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Boston, MA -- The death of a spouse often means the loss of intimacy, companionship and everyday support for older adults. A new study finds that widowhood can have another profound effect: It may accelerate cognitive decline. Investigators from Brigham and Women's Hospital and Massachusetts General Hospital analyzed older, cognitively normal Americans enrolled in the Harvard Aging Brain Study whose marital status and brain β-amyloid levels -- a marker of Alzheimer's disease -- were determined at the beginning of the study. The team found that individuals who were widowed experienced a sharper cognitive decline than their married counterparts, especially among those who had high β-amyloid levels. The study suggests that widowhood may be an important and understudied risk factor for cognitive decline associated with Alzheimer's disease and highlights the need for increased focus on this high-risk population. Findings are published in JAMA Network Open.

"We know that social relationships can be an important buffer against cognitive decline," said senior author Nancy Donovan, MD, of the Division of Geriatric Psychiatry at the Brigham and an associate researcher at Mass General. "Being married provides opportunity for more social engagement and emotional support from a spouse, it expands one's social network and it provides more opportunity for cognitive stimulation. All of these benefits are lost in widowhood. Importantly, loss of a spouse is a highly stressful life event which can have deleterious effects on the brain."

Women are at increased risk for both widowhood and Alzheimer's disease, both of which increase in frequency with age. The study, which included 260 cognitively unimpaired adults ages 62 to 89 -- 153 women and 107 men -- classified its subjects into three groups: married, widowed or unmarried (divorced, single, separated or never married). Of these subjects, 66 women and 79 men were married; 31 women and four men were widowed. The researchers measured the subjects' β-amyloid levels using PET scans at the beginning of the study.

Donovan and colleagues evaluated a participant's cognitive performance each year for four years using a series of tests to analyze various dimensions of cognition. They found that cognitive performance declined in the widowed group, differing significantly from the married group. There was no difference between the married group and the unmarried group. In addition, they found that among adults with the highest β-amyloid levels, those who were widowed had the sharpest decline in cognition compared to those who were married, declining at a rate three times faster. This finding was independent of many factors including age, sex, socioeconomic status, and depression.

The authors note this is the first study to show a combined and synergistic effect of widowhood and β-amyloid on cognitive decline and will need to be replicated in other studies.

"Our division has become very interested in understanding the physiological effects of widowhood so that we can develop interventions to try to alter these trajectories," said Donovan. "Our findings also suggest that researchers engaged in Alzheimer's disease prevention trials may want to pay particular attention to widowed older adults to tailor interventions for this especially susceptible group of patients."

Multiple sclerosis (MS) is a progressive, chronic disorder in which the body's immune system attacks the central nervous system, resulting in multiple adverse effects, from numbness, fatigue and impaired speech to loss of muscle control and vision. There is no cure for MS; treatment focuses upon managing symptoms and slowing progression.

As a result, the ability to precisely assess the extent of MS-related disability and disease advancement is critical to effective treatment. In a new study, published in the February 26, 2020 online issue of Annals of Clinical and Translational Neurology, an international team of scientists, led by researchers at University of California San Diego School of Medicine, describe a new, multi-sensor tool that measures subtle changes in MS patients, allowing physicians to more frequently and more quickly respond to changes in symptoms or patient condition.

"We currently lack reliable measures of subtle MS disability progression over short time intervals," said senior study author Jennifer Graves, MD, PhD, a neurologist at UC San Diego Health and associate professor of neurosciences at UC San Diego School of Medicine.

"For example, a patient may tell us that that she can no longer play piano, but our 150-year-old bedside neurological exam techniques can't quantify this. In a standard clinical trial, this patient would be rated stable and not progressing. Developing tools that can capture MS progression reliably within six to 12 months instead of three to five years will drive faster drug development for the most disabling forms of MS."

MS affects approximately 1 million persons in the United States and 2.5 million worldwide. The cause is unknown, but the condition, which typically appears between the ages of 20 and 40, is more common in women. MS is one of the most common causes of non-traumatic disability among young and middle-aged adults.

Traditional assessment of MS has involved periodic clinical exams, which may only produce actionable findings over the course of several years. There are no tools to measure smaller, more subtle changes in the disease that may happen in shorter intervals.

The new device employs a combination of sensors, such as accelerometers, gyroscopes and surface electromyography (which records nerve electrical impulses using electrodes placed on the skin), that have been repurposed from commercial uses.

"The use of multi-sensors allows for use of complementary data-types that can be employed for a more comprehensive view of the movement," said Graves. "The types of sensors we used are widely available in different hardware products. We used a product that could be purchased off Amazon and was originally used for gaming and other gesture control tasks. The critical steps in our work involved the data processing and analyses, including use of artificial intelligence approaches."

The device involves wearing a small, sensor-laden band on the forearm or calf, then completing 20 finger or foot taps. Data is wirelessly downloaded to a computer in real-time. The procedure is repeated on all four limbs of the patient, and takes less than five minutes.

"A great advantage is potential use by non-experts and even non-clinicians, such as medical assistants or research coordinators," Graves said. The researchers are now preparing to publish a longitudinal analysis demonstrating the device's sensitivity to within patient changes over short time periods. Subsequent steps include validation in a multi-site study and development of commercial grade software to allow more expansive dissemination.

An investigational drug that binds bile acids in the stomach can reduce the severity of heartburn symptoms in patients with treatment-resistant gastroesophageal reflux disease (GERD) when combined with a proton pump inhibitor (PPI), a new study suggests.

Michael F. Vaezi, MD, PhD, MSc, director of the Center for Swallowing and Esophageal Disorders at Vanderbilt University Medical Center (VUMC), is corresponding author of the report published in the journal Gastroenterology. The study was conducted by Cambridge, Mass.-based Ironwood Pharmaceuticals.

"As a physician, it is very challenging to have nothing new to offer patients for whom standard treatments don't work," Vaezi said. "But the reality is many of our patients continue to struggle with frequent heartburn and regurgitation despite taking their PPIs.

"These data provide strong evidence that bile acid plays a key role in refractory GERD and that IW-3718 may have the potential to make a meaningful difference for patients," he added.

Vaezi is professor of Medicine and clinical director of the Division of Gastroenterology, Hepatology and Nutrition in the Department of Medicine, Vanderbilt University School of Medicine. PPIs such as Prilosec and Nexium reduce the production of stomach acid.

Each week approximately 20% of the adult U.S. population reports GERD-related symptoms, including heartburn and regurgitation. Seven percent experience daily symptoms. Despite once-daily PPI therapy, the "mainstay" treatment for GERD, approximately 30% of patients continue to have symptoms.

IW-3718, which was developed by Ironwood Pharmaceuticals, combines an established drug that binds bile acids in the stomach with a technology that controls the release of drugs in the gastrointestinal tract. Bile acids have been shown to injure the lining of the esophagus as well as stomach and colon.

Fifty-two centers in the United States, including VUMC, participated in the randomized, double-blind study from March 2016 to April 2017. A total of 280 adult patients with refractory GERD were divided into four groups, one which received an inactive placebo and the others ascending doses of IW-3718 twice a day.

Heartburn symptoms were significantly reduced in the group receiving the highest dose, 1,500-milligrams twice daily, compared to the placebo group. Regurgitation symptoms also decreased. The drug was well tolerated. There were no drug-related serious adverse events.

"These results suggest that IW-3718 may provide a therapeutic option for refractory-GERD patients with continued symptoms despite once-daily PPI therapy," the researchers concluded.

PHILADELPHIA (Feb. 26, 2020) - One year into Philadelphia's 1.5-cents-per-ounce "soda tax," new findings show that the law had minimal to no influence on what Philadelphians are drinking. The results were published this month in the International Journal of Environmental Research and Public Health from researchers at Drexel University's Dornsife School of Public Health.

The team conducted a random phone survey of 515 adult residents of Philadelphia and neighboring cities of Camden and Trenton, New Jersey, and Wilmington, Delaware. Respondents shared how much and how frequently they drink soda, fruit drinks, energy drinks and bottled water during a 30-day period when the tax was first implemented, in Dec. 2016 - Jan. 2017, and again reported their consumption over a 30-day period during a follow-up survey a year later in Dec. 2017-Feb. 2018.

Taking into account other health behaviors and socio-demographics, at the one-year mark, 39% of Philadelphians, and 34% of those in surrounding cities, reported drinking fewer sugar-sweetened beverages. This amounts to only three fewer sugary beverages for Philadelphians each month -- not a statistically significant difference.

Previous studies have looked at sales of sugary drinks after the tax was implemented, but did not evaluate consumption of the taxed drinks. A previous study looked at similar changes in consumption after the tax -- finding that one year after the tax, adults consumed fewer sugary beverages in Philadelphia relative to outside Philadelphia (about 10 fewer occasions per month) -- that study focused on lower-income Philadelphians who lived with children and, on average, consumed a sugary beverage every day. The current study differs from that one as it was population-based and thus reflects the response of a typical adult. In this sample, only 25% consumed sugary beverages every day.

"We have ample evidence that sugary beverages are connected to type 2 diabetes, obesity, cardiovascular disease, and other health issues, but we're seeing that raising the price of sugary-beverages may not impact consumers who don't drink a lot of soda," said study co-author Amy Auchincloss, PhD, an associate professor in the Dornsife School of Public Health.

"The availability of untaxed sugary beverages outside of Philadelphia, the still relatively lower price of these drinks compared to healthier ones and marketing and advertising may explain the low effect of the tax," said lead author Yichen Zhong, a doctoral student at the Dornsife School of Public Health.

Unlike other cities that enacted a similar beverage tax to increase general revenue, Philadelphia's tax, was enacted with the goal of financing universal pre-kindergarten and parks and recreation programs in the City.

"Although this law was not passed for health reasons, the tax has the potential to generate long- term health benefits for many Philadelphians because revenue from the tax is being directed toward expanding access to quality early childhood education for children in lower-income families -- and education has a positive effect on many health outcomes," said senior author Brent Langellier, PhD, an assistant professor in the Dornsife School of Public Health.

CHICAGO (February 26, 2020): The best approach for surgeons to identify malnourished cancer patients before they have a cancer operation may be specifically related to the type of cancer the patient has, according to researchers who found that common definitions of malnutrition do not apply equally to all cancers in assessment of preoperative risk. The study is published as an "article in press" on the Journal of the American College of Surgeons website ahead of print.

Cancer-related malnutrition is common--affecting between 20 and 70 percent of cancer patients1--because of the disease or its treatment. Many studies show that malnutrition raises the risk of complications from a major cancer operation, but patients can improve their nutritional status through preoperative rehabilitation, or "prehabilitation," programs involving nutrition counseling, nutritional supplementation, and exercise.

"Surgeons must know a patient's nutritional status to predict outcomes and direct therapy," said study coauthor Robert Cima, MD, FACS, a general surgeon at Mayo Clinic, Rochester, Minn. "A malnutrition screening tool meant for the general population is not useful in patients with cancer. Their cancer diagnosis already places them at high risk of malnutrition."

Yet, the common definitions of malnutrition that surgeons use for risk assessment vary widely, and the best definition is unclear, said lead study author Nicholas P. McKenna, MD, a third-year surgical resident at Mayo Clinic. The simplest malnutrition definitions, Dr. McKenna said, rely on unintentional weight loss and/or body mass index (BMI), a measure of body fat based on height and weight.

To determine the best simple definition of malnutrition in cancer patients for preoperative risk assessment, the investigators studied clinical registry data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP®) database. ACS NSQIP is the leading nationally validated, risk-adjusted, outcomes-based program to measure and improve the quality of surgical care in hospitals. Using ACS NSQIP data, the researchers identified 205,840 major cancer resection (removal) operations performed from 2005 to 2017 for six types of cancer: colorectal, esophageal, gastric, liver, lung, and pancreatic. Using statistical analyses, the research team studied the effect of malnutrition on the risk of any major postoperative complication (a composite including infections, pulmonary problems, stroke, and heart attack) or death within 30 days of the operation.

Malnutrition definitions

The researchers evaluated patients' nutritional status using several current classifications: the European Society for Clinical Nutrition and Metabolism (ESPEN) diagnostic criteria for malnutrition,2 the ACS NSQIP risk factor of more than 10 percent weight loss over the prior six months, and the World Health Organization (WHO) BMI classification.3

ESPEN defines malnutrition in two ways, according to Dr. McKenna: (1) by age: for patients younger than 70 years, BMI below 20 kilograms per meter squared (kg/m2), or for patients 70 or older, BMI below 22 plus unintended weight loss either greater than 10 percent of body weight over any time or more than 5 percent in the past three months; or (2) a BMI below 18.5 alone, which the WHO considers severely thin. The study authors called these definitions ESPEN 1 and 2.

Using those definitions, the researchers added their own definitions of "severe malnutrition," a combination of BMI under 18.5 kg/m2 and more than 10 percent weight loss, and "mild malnutrition," a BMI of 18.5 to 20 for patients younger than 70 or BMI under 22 if age was 70 or above. They called the final malnutrition definition "NSQIP": more than 10 percent weight loss with a normal BMI (above 20 for ages less than 70 and above 22 for ages 70 and older).

Next, they looked at the risk of major postoperative complications associated with each nutrition category, including obesity and no malnutrition, for all patients and by cancer type.

Implications for surgeons and patients

"We found that using one-size-fits-all definitions of malnutrition across all cancer types when counseling a cancer patient preoperatively could result in overestimating or underestimating the patient's risk of complications after a major cancer resection procedure," Dr. McKenna said.

They found that the malnutrition (undernutrition) definition that best predicted postoperative risk differed for six cancer types as follows:

Colorectal: severe malnutrition
Esophageal: ESPEN 2
Gastric: ESPEN 1
Liver: NSQIP
Lung: ESPEN 1
Pancreatic: ESPEN 1

The best malnutrition definition also varied by cancer type for predicting the risk of dying within a month after a cancer operation, the researchers reported.

"Because it is uncommon for surgeons to look at cancer type when estimating malnutrition-related preoperative risk, these results could potentially change surgeons' view of how to evaluate cancer patients," Dr. Cima said.

He recommended that surgeons consider, "What is the best marker of nutritional status for this cancer type?"

"Cancer patients should understand that good nutrition before having an operation is very important," Dr. Cima concluded.

For the first time, a team of scientists at the University of Central Florida has created functional nanomaterials with hollow interiors that can be used to create highly sensitive biosensors for early cancer detection.

Xiaohu Xia, an assistant professor of chemistry with a joint appointment in the NanoScience Technology Center, and his team developed the new method and recently published their work in the journal ACS Nano.

"These advanced hollow nanomaterials hold great potential to enable high-performance technologies in various areas," says Xia. "Potentially we could be talking about a better and less expensive diagnostic tool, sensitive enough to detect biomarkers at low concentrations, which could make it invaluable for early detection of cancers and infectious diseases."

Because hollow nanomaterials made of gold and silver alloys display superior optical properties, they could be particularly good for developing better test strip technology, similar to over-the-counter pregnancy tests. Currently the technology used to indicate positive or negative symbols on the test stick is not sensitive enough to pick up markers that indicate certain types of cancer. But Xia's new method of creating hollow nanomaterials could change that.

More advance warning could help doctors save more lives.

In conventional test strips, solid gold nanoparticles are often used as labels, where they are connected with antibodies and specifically generate color signal due to an optical phenomenon called localized surface plasmon resonance. Under Xia's technique, metallic nanomaterials can be crafted with hollow interiors. Compared to the solid counterparts, these hollow nanostructures possess much stronger LSPR activities and thus offer more intense color signal. Therefore, when the hollow nanomaterials are used as labels in test strips they can induce sensitive color change, enabling the strips to detect biomarkers at lower concentrations.

"Test-strip technology gets upgraded by simply replacing solid gold nanoparticles with the unique hollow nanoparticles, while all other components of a test strip are kept unchanged," says Xia. "Just like the pregnancy test, the new test strip can be performed by non-skilled persons, and the results can be determined with the naked eye without the need of any equipment. These features make the strip extremely suitable for use in challenging locations such as remote villages."

The UCF study focused on prostate-specific antigen, a biomarker for prostate cancer. The new test strip based on hollow nanomaterials was able to detect PSA as low as 0.1 nanogram per milliliter (ng/mL), which is sufficiently sensitive for clinical diagnostics of prostate cancer. The published study includes electron microscope images of the metallic hollow nanomaterials.

"I hope that by providing a general and versatile platform to engineer functional hollow nanomaterials with desired properties, new research with the potential for other applications beyond biosensing can be launched," Xia says.

Collaborators on the study include Zhuangqiang Gao, Zheng Xi, Haihang Ye, Zhiyuan Wei and Shikuan Shao from UCF's chemistry department; Qingxiao Wang and Moon J. Kim from the University of Texas at Dallas, and Dianyong Tang from Chongqing University of Arts and Sciences in China.

Gao and Xi are postdoctoral scholars in Xia's lab, partially funded through UCF's Preeminent Postdoctoral Program.

The study was partially funded through a National Science Foundation CAREER grant (CHE-1834874).

Xia, who has a joint appointment at the NanoScience Technoloyg Center, has multiple degrees in biomedical engineering and worked at Georgia Tech as a postdoctoral fellow and at Michigan Tech as an assistant professor before joining UCF in 2018. He has published more than 50 journal articles and has more than 5,800 citations. He has received multiple grants and presented around the world.

February 26, 2020 - As patients continue to seek non-invasive treatments across the cosmetic spectrum, "liquid rhinoplasty" is emerging as the non-surgical alternative to the traditional nose job. Using dermal fillers to change the appearance of the nose, non-surgical rhinoplasty is gaining in popularity due to its relatively low cost, convenience, and short recovery time.

There has previously been debate regarding the safety and effectiveness of this procedure - especially in the absence of large-scale studies reporting on the patient outcomes. To address this gap, the March issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS), features a new study that includes an analysis of 5,000 non-surgical rhinoplasties performed between 2015 and 2019 - the largest published experience of non-surgical rhinoplasty to date.

The study's lead author, Ayad Harb, FRCSPlast, is a London Consultant Plastic Surgeon and world authority on this increasingly popular procedure.

"We find this treatment an excellent alternative to surgical rhinoplasty in those patients who do not want, cannot have, or do not need surgery," writes Dr. Harb. "This study demonstrates high efficacy and safety, and relatively low complication rates in the hands of an experienced clinician."

The study outlines a safe and effective non-surgical rhinoplasty technique, which focuses on three critical aesthetic points of the nose--the radix, bridge and tip.

"The injections are carried out at the radix and move caudally with a micro-droplet technique. Boluses of no more than 0.1 mL at any one point," writes Dr. Harb. "Frequently, and especially nearer the tip, deposits of filler can be as small as 0.02 mL per site. With each injection point, the gel implant is massaged into place and can be maneuverer to produce a smooth and symmetrical surface. The injections continue in the midline until the tip is reached. The tip is injected perpendicular to the skin to improve projection and definition."

According to the study, hyaluronic acid is the preferred filler because of its reversibility in the event of vascular occlusion. Another benefit is that it can be pre-mixed with local anaesthetic, avoiding the requirement for pre-procedural local anaesthetic which can distort or mask subtle deformities that one is looking to correct.

The patients' mean age was 27 years old (range 18 - 78), and the largest age group was 25-34 years, totalling 52% of the cohort, with a female predominance in the cohort. The average procedure time was just 12 minutes, while the average of filler injected was less than one millilitre (0.72 mL), and the average pain score was only 2 on a 10-point scale.

The most common patient complaint was a dorsal hump, affecting 44 percent. About 20 percent of patients were seeking to refine their results after previous rhinoplasty surgery. Liquid rhinoplasty was also used to treat other patient concerns, such as drooping nasal tip (about 15 percent), lack of definition (almost nine percent), frontal asymmetry (seven percent) and bulbous tip (six percent).

"Practitioners who undertake non-surgical rhinoplasty must have a comprehensive understanding of nasal anatomy and aesthetics. It is also vital to maintain an acute ability to recognise immediate complications and a readiness to treat," wrote Dr. Harb. "This study demonstrates low complication rates, with an infection and skin necrosis rate of 0.04 and 0.06 percent, respectively."

Erythema and swelling were a common observation in the first five days, but generally settle with time. Other complications were infrequent. A small number of patients (0.5 percent) showed signs of vascular occlusion; in most cases, blood flow was restored with simple measures. If not, a hyaluronidase enzyme injection was performed to immediately dissolve the dermal filler.

The duration of results was 9 to 12 months. Approximately 32 percent of patients returned at 12 months, most of whom were treated. Many patients demonstrate long-lasting results, some not requiring further treatment even at 24-month follow up.

Click here to read "The Nonsurgical Rhinoplasty: A Retrospective Review of 5000 Treatments."
DOI: 10.1097/PRS.0000000000006554

Results from one of the first studies to determine the effects of pre-surgical, or neoadjuvant, chemotherapy on the breast cancer genome offer up two key insights. One is a before treatment finding that can help predict which patients would most benefit from pre-surgical chemo, and the other an after treatment finding which sheds light on how cancer cells survive chemotherapy. Findings appear in Clinical Cancer Research.

SWOG Cancer Research Network made the work possible. Ten years ago, a SWOG team launched S0800, an innovative trial that compared two 20-week chemotherapy treatments before surgery for patients with HER2-negative, locally advanced, or inflammatory breast cancers. For the study, tumor tissue samples were taken before and after chemotherapy and stored in SWOG's biospecimen bank, a resource open to scientists around the world.

SWOG investigators Lajos Pusztai, MD, and Ryan Powles, PhD, both at Yale Cancer Center when the study was conducted, used those banked samples to conduct their study. They submitted the samples to whole exome sequencing, a laboratory technique that catalogues a genome's protein-coding regions, a small fraction of the human genome known as the exome.

For their study, Pusztai and Powles analyzed 29 pre-treatment biopsies from S0800 to identify DNA mutational patterns, then look at post-treatment chemotherapy response to see if any patterns emerged. They found that patients whose breast cancer was completely eradicated by chemo had a higher proportion of DNA mutational "signature 3," a pattern that indicates defects in DNA repair and could be caused by damage to genes like BRCA.

"This is a clue," said Powles, a former PhD student in the Pusztai lab at Yale and now a research investigator at Bristol-Myers Squibb. "Doctors can look at the results of genetic testing to see which of their breast cancer patients might respond best to neoadjuvant chemotherapy, and which patients may need a different, or additional, course of treatment."

For their post-treatment analysis, Pusztai and Powles were only able to analyze nine of the 29 pre- and post-chemo samples. That's because the treatment killed so many tumor cells that most samples were too small to examine. However, the nine remaining samples were well-suited to study chemotherapy resistance. The SWOG team found no single gene or gene mutation present in tumor tissue that survived chemo. Rather, these tumor cells featured mutations that belonged to two biological pathways - E2F Targets and G2M Checkpoint. These pathways are sets of genes that act together to regulate cell growth, a process that can cause cancer if it goes awry.

"What is important about this paper is that it demonstrates that while each cancer acquires mutations in different genes, the affected genes are not random," said Pusztai, chair of SWOG's breast cancer research committee and director of breast cancer translational research at Yale Cancer Center. "Cancer cells that survived chemotherapy all had alterations in cell growth regulation at various levels. So, while the genes may be different, they do the same work."

Researchers at the University of Cincinnati have uncovered a potentially more beneficial treatment regimen for patients with metastatic melanoma.

The results, published in the International Journal of Radiation Oncology, Biology and Physics, show that radiation before immunotherapy may prolong lives of patients with melanoma that has spread to the brain.

"Melanoma brain metastases occur in more than 50% of melanoma patients," says corresponding author Dr. Soma Sengupta, associate professor of neurology at UC, UC Health physician and co-director of the UC Gardner Neuroscience Institute's Brain Tumor Center. She is also the inaugural recipient of the Harold C. Schott Endowed Chair of Molecular Therapeutics.

"While both radiation therapy and 'immune checkpoint inhibitors,' a form of immunotherapy, are used alone or in combination for treatment of this cancer, the role of combination therapies and how these treatments could best be sequenced remains unclear," Sengupta adds.

Immunotherapy is a type of cancer treatment that boosts the body's natural defenses to fight cancer. It uses substances made by the body or in a laboratory to improve or restore immune system function and may work by stopping or slowing the growth of cancer cells. Immune checkpoint inhibitors work by blocking checkpoint proteins from binding with their partner proteins. This prevents the "off" signal from being sent, allowing the T-cells to kill cancer cells.

In this study, the team conducted a retrospective analysis of patients with surgically removed melanoma brain metastases who underwent treatment with either radiation, immunotherapy or a combination of both between 2010 and 2018. Of 79 specimens, only 17 samples were eligible for this study.

"Among the latter, we specifically investigated the gene expression between patients who received radiation therapy first then immune checkpoint inhibitors in comparison to the reverse," says Daniel Pomeranz Krummel, research associate professor of neurology at UC and lead author of the paper. "We used a melanoma brain metastases animal model for validation experiments, as well."

Pomeranz Krummel says results showed that the combination of radiation therapy and immune checkpoint inhibitors correlated to better patient survival when compared to radiation therapy alone.

"Specifically, we found that radiation followed by immunotherapy was superior compared to immunotherapy followed by radiation therapy," he says, adding that his observation in patients was also observed in the melanoma animal model. "More genetic analysis of the tissue showed that radiation therapy followed by immunotherapy showed that the genes causing cell death signaling, usually fighting the cancer, were restricted and key indicators of inflammation were present."

"Our study provides initial insights into the optimal sequence of treatment following surgical removal of melanoma brain metastases," adds Sengupta, noting that this was a small sample of patients and that follow up studies are needed. "Clinical trials examining the best sequence of these treatments are necessary."

PHILADELPHIA - Non-small cell lung cancer (NSCLC) patients with higher measures of tumor mutations that show up in a blood test generally have a better clinical response to PD-1-based immunotherapy treatments than patients with a lower measure of mutations. A clinical trial led by researchers from the Perelman School of Medicine at the University of Pennsylvania and Penn's Abramson Cancer Center shows that in cases where the liquid biopsy detects higher volumes of mutations, patients with cancers that have spread are more likely to see a clinical benefit at six months, as well as to survive longer without seeing their disease progress. The findings published today in Clinical Cancer Research, a journal of the American Association for Cancer Research.

NSCLC is the most common form of lung cancer, accounting for about 84 percent of all lung cancer cases. In patients with metastatic disease - meaning the tumor has spread from the lungs to distant parts of the body - the five-year survival rate is just six percent. Immunotherapy with a PD-1 inhibitor, either alone or in combination with chemotherapy, is the standard first-line treatment in these cases when cancers do not have a targetable mutation. Historically, doctors have used a tissue sample to look for a protein called PD-L1, which can predict response. However, it's an imperfect biomarker and requires the availability of tissue. Instead, the Penn trial focused on biomarkers found in more easily-obtained blood samples.

"While some people see a benefit from these therapies, unfortunately not everyone does. There is an important clinical need to identify new, non-invasive biomarkers to help us guide each patient to the treatments that have the best chance of success for them, and our findings show we may now have a tool to help us do that," said the study's lead author Charu Aggarwal, MD, MPH, the Leslye M. Heisler Assistant Professor for Lung Cancer Excellence at Penn.

With a simple blood draw, researchers can screen for mutations in 500 different genes. They used this liquid biopsy panel to measure the tumor mutational burden (TMB) - essentially the number of mutations detectable in the blood - of 66 patients, 52 of whom were evaluable for this trial. TMB is typically reported as mutations per megabase (Mb), which is the number non-synonymous, somatic mutations divided by the size of the genome coding area. The median TMB was 16.8 mutations per Mb and was significantly higher for patients who experienced a durable clinical benefit (DCB) compared to those who did not. A DCB means a patient experienced a complete response, a partial response, or stable disease for more than six months. Patients who achieved a DCB had a median of 21.3 mutations per Mb, compared to 12.4 in patients who did not achieve a DCB.

The researchers then examined the progression-free survival (PFS) and overall survival (OS) of both groups. The 28 patients with more than 16 detectable mutations per Mb had a median PFS of 14.1 months compared to 4.7 months for the 24 patients in the lower TMB group. Median OS was not reached for the high TMB group. The low TMB group had a median OS of 8.8 months.

"We believe this is the largest study to show correlation between blood-based tumor mutational burden and clinical outcomes after first-line PD-1-based treatment, including combination chemo-immunotherapy, for NSCLC," said the study's senior author Erica L. Carpenter, MBA, PhD, director of the Liquid Biopsy Laboratory and a research assistant professor of Medicine at Penn.

The researchers say a larger trial is needed to confirm the findings.

NEW YORK (February 26, 2020) -- Vaporized hydrogen peroxide (VHP) failed to completely sterilize surgical tools 76 percent of the time when the tools were soiled with salts or blood and not cleaned prior to sterilization, according to a study published today in Infection Control & Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America.

"While sterilization technology is capable of killing billions of microorganisms on instruments, some low temperature processes are unintentionally undermined when surgical instruments are improperly cleaned before sterilization," said William A. Rutala, PhD, MPH, director of the North Carolina Statewide Infection Control and Epidemiology Program.

Researchers at the University of North Carolina at Chapel Hill simulated the impact of proteins and salts left on surgical tools prior to sterilization to test the effectiveness of three low-temperature technologies, increasingly required for plastic tools, compared to steam sterilization.

Stainless steel test carriers, which simulated surgical tools, were soiled with salt and blood and contaminated with common bacteria found in healthcare settings -- Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, vancomycin-resistant Enterococcus, Mycobacterium terrae, or spores of Bacillus atrophaeus, Geobacillus stearothermophilus, or Clostridioides difficile. The equipment was then sterilized with VHP, ethylene oxide (ETO), hydrogen peroxide gas plasma (HPGP), or steam.

VHP had the highest failure rate, 76.3 percent, with salt being the main component interfering with this technique. HPGP and ETO had failure rates of 1.9 percent. Steam sterilization, which is most common technique used for sterilization of heat-resistant instruments, was the most effective and robust sterilization technology with no failures.

"If instruments are not properly cleaned prior to sterilization and then placed in a low-temperature sterilization technology such as vaporized hydrogen peroxide, there is a possibility of failure," Rutala said. "Effectively cleaning, removing visible soil and microbial contaminants from objects, must precede sterilization to ensure tools are thoroughly and optimally sterilized."

The authors noted that cleaning complex medical equipment, such as surgical instruments and endoscopes with hinges, sharp bends, and lumens, present a special challenge for cleaning and sterilization as could naturally occurring biofilm build-up on medical and surgical instruments.

DALLAS, Feb. 26, 2020 -- For most people, the benefits of aerobic exercise far outweigh the risks, however, extreme endurance exercise - such as participation in marathons and triathlons for people who aren't accustomed to high-intensity exercise - can raise the risk of sudden cardiac arrest, atrial fibrillation (a heart rhythm disorder) or heart attacks, according to a new Scientific Statement "Exercise-Related Acute Cardiovascular Events and Potential Deleterious Adaptations Following Long-Term Exercise Training: Placing the Risks Into Perspective-An Update from the American Heart Association," published today in the Association's premier journal Circulation.

Aerobic exercises are activities in which the large muscles move in a rhythmic manner for a sustained time. They can be done at low intensity or high intensity and include walking, brisk walking, running, bicycling, swimming and many others.

"Exercise is medicine, and there is no question that moderate to vigorous physical activity is beneficial to overall cardiovascular health. However, like medicine, it is possible to underdose and overdose on exercise - more is not always better and can lead to cardiac events, particularly when performed by inactive, unfit, individuals with known or undiagnosed heart disease," said Barry A. Franklin, Ph.D., chair of the writing committee for the new Scientific Statement, director of preventive cardiology and cardiac rehabilitation at Beaumont Health in Royal Oak, Michigan, professor of internal medicine at Oakland University William Beaumont School of Medicine in Rochester, Michigan.

"More people are running marathons, participating in triathlons and doing high-intensity interval training. The purpose of this statement is to put the benefits and risks of these vigorous exercise programs in perspective," said Franklin.

After reviewing more than 300 scientific studies, the writing committee found that, for the vast majority of people, the benefits of exercise and improving physical fitness outweigh the risks. Physically active people, such as regular walkers, have up to a 50% lower risk of heart attack and sudden cardiac death. However, the committee also identified potential risks with intense exercise training.

The writing group also reviewed a small study that concluded the risk of sudden cardiac death or heart attack is low among people participating in high-intensity exercise such as marathons and triathlons. However, over time, the risk of heart attack or sudden cardiac death among male marathon participants has risen, suggesting that these events are attracting higher risk participants (those who may have an underlying or undiagnosed cardiovascular condition such as heart rhythm abnormalities or a prior heart attack). For women, who comprised only 15% of the study population, the occurrence of sudden cardiac death was 3.5-fold less than in men.

Among participants in triathlons almost 40% of cardiac events occurred in first-time participants, indicating that inadequate training or underlying heart problems may be involved. The writing group also found that:

Half of cardiac events occur in the last mile of a marathon or half-marathon, so maintaining a steady pace rather than sprinting is advised;

The risk of cardiac events is greater at high altitudes, but can be decreased by spending at least one day acclimating to the elevation prior to strenuous activity;; and

Risk of atrial fibrillation (AFib), a common heart arrhythmia that raises the risk of stroke, is beneficially reduced with moderate exercise volumes but is highest in people who are sedentary and almost as high in people who are engaged in very high volumes of exercise training, that is, high-intensity training (such as running 60-80 miles a week).

For people who want to become more active, the Association suggests that most people can start a light program of exercise and build up slowly to a moderate to vigorous exercise regimen without seeing a physician first, unless they have physical symptoms such as chest pain, chest pressure or severe shortness of breath while exercising. "It is important to start exercising - but go slow, even if you were an athlete in high school," said Franklin.

In addition, people with known heart disease (such as a previous heart attack, bypass surgery or angioplasty) should get their doctor's approval prior to starting an exercise program.

For currently inactive/sedentary people, the Association also suggests checking with your doctor before engaging in any strenuous activities such as shoveling snow or racquet sports, which create rapid increases in heart rate and blood pressure and greatly increase the strain on the heart.

To implement a healthy physical activity program:

Warm up before exercise by doing the planned activity - such as walking - at a slower pace to let your heart rate rise gradually;

Walk on a level surface for 6-8 weeks, progressing to walking up hills, jogging or taking part in more vigorous activities as long as no symptoms occur such as shortness of breath, lightheadedness, chest pain or chest pressure;

Increase the amount of time spent on exercise incrementally from five to ten minutes at the beginning and build up slowly to the desired time;

Lower the intensity of your exercise when environmental conditions place a greater strain on the heart, such as high humidity or high altitude to which you are not accustomed;

Cool down after exercise by walking at a slow pace to let your heart rate return to normal; and

Stop and seek medical evaluation if you experience any heart-related symptoms such as lightheadedness, shortness of breath, or chest pain or pressure.

A portable 'electronic nose' can accurately pick up the precursor condition to food pipe (oesophageal) cancer, known as Barrett's oesophagus, indicates a proof of principle study, published online in the journal Gut.

This inexpensive and non-invasive technique may be a promising test for diagnosing oesophageal cancer in primary care, say the researchers.

The number of new cases of this cancer has risen sixfold over the past few decades, with most cases being diagnosed when the disease is already advanced and difficult to treat.

Barrett's oesophagus, a condition in which healthy cells lining the food pipe are replaced by abnormal cells, is a known precursor to the disease.

It can be diagnosed using a long flexible tube with a camera on the end (endoscope). But the procedure is expensive and unpleasant for patients, making it unsuitable for population screening.

So scientists have been exploring other less invasive and cheaper options, including analysis of volatile organic compounds, or VOCs for short.

VOCs are gaseous compounds produced by metabolic processes in the body, including inflammation and abnormal cellular activity, which can be detected in a person's breath.

The researchers wanted to see how effective and accurate a portable 'electronic nose' device would be for picking up Barrett's oesophagus.

Some 402 adults scheduled for endoscopy breathed into a highly sensitive electronic nose, designed to detect subtle differences in VOC patterns, for 5 minutes.

Of this group, 129 patients had Barrett's oesophagus; 141 had acid reflux disease, including 50 who had an inflamed oesophagus as a result; and 132 had a normal oesophagus or hiatus hernia that accounted for their symptoms.

Analysis of the VOC profiles detected by the electronic nose showed that these differed significantly among patients with Barrett's oesophagus, acid reflux, and those with a normal oesophagus/hernia.

The sensitivity of the device was 91%--in other words, its ability to pick up Barrett's oesophagus--and its specificity was 74%--in other words, its ability to detect those without the condition.

When the analysis was further restricted to patients who had been taking drugs (proton pump inhibitors) to curb stomach acid production for at least a month or those with a hiatus hernia, both of which are likely to muddy the diagnostic waters, its accuracy was still good.

"The findings of our study provide evidence that patients with [Barrett's oesophagus] have VOC breath prints different from those without," they write.

While it's still not clear exactly how breath VOCs indicate cancerous cell changes, the sensitivity and specificity of VOC breath testing for Barrett's oesophagus is comparable to that of breast cancer and bowel cancer screening, they explain.

Chemical analytical techniques for VOC analysis have also been used, and are very effective, but they are also expensive. What's more, they are time consuming and require highly skilled staff to operate them and analyse the results, point out the researchers.

Further research will be required to validate these findings in a much larger study, they emphasise. But they conclude: "Given the high tolerability, high acceptability and low costs, breath testing may be a promising approach to be used for non-invasive screening for [Barrett's oesophagus] in a primary care setting."

Mid-life weight gain is linked to an acceleration in the natural decline in lung capacity that comes with ageing, reveals a 20-year study published online in the journal Thorax.

But mid-life weight loss is associated with the slowing of this ageing process, emphasising the importance of maintaining a healthy weight, to stave off serious respiratory ill health, say the researchers.

Lung capacity is measured by forced vital capacity (FVC) and forced expiratory volume (FEV). It's an important indicator of future ill health and life expectancy.

There's plenty of evidence linking overweight and obesity in adulthood with poorer lung capacity, but most of the studies have been relatively short term, and tracked the respiratory health of people only up to the age of 50.

To gauge the potentially longer term impact of changes in weight, the researchers drew on data from the European Community Respiratory Health Survey (ECRHS). This has been tracking the health of more than 10,000 adults aged 20 to 44 since the early 1990s.

For the purposes of this study, the researchers included 3673 participants from 26 locations in 12 countries in Europe and Australia. Their weight, height, and lung function were measured at three time points over a period of 20 years.

Information on other potentially influential factors was also collected: whether they smoked or had been exposed to secondhand smoke; whether they had asthma; how often they exercised; and whether they had any other serious condition, such as diabetes or cancer.

Their average age was 34 at the start of the study, and 54 when they had their last check-up. At the start of the study, around one in eight (12%) was underweight; over half (57%) were of normal weight; around one in four (24%) was overweight; around one in 20 (6%) was obese.

During the monitoring period, almost 4% of participants lost weight, while weight didn't change in around a third (34%). Around half (53%) put on a moderate amount of weight (0.25-1 kg/year), and around one in 10 (9%) put on a lot of weight (more than 1 kg/year).

Analysis of the results showed that changes in weight over the 20 years were associated with the rate at which lung capacity declined.

Among those with a healthy weight, or who were overweight or obese as young adults, moderate and high weight gain were associated with a speeding up of the decline in lung capacity.

On the other hand, weight loss among those who were obese as young adults over the following 20 years was associated with a slowing in this decline.

This was also the case for those who had been underweight at the start of the study, and whose weight remained stable throughout the monitoring period. But decline was also faster among the underweight who put on a moderate amount of weight.

This is an observational study, and as such, can't establish cause, added to which the findings drew on total body weight, which can't distinguish between muscle and fat. Nor were the researchers able to assess how long it takes for a change in weight to affect the lungs.

Nevertheless, the findings echo those of previous studies, they say. And, together, they "reinforce the public health message that overweight and obesity have deleterious effects on health, including respiratory health," they write.

"However, the negative effects of overweight and obesity on lung function can be reversed by weight loss even in later adult life," they point out. "Therefore, public health policies that promote healthy lifestyles and body weight may be important for maintaining good lung function in adult life," they conclude.

The age at which a woman's periods stop, and the menopause starts, doesn't seem to be linked to the development of the risk factors typically associated with cardiovascular disease, suggests research published online in the journal Heart.

But the loss of oestrogen production does compromise heart health, so women should routinely be given hormone replacement therapy (HRT) to stave this off, argue specialists in a linked editorial.

Previously published research suggests that the age at which the menopause starts is linked to a heightened risk of cardiovascular disease, particularly if this is before the age of 45.

But no study has looked at the potential impact of the timing of typical risk factors for cardiovascular disease arising after the menopause, such as weight gain and disordered blood fats.

To explore this further, the researchers studied data gathered repeatedly from women between the ages of 36, 53, and 69, all of whom were part of the UK Medical Research Council National Survey of Health and Development.

They looked specifically at increases in blood pressure, unhealthy blood fats, weight (BMI), fasting blood glucose, and waist circumference--an indicator of a potentially harmful midriff bulge--over time--in around 1000 women.

They found no evidence that the age at which the menopause began was associated with a rise in unhealthy blood fats between the ages of 53 and 69, or with rises in blood pressure between the ages of 36 and 69.

These findings held true, irrespective of whether the menopause had occurred naturally or had been surgically induced by a hysterectomy.

There was some link between the age at which periods stopped and increases in weight, waist circumference, and fasting blood glucose. But these changes weren't consistent and the differences were negligible by the age of 69.

This is an observational study, and as such, can't establish cause. But the findings suggest that conventional risk factors for cardiovascular disease aren't to blame for the associations found between loss of oestrogen production and heightened risk of heart disease/stroke, say the researchers.

Although larger studies are needed, "The findings also have important implications for women and clinicians, as they suggest that any impact of age and type of period cessation on conventional [cardiovascular disease] intermediates over the long term is likely to be small," they conclude.

In a linked editorial, Dr Carl Lavie, of John Ochsner Heart and Vascular Institute, and Dr Felice Gersh of the Division of Integrative Medicine, University of Arizona College of Medicine, argue that the loss of oestrogen production is still harmful to women's heart health and that these harms should be prevented with HRT.

It's time to dispel the unintended scary legacy of the Women's Health Initiative (WHI) study, which tested the 'wrong' hormones on women who were too old, they contend.

"There is...no doubt that with the arrival of menopause, the progression of the insidious diseases of ageing, and of [cardiovascular] dysfunction, accelerate," they write. "Estradiol, the principle oestrogen produced by the ovaries, supports all aspects of the [cardiovascular system," they add.

Yet, despite the wealth of evidence on the myriad ways in which oestrogen protects women's heart health, "it remains entrenched in the medical management of menopausal women that HRT, if prescribed at all, should remain a short term solution, using the lowest dose possible to minimise night sweats, and only be considered for system use to address night sweats and hot flashes, rather than to maintain optimal [cardiovascular] function," they point out.

"Numerous conditions linked to both ageing and oestrogen deficiency, such as joint damage from osteoarthritis, vision loss due to cataracts, tooth loss due to periodontal disease and fractures from osteoporosis, are readily treated by the medical community, so why should the recognised harms of menopause to the [cardiovascular] system not be proactively treated with HRT," they ask?

"The time has arrived to shelve the WHI and its limited applicability to the lives of menopausal women...They deserve to be offered HRT, using hormones identical to those produced by human ovaries, and the hormones should be prescribed in the most physiological manner possible," they write.