Body

MINNEAPOLIS, MN- September 18, 2019 - An international research consortium, which included faculty members from the University of Minnesota Medical School, was able to identify what is likely an optimal combination of chest compression frequency and depth when performing CPR.

The investigation was led by Sue Duval, PhD, Associate Professor of Medicine and Biostatistics at the U of M Medical School, assisted by an international team of resuscitation investigators based at UT Southwestern, Medical College of Wisconsin, University of Oklahoma School of Community Medicine, the University Hospital of Grenoble Alpes in France, and Toho University in Tokyo, Japan.

The findings, published in JAMA Cardiology, suggest the combination of 107 compressions per minute and a depth of 4.7 cm (about 2 inches) in the first five minutes of CPR can be associated with significantly improved outcomes when Emergency Medical Services (EMS) rescuers are treating cardiac arrest outside the hospital.

In addition, the optimal combination identified did not seem to significantly vary when analyzed according to age, sex, presenting cardiac rhythm or the use of a specialized device attached to the airway during CPR. Moreover, the investigators showed that the use of the device significantly improved outcomes when the target combination of rate and depth was utilized.

The researchers found that even when CPR was performed within 20% of those chest compression values, neurologically intact survival was significantly higher -- 6% vs. 4.3% outside that range. Considering an estimated 300,000 or more out-of-hospital cardiac arrests occur each year nationally, this could translate into thousands of additional lives being saved annually in the United States alone and perhaps more if the target combination could be achieved routinely.

"What also makes this particular study especially novel for the resuscitation research community is the presentation of the data using contour plots -- graphical representation similar to a temperature map -- where the hottest points correspond to the best chance for neurologically intact survival," said Duval. "I believe this was another pivotal step in the continuum of research efforts to further save lives through robust data analysis."

The premise for this work stemmed in large part from prior National Institutes of Health (NIH) studies in which improved outcomes were observed when CPR was performed within a specified range of compression rates (100 to 120 per minute). Soon garnering the moniker the "sweet spot" of CPR, similar studies were performed showing improved outcomes within a range of compression depth as well. But because variations in rate can affect depth, and vice versa, the current investigators sought to take the next step to identify the optimal combination of the two, a "sweeter spot," to better guide rescuers in the future.

"The findings here not only emphasize the importance of quality CPR performance, but they will likely help paramedics and others on the frontlines save many more lives," said Paul Pepe, MD, Professor of Emergency Medicine at UT Southwestern. "We knew that both the depth and frequency of chest compressions could each affect outcomes, but we still had yet to better identify the optimal combination of the two - and, perhaps more importantly, whether that optimal target would vary if you were a man or woman, or if you were older or had a longer period of cardiac arrest before rescuers reached you. This study provided critical new knowledge toward that end."

Whether the findings would be universally applicable in all EMS systems has yet to be confirmed, but this study, conducted across 150 different EMS agencies in the U.S. and Canada, may be the best available findings to date. The researchers still advise that further validation of this target combination is recommended, especially when new devices, procedures or mechanical CPR tools are being introduced into the situation.

The study reviewed data from more than 3,600 patients who experienced cardiac arrest outside the hospital. Compression rate and depth were being recorded as part of a clinical trial conducted by the NIH Resuscitation Outcomes Consortium, with the use of a specific CPR device called the impedance threshold device (ITD). It was the first multicenter trial to use electronically documented measurements of both chest compression rates and chest compression depth.

A team at the Technical University of Munich (TUM) has completed the first study of the effects of a simultaneous infection with blood flukes (schistosomes) and the bacterium Helicobacter pylori - a fairly common occurrence in some parts of the world. They identified a complex interaction which resulted - among other effects - in a weakening of the adverse impact of the pathogens acting individually.

Around 240 million people worldwide are afflicted with schistosomiasis, an illness caused by flatworms of the genus schistosoma, commonly known as blood flukes. These parasites generally enter the human body with water from lakes, ponds or rivers. Worms, larvae and eggs are transported to various organs in the body through the bloodstream. The species Schistosoma mansoni is especially damaging to the liver, where it causes cirrhosis.

Helicobacter pylori is a bacterium that colonizes the human stomach. One in three people in Germany carry it and the worldwide rate is actually around 50%. Infections are associated with stomach ulcers and cancer. In places where schistosomes are widespread, as in some African countries south of the Sahara, co-infections with Helicobacter pylori are frequent. A team headed by Prof. Clarissa Prazeres da Costa and Prof. Markus Gerhard of the Institute for Medical Microbiology, Immunology and Hygiene at TUM used mice to study what happens in a co-infection with Helicobacter pylori and Schistosoma mansoni.

Misdirection of T-cells and reduction of liver cirrhosis

In a schistosomiasis infection, the initial infection is followed by an acute phase, superseded about five weeks later by a chronic phase. In their study, Prazeres da Costa and Gerhard show that fewer T-cells are found in the stomach during the acute phase of schistosomiasis. In hosts infected only by Helicobacter pylori, these immune cells are more numerous in the stomach and cause inflammation there. "We show that the schistosomiasis drives an increase in chemokine levels in the liver. The chemokines attract the T-cells and, in a sense, misdirect them to the liver," says Markus Gerhard. This leads to a reduction in stomach inflammation, he explains.

This effect fades away when the chronic phase begins, however. While hosts infected with schistosomiasis alone often suffer liver damage during that phase, this is less common with co-infections. In their investigations, Prazeres da Costa and Gerhard detected elevated quantities of the signalling protein IL-13dRa2 in the blood of mice infected with the bacteria. "IL-13dRa2 can provide protection against cirrhosis and can even reverse tissue changes," says Clarissa Prazeres da Costa. "We therefore believe that they could play a decisive role to reduce the extent of liver cirrhosis in co-infections."

Possible effects on vaccines

In everyday life, many people are repeatedly re-infected with schistosomes because they come into frequent contact with water containing the worms. „As a result, there is no time limit on the diversion of T-cells to the liver because the chronic and acute phases occur simultaneously," explains Clarissa Prazeres da Costa.

At first glance, the interactions in case of a co-infection may look like a positive side effect: Although the infected individual is suffering from two illnesses, the harmful effects of both are seemingly reduced. "Co-infections can have other consequences, however. For example, the changed immune response can limit the effectiveness of vaccines," says Markus Gerhard. "Co-infections are widespread especially in poorer regions," adds Clarissa Prazeres da Costa. "We urgently need more studies on their effects and ways of dealing with them, for example in order to develop new and more effective vaccination strategies."

Texas is ranked in the top quarter of the U.S. for its worksite lactation support initiatives, according to research led by The University of Texas Health Science Center at Houston (UTHealth) School of Public Health. The study, published recently in the Journal of Human Lactation, was the first of its kind to identify and describe statewide worksite breastfeeding initiatives. These initiatives recognize employers in the state that support their breastfeeding employees.

The American Academy of Pediatrics recommends infants be exclusively fed breast milk for the first six months following birth. The study notes that, although there are various reasons why a mother discontinues breastfeeding, an unsupportive work environment is an often-reported obstacle.

"Many women would like to continue breastfeeding after they return to work, but it isn't always easy. By providing flexibility in scheduling and a private place to express breast milk, an employer can help a woman to meet her personal breastfeeding goals. We knew that Texas has had an initiative to recognize supportive employers for several decades, and we were interested to learn if other states had similar initiatives," said the study's senior author Courtney Byrd-Williams, PhD, an assistant professor in the Michael and Susan Dell Center for Healthy Living at UTHealth School of Public Health.

The health benefits of breastfeeding can include decreased rates of breast and ovarian cancer, obesity, and Type 2 diabetes for mothers, as well as decreased rates of respiratory and gastrointestinal infections, asthma, and overweight/obesity for infants.

Despite the numerous health benefits for both mother and baby associated with breastfeeding, only 26 states were identified as having any form of worksite lactation support initiatives. Texas is in an elite group of 12 states recognized as having enhanced levels of recognition for employers with more comprehensive lactation support programs.

According to the Centers for Disease Control and Prevention, ensuring women receive worksite breastfeeding support is crucial as they return to work. Healthy People 2020, a decade-long agenda for improving the nation's health, includes a goal of increasing the number of employers that offer these programs.

Texas has long been a leader in supporting women who choose to breastfeed. The Texas Legislature passed Health and Safety Code 165 in 1995, asserting a mother's right to breastfeed anywhere she is authorized to be, as well as establishing the Mother-Friendly Worksite designation. Mother-Friendly Worksites are businesses and employers that have policies in place to proactively support employees who choose to breastfeed their infants.

Research was conducted by interviewing participants designated as breastfeeding experts from all 50 states, as well as Washington, D.C. Experts in states with a recognized initiative were asked to provide information regarding its background, structure, and requirements.

Initiatives were evaluated on eight minimum specified requirements, including a private space to express milk, flexible work schedule, written policy, verbal agreement, sink access, communication of provisions to employees, breastfeeding support resources, and a space to store breast milk.

The authors noted that though this study is the first of its kind, future research should help determine the best practices of statewide initiatives to help increase breastfeeding rates.

BOSTON - Obesity affects approximately 40 percent of Americans, according to the Centers for Disease Control and Prevention (CDC). While obesity is known to be associated with increased risk of other health conditions - such as heart disease, diabetes and gastrointestinal diseases - less is known about the relationship between obesity and abnormal bowel habits. In the most comprehensive analysis of the relationship between Body Mass Index (BMI) and bowel habits to date, published today in Alimentary Pharmacology & Therapeutics, a team of physician-researchers at Beth Israel Deaconess Medical Center (BIDMC) found a strong association between obesity and chronic diarrhea independent of an individual's dietary, lifestyle, psychological factors or medical conditions. The findings could have important implications for how physicians might approach and treat symptoms of diarrhea in patients with obesity.

"While several previous studies have pointed to an association between obesity and bowel habits, all lacked data on whether dietary or other factors drive the connection," said corresponding author Sarah Ballou, PhD, a health psychologist in the Division of Gastroenterology, Hepatology, and Nutrition at BIDMC. "Our research confirms a positive association between obesity and chronic diarrhea and reveals for the first time that this relationship is not driven by confounding factors such as diet or physical activity level."

Using the 2009-2010 National Health and Nutrition Examination Survey (NHANES) - a program of studies administered by the CDC designed to assess the health and nutritional status of adults and children in the United States - Ballou and colleagues analyzed the bowel health questionnaire responses of 5,126 patients over the age of 20 years who did not report a history of irritable bowel syndrome, celiac disease or colon cancer. The team compared the reported bowel habits of patients who had a BMI associated with being underweight, normal weight, overweight, obese and severely obese.

After controlling for dietary, physical activity, diabetes, laxative use, and demographic factors, the team found that respondents who were obese or severely obese were 60 percent more likely to have experienced chronic diarrhea compared to those with normal bowel habits or constipation.

While the study reveals the association is not driven by compounding factors the team controlled for, questions still remain about what underlying causes may explain why obese individuals would be more likely than non-obese individuals to have diarrhea. One possible explanation may be related to the link between obesity and chronic low-grade inflammation, which may contribute to diarrhea. Future research clarifying this relationship and determining how obesity triggers inflammation could serve as a base for how physicians approach treating abnormal bowel habits with this patient population.

"The treatment of obesity and obesity-related medical conditions requires multidisciplinary management," said senior author Anthony Lembo, MD, a gastroenterologist in the Division of Gastroenterology, Hepatology, and Nutrition at BIDMC. "Clinicians should be aware of the relationship between obesity and diarrhea, especially considering the potential negative impacts altered bowel habits can have on quality of life."

Galaxies come in a wide variety of shapes, sizes and brightnesses, ranging from humdrum ordinary galaxies to luminous active galaxies. While an ordinary galaxy is visible mainly because of the light from its stars, an active galaxy shines brightest at its center, or nucleus, where a supermassive black hole emits a steady blast of bright light as it voraciously consumes nearby gas and dust.

Sitting somewhere on the spectrum between ordinary and active galaxies is another class, known as low-ionization nuclear emission-line region (LINER) galaxies. While LINERs are relatively common, accounting for roughly one-third of all nearby galaxies, astronomers have fiercely debated the main source of light emission from LINERs. Some argue that weakly active galactic nuclei are responsible, while others maintain that star-forming regions outside the galactic nucleus produce the most light.

A team of astronomers observed six mild-mannered LINER galaxies suddenly and surprisingly transforming into ravenous quasars--home to the brightest of all active galactic nuclei. The team reported their observations, which could help demystify the nature of both LINERs and quasars while answering some burning questions about galactic evolution, in the Astrophysical Journal on September 18, 2019. Based on their analysis, the researchers suggest they have discovered an entirely new type of black hole activity at the centers of these six LINER galaxies.

"For one of the six objects, we first thought we had observed a tidal disruption event, which happens when a star passes too close to a supermassive black hole and gets shredded," said Sara Frederick, a graduate student in the University of Maryland Department of Astronomy and the lead author of the research paper. "But we later found it was a previously dormant black hole undergoing a transition that astronomers call a 'changing look,' resulting in a bright quasar. Observing six of these transitions, all in relatively quiet LINER galaxies, suggests that we've identified a totally new class of active galactic nucleus."

All six of the surprising transitions were observed during the first nine months of the Zwicky Transient Facility (ZTF), an automated sky survey project based at Caltech's Palomar Observatory near San Diego, California, which began observations in March 2018. UMD is a partner in the ZTF effort, facilitated by the Joint Space-Science Institute (JSI), a partnership between UMD and NASA's Goddard Space Flight Center.

Changing look transitions have been documented in other galaxies--most commonly in a class of active galaxies known as Seyfert galaxies. By definition, Seyfert galaxies all have a bright, active galactic nucleus, but Type 1 and Type 2 Seyfert galaxies differ in the amount of light they emit at specific wavelengths. According to Frederick, many astronomers suspect that the difference results from the angle at which astronomers view the galaxies.

Type 1 Seyfert galaxies are thought to face Earth head-on, giving an unobstructed view of their nuclei, while Type 2 Seyfert galaxies are tilted at an oblique angle, such that their nuclei are partially obscured by a donut-shaped ring of dense, dusty gas clouds. Thus, changing look transitions between these two classes present a puzzle for astronomers, since a galaxy's orientation towards Earth is not expected to change.

Frederick and her colleagues' new observations may call these assumptions into question.

"We started out trying to understand changing look transformations in Seyfert galaxies. But instead, we found a whole new class of active galactic nucleus capable of transforming a wimpy galaxy to a luminous quasar," said Suvi Gezari, an associate professor of astronomy at UMD, a co-director of JSI and a co-author of the research paper. "Theory suggests that a quasar should take thousands of years to turn on, but these observations suggest that it can happen very quickly. It tells us that the theory is all wrong. We thought that Seyfert transformation was the major puzzle. But now we have a bigger issue to solve."

Frederick and her colleagues want to understand how a previously quiet galaxy with a calm nucleus can suddenly transition to a bright beacon of galactic radiation. To learn more, they performed follow-up observations on the objects with the Discovery Channel Telescope, which is operated by the Lowell Observatory in partnership with UMD, Boston University, the University of Toledo and Northern Arizona University. These observations helped to clarify aspects of the transitions, including how the rapidly transforming galactic nuclei interacted with their host galaxies.

"Our findings confirm that LINERs can, in fact, host active supermassive black holes at their centers," Frederick said. "But these six transitions were so sudden and dramatic, it tells us that there is something altogether different going on in these galaxies. We want to know how such massive amounts of gas and dust can suddenly start falling into a black hole. Because we caught these transitions in the act, it opens up a lot of opportunities to compare what the nuclei looked like before and after the transformation."

Unlike most quasars, which light up the surrounding clouds of gas and dust far beyond the galactic nucleus, the researchers found that only the gas and dust closest to the nucleus had been turned on. Frederick, Gezari and their collaborators suspect that this activity gradually spreads from the galactic nucleus--and may provide the opportunity to map the development of a newborn quasar.

"It's surprising that any galaxy can change its look on human time scales. These changes are taking place much more quickly than we can explain with current quasar theory," Frederick said. "It will take some work to understand what can disrupt a galaxy's accretion structure and cause these changes on such short order. The forces at play must be very extreme and very dramatic."

A treatment for psoriasis could be repurposed to treat a rare but aggressive form of youth cancer, new findings from the Garvan Institute of Medical Research suggest.

In an animal model, researchers demonstrated that the immune molecule IL23 is central to the development of osteosarcoma, a cancer of the bone. By targeting IL23, study authors successfully shrank osteosarcoma tumours in mice.

The findings, published this week in Cancer Discovery, uncover an opportunity to repurpose an existing medication and bring new hope to those suffering from osteosarcoma.

"There has been no real advance in treatments for this form of cancer in four decades - we have uncovered a new target that we know can be modulated with existing therapy," says senior author Professor David Thomas, Garvan Cancer Research Theme Leader and Director of the Kinghorn Cancer Centre. "We hope our findings will lead to clinical trials that will provide better outcomes for patients with this rare form of cancer."

Urgent need for new treatments

Osteosarcoma is a rare cancer, but among the ten most common cancers affecting males between ages 15 to 29, in Australia. Arising in bone, osteosarcoma is often dismissed as growing pain or injury, and in many cases only detected after it has spread to other parts of the body.

The five-year survival rate of osteosarcoma remains as low as 65%.

"Our search for new potential treatments for osteosarcoma began in 2013 when we investigated genetic risk factors for this form of cancer," says first author Dr Maya Kansara, who leads the Immunobiology of Cancer Group at Garvan.

"From genome-wide association studies conducted with the U.S. National Institutes of Health we saw that variants in a gene that encodes the protein GRM4 were frequently associated with osteosarcoma."

The immune system's link to osteosarcoma

"In a mouse model of osteosarcoma, we investigated the role of GRM4, as well as a number of immune molecules, the production of which is regulated by GRM4," says Dr Kansaras. "In our model, we discovered that the inflammatory molecule IL23 was critical to osteosarcoma formation and progression."

When the researchers removed IL23 in mice, they were protected from developing osteosarcomas. Further, when the researchers blocked IL23 in mice with existing osteosarcoma, tumour growth was slowed, and in synergism with doxorubicin, a current standard of care treatment for this form of cancer, tumour growth was even further suppressed.

The team analysed human osteosarcoma biopsies and found that more than 70% of samples had significantly higher levels of IL23 than non-tumour tissue. As the expression of IL23 is higher in multiple cancer types, the researchers say these findings may have broader implications for cancer outcomes.

Opportunity for repurposed therapy

Therapies targeting IL23 have been investigated extensively for a number of autoimmune diseases, including arthritis, intestinal inflammation and the skin condition psoriasis.

"Drugs that block IL23 are approved and well tolerated, and on the market now for the treatment of psoriasis," says Professor Thomas. "We are now designing clinical trials to see whether they can provide much-needed improved health outcomes for osteosarcoma patients."

Interestingly, data from a Danish cohort study published in 2017 suggested that patients with psoriasis were almost five times more likely to develop sarcomas than individuals without the skin condition. "This data reaffirms the central role IL23 plays in osteosarcoma, and that we're on the right track," says Dr Kansara.

Philadelphia, September 16, 2019 - Female athletes seek specialty medical treatment later than male athletes for sports-related concussions (SRC), and this delay may cause them to experience more symptoms and longer recoveries. Researchers from the Sports Medicine Program at Children's Hospital of Philadelphia (CHOP), reported these findings after analyzing electronic health records of sports participants aged 7 to 18.

The study raises the question of whether, in youth and high school sports, inequities in medical and athletic trainer coverage on the sidelines are contributing to delayed identification and specialized treatment of concussion for female athletes, leading to more symptoms and longer recovery trajectories. The study was published in the Clinical Journal of Sports Medicine.

"There is speculation in the scientific community that the reasons adolescent female athletes might suffer more symptoms and prolonged recoveries than their male counterparts include weaker neck musculature and hormonal differences," says senior author Christina Master, MD, a pediatric and adolescent primary care sports medicine specialist and Senior Fellow at CHOP's Center for Injury Research and Prevention. "We now see that delayed presentation to specialty care for concussion is associated with prolonged recovery, and that is something we can potentially address."

Dr. Master and her team analyzed a dataset containing records of 192 children between 7 and 18 who were diagnosed with an SRC and seen by a sports medicine specialist. Females took longer to present to specialist care and had longer recovery trajectories than males. The median days to presentation for a subspecialty evaluation was 15 for females with SRC and 9 for males. This delay is important since time to presentation to specialized care greater than 1 week has been described as a factor associated with prolonged recovery.

Five distinct outcomes indicating return to preinjury function were measured to determine "recovery" in this group of athletes. By looking at average-days-to-recovery for female and male patients across these outcomes, researchers found that females returned to school later (4 vs. 3 days), returned to exercise later (13 vs. 7 days), had neurocognitive recovery later (68 vs. 40 days), had later vision and vestibular (balance) recovery (77 vs. 34 days) and returned to full sport far later (119 vs. 45 days).

Importantly, when researchers limited the analysis to those female and male patients that presented to the specialty practice for evaluation within the first 7 days of injury, the differences between males and females on all outcomes disappeared.

In sports where females sustain the highest rates of concussion- - including those in this cohort of patients -- specifically soccer, basketball, and cheerleading, there is generally less sideline medical coverage for games and inconsistent athletic training coverage for practice because they are categorized as "moderate-risk sports" based on all-cause injury. In stark contrast, many high school leagues require athletic training coverage at all football, ice hockey and men's basketball practices and games.

"It is possible that the lack of athletic training coverage at the time of injury may affect the time to concussion recognition during the first critical hours and days after injury," says Dr. Master. "This period is a window of opportunity where specific clinical management, such as immediate removal from play, activity modification and sub-symptom threshold exercise is correlated with more rapid recovery."

Those who study pediatric concussion have been investigating why some concussions take longer to resolve than others so that they can identify those concussions early and implement appropriate concussion management plans to hopefully prevent persistent post-concussion symptoms. This study builds on that knowledge and suggests a tangible cause and solution: close the gap in athletic training and medical coverage between female and male sports.

An electronic nose that detects chemicals in the breath of lung cancer patients can identify with 85% accuracy those who will or will not respond to immunotherapy, according to new research published in the leading cancer journal Annals of Oncology [1] today (Wednesday).

The results of the first study to investigate this show that the eNose is more accurate than the current gold standard of immunohistochemistry (IHC) for selecting patients who will respond to anti-PD-1 immunotherapies such as nivolumab or pembrolizumab. IHC involves testing tissue samples for the presence of the protein called programmed death ligand 1 (PD-L1), which is the target for anti-PD 1 therapies, but it is invasive and takes time to obtain results.

Professor Michel van den Heuvel, professor of thoracic oncology at the Radboud University Medical Centre (Nijmegen,The Netherlands), who led the research, said: "The introduction of immunotherapy has dramatically improved the treatment of advanced stage non-small cell lung cancer but unfortunately it is only effective in a subset of patients, which was about 20% when we started the study. Currently, there is no test available that can accurately predict who will benefit from this treatment, apart from PD-L1 testing by immunohistochemistry. This is today's biomarker of choice, despite its analytic and predictive limitations, when making clinical decisions about whether or not to treat a patient with immunotherapy."

Ms Rianne de Vries, a PhD student in the department of respiratory medicine at Amsterdam University Medical Centres (The Netherlands), who is joint first author of the study, said: "We hypothesised that exhaled breath analysis using eNose technology might be a non-invasive and rapid alternative to the current standard and would enable doctors to avoid treating patients with an immunotherapy to which they would not respond."

The eNose is a small device [2] that contains sensors to detect chemicals called volatile organic compounds (VOCs), which are present in about one per cent of our exhaled breath. The rest of our breath mainly consists of nitrogen, oxygen, carbon dioxide and water. The researchers thought that the mix of VOCs in the breath of patients with advanced non-small cell lung cancer (NSCLC) might indicate whether or not the patient would respond to anti-PD1 therapy; VOCs can vary depending on metabolic processes that occur in the whole body or in parts of it, such as the lungs.

Ms de Vries, who is also chief operating officer of Breathomix, which is currently producing the eNose, continued: "When using the eNose, the patient takes a deep breath, holds it for five seconds and then slowly exhales into the device. The eNose sensors respond to the complete mixture of VOCs in the exhaled breath; each sensor has its highest sensitivity to a different group of molecules. The sensor readings are sent directly to and stored at an online server for real-time processing of the data and for ambient air correction because the air that you exhale is influenced by the air that you inhale. The measurement takes less than a minute, and the results are compared to an online database where machine-learning algorithms immediately identify whether or not the patient is likely to respond to anti-PD1 therapy."

Between March 2016 and February 2018, the researchers at The Netherlands Cancer Institute, Amsterdam, recruited 143 patients with advanced NSCLC. They used the eNose to take the breath profiles of the patients two weeks before they started treatment with nivolumab or pembrolizumab, and after three months they used standard criteria (Response Evaluation Criteria of Solid Tumours, RECIST) to assess whether the patients were responding to the treatment nor not. Results from the first 92 patients (who started treatment between March 2016 and February 2017) were validated by the results from the remaining 51 patients (who started treatment after April 2017).

The other first author of the study, Dr Mirte Muller, a PhD student in the department of thoracic oncology at The Netherlands Cancer Institute, said: "We found that before the start of treatment with immunotherapy, the eNose analysis of exhaled breath from the patients with non-small cell lung cancer could distinguish between responders and non-responders with an accuracy of 85%.

"Our findings show that breath analysis by eNose can potentially avoid application of ineffective treatment to patients that are identified by eNose as being non-responders to immunotherapy, which in our study was 24% of the patients. This means that in 24% of NSCLC patients this treatment could be avoided, without denying anyone effective treatment.

"ENose technology is cheap compared to other available medical technologies and diagnostic tests and biomarkers. The eNose qualifies as a non-invasive and rapid point-of-care test that provides feedback within seconds in the doctor's office. Our results form a solid base for taking the next step to validate these findings in a large prospective multi-centre study."

Although immunotherapy tends to have fewer side effects than chemotherapy, with fatigue being the most common, it can trigger more serious side effects in about 10% of patients. Organs such as the lungs, liver and bowel can become inflamed when the body's immune system starts to attack its own cells. By correctly identifying patients who will not respond to immunotherapy, side effects related to the treatment can be avoided.

Prof van den Heuvel concluded: "We are convinced that this study merely scratches the surface. It represents the first introduction of modern precision medicine, namely that molecular fingerprints can be easily obtained and quickly analysed on the spot. This truly offers new possibilities for the individual patient and the doctor. The power of this eNose system is that it has been properly validated, both technically and clinically, which is essential. We believe that analysis of exhaled breath is going to become an important diagnostic tool and will guide future treatment in oncology as well as in many other diseases."

New research presented at this year's Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain (16-20 September) shows that the proportion of younger adults being diagnosed with type 2 diabetes (T2D) has increased since the start of the century. The study is by Professor Sanjoy Ketan Paul, Chair in Clinical Epidemiology, Biostatistics & Health Services Research, Department of Medicine, University of Melbourne and Dr Digsu Koye, University of Melbourne, Australia and colleagues.

The changes over time, co-existing conditions (comorbidities) and long-term outcomes in young-onset T2D compared to older people with T2D have not been well studied. In this news study, the authors investigated temporal changes over time in young-onset T2D, risk factor control, comorbidities and the risk of developing atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality separately by age groups at diagnosis.

Using nationally representative UK primary care electronic medical records, 370,854 people diagnosed with T2D from January 2000 were identified. The authors extracted data on anthropometric (physical measurements), clinical and laboratory measures and comorbidities (co-existing conditions) at diagnosis of T2D, and ASCVD and all-cause mortality during a median of seven years follow-up. The changes over time (temporal trend) in the proportion of people at diagnosis in the age groups 18-40, 41-50, 51-60, 61-70 and 71-80 were evaluated from 2000 to 2017. The temporal trend of rate / 1000 person years for ASCVD and all-cause mortality were calculated.

Of the 370,854 incident cases of T2DM identified, the mean age was 53 years, and 11% and 16% were in the 18-40 and 41-50 years age groups respectively. Proportion of people in these age groups marginally increased from 9.5% to 12.5% (18-40 years) and 14% to 17.5% (41-50 years) respectively over the 17 years of the study. Thus, in the UK today, around 1 in 8 new cases of T2D is in someone aged 18-40 years, compared to one in 10 in the year 2000.

The youngest group had significantly higher BMI (mean: 35 kg/m2, 71% obese), high blood glucose level (mean HbA1c: 8.6%; 58% with glycated haemoglobin HbA1c ? 7.5%) and levels of low density lipoprotein (bad) cholesterol (71% with LDL-C ? 100 mg/dL) compared to older people.

Furthermore, in the 18-40 years group about one-third had high blood pressure, 2% had ASCVD and 4% had chronic kidney disease. Almost a quarter 23% were identified as having increased cardiovascular risk without the history of ASCVD. In people in the age group 40-49 years at diagnosis, the mean BMI was 34 kg/m2 with 70% being obese, with 55% of patients with HbA1c of 7.5% or over. In the newly diagnosed patients aged 60-69 years, the mean BMI was down to 32 kg/m2 and 57% were obese, with only 38% with HbA1c over 7.5%. (SEE FULL TABLE LINK BELOW)

Rate of ASCVD was declining in all age groups between 2000 and 2006, followed by a stable and similar pattern for all age groups after 2007. The all-cause mortality rate declined over time by around 20% in those 60-69 years group and by around 30% in those 70-79 years group, but remained unchanged in the 18-59 years age groups. The average time to ASCVD or death was not different between high and low-risk status patients in the youngest people with T2DM.

The authors conclude: "The proportion of young-onset T2DM has increased from 2000 to 2017. Young people with T2DM have a higher cardiovascular risk factor burden. While cardiovascular morbidity and mortality risks have declined substantially over the years for older people with T2DM, they remain unchanged for younger people. Young-onset diabetes has a more aggressive phenotype compared to older-onset diabetes. More intense strategies are required to improve longer term cardiovascular and mortality outcomes in this population."

A new study presented at this year's Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain (16-20 September) highlights the negative health effects of even short periods of physical inactivity and stresses the importance of staying physically active.

The research was conducted by Dr Kelly Bowden Davies, Newcastle University, UK and the University of Liverpool, UK and colleagues, and analysed the effects of a short-term reduction in physical activity on metabolic profiles, body composition and cardiovascular (endothelial) function.

Low levels of physical activity and sedentary lifestyles are known to confer a significantly increased risk of metabolic problems including obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. The goal of the study was to determine whether adverse effects linked to these conditions would begin to appear in previously active individuals after a period of just 14 days of reduced physical activity.

The team recruited a study group of habitually active (>10,000 steps/day) individuals (18 female, 10 male) with a mean age of 32 and an average BMI of 24.3 kg/m2 (within the 'healthy' range). Assessments were performed at baseline, 14 days after adopting a more sedentary lifestyle, and 14 days after resuming their previous activity level. Participants' cardiorespiratory fitness (V?O2 peak), body composition (dual-energy x-ray absorptiometry/magnetic resonance spectroscopy) and cardiovascular function (flow mediated dilation; FMD) were determined at each time point, and their physical activity (SenseWear armband) was monitored throughout.

Study participants reduced their step count by an average of around 10,000 steps/day measured in comparison to each individual's baseline activity, increasing their waking sedentary time by an average 103 minutes/day.

Cardiovascular function as measured by FMD decreased by 1.8% following 14 days of relative inactivity, but returned to comparable baseline levels 14 days after the resumption of normal activity. The researchers also found that: "In parallel, total body fat, waist circumference, liver fat, insulin sensitivity and cardiorespiratory fitness were all adversely affected by 14 days step-reduction, but returned to comparable baseline levels following resumption of habitual activity."

The authors conclude: "In young non-obese adults, short-term physical inactivity and increased sedentary behaviour led to decreased cardiorespiratory fitness and increasing waist circumference, liver fat deposition and insulin resistance, and led to a significant decline in endothelial function, a sign of developing cardiovascular disease."

They add: "Public health messages need to emphasise the harmful effect of even short-term physical inactivity, and that habitual activity appears to offset these negative consequences. Even small alterations in physical activity in daily living can have an impact on health - positively, or negatively. People should be encouraged to increase their physical activity levels, in any way possible. Often, we hear of 'barriers to exercise', such as energy or lack of enjoyment, but simply increasing daily physical activity can have benefit, as shown here by only changes daily steps."

Advanced radiotherapy technology could safely deliver curative treatment for some prostate cancer patients in just one or two weeks, according to new research published today. This is a significant reduction from the current standard of care, which is one to two months and the first time such a short timeframe of treatment has been investigated in a phase III trial.

In the PACE-B trial, published today (Tuesday 17 Sept 23:30 UK BST) in The Lancet Oncology, researchers at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, used ultra-hypofractionated stereotactic body radiotherapy (SBRT) to deliver five higher doses of radiation to patients over one to two weeks. Researchers found in the three months after treatment, side effects were no worse when compared with patients who had conventional therapy with more moderate doses over a much longer period of time.

They are still awaiting data on long-term side effects and overall efficacy; in the UK the treatment technique currently only available in a trial setting.

SBRT allows clinicans to target tumours to sub-millimetre precision. Greater accuracy reduces the chance of damaging surrounding healthy tissue, which can lead to urinary and rectal side effects such as more frequent or urgent urination and diarrhoea. In the PACE-B study researchers wanted to understand whether they could safely increase the dose of this targeted radiation, and so reduce the number of treatments required, or if this carried a risk of worse toxicity. When treating patients, clinicians have to consider whether the higher doses in a shorter time period is the best option; the potential side effects are a critical factor in making this decision.

847 patients with prostate cancer were randomised to two groups. 432 patients were allocated the current standard of care receiving moderate hypofractionation radiotherapy (CFMHRT) for either 39 doses over seven/eight weeks, or 20 doses over four weeks. 415 patients were allocated ultra-hypofractionated SBRT, receiving five doses of treatment over one or two weeks. For both groups of patients, 90 per cent of whom had intermediate risk prostate cancer, this was intended to be curative treatment with no further treatment planned.

Patients on the control arm were assessed every other week, and on the SBRT arms assessed after the final dose day, and weeks two, four, eight and twelve after the end of treatment. Researchers incorporated both assessments by clinicians and questionnaires completed by patients. They found patients in both groups had similar levels of side effects over the three months after treatment. They also found side effects in both groups were less overall than had been previously published.

Chief Investigator Dr Nicholas van As, Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust, and Reader at The Institute of Cancer Research, London, said: "At The Royal Marsden and the ICR we are focused on developing smarter, better and kinder treatments for patients across the UK and internationally. Developments in radiotherapy such as SBRT mean we can target tumours much more effectively.

"It is reassuring to see from this trial that SBRT does not significantly impact patients' quality of life in the short term, compared with the current standard of care. Using SBRT to deliver this treatment would mean that patients could be spared numerous visits to hospital, allowing them to get back to their lives sooner."

Dr van As, who is also Medical Director at The Royal Marsden, added: "These results are promising, and for the first time show in a large patient group that giving five large doses of SBRT is safe in the short term. It is important to point out that we will not know for another few years about the long term side effects and outcomes of treatment, and that this treatment technique is still only available in a trial setting in the UK.

Study author Dr Douglas Brand, Research Fellow in Clinical Oncology at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, said:

"The new results from our clinical trial have shown that a much shorter course of higher-dose radiotherapy does not increase short term side effects compared with the current standard of care.

"If the data on longer-term side effects and efficacy are also positive, we expect our trial could be practice-changing. This would enable us to deliver curative treatment over fewer days - meaning that men would get the same benefit from their radiotherapy while having to spend less time in hospital."

Dr Brand presented the patient outcomes from PACE-B at today's American Society for Radiation Oncology Annual Meeting (Tuesday 17 September)

Alfred, 84, was diagnosed with prostate cancer in 2013 at The Royal Marsden NHS Foundation Trust. He was able to go onto the PACE B trial for his treatment, and was randomised into the group to receive SBRT.

Alfred says: "I only had to go into The Royal Marsden five times over two weeks to have my radiotherapy treatment with CyberKnife. I was made very comfortable and overall - and not something I'd usually associate with cancer treatment - it was a breeze. I didn't have many symptoms afterwards and was able to get back to my life. In the six years since, I've not had to have any further treatment. The Royal Marsden was excellent - I really couldn't have asked for more."

Bottom Line: Adding behavioral and physical therapy before and after surgery for women with stress and urgency urinary incontinence resulted in a small improvement in symptoms compared to women who just had surgery but that difference in symptoms may not be clinically important. There have been a lack of studies examining treatments for women with both stress and urgency urinary incontinence also called mixed urinary incontinence. This randomized clinical trial included 480 women with symptoms of mixed urinary incontinence and compared the effect among women of having sessions of behavioral and pelvic floor muscle therapy before and after midurethral sling surgery for incontinence or surgery alone. The authors report that after 12 months, compared to women who just had surgery, women in the combined therapy and surgery group had a small improvement in symptoms of mixed urinary incontinence but that difference didn't meet the threshold set for clinical importance. A limitation of the study was a lack of well-established thresholds when this study was designed for determining minimal clinically important differences for women with mixed urinary incontinence.

Authors: Vivian W. Sung, M.D., M.P.H., Alpert Medical School of Brown University, Providence, Rhode Island, and coauthors

(doi:10.1001/jama.2019.12467)

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.

PASADENA, Calif., September 17, 2019 - Individuals with familial hypercholesterolemia (FH) were able to lower their cholesterol under FH specialty care, but many are still not meeting LDL-cholesterol targets, according to the FH Foundation's CASCADE FH® Registry. In new research published in the October issue of Atherosclerosis, 52 percent of adults with FH still had LDL-cholesterol over 100 mg/dL despite being on multiple cholesterol-lowering treatments. In addition, these individuals with FH had high heart attack, stroke, and vascular procedure rates, with an annualized cardiovascular event rate of 2.21 per 100 patient years overall, and 4.57 if an individual had a prior cardiovascular event.

"These data from the CASCADE FH Registry demonstrate that individuals with FH are truly a vulnerable, high-risk population for future heart and stroke events, despite being on multiple treatments," said P. Barton Duell, MD, Professor of Medicine, Director, Lipid-Atherosclerosis Laboratory, Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University. "These data suggest that FH patients without known heart disease may actually have a risk of heart attack that is comparable to the risk in patients without FH who have already had a heart attack. Most individuals with FH will require multiple medications to adequately lower the LDL-cholesterol level to below goal. Adding additional medications to achieve an LDL-C level that can help prevent a heart attack, particularly for those who already have heart disease, needs to become the standard of care."

While cardiovascular event rates were high overall, rates of major cardiovascular events were almost six times higher among individuals with prior cardiovascular disease compared to those without. These data underscore the need to treat most patients with FH much more aggressively, possibly with an optimal LDL-C target that may be

"These five years of data from across the United States underscore the impact of life-long exposure to LDL cholesterol in the FH population," said Katherine Wilemon, Founder and CEO of the FH Foundation. "The vast majority of individuals with FH in the United States continue to live without a diagnosis, barring them from the opportunity to receive appropriate care. Finding these individuals and initiating intensive treatment early in life is critical to preventing heart disease."

The results confirmed very late diagnosis of FH, at age 50 (plus or minus 18 years). Lack of awareness of FH in the public and medical community contributes to low diagnosis rates in the United States.

The results also highlighted the broad number of treatments that are now available for FH and the benefit individuals received by being on multiple therapies. The majority of patients are on three to six treatments to lower their LDL-C. Specifically, the use of high intensity statins and PCSK9 inhibitors, as well as treatment with LDL apheresis, at enrollment were associated with a higher likelihood of reaching LDL-C goals. Individuals who achieved more than a 50 percent reduction in LDL-C took more lipid lowering therapies during follow-up, compared to those who achieved less than a 50 percent reduction.

"Today, there are more safe and effective treatments for individuals with FH. With multiple LDL-C lowering drugs, plant sterols, LDL apheresis and exciting experimental therapies in development, individuals should advocate with their healthcare providers to add treatments until their LDL targets are achieved," added Samuel Gidding, MD, chief medical officer for the FH Foundation.

Phoenix, AZ (September 17, 2019) - There is finally some encouraging news for the millions of Americans suffering from Alzheimer's Disease. NeuroEM Therapeutics today announced findings from an open label clinical trial showing reversal of cognitive impairment in Alzheimer's Disease patients after just two months of treatment using the company's wearable head device for in-home treatment.

Results demonstrate that TEMT was safe in all eight participating patients with mild to moderate AD and enhanced cognitive performance in seven of them, as measured by their ADAS-cog score, which is the benchmark for testing AD therapeutics. The study is being published in the new issue of the Journal of Alzheimer's Disease.

The investigators had previously demonstrated that treating AD mice with electromagnetic waves in the radiofrequency range resulted in protection against memory impairment in young AD mice and reversal of memory impairment in aged AD mice.

For the present clinical study in humans, the investigators used the same treatment (twice daily for 1-hour) through creation of NeuroEM's first-in-class MemorEMTM head device. The device has multiple, highly-specialized emitters positioned within a head cap that are activated sequentially, with treatments easily administered in-home by the patient's caregiver. As well, the device allows for near complete mobility to perform nearly all household activities during treatments.

"Perhaps the best indication that the two months of treatment was having a clinically-important effect on the AD patients in this study is that none of the patients wanted to return their head device to the University of South Florida/Byrd Alzheimer's Institute after the study was completed", said Dr.Gary Arendash, CEO of NeuroEM Therapeutics. One patient even exclaimed "I've come back."

The investigators indicated they have strong evidence that TEMT is directly affecting the Alzheimer's disease process by easily penetrating the brain and brain cells to break up aggregates of two toxic proteins inside brain cells called A-beta and tau.

TEMT's ability to disaggregate both toxic proteins inside brain cells (neurons) appears to be key to stopping and reversing the cognitive loss of AD. Present AD drugs in clinical trials have great difficulty getting into the brain and then into brain cells. Even if they succeeded in doing so, they do not yet have the capacity to target the small aggregates of A-beta and tau proteins that appear to be causative to AD.

NeuroEM Therapeutics is planning for a pivotal clinical trial to begin recruitment of approximately 150 mild/moderate AD subjects later this year for treatment with the company's MemorEMTM device. If that trial shows continued safety and cognitive benefits, NeuroEM Therapeutics plans to ask the FDA for approval of the MemorEM device for treatment of AD. The clinical locations for this multi-site trial have not yet been determined.

"Despite significant efforts for nearly 20 years, stopping or reversing memory impairment in people with Alzheimer's disease has eluded researchers," said co-author Amanda Smith, M.D., Director of Clinical Research, University of South Florida Health, Byrd Alzheimer's Institute, the clinical center for the study. "These results provide preliminary evidence that TEMT administration we assessed in this small AD study may have the capacity to enhance cognitive performance in patients with mild to moderate disease."

After two months of treatment administered at home by their caregivers, none of the eight patients in the study exhibited any deleterious side effects on behavior or physiologic measures, as recorded by caregivers in daily diaries. Moreover, post-treatment brain scans revealed no visible induction of tumors or brain bleedings called microhemorrhages.

Using the benchmark ADAS-cog task to assess a variety of cognitive measures, seven of the eight AD patients collectively responded to treatment with a 4+ point increase in cognitive performance by the end of the 2-month treatment period -- the results indicate a very large and clinically-important effect.

Since AD patients typically show a 4+ point decline in ADAS-cog performance over a given one year period, the 4+ point improvement provided by TEMT was as if the treated patients had gone back in time to their better cognitive performance of one year earlier.

"We were particularly surprised that this highly significant improvement in the ADAS-cog was maintained even two weeks after treatment was completed", stated Dr. Arendash. "The most likely explanation for continued benefit after cessation of treatment is that the Alzheimer's Disease process itself was being affected.

Cognitive abilities were improved in other tasks as well, such as the Rey AVLT task, wherein clinically important increases in word recall were present after treatment for 2 months and at two weeks thereafter. Even a 50% reduction in forgetting was observed in this important task.

In addition to cognitive assessment, the study also involved analysis of AD markers in both the blood and the cerebrospinal fluid (CSF) before and at the end of the 2-month treatment period. These AD markers were changed in directions expected for TEMT disaggregating the two toxic proteins (A-beta and tau) that appear to be the disease's root causes.

Also, MRI brain scans in individual AD patients revealed evidence of increased communication between neurons in a brain area critical for cognitive integration called the cingulate cortex/cingulum.

The investigators believe that TEMT may be an entirely new therapeutic intervention against Alzheimer's disease and that NeuroEM's bioengineering technology may be succeeding where drug therapy against this devastating disease has thus far failed.

Based on the findings and the enthusiasm for continued treatment that all patients expressed, patients were offered and accepted continued TEMT in a now on-going extension study averaging 17 months between initial study start and extension study finish. More information about both the completed and on-going clinical trials is available at NeuroEM's website.

About one in three Americans have high blood pressure, called hypertension, but only about half of them have their condition under control. A major factor is that many do not consistently take their medications for the condition, which leads to poor health outcomes such as heart attack or stroke. Researchers from Penn Medicine tested new tactics, including text messaging and remote monitoring via an electronic pill bottle, to see if they might affect blood pressure levels. They found that while each method did appear to keep medication adherence high, neither method appeared to drive down blood pressure levels. These findings were published in the Journal of General Internal Medicine.

"We had experience with electronic pill bottles to monitor adherence in the past, but they were expensive and sometimes technically challenging to administer to patients," said the study's lead author, Shivan Mehta, MD, MBA, associate chief innovation officer at Penn Medicine and an assistant professor of Medicine. "For this study, we hypothesized that bidirectional -- two-way, conversational -- text messaging could have similar functionality but with better user experience. However, we did not see a difference in blood pressure for either method."

Nearly 150 patients who take medication for their high blood pressure across four Philadelphia primary care practices participated in the study. They were split into three groups: one that received standard of care, another group was mailed an electronic pill bottle that monitored their medication adherence, and the third group that received automated text messages asking about medication adherence. Groups two and three also received daily text messaging prompting them to take their medications.

The electronic pill bottles recorded every time they were opened and transmitted that data to the researchers using Penn Medicine's Way to Health automated technology platform. Each day, participants received one of two text messages: One congratulating them for taking their medication the previous day (if the bottle detected being opened), or another acknowledging that they didn't take their medication the previous day (if the bottle was not opened). Both messages featured a reminder to take the medication that day.

Participants using two-way text messaging were asked -- also via Way to Health -- to respond "yes" or "no" to whether they took their medication. Automated messages also either congratulated them for taking their medication the day before or acknowledged that they hadn't. Adherence to medication was found to be high among the study's participants, both hovering near 80 percent. Despite the extra methods employed, the researchers found that both blood pressure levels and rates of adherence to blood pressure medication remained similar to patients in the control group - those who didn't have the electronic pill bottles or the texting.

The blood pressure levels might not have been improved because adherence levels didn't increase enough, Mehta explained. It's also possible that the patients may have needed higher doses of their medications or new medications.

There are also a few other ways that patient outcomes could be influenced by leveraging new insights from behavioral economics. For instance, Mehta is already testing out the social support factor in a new trial that also offered blood pressure cuffs and remote monitoring to 250 patients. Additionally, the new study has built in "nudges" for clinicians to consider dose escalation or additional medications among their hypertension patients.