands and Belgium added: "If consumers feel unwell after taking a food supplement, they should immediately stop taking it ¬and seek medical advice," urged Dr. Bastiaan Venhuis, senior researcher at RIVM and Celine Vanhee, senior researcher at Sciensano. "Clinicians can then send the food supplement to independent testing authorities in order to exactly pinpoint the cause of the adverse effect."

BOSTON - An analysis of sex differences in the genetics of schizophrenia, bipolar disorder and major depressive disorders indicates that while there is substantial genetic overlap between males and females, there are noticeable sex-dependent differences in how genes related to the central nervous system, immune system, and blood vessels affect people with these disorders.

The findings, from a multinational consortium of psychiatric researchers including investigators and a senior author at Massachusetts General Hospital (MGH), could spur better treatments for major psychiatric disorders. They are published in the journal Biological Psychiatry.

The findings were made possible only through the cooperation of more than 100 investigators and research groups, who combed through the genomes of 33,403 people with schizophrenia, 19,924 with bipolar disorder, and 32,408 with major depressive disorder, as well as 109,946 controls (people without any of these diagnoses).

Their goal was to understand why these major psychiatric disorders differed between the sexes. For example, women have a significantly higher risk for major depressive disorder, whereas the risk for schizophrenia is significantly higher among men. The risk of bipolar disorder is about the same for both women and men, but disease onset, course, and prognosis differ markedly between the two.

"We're in the era of Big Data, and we're looking for genes that are associated with illnesses to identify druggable targets associated with the genotype, in order to develop more effective treatments for that illness that may differ by sex," says senior author Jill M. Goldstein, PhD, founder and executive director of the Innovation Center on Sex Differences in Medicine (ICON) at MGH.

Goldstein and colleagues searched for clues in the form of single nucleotide polymorphisms, or SNPs ("snips"), in which a single DNA "letter" (nucleotide) differs from one person to the next and between sexes.

"There are sex differences in the frequency of chronic diseases and cancers as well. It's pervasive," says Goldstein, who is also a professor of Psychiatry and Medicine at Harvard Medical School. "But medicine, essentially, has been built on models of men's health and male animals. We need to develop our precision medicine models incorporating the effect of sex."

By taking advantage of large psychiatric databases, the investigators were able to demonstrate that the risks for schizophrenia, bipolar disorder and major depressive disorder are affected by interactions of specific genes with sex, apart from the effects of sex hormones such as estradiol or testosterone.

For example, the investigators found interactions with schizophrenia and depression and sex in genes controlling for the production of vascular endothelial growth factor, a protein that promotes the growth of new blood vessels.

"My lab is studying the substantial co-occurrence of depression and cardiovascular disease. It turns out that both depression and schizophrenia have a very high co-occurrence with cardiovascular disease. We believe there are shared causes between psychiatric and cardiovascular diseases that are not due to the effects of medication," she says. "In addition, the co-occurrence of depression and cardiovascular disease is twice as high in women as in men, and this may, in part, be associated with our finding in depression of sex differences in a gene controlling vascular endothelial growth factor."

The investigators emphasize that although the specific causes of the diseases they studied are still unknown, "our study underscores the importance of designing large-scale genetic studies that have the statistical power to test for interactions with sex. Dissecting the impact of sex, genes, and pathophysiology will identify potential targets for sex-dependent or sex-specific therapeutic interventions creating more effective therapies for both men and women," she says.

A new technique that can trace which tissues and organs the DNA in our blood comes from has been reported today in the open-access eLife journal.

The method, called GETMap, could be used in prenatal screening, to monitor organ transplant rejection, or test for cancers that are concealed in the body.

"Analysis of circulating free DNA has been shown to be useful for screening for early asymptomatic cancers," explains first author Wanxia Gai, Postdoctoral Fellow at the Chinese University of Hong Kong, Hong Kong SAR, China. "As cancer-associated DNA changes are present in a wide range of cancer types, detection of such changes can be used as a universal test for concealed cancers. However, in patients with a positive test result, you still need to follow up with tests to find the tumour's location, for example, with a whole-body positron emission tomography, or PET, scan."

To address this, the team developed a test that looks for genetic differences, as well as epigenetic changes to DNA (changes which do not affect DNA sequences) known as methylation. The DNA in our cells has a unique methylation 'fingerprint'. Comparing the methylation fingerprints of different genetic types of DNA molecules circulating in the blood, for example molecules from a foetus, transplanted organ or tumour, with that of different tissues identifies where the DNA has come from.

The team first tested their approach in pregnant women, where they knew that blood DNA would include DNA from the mother, foetus, or both. As expected, GETMap found that DNA carrying foetus-specific genetic markers carried methylation signatures exclusively from the placenta. On the other hand, DNA molecules carrying mother-specific genetic markers carried methylation signatures from white blood cells. DNA molecules carrying genetic markers shared by both the mother and foetus were derived from both tissues.

Next, they tested the approach in blood donated by patients following a lung transplant. Detecting unusually high concentrations of DNA from a transplanted organ in blood can be a sign of organ rejection. But immediately after a transplant, there is often an unexplained surge in donor-derived DNA in the transplant recipient's blood. This makes it challenging to detect whether the organ is being rejected if only genetic markers are used. By using a combination of genetic and epigenetic markers, the team identified the origins of this surge in donor DNA. At 72 hours after transplantation, only 17% of the circulating DNA was from the lung, compared with 78% from blood cells. This surprisingly high contribution from the blood cells was likely due to the release of DNA from blood cells in the blood vessels of the transplanted lung. With time, the amount of circulating DNA from the lung increased, and the amount from blood cells decreased. There also seemed to be more donor lung DNA in the blood of patients whose new lungs were rejected, compared to those who had a successful transplant.

The team also tested whether GETMap could detect the origin of tumour-derived DNA in the blood. In two patients with liver cancer, they found that 90% and 87% of the plasma DNA carrying mutations had come from the liver. To test this, they needed to know the exact tumour mutations they were looking for, and tumour tissue is not always available if its location is unknown. The team therefore tried to use methylation fingerprints to identify cancer mutations directly from blood DNA rather than tumour tissue. Although fewer mutations were found, the liver was still correctly identified as the source of the tumour-derived molecules. This suggests GETMap could help to reveal the tissue and location of concealed cancers in people who have tumour markers in their blood.

Finally, they challenged the GETMap test in a woman who developed lymphoma during pregnancy. In this instance, they were able to distinguish between the foetal-specific genes which were derived from the placenta, and the tumour-specific genes which originated solely from a family of white blood cells that were related to the cell type of the lymphoma.

"We have demonstrated the powerful synergy between genetic and epigenetic approaches for identifying the origin of circulating DNA in the blood, and shown its potential applications in cancer screening, prenatal testing and organ transplant monitoring," says co-senior author Dennis Lo, Director of the Li Ka Shing Institute of Health Sciences, and the Li Ka Shing Professor of Medicine at the Chinese University of Hong Kong.

"Our test could bring us closer to the vision of a blood test for a universal cancer marker, by allowing more targeted follow-up tests in specific organs," concludes co-senior author Allen Chan, Professor of Chemical Pathology at the Chinese University of Hong Kong. "This could make cancer diagnosis earlier and more accurate, and reduce the use of whole-body scans and the associated exposure to radiation."

DALLAS - March 23, 2021 - Vaccinating health care workers resulted in an immediate and notable reduction of positive COVID-19 cases among employees, reducing the number of required isolations and quarantines by more than 90 percent, according to data at UT Southwestern Medical Center published in the New England Journal of Medicine.

Health care workers were among the first groups to be eligible for vaccination.

"Real-world experience with SARS-CoV-2 vaccination at UT Southwestern demonstrated a marked reduction in the incidence of infections among our employees, preserving the workforce when it was most needed," notes Daniel K. Podolsky, M.D., president of UT Southwestern and senior author.

During the first 31 days of vaccinations becoming available, UT Southwestern provided a first dose to 59 percent of roughly 23,000 employees, while 30 percent were able to be fully vaccinated in that time frame. Among the findings:

1.5 percent became infected.
Infection rates were highest - 2.6 percent - among nonvaccinated employees.
Infection rates were lowest - .05 percent - among those fully vaccinated.

"Our ability to quickly vaccinate a majority of our workforce in the midst of what became the largest surge to date in the region made a critical difference in ensuring we were able to continue providing top-flight care while health systems were strained," says John Warner, M.D., executive vice president for health system affairs at UT Southwestern.

Researchers also saw advantages among partially vaccinated individuals, and from Jan. 9, the actual number of positive tests among all UT Southwestern employees was consistently lower than the number projected.

The data also show continued need to address vaccine hesitancy, with UT Southwestern now approaching 70 percent immunization among its workforce.

"In light of this real-world experience clearly demonstrating the effectiveness of immunization, further understanding of the reticence of some individuals to take advantage of vaccination bears even greater importance," says first author William Daniel, M.D., vice president and chief quality officer at UT Southwestern.

UT Southwestern has provided educational outreach to community groups and businesses, developed extensive online resources including Q&As and blogs, and is preparing to launch a multilingual public service announcement campaign to help educate diverse communities about vaccination and address issues of hesitancy.

"It is important to reach out across multiple platforms to effectively address people's questions so that we can continue to make progress on vaccine hesitancy," says Marc Nivet, Ed.D., executive vice president for institutional advancement at UT Southwestern.

A pilot study from North Carolina State University and the University of North Carolina at Chapel Hill has found evidence of Bartonella infection in the blood of people with schizophrenia and schizoaffective disorder.

"Researchers have been looking at the connection between bacterial infection and neuropsychiatric disease for some time," says Dr. Erin Lashnits, a former veterinary internist at NC State, current faculty member at the University of Wisconsin and first author of the study.

"Specifically, there has been research suggesting that cat ownership is associated with schizophrenia due to the zoonotic parasite Toxoplasma gondii, but to date there has been no conclusive evidence in support of a causative role for this parasite. So we decided to look at another cat-associated infectious agent, Bartonella, to see if there could be a connection."

Bartonella are bacteria historically associated with cat-scratch disease, which until recently was thought to be solely a short-lived (or self-limiting) infection. Cats can become infected with Bartonella via exposure to fleas and potentially ticks, which are natural vectors of the bacteria. The cat is a host for at least three of the 40 known Bartonella species: Bartonella henselae, Bartonella clarridgeiae and Bartonella koehlerae.

"While there is emerging understanding of neuropsychiatric illnesses such as schizophrenia as disorders of brain networks, the question about the actual causes remains unanswered," says corresponding author Flavio Frohlich, associate professor of psychiatry at the UNC School of Medicine. "It was an exciting opportunity for us in the UNC Department of Psychiatry to team up with the leading experts on Bartonella to pursue this innovative idea of a potential link to schizophrenia. To our knowledge, this is the very first work that examines a potential role of Bartonella in schizophrenia."

The research team enrolled a group of 17 people with stable, medically managed schizophrenia or schizoaffective disorder, and a control group of 13 healthy adults, to test for evidence of Bartonella infection.

All participants filled out questionnaires on severity of symptoms and potential Bartonella exposure. Blood samples were taken from participants twice in a one-week period. The samples were cultured in a growth medium, and both cultured and whole blood samples underwent qPCR and droplet digital, or ddPCR testing, at seven-, 14- and 21-day intervals, to look for evidence of Bartonella organism-specific DNA. Blood samples were also tested for Bartonella species-specific antibodies.

Of the 17 patients with schizophrenia, 12 had Bartonella DNA in their blood, as compared to only one of 13 in the control group. According to the questionnaires, both patients and controls reported similar pet ownership and flea exposures.

"Bartonella ddPCR, a very new diagnostic technology, provides a more sensitive molecular test than we've previously had access to," says Dr. Ed Breitschwerdt, Melanie S. Steele Distinguished Professor of Internal Medicine at NC State and study coauthor. "If we had not used ddPCR to test this cohort of individuals, we would not have found Bartonella DNA in any of the participants, either case or control."

"It is important to remember that our study was by design not able to demonstrate a causal link between Bartonella infection and schizophrenia," Frohlich says. "However, we believe this initial observational study strongly supports the need for follow-up research."

The researchers plan to proceed with a larger study to see whether their preliminary results are borne out.

"Many of these patients have been undergoing care for years," Breitschwerdt says. "What we're starting to see is a pattern - Bartonella can persist for a long time. And for the subset of people who can't eliminate the infection, the bacteria can cause chronic or progressive illness."

By targeting an enzyme that plays a key role in head and neck cancer cells, researchers from the UCLA School of Dentistry were able to significantly slow the growth and spread of tumors in mice and enhance the effectiveness of an immunotherapy to which these types of cancers often become resistant.

Their findings, published online in the journal Molecular Cell, could help researchers develop more refined approaches to combatting highly invasive head and neck squamous cell cancers, which primarily affect the mouth, nose and throat.

Immunotherapy, which is used as a clinical treatment for various cancers, harnesses the body's natural defenses to combat disease. Yet some cancers, including head and neck squamous cell carcinomas, don't respond as well to the therapy as others do. The prognosis for these head and neck cancers is poor, with a high five-year mortality rate, and there is an urgent need for effective treatments.

The UCLA research team, led by distinguished professor Dr. Cun-Yu Wang, chair of oral biology at the dentistry school, demonstrated that by targeting a vulnerability in the cellular process of tumor duplication and immunity, they could affect tumor cells' response to immunotherapy.

The enzyme they focused on, KDM4A, is what is known as an epigenetic factor -- a molecule that regulates gene expression, silencing some genes in cells and activating others. In squamous cell head and neck cancers, overexpression of KDM4A promotes gene expression associated with cancer cell replication and spread.

It is well known that tumor cells can spread undetected by the immune system and, without surveillance, can metastasize to lymph nodes or other parts of the body. In this instance, tumor cells that develop in the epithelial layer that lines the structures of the head and neck can turn into head and neck squamous cell carcinoma when unchecked.

Cancer cell replication occurs through the abnormal spread and activation of signaling pathways for cancer cells, and the researchers asked the question: If we can disrupt these processes and identify a vulnerability, can we change the body's response to fighting cancer cells and its response to outside immunotherapy?

"We know that the KDM4A gene plays a critical role in cancer cell replication and spread, so we focused our study on removing this gene to see if we would get an opposite response," said Wang, the study's corresponding author and a member of the UCLA Jonsson Comprehensive Cancer Center.

By removing the KDM4A gene in their mouse models, the researchers witnessed a notable decrease in squamous cell carcinomas and far less metastasis of cancer to the lymph nodes -- a precursor to the spread of the disease throughout the body. Surprisingly, they also discovered that the KDM4A's removal also led to the recruitment and activation of the body's infection-fighting T cells, which killed cancer cells and stimulated inherent tumor immunity.

They then sought to uncover why the squamous carcinoma cells had such a poor response to immunotherapy treatment. In another set of mouse models, they again removed KDM4A and introduced a PD-1 blockade, which signals immunotherapy drugs to attack cancer cells. The combination of immunotherapy and KDM4A removal further decreased squamous cell cancer growth and lymph node metastasis.

Next, the researchers tested whether a small-molecule inhibitor of KDM4A could improve the efficacy of the original PD-1 blockade-based immunotherapy. They found that the inhibitor also significantly helped remove cancer stem cells, which are associated with cancer relapse.

The findings hold promise for the development of more specific inhibitors for KDM4A and more effective cancer immunotherapies.

"I am continuously impressed by Dr. Cun-Yu Wang and his team for breaking through barriers in our understanding of cancer-causing cellular processes," said Dr. Paul Krebsbach, dean and professor at the UCLA School of Dentistry. "The results of this study have major implications for the development of more effective, life-saving cancer therapies."

People who received a flu shot last flu season were significantly less likely to test positive for a COVID-19 infection when the pandemic hit, according to a new study. And those who did test positive for COVID-19 had fewer complications if they received their flu shot.

These new findings mean senior author Marion Hofmann Bowman, M.D., is continuing to recommend the flu shot to her patients even as the flu season may be winding down.

"It's particularly relevant for vaccine hesitance, and maybe taking the flu shot this year can ease some angst about the new COVID-19 vaccine," says Hofmann, an associate professor of internal medicine and a cardiologist at the Michigan Medicine Frankel Cardiovascular Center. Michigan Medicine is the academic medical center of the University of Michigan.

Researchers reviewed medical charts for more than 27,000 patients who were tested for a COVID-19 infection at Michigan Medicine between March and mid-July of 2020. Of the nearly 13,000 who got a flu shot in the previous year, 4% tested positive for COVID-19. Of the 14,000 who hadn't gotten a flu shot, nearly 5% tested positive for COVID-19. The association remained significant after controlling for other variables including ethnicity, race, gender, age, BMI, smoking status and many comorbid conditions, Hofmann says.

People who received their flu shot were also significantly less likely to require hospitalization, although the researchers didn't find a significant difference in mortality between the two groups. No one in the study tested positive for both infections at the same time.

The underlying mechanism behind the association isn't yet clear, Hofmann says.

"It is possible that patients who receive their flu vaccine are also people who are practicing more social distancing and following CDC guidelines. However, it is also plausible that there could be a direct biological effect of the flu vaccine on the immune system relevant for the fight against SARS-CoV-2 virus," she says.

Prospective longitudinal studies to examine the effect of the flu vaccine on respiratory illness are ongoing, including the Household Influenza Vaccine Evaluation (HIVE) study through the University of Michigan's School of Public Health.

"It's powerful to give providers another tool to encourage their patients to take advantage of available, effective, safe immunizations," says co-first author Carmel Ashur, M.D., M.S., an assistant professor of internal medicine and a hospitalist at Michigan Medicine.

Months ago, Hofmann was concerned about misinformation she kept seeing online that connected the flu vaccine with a COVID-19 infection. Prominent media outlets like Reuters debunked this theory, and she knew her team's data could also help address vaccine hesitancy.

"Instead of a concerning connection between COVID-19 and the flu shot, our publication provides more confidence that getting your flu shot is associated with staying out of the hospital for COVID-19," she says.

Before the pandemic hit, Hofmann and co-first author Anna Conlon, Ph.D., a U-M Medical School student, educated Frankel CVC patients about another encouraging association with the flu vaccine: cardiovascular protective effects.

"There's robust data that the flu shot prevents heart attack and hospitalizations for heart failure, which is an additional reason to get your vaccine every flu season," Conlon says.

WASHINGTON--Exposure in the womb to a drug used to prevent miscarriage appears to raise the offspring's cancer risk decades later, especially for colorectal and prostate cancers, researchers have found. They will present the results of their new study Tuesday at ENDO 2021, the Endocrine Society's annual meeting.

Some adult children of women who received the drug, hydroxyprogesterone caproate (OHPC or 17-OHPC), during pregnancy in the 1950s and 1960s are now experiencing more than twice the odds of cancer, said the study's lead researcher, Caitlin Murphy, Ph.D., M.P.H., an assistant professor at the University of Texas Southwestern Medical Center in Dallas, Texas.

OHPC is a synthetic progestogen hormone that was first marketed in the mid-1950s (as Delalutin in the United States) to treat pregnant women with recurrent or threatened miscarriage. It is still available in the United States for pregnant women (under the trade name Makena) to prevent preterm birth.

"There is compelling evidence that some synthetic hormones cause endocrine disruption during early fetal development that may lead to cancer later in life for the offspring," Murphy said.

As an example, she cited the synthetic estrogen diethylstilbestrol (DES) that some pregnant women took in the 1970s and that years later was found to increase the risk of certain cancers in adult daughters of those women.

"The rates of some cancers, such as colorectal cancer, are increasing in adults younger than 50, and we wondered if endocrine disruption in utero--in the womb--may partly contribute to this increase," she said.

Murphy and her colleagues examined the effect of OHPC exposure on the cancer risk among adult offspring of mothers who used OHPC during the pregnancy with them versus offspring whose mothers did not. All mothers were participants in the Child Health and Development Studies, a group who received prenatal care between June 1959 and June 1967 in the Kaiser Foundation Health Plan in Oakland, Calif. The researchers used the California Cancer Registry to identify cancers diagnosed in the adult children through 2018.

Among more than 18,751 live births, 954 cancer diagnoses were made in offspring ages 18 to 58 years, the researchers found. A total of 181 women received OHPC during pregnancy. The children they gave birth to had cancer detected in adulthood more than twice as often as nonexposed offspring. Most of these cancers--65 percent--occurred in people younger than age 50, Murphy noted.

Furthermore, OHPC-exposed offspring had a nearly five times higher rate of colon and rectal cancers and almost four times the rate of prostate cancer compared with nonexposed offspring, according to Murphy, who said the strength of this association surprised them. Rates of breast cancer and cervical cancer also were elevated in exposed offspring but not as dramatically, she said.

"Our findings suggest multiple organ systems are susceptible to endocrine disruption during early development, which may increase risk of cancer decades later," Murphy said. "Caution using OHPC and other endocrine-active pharmaceuticals in early pregnancy is warranted."

The U.S. Food and Drug Administration proposed in October 2020 that OHPC be withdrawn from the market because postmarket studies failed to verify clinical benefits.

WASHINGTON, March 23, 2021 -- Scientists have been working for the past year to find ways to curb the effects of the COVID-19 pandemic. Though it is outside their typical realm of study, physicists have been playing an important role in many aspects of research about the pandemic and its impact on people.

Particle physicists' keen understanding of gas handling systems positioned them at the forefront for pioneering low-cost, mass-producible ventilators to help address the worldwide shortage. Led by Cristian Galbiati, professor of physics at Princeton University and the Gran Sasso Science Institute, an international, interdisciplinary team called the Mechanical Ventilator Milano (MVM) collaboration spearheaded one effort and presents the design in the journal Physics of Fluids, from AIP Publishing.

The project began in March 2020, shortly after Italy went into lockdown. Only one week later, the MVM collaboration had a working prototype.

The ventilator consists of a gas inlet valve and a gas outlet valve, along with a series of controls and alarms to ensure proper monitoring and customizability from patient to patient. The design is built from readily available parts and is presented under an open license, allowing developing countries to quickly and easily manufacture their own units.

"The idea behind the design was to have a system as simple as possible -- delivery of air through a single valve, exhaust of air through a single valve," said Galbiati.

Because the MVM is developed specifically for COVID-19 patients, it has reduced functionality compared to typical ventilators. This simpler design cuts the cost of production up to fivefold to under $10,000 per unit.

"This pandemic comes upon us, and you feel somewhat helpless as someone who isn't a medical physicist," said physics Nobel laureate Arthur McDonald, at Queen's University and a co-author on the paper. "Our collaboration of particle physicists, engineers, and software specialists from national labs, academia, and industry have applied their existing talents to create a new, accessible design and to provide a new manufacturing capability internationally to address the most serious cases during the pandemic."

"For a scientist committed to fundamental research, such as the search for the dark matter of the universe, it is extremely important to devote time and experience to build devices that can help to improve people's health," said Walter Bonivento, a senior scientist at INFN Cagliari and co-author on the paper.

The MVM has already received emergency use authorization from the U.S. Food and Drug Administration and received Health Canada Medical Device Directorate authorization. About 6,000 units have been delivered to date under a contract from the Canadian government for its stockpile, with the potential for more, if requested. Donations from Canada to developing countries in need have also been considered from the beginning of the contract award.

What The Study Did: Employees of a health care system were surveyed on the eve of vaccine distribution to encourage them to receive a COVID-19 vaccine, assess their intentions to do so and understand reasons for hesitancy.

Authors: Michelle N. Meyer, Ph.D., J.D., Center for Translational Bioethics and Health Care Policy at the Geisinger Health System in Danville, Pennsylvania, 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/jamanetworkopen.2021.5344)

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

Incorporating Black churches and clergy in COVID-19 vaccination education and distribution has been found to be an effective model in helping to increase vaccination delivery to historically at-risk populations in San Bernardino County, a study says.

Focused education efforts and an on-site mobile clinic in Black church parking lots resulted in the vaccinations of 417 people, 84% of whom were Black. The study also found an increase in Black attendance of mass vaccination clinics to 3.6% of total patients, up from 3%, in the week post-initiative.

Researchers at Loma Linda University School of Pharmacy published their findings on March 10 in The Lancet Global Health, highlighting their model that sought to ensure equitable distribution of vaccines among a diverse population. The study, A three-tiered approach to address barriers to COVID-19 vaccine delivery in the Black community, illustrates a method of partnership among Black faith leaders, public health officials, and Black medical professionals that has led to more COVID-19 vaccinations in the Black community.

The initiative was developed in the wake of decades of the Black community's institutional distrust, inadequate access to healthcare, and ultimately, the absence of transparency in vaccine allocation to heavily disparaged areas, which have left them at a disadvantage, researchers said.

"The U.S. is considered a highly religious nation, and prayer, as well as the promotion of medical treatment by religious leaders, has been historically important in establishing trust in healthcare among Black Americans," said Jacinda Abdul-Mutakabbir, PharmD, assistant professor at Loma Linda University School of Pharmacy and first author of the paper. "The pastors' leadership was integral to the success of this initiative, as they are well acquainted and had established direct communication with individuals in the Black community."

Various barriers to vaccination disproportionately affect Black communities, such as access to the internet and computers, and lack of transportation, Abdul-Mutakabbir said. In the United States, particularly in California, the delivery of COVID-19 vaccinations to Black individuals continues to lag significantly behind that of their non-Hispanic white counterparts, according to the Centers for Disease Control and Prevention, and COVID-19 death rates among Black, Hispanic and Native Americans are three times higher than the rate of white Americans.

Public health officials joined researchers in mobilizing their efforts around Loma Linda University Health's mass vaccination clinics, which is the largest vaccination effort for residents of San Bernardino County. Three major sites deliver approximately 2,000 vaccines a day. Like other nationwide vaccination efforts, the sites in Loma Linda are located in a suburban area, appointments are made online, and vaccines are available to individuals free of charge. Public health officials lamented the low percentage of Black individuals coming through the clinics.

"A more proactive approach was clearly required," Abdul-Mutakabbir said.

Researchers developed relationships with two organizations dedicated to confronting prominent issues in the Black community: Inland Empire Concerned African American Churches (IECAAC) and Congregations Organized for Prophetic Engagement (COPE) to assist Loma Linda University in organizing a COVID-19 faith summit -- a comprehensive COVID-19 information session to gain the pastors' support of the available vaccines.

After the summit, pastors advertised and coordinated educational webinars about the COVID-19 vaccinations, distributed registration paperwork designed to ensure internet access was not a barrier, and managed appointment lists for their community members before they attended the vaccination clinic.

Recognizing the need for intended education measures to decrease COVID-19 vaccine hesitancy, Abdul-Mutakabbir a Black pharmacist with specialized infectious disease training, provided several COVID-19 vaccination webinars before the mobile vaccination clinic date.

Abdul-Mutakabbir also managed transportation of the vaccines to the clinic and ensured each vaccine was properly drawn from the vials before administration to individuals during the clinic visits. These efforts resulted in establishing a trusting environment of familiarity among Black faith leaders and community members.

"The equitable allocation of the COVID-19 vaccines is essential to confronting the racial disparities magnified by the current pandemic," Abdul-Mutakabbir said. "We hope to continue our efforts using the power of faith and science to keep these vulnerable populations healthy and protected from the virus."

Hennigsdorf/Berlin, Germany, March 23, 2021 - Diagnostics company SphingoTec GmbH ("SphingoTec") announced today the first published data (1) on the biomarker DPP3 that can predict the evolution of organ function and survival in septic patients. Measured on top of routinely used standard parameters, such as Lactate and Procalcitonin, DPP3 is an early indicator of short-term outcomes and patient severity. Sepsis is a medical emergency caused by a dysregulated host response to an infection, with mortality rates increasing rapidly for each hour that appropriate treatment is delayed (2). The rapid evolution of sepsis into its severe form, septic shock, raises the need for more precise and faster testing to support better clinical decision-making.

DPP3 is an enzyme at the core of a newly discovered disease mechanism responsible for cardiovascular depression and short-term organ failure in critically ill patients. Although intracellular DPP3 is involved in normal metabolic processes (3), massive cell death leads to DPP3 release into the bloodstream. Circulating DPP3 inactivates Angiotensin II, a hormone regulating the renin-angiotensin-aldosterone system (RAAS), which ultimately controls hemodynamics (4,5). Angiotensin II depletion leads to cardiovascular depression (6,7,9,10) and reduced vascular tone (6,8), a hemodynamic instability that quickly escalates in multiple organ failure. DPP3 was already shown to add value in various critical care settings such as cardiogenic shock (7,9) and burn shock (10).

The data from the prospective observational multi-center AdrenoOSS-1 study enrolling about 600 patients with sepsis and septic shock have shown that DPP3 levels can predict multiple short-term organ failure and the need for organ support therapies in this population (1). High or increasing DPP3 blood levels precede organ injury and predict the need for vasopressor/inotropic use, mechanical ventilation, and renal replacement therapy. DPP3 blood levels also reflect patient severity, with septic shock patients having a significantly higher DPP3 concentration than patients with severe sepsis (1,3). The study data further show that low or decreasing levels of DPP3 in the first 24 hours of ICU admission predict an improvement of organ function and better outcomes. The dynamic nature of the biomarker can guide intensivists in the early management of septic shock patients.

Dr. Andreas Bergmann, founder of various companies, where new tools to fight sepsis mortality are developed, and CEO of critical care diagnostics company SphingoTec commented: "This newly discovered biomarker makes it easy to identify a distinct pathophysiological mechanism leading to mortality in sepsis and uncovers the etiology of clinical symptoms. The published data show that measuring DPP3 levels add value in the clinical practice by early revealing organ injury and adding information on top of standard parameters. This can help guide intensivists in the early management of septic patients."

The in vitro diagnostic test for DPP3 is available as a microtiter plate as well as a near-patient rapid test (IB10 sphingotest® DPP3). SphingoTec has made the test available for the critical care community to further assess the clinical utility of the DPP3 biomarker in acute care settings.

Consumption of ultra-processed foods and drink could increase the risk of developing colorectal cancer. This was the conclusion of a large study undertaken by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the "la Caixa" Foundation, based on questionnaires about food behaviours completed by around 8,000 people in Spain. The study, the first of its kind in the country, also analysed the relationship between ultra-processed food and drink products and two other cancers; while no association was observed with prostate cancer, in the case of breast cancer a higher risk was observed in the sub-group of former and current smokers who reported a diet high in ultra-processed products.

Social, economic and industrial changes have driven a rise in ultra-processed food and drink consumption, which currently accounts for between 25% and 50% of the total energy intake in diets in Europe and in high- and middle-income countries. The Nova classification system groups all foods and drinks into four categories according to how much processing they undergo. Ultra-processed foods--those that undergo the most processing--are industrial formulations with more than five ingredients which usually contain additional substances, such as sugar, fats, salt and additives. Examples of products in this category include sugary soft drinks, ready meals and mass-produced industrial baked goods.

Several studies have linked the consumption of ultra-processed foods and drinks to health risk factors, cardiovascular diseases, type 2 diabetes and an increased risk of premature death. There are only a few studies on the relationship of these food products with cancer and the results are not entirely conclusive. A French study found an association between the consumption of ultra-processed foods and an increased cancer risk. A Canadian study found an increased risk of developing prostate cancer with a higher intake of processed foods, but not with ultra-processed foods.

The aim of the present study was to assess whether the consumption of ultra-processed foods and drinks is associated with an increased risk of colorectal, breast or prostate cancer. To this end, the researchers undertook a case-control study of 7,843 adults living in different Spanish provinces: half of the participants had a diagnosis of colorectal (1,852), breast (1,486) or prostate cancer (953); and the other half were people with the same characteristics who did not have cancer. Data were obtained from the multicase-control study MCC-Spain. Dietary data was collected using a validated questionnaire designed to evaluate the frequency of consumption of usual food and drink items over a one-year period. The results were then classified according to the level of processing using the Nova classification.

The study, published in Clinical Nutrition, concluded that the consumption of ultra-processed foods and beverages is associated with an increased risk of colorectal cancer: a 10% increment in the consumption of ultra-processed foods and drinks was found to be associated with an 11% increase in the risk of developing colorectal cancer.

Dora Romaguera, first author of the study and researcher at ISGlobal, the Institut d'Investigació Sanitària Illes Balears (IdISBA) and the CIBEROBN, says that this relationship can be explained, in part, "by the low intake of fibre, fruits and vegetables, which are known to offer protection against colorectal cancer, among people who eat a lot of ultra-processed foods, but also by the additives and other substances with carcinogenic potential typically used in processed food products."

In the case of breast cancer, no strong relationship was found, but an association was observed in the group of current and former smokers. Romaguera explains that "smoking is a risk factor for breast cancer, and smoking and certain dietary factors, such as the consumption of ultra-processed foods and beverages, are known to have synergetic effects on cancer development."

No association was found between prostate cancer and a diet high in ultra-processed products. "This finding is not surprising and is consistent with the results of previous studies of dietary factors and prostate cancer risk, in which no link was found," adds Romaguera.

Colorectal and Breast Cancer Cases: Less Healthy Diets

The results of the study showed that people with breast and colorectal cancer, but not those with prostate cancer, reported less healthy diets than people without cancer in the control group. "We found differences in terms of their intake of energy, fibre, energy density and saturated fatty acids. Consumption of ultra-processed foods and beverages was higher among colorectal and breast cancer cases than in the controls", says ISGlobal researcher Sílvia Fernández, joint first author of the study.

The food groups that accounted for the largest proportion of ultra-processed food consumption were sugary beverages (35%), sugary products (19%), ready-to-eat foods (16%) and processed meats (12%). Processed meats have already been classified as carcinogenic by the International Agency for Research on Cancer (IARC). However, according to Pilar Amiano, researcher at the Guipúzcoa Public Health Service, which coordinated the study: "ultra-processed foods and drinks in general are not yet classified as carcinogenic because the aim of the IARC was not to assess the overall risk of an individual's diet, but rather to focus on specific components that might be dangerous, such as processed meats".

She goes on to say that, in light of the results of the present study and the current scientific evidence on the health risks associated with ultra-processed foods and drinks, in particular with respect to cancer, the authors believe "that food and public health policies and the IARC should already be taking food processing into account and discouraging the consumption of ultra-processed products".