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Patients with Lyme disease in England and Wales hospitals appear to be predominantly white, female and living in areas of low deprivation, according to a study published in the open access journal BMC Public Health. The study, which examined data on 2,361 hospital patients collected between 1998 and 2015, also found an increase in Lyme disease incidence over time, with the number of new cases peaking in August each year and higher rates in central southern and western England. The findings may inform and help target health promotion messages.

Dr John Tulloch, NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, the corresponding author said: "In the United Kingdom information relating to infected Lyme disease patients' characteristics, where they live and how they are managed within the National Health Service (NHS) is not fully understood. Through our analysis of NHS hospital data we were able to identify demographic information about Lyme disease patients accessing hospitals for management and treatment and, for the first time, start to describe how they progress through the healthcare system."

The authors identified 2,259 Lyme disease patients within anonymised health records in England and 102 patients within records in Wales, respectively. Out of all identified cases, 1,005 (60.1%) were women or girls, with peaks of new cases at the ages between six and ten, and 61 and 65 years. Out of the 1,877 patients for whom ethnicity information was recorded 1,803 (96%) self-identified as white.

John Tulloch said: "These data display a predominance of female cases of certain age groups, most of whom identify as white. The reasons for this are hard to explain, but could be related to differences in health seeking behaviour between women and men and an increased exposure to tick habitats due to leisure activities in children and older people, as opposed to occupational exposure in younger adults. The apparent association between ethnicity and Lyme disease is most likely due to sociocultural and behavioural reasons, for example living in areas that are more likely to see a higher abundance of disease-transmitting ticks."

Analysing the data over time, the authors found that the number of new cases rose from 0.08 per 100,000 people in 1998 to 0.53 cases per 100,000 people in 2015. The exact cause for the increase in Lyme disease incidence remains unclear, but may be the result of various factors, such as increased awareness by the public and/or hospital clinicians, increase in referrals by clinicians in primary care, or a true increase in incidence within England and Wales, according to the authors.

Based on the geographical information that was included in the health records, the authors showed that the highest number of Lyme disease cases were located in the south west of England. The local authorities with the highest number of cases were Purbeck with 3.13 cases per 100,000 people per year, New Forest (2.58 cases), and East Dorset (2.32 cases). Lyme disease patients were more likely to live in rural rather than urban areas.

John Tulloch said: "Almost all parts of England and Wales reported Lyme disease cases attending hospitals with clear hotspots of disease in central southern England. This highlights that while Lyme disease poses a risk across both countries, for the majority of people the risk is likely to be very low."

The authors also found that 30% of Lyme disease hospital admissions in England and 67.6% in Wales originated from the A&E department. The findings suggest a poor understanding of the recommended care pathways for symptoms related to Lyme disease by the general population.

John Tulloch said: "It would be unlikely that the numbers of patients admitted in our study have acute/severe presentations of disease that require immediate hospital attendance. Further work is needed to explore why so many patients would seek treatment at a hospital when, for the majority of cases, management could occur at primary care level."

He added: "Being aware of the signs and symptoms of Lyme disease is important so that patients can receive early diagnosis and treatment from their family doctor. Symptoms typically develop up to three weeks after being bitten by a tick and include a spreading circular red rash or flu-like symptoms. When patients visit their GP or call NHS 111, it is important to tell them where patients have been and if they remember being bitten."

An international team of researchers led by scientists at Washington University School of Medicine in St. Louis has identified a pair of genes that influence risk for both late-onset and early-onset Alzheimer's disease.

Most genes implicated thus far in Alzheimer's affect neurons that transmit messages, allowing different regions of the brain to communicate with one another. But the newly identified genes affect an entirely different population of cells: the brain's immune cells. The findings, published online Aug. 14 in the journal Science Translational Medicine, could provide scientists with new targets and a strategy for delaying the onset of Alzheimer's symptoms.

The genes -- known as MS4A4A and TREM2 -- operate in the microglia, the brain's immune cells. They influence Alzheimer's risk by altering levels of TREM2, a protein that is believed to help microglia cells clear excessive amounts of the Alzheimer's proteins amyloid and tau from the brain.

"The findings point to a new therapeutic strategy," said co-senior investigator Carlos Cruchaga, PhD, a professor of psychiatry and director of the NeuroGenomics and Informatics Group. "If we can do something to raise levels of the TREM2 protein in the cerebrospinal fluid, we may be able to protect against Alzheimer's disease or slow its development."

In this study, the researchers measured soluble TREM2 levels in the cerebrospinal fluid of 813 older adults, most of whom were ages 55 to 90. Of those subjects, 172 had Alzheimer's disease, 169 were cognitively normal, and another 183 had early mild cognitive impairment. They also analyzed the participants' DNA, conducting genomewide association studies to look for regions of the genome that may influence TREM2 levels in the cerebrospinal fluid.

Although variants in TREM2 are found in a very small percentage of patients with Alzheimer's disease, the gene previously had been linked to the disorder. People who carried those previously identified risk mutations were excluded from the study. Common variants in the MS4A4A gene also had been associated with risk for Alzheimer's, but this study connects those genes.

"We observed TREM2 risk variants more often in people who had Alzheimer's or were mildly cognitively impaired, compared with those who were cognitively normal," said co-senior investigator Celeste Karch, PhD, an assistant professor in the Department of Psychiatry. "It turns out that about 30 percent of the population in the study had variations in the MS4A4A gene that appear to affect their risk for developing Alzheimer's disease. Some variants protected people from Alzheimer's or made them more resilient while others increased their risk."

When the researchers dug further, they noted that variants in the MS4A4A gene cluster linked to an increase in risk for developing Alzheimer's disease are associated with lower levels of soluble TREM2 protein. The other variant, associated with higher levels of TREM2 in the cerebrospinal fluid, seemed to protect against Alzheimer's.

The research team validated its results in DNA from another 580 older adults. Once again, they found that higher soluble TREM2 levels in the cerebrospinal fluid seemed protective, while lower levels increased risk. And those protein levels -- whether high or low -- were linked to variants in the MS4A4A gene.

"For the past several years, we've been looking at TREM2 and increasing our focus on the involvement of the brain's immune cells in Alzheimer's disease" said another co-senior author, Bruno A. Benitez, MD, an assistant professor of psychiatry. "These findings give us a new therapeutic strategy to pursue, one focusing not only on neurons but on how the microglia may be involved in helping to clear damaging proteins, such as beta amyloid and tau, that are linked to Alzheimer's disease."

Those gene variants also may play a role in other diseases of the central nervous system, according to Laura Piccio, MD, PhD, an associate professor of neurology and another co-senior author.

"By combining large genetic and spinal fluid analyses with laboratory work, we have provided strong evidence of a biological link between TREM2 and proteins in the MS4A gene cluster, both of which previously had been associated with Alzheimer's disease," Piccio said. "We are beginning to elucidate a molecular pathway in microglia that could be critical not only in Alzheimer's disease but also in other neurodegenerative and inflammatory diseases in the central nervous system."

Having a hernia repaired, or an appendix or gallbladder removed, hurts. And for the past two decades, patients having these common operations in the U.S. have gone home from the hospital with prescriptions for dozens of opioid pills to ease that pain.

But with rising concern about the role of those pills in the national opioid epidemic, a new study shows how one state's surgeons reduced the number of opioids they prescribed to thousands of patients -- without causing patients to feel more pain or less satisfied with their surgical experience.

In a new research letter in the New England Journal of Medicine, a team from the Michigan Opioid Prescribing Engagement Network reports the results of a collaborative effort to help surgical teams follow evidence-based opioid prescribing guidelines developed at the University of Michigan.

In just one year, teams at 43 hospitals across the state reduced by nearly one-third the number of opioid pills they prescribed to patients having nine common operations, from an average of 26 per patient to an average of 18.

But the ratings their patients gave for their post-surgery pain and satisfaction didn't change from the ratings given by patients treated in the six months before the opioid-reducing effort.

In fact, patients throughout the study period reported that they only took half the opioids prescribed to them - even as the prescription sizes shrank. The researchers attribute this drop in part to improved pre-surgery counseling about pain expectations and non-opioid pain control options.

"These results happened because of the work of many members of the care teams at these hospitals - surgeons, nurses, pharmacists and others all took it upon themselves to change their prescribing practices," says Joceline Vu, M.D., first author of the new research letter. "We hope that other hospital teams can learn from this effort, use the guidelines and patient education materials we've developed, and gather data on their current surgical opioid prescribing patterns and their own processes to achieve change."

Vu, a surgical resident at Michigan Medicine, U-M's academic medical center, recently completed a research fellowship with Michigan-OPEN.

The study includes prescription data from 11,716 patients who had operations at hospitals participating in the Michigan Surgical Quality Collaborative. Just over half of the patients also filled out surveys sent to their homes after their operations, reporting on their pain, satisfaction and opioid use after surgery.

Michael Englesbe, M.D., is the U-M surgery professor who heads MSQC and co-directs Michigan-OPEN.

"The success of the statewide effort suggests an opportunity for other states to build on Michigan's experience, and room for even further reductions in prescription size," he says. "At the same time, we need to make sure that patients also know how to safely dispose of any leftover opioids they don't take."

The Michigan-OPEN team has worked since 2016 to study the role of surgical opioid prescribing in the start of new persistent opioid-taking behavior among patients, and to quantify how prescription size relates to number of opioids patients take, and their pain control.

That research led to the development of evidence-based opioid prescribing guidelines that were first tested on gallbladder surgery patients at Michigan Medicine, before being expanded to other types of surgery.

The team has also worked to improve proper disposal, to reduce the risk that excess opioids could be taken deliberately or accidentally by patients or their loved ones.

In the time since the study ended, the Michigan-OPEN team has revised its surgical prescribing guideline to suggest even smaller prescriptions for these operations, and has added over 15 other operations and procedures. Meanwhile, a Michigan law aimed at reducing excess opioid prescribing for acute pain took effect just after the study period, though the law allows for a much larger prescription than the Michigan-OPEN guidelines recommend.

Vu notes that the new study represents a success for the concept of a "learning health system" - the ability to translate data about practice patterns into rapid provider-driven change for the benefit of patients. "Just as the airline industry sees every flight as a learning opportunity, and a chance to identify new practices to implement quickly, we can do the same in medicine to identify issues, get data, create recommendations, implement them and continuously evaluate how to improve."

Immunotherapeutic drugs are a potent way of transforming the immune system into a ferocious guard dog that can sniff out and destroy tumor cells. But for some therapies, it helps to have a leash. Without one, immunotherapies can do their job too well, stimulating the immune system to overreact, causing systemic toxicity. A new clinical trial by investigators from Brigham and Women's Hospital and Dana-Farber Cancer Institute set out to test the safety and effectiveness of controlling a powerful immunotherapy, known as human interleukin-12 (hIL-12), by using an oral activator -- a drug that can give finer control over when a gene gets turned on -- in patients with recurrent glioblastoma. The protein hIL-12 can stimulate many branches of the immune system, but previous clinical trials that leveraged it were halted because of toxicity. Results from the new clinical trial, sponsored by Ziopharm Oncology, Inc., are more promising: the drug-inducible gene therapy approach showed anti-tumor effects, with tolerable and reversible side effects. The study lays groundwork for more robust clinical trials of this therapy, with potential applications for glioblastoma and beyond. Results are published in Science Translational Medicine.

"In a phase 1 trial, we're always trying to find a glimmer: Is there any evidence of efficacy? These results give us that glimmer of hope," said corresponding author Antonio Chiocca, MD, PhD, chair of the Department of Neurosurgery at the Brigham. "We believe it is now possible to do regulatable immunotherapy via genes. It's well-tolerated in patients with glioblastoma, with some encouraging evidence that the drug is having its intended effect."

Glioblastoma is an aggressive, incurable cancer with a median overall survival of 15 months. Patients with glioblastoma receive surgery, radiation and chemotherapy, but in almost all cases, tumors return within months. When glioblastoma recurs, median overall survival is only a few months. In the current, multi-center study, 31 patients with recurrent glioblastoma received a dose of veledimex, the oral activator, before surgery to remove brain tumors. They received an injection of an hIL-12 vector (Ad-RTS-hIL-12), which delivered an IL-12 drug, at the time of surgery. They then continued taking veledimex for 14 days.

Patients received 10-40 mg of veledimex, and the researchers reported dose-related increases of veledimex, IL-12, and other measures of immune activity in the blood of patients. Frequency and severity of adverse events, including cytokine release syndrome, correlated with the veledimex dose, reversing promptly upon discontinuation. Patients taking the 20 mg dose of veledimex had a median overall survival rate of 12.7 months.

The team found that taking corticosteroids while on the IL-12 gene therapy negatively impacted survival. Corticosteroids are prescribed to relieve brain swelling but are also immunosuppressive, potentially dampening the effectiveness of the therapy. Overall, Patients taking 20 mg of veledimex with minimal corticosteroids had a median overall survival of 17.8 months (6.4 months for those on corticosteroids).

While these median overall survival times are favorable compared to recurrent glioblastoma historical controls (numbers reported in previous studies), more advanced studies with more patients will need to be performed to confirm if the treatment is truly efficacious.

When Chiocca and colleagues had access to tissue from tumors that had been treated with the IL-12 gene therapy, they saw evidence that immune cells had infiltrated the tumor -- a good sign -- but also saw evidence of increased checkpoint signaling, a trick that cancer cells use to stop the immune system. As a next step, the team is combining IL-12 gene therapy with intravenous checkpoint inhibitors. A phase 1 clinical trial is now underway.

Abnormal breast growth in young girls is linked to lavender oil exposure, according to a recent study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Previous research has associated breast growth in boys with lavender-containing fragrances. This study, "Lavender Products Associated With Premature Thelarche and Prepubertal Gynecomastia: Case Reports and EDC Activities," is the first to report abnormal breast growth in young girls.

The researchers found that breast growth in young girls and boys resolved after discontinuing lavender-containing fragranced products. They also determined that certain components of essential oils mimic estrogen and block testosterone, indicating that essential oils could be a source for the breast growth observed in these cases.

"The public should be aware of these findings and consider all evidence before deciding when to use essential oils," said study lead investigator J. Tyler Ramsey, a second year medical student at Campbell University and postbaccalaureate research fellow at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health. "It's also important that physicians are aware that lavender and tea tree oils contain endocrine-disrupting chemicals and should be considered in the evaluation of premature breast development in young girls and boys, and the swelling of breast tissue in adult men."

"It appears that essential oil products have the potential to cause premature breast growth in young girls and boys, so it may be best to discontinue using them on children," Ramsey said.

FINDINGS

Cancer that has spread to the central nervous system is notoriously difficult to treat. Now, UCLA researchers have developed a drug delivery system that breaks through the blood-brain barrier in order to reach and treat cancer that has spread to the central nervous system.

In research conducted in mice, a single dose of cancer drugs in a nanoscale capsule developed by the scientists eliminated all B-cell lymphoma that had metastasized to the animals' central nervous system.

BACKGROUND

About 15% to 40% of all cancers spread to the nervous system, but there are few treatment options and they only work in a small number of patients. One reason treatments are ineffective is that the blood-brain barrier, a natural defense system that prevents harmful agents from entering the brain, blocks many drugs, preventing them from reaching cancer that has spread to the central nervous system.

METHOD

To create a vessel that could carry cancer drugs to the central nervous system, the scientists produced a capsule measuring about one nanometer, or one billionth of a meter, across. (For reference, a sheet of paper is about 100,000 nanometers thick.) The capsule is coated with a substance called 2-methacryloyloxyethyl phosphorylcholine, which they hypothesized would be unlikely to be blocked by the blood-brain barrier, which would enable the capsule to release antibodies when it came into close proximity with cancerous cells.

The researchers loaded nanocapsules with the cancer-fighting drug rituximab and then administered them to mice with a human B-cell lymphoma that had metastasized to the animals' central nervous system. The scientists tracked how the tumors grew or shrank over a period of four months.

IMPACT

Pending additional research, including testing in human subjects, the UCLA-engineered capsule could be used to carry drugs that have already been approved by the FDA to treat cancer that has spread to the central nervous system.

The approach could be useful not only for cancers that metastasize to the central nervous system -- such as breast cancer, small cell lung cancer and melanoma -- but also for primary brain tumors or other brain diseases.

For children with Ewing sarcoma, an aggressive bone cancer, a combination of two different classes of drugs may work synergistically to turn off the drivers fueling this disease, finds a new study. The combination appears to be more powerful than relying on either treatment alone.

The study, published online last month in Clinical Cancer Research, is the latest in a series of investigations performed by researchers at Dana Farber/Boston Children's Cancer and Blood Disorders Center and their collaborators from other leading cancer centers. Their efforts are shedding new light on the biology that fuels the aggressive nature of Ewing sarcoma cells and is leading to new drug targets for this and other forms of pediatric cancer.

A challenging disease to tackle

While current treatment methods have been found to cure about 70 percent of children with a localized form of Ewing sarcoma, they often involve a combination of aggressive chemotherapy, radiation, and surgery that can be difficult for young patients to tolerate. For children with metastatic disease or those who relapse after completing first-line therapy, treatment options are limited and rarely result in a cure.

Further compounding matters is that children face long delays in accessing clinical trials of less toxic medications that target the mutations that drive their cancer, says Kimberly Stegmaier, MD, co-director of the pediatric hematologic malignancy program at Dana-Farber/Boston Children's Cancer and Blood Disorders Center and a member of the Broad Institute.

Identifying a two-pronged treatment approach

Stegmaier and Dana Farber/Boston Children's colleague Brian Crompton, MD, are both corresponding authors of the latest study. In previous work, they demonstrated that Ewing sarcoma is dependent on the activity of a protein called focal adhesion kinase (FAK), and that inhibition of FAK activity slows Ewing tumor growth. However, numerous studies have demonstrated that treatment with a single drug is insufficient. Rather than combining FAK inhibitors with chemotherapy, Stegmaier and Crompton set out to find other less toxic targeted therapies that could be paired with FAK inhibitors to more effectively kill Ewing sarcoma cells.

In their new study, Stegmaier and Crompton screened a large collection of cancer drugs to identify agents that would synergize with FAK inhibition to kill Ewing sarcoma cells. They found that combining FAK inhibitors with drugs targeting a protein required for cells to divide, aurora kinase B, resulted in more Ewing sarcoma cell death and significantly inhibited tumor progression more than either treatment did on its own.

Building on past findings

The discovery comes on the heels of two other published studies on Ewing sarcoma that identify novel treatment approaches for this disease.

Stegmaier was senior author on a study published in Cancer Cell in early 2018, which explored how to target challenging cancers such as Ewing sarcoma that are driven by oncogenic transcription factors (proteins that turn genes on or off). The researchers discovered that CDK12 inhibitors, when combined with a PARP inhibitor drug, can have a dramatic impact on Ewing sarcoma cells, a combination expected to be less toxic to patients than chemotherapy.

Another recently published study used a CRISPR-Cas9 editing screen to probe for genetic weaknesses. The researchers were able to identify genes whose activity promotes proliferation of Ewing sarcoma cells in which p53, a protective gene that is mutated in most adult cancers, is intact. By targeting these genes, they were able to kill Ewing sarcoma cells in a dish and slow tumor growth in mouse models. These findings, published last summer, have also led to a clinical trial in patients with Ewing sarcoma and several other types of cancer.

Offering new hope for pediatric cancer patients

"These studies are beginning to pave the way for the development of new and more effective treatments for patients with Ewing sarcoma that are expected to have less toxicity than the current standard treatment for this disease," Crompton says.

They may also provide much-needed therapeutic options for patients who relapse after receiving front-line therapy, offering new hope for children and their families.

A phase 1 clinical trial has demonstrated that a two-step gene therapy treatment was safe and effective in 31 patients with recurrent glioblastoma - a stubborn form of brain cancer - potentially overcoming a major hurdle that has hindered the use of systemically administered interleukin 12 (IL-12)-based regimens. The therapy boosted the infiltration of immune cells into tumors and showed encouraging preliminary benefits, indicating it has promise as a treatment for patients with this usually fatal disease. Glioblastoma has several approved treatments, but there are currently no curative options. Studies have found that interleukin 12 (IL-12) - an antitumor molecule - has beneficial effects against cancer, but IL-12 cannot be administered systemically due to its unfavorable safety profile. In search of a much-needed treatment alternative, E. Antonio Chiocca and colleagues developed an approach that leverages the anticancer benefits of IL-12, while limiting its toxicity. Their two-step approach (conducted after surgical removal of the tumor) involves injecting the tumor site with a viral vector that delivers the gene for IL-12, followed by oral administration of a drug candidate named veledimex that triggers the production of IL-12. In a multicenter phase 1 trial, the regimen boosted IL-12 production in the brains of 31 patients with recurrent glioblastoma while limiting the amount of IL-12 that entered systemic circulation. Although some patients exhibited serious side effects, they were easily reversed after discontinuing the treatment and were less severe in patients receiving lower doses of veledimex. Antitumor immune cells penetrated the tumor more effectively after treatment, and the scientists saw signs that the therapy may have boosted overall survival. Patients who received restricted doses of the corticosteroid dexamethasone throughout IL-12 treatment showed greater survival benefits, hinting that limiting corticosteroid use could maximize the benefits of IL-12 treatment and similar immunotherapies.

PHILADELPHIA - Five years ago, David C. Fajgenbaum, MD, MBA, MSc, both a Penn Medicine researcher and patient, tried an experimental treatment on himself based on his laboratory research findings in the hopes of saving his own life. He has been in remission ever since. Now his research is shedding new light on why it worked, paving the way for further testing of a new treatment approach in Castleman disease, a rare and deadly condition with limited options for patients. The work is led by Fajgenbaum, who is both the director of the Center for Study & Treatment of Castleman's & Inflammatory Lymphadenopathies (CSTL) in the Perelman School of Medicine at the University of Pennsylvania as well as Patient 1 in the study. The findings show patients who do not respond to the only drug currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of the disease may have another option that targets a specific pathway called PI3K/Akt/mTOR. The research is published in the Journal of Clinical Investigation today.

Castleman disease isn't actually a single disease. The term describes a group of inflammatory disorders that share a common appearance under the microscope. It's diagnosed in about 5,000 people of all ages each year in the United States, which makes it roughly as common as Lou Gehrig's disease, also called ALS. Patients experience a range of symptoms - from a single abnormal lymph node with mild flu-like symptoms to abnormal lymph nodes located throughout their entire body, abnormal blood cell counts, and life-threatening failure of multiple organ systems, such as the kidneys, liver, heart, and lungs.

The most severe subtype, idiopathic multicentric Castleman disease (iMCD), has similarities to both autoimmune conditions as well as cancer. About 35 percent of patients with iMCD will die within five years of diagnosis. In 2014, the FDA approved the drug siltuximab to treat iMCD, and studies have shown it can send between one-third and one-half of patients into a remission that generally lasts for years.

"Patients who don't respond to siltuximab have limited options. They typically receive chemotherapy but often relapse," said Fajgenbaum, who is also an assistant professor of Medicine in the division of Translational Medicine & Human Genetics at Penn and executive director of the Castleman Disease Collaborative Network. The study's senior authors are Thomas S. Uldrick, MD, MS, the deputy head of Global Oncology at Fred Hutchinson Cancer Research Center who was also Fajgenbaum's treating physician while practicing at the National Institutes of Health, and Frits van Rhee, MD, PhD, the clinical director of the Myeloma Center at the University of Arkansas for Medical Sciences.

A med student, a former Division I quarterback, and a state-champion weight lifter, Fajgenbaum suddenly became sick in July 2010. In 2012, after failing to respond to other therapies and having relapsed multiple times after chemo, Fajgenbaum's research on his own condition suggested that an inhibitor drug called sirolimus that blocked the PI3K/Akt/mTOR pathway could be effective. This drug is already available for the treatment of other conditions, particularly to prevent organ rejection after kidney transplantation. Fajgenbaum's decision to test it on himself, which was based on his own research and made in consultation with Uldrick, his treating physician, has kept him in remission ever since. This study also examines two additional patients treated with the same approach who also achieved a sustained remission. Research showed all three patients saw an increase in two aspects of the immune system - increased numbers of activated T cells and elevated levels of a protein called VEGF-A that causes blood vessel growth - before a flare up, then a return to normal levels once remission began.

"Our findings are the first to link T cells, VEGF-A, and the PI3K/Akt/mTOR pathway to iMCD," Fajgenbaum said. "Most importantly, these patients improved when we inhibited mTOR. This is crucial because it gives us a therapeutic target for patients who don't respond to siltuximab."

Fajgenbaum and his team will test the treatment in a clinical trial (NCT03933904) set to open in the coming weeks at the University of Pennsylvania, with Sunita Nasta, MD, FACP, an associate professor of Hematology-Oncology, and Adam Cohen, MD, an assistant professor of Hematology-Oncology, enrolling and treating patients. The University of Arkansas for Medical Sciences will also serve as a trial site under the direction of van Rhee.

Fajgenbaum also points out the larger implications this research has for the rare disease community.

"This highlights the potential for the approximately 1,500 drugs already approved for one condition to also be treatments or cures for the 7,000 diseases with no or insufficient treatment options like ALS and many pediatric cancers," Fajgenbaum said.

NEWTOWN SQUARE, Penn., Aug. 13, 2019 - In addition to cleaning the air and water, forests hold a tremendous amount of sequestered carbon. When trees die and then decay on the forest floor, that carbon is released into the atmosphere, a phenomenon that is one of the drivers of climate change. A first-of-its-kind study by a team that included the United States Department of Agriculture's Forest Service and Purdue University scientists finds that non-native invasive insects and diseases are reducing the amount of carbon stored in trees across the United States.

The study by Forest Service scientists Randall Morin, Chris Oswalt and Andrew Liebhold with lead author Songlin Fei of Purdue University used data from 92,978 field plots sampled by the Forest Service's Forest Inventory and Analysis (FIA) program in is the first attempt to comprehensively quantify the cumulative losses of trees following invasion by all species of non-native insects and diseases at a national scale.

The study, "Biomass losses resulting from insect and disease invasions in USA forests," is available at: https://www.nrs.fs.fed.us/pubs/58371.

In North America, forests account for an estimated 76 percent of carbon sequestration, or removal from the atmosphere and storage globally. "The key impact of the tree-killing alien insects and diseases is that they are greatly increasing the rate at which trees die on average," Liebhold said. "This transfers carbon stored in live trees to dead material and much of this carbon will likely return to the atmosphere."

Scientists emphasized that the study does not suggest that insect-killed trees become instant sources of carbon emissions. "Carbon transfers from living trees and plants to dead organic matter, and the release of carbon occurs gradually with decomposition of organic matter," Fei said. "However, the total amount of carbon in these dead materials are substantial, which is comparable to carbon emissions from 4.4 million cars or nearly one-fifth of all wildfires in the United States annually."

More than 430 non-native insects and diseases have found their way to U.S. forests. Most of these species have little known effects on forests, however 83 have caused noticeable damage. In their study, Fei and Forest Service scientists examined the impacts of these 83 known damaging non-native forest insect and disease species and estimated the rate at which live tree biomass has been killed by the 15 species that have had the greatest impacts on forests. Insects such as the emerald ash borer, gypsy moth, and hemlock woolly adelgid and diseases including Dutch elm disease, beech bark disease and laurel wilt disease are among the 15 most damaging non-native species.

As these insects and diseases continue to spread and tree mortality increases, the toll on forested landscapes and associated carbon storage will continue; the study suggests that 41 percent of the total live forest biomass remaining in the conterminous United States is threatened.

For more than 80 years, FIA has been collecting data that informs forest management. Historically the large dataset has been used by states and private groups to monitor forest area, health, and conditions. Recent collaborations have demonstrated novel, interdisciplinary applications. "This study demonstrates the power of the FIA data to quantify the impact that non-native forest pests are having in the United States," Morin said.

Family physicians typically don't consider where patients live when assessing their health care needs, despite research that indicates a person's environment can significantly affect their health. Things like access to health care and nutritious food and the quality of housing, education, water and air all play a role in health.

With the emergence of value-based health care, there are more incentives for providers to take those factors into account. Doctors are rewarded for actually improving a patients' health in a value-based delivery model, instead of being paid for each visit, procedure or test, regardless of the outcome.

However, a study published in the Annals of Family Medicine found that family physicians could not accurately estimate where their patients actually live. Study participants overestimated the geographic footprint of their practice by 112% on average, or 166 miles. In other words, they perceived their patients were more widely distributed in the region than they actually were.

Understanding the communities they serve is a critical first step for physicians to implement a more community-oriented approach to care, according to Dr. Winston Liaw, chair of the Department of Health Systems and Population Health Sciences at the University of Houston College of Medicine. He believes this lack of awareness ultimately leaves clinicians feeling unprepared and communities underserved.

"The idea of thinking about where patients live is radical, because we're not trained to ask for that information," said Liaw, study co-investigator. "We need to get providers to integrate geography into their practice data and get them thinking about the health needs of specific communities."

To address this gap, more practices are moving services out of the clinic and directly into the community, making it vital to "understand a community's needs, identify those in need not accessing care, engage potential community partners for collaborative care, and consider novel community-based interventions," according to the study.

Information about the health challenges faced by specific communities should be integrated into electronic health records and used to develop strategic interventions, according to Liaw.

"If I wanted to push a diabetic educator into the community, for example, then I need to know where to put them. I need to know the neighborhoods my clinic serves and more specifically, where diabetic patients are living. Otherwise we're just guessing," said Liaw. "We need data in order to figure out how to allocate our resources on a geographic level."

The UH College of Medicine, while still pending accreditation, is taking a new approach to medical education that will prepare primary care doctors to be more effective with underserved populations, key to improving the overall health and health care of people in Houston and Texas. Understanding the social factors that influence health is a major focus.

"As we develop an innovative curriculum, much of it will be about neighborhoods, geography and population health," said Liaw. "We need to train doctors to think about health in a more geographically informed way."

The study was funded through a pilot grant from the Virginia Commonwealth University Wright Center for Clinical and Translational Research.

"The intention was to gain a better understanding of patients' social determinants of health risks based on where they lived," said Dr. Alex Krist, study co-investigator and professor of family medicine at VCU and co-director of community-engaged research at the Wright Center. "We found that patients who come from more disadvantaged communities were less likely to get the care they needed."

Krist said the study quantitatively reinforced what he has observed through interactions with patients at the family medicine clinic where he practices.

"It is important for a doctor to know where their patient comes from," he said. "This study revealed that doctors don't understand the footprint of where their patients came from as well as they thought."

AUSTIN, Texas -- For adults with high blood pressure, greater blood pressure control than what's currently considered standard is associated with fewer adverse changes of the brain, which could mean lower risks of dementia and cognitive impairment, according to new research published in the Journal of the American Medical Association.

Specifically, the magnetic resonance imaging (MRI) study of 449 adults showed that those with high blood pressure who achieved systolic blood pressure of less than 120 mm Hg - known as "intensive" blood pressure control - had a small but significantly lower amount of white matter lesions on their brain but a slightly greater decrease in brain volume than similar patients who achieved the current standard for healthy blood pressure of 140 mm Hg.

"The great news from this research is that high blood pressure is a treatable condition, and if you treat high blood pressure aggressively, you could have a positive benefit on cognition and brain structure," said R. Nick Bryan, M.D., Ph.D., chair and professor of the Department of Diagnostic Medicine at Dell Medical School at The University of Texas at Austin. "Though the benefit may be small, it's one of the few impactful cognition-related interventions we have."

White matter brain lesions are well-documented to be associated with a greater likelihood or intensity of cognitive decline. According to the American Heart Association, high blood pressure is considered 130 mm Hg or higher.

The current study supports the findings of a related study published in January that showed intensive blood pressure control is associated with fewer incidents of cognitive adverse events. Both studies were part of a larger body of NIH-funded research known as Systolic Blood Pressure Intervention Trial (SPRINT), designed to determine the protective value of lower blood pressure for heart, kidney and brain health. Previous research within SPRINT also showed that intensive blood pressure control among people with hypertension is linked to better outcomes in terms of risks of heart attack, heart failure and death.

In the current study, researchers compared MRI scans of adults age 50 and older, average age 67 years old, with systolic blood pressure between 130 and 180 mm Hg at baseline and four years later, noting white matter lesions and brain volume.

The next step in this investigation is to understand the effects of intensive blood pressure control among younger adults, such as those in their 40s, said Bryan. "We need to understand how aggressive should we be with blood pressure control when we're earlier on in the process," he said.

Sepsis occurs when the body goes overboard in its attempt to fight off an infection. Immune cells rush in, overreact and wreak havoc on tissues and organs, often resulting in organ failure and death.

Researchers at University of California San Diego School of Medicine recently found that removing the enzyme PHLPP1 improved outcomes in a mouse model of sepsis. PHLPP1 controls many cell behaviors by removing phosphates (small chemical tags) from other proteins. And, it now turns out, PHLPP1 also influences inflammation.

The study, published August 13, 2019 in eLife, introduces the possibility that inhibiting PHLPP1 could form the basis for new sepsis treatments in humans.

"Most research on inflammation has typically focused on kinases, enzymes that add phosphate tags to other proteins," said senior author Alexandra Newton, PhD, professor in the Department of Pharmacology at UC San Diego School of Medicine. "It's exciting to have a completely new target for sepsis -- the enzymes that remove them."

Newton's team discovered PHLPP1 a few years ago and have since detailed its role in suppressing tumors. Following up on these findings, Newton reached out to UC San Diego School of Medicine colleague Chris Glass, PhD, an expert on inflammation.

Together, their teams uncovered many immune cell genes that are influenced by PHLPP1. But PHLPP1's particular influence on inflammation could be linked to the fact that it removes phosphates from a transcription factor called STAT1, which is known for controlling inflammatory genes.

Newton's team took mice modified to lack the PHLPP1 gene to another UC San Diego School of Medicine colleague, Victor Nizet, MD, an expert on bacterial infections. In separate experiments, Nizet's team administered live E. coli bacteria and lipopolysaccharide (LPS), a component of the bacterium's cell wall that drives immune systems wild, to both PHLPP1-deficient and normal mice.

The difference surprised Newton: Mice without PHLPP1 fared much better. While all normal mice died of the infection-induced sepsis after five days, half of the PHLPP1-deficient mice survived.

Newton's team had already been working with additional collaborators to screen thousands of chemical compounds to identify those few that inhibit PHLPP1. Now that they know PHLPP1 inhibitors might form the basis for new anti-sepsis drugs, the researchers hope to test these compounds on immune cells in the lab and in the mouse model of sepsis.

Currently, sepsis is addressed by preventing and treating the source infection, often with antibiotics, while maintaining organ health with oxygen and intravenous fluids. Nonetheless, according to the Centers for Disease Control and Prevention, at least 1.7 million adults in the U.S. develop sepsis each year, and nearly 270,000 die as a result. One in three patients who die in a hospital have sepsis.

"Sepsis is the leading cause of death in intensive care units throughout the world, but unfortunately there is not a single approved drug treatment for sepsis," Nizet said. "Discoveries like ours of fundamental signaling pathways that control immune cell behavior during sepsis offer clues for controlling the dangerous inflammation of sepsis while preserving the critical bacterial killing properties of white blood cells."

Bottom Line: Intensive blood pressure control among adults with high blood pressure was associated with a smaller increase in brain white matter lesions (a marker of small vessel disease and a risk factor for dementia) compared to standard blood pressure control, although the difference was small. Hypertension is a risk factor for developing white matter lesions. This analysis is a substudy of a randomized clinical of 449 patients with high blood pressure who had initial brain magnetic resonance imaging (MRI) and a follow-up MRI after four years. Researchers report intensive systolic blood pressure control (goal of less than 120 mm Hg) was associated with a smaller increase in white matter lesion volume compared with standard treatment (goal of less than 140 mm Hg). There also was a greater decrease in total brain volume, although the difference was small and the significance of this finding is unclear. Limitations of the study include the relatively short duration of the intervention and follow-up. Given the limited size of this study, it's also not possible to correlate changes in brain structure with dementia occurrence.

Authors: R. Nick Bryan, M.D., Ph.D., University of Texas at Austin, and coauthors

(doi:10.1001/jama.2019.10551)

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

NASA's Aqua satellite passed over the Northwestern Pacific Ocean and captured a good shot of the wide, ragged center of circulation in Tropical Storm Krosa.

On Aug. 13 at 12:20 a.m. EDT (0420 UTC), the Moderate Resolution Imaging Spectroradiometer or MODIS instrument aboard NASA's Aqua satellite provided a visible image of Krosa that showed a large center of circulation, surrounded by fragmented bands of thunderstorms.

At 5 a.m. EDT (0900 UTC), the center of Krosa was located near latitude 28.2 degrees north and longitude 133.9 degrees east. Krosa was about 397 nautical miles south-southeast of Iwakuni, Japan. Krosa was moving to the west-northwest and had maximum sustained winds near 45 knots (52 mph/83 kph).

The Japan Meteorological Agency has issued warnings for storm surge, heavy rains and tropical storm-force winds along coastal areas in southeastern Japan.

The Joint Typhoon Warning Center said that Krosa is expected to intensify to 50 knots (58 mph/92 kph) as it approaches landfall in southwestern Japan on August 14.