Human blood from donors can be stored for use up to 42 days, and it is a mainstay therapy in transfusion medicine. However, recent studies looking back at patient records have shown that transfusion with older, stored blood is associated with adverse effects.
For severely injured patients who have massive bleeding and receive many transfusion units, older blood was associated with dysfunction in blood flow, increased injury and inflammation in critical end organs, and lung infection.
In a collaborative study using a mouse model, University of Alabama at Birmingham researchers from the departments of Anaesthesiology and Perioperative Medicine, Biostatistics, Emergency Medicine, Pathology, and Surgery have found mechanistic links between older stored red blood cell transfusions and subsequent bacterial pneumonia.
This may reveal new approaches to improve safety of stored red blood cell transfusions.
The key player is free heme, a breakdown product from degraded red blood cells. Heme is part of the oxygen-binding haemoglobin pigment that gives blood cells their red colour and carries oxygen through the body from the lungs. While in the red blood cell, heme is relatively safe; but once outside the confines of the red cells, free heme is toxic and can cause tissue injury. During storage and upon transfusion, stored red blood cells lyse open, releasing free heme.
An adverse role for heme suggests that finding ways to limit heme exposure or prevent heme toxicity may improve safety of stored red blood cell transfusions, say UAB researchers Rakesh Patel, Ph.D., and Jean-Francois Pittet, M.D.
Patel is a professor of pathology and director of the Center for Free Radical Biology, and Pittet is a professor of anesthesiology and perioperative medicine at the UAB School of Medicine.
University of Alabama at Birminghamwww.uab.edu/news/research/item/9221-blood-stored-longer-may-be-less-safe-for-patients-with-massive-blood-loss-and-shock
 

Heart disease is the leading cause of death for both men and women, according to the Centers for Disease Control and Prevention (CDC). In the U.S., one in every four deaths is a result of heart disease, which includes a range of conditions from arrhythmias, or abnormal heart rhythms, to defects, as well as blood vessel diseases, more commonly known as cardiovascular diseases.
Predicting and monitoring cardiovascular disease is often expensive and tenuous, involving high-tech equipment and intrusive procedures. However, a new method developed by researchers at USC Viterbi School of Engineering offers a better way. By coupling a machine learning model with a patient’s pulse data, they are able to measure a key risk factor for cardiovascular diseases and arterial stiffness, using just a smart phone.
Arterial stiffening, in which arteries become less elastic and more rigid, can result in increased blood and pulse pressure. In addition to being a known risk factor for cardiovascular diseases, it is also associated with diseases like diabetes and renal failure.
“If the aorta is stiff, then when it transfers the pulse energy all the way to the peripheral vasculature – to small vessels – it can cause end organ damage. So, if the kidneys are sitting at the end, the kidneys get hurt; if the brain is sitting at the end, the brain gets hurt,” said Niema Pahlevan, assistant professor of aerospace and mechanical engineering and medicine.
By measuring pulse wave velocity, which is the speed that the arterial pulse propagates through the circulatory system, clinicians are able to determine arterial stiffness. Current measurement methods include MRI, which is expensive and often not feasible, or tonometry, which requires two pressure measurements and an electrocardiogram to match the phases of the two pressure waves.
The novel method developed by Pahlevan, Marianne Razavi and Peyman Tavallali uses a single, uncalibrated carotid pressure wave that can be captured with a smart phone’s camera. In a previous study, the team used the same technology to develop an iPhone app that can detect heart failure using the slight perturbations of your pulse beneath your skin to record a pulse wave. In the same fashion, they are able to determine arterial stiffness.
“An uncalibrated, single waveform – that means that you eliminated two steps. That’s how you go from an $18,000 (€15,000)tonometry device and intrusive procedure to an iPhone app,” Pahlevan said.
“It’s very easy to operate,” added Razavi, who is the director of biostatistics for Avicena LLC, the startup company developing the app. “I actually taught my kid to do it.”
Instead of a detailed waveform required with tonometry, their method needs just the shape of a patient’s pulse wave for the mathematical model, called intrinsic frequency, to calculate key variables related to the phases of the patient’s heartbeat. These variables are then used in a machine learning model that determines pulse wave velocity (PWV) and, therefore, arterial stiffness.
To validate their method, they used existing tonometry data collected from the Framingham Heart Study, a long-term epidemiological cohort analysis. Using 5,012 patients, they calculated their own PWV measurements and compared them with the tonometry measurements from the study, finding an 85 percent correlation between the two.
But more importantly, they needed to determine whether their method could be used to predict cardiovascular disease.
“What the clinician wants to know is whether or not you’re helping them to improve outcome,” Pahlevan said. “And we showed that it is as predictive as the actual tonometry.”
Through a prospective study using 4,798 patients, they showed that their PWV measurement was significantly associated with the onset of cardiovascular diseases over a ten-year follow up period. Their study was published in Nature Scientific Reports in January.
 “A lot of people have tried to bring machine learning to medical devices, but pure AI by itself doesn’t work,” Pahlevan said. “When you get a high correlation, you can be missing all of the diseased patients because, in medicine, the outliers are the cases you want to capture – they’re the important ones.”
The reason their machine learning method is able to capture clinically significant outcomes is due to their intrinsic frequency algorithm, which is the mathematical analysis used to calculate physically relevant variables relating to the patient’s heart and vascular function. The main variables represent the heart’s performance during the contraction phase (systole) and the vasculature’s performance during the relaxed phase (diastole).
The method was developed just three years ago during Pahlevan’s postdoctoral work.  The team plans on expanding on the intrinsic frequency algorithm so that it can be applied to a number of other applications, such as detecting silent heart attacks.

USC Viterbi School of Engineeringhttps://tinyurl.com/y74uolb2

The world’s largest randomized controlled trial of acupuncture in emergency departments has found the treatment is a safe and effective alternative to pain-relieving drugs for some patients.
Led by RMIT University, the study found acupuncture was as effective as pain medicine in providing long-term relief for patients who came to emergency in considerable pain.  But the trial, conducted in the emergency departments of four Melbourne hospitals, showed pain management remains a critical issue, with neither treatment providing adequate immediate relief.
Lead investigator Professor Marc Cohen, from RMIT’s School of Health and Biomedical Sciences, said pain was the most common reason people came to emergency, but was often inadequately managed.
“While acupuncture is widely used by practitioners in community settings for treating pain, it is rarely used in hospital emergency departments,” Cohen said.
“Emergency nurses and doctors need a variety of pain-relieving options when treating patients, given the concerns around opioids such as morphine, which carry the risk of addiction when used long-term.
“Our study has shown acupuncture is a viable alternative, and would be especially beneficial for patients who are unable to take standard pain-relieving drugs because of other medical conditions.
“But it’s clear we need more research overall to develop better medical approaches to pain management, as the study also showed patients initially remained in some pain, no matter what treatment they received.”
Patients who identified their level of pain as at least 4 on a 10-point scale randomly received one of three types of treatment: acupuncture alone, acupuncture plus pharmacotherapy or pharmacotherapy alone.
One hour after treatment, less than 40 per cent of patients across all three groups felt any significant pain reduction (2 or more pain points), while more than 80 per cent continued to have a pain rating of at least 4.
But 48 hours later, the vast majority found their treatment acceptable, with 82.8 per cent of acupuncture-only patients saying they would probably or definitely repeat their treatment, compared with 80.8 per cent in the combined group, and 78.2 per cent in the pharmacotherapy-only group.
RMIT Universityhttps://tinyurl.com/yaclex5p

A small clinical trial led by Richard S. Hotchkiss, MD, at Washington University School of Medicine in St. Louis, shows that a drug that revs up the immune system holds promise in treating sepsis. The approach goes against the grain of earlier strategies that have relied on antibiotics and inflammatory medications to tamp down the immune system.
While many people have never heard of sepsis, it causes about 250,000 deaths annually in the United States. The condition develops when an infection triggers an overwhelming immune response, ultimately wreaking havoc on the immune system. Standard treatment involves high doses of antibiotics that fight the infection, but they often don’t work well and fail to boost the body’s immune defences.
Now, a small clinical trial led by researchers at Washington University School of Medicine in St. Louis shows that a drug that revs up the immune system holds promise. The approach goes against the grain of earlier strategies that have relied on antibiotics and inflammatory medications to tamp down the immune system.
 “Mortality rates from sepsis have remained essentially the same over the last 50 years,” said senior investigator Richard S. Hotchkiss, MD, a professor of anaesthesiology, of medicine and of surgery. “Hundreds of drugs have been tried and have failed. It may sound counterintuitive when inflammation is such a problem early in sepsis, but our approach is to stimulate certain immune cells to help the patient’s system take control of the infection.”
The trial involved 27 sepsis patients, ages 33 to 82, who were treated at Barnes-Jewish Hospital in St. Louis, Vanderbilt University Medical Center in Nashville or two medical centers in France — Dupuytren University Hospital in Limoges and Edouard Herriot Hospital in Lyon. Although the study was too small to see a statistical benefit in mortality, the researchers noted an improved immune response in patients who were given a drug to beef up their immunity.
The patients were treated with a drug made of interleukin-7 (IL-7), which enhances the proliferation and survival of two types of immune cells: CD4 and CD8. These cells are important because they recruit other immune cells to fight severe infections that can lead to organ failure and death.
“Patients who develop the most serious form of sepsis, called septic shock, often have very low counts of these key immune cells,” said co-investigator Edward R. Sherwood, MD, PhD, a professor of anaesthesiology at Vanderbilt. “We believe that could play a role in the development and course of sepsis because without those cells, patients aren’t able to clear as much harmful bacteria.”
The patients in the trial, who were hospitalized and severely ill with septic shock, were randomly assigned to one of two therapies. Seventeen patients received the IL-7 drug, and 10 received a standard treatment. Those who received the drug experienced a threefold to fourfold increase in CD4 and CD8 counts.
“Even though the study was small, we were encouraged that IL-7 helped restore key cells in the immune systems of these patients,” said Andrew H. Walton, a staff scientist in the Hotchkiss lab and co-author of the study. “Overall, that should help improve patient survival.”
The researchers showed that IL-7 boosts adaptive immunity, in which CD4 and CD8 T cells help recruit other immune cells — called macrophages, monocytes, neutrophils and dendritic cells — to kill bacteria that cause infections. Traditional approaches to sepsis therapy do not address the critical problem of patients’ severely compromised immune systems. Without restoring immune function, Hotchkiss said, many patients develop lingering infections and are helpless to fight any new infections.
“We know that 40 percent of patients die in the 30- to 90-day period after the initial septic infection,” Hotchkiss said. “Their bodies can’t fight secondary infections, such as the blood infections and staph infections that can develop later on because their immune systems are shot. By strengthening adaptive immunity with IL-7 and increasing the numbers of CD4 and CD8 cells available to help fight infections, we think this approach can make a big difference.”
Hotchkiss credits recent approaches to cancer treatment as evidence that this strategy for sepsis therapy may be a game changer for many patients. Several cancer researchers have begun using IL-7 to rev up a patient’s own immune system to fight cancer. In addition, under compassionate-use guidelines, IL-7 has been given to some critically ill patients with serious viral infections and has successfully restored their CD4 and CD8 counts while improving survival.
As a next step, Hotchkiss and Sherwood are planning a larger trial to determine whether the same holds true for sepsis patients. They estimate a study involving 300 to 400 patients should have the statistical strength to determine whether IL-7 can improve survival rates.
Washington University School of Medicinemedicine.wustl.edu/news/new-way-fight-sepsis-rev-patients-immune-systems

A new kind of MRI component in the shape of a glove delivers the first clear images of bones, tendons and ligaments moving together, a new study finds.
Led by NYU School of Medicine, the study shows how a new MRI element design woven into garment-like detectors can capture high-quality images of moving joints for the first time.
The study authors say their MRI glove prototype promises to become useful in the future diagnosis of repetitive strain injuries like carpal tunnel syndrome in office workers, athletes, and musicians. Because the invention shows how different tissue types impinge on each other as they move, the authors say it could also enable the construction of a more versatile atlas of hand anatomy, guide surgery with hand images in more realistic positions, or aid in the design of better prosthetics.
"Our results represent the first demonstration of an MRI technology that is both flexible and sensitive enough to capture the complexity of soft-tissue mechanics in the hand," says lead author Bei Zhang, PhD, research scientist at the Center for Advanced Imaging Innovation and Research (CAI2R), within the Department of Radiology at NYU Langone Health.
Since its emergence in the 1970s, magnetic resonance imaging (MRI) has given physicians a better look inside tissues, helping to diagnose millions of maladies per year, from brain tumours to internal bleeding to torn ligaments. Despite this impact, the technology has long struggled with a basic limitation.
MRI works by immersing tissues in a magnetic field such that any hydrogen atoms present align to create an average magnetic force in one direction in each tissue slice. These "little magnets" can then be tipped out of equilibrium by waves of electromagnetic force (radio waves). Once tipped, they spin like tops and also emit radio signals, which reveal their positions and can be rebuilt into images.
Also fundamental to MRI is the ability of radiofrequency coils to convert radio waves into a detectable electric current. Unfortunately, this means that the captured ("spinning top") radio waves produce little currents inside receiver coils, which in turn create their own magnetic fields and prevent nearby coils from capturing clean signals.
Over the last 30 years, attempts to manage interactions between neighboring coils have resulted in state-of-the-art MRI scanners in which receiver coils are painstakingly arranged to cancel out magnetic fields in neighbouring coils. Once the best arrangement is set, coils can no longer move relative to one another, constraining the ability of MRI to image complex, moving joints.
 
Solving the Problem
As all current MRI scanners measure signals that create currents in receiver coils (detectors), such coils have always been designed as "low impedance" structures that let the current flow easily. The leap made by the study authors was to design a "high impedance" structure that blocks current, and then measures how hard the force in magnetic waves "pushes" (the voltage) as it attempts to establish a current in the coil.
With no electric current created by the MR signal, the new receiver coils no longer create magnetic fields that interfere with neighbouring receivers, thus removing the need for rigid structures. The researchers found that their system, with the new coils stitched into a cotton glove, generated "exquisite" images of freely moving muscles, tendons and ligaments in a hand as it played piano and grabbed objects.
The MRI signal is produced by hydrogen atoms (protons), and so this technology excels at imaging soft tissue structures rich in water, each molecule of which includes two atoms of hydrogen. For this reason, MRI is great at imaging muscles, nerves, and even cartilage, which are difficult to study using other non-invasive methods. Tendons and ligaments, however, which are made of dense proteins instead of fluid, remain difficult to see independently, because both appear as black bands running alongside bone.
The new study found that, in visualizing fingers as they flexed, the new coils revealed how the black bands moved in concert with the bones, which could help to catalogue differences that come with injury.
"We wanted to try our new elements in an application that could never be done with traditional coils, and settled on an attempt to capture images with a glove," says senior author Martijn Cloos, PhD, assistant professor from the CAI2R institute in the Department of Radiology at NYU Langone Health. "We hope that this result ushers in a new era of MRI design, perhaps including flexible sleeve arrays around injured knees, or comfy beanies to study the developing brains of newborns."

TechXploretechxplore.com/news/2018-05-mri-glove-anatomy.html