Fast, accurate and inexpensive medical tests in a doctor’s office are only possible for some conditions. To create new in-office diagnostics for additional diseases, researchers report a new technique that uses ultrasound to concentrate fluorescently-labelled disease biomarkers otherwise impossible to detect with current equipment in an office setting. The markers’ signal could someday be analysed via a smartphone app. Ultrasound is a safe, non-invasive, inexpensive and portable technique best known for monitoring pregnancies. But these high-frequency acoustic waves can also be used to gently handle blood components, cells and protein crystals at the microscopic level. With an eye toward point-of-care diagnostic applications, Tony Huang, Zhangming Mao and colleagues wanted to harness these sound waves to help detect even smaller particles and biomarkers for diseases such as cancer that often require special laboratory equipment to detect. The researchers developed an acoustofluidic chip that, though vibrations, can form a streaming vortex inside a tiny glass capillary tube using a minimal amount of energy. Testing showed that the vortex could force nanoparticles ranging in diameter from 80 to 500 nanometers to swirl into the centre of the capillary. The nanoparticles captured biomarkers labelled with a fluorescent tag, concentrating them in the capillary to boost their signal. This increased brightness could make the signal readable with a smartphone camera.
American Chemical Societyhttp://tinyurl.com/yd5ltoul
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Of the quarter- million women diagnosed with breast cancer every year in the United States, about 180,000 undergo surgery to remove the cancerous tissue while preserving as much healthy breast tissue as possible. However, there’s no accurate method to tell during surgery whether all of the cancerous tissue has been successfully removed. The gold-standard analysis takes a day or more, much too long for a surgeon to wait before wrapping up an operation. As a result, about a quarter of women who undergo lumpectomies receive word later that they will need a second surgery because a portion of the tumour was left behind. Now, researchers at Washington University School of Medicine in St. Louis and California Institute of Technology report that they have developed a technology to scan a tumour sample and produce images detailed and accurate enough to be used to check whether a tumour has been completely removed. Called photoacoustic imaging, the new technology takes less time than standard analysis techniques. But more work is needed before it is fast enough to be used during an operation. "This is a proof of concept that we can use photoacoustic imaging on breast tissue and get images that look similar to traditional staining methods without any sort of tissue processing," said Deborah Novack, MD, PhD, an associate professor of medicine, and of pathology and immunology, and a co-senior author on the study. The researchers are working on improvements that they expect will bring the time needed to scan a specimen down to 10 minutes, fast enough to be used during an operation. The current gold-standard method of analysis, which is based on preserving the tissue and then staining it to make the cells easier to see, hasn’t gotten any faster since it was first developed in the mid-20th century. To speed up the process, the researchers took advantage of a phenomenon known as the photoacoustic effect. When a beam of light of the right wavelength hits a molecule, some of the energy is absorbed and then released as sound in the ultrasound range. These sound waves can be detected and used to create an image. "All molecules absorb light at some wavelength," said co-senior author Lihong Wang, PhD, who conducted the work when he was a professor of biomedical engineering at Washington University’s School of Engineering & Applied Science. He is now at Caltech. "This is what makes photoacoustic imaging so powerful. Essentially, you can see any molecule, provided you have the ability to produce light of any wavelength. None of the other imaging technologies can do that. Ultrasound will not do that. X-rays will not do that. Light is the only tool that allows us to provide biochemical information." The researchers tested their technique by scanning slices of tumours removed from three breast cancer patients. For comparison, they also stained each specimen according to standard procedures. The photoacoustic image matched the stained samples in all key features. The architecture of the tissue and subcellular detail such as the size of nuclei were clearly visible. "It’s the pattern of cells – their growth pattern, their size, their relationship to one another – that tells us if this is normal tissue or something malignant," Novack said. "Overall, the photoacoustic images had a lot of the same features that we see with standard staining, which means we can use the same criteria to interpret the photoacoustic imaging. We don’t have to come up with new criteria." Having established that photoacoustic techniques can produce usable images, the researchers are working on reducing the scanning time.
Siteman Cancer Center http://tinyurl.com/y87u35l5
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Postmenopausal hormone therapy is not associated with increased risk of stroke, provided that it is started early, according to a report from Karolinska Institutet. Roughly three in ten women in the menopause transition are afflicted by symptoms that seriously affect their wellbeing, such as hot flushes, dry mucosa and insomnia. However, although the symptoms can be treated effectively with female sex hormones, prescriptions have been low over the past 15 years as researchers have demonstrated a link between such therapy and an increased risk of certain diseases, including stroke. There is still, however, a need for more research on the issue, as the risk can be influenced by the time of the treatment and other factors, reasons Karin Leander, researcher at Karolinska Institutet’s Institute of Environmental Medicine. “New research shows us that hormone therapy actually has a positive effect on blood vessels if initiated early on in the menopause, but not if initiated late,” says Dr Leander. “So there was reason to re-examine whether hormone therapy is linked to the risk of stroke, taking, of course, the time of administering into consideration.” Dr Leander and her colleagues have now analysed data on postmenopausal hormone therapy from five Swedish cohort studies covering a total of 88,914 women, combined with data from national registries on diagnoses and causes of death during a follow-up period. Hormone therapy was not linked to increased risk of stroke (ischemic and hemorrhagic stroke combined) if the therapy was initiated within five years of menopausal onset, regardless of means of administration (oral, via the skin or vaginal), type of therapy (combination or estrogen only), active substance and treatment duration. In sub-analyses, however, there was an observable increase in risk for hemorrhagic stroke (the less common form) if the therapy contained the active substance conjugated equine estrogens. Drugs containing estradiol, on the other hand, were not associated with a higher risk. A higher risk was also seen for both ischemic and hemorrhagic stroke if the treatment was initiated later than five years after the onset of menopause and contained conjugated equine estrogens. “The risk of stroke seems virtually eradicable if treatment commences early, but it’s naturally important to take account of the increase in risk that exists under certain circumstances,” says Dr Leander. “These results provide doctors with a better scientific base on which to take decisions on treatment for menopausal symptoms.”
Karolinska Institutehttps://tinyurl.com/ycqy6tdg
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Continuously recording the brain’s electrical signals and examining how those impulses evolve over time is a more reliable way to identify infants at risk for brain injury, compared with doing snapshot evaluations, according to a prospective cohort study led by Children’s National Health System research-clinicians. Amplitude-integrated electroencephalogram (aEEG) is a bedside tool that involves attaching tiny electrodes to the newborn’s scalp to permit clinicians to monitor the complex electrical activity of the child’s brain over time. It’s a positive sign when an aEEG shows babies beginning to sleep and wake normally by the time they are 3 days old. Conversely, severely abnormal aEEG readings in the first days of life predict poor outcomes. The Children’s team used aEEG with infants born with hypoxic-ischemic encephalopathy (HIE), one of the most severe complications that can affect full-term infants. During pregnancy, birth or shortly after birth, a hypoxic-ischemic event can occur that impedes blood flow and oxygen delivery to the brain, resulting in destruction of brain tissue. Cooling (therapeutic hypothermia) is now standard for newborns with HIE in order to stave off life-long consequences, but deaths and neurodevelopmental disability still can occur. “We know whole-body cooling─or lowering the body’s temperature by about 3 degrees Celsius─can help vulnerable newborns survive and can protect their brains from suffering profound injuries,” says An N. Massaro, M.D., a Children’s National neonatologist and senior author of the study. “What we were trying to determine with this study is whether evaluating the pattern of evolution of the aEEG as a whole provides more information compared with looking at snapshots in time.” Eighty infants undergoing therapeutic cooling who met the inclusion criteria were enrolled in the five-year study, one of the largest such studies to date. The babies weighed more than 1,800 grams and were older than 35 weeks’ gestational age at birth, and either needed prolonged resuscitation after birth or had low APGAR scores─ a measure of how well newborns fare outside the womb. Continuous recordings of EEG data occurred from the time of admission up to 12 hours after the infants temperatures were raised to normal and aEEG tracings were calculated. After the therapeutic cooling blankets were removed, the infants underwent at least one magnetic resonance imaging (MRI) scan prior to discharge. During the routine follow-up check at about 18 months of age, the HIE survivors’ cognitive and motor skills were assessed using validated instruments. Fifty-six of the infants in the study had favourable outcomes. Twenty-four infants had adverse outcomes, including 15 with severe brain injury detected by MRI and nine infants who died. These children had lower APGAR scores at five minutes, and were more likely to have severe HIE and to have experienced more frequent seizures. “Infants whose aEEG abnormalities do not improve were at increased risk: Infants who do not reach a discontinuous background pattern by 15.5 hours of life, achieve cycling by 45.5 hours after birth and who fail to achieve continuous normal voltage by 78 hours after birth are most at risk for adverse outcomes,” Dr. Massaro says. “In addition to defining worrisome trends, we found that overall assessment of continuous aEEG readings through the course of hypothermia treatment provide the most meaningful predictive power. This means we can speak with families at the bedside with more confidence about their child’s outcomes after the infant undergoes cooling therapy.” Children’s National Health System childrensnational.org/news-and-events/childrens-newsroom/2017/continuous-eeg-better-at-identifying-oxygen-deprived-newborns-most-at-risk
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It’s no secret that depression is a commonly reported symptom of the menopause transition. Several small trials have previously suggested that transdermal estradiol therapy (i.e., an estrogen patch) effectivelytreats perimenopausal depression. But this is the first study to examine its effectiveness in preventing the onset of perimenopausal depression among women who were previously not depressed. Estradiol is the primary estrogen (female sex hormone) that is produced during a woman’s reproductive years, impacting reproduction as well as sexual function. A 12-month intervention conducted by Drs. David Rubinow and Susan Girdler and their team at the University of North Carolina at Chapel Hill demonstrated that transdermal estradiol was more effective than placebo in maintaining a more positive mood and in preventing the emergence of clinically significant depression particularly among women in the early menopause transition (as opposed to women in the late menopause transition or postmenopausal period). The effectiveness of treatment on mood was also stronger in women who reported a greater number of stressful events in the six months preceding enrollment. “This study suggests that the stabilization of fluctuating estradiol levels, which are characteristic of the menopause transition, with transdermal estradiol may represent one option for preventing the development of depressive symptoms in the menopause transition,” says Dr. Jennifer Gordon, a lead researcher on the study team from the University of Regina in Saskatchewan, Canada. “An interesting finding in this study is the impact of recent life events, which signals that healthcare providers may need to inquire about such events when determining whether or not to prescribe transdermal estradiol to influence mood in perimenopausal women experiencing depressive symptoms,” says Dr. JoAnn Pinkerton, NAMS executive director.”
The North American Menopause Society www.menopause.org/docs/default-source/default-document-library/transdermal-estradiol-for-depression-10-2-17.pdf
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Doctors are often deluged by signals from charts, test results, and other metrics to keep track of. It can be difficult to integrate and monitor all of these data for multiple patients while making real-time treatment decisions, especially when data is documented inconsistently across hospitals. In a new pair of papers, researchers from MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) explore ways for computers to help doctors make better medical decisions. One team created a machine-learning approach called “ICU Intervene” that takes large amounts of intensive-care-unit (ICU) data, from vitals and labs to notes and demographics, to determine what kinds of treatments are needed for different symptoms. The system uses “deep learning” to make real-time predictions, learning from past ICU cases to make suggestions for critical care, while also explaining the reasoning behind these decisions. “The system could potentially be an aid for doctors in the ICU, which is a high-stress, high-demand environment,” says PhD student Harini Suresh, lead author on the paper about ICU Intervene. “The goal is to leverage data from medical records to improve health care and predict actionable interventions.” Another team developed an approach called “EHR Model Transfer” that can facilitate the application of predictive models on an electronic health record (EHR) system, despite being trained on data from a different EHR system. Specifically, using this approach the team showed that predictive models for mortality and prolonged length of stay can be trained on one EHR system and used to make predictions in another. ICU Intervene was co-developed by Suresh, undergraduate student Nathan Hunt, postdoc Alistair Johnson, researcher Leo Anthony Celi, MIT Professor Peter Szolovits, and PhD student Marzyeh Ghassemi. It was presented this month at the Machine Learning for Healthcare Conference in Boston. EHR Model Transfer was co-developed by lead authors Jen Gong and Tristan Naumann, both PhD students at CSAIL, as well as Szolovits and John Guttag, who is the Dugald C. Jackson Professor in Electrical Engineering. It was presented at the ACM’s Special Interest Group on Knowledge Discovery and Data Mining in Halifax, Canada. Both models were trained using data from the critical care database MIMIC, which includes de-identified data from roughly 40,000 critical care patients and was developed by the MIT Lab for Computational Physiology.
MIT CSAIL www.csail.mit.edu/using_machine_learning_to_improve_patient_care%20
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Sphere Medical, an innovative company in critical care monitoring and diagnostics equipment, announces that its Proxima™ bedside blood gas monitoring system is compatible with Philips IntelliVue Patient Monitoring Systems through the Philips IntelliBridge Interface Module. Sphere Medical’s Proxima is an acute respiratory and metabolic monitoring system used in critical care settings which supports proactive patient care, particularly at critical times. It enables rapid and frequent blood gas, glucose and electrolyte measurements directly at the bedside without the caregiver leaving the patient. Philips compatibility means that Proxima’s results can be recorded and displayed alongside other critical monitoring information, such as blood pressure, ECG, EEG, respiratory rate, cardiac output and temperature. Such consolidated information gives a comprehensive patient overview, enhancing patient management. With the increasing adoption of electronic data record systems in critical care settings, Philips compatibility will also give Proxima customers a very simple means of integrating their data into electronic medical record systems (EMR). Commenting on the additional point-of-care connectivity functionality of the Proxima bedside blood gas analyser, Wolfgang Rencken, CEO of Sphere Medical said, “We are extremely pleased with the confirmation that Proxima is compatible with Philips IntelliVue patient monitors through the Philips IntelliBridge EC10 medical device interfacing module. Many of our customers use Philips monitoring and data management systems and this connectivity further helps the practical implementation of Proxima as an acute respiratory and metabolic monitoring device in critical care settings.”
www.spheremedical.com
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Severe acute liver failure (ALF), a rare but life-threatening illness, is associated with high death rates if patients don’t receive timely treatment or a liver transplant. Unlike the heart or the kidneys, there is no established mechanical device to replace the liver’s function. Now, University of Maryland School of Medicine (UM SOM) researchers report that a device that removes toxins from the blood can also effectively provide a bridge to liver transplantation or buy time for a traumatically injured liver to heal, suggesting broader uses for the device than previously thought. The researchers, present the largest series of cases in the United States in which the Molecular Adsorbent Recirculating System has been used as temporary liver replacement for ALF. MARS can be likened to a dialysis machine for the liver. It essentially “washes” a patient’s blood with a solution containing albumin – normally produced by healthy livers – to remove toxins such as bile acids, ammonia, bilirubin, copper, iron and phenols from the blood. “We’ve found in the use of MARS that we’re able to get trauma patients with massive liver injury to recovery and, in patients who are deemed good transplant candidates, get them to transplant with excellent survivals,” says lead researcher, Steven I. Hanish, MD, associate professor of surgery at UM SOM and a liver transplant surgeon at the University of Maryland Medical Center (UMMC). The US Food and Drug Administration (FDA) has approved the device to clear the liver after overdoses and poisonings, and reduce the effects of brain swelling related to liver failure. However, it is not yet FDA-approved as a bridge to transplant.
University of Maryland School of Medicine http://tinyurl.com/ya32cuxm
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University of Sheffield scientists discover drug used for arthritis could be used to treat blood cancer Every year 3,000 people in the UK are diagnosed with Polycythemia Vera (PV), a type of blood cancer which causes an overproduction of red blood cells. Patients suffer with itching, headaches, weight loss, fatigue and night sweats. Current treatments do not slow the disease progression and provide little relief from symptoms. Dr Martin Zeidler, from the University of Sheffield’s Department of Biomedical Science, working with colleagues from the Department of Haematology at the Royal Hallamshire Hospital, and funded by the Medical Research Council (MRC) have discovered that methotrexate (MTX) – a drug on the World Health Organisation list of essential medicines and commonly used to treat arthritis – works by directly inhibiting the molecular pathway responsible for causing disease. Initial tests were carried out on fruit fly cells to screen for small molecules that modulate JAK/STAT signalling – a signalling pathway whose misregulation is central to the development in humans of Myeloproliferative neoplasms (MPNs), the collective term for progressive blood cancers like PV. Further testing in human cells showed that methotrexate acts as a potent suppressor of JAK/STAT pathway activation – even in cells carrying the mutated gene responsible for MPNs in patients. Dr Martin Zeidler said the latest tests on mice were entirely consistent with the cell-based studies. The tests showed low-dose MTX suppresses JAK/STAT pathway activity and is able to normalise both the raised blood counts and the increase in spleen size associated with the disease in these mice. “We have now shown pretty conclusively that we can use this approach to treat mouse models of human MPNs, results which provide a much more tangible prospect of success in humans,” he said. “Repurposing MTX has the potential to provide a new, molecularly targeted treatment for MPN patients within a budget accessible to healthcare systems throughout the world – a development that may ultimately provide substantial clinical and health economic benefits.” MTX has been used for 35 years to treat inflammatory diseases including rheumatoid arthritis, Crohn’s disease and psoriasis. Even though the mechanisms by which MTX acts in these diseases had not previously been understood, the safety and effectiveness of MTX is well documented and many millions of patients regularly take the drug. Strikingly, diseases such as rheumatoid arthritis all feature inflammatory processes driven by JAK/STAT activity and the effectiveness of MTX in these inflammatory diseases may well be a consequence of its ability to dampen the JAK/STAT pathway.
The University of Sheffield
www.sheffield.ac.uk/news/nr/blood-cancer-athritis-1.720503
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Video laryngoscopy did not improve first-pass orotracheal intubation rates in the intensive care unit (ICU) and was associated with higher rates of life-threatening complications, in a multicentre study in France. “Previous studies have shown conflicting results regarding the systematic use of video laryngoscopy for intubation in the ICU,” Dr. Jean Baptiste Lascarrou of District Hospital Center in La Roche Sur Yon told Reuters Health by email. Part of the reason could be that, in contrast to the operating room, “intubation in the ICU is frequently performed by residents and patients are in acute respiratory and/or circulatory failure.” In 2015 and 2016, Dr. Lascarrou and colleagues at seven ICUs in France randomized 371 adults (mean age, 63; 37% women) to intubation with the McGrath Mac Videolaryngoscope or the Macintosh Laryngoscope. The proportion of patients with successful first-pass intubation did not differ significantly between the groups (67.7% for video versus 70.3% for direct laryngoscopy; P=0.60). Similarly, the proportion of first-attempt intubations performed by non-experts – mainly residents – did not differ between the groups (84.4% with video versus 83.2% with direct laryngoscopy; P=0.76). For video laryngoscopy, first intubation attempts were successful more often when performed by experts (55 of 60 patients, or 91.7%) versus non-experts (201 of 311 patients, or 64.6%; P=0.001) Median time to successful intubation was three minutes for both groups (P=0.95). The proportion of patients with severe life-threatening complications was higher in the video group compared to the direct laryngoscopy group (9.5% versus 2.8%, respectively; P=0.01). No significant between-group difference was found for mild-to-moderate life-threatening complications. Dr. Lascarrou noted that “the frequency of life-threatening complications was relatively low overall compared to older studies, probably due to the systematic application of an intubation protocol that includes pre-oxygenation and neuromuscular blockade use.” Nonetheless, he concluded, “Clinicians have a long way to go before the intubation process is safer in the ICU.” Editorialists Drs. Brian O’Gara and Daniel Talmor, from the Department of Anesthesia, Critical Care, and Pain Medicine at Beth Israel Deaconess Medical Center in Boston, told Reuters Health, “This trial illustrates an important concept in modern medicine. The proliferation and increased availability of sophisticated devices such as the video laryngoscope with proven benefit in limited populations may sometimes lead clinicians to assume that such benefits can be applied to larger patient groups.” “Studies such as (this) are important so that clinicians who may be using such devices can be informed as to their potential benefit or harm in patient groups who are different from the originally intended population,” they said by email.
Medscapehttp://tinyurl.com/y9ddlxov
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