The heart is capable of terminating arrhythmias itself after local gene therapy, potentially avoiding the need for patients to undergo painful electric shocks, according to a proof-of-concept study.
Atrial fibrillation is the most common heart rhythm disorder (arrhythmia). Treatment aims to restore the heart’s normal rhythm and includes drugs, which are not effective in all patients, ablation, for which efficiency remains suboptimal in the long-term, and electric shocks, which are effective but painful and require hospitalization. This leaves a large and growing group of patients without optimal treatment options.
That is why study author Dr Emile Nyns, a physician and PhD candidate in the laboratory of Daniël Pijnappels at the Leiden University Medical Centre, Leiden, the Netherlands, took a completely different approach. He said: “As the heart itself is already electrically active, we tested whether and how it could generate the electrical current needed for arrhythmia termination.”
The researchers used a technique called optogenetics, which uses light to control functioning of cells that have been genetically modified to express light-sensitive ion channels.
First they genetically modified the right atrium in eight adult rats using a process called gene painting, which involves a small thoracic incision and actually painting the atrium with vectors coding for these ion channels.
The researchers waited four to six weeks for the light-sensitive ion channels to be expressed, then made a small incision in the thorax of each rat and induced atrial fibrillation. Next they shone a light on the atrium for one second. This terminated 94% of atrial fibrillation.
Dr Nyns said: “Shining light on the atrium opened the light-sensitive ion channels. This led to depolarization of the atrium, which terminated atrial fibrillation and restored the heart’s normal rhythm. We only needed a single light pulse of one second to terminate nearly all arrhythmias.
“The heart itself generated the electrical current needed to stop the arrhythmias,” he continued. “It is completely pain free, unlike electric shocks.”
He said: “Our study provides proof-of-concept that the heart can be enabled to terminate atrial fibrillation by itself after optogenetic gene therapy.”
In future Dr Nyns envisages that the technique could be used in atrial fibrillation patients together with an implantable light-emitting diode (LED) device. “The result would be continuous, ambulatory and pain-free maintenance of the heart’s normal rhythm, something that cannot be achieved today,” he said. “The quality of life and prognosis of AF patients could be significantly increased, especially for patients with frequent episodes of drug refractory, symptomatic atrial fibrillation, despite ablation therapy.”
The researchers did not observe adverse effects from the method, but Dr Nyns said: “Further research is certainly needed before this technique can be used in patients. However, the results are promising and we believe that the time has come to develop the next generation of therapy for cardiac arrhythmias, which do not rely on pills or electronics, but on biology instead.”

ScienceDailyhttps://tinyurl.com/yc4atkg8

The ability to quantify the extent of kidney damage and predict the life remaining in the kidney, using an image obtained at the time when a patient visits the hospital for a kidney biopsy, now is possible using a computer model based on artificial intelligence (AI).
The findings can help make predictions at the point-of-care and assist clinical decision-making.
Nephropathology is a specialization that analyses kidney biopsy images. While large clinical centres in the U.S. might greatly benefit from having ‘in-house’ nephropathologists, this is not the case in most parts of the country or around the world.
According to the researchers, the application of machine learning frameworks, such as convolutional neural networks (CNN) for object recognition tasks, is proving to be valuable for classification of diseases as well as reliable for the analysis of radiology images including malignancies.
To test the feasibility of applying this technology to the analysis of routinely-obtained kidney biopsies, the researchers performed a proof of principle study on kidney biopsy sections with various amounts of kidney fibrosis (also commonly known as scarring of tissue). The machine learning framework based on CNN relied on pixel density of digitized images, while the severity of disease was determined by several clinical laboratory measures and renal survival. CNN model performance then was compared with that of the models generated using the amount of fibrosis reported by a nephropathologist as the sole input and corresponding lab measures and renal survival as the outputs. For all scenarios, CNN models outperformed the other models.
“While the trained eyes of expert pathologists are able to gauge the severity of disease and detect nuances of kidney damage with remarkable accuracy, such expertise is not available in all locations, especially at a global level. Moreover, there is an urgent need to standardize the quantification of kidney disease severity such that the efficacy of therapies established in clinical trials can be applied to treat patients with equally severe disease in routine practice,” explained corresponding author Vijaya B. Kolachalama, PhD, assistant professor of medicine at Boston University School of Medicine. “When implemented in the clinical setting, our work will allow pathologists to see things early and obtain insights that were not previously available,” said Kolachalama.
The researchers believe their model has both diagnostic and prognostic applications and may lead to the development of a software application for diagnosing kidney disease and predicting kidney survival. “If healthcare providers around the world can have the ability to classify kidney biopsy images with the accuracy of a nephropathologist right at the point-of-care, then this can significantly impact renal practice. In essence, our model has the potential to act as a surrogate nephropathologist, especially in resource-limited settings,” said Kolachalama.
Boston University School of Medicinehttps://tinyurl.com/y7p83anb

NUST MISIS scientists jointly with their colleagues from the Ecole de Technologie Superiore (Montreal, Canada) have experienced a new combination of alloy processing that produces solid and durable implants that are fully compatible with the human body.
The authors sought to develop an industrial technology for the production of metal rod stocks which are used in the production of modern bone implants, and in particular, for treatment of spinal problems.
This new generation of alloys made on the basis of Ti-Zr-Nb (titanium-zirconium-niobium) which possesses a high functional complex and so-called “superelasticity” (able to restore the original shape against large and repeated deformation) are the working material.
According to scientists, these alloys are the most promising class of metallic biomaterials. This is due to the unique combination of their biochemical and biomechanical properties: Ti-Zr-Nb differs from the complete biocompatibility of composition and high corrosion resistance, while at the same time exhibiting hyperelastic behaviour — very similar to “normal” bone behaviour.
“Our method of combined thermomechanical processing of alloys — in particular, radial-displacement rolling and rotary forging — allows researchers to get the highest quality blanks for biocompatible implants by controlling their structure and properties. Such processing of blanks gives them an outstanding resistance to fatigue and overall functional stability”, said Vadim Sheremetyev, one of research authors, and a senior research associate at NUST MISIS.
According to him, the high-quality rod stocks have already found a potential customer. A large Russian manufacturer of medical products made of titanium is an industrial partner of NUST MISIS`s project. Together with them, scientists are now developing a technology to obtain beams for spinal transpedicular fixation, which should improve the therapy quality in severe cases of scoliosis.
Additionally, scientists are now aimed at developing the thermomechanical processing and optimizing technology modes to obtain materials of the necessary form and sizes with the best complexity of properties.
NUST MISISen.misis.ru/university/news/science/2018-03/5281/

A population heath study from the Regenstrief Institute and Indiana University Center for Aging Research has determined that haloperidol, the drug most commonly used to treat delirium in hospital medical and surgical intensive care units (ICUs), did not benefit elective thoracic surgery ICU patients when given prophylactically, with the possible exception of those who have had surgery to remove their oesophagus. The study results indicate the need for a personalized approach to delirium in the ICU.
The work is the first to evaluate the use of the antipsychotic drug haloperidol to reduce post-operative delirium in elderly patients undergoing elective non-cardiac thoracic surgery.
Researchers found no differences in delirium incidence or severity between haloperidol and placebo in patients who had undergone elective non-cardiac thoracic surgery except in the small number of study participants who were admitted to the ICU after removal of the oesophagus, a procedure known as oesophagectomy. Removal of this organ is a treatment for oesophageal cancer.
“Our work suggests that just as you can’t lump all cancer patients together for treatment, you can’t put all delirium patients in the same bucket,” said Regenstrief Institute investigator Babar A, Khan, M.D., M.S., who led the new study. “We need a personalized approach to delirium, focusing on people at higher risk of developing this complication.”
He notes that while elective surgery patients typically are healthier than other ICU patients, they are very much at risk of delirium. He counsels those considering elective surgery to consult with their primary care clinicians and their surgeon to weigh the significant risks of delirium with the benefits of the proposed procedure.
“Because we now know that haloperidol, the most commonly used drug to treat ICU delirium doesn’t, with possibly few exceptions, work, we need to focus on non-pharmacological therapies and vigilantly curtail administration of drugs that are harmful to the brain, especially the aging brain,” said Dr. Khan.
Approximately five million Americans are admitted to a surgical or medical ICU annually. Delirium, a sudden and serious change in brain function causing confusion, occurs in as many as three quarters of those treated in the ICU. Causes include sepsis, metabolic problems such as liver and kidney disease as well as drugs that injure the brain.
Individuals who experience delirium are more likely to have longer hospital stays and hospital-associated complications. They also have a greater likelihood of dying in the hospital for up to a year after their hospital stay than ICU patients who did not experience delirium. They are also more likely to lose physical functioning and experience cognitive impairment.

Regenstrief Institute
www.regenstrief.org/article/icu-acquired-delirium-requires-personalized-approach/

Patients who survive acute respiratory distress syndrome (ARDS) often leave a hospital intensive care unit with debilitating mental, physical, or cognitive problems that may limit their quality of life.
Now, a new study of 645 ARDS survivors by researchers at Intermountain Medical Center, Johns Hopkins University, and the University of Utah, has identified subgroups of ARDS survivors who suffer what’s been called post-intensive care syndrome, a collection of symptoms that can linger for years.
ARDS is a potentially life-threatening injury to the lungs that occurs most often in an intensive care unit among critically-ill patients with pneumonia or other infections, although it can have other causes.
For many ARDS patients, the primary symptom is shortness of breath so severe they require lung life-support therapies in order to breathe. ARDS can kill, and older patients are especially vulnerable.
Many ARDS survivors leave the hospital with an array of challenges that form post-intensive care syndrome. The survivors may live with long-term effects, including permanent lung damage and different degrees of physical, cognitive, and mental health problems.
During the last quarter-century, the symptoms of post-intensive care syndrome have been increasingly recognized and understood. Critical care specialists say between half and two-thirds of ARDS survivors struggle with it after they’re released from the hospital.
To that end, researchers at Intermountain Medical Center and Johns Hopkins University have been seeking common threads among survivors, focusing on combinations of impairments, including physical health, mental health, and brain function. The study builds on previous research by the team.
Researchers say the threads within survivor subgroups may help them better identify factors that increase risk, and could potentially lead to tailored treatments to bolster patients’ recovery.
In the study of ARDS survivors six months out of intensive care, the researchers found four different patient subgroups:

• those with mildly impaired physical and mental health (22% of patients)
• those with moderately impaired physical and mental health (39%)
• those with severely impaired physical health and moderately impaired mental health (15%)
• those with severe physical and mental health impairments (24%).

According to the research, physical and psychological injuries tend to go hand in hand. Cognitive impairment is independent of those two, however.
The study found people who have worse physical problems have worse symptoms of anxiety, depression, or post-traumatic stress disorder. The one exception was a small but distinct group (15% of all survivors) who had severe physical limitations, but only moderately severe mental health problems.
Researchers speculate that could mean those individuals already had some chronic physical challenges before developing ARDS and were more accustomed to living with physical limitations.
“It’s also possible that group might have more resilience, so they’re better able to respond to the new physical disability, which is consistent with other recent studies suggesting that improving resilience may help ARDS survivors,” Dr. Brown said.
The study noted that six months after leaving intensive care, about half of the subjects in the study still weren’t living independently, even though 91 percent of them had done so prior to contracting ARDS. Instead, they lived in nursing homes or with relatives.

Intermountain Healthcarehttps://tinyurl.com/ycfcnl8s