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A large, retrospective, multicenter study involving Washington University School of Medicine in St. Louis indicates that convalescent plasma from recovered COVID-19 patients can dramatically improve likelihood of survival among blood cancer patients hospitalized with the virus.

The therapy involves transfusing plasma -- the pale yellow liquid in blood that is rich in antibodies -- from people who have recovered from COVID-19 into patients who have leukemia, lymphoma or other blood cancers and are hospitalized with the viral infection. The goal is to accelerate their disease-fighting response. Cancer patients may be at a higher risk of death related to COVID-19 because of their weakened immune systems.

The data, collected as part of a national registry, indicate that patients who received convalescent plasma from donors who had recovered from COVID-19 had a death rate of 13.3% compared with 24.8% for those who did not receive it.

The difference was especially striking among severely ill patients admitted to intensive care units (ICUs). Such patients treated with convalescent plasma had a death rate of 15.8% compared with 46.9% for those who didn't receive the treatment.

"These results suggest that convalescent plasma may not only help COVID-19 patients with blood cancers whose immune systems are compromised, it may also help patients with other illnesses who have weakened antibody responses to this virus or to the vaccines," said Jeffrey P. Henderson, MD, PhD, an associate professor of medicine and of molecular microbiology at Washington University. "The data also emphasize the value of an antibody therapy such as convalescent plasma as a virus-directed treatment option for hospitalized COVID-19 patients."

The research is published June 17 in the journal JAMA Oncology.

Henderson collaborated with researchers from the international COVID-19 & Cancer Consortium (CCC19) formed over a year ago to collect and analyze data on the disease's unique interactions. More than 70 institutions in the consortium -- including Advocate Aurora Health in Wisconsin and Illinois, Vanderbilt University Medical Center in Nashville, Tenn., and the Mayo Clinic in Rochester, Minn. -- participated in this study.

The scientists looked back at patient data to compare the 30-day mortality of 966 hospitalized adults with a blood cancer, such as leukemia, lymphoma or multiple myeloma, who also were diagnosed with COVID-19. The patients, whose average age was 67, were hospitalized at some point from March 17, 2020, through Jan. 21, 2021, due to complications from COVID-19.

Of the patients studied, 143 received convalescent plasma, and 823 did not. Of the 338 patients admitted to ICUs because of severe COVID-19 symptoms, such as difficulty breathing or cardiac distress, those who received the treatment were more than twice as likely to survive.

"In March 2020, the Food and Drug Administration provided a pathway for hospitalized patients to receive COVID-19 convalescent plasma if requested by their physicians," Henderson explained. "After this, the decision to give convalescent plasma was made by physicians and patients on a case-by-case basis. There were no restrictions on when during the course of illness convalescent plasma could be given to patients."

Early in the pandemic, many scientists urged evaluation of convalescent plasma to treat the virus, based on the plasma's historical effectiveness in fighting other viruses. During the 1918 Spanish flu pandemic, some newly infected patients were treated successfully with plasma from people who had recovered from the flu. Additionally, during the outbreaks of severe acute respiratory syndrome (SARS) in 2002 and 2003, health-care workers used plasma transfusion experimentally and, in many cases, successfully to treat small numbers of people. SARS is caused by a coronavirus closely related to the one that causes COVID-19.

However, limited data on the novel coronavirus also caused pause among physicians. Randomized controlled trials -- the gold standard in research -- proved elusive, in most cases, due to the time required to prepare and coordinate adequate trials, and the need for scientists to prioritize among multiple investigational treatment options. Some preliminary results also disappointed, showing convalescent plasma only worked as a treatment in the general patient population if infused within days after diagnosis in patients who hadn't yet progressed to having severe complications.

"As more COVID-19 patients began receiving convalescent plasma, we started hearing physicians around the country report remarkable clinical improvements following convalescent plasma infusions in COVID-19 patients with blood cancers and antibody deficiencies, some of whom were already very ill," said Henderson, one of several physicians who formed the COVID-19 Convalescent Plasma Program Leadership Group to study the use of convalescent plasma for treating COVID-19. "I have seen one of my own patients with blood cancer quickly improve after receiving convalescent plasma. Similar stories that were often very detailed suggested that a formal study would help physicians with decisions they were already making on a daily basis."

During the past year, over phone calls, emails and Zoom chats, updates on convalescent plasma -- its historical success and its prospects for COVID-19 -- were a staple in conversations between Henderson and his longtime friend and co-author Michael Thompson, MD, PhD, who also was his roommate during undergraduate school at the University of Wisconsin in Madison. Thompson is now an oncologist and hematologist at Advocate Aurora Health, and Advocate Aurora Research Institute, both in Wisconsin, as well as a member of the steering committee of the COVID-19 & Cancer Consortium.

"It became increasingly evident that patients with leukemia, lymphoma and other blood cancers were particularly susceptible to severe COVID-19 and that COVID-19 may develop in a unique way in these patients," said Henderson. "We discussed that we might learn something from patients in the COVID-19 & Cancer Consortium, and things started to snowball from there."

Henderson contacted fellow researchers in the COVID-19 Convalescent Plasma Program, including Michael J. Joyner, MD, who is a professor of anesthesiology at the Mayo Clinic and works closely with the FDA. Thompson reached out to Jeremy Warner, MD -- a professor of medicine at Vanderbilt, a steering committee member of the COVID-19 consortium and who operates the CCC19 registry. Together, the researchers plumbed the group's registry of de-identified data abstracted from medical records.

"The data started coming fast and furious," Henderson recalled.

"Given that patients with blood cancers have higher mortality rates from COVID-19, we suspect our findings, along with other similar cases not in this database, support using convalescent plasma to improve survival in these patients," Thompson said.

Henderson and Thompson contributed equally as the study's first authors. Joyner is a co-author, and Warner is the senior author. "Despite the inevitable limitations of retrospective data, we find these results compelling and certainly hope that they will be quickly investigated in a prospective clinical trial," Warner added. "We are exploring future research, including whether there is an interplay between patient factors and treatments received prior to the development of COVID-19, such as B-cell depleting monoclonal antibodies."

New Brunswick, N.J. (June 17, 2021) - Babies born by cesarean section don't have the same healthy bacteria as those born vaginally, but a Rutgers-led study for the first time finds that these natural bacteria can be restored.

The study appears in the journal Med.

The human microbiota consists of trillions of bacteria, viruses, fungi and other microorganisms - some beneficial, some harmful -- that live in and on our bodies. Women naturally provide these pioneer colonizers to their babies' sterile bodies during labor and birth, helping their immune system to develop. But antibiotics and C-sections disturb this passing of microbes and are related to increased risks of obesity, asthma and metabolic diseases.

The researchers followed 177 babies from four countries over the first year of their lives -- 98 were born vaginally and 79 were born by C-section, 30 of which were swabbed with a maternal vaginal gauze right after birth.

Lab analysis showed that the microbiota of the C-section babies swabbed with their mother's vaginal fluids was close to that of vaginally born babies. Also, the mother's vaginal microbiomes on the day of birth were similar to other areas of their bodies (gut, mouth and skin), showing that maternal vaginal fluids help to colonize bacteria across their babies' bodies.

This was the first large observational study to show that restoring a C-section baby's natural exposure to maternal vaginal microbes at birth normalizes the microbiome development during their first year of life. The researchers said the next step is conducting randomized clinical trials to determine if the microbiota normalization translates into disease protection.

"Further research is needed to determine which bacteria protect against obesity, asthma and allergies, diseases with underlying inflammation," said senior author Maria Gloria Dominguez Bello, a professor in the Department of Biochemistry and Microbiology in the School of Environmental and Biological Sciences at Rutgers University-New Brunswick. "Our results support the hypothesis that acquiring maternal vaginal microbes normalizes microbiome development in the babies."

According to the World Health Organization, C-section is needed in about 15 percent of births to avoid risking the life of the mother or child, but in many countries such as in Brazil, the Dominican Republic, Iran and China, C-section is performed in more than 70% of urban births.

KIYATEC, Inc. announced today the publication of new peer-reviewed data that establishes clinically meaningful prediction of patient-specific responses to standard of care therapy, prior to treatment, in newly diagnosed glioblastoma (GBM) and other high-grade glioma (HGG) patients. The results, the interim data analysis of the company's 3D-PREDICT clinical study, were published June 16, 2021 in Neuro-Oncology Advances, an open access clinical journal.

A goal of the study, which continues to enroll, was for the test's prospective, patient-specific response prediction to achieve statistical significance for predictive accuracy. The 3D-PREDICT study met this goal early, at its interim data analysis, an achievement that is uncommon for innovations in oncology. For clinicians and payors, the publication establishes the successful analytical validation and early clinical validation of KIYATEC's 3D Predict™ Glioma assay.

The recent bipartisan resolution passed by the US Senate designating July 21, 2021 as Glioblastoma Awareness Day highlights the severity of this aggressive brain cancer. Fewer than 10% of patients survive longer than five years. Pharmaceutical and clinical efforts have only resulted in modest increases in overall survival since the disease was first described in the 1920s. Today, most newly diagnosed patients receive the same treatment regimen (radiation therapy and temozolomide), presenting an opportunity to improve care through shifting the paradigm toward individualized medicine for HGG treatment.

KIYATEC's test results accurately identified the patients as future temozolomide responders or future non-responders prior to the initiation of drug treatment. The future responder group had a statistically significant 6-month comparative increase in overall survival. Since test results are available only seven days after surgery, this creates an opportunity to improve outcomes for each predicted non-responder by providing the possibility of patient-specific treatment strategies. In the future, KIYATEC's results may also prove useful to improve outcomes for each predicted responder through patient-specific combination strategies.

Successful response-prediction for newly diagnosed patients follows the company's previous success with predicting treatment response in recurrent high-grade glioma patients. In December 2020, KIYATEC announced a clinical case series demonstrating that use of their test doubled these patients' median time to progression over what would be expected without use of the test. In addition, the earlier announcement demonstrated successful clinical use of the targeted agent dabrafenib in two patients that were not identified by genetic sequencing. By identifying successful response to drugs that would have been missed by today's testing, KIYATEC's results expanded the successful treatment options for these patients.

"Decision making in our framework is based on patient-specific evidence, embodying truly personalized medicine. Evidence of response before the first dose is administered creates options that were not previously available when it comes to treatment," said Matthew Gevaert, PhD, CEO of KIYATEC.

Versus other approaches, tests developed using KIYATEC's 3D ex vivo cell culture platform demonstrate increased biological fidelity, which was first reported in 2019 in ovarian cancer. In newly diagnosed ovarian cancer patients, KIYATEC's test prospectively and accurately predicted response to first-line chemotherapy with 89% accuracy. The new GBM results now establish comparable predictive accuracy in two solid tumors, with eight additional cancers in the company's pipeline.

In a bid to find or refine laboratory research models for cancer that better compare with what happens in living people, Johns Hopkins Medicine scientists report they have developed a new computer-based technique showing that human cancer cells grown in culture dishes are the least genetically similar to their human sources.

The finding, they say, should help focus more resources on cancer research models such as genetically engineered mice and 3D balls of human tissue known as "tumoroids" to better evaluate human cancer biology and treatments, and the genetic errors responsible for cancer growth and progress.

"It may not be a surprise to scientists that cancer cell lines are genetically inferior to other models, but we were surprised that genetically engineered mice and tumoroids performed so very well by comparison," says Patrick Cahan, Ph.D., associate professor of biomedical engineering at The Johns Hopkins University and the Johns Hopkins University School of Medicine and lead investigator of the new study.

The new technique, dubbed CancerCellNet, uses computer models to compare the RNA sequences of a research model with data from a cancer genome atlas to compare how closely the two sets match up.

The researchers found that, on average, genetically engineered mice and tumoroids have RNA sequences most closely aligned with the genome atlas baseline data in 4 out of every 5 tumor types they tested, including breast, lung and ovarian cancers.

The investigators say their work adds to evidence that cancer cell lines grown in the laboratory have less parity with their human source because of the complex differences between a human cell's natural environment and a laboratory growth environment. "Once you take tumors out of their natural environment, cell lines start to change," says Cahan.

Scientists worldwide rely on a range of research models to improve their understanding of cancer and other disease biology and develop treatments for conditions. Among the most widely used cancer research models are cell lines created by extracting cells from human tumors and growing them with various nutrients in laboratory flasks.

Researchers also use mice that have been genetically engineered to develop cancer. In other cases, they implant human tumors into mice, a process called xenografting, or use tumoroids.

To evaluate how well any of these research models align with what may be happening in people, scientists often transplant lab-cultured cells or cells from tumoroids or xenografts into mice and see if the cells behave as they should -- that is, grow and spread and retain the genetic hallmarks of cancer. However, the Johns Hopkins researchers say this process is expensive, time-consuming and scientifically challenging.

The goal of the new work was to develop a computational approach to evaluating research models in a less cumbersome and accurate way. A report on the work was published April 29 in Genome Medicine, and the researchers have filed for a provisional patent on what they named CancerCellNet.

The new technique is based on genetic information about cellular RNA, a molecular string of chemicals similar to DNA and an intermediate set of instructions cells used to translate DNA into the manufacture of proteins.

"RNA is a pretty good surrogate for cell type and cell identity, which are key to determining whether lab-developed cells resemble their human counterparts," says Cahan. "RNA expression data is very standardized and available to researchers, and less subject to technical variation that can confound a study's results."

First, Cahan and his team had to choose a standard set of data that acted as a baseline to compare the research models. Data from The Cancer Genome Atlas served as the so-called "training" data, which includes RNA expression information of hundreds of patient tumor samples, and their corresponding stage, grade and other tumor information.

They also tested their CancerCellNet tool by applying it to data where the tumor type was already known, such as from the International Human Genome Sequencing Consortium.

Members of the research team combed through The Cancer Genome Atlas data to determine 22 types of tumors to study. They used the genome atlas data as the baseline for comparing RNA expression data from 657 cancer cell lines grown in labs worldwide, some of which were established decades ago, 415 xenografts, 26 genetically engineered mouse models and 131 tumoroids.

In one example from the study, prostate cancer cells from a line called PC3 start to look genetically more like bladder cancer, he notes. It's also possible, he says, that the cell line was originally labeled incorrectly or it could have actually been derived from bladder cancer. But the bottom line was that from a genetic standpoint, the prostate cancer cell line was not a representative surrogate for what happens in a typical human with prostate cancer.

The investigators found that, using a 0-1 scoring method, cell lines had, on average, lower scoring alignment to atlas data than tumoroids and xenografts.

Cahan says he and his team will be adding additional RNA sequencing data to improve the reliability of CancerCellNet.

Leesburg, VA, June 17, 2021--According to ARRS' American Journal of Roentgenology (AJR), a reduced dose of gadobutrol is non-inferior to 100%-standard dose of gadoterate for contrast-enhanced brain MRI.

"A 25% reduced gadobutrol dose demonstrated non-inferior efficacy versus standard dose gadoterate for contrast-enhanced brain MRI," corresponding author Jan Endrikat of Germany's University Medical School of Saarland elaborated, "warranting particular consideration in patients undergoing multiple contrast-enhanced examinations."

In this international, prospective, multicenter, open-label, crossover trial (LEADER-75), 141 patients (78 men, 63 women; mean age, 58.5 years) with known or suspected CNS pathology underwent contrast-enhanced brain MRI with standard-dose gadoterate (0.1 mmol/ kg). If an enhancing lesion was identified, a second MRI with reduced-dose gadobutrol (0.075 mmol/kg) was performed within 15 days.

Comparison of reduced-dose gadobutrol and standard-dose gadoterate versus unenhanced imaging demonstrated noninferiority using 20% margin for three primary efficacy measures: subjective lesion enhancement, lesion border delineation, lesion internal morphology.

Furthermore, in post-hoc analysis, mean readings for subjective lesion enhancement, lesion border delineation, and lesion internal morphology differed by less than 1%--supporting equivalence using a narrow ±5% margin.

"Various secondary variables also supported non-inferiority of reduced-dose gadobutrol," the authors of the AJR article added.

Sophia Antipolis - 17 June 2021: People living with obesity who attended a non-judgemental and personalised lifestyle modification programme improved their cardiovascular and mental health during just 10 weeks, according to a study presented today at EuroHeartCare - ACNAP Congress 2021, an online scientific congress of the European Society of Cardiology (ESC).1 Participants lost weight and achieved benefits in anxiety and depression and physical measurements including blood pressure.

"We focus on changing behaviours and improving people's relationship with food," said study author Ms. Aisling Harris, cardiac and weight management dietitian, Croi Heart and Stroke Centre, Galway, Ireland. "Many participants have tried diets with strict rules and have fears about foods they can't eat. Our programme has no diet or meal plan, and no foods are excluded. Each person sets their own goals, which are reviewed weekly, and our approach is non-judgemental, which builds rapport and gains trust."

"Obesity develops for multiple reasons and blaming someone for their weight can stop them from getting healthcare and advice," said Ms. Harris. "It can lead to emotional eating and feeling too self-conscious to exercise. By identifying each person's triggers, we can develop alternative coping strategies, all within the context of their job, caring responsibilities, external stresses, and so on. For some people, coming to a group like this might be the only social contact that they've had in the week or that they've had in years. People share experiences and support their peers."

Both overweight and obesity are associated with an increased risk of dying from cardiovascular disease.2 Weight loss is recommended to reduce blood pressure, blood lipids, and the risk of developing type 2 diabetes, and thus lower the likelihood of heart disease. This study analysed the impact of a community-based, lifestyle modification programme on the physical and mental health of people living with obesity referred from a specialist bariatric service at Galway University Hospital. The researchers reviewed data from 1,122 participants between 2013 and 2019.

The 10-week Croí CLANN (Changing Lifestyle with Activity and Nutrition) programme started with an assessment by a nurse, dietitian and physiotherapist and baseline measurements of weight, blood pressure, cholesterol, blood glucose, fitness, and levels of anxiety and depression. Personalised goals and a management plan were agreed in collaboration with each patient.

Participants attended a 2.5-hour session each week for 8 weeks. The first 30 minutes were devoted to one-to-one goal setting. Next was a 1-hour exercise class led by the physiotherapist. A 1-hour health promotion talk followed on topics such as healthy eating, portion sizes, reading food labels, emotional versus physical hunger, stress management techniques (e.g. meditation), physical activity, sedentary behaviour, cardiovascular risk factors, and making and maintaining changes. Participants used activity trackers and kept food diaries to identify triggers for emotional eating.

In the last week patients had an end of programme assessment with the nurse, dietitian and physiotherapist to look at outcomes. They were then referred back to the hospital.

At baseline, the average body mass index (BMI) was 47.0 kg/m2 and 56.4% of participants had a BMI above 45 kg/m2. In addition, 26.7% had type 2 diabetes, and 31.4% had a history of depression.

More than three-quarters of participants (78%) completed the programme. Psychosocial health was assessed using the 21-point Hospital Anxiety and Depression Scale (HADS), where 0-7 is normal, 8-10 is mild, 11-15 is moderate, and 16-21 is severe. Anxiety and depression scores decreased by 1.5 and 2.2 points, respectively, over the course of the programme. The proportion with an anxiety score greater than 11 at the start was 30.8% and reduced to 19.9%; for depression the corresponding proportions were 21.8%, falling to 9.5%.

The average reduction in body weight was 2.0 kg overall, with 27.2% of participants losing more than 3% of their initial weight. The proportion achieving recommended physical activity levels rose by 31%. There were significant reductions in total cholesterol, low-density lipoprotein (LDL) cholesterol, and blood pressure. The proportion with high blood pressure fell from 37.4% at baseline to 31.1% at 10 weeks. In those with type 2 diabetes, the proportion achieving the recommended blood sugar target rose from 47.6% to 57.4%.

Ms. Harris concluded: "Nearly eight in ten people finished the programme which suggests that the content and format were acceptable. We observed improvements across all psychosocial and health outcomes during a relatively short period indicating that this could be a model of service delivery for other centres."

Researchers have designed a device that delivers two medications that help stop HIV transmission.

Although condom usage is the best strategy for preventing HIV transmission, the researchers are working to design a device that can be used by sex workers and in situations where women are not in a position to negotiate condom use.

The device is an intravaginal ring (IVR ) that can be inserted into the female genital tract where it will deliver medications known to decrease the transmission of HIV. The researchers examined how effectively their IVR delivered two medications - hydroxychloroquine (HCQ), an FDA approved medication, and a nanomedicine gene therapy developed by the team in previous research. Their results were published in a recent study.

"We've specifically engineered a combination IVR that can deliver two unique medications targeting different aspects of the HIV infection process," said Emmanuel Ho, a professor in the University of Waterloo's School of Pharmacy and study author. "Before, only one drug could be delivered from an intravaginal ring."

The ring is made of medical-grade plastic and contains two segmented sections. One section is solid and coated in a pH-sensitive polymer that releases the customized gene-therapy treatment specifically during sexual intercourse. The other half is a hollow ring with tiny pores that releases HCQ slowly over twenty-five days.

The HCQ is the first line of defence that reduces the immune cell activation - meaning HIV cells have fewer host target cells to interact with. Doing this buys time for the gene therapy treatment which comes in specifically during sexual intercourse to further suppress the expression of cellular receptors that HIV cells attach to.

The team, which has previously partnered with the University of Nairobi in Kenya on related research, recognizes the importance of using medications as judiciously as possible given potentially limited healthcare resources.

The researchers wanted to have a system that can be placed in the vaginal tract but that only acts when there is sexual intercourse. The presence of semen increases the pH of the genital tract. Therefore, they designed the "smart" gene-therapy segment of the IVR to detect that change in pH and to release the nanomedicine at that point in time only.

"This IVR system will help women to protect themselves against HIV infection and greatly reduce drug usage when it is not necessary," says Yannick Traore, a recent Waterloo PhD graduate and lead author on the study. "We are hoping that this will reduce the cost of drug therapy and also prevent users from developing drug resistance."

The unique, segmented design of the IVR is effective. In lab tests, the HCQ segment successfully released the drug slowly and effectively over 25 days and the gene therapy segment responded to the presence of seminal fluid simulant by releasing 20 times more nanomedicine than was released in an environment of only vaginal fluid simulant. The next steps involve testing the IVR in animal models.

African American mothers continue to have the lowest breastfeeding rates, even as the breastfeeding rates have risen in the U.S. over the past 25 years. Racism is an important barrier to breastfeeding, as examined in Part 2 of a special issue on "Breastfeeding and the Black/African American Experience: Cultural, Sociological, and Health Dimensions Through an Equity Lens," published in the peer-reviewed journal Breastfeeding Medicine. Click here to read the issue now.

The special issue is led by Guest Editor Sahira Long, MD, a pediatrician and lactation consultant.

Exploring how racism creates barriers to breastfeeding for Black mothers and how Black women resist racism during their quest to breastfeed are Catasha Davis, PhD and Aubrey Van Kirk Villalobos, DrPH, Milken Institute School of Public Health at the George Washington University, and coauthors. In their article, the authors identify three forms of institutionalized racism as significant barriers to breastfeeding: the historic exploitation of Black women's labor; institutions pushing formula on Black mothers; and lack of economic and employer-based support.

"Institutional support for breastfeeding from employers and hospitals is an essential ingredient for countering institutionalized racism," state the authors.

In the article "Reimagining Racial Trauma as a Barrier to Breastfeeding versus Childhood Trauma and Depression among African American Mothers," Maria Muzik, MD, Michigan Medicine and colleagues examined the relationship between several maternal risk factors and breastfeeding status at 6-months postpartum.

"We found that African American mothers had reduced rates of breastfeeding at 6 months, above and beyond all the other risk factors in the model," said the researchers.

Arthur I. Eidelman, MD, Editor-in-Chief of Breastfeeding Medicine, states: "This two-part Special Issue addresses the multiple facets of this ongoing public health crisis, and will assist in mobilizing our nation's resources in remedying the consequences of institutionalized racism."

Since 2005, the guidelines for the care of unconscious cardiac arrest patients have been to cool the body temperature down to 33 degrees Celsius. A large, randomised clinical trial led by Lund University and Region Skåne in Sweden has shown that this treatment does not improve survival. The study is published in the New England Journal of Medicine.

"These results will affect the current guidelines", says Niklas Nielsen, researcher at Lund University and consultant in anaesthesiology and intensive care at Helsingborg Hospital, who led the study.

In the early 2000s, two studies in the New England Journal of Medicine showed that induced hypothermia in unconscious cardiac arrest patients greatly improved patient survival. The studies changed existing treatment practices, and led to the introduction of new guidelines around the world. However, the evidence for the guidelines was considered by many to be weak. As a result, a large international randomised clinical trial was initiated, and led by researchers at Lund University and Helsingborg Hospital.

The results of the comprehensive study, which has now been published in the same journal, show that hypothermia does not reduce mortality in unconscious patients with suspected cardiac arrest.

"It is important to set high standards for clinical studies, partly to determine what should be introduced in healthcare, partly to challenge the practices that are already in use - to ensure that we have got it right and that healthcare is evidence-based. The results produced strongly indicate that normal temperature should be recommended, not hypothermia", says Niklas Nielsen.

In total, 1900 adult patients who suffered cardiac arrest and were unconscious when admitted to hospital were included in the study. Between November 2017 and January 2020, a total of 61 hospitals around the world participated in the study which has now been published. The patients included in the study had suffered unexpected out-of-hospital cardiac arrest.

The patients were randomised into two groups when they were admitted to hospital. In one group, the patients were cooled down to 33 degrees according to existing guidelines, a temperature that was maintained for 28 hours. In the second group, the patient's body temperature was monitored, and the patients who developed a fever (about half of the participants in this group) were treated with the same method of temperature control, but kept at a normal temperature. The study was ethically approved in participating countries.

Researchers followed up on survival rates for patients six months after receiving care for cardiac arrest. They also investigated how functionality in everyday life was affected in the surviving patients.

1850 patients were included in the survival analysis*. Six months after the patients suffered the cardiac arrest, a total of 465 of 925 participants in the group who were induced with hypothermia had died, approximately 50%. In the normothermia group, 446 out of 925 had died, corresponding to 48%. Researchers saw a slightly increased risk of impact on blood circulation, cardiac arrhythmia, in the group treated with hypothermia.

1747 patients were included in the analysis of patients' ability to function in everyday life (functional status). In the group treated with hypothermia, 488 of 881 (55%) either died or had a severe functional impairment 6 months later, which can be compared to 479 of 866 (55%) in the normothermia group.

"Since it is a large study involving many hospitals in different countries, it has been logistically challenging to follow up six months after the cardiac arrest. A dedicated effort has been put in to obtaining data. This has meant that sometimes patients have had to be visited at home, some patients have moved, and some suffered cardiac arrest in a country other than their homeland", says Gisela Lilja, researcher at Lund University and chief occupational therapist at Skåne University Hospital, who coordinated the follow-up in the study.

"The results are important, but not unexpected. For 20 years we have applied and believed in these practices which we now see do not make a difference for survival. Now we can use the resources on other things, and prioritise other aspects of the acute phase of cardiac arrest", says Josef Dankiewicz, researcher at Lund University and resident physician at Skåne University Hospital, and first author of the study.

Researchers now plan to further analyse patient data to learn more about who is affected, and about recovery after cardiac arrest.

* 36 patients declined to be part of the study, and there is data missing on 11 participants (6 in the hypothermia group and 5 in the other group)

Ibaraki, Japan - Severe childhood restrictive cardiomyopathy is a condition that causes the muscles in the walls of the heart to become stiff, so that the heart is unable to fill properly with blood. A mutation in a protein called BAG3 is known to result in restrictive cardiomyopathy, muscle weakness, difficulty taking in enough oxygen, and damage to multiple peripheral nerves, often shortening the patient's lifespan significantly. Until now there has been no successful model for the disease, making it extremely difficult to study.

However, researchers in Japan and Germany have now created a mouse model that mimics the human pathology, allowing the disease to be studied more easily. The team's data suggest that the restrictive cardiomyopathy caused by BAG3 mutation changes the process by which damaged proteins are broken down and removed. This causes proteins to build up in the cells, disrupting the cardiac muscle.

The team was able to express a human version of the mutant BAG3 protein in mouse cardiomyocytes, the cells that make up the heart muscle. "Our mouse model successfully mimicked the human disease," says lead author Assistant Professor Kenichi Kimura. "The mice had increasingly severe symptoms of heart failure and growth retardation starting shortly after birth, and only survived for around five weeks".

The team studied the heart tissue of the mice expressing the mutant human BAG3 protein, and uncovered changes to the protein quality control system, which ensures proteins are correctly folded, alongside increased levels of autophagy, a process by which damaged cells are removed and recycled. BAG3 is involved in the breakdown of proteins that have become damaged due to mechanical stress. The mutation that causes restrictive cardiomyopathy involves the alteration of just a single base in the DNA, leading to a leucine amino acid in the mutant BAG3 protein where there should be a proline.

The team showed that this leads to the mutant protein having reduced solubility and mobility, causing it to build up in the muscle cells. This causes fibrosis, or scarring, and results in the heart muscle stiffening and losing the ability to fully relax, meaning that the heart is unable to properly fill with blood. Moreover, in preliminary investigations using a technique to knockdown and reduce the mutant protein expression, the researchers were able to mitigate the disease symptoms in the mouse model.

Childhood restrictive cardiomyopathy is a rare but very serious disease. Hopefully, the knowledge provided in this study, and the establishment of a mouse model of the disease to support further research, will bring about the development of better treatments for children with this condition.

New research published in BMJ Open shows that community pharmacy could play a 'key clinical role' in the future role of COVID-19 vaccination programmes, according to a study led by Aston University in Birmingham, UK, in collaboration with UK and international researchers.

The team found that community pharmacists, as a 'skilled clinical workforce', could positively contribute, supporting the community in which they serve - by playing a critical role in ongoing COVID-19 vaccination campaigns.

The researchers working on the PERISCOPE study found that community pharmacy is uniquely placed to support individuals, because it is seen by the public as a credible, trustworthy service, which could be key to any future clinical role it might play, especially where addressing vaccine hesitancy in 'hard to reach' communities. They are therefore calling on decision-makers to endorse and provide their support for a clearly defined public health role for community pharmacy.

Across the UK, community pharmacy is a critical part of primary care. According to the Kings Fund, as of the end of March 2019, there were more than 11,500 community pharmacies in England alone. It is viewed as one of the four pillars of the primary care system, along with general practice, optical services and dentistry. It has also, in areas of the UK, helped to deliver COVID-19 vaccinations.

The study included partners from the Universities of Sheffield, Oxford, Hull and Bradford in the UK, as well as internationally, the University of British Columbia and University of Tasmania. The group reviewed more than a hundred documents including peer reviewed articles, blogs and websites on the role of community pharmacy during COVID-19 and other previous pandemics.

Their findings were discussed with more than 30 health professionals and members of the public, to ensure that the findings made sense in the real world. Health professionals included pharmacists, pharmacy technicians, dispensers, counter assistants, and GPs, together with members of the public from a range of diverse ethnic backgrounds.

Several recommendations were made by the researchers from the findings of the study. Most significantly the group found it was imperative that policy and practice should focus on the clinical role of community pharmacy.

Dr Ian Maidment, reader in clinical pharmacy at Aston University and former community pharmacist leading PERSICOPE, said:

"We need to use community pharmacy to a much greater extent for COVID-19 vaccination, particularly for boosters against new variants such as the Delta (Indian) variant. The current model (for example, the large hubs) may not be sustainable in the longer term, particularly if annual COVID-19 vaccination is required.

"Our work found some key ways to make this happen. The easy access and local convenience of high street pharmacies makes them an ideal location for vaccinating at-risk populations."

The study includes guidance for policy makers:

* Have a clear role for community pharmacy in response to the public health agenda, with that role championed by decision-makers
* Involve frontline community pharmacists in the development of policy and service specification in relation to vaccination
* Provide prompt, clear, consistent guidelines with adequate detail and enough flexibility to allow community pharmacies to adapt the guidelines to meet the needs of their local population
* Provide adequate funding and reimbursement for the delivery and necessary adaptations of any new services community pharmacies are asked to deliver
* Provide pharmacy teams with adequate systems to deliver this new role and then trust them to deliver.

Hadar Zaman, head of pharmacy and medical sciences at University of Bradford and a community pharmacist, said:

"Our research has highlighted the important role community pharmacy has played in overcoming vaccine hesitancy, particularly in ethnic minority communities who have been disproportionately affected by COVID and subsequent mortality.

"What comes out very strongly, especially in areas of high social deprivation, is that community pharmacists have worked very closely with their local communities addressing concerns around vaccine safety.

"It is through these strongly rooted relationships in local communities that we will ensure vaccine uptake rates in ethnic minority and the wider population can be further improved. Therefore, community pharmacy needs to be seen as an essential delivery partner if the Government is to achieve its national vaccination coverage in the short and long term".

PERISCOPE searched for the best evidence across the world and the team included international collaborators. The findings therefore have international relevance.

Maura MacPhee, professor of nursing, University of British Columbia and member of the research team, said: "Our review findings and recommendations for decision-makers, community pharmacists and pharmacy users are adaptable and relevant internationally, including my country, Canada, where community pharmacy has a major role to play in COVID-19 vaccination programmes."

Juanita Breen, also a member of the PERISCOPE team and associate professor of dementia studies at Wicking Dementia Centre, School of Health and Medicine, University of Tasmania, added: "This study demonstrates how pharmacists can contribute towards this important public health initiative and enhance the uptake of the vaccine.

"It provides important learnings for other countries on how best to utilise the skills of our most accessible health professional - the community pharmacist."

Professor Claire Anderson, chair of the Royal Pharmaceutical Society's English Board said:

"This research clearly demonstrates the vital role community pharmacy has played during the pandemic, providing essential advice to communities and tackling health inequalities in areas of high social deprivation.

"Policy makers and commissioners need to take forward the recommendations of this research and ensure the strengths of the community pharmacy network are maximised for the benefits of patients."

Alastair Buxton, director of NHS Services at the Pharmaceutical Services Negotiating Committee, said:

"This research provides a timely examination of the role community pharmacy teams have played in supporting their communities to fight back against COVID-19.

"By keeping their doors open throughout, pharmacies have maintained day-to-day activities, and managed increased demand for many services - including advice on the management of minor illness. They have also substantially increased the number of flu vaccinations administered and played a key part in the COVID-19 vaccination programme.

"These findings will help guide policy in the later stages of the pandemic and guide practice in any future pandemics."

Tony Kelly, a diabetes ambassador, Diabetes Strategic Patient Partner - NHS Birmingham and Solihull Clinical Commissioning Group and member of PERISCOPE, said:

"Community pharmacists are ideally placed at the forefront of the vaccination agenda as they are the nucleus of ethnically diverse communities and are often the first point of contact for most people."

June 16, 2021, CLEVELAND: New findings from Cleveland Clinic researchers show for the first time that the gut microbiome impacts stroke severity and functional impairment following stroke. The results, published in Cell Host & Microbe, lay the groundwork for potential new interventions to help treat or prevent stroke.

The research was led by Weifei Zhu, Ph.D., and Stanley Hazen, M.D., Ph.D., of Cleveland Clinic's Lerner Research Institute. The study builds on more than a decade of research spearheaded by Dr. Hazen and his team related to the gut microbiome's role in cardiovascular health and disease, including the adverse effects of TMAO (trimethylamine N-oxide) - a byproduct produced when gut bacteria digest certain nutrients abundant in red meat and other animal products.

"In this study we found that dietary choline and TMAO produced greater stroke size and severity, and poorer outcomes in animal models," said Dr. Hazen, chair of the Department of Cardiovascular & Metabolic Sciences and director of Cleveland Clinic's Center for Microbiome & Human Health. "Remarkably, simply transplanting gut microbes capable of making TMAO was enough to cause a profound change in stroke severity."

Previously, Dr. Hazen and his team discovered that elevated TMAO levels can lead to the development of cardiovascular disease. In clinical studies involving thousands of patients, they have shown that blood levels of TMAO predict future risk of heart attack, stroke and death -findings that have been replicated around the world. Earlier studies, also led by Drs. Zhu and Hazen, were the first to show a link between TMAO and enhanced risk for blood clotting.

"This new study expands on these findings, and for the first time provides proof that gut microbes in general - and through TMAO specifically - can directly impact stroke severity or post-stroke functional impairment," said Dr. Hazen.

The researchers compared brain damage in preclinical stroke models between those with elevated or reduced TMAO levels. Over time, those with higher levels of TMAO had more extensive brain damage and a greater degree of motor and cognitive functional deficits following stroke. The researchers also found that dietary changes that alter TMAO levels, such as eating less red meat and eggs, impacted stroke severity.

"Functionality after a stroke - which occurs when blood flow to the brain is blocked - is a major concern for patients," said Dr. Hazen, who is also co-section head of Preventive Cardiology & Cardiac Rehabilitation in Cleveland Clinic's Miller Heart, Vascular & Thoracic Institute. "To understand if choline and TMAO affect post-stroke functionality, in addition to stroke severity, we compared performance on various tasks pre-stroke, and then both in the short- and long-term following stroke."

The team found that a gut microbe enzyme critical to TMAO production called CutC drove heightened stroke severity and worsened outcomes.

According to Dr. Zhu, targeting this gut microbe enzyme may be a promising approach to prevent stroke. "When we genetically silenced the gut microbe gene that encodes CutC, stroke severity significantly diminished," she said. "Ongoing research is exploring this treatment approach, as well as the potential for dietary interventions to help reduce TMAO levels and stroke risk, since both a Western diet and a diet rich in red meat are known to elevate TMAO levels. Switching to plant-based protein sources helps to lower TMAO."

New research published this week challenges a popular belief that intermittent fasting diets such as alternate day fasting or the '5:2' are the most effective ways to lose weight.

Over recent years, diets which see people fast on a few days each week have increased in popularity, reinforced by images of people's miraculous weight transformations, and backed by celebrity endorsements.

However, evidence to date about the effectiveness of fasting compared with more traditional diets which aim to reduce calorie intake over the course of a full week has been limited.

Published in the prestigious journal Science Translational Medicine, the new study from a team of physiologists at the University of Bath builds this evidence and indicates that there is 'nothing special' about fasting.

Participants in their randomised control trial lost less weight when fasting in comparison with those following a traditional diet - even when their calorie intake was the same overall.

The trial, organised by a team from the University's Centre for Nutrition, Exercise & Metabolism (CNEM), saw participants allocated into one of three groups:

Group 1 which fasted on alternate days with their fast day followed by a day of eating 50% more than usual.

Group 2 which reduced calories across all meals everyday by 25%.

Group 3 which fasted on alternate days (in the same way as Group 1) but followed their fast day with one day eating 100% more than usual.

Participants across all three groups were consuming a typical diet of around 2000-2500 kcal per day on average at the start of the study. Over the course of the three-week monitoring period, the two energy restricted groups reduced this to be between 1500-2000 kcal on average.
Whereas groups 1 and 2 reduced their calorie intake by the same amount in different ways, group 3's diet saw them fast without reducing overall calories.

Their results found that the non-fasting dieting group (Group 2) lost 1.9 kg in just three weeks, and DEXA body scans revealed this weight loss was almost entirely due to a reduction in body fat content.

By contrast, the first fasting group (Group 1) who experienced the same reduced calorie intake by fasting on alternate days and eating 50% more on non-fasting days, lost almost as much body weight (1.6 kg) but only half this weight loss was from reduced body fat with the remainder from muscle mass.

Group 3, who fasted but increased their energy intake by 100% on non-fasting days, did not need to draw on their body's fat stores for energy and therefore weight loss was negligible.

Professor James Betts, Director of the Centre for Nutrition, Exercise & Metabolism at the University of Bath who led the research explains: "Many people believe that diets based on fasting are especially effective for weight loss or that these diets have particular metabolic health benefits even if you don't lose weight.

"But intermittent fasting is no magic bullet and the findings of our experiment suggest that there is nothing special about fasting when compared with more traditional, standard diets people might follow.

"Most significantly, if you are following a fasting diet it is worth thinking about whether prolonged fasting periods is actually making it harder to maintain muscle mass and physical activity levels, which are known to be very important factors for long-term health."

These results focused on participants who were defined as 'lean' (i.e. body mass index 20-25 kg/m2). 36 people participated in the study which was conducted between 2018 - 2020 and funded by the University of Bath.

With increasing vaccination rates and decreasing numbers of infections, the population's feeling of safety is also rising. As the results of the 37th edition of the BfR-Corona-Monitor, a regular survey conducted by the German Federal Institute for Risk Assessment (BfR), show, the majority of the population in Germany thinks it can control its risk of an infection well. "62 percent are confident that they can protect themselves from an infection with the coronavirus," says BfR-President Professor Dr. Dr. Andreas Hensel. "We see that the feeling of safety has increased considerably. At the end of March of this year, only 40 percent of the respondents felt they could protect themselves from an infection."

At the same time, fewer people consider the probability of contracting the coronavirus through proximity to other people to be high. A difference can be seen in the age groups: While 70 percent of those under 40 consider an infection through proximity to others to be likely, only 55 percent of those over 60 do so - possibly because more people in this age group have already been vaccinated.

The greater perceived safety from an infection also seems to have an impact on the population's leisure behaviour. For example, 59 percent of respondents say they have left the house less often in the past two weeks and 71 percent say they have limited personal contacts. At the end of March 2021, when infection rates were starting to increase again, these figures were both 10 percentage points higher.

In addition to increasing contacts and more activities outside the home, it is evident that the population is also less concerned about their social relationships. Since the end of April 2021, the proportion of respondents who are worried about this has fallen from 40 percent to currently 24 percent. Concerns about the economic situation and physical and mental health are also slowly declining among the population.

Researchers from the University of Kent's School of Psychology have found that when people are presented with the idea of a Covid-19 "immunity passport", they show less willingness to follow social distancing and face covering guidelines. However, this willingness seems to return when people read more cautious information about Covid-19 immunity.

PhD students Ricky Green and Mikey Biddlestone and Professor Karen Douglas asked participants from the UK and USA to imagine they had either recovered from Covid-19 or were currently infected. Participants asked to imagine that they had recovered were also presented with information regarding "immunity passports" and cautious versus incautious Covid-19 immunity information. Cautious information emphasised that past infection does not equal immunity whereas incautious information argued that past infection does equal immunity.

The research published by the Journal of Applied Social Psychology showed that for people asked to imagine past Covid-19 infection, reading about "immunity passports" was associated with lower social distancing and face covering intentions. Participants who then read incautious immunity information reported even lower intentions. However, when participants were presented with cautious immunity information these negative effects vanished. People asked to imagine that they were infected reported higher social distancing and hygiene intentions.

Lead researcher Ricky Green said: 'People who suspect they have previously had Covid-19 show less willingness to follow pandemic guidelines, presumably because they assume they have become immune to the virus since they were infected. This is concerning because social distancing guidelines are in place to protect others as well as oneself, and the exact nature of infection-acquired immunity is still not clear.

'This research suggests that early public announcements surrounding immunity passports, without prefacing them with cautious information about the unclear evidence on Covid-19 immunity, may have undermined efforts to promote virus-mitigating behaviours. Focusing on "acting like you have it" appears to be helpful in encouraging better public behaviour.'