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The American Heart Association and the American College of Cardiology today released an updated guideline for managing patients with hypertrophic cardiomyopathy (HCM). The guideline encourages shared decision-making between the clinician and patient as essential when determining treatment course and updates recommendations for sudden cardiac death (SCD) risk assessment and HCM center referrals based on the latest evidence.

HCM is a disease that causes the heart muscle to become abnormally thick, which can make it harder for the heart to pump enough blood to the body. It's estimated that 1 in every 500 people have HCM, but a large percentage of patients are undiagnosed. Many patients with HCM are asymptomatic, but those who do have symptoms suffer from fainting, chest pain, shortness of breath or heart palpitations.

The guideline updates the previous version, which was issued in 2011, to offer recommendations on the evaluation and management of patients with HCM and is geared to cardiovascular clinicians as well as non-cardiovascular clinicians.

Recommendations reflect recent evidence about diagnostic modalities such as electrocardiography, imaging and genetic testing; management of patients including medical therapies, septal reduction therapies and SCD risk assessment/prevention; and other considerations such as participation in activities/sports, occupation and pregnancy.

People with HCM may have additional medical conditions such as heart failure, atrial fibrillation and ventricular arrythmias, which means treatment decisions are not always clear cut. The updated guideline clarifies the varied treatments that may include medications such as a beta-blocker and/or a calcium channel blocker, a surgical procedure and/or device like an implantable cardioverter defibrillator (ICD). Different from the previous 2011 guideline, the updated guideline emphasizes shared decision-making in the management of HCM to personalize treatment options based on the patient's goals and concerns.

"Shared decision-making, a dialogue between patients and their care team that includes full disclosure of all testing and treatment options, discussion of the risks and benefits of those options and, importantly, engagement of the patient to express their own goals, is particularly relevant in the management of conditions such as hypertrophic cardiomyopathy," said Steve R. Ommen, MD, FACC, FAHA, professor of medicine at the Mayo Clinic College of Medicine and consultant in the department of cardiovascular medicine and chair of the writing committee for the guideline. "This updated guideline places emphasis on including the patient in the decision-making process rather than simply providing dogmatic lists of do's and don'ts."

While the guideline writers recognize that patients with HCM can be evaluated and treated by a cardiovascular care team, recommendations are made for patients with severe HCM, or those facing complex decisions, to be referred to multidisciplinary HCM centers to receive optimal care.

Guidance around participation in healthy physical activity has also been updated to make it clearer that recreational exercise is an option for patients with HCM. According to the updated guideline, participation in competitive sports may also now be considered in selected patients after a complete discussion between patients with HCM and their doctors about the potential risks.

"Increasingly, data affirm that the beneficial effects of exercise on general health can be extended to patients with HCM," Ommen said. "Healthy recreational exercise (moderate intensity) has not been associated with increased risk of ventricular arrhythmia events in recent studies."

Furthering the personalized approach to care, the updated HCM Guideline also includes updated recommendations for assessing individual risk markers for SCD, which can help identify patients who may need an ICD, and counseling patients about the potential genetic transmission of HCM and screening options for family members.

The 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients with Hypertrophic Cardiomyopathy will publish in the Journal of the American College of Cardiology and Circulation.

The guideline was written in collaboration with the Heart Failure Society of America, the American Society of Echocardiography, the Heart Rhythm Society, the Society of Cardiovascular Magnetic Resonance, the American Academy of Thoracic Surgery, and the Society for Cardiovascular Angiography and Interventions and was endorsed by the Pediatric & Congenital Electrophysiology Society.

Tampa, Fla. (Nov 20, 2020) - A survey of resident physicians in Florida indicates they are interested in treating opioid addiction but face barriers to offering patients treatment using buprenorphine, an FDA-approved medication shown to successfully decrease opioid use, overdose events, and deaths associated with opioids.

Resident physicians often care for patients with opioid addiction, described in medical terms as Opioid Use Disorder (OUD), but do not have the skill set or knowledge to treat OUD.

These are the findings from a study, led by University of South Florida Health (USF Health) physician researchers, that were recently published in the Journal of Addiction Medicine. The study is one of the first to evaluate what barriers resident physicians face in prescribing buprenorphine for opioid addiction and their attitudes towards treating opioid addiction.

Currently, health care providers must complete training in order to obtain a waiver to prescribe buprenorphine, but only 5% of all practicing physicians have this waiver.

The USF Health researchers surveyed resident physicians across all 35 Internal Medicine residency training programs in Florida that are accredited by the Accreditation Council for Graduate Medical Education (ACGME). They found that 42% of respondents planned to obtain a buprenorphine waiver and that only 3% of these residents were currently waivered.

"The opioid epidemic continues to claim over 45,000 deaths per year -unfortunately, only 20% of patients with opioid addiction receive medical treatment. Medications like buprenorphine can radically improve the lives of people who have opioid addiction, but these medications are underutilized by providers," said the study's lead author Bryant Shuey, MD, a third-year resident for the Department of Internal Medicine in the USF Health Morsani College of Medicine in Tampa, Fla.

"Providers must complete a training in order to obtain a waiver to prescribe buprenorphine. But only 5% of practicing physicians have this waiver, leaving few prescribers prepared to address the opioid epidemic. Resident physicians are the front line of our health care workforce and are poised to be leaders in treating opioid addiction. Yet, few studies have evaluated what residents know about opioid addiction and what barriers they face when trying to manage opioid addiction. This study is one of the first to evaluate what barriers resident physicians face in prescribing buprenorphine for opioid addiction and their attitudes towards treating opioid addiction."

The survey also found that:

73% of residents cared for patients with opioid addiction more than once per month.

Three-quarters of residents reported that their programs do not provide training in treatment of OUD using buprenorphine.

Residents scored poorly on survey knowledge questions about treating opioid addiction.

Residents described limited knowledge about diagnosis and management of opioid addiction as the most important barrier to prescribing buprenorphine followed by a lack of awareness of the medication.

Residents interested in general medicine and those who cared for patients more frequently with opioid addiction were more likely to be interested in obtaining a buprenorphine waiver.

"Residents in our study overwhelmingly support deregulating buprenorphine for the treatment of OUD," Shuey said, referencing calls by national addiction experts to remove the waiver requirement to prescribe buprenorphine altogether. "Ultimately, residents are interested in expanding their role in treating opioid addiction but face significant limitations in knowledge, experience, and skills."

More than 40 states have reported increased deaths from opioids since the COVID-19 pandemic began, underscoring the need to remove barriers to treatment, according to the American Medical Association.

A Basel-led international research team has discovered a connection between the intestinal flora and sites of inflammation in the central nervous system in multiple sclerosis. A specific class of immune cell plays a central role in this newly identified gut-brain axis. The discovery could pave the way for new treatments for MS that target the intestinal flora.

What do you do when your own immune system attacks your nervous system? Newer treatments for the autoimmune disease multiple sclerosis (MS) rely on removing specific immune cells (B cells) from the blood of patients. However, researchers at both the University of Basel and the University Hospital Basel discovered several years ago that it's better not to remove too broad a range of B cells, as this can aggravate the disease.

A new study in the journal Science Immunology sheds more light on this observation: an international team of researchers, led by Dr. Anne-Katrin Pröbstel at the University of Basel and University Hospital Basel, has discovered that specific B cells form a kind of bridge between the intestinal flora and the sites of inflammation in the central nervous system, exerting an anti-inflammatory effect.

"We knew from earlier studies that the composition of intestinal flora plays a role in MS. But how exactly intestinal bacteria and immune cells influence one another was previously unknown," explains Pröbstel, the study's lead author.

Immune cells for gut and brain

At the heart of the new study are IgA-producing B cells, or IgA B cells in short. Immunoglobulin A (IgA) is a class of antibodies that specializes in immune defense of mucous membranes; the IgA B cells are key to intestinal health.

By analyzing stool samples from MS patients and healthy people, the researchers discovered that MS patients have IgA B cells in their intestines that target in particular bacteria typical of MS - i.e. bacteria that are more common in MS sufferers.

In a next step, the researchers analyzed the role of these immune cells during acute flares of the illness in a total of 56 MS patients. They found that IgA B cells accumulated in the cerebrospinal fluid and brain tissue of MS patients with acute sites of inflammation. "Apparently, these immune cells migrate from the intestine to the inflammation sites in the central nervous system, where they release an anti-inflammatory messenger substance," says Pröbstel. "That could explain why the illness worsens if these immune cells are removed from the blood with medication."

Trigger still unknown

What exactly activates the IgA B cells as helpers against MS and triggers their migration from the intestine to the central nervous system is still being investigated. "If we find the trigger for that, we could use it to treat MS," says Pröbstel. For example, it may be conceivable to change the composition of the intestinal flora of MS sufferers in a targeted way in order to mobilize IgA B cells as helpers against inflammation in the nervous system.

In addition to the University of Basel, other participants in the study included the University of California San Francisco, the Technical University of Munich, the universities of Heidelberg, Umeå (Sweden) and Toronto (Canada), and the Max Planck Institute of Colloids and Interfaces in Potsdam. The study was funded among others by the National Multiple Sclerosis Society and the Swiss National Science Foundation.

Nursing home residents with medical order forms indicating their treatment preferences were three times more likely to have their current preferences documented in their medical record than residents without the forms, according to a study from Indiana University School of Nursing and IU Center for Aging Research at Regenstrief Institute.

POLST is a medical order form that documents what sort of life-sustaining treatments a person prefers to receive or not receive, such as hospitalization or comfort-focused care. POLST provides more specific directions than advance directives. The POLST form is used widely in nursing homes throughout the United States, though the name varies by state.

"POLST forms are a critical part of communication to ensure that patients with serious illness receive care that aligns with their goals," said study first author Susan Hickman, PhD, director of the IU Center for Aging Research at Regenstrief and professor at IU School of Medicine and IU School of Nursing. "Often, preferences are not communicated with providers, which can lead to more aggressive care than what the patient wanted. This research shows that POLST forms are effective at communicating current care preferences and increases the likelihood that treatments will match preferences."

The study team measured concordance between documentation and current preferences for nursing home residents in 40 Indiana facilities. The researchers compared residents in long-stay facilities who used POLST forms with residents in facilities that did not. They found that preference matched documentation 59 percent of the time for residents with a POLST and 35 percent for residents without.

"The difference in concordance shows that having a written record is useful and does lead to care better matching preferences, however, it also shows that there is still room for improvement in ensuring preferences are known," said Dr. Hickman. "Advance care planning conversations can be difficult. We need to provide support to residents and families who are making these decisions and encourage revisiting decisions as circumstances change."

LOS ANGELES (Nov. 20, 2020) -- A widely used tuberculosis vaccine is associated with reduced likelihood of contracting COVID-19 (coronavirus), according to a new study by Cedars-Sinai. The findings raise the possibility that a vaccine already approved by the U.S. Food and Drug Administration may help prevent coronavirus infections or reduce severity of the disease.

The vaccine, known as Bacillus Calmette-Guérin (BCG), was developed between1908 and 1921 and is administered to more than 100 million children around the world every year. In the U.S., it is FDA-approved as a drug to treat bladder cancer and as a vaccine for people at high risk of contracting TB. The BCG vaccine is currently being tested in multiple clinical trials worldwide for effectiveness against COVID-19.

In the new study, published online Nov. 19 in The Journal of Clinical Investigation, investigators tested the blood of more than 6,000 healthcare workers in the Cedars-Sinai Health System for evidence of antibodies to SARS-CoV-2, the virus that causes COVID-19, and also asked them about their medical and vaccination histories.

They found that workers who had received BCG vaccinations in the past-nearly 30% of those studied-were significantly less likely to test positive for SARS-CoV-2 antibodies in their blood or to report having had infections with coronavirus or coronavirus-associated symptoms over the prior six months than those who had not received BCG. These effects were not related to whether workers had received meningococcal, pneumococcal or influenza vaccinations.

The reasons for the lower SARS-CoV-2 antibody levels in the BCG group were not clear, according to Moshe Arditi, MD, director of the Pediatric and Infectious Diseases and Immunology Division at Cedars-Sinai and co-senior author of the study.

"It appears that BCG-vaccinated individuals either may have been less sick and therefore produced fewer anti-SARS-CoV-2 antibodies, or they may have mounted a more efficient cellular immune response against the virus," said Arditi, professor of Pediatrics and Biomedical Sciences. "We were interested in studying the BCG vaccine because it has long been known to have a general protective effect against a range of bacterial and viral diseases other than TB, including neonatal sepsis and respiratory infections."

In the new study, the lower antibody levels in the BCG group persisted despite the fact that these individuals had higher frequencies of hypertension, diabetes, cardiovascular diseases and COPD, which are known risk factors for being more susceptible to SARS-CoV-2 and developing the more severe forms of COVID-19 illness.

While noting that no one believes BCG will be more effective than a specific vaccine for COVID-19, Arditi explained that it could be more quickly approved and made available, given that it has a strong safety profile demonstrated by many years of use. "It is a potentially important bridge that could offer some benefit until we have the most effective and safe COVID19 vaccines made widely available," he said.

"Given our findings, we believe that large, randomized clinical trials are urgently needed to confirm whether BCG vaccination can induce a protective effect against SARS-CoV2 infection," said Susan Cheng, MD, MPH, MMSc, associate professor of Cardiology and director of Public Health Research at the Smidt Heart Institute at Cedars-Sinai. She was the other co-senior author of the study. The first author was Magali Noval Rivas, PhD, assistant professor of Pediatrics at Cedars-Sinai.

In fact, a number of randomized clinical trials have been launched to study the potential protective effects of BCG vaccination against COVID-19. Along with Texas A&M University, Baylor College of Medicine, and the University of Texas MD Anderson Cancer Center, Cedars Sinai is a site for the U.S. arm of this ongoing trial, which is recruiting hundreds of healthcare workers. Arditi serves as the principal investigator of this clinical trial at Cedars-Sinai.

"It would it be wonderful if one of the oldest vaccines that we have could help defeat the world's newest pandemic," Arditi said.

It isn't a death sentence if a COVID-19 patient suffers a cardiac arrest while getting treatment for the virus in the hospital, according to new research that contradicts reports from early on in the pandemic. The new insight from a researcher in the Perelman School of Medicine at the University of Pennsylvania still shows that such events remain deadly, but can be survived at a rate likely near what it was among other hospital inpatients before the pandemic broke out. This analysis was presented during the American Heart Association's annual scientific meeting this month.

"Early studies showed extremely low rates of COVID-19 patients who were resuscitated successfully and went on to survive after suffering from cardiac arrest. The first study from Wuhan demonstrated just a 2.9 percent 30-day survival rate and a second small cohort from New York City showed absolutely no survival," said Oscar Mitchell, MD, a fellow in Pulmonary and Critical Care Medicine at the Hospital of the University of Pennsylvania and the Center for Resuscitation Science. "These results, of course, raised concerns that offering CPR to these patients wasn't accomplishing anything and may have just been exposing hospital staff to the virus. But our results showed survival with a good neurological status is very possible if CPR is attempted."

Examining data from between March and the end of May 2020 at 11 different hospitals across the United States, Mitchell and his fellow researchers identified 260 patients with COVID-19 who suffered cardiac arrest -- a complete loss of heart rhythm -- while in the hospital for treatment. During that time, the data showed that 22 percent of those patients were able to be revived. After their cardiac arrests, 12 percent of patients survived the events for at least a month, a standard marker for mortality when researching adverse health events.

Overall, the rates of successful resuscitation were still about a third of what they were before COVID-19, and the 30-day survival numbers were half. However, those rates could have been skewed by the variation in outcomes by hospital.

The New York City hospitals included in the study treated the lion's share of the patients (204). However, the rate of successful resuscitation for the New York patients was 11 percent compared to 64 percent in the other hospitals. Moreover, the 30-day survival rate was 6 percent in New York compared to 36 percent elsewhere. As such, the non-New York hospitals' numbers were, in fact, right in-line with what could be expected for other hospital patients experiencing cardiac arrest pre-COVID.

"What this shows is that these patients have a survival rate similar to what it was before the pandemic," said one of the senior researchers on the study, Benjamin Abella, MD, a professor of Emergency Medicine. "It demonstrates that our regular means of treating in-hospital cardiac arrest may still be effective in COVID-19 patients and we should consider it as something that is eminently survivable."

The difference in numbers by location may have been the result of differences in circumstances at each site, the researchers hypothesized.

"The strains of the COVID-19 pandemic on hospital resources may have amplified variations in things like detection of cardiac arrest, how patients were handled during the cardiac arrest, and post-event care," Mitchell said.

New research has discovered a cell type that governs the way bones form and maintain themselves, opening up a potential target for future therapies for bone disorders like osteoporosis. Led by faculty from the Perelman School of Medicine at the University of Pennsylvania, a rodent study showed that bone marrow adipogenic lineage precursors (MALPs) play a distinct role in the way bones remodel themselves. Defects in this process are the key issue at play in osteoporosis, so a therapy using these MALP cells to better regulate bone remodeling could result in better treatments. This research was published in the Journal of Clinical Investigation.

"Discovering new cellular and molecular mechanisms to control bone turnover will enable fine-tuning of existing therapies or design of novel therapeutics," said the study's senior author, Ling Qin, PhD, an associate professor of Orthopaedic Surgery. "For example, with the advance of gene-editing technology and novel cell-specific delivery approaches, in the future it would be possible to regulate MALP behavior as a therapy for bone disorders like osteoporosis."

Healthy bone maintenance is a balance between osteoblasts, which secrete the materials necessary to form new bone, and osteoclasts, which absorb old bone material to make way for the new. A disruption in this balance one way or the other can result in unhealthy bone. In the case of osteoporosis, overactive osteoclasts eat away at bone faster than it can be reformed, resulting in bones that are less dense and more susceptible to fracture.

The general consensus among scientists was that osteoblasts and osteocytes, the cells within fully-formed bone, were the ones that kicked off the production of osteoclasts to begin the remodeling of bone. On the other hand, the role of adipocyte lineage cells, such as MALPs, in regulating the resorption of bone was not known.

Earlier in 2020, Qin's group discovered the abundant existence of MALPs within bone. MALPs are the precursors for adipocytes that carry fats, called lipids, inside bone marrow. And recent studies by Qin and her fellow researchers better cleared up how MALPs appear to factor in bone turnover. They showed that MALPs, but not osteoblast or osteocytes, have cell-to-cell contact with osteoclasts. Additionally, using advanced sequencing techniques at a single cell level, Qin and her colleagues found that MALPs secrete RANKL, a protein essential for forming osteoclasts, at a high level.

With that information, the researchers for this study, who included lead author Wei Yu, MD, PhD, working as a visiting scholar at Penn Medicine, studied mice with RANKL deficiencies in their MALPs. From the point those mice turned a month old, the researchers saw 60 to 100 percent higher density of the spongy components of long bones (like the femur) and vertebrae, something the researchers qualified as "a drastic increase" compared to typical mouse bone mass.

Since the osteoblasts and osteocytes continued to work as they always do, it would seem that MALPs and their RANKL secretions have been pinpointed as the main driver of osteoclast function and the absorption of existing bone.

"By identifying what appears to be the full function of MALP cells, we believe that we have uncovered an extremely promising target that would never have been considered before," Qin said. "If their RANKL secretions can be reliably disabled, it could rebalance bone remodeling in people with osteoporosis and allow for osteoblasts and osteocytes to 'catch up.'"

Qin's co-author, Jaimo Ahn, MD, PhD, a former faculty member at Penn Medicine now chief of orthopaedic trauma and associate chair of orthopaedic surgery at the University of Michigan, believes these discoveries could be very useful in more effectively rebuilding bone.
"An exciting future step, with an eye toward clinical application, would be to target MALPs in a timed and therapeutic fashion to test how well they simultaneously decrease the bone resorption and increase bone formation," Ahn said.

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

Ethical and Scientific Considerations Regarding the Early Approval and Deployment of a COVID-19 Vaccine

The COVID-19 pandemic demands early licensing and deployment of a vaccine that provides worthwhile efficacy, but accomplishing this goal could compromise two ethical principles that guide clinical research: scientific validity and social value.

Currently, five Western companies are conducting placebo-controlled, phase 3, randomized clinical trials (RCTs) whose primary outcome is the prevention of clinical disease. As soon as two months of data from one of these RCTs establishes vaccine efficacy, the U.S. Food and Drug Administration (FDA) could license the vaccine or provide Emergency Use Authorization (EUA) within a few days or weeks. The authors of this commentary point out this scenario will not answer questions about long-term efficacy and safety, which would require more months of data. To understand how to deploy different vaccines in the most optimal way, we must know their different characteristics and especially their long-term effects.

While vaccinating everyone in the U.S. who wants a vaccine by April 2021 as recent predictions state would be a great achievement, it would also intensify concerns about ethical issues surrounding early vaccine approval and deployment. The authors stress that it is important for us to plan to deal with those issues. This commentary is published in Annals of Internal Medicine. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-7357.

Media contacts: A PDF for this article is not yet available. Please click the link to read the full text. The lead author, Rafael Dal-Ré, MD, PhD, MPH, can be reached directly at rafael.dalre@quironsalud.es.

Glaucoma is a chronic condition that affects cells at the back of the eye. It is the leading cause of irreversible blindness worldwide, and is responsible for 1 in 10 cases of serious sight impairment in the UK.

People with glaucoma, or at risk of developing glaucoma, require lifelong monitoring, including regular eye tests to track the progression of the disease. Currently, these examinations require regular hospital visits (e.g., twice yearly, for life) and use expensive, specialist equipment.

Aging populations make this hospital-only model of patient-management unsustainable, and many clinics are already overstretched, with appointments routinely delayed or cancelled. In the UK today, around 20 people a month are going blind as a result of this appointment backlog.

This situation has been compounded by the COVID-19 pandemic, since the inability to sanitise equipment between use has led to all routine sight assessments being suspended in the UK. The long-term effects of this are unknown, but experts suggest that further increases in appointment delays and avoidable blindness appear inevitable.

Even if routine assessments are ever fully resumed, it is also thought that the current system of annual hospital visits is insufficient to track the most aggressive forms of glaucoma. Multiple studies have already suggested that more frequent (e.g., monthly) glaucoma eye tests could substantially improve clinical outcomes: allowing high risk patients to be treated sooner and more appropriately.

A new study from City, University of London adds to a body of evidence suggesting that the solution to all these problems may lie in home-monitoring.

The research involved 20 NHS glaucoma patients from across England and Wales who were provided with a prototype, tablet-based eye test ('Eyecatcher') for six months. Using the device, they were asked to run the home glaucoma eye test themselves, testing each of their eyes once a month.

Similar to conventional eye tests for glaucoma, patients looked at a central cross presented on the device, and pressed a button when they saw a flash of light, which appeared at different locations and was of variable intensity. The computer's front-facing camera also recorded them during the test, and artificial intelligence (AI) was used to perform facial recognition and head-/eye-tracking, to ensure people performed the test correctly.

Accuracy was assessed by comparing measurements made at home to conventional 'gold standard' assessments performed in clinic at both the start and end of the study. Adherence was quantified as the percentage of tests completed.

The study found that 98% of home tests were completed successfully (high adherence), and that the data from the home-monitoring tests were in strong agreement with the gold standard clinical assessments (high accuracy).

The use of home-monitoring data was also shown to reduce measurement error when combined with current clinical data (by over 50% in 90% of eyes). This could potentially allow cases of rapid sight loss to be detected months or even years earlier.

This is the first study in the world that suggests glaucoma eye tests can be performed accurately at home by patients themselves.

Future studies will examine whether home-monitoring is sustainable over longer periods, and is capable of detecting rapidly progressing cases of glaucoma.

The study authors are also preparing a follow-up study that will present the views and opinions of people with glaucoma, regarding home-monitoring.

Dr Pete Jones, first author of the study, and Lecturer at the Division of Optometry and Visual Sciences, City, University of London said:

"This is tremendously exciting news. Effective home-monitoring would be a win-win-win for patients, clinicians, and the taxpayer alike, and it looks like the technology finally exists to make it a reality. This news is particularly timely, since home-monitoring is just one of the ways we can help make the NHS more resilient and sustainable, post-COVID."

Women with breast cancer whose eggs or ovarian tissue were frozen had more children after their diagnosis than women who did not undergo fertility preservation using those methods before start of cancer treatment. That is according to a study by researchers at Karolinska Institutet in Sweden that is published in the journal JAMA Oncology. According to the researchers, the result highlights the importance of reproductive counseling and fertility preservation for women who are diagnosed with cancer at a young age.

"Information about the possibilities of having children after breast cancer treatment, with or without fertility preservation, is very important for women who suffer from breast cancer at reproductive age," says Anna Marklund, first author of the study and PhD student at the Department of Oncology-Pathology, Karolinska Institutet. "We hope that the conclusions of our study can increase the body of knowledge so that more women with breast cancer who want to have children can make informed decisions in consultation with their doctors."

Breast cancer is the most common type of cancer among women. Nearly 10 percent of breast cancer cases occur in women younger than 45 years of age, some of whom have not had their first child when they receive their diagnosis. Breast cancer treatment often includes chemotherapy, which can damage ovarian tissue, and long-term hormonal treatment, which pushes many into early menopause.

Women with cancer who want to have biological children in the future are often recommended fertility preservation in the form of the freezing of eggs, embryos, or small pieces of ovarian tissue. In Sweden, such treatments are offered free of charge to women below 40 years of age who have no more than one child and suffer an illness where the treatment poses a risk to fertility.

In this prospective cohort study, the researchers followed all women with breast cancer (425) who had fertility preservation treatment at Swedish university hospitals between 1994 and 2017. They compared childbirth by these women with a matched control group of 850 breast cancer patients who did not have fertility preservation.

The study showed that childbirth and treatments with assisted reproduction were 2.3 times and 4.8 times, respectively, more common in the group with fertility preservation. Twenty-three percent of the women with fertility preservation gave birth to at least one child within the average span of 4.6 years after diagnosis, compared with 9 percent of the women in the control group who were followed for an average of 4.8 years. Of the women who were followed for 10 years, 41 percent in the group with fertility preservation had at least one child while the corresponding number for the women without fertility preservation treatment was only 16 percent.

One interesting finding in this study is that the mortality rate was lower in the fertility preservation group (5.3 percent), compared with the control group (11.1 percent). It is, however, not possible to draw any conclusions about causality based on the register data the researchers analyzed, since only total survival, not disease-specific survival, was included.

A limitation of the study was a lack of information about why the women in the control group didn't have fertility preservation treatment and whether they wanted to have children when they received their breast cancer diagnosis.

"It is possible that the desire, and not just the ability, to have children differed between the groups and that this, at least to some degree, explains the difference in childbirths. This is something that future research will have to expand on," says Kenny Rodriguez-Wallberg, the study's senior author and researcher at the Department of Oncology-Pathology, Karolinska Institutet. "We can, however, draw the conclusion that fertility preservation is safe in breast cancer patients and that there is a link between this treatment and the probability of having children after breast cancer."

A novel method that combines artificial intelligence with remote sensing satellite technologies has produced the most detailed coverage of air pollution in Britain to date.

Highlighted by new research led by the London School of Hygiene & Tropical Medicine (LSHTM) and published in Remote Sensing, the methodology provides accurate estimates of concentrations of air pollution across Great Britain. The model offers an impressive level of details, with measurements provided at daily level and in a 1x1km grid across the whole Great Britain.

Results indicate that the South-East of England is the most polluted region, and they identify hot spots in urban and industrial areas. Encouragingly, the findings also show an overall decline in air pollution in Great Britain during the last decade.

The researchers say this novel approach could revolutionise the assessment of exposure to air pollution and our understanding of the related health risks, by linking country-wide exposure maps and health databases.

Currently, scientists rely on ground-based monitors to measure air pollution, however, these are sparsely located, mostly concentrated in urban areas, and are not always taking measurements continuously. This means there are no nationwide air pollution records accurate enough to be used in epidemiological analyses to evaluate health risks.

In this study, the researchers applied an innovative methodology that uses artificial intelligence and satellite-based data to estimate the daily human exposure to fine particles of air pollution from 2008-2018.

The team combined readings from existing ground-based monitors with data from earth observation satellite instruments, which provides information on weather patterns, aerosols suspended in the atmosphere, land use and vegetation cover. They also incorporated data from other sources, including population density, road density and the location of airports.

Using sophisticated machine learning algorithms, they combined the datasets to produce estimates of the ground-level concentration of fine particulate matter (less than 2.5 micron in size, PM2.5), one of the most dangerous air pollutants. They divided Great Britain into grid cells and derived daily pollution series in the period 2008-18.

Dr Rochelle Schneider, first author who led the analysis, said: "This research uses the power of artificial intelligence to advance environmental modelling and address public health challenges. This impressive air pollution dataset represents PM2.5 records for 4,018 days in a spatial domain of 234,429 grid cells. This provides a remarkable total of 950 million data points that comprehensively quantify the level of air pollution across the whole of Great Britain in an eleven-year period."

The results of the study were cross-validated by comparing the estimates produced by the model to measurements taken from particular ground-based monitors, and were found to be closely aligned.

The team now intend to combine the data with local health records. This linked information will be used in cutting-edge epidemiological analyses to reveal a highly granular picture of the association between air pollution and health outcomes across Great Britain.

Professor Antonio Gasparrini, Professor of Biostatistics and Epidemiology at LSHTM and senior author of the study, said: "This study demonstrates how cutting-edge techniques based on artificial intelligence and satellite technologies can benefit public health research. The output reveals the shifting patterns of air pollution across Great Britain and in time with extraordinary detail. We now hope to use this information to better understand how pollution is affecting the nation's health, so we can take steps to minimise the risk. The vast amount of data produced will provide a vital tool for public health researchers investigating the effects of air pollution."

The World Health Organization estimates that there are seven million deaths per year worldwide due to air pollution, which causes lung disease, lung cancer, heart disease and strokes.

Dr Vincent-Henri Peuch, Director of Copernicus Atmosphere Monitoring Service (CAMS) at European Centre for Medium-Range Weather Forecasts (ECMWF), said: "This innovative method has combined the strengths of different data sources to give accurate and comprehensive estimates of air pollution exposure, including ground-based sensors, satellite data, and model reanalyses developed by ECMWF as part of the EU Copernicus programme. Dr Schneider and co-authors convincingly demonstrate its performance over Great Britain, paving the way for many future studies into the health effects of air pollution."

Dr Pierre-Philippe Mathieu, Head of Phi-lab Explore Office at European Space Agency (ESA), said: "It's exciting to see data from Earth observation satellites being used in public health research to advance our understanding of the intricate relationship between health and air quality, improving lives in Great Britain, Europe and the rest of the world."

The study is limited by the fact that the method could not reliably recover air pollution levels from years before 2008, given the limited number of PM2.5 monitors available. In addition, the performance of the model can be lower in remote areas characterised by limited coverage of ground monitoring network. The LSHTM team plans to extend this model and reconstruct high-resolution data of other air pollutants.

Researchers at McMaster University, the Montreal Clinical Research Institute and the University of Montreal think they’ve found a fountain of youth – and it’s unique to a few French Canadian families.

November 19, 2020 - Canadian scientists looking at a rare genetic mutation think they may have discovered the proverbial fountain of youth. But it's not for everyone: so far, the mutation has only been found in a handful of French-Canadian families.

Called PCSK9Q152H, the mutation of the PCSK9 gene was initially thought to protect against cardiovascular diseases. Recent studies reveal that it may protect against other human illnesses, mainly liver diseases. It may allow the lucky PCSK9Q152H mutant subjects to stay in good health and live longer, the researchers say in a study published today in the prestigious Journal of Clinical Investigation.

The work was led by vascular biologists Richard Austin and Paul Lebeau of McMaster University and by Montreal Clinical Research Institute endocrinologist Michel Chrétien, an emeritus professor at the University of Montreal.

Gene therapy next?

"These are exciting findings -- what we've found may represent a kind of fountain of youth," said Austin, a medical professor and one of the senior authors of the study. "Now we want to see whether we can come up with a gene therapy approach to overexpress this specific mutant gene variant in the liver, and thereby offer an innovative treatment for a number of diseases that normally lead to early death."

News of the PCSK9Q152H mutation was first published in 2011, after Chrétien, the current study's lead clinical investigator, discovered it in a French-Canadian family. Mainly expressed in the liver, the mutated gene lowers a person's plasma LDL-cholesterol ('bad') and prevents cardiovascular diseases. Chrétien and his IRCM colleague Hanny Wassef found it in two other large French-Canadian families, as well.

People carrying this gene mutation are surprisingly healthy well into their late 80s and mid-90s. In addition to their low plasma LDL-cholesterol and their low risk of cardiovascular diseases, their liver function is completely normal when measured through imaging and a complete medical evaluation, the Montreal scientists found.

Until now, however, the underlying mechanism by which the mutation represented a health benefit other than cardiovascular was a mystery.

A surprising protective effect

In the new study, the McMaster researchers show that overexpression of this gene variant in the livers of mice who don't carry PCSK9Q152H had a surprising protective effect against injury and dysfunction of their liver. As well, overexpression led to a large reduction in their circulating PCSK9 levels -- just as it does in people, decreasing individuals' bad cholesterol and keeping them in good cardiovascular health.

"When we initiated these studies, we had speculated that introducing the mutant PCSK9Q152H protein into the liver of mice would cause liver injury or dysfunction," Austin said. But "to our amazement," added Lebeau, "overexpression of the mutant gene variant in the livers of mice failed to cause stress in the cellular manufacturing and packaging system called the endoplasmic reticulum, or ER, and actually protected against ER stress-induced liver injury."

In their laboratory, the McMaster scientists went on to show that the mutant gene variant acts as a unique co-chaperone protein to stabilize several well-known ER chaperones, namely GRP78 and GRP94, and to increase their protective activity against liver damage.

'Particularly gratifying results'

"These results from Dr. Austin's group are particularly gratifying since they experimentally explain that this gene mutation, known to lower cardiovascular accidents, also protects against liver injury and dysfunction, even in individuals who are in their late 80s and mid-90s," said Chrétien, also an emeritus scientist at the Ottawa Hospital Research Institute.

"Furthermore, these findings should allow us to determine whether this unique mutation provides additional protection against liver diseases such as cancer, over and above its protective effect against cardiovascular accidents."

The Mediterranean (MED) diet -- rich in olive oil, fruits, vegetables, legumes, nuts and seeds -- is a recommended way to reduce the risk of heart disease, type 2 diabetes and other adverse health outcomes. But exactly how and why the MED diet lowers risk for type 2 diabetes has remained unclear. In a study conducted by investigators from Brigham and Women's Hospital, researchers examined outcomes for more than 25,000 participants in the Women's Health Study, a longitudinal cohort study that followed female health professionals for more than 20 years. In a paper published in JAMA Network Open, the investigators report that women who adhered to a more MED-like diet had a 30 percent lower rate of type 2 diabetes than women who did not. The team examined several biomarkers to look for biological explanations for these results, finding key mechanisms including insulin resistance, body mass index, lipoprotein metabolism and inflammation.

"Our findings support the idea that by improving their diet, people can improve their future risk of type 2 diabetes, particularly if they are overweight or have obesity," said corresponding author Samia Mora, MD, MHS, of the Brigham's divisions of Preventive Medicine and Cardiovascular Medicine and an associate professor at Harvard Medical School. "A lot of the benefit we see can be explained through just a few pathways. And it's important to note that many of these changes don't happen right away -- while metabolism can change over a short period of time, our study indicates that there are longer term changes happening that may provide protection over decades."

The Women's Health Study (WHS) enrolled female health care professionals between 1992 and 1995, collecting data through December 2017. It was designed to evaluate the effects of vitamin E and low-dose aspirin on risk of heart disease and cancer. Additionally, participants were asked to complete food frequency questionnaires (FFQs) about dietary intake when the study began and answer other questions about lifestyle, medical history, demographics and more. More than 28,000 women provided blood samples at the beginning of the trial.

Mora and colleagues leveraged data from the FFQs and blood samples to investigate the relationship between the MED diet, type 2 diabetes and biomarkers that might explain the connection. To do so, they assigned each participant a MED diet intake score from 0 to 9, with points assigned for higher intake of fruits, vegetables, whole grains, legumes, nuts and fish, moderate intake of alcohol, and lower intake red meat or processed meat. The team measured a range of biomarkers, including traditional ones such as cholesterol, and more specialized ones that can only be detected using nucleic magnetic resonance. These included lipoproteins -- molecules that pack and transport fats and proteins -- and measures of insulin resistance, a condition in which muscle, liver and fat cells do not respond to normal amounts of insulin. Insulin resistance is often a precursor to diabetes.

Of the more than 25,000 participants in the WHS, 2,307 developed type 2 diabetes. Participants with higher MED intake at the beginning of the study (scores greater than or equal to 6) developed diabetes at rates that were 30 percent lower than participants with lower MED intake (scores less than or equal to 3). This effect was seen only among participants with a body mass index greater than 25 (overweight or obese range) and not among participants whose BMI was less than 25 (normal or underweight).

Biomarkers of insulin resistance appeared to be the biggest contributor to lower risk, followed by biomarkers of body mass index, high-density lipoprotein measures and inflammation.

"Most of this reduced risk associated with the Mediterranean diet and type 2 diabetes was explained through the biomarkers related to insulin resistance, adiposity, lipoprotein metabolism and inflammation," said first author Shafqat Ahmad, PhD, a researcher in the Molecular Epidemiology Unit at Uppsala University, Sweden, who helped conduct the study while working at the Brigham. "This understanding may have important downstream consequences for the primary prevention of diabetes disease."

One of the strengths of the study was its length -- unlike many previous studies that have only looked at short-term effects of diets, the WHS followed participants for up to 25 years to see who developed type 2 diabetes. But the authors note several limitations, including that study participants were predominantly white and well educated, and all were female health professionals. In addition, dietary intake was self-reported and only examined at the start of the study. Biomarkers were also only measured when participants entered the study.

Mora emphasizes that insights into the biology that explains how the Mediterranean diet may help protect against diabetes could be helpful in preventive medicine and for physicians speaking to patients about dietary changes.

"Even small changes can add up over time," she said. "And there may be many biological pathways that lead to a benefit. One of the best things patients can do for future health is to improve their diet, and now we are beginning to understand why."

During the pandemic, handy meal kit delivery services are helping to develop home cooking habits incorporating healthy ingredients such as vegetables, and a balance of less harmful fats and salt.

Meal kits services seem to be growing in popularity but there is very little research on those who use meal kits and what the potential nutritional benefits and risks may be," Australian nutrition and dietetics researchers say in a new paper in Health Promotion International.

"For example, we really don't know if they are better or worse than home cooking or takeaway food," says lead author Dr Carly Moores, Registered Nutritionist, a Flinders University graduate and now postdoctoral research fellow at the University of Adelaide

The researchers reviewed a year's worth of recipes from a popular meal kit service, focusing on the qualities of the recipes - including ingredients and time to prepare meals.

Co-author Flinders University academic and Accredited Practising Dietitian Dr Kacie Dickinson says a typical recipe contained about nine different ingredients, averaging three vegetables and three ingredients from the home pantry.

The meals took about 35?minutes to prepare and were found to be relatively high in energy from fat and protein. Meals were also relatively high in sodium with some exceeding the Australian Suggested Dietary Target for sodium (

"This could be improved by increasing the vegetables and wholegrain ingredients in meals, or by reducing portion sizes," Dr Dickinson says.

Meal kits are advertised widely, including to families, so it was important to find meals also had positive qualities, for example included a number of different vegetables. This is important as know that vegetable intake is important for health, but intake is too low in most Australian adults and children.

"It's really important to understand the qualities of these recipes, which vary from week to week, before deciding whether the meal kit is a suitable service for you and your family's nutritional needs and preferences," adds Dr Moores.

An international team of researchers have uncovered a drug-like compound that blocks a crucial inflammatory pathway, potentially paving the way for a new treatment for a host of diseases - including COVID-19.

WEHI's Associate Professor Seth Masters and his research team discovered the compound could prevent up-regulation of CD14, a key inflammatory protein. The discovery was recently published in EBioMedicine.

At a glance

Researchers have uncovered a drug-like compound that blocks a key inflammatory pathway, involving the immune cell protein CD14.

In the laboratory, the compound reduced CD14 levels, limiting inflammation and preventing it from overwhelming the body.

The team hope the compound could lead to the development of new medicines for inflammatory diseases, including COVID-19.

Targeting inflammation

Inflammation is our body's natural reaction to infection, said Associate Professor Masters. "In the beginning, it helps you fight the infection - but too much inflammation is linked to a range of chronic and acute diseases," he said.

"In a viral disease such as COVID-19, some patients experience excessive inflammation - called a 'cytokine storm' - which can lead to hospitalisation or death. Blocking the CD14 pathway can reduce the severity of many diseases, and potentially save lives.

The team focussed their research on a protein called CD14, that is found on certain inflammatory immune cells called macrophages.

"CD14's job is to detect infection, helping to drive inflammation to clear a pathogen. But we know that the amount of CD14 increases on macrophages as inflammation progresses, potentially getting out of control, which could lead to worse outcomes for infections or other diseases," Associate Professor Masters said.

"Our team used CRISPR technology to search for genes that help CD14 levels to rise.

"We found many really interesting genes that were critical - and when we turned these genes off, they could prevent CD14-driven inflammation from overwhelming the body.

"Excitingly, a drug-like inhibitor blocks the protein produced by one of these genes. We found this compound could block the rise in CD14 and consequent inflammation in the laboratory, which is incredibly promising," Associate Professor Masters said.

Vital first step towards a treatment

Associate Professor Masters said the discovery of a potential anti-inflammatory compound opened the doors for new anti-inflammatory therapies.

"If this compound could be developed into a safe and effective drug, it could potentially assist in the treatment of many inflammatory diseases,

However, once available, the drug would only be beneficial for curbing severe inflammation.

"Inflammation is a critical process for fighting many infectious, so we only need to use an anti-inflammatory drug for the most severe and life-threatening forms of inflammation," Associate Professor Masters said.

"The next step in this research would be to see if this drug candidate worked against particular diseases in pre-clinical trials. There is great hope this research will one day be translated into an effective treatment for inflammatory illnesses."