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 new study from Karolinska Institutet shows that short-course preoperative radiotherapy combined with delayed surgery reduces the adverse side-effects of rectal cancer surgery without compromising its efficacy.

Rectal cancer affects some 2,000 men and women in Sweden every year. Preoperative radiotherapy was gradually introduced in the early 1990s, with a consequent improvement in prognosis for people with rectal cancer and reduction in the risk of local recurrence.

‘Back then we showed that preoperative radiotherapy reduces the risk of local recurrence by over 50 per cent for patients with rectal cancer,’ says principal investigator Anna Martling, senior consultant surgeon and professor at Karolinska Institutet’s Department of Molecular Medicine and Surgery. ‘Thanks to our results, radiotherapy is recommended to many rectal cancer patients.’
However, radiotherapy can cause adverse reactions and the optimal radiotherapeutic method and the interval between it and the ensuing surgery have been mooted.

The study is based on the claim that the adverse effects of rectal cancer treatment can be reduced by administering more but lower doses of radiation for a longer time, or by increasing the interval between radiotherapy and surgery. These hypotheses have now been tested in a study in which rectal cancer patients were randomly assigned to three different treatment arms:

• Standard therapy, i.e. short-course (5×5 Gy) radiotherapy with direct surgery within a week.
• Delayed surgery with short-course (5×5 Gy) radiotherapy followed by surgery after 4-8 weeks.
• Delayed surgery with long-course (25×2 Gy) radiotherapy followed by surgery after 4-8 weeks.

The results of the study show that patients with delayed surgery develop fewer complications with equally good oncological outcomes. It also showed that there is no difference between long-course and short-course radiotherapy other than that the former considerably lengthens the time for treatment.
Improved therapeutic strategies
‘The results of the study will give rise to improved therapeutic strategies, fewer complications with a sustained low incidence of local recurrence, and better survival rates for rectal cancer patients,’ says Professor Martling. ‘The results can now be immediately put to clinical use to the considerable benefit of the patients.’

Karolinska Institute ki.se/en/news/new-method-reduces-adverse-effects-of-rectal-cancer-treatment

Full thickness skin grafts are the golden standard for treating burn wounds. But most skin grafts for severe burns require a donor, and for large or complicated injury sites, a full thickness skin graft is hard to come by. Split thickness skin grafts that use tissue from the patient may be a solution-but not by themselves.

By combining the graft technique with a specially engineered sheet of stem cells, researchers from Michigan Tech and the First Affiliated Hospital of Sun Yat-sen University in Guangzhou, China demonstrate an improved skin graft process. Their work focuses on creating engineered tissue that maximizes a body’s natural healing power.

Veins, arteries and capillaries move oxygen and nutrients to tissue and the lymphatic system removes waste-vascularized tissue is crosscut with many of these tiny tubes. Healing burn wounds then is not only about re-growing skin, but also about making sure these vascular systems are hooked up. The more vasculature, the more healing can happen.

Feng Zhao, an associate professor of biomedical engineering at Michigan Tech, works on creating engineered tissues that are pre-vascularized. In other words, the tissue gets a head start on the healing process. This is key when coupling the technology with split thickness skin grafts, or STSG for short.

‘STSG can be used under unfavourable conditions, such as a recipient’s wound having moderate infection or less vasculature, where full thickness skin grafts would fail,’ Zhao says. ‘However, STSG are more fragile than full thickness skin grafts and can contract significantly during the healing process.’

To help prevent graft contraction and encourage early vascularization to improve wound repair, Zhao and her team turned to the most basic of cells.

Stem cells are unique because of their potential. Unlike neurons in a brain or beta cells in a liver, stem cells lack a defining cellular purpose. In terms of healing, this means they can adapt to their surroundings; when modified to increase vascularization, they can do wonders.

The team’s transplantation in a rat model showed promising results. Not only did the implantations show less contracted and puckered skin, but also less cellular inflammation and a thinner outer skin (epidermal) thickness along with more robust blood micro-circulation in the skin tissue. The combined STSG and stem cell sheet grafts also preserved features like hair follicles and sebaceous glands that secrete a lubricating oil for skin and hair.

The team attributes the success to the vascularized stem cell sheet’s elevated levels of growth factors and proteins called cytokines used in healing tissue.

‘The engineered stem cell sheet will overcome the limitation of current treatments for extensive and severe wounds, such as for acute burn injuries,’ Zhao says, ‘and significantly improve the quality of life for patients suffering from burns.’

Michigan Technological University www.mtu.edu/news/stories/2016/october/skin-graft-for-bad-burns.html

During heart surgery, it is sometimes necessary to temporarily stop cardiac activity, a process known as cardioplegia. Specific myocardial protection techniques are necessary for pediatric use. At the 96th AATS Annual Meeting, cardiac surgeons present the results of a prospective, randomized trial of pediatric heart surgery patients that shows that the del Nido cardioplegia solution, a new, longacting agent, offers significant advantages over conventional cardioplegia, including reduced cardiopulmonary bypass and aortic cross-clamp times and faster onset of action. ‘Overall, del Nido cardioplegic solution is a simple and safe cardioprotective strategy. Cardiac performance is satisfactory in the postoperative period with a better cardiac index profile, lesser troponin-I release, and decreased morbidity,’ explained Sachin Talwar, MCh, of the Department of Cardiothoracic and Vascular Surgery at the All India Institute of Medical Sciences (New Delhi, India).
The del Nido solution was first proposed by researchers at the University of Pittsburgh in 1990. It offers several advantages, including prolonged action with
single dose administration, which helps to avoid the harmful effects of dose repetition.
It also contains lidocaine to slow down energy consumption and calciumcompeting ions like magnesium to prevent damaging intracellular build-up of calcium. In practice, it can be given as a single dose through the aortic root. In comparison, the conventional method of cardioplegia tested was St. Thomas cold blood cardioplegia. This requires an initial dose of solution, followed by repeated dosing at 25-30 minute intervals during surgery.
In the first study of its kind, the investigators randomized 100 pediatric patients
younger than 12 years old to del Nido and cold blood cardioplegia (STH) groups.
The patients underwent elective repair of ventricular septal defects and tetralogy of Fallot between August 2014 and July 2015. Intraoperative parameters and postoperative events were recorded. Cardiac index was calculated at four different time points, while troponin-I, interleukin-6, and tissue necrosis factor-alpha were estimated. The right ventricle was biopsied in order to examine the ultra-structural changes using electron microscopy.
The del Nido group had significantly shorter mean cardiopulmonary bypass
time (67 min vs. 78 min) and mean aortic cross-clamp time (40 min vs. 48 min)
than the STH group, respectively. ‘This is very important because long aortic crossclamp time is an independent risk factor for increased duration of mechanical ventilation, high incidence of low cardiac output syndrome, renal complications, and immediate post-operative mortality,’ commented Dr. Talwar.
The total amount of cardioplegia given was significantly higher in STH group
(673 mL), compared with the del Nido group (372 mL), according to Dr. Talwar.
Overall, the postoperative course was better in the del Nido group with shorter
mechanical ventilatory time and ICU stay, faster recovery of cardiac index,
and less need for inotropic support. The researchers biopsied the heart muscle to see if there were microscopic effects of the different cardioplegia agents. Ultrastructural study of myocardium showed no statistically significant difference in data obtained for nuclear changes, mitochondrial changes, sarcoplasmic reticulum, and glycogen depletion. Myofibrillar disarray was significantly more evident in the STH group, while cellular edema was significantly greater in the del Nido group.

American Association for Thoracic Surgery http://tinyurl.com/jcqsqvd

Intensive Care Units (ICUs), which provide the most expensive and invasive forms of care in a hospital setting, are being used too often for patients who don’t need that level of care, according to a new study by LA BioMed and UCLA researchers .
The researchers studied 808 ICU admissions from July 1, 2015 to June 15, 2016 at Harbor-UCLA Medical Center and found that more than half the patients could have been cared for in less expensive and invasive settings.
Of the patients in the study, 23.4percent were in need of close monitoring but not ICU-level care. Another 20.9percent of the patients were critically ill but unlikely to recover because they had underlying illnesses or severity of acute illness. For another 8percent, death was imminent or the same outcomes were expected in non-ICU care.
‘Our study found over 50percent of patients admitted to the ICU were categorized into groups suggesting that they were potentially either too well or too sick to benefit from ICU care or could have received equivalent care in non-ICU settings,’ said Dong W. Chang, MD, an LA BioMed researcher and the corresponding author for the study. ‘This research indicates that ICU care is inefficient because it is devoting substantial resources to patients who are less likely to benefit from this level of care. These findings are a concern for patients, providers and the healthcare system because ICU care is frequently invasive and comes at a substantial cost.’
The researchers added up the number of days each of the patients in the study spent in ICU and found nearly 65percent of the total number of days those patients spent in ICU were allocated to care that was considered discretionary monitoring, had a low likelihood of benefit despite critical illness or would have been manageable in non-ICU settings.
‘While this is a study of just one hospital and results may differ at other medical centres, we suspect that these characteristics of ICU utilization are commonplace and prevalent in many institutions,’ said Dr. Chang.
The researchers also noted that in other hospitals, the ICU may be the most appropriate level of care because the hospitals don’t have appropriate levels of care for those patients outside the ICU.
‘However, there is likely to be a subset of patients in which ICU care leads to unwanted, invasive care without significant clinical benefit,’ said Dr. Chang. ‘Refining our ability to identify these patients and developing approaches to improve ICU utilization for those patients are important steps to assure the best care for patients and the most efficient use of the healthcare system’s limited resources.’

LA BioMed http://tinyurl.com/ztppu5j