Paediatric researchers have devised an innovative, safe and minimally invasive procedure that helps relieve rare but potentially life-threatening airway blockages occurring in children who had surgery for congenital heart defects.
The physician-researchers developed new imaging tools and used minimally invasive catheterization techniques to treat plastic bronchitis, a condition in which abnormal circulation causes lymphatic fluid to dry into solid casts that clog a child’s airways.
The study, which describes the pathophysiological mechanism of plastic bronchitis and a treatment approach, arose from collaboration between Maxim Itkin, MD, an associate professor of Radiology in the Perelman School of Medicine at the University of Pennsylvania, and Yoav Dori, MD, a pediatric cardiologist in the Cardiac Center at The Children’s Hospital of Philadelphia (CHOP). They co-lead a specialized team dedicated to the care of lymphatic disorders as part of the Center for Lymphatic Imaging and Interventions at The Children’s Hospital of Philadelphia and the Hospital of the University of Pennsylvania.
‘This is a new treatment option for children with plastic bronchitis and has the potential to offer long-term improvement of this condition,’ said Dori. ‘This procedure may even provide cure and avoid the need for a heart transplant.’
The current study builds on the team’s 2014 article in Pediatrics, the first case report of the successful use of their technique in a patient with plastic bronchitis. ‘We have expanded on that study to report short-term outcomes in a larger group and to share insights into the development of plastic bronchitis, which has been poorly understood,’ said Itkin. In addition to heart patients, children and adults with idiopathic plastic bronchitis, in which the cause is unknown, have also been treated successfully using these techniques.
Itkin and Dori discovered that the primary cause of plastic bronchitis is a lymphatic flow disorder, due to abnormal lymphatic flow into lung tissue. Because physical examinations and conventional imaging may not provide specific findings, lymphatic flow disorders often go undiagnosed.
Over the past several years, Itkin and Dori developed a customized form of magnetic resonance imaging (MRI), called dynamic contrast enhanced MR lymphangiogram, to visualize the anatomy and flow pattern of a patient’s lymphatic system. This technique allows clinicians to locate the site at which lymph leaks into the airways.
Plastic bronchitis may occur in children as a rare complication of early-childhood heart surgeries used for single-ventricle disease, in which one of the heart’s pumping chambers is severely underdeveloped. Approximately 5 percent of children surviving this surgery experience plastic bronchitis because the surgery alters venous and lymphatic pressure. The authors argue that this altered pressure may interact with pre-existing anatomical differences in the patients’ lymphatic vessels.
The abnormal circulation causes lymph to ooze backward into a child’s airways, drying into a caulk-like cast formation that takes the shape of the airways. The first sign of plastic bronchitis may be when a child coughs out the cast. However, if unable to cough it up, a child may suffer fatal asphyxiation.
After identifying the leakage site in a lymphatic vessel, the lymphatic team intervenes, using a technique called lymphatic embolization. Through small catheters, the team blocks the abnormal flow with a variety of tools: coils, iodized oil, and covered stents, based on an individual patient’s needs.
In the current report, the team was able to perform lymphatic embolization in 17 of their 18 patients, ranging from age 2 to age 15 (median age 8.6 years). Fifteen of those 17 patients had significant improvements in cast formation, in some cases being cast-free longer than two years. Patients had transient side effects of abdominal pain and hypotension (low blood pressure), but the authors reported the procedure appeared safe in their patient group.

The Children’s Hospital of Philadelphia http://tinyurl.com/hjr4jps

Computational modelling makes it possible to predict the onset and progression of knee osteoarthritis in overweight people, shows a new study from the University of Eastern Finland. A computational model based on the degradation of the collagen fibril network in the articular cartilage was able to predict the onset and progression of osteoarthritis in overweight people during a four-year follow-up. In normal-weight people, osteoarthritis did not develop within this time span.

The study also developed a model of the knee joint which makes it possible to evaluate the mechanical responses experienced by cartilage cells in healthy and osteoarthritic cartilage during daily activities such as walking. The model demonstrated that both menisectomy and osteoarthritic changes to the cartilage cause significant alterations in cartilage cell responses.

Osteoarthritis is a joint disease estimated to affect around 5% of the total world population. Osteoarthritis is the most common in the knee or hip joint and it often develops as a result of ageing, but it can also develop due to excessive loading or joint injury. In Europe, over 100 million people have arthritis, and in America, direct costs of arthritis were $51.1 billion in 2004. In addition, it has been predicted that the number of patients with knee osteoarthritis increases by 40% by the end of 2050.

Osteoarthritis proceeds gradually, weakening the articular cartilage and ultimately wearing it off completely from the ends of articulating bones. In these cases, the patient suffers from heavy joint pain and the joint becomes stiff, often leading to incapacity for work. Joint replacement surgery is the only effective treatment for osteoarthritis, which is why the prevention of osteoarthritis would be a cost-effective alternative both for the patient and society at large.

The study utilised a computational modelling method integrating the tissue and cellular levels of the articular cartilage in order to analyse the function of the articular cartilage during the onset and progression of osteoarthritis. The method simulated the effect of articular cartilage composition, structure and various loadings on the volume, shape and mechanical responses of cartilage cells.

Compared to healthy cartilage, the cell volume of osteoarthritic cartilage increased as a result of mechanical loading. The modelling indicated that the most important explanatory factors for the cell volume increase were the pericellular fixed charge density, i.e. the number of proteoglycan molecules, and the stiffness of the collagen fibril network.

The study also analysed the effect of menisectomy, a commonly used method in knee surgery, and simulated overweight on cell responses. Both menisectomy and simulated overweight substantially increased fluid pressures in the cell and cartilage tissue during walking, but they did not have an effect on the cell shape or volume in healthy cartilage. In osteoarthritic cartilage, however, cells were compressed and elongated more, probably due to altered cartilage integrity.

During standing, the strains were amplified more in the cell than in pericellullar tissue in healthy joint cartilages, but the opposite was observed in osteoarthritic joint cartilage. It is possible that the pericellular tissue’s function is to protect cartilage cells from sudden changes and to promote cartilage health.

The study also developed computational algorithms for the degradation of the collagen fibril network in the articular cartilage and its reorganisation in order to predict the development and progression of osteoarthritis caused by overweight and cartilage damage. The estimate obtained from the degradation algorithm was well in line with the clinically observed progression of osteoarthritis during a four-year follow-up. Furthermore, the collagen fibril network structure in the mechanically injured cartilage was observed to be disorganised in the vicinity of the injury, suggesting that a cartilage injury exposes cartilage to further damage.

In-depth understanding of the effects of abnormal loading, early osteoarthritis and mechanical injuries on cellular and tissue responses in cartilage makes it possible to develop new strategies for the recognition, prevention and slowing down the progression of the disease. The methods developed in the study may become widespread in specialised health care in the future. However, rigorous clinical validation will be necessary before they can be introduced to clinical use.

University of Eastern Finlandwww.uef.fi/-/computational-modelling-can-predict-onset-and-progression-of-knee-osteoarthritis-in-overweight-people

Early bicycle exercise during their stay in a hospital intensive care unit (ICU) may help some patients recover more quickly.
Researchers at McMaster University and St. Joseph’s Healthcare Hamilton have demonstrated that physiotherapists can safely start in-bed cycling sessions with critically ill, mechanically ventilated patients early on in their ICU stay.
‘People may think that ICU patients are too sick for physical activity, but we know that if patients start in-bed cycling two weeks into their ICU stay, they will walk farther at hospital discharge,’ says the study’s lead author Michelle Kho, an assistant professor with the School of Rehabilitation Science at McMaster University and physiotherapist at St. Joseph’s Healthcare Hamilton.
‘Our TryCYCLE study builds on this previous work and finds it is safe and feasible to systematically start in-bed cycling within the first four days of mechanical ventilation and continue throughout a patient’s ICU stay.’
Patients who survive their ICU stay are at high risk for muscle weakness and disability, and muscle atrophy and weakness starts within days of a patient’s admission to the ICU. Cycling targets the legs, especially the hip flexors, which are most vulnerable to these effects during bed rest.
By strengthening their muscles and overall health, patients may go home sooner, stronger and happier. This not only benefits the patient, but could alleviate the high cost of critical care for the healthcare system. TryCYCLE is the first of a series of studies that will determine the effects of early in-bed cycling with critically ill patients.
Over a year, Kho and her team conducted a study of 33 patients in the ICU at St. Joseph’s Healthcare Hamilton. The special in-bed cycling equipment was provided by the St. Joseph’s Healthcare Foundation.
Patients were 18 years of age or older, receiving mechanical ventilation, and walking independently prior to admission to the ICU. The treatment in the ICU was 30 minutes of supine cycling using a motorized stationary bicycle affixed to the bed, six days a week.
The researchers found that early cycling within the first four days of mechanical ventilation among patients with stable blood flow is safe and feasible. Patients started cycling within the first three days of ICU admission and cycled about 9 km on average during their ICU stay.

McMaster University http://tinyurl.com/h7bqgbv

Researchers from the UCL GOS Institute of Child Health have discovered a new gene change that identifies a type of the movement disorder, muscle dystonia. This new discovery will allow doctors to more easily identify patients who can benefit from treatment so effective that it can restore the ability to walk.
The team from UCL Great Ormond Street Institute of Child Health, along with colleagues at the University of Cambridge and the NIHR Rare Disease Bioresource, identified a change in a gene, called KMT2B, in 28 patients who had dystonia.

Dystonia is one of the most common movement disorders and is thought to affect 70,000 people in the UK. It can cause a wide range of disabling symptoms, including painful muscle spasms and abnormal postures, and can affect walking and speech. In most of the 28 cases, the patients – many of whom were young children who were thought to have a diagnosis of cerebral palsy – were unable to walk.

For some patients, treatment with Deep Brain Stimulation, in which electrical impulses are delivered to a specific area in the brain, either restored or significantly improved independent walking and improved hand and arm movement. In one patient, improvements have been sustained over six years.

Given the findings, the team now suggest that testing for these changes in the gene should form part of standard testing for patients with dystonia. This will allow the most effective treatment to be offered to patients early on.

Dr Manju Kurian, paediatric neurologist at Great Ormond Street Hospital and lead researcher on the paper, says ‘Through DNA sequencing, we have identified a new genetic movement disorder that can be treated with Deep Brain Stimulation. This can dramatically improve the lives of children with the condition and enable them to have a wider range of movement with long-lasting effects,’

‘Remarkably nearly all patients who had Deep Brain Stimulation showed considerable improvements. One patient was able to walk independently within two weeks; in five patients, the improvement has lasted for more than three years. It is an astounding result.’

Former GOSH patient, Dominika, aged 21, was diagnosed with dystonia when she was 13 and had deep brain stimulation treatment two years ago:

When I was young I was able to speak and write normally but I started to have problems with walking when I was about 10. By the time I was 11 or 12, my walking had got worse and I started to notice my writing and speech was deteriorating.
Throughout high school, I had lots of different tests to try and find out what was wrong with me and I first came to GOSH just after my 13th birthday. They gave me lots more tests and told me that I had a type of dystonia which means my muscles aren’t working properly and I can’t move my body as well as I should.

By the time I got to the last year in high school, I was finding walking very difficult and so I started using a wheelchair because it was easier and less painful.

I was given a drug treatment for my dystonia but it didn’t seem to be making things much better so when I was 19, I was offered deep brain stimulation surgery.

Since the operation, life has been good and the surgery has really changed things for me. It has allowed me to walk around mostly unaided. I have seen a big difference with my hands – I can now write and draw, something I wasn’t able to do before. Now, I just do physiotherapy exercises at home to keep my movement as strong as possible. This has meant that I have been able to go to university and I am currently in my final year studying Computer Game Art. I get to practise my drawing using traditional and digital media, and hopefully one day I can get a job doing the two things I love best, drawing and playing video games.

Great Ormond Street Hospital for Children www.gosh.nhs.uk/news/latest-press-releases/2016-press-releases/remarkable-recovery-patients-diagnosed-newly-defined-movement-disorder-0

A unique new imaging method, called ‘polarized nuclear imaging’ – combining powerful aspects of both magnetic resonance imaging and gamma-ray imaging and developed by physicists in the University of Virginia’s departments of Physics and Radiology – has potential for new types of high-resolution medical diagnostics as well as industrial and physics research applications.
‘This method makes possible a truly new, absolutely different class of medical diagnostics,’ said Wilson Miller, who, along with his colleague Gordon Cates, directed the research. ‘We’re combining the advantages of using highly detectable nuclear tracers with the spectral sensitivity and diagnostic power of MRI techniques.’
‘We have demonstrated the feasibility of the new technique by producing a proof-of-principle image in a manner never before accomplished,’ Cates said. ‘In our technique, rather than imaging protons in water, as in MRI, we image a radioactive isotope of xenon that has been polarized using laser techniques.’
Cates and his colleagues believe that the technique, once refined, could provide a new, relatively inexpensive way to visualize the gas space of the lungs by having patients inhale a gas containing the isotopes and using PNI to produce an image. The method likewise might work to image targeted areas of the body by injecting isotopes into the bloodstream. Because the technique would use such small quantities of tracer material, when it comes to medical use, the radioactivity would pose little to no danger to people.
MRI, is effective because it uses a variety of contrast mechanisms to sort out specific characteristics in an image. And highly sensitive gamma-ray detectors can resolve minuscule amounts of radioactive tracer material, key to homing in on points of particular interest.
The new UVA technique uses magnetic resonance to obtain the spatial information, and then collects image information by detecting gamma rays produced by the tracer material – an isotope of xenon Xe-131m, which is a by-product of Iodine 131 (used for treatment of thyroid problems).
‘Unlike MRI, which detects faint radio waves, we detect gamma rays that are emitted from the xenon isotope,’ Cates said. ‘Since it is possible to detect a gamma ray from even a single atom, we gain an enormous increase in imaging sensitivity, and dramatically reduce the amount of material needed for performing magnetic-resonance techniques.’
As an example, had Cates and Miller filled their imaging subject – in this case a small glass cell shaped like the Chinese symbol for the word ‘middle’ – with water rather than the radioactive isotope, they would have needed about 10 billion times more water molecules than the number of isotope atoms they used to achieve the same image quality.
This means that with minute quantities of material, they can achieve detailed imagery using magnetic-resonance techniques that would otherwise be
impossible using a radioactive tracer.
The authors note that considerable work still needs to be done to demonstrate the utility of the new technique in living subjects, but the unique approach ‘represents an exciting new technology.’
To develop it for practical use, the researchers say they would need to increase the size of the detectors or the amounts of tracer material, and they are seeking alternative radioactive isotopes that would retain their polarization once inside a living subject.

University of Virginia http://tinyurl.com/zpobeo7