AF (atrial fibrillation) is a common cardiac rhythm disturbance that can lead to severe consequences such as stroke and heart failure. AF can be triggered by various stressful conditions and about 30% of patients undergoing cardiac operations suffer from post-operative AF.
Harri Hemilä from the University of Helsinki, Finland, and Timo Suonsyrjä from the Helsinki University Central Hospital, Finland, carried out a systematic review of vitamin C for preventing AF in high risk patients. They identified 14 randomized trials totalling 2006 patients who had undergone cardiac surgery, and one trial with 44 patients that had investigated the recurrence of AF after a successful cardioversion.
There was substantial heterogeneity between the 14 cardiac surgery trials, but the heterogeneity was explained by the division of them between five trials carried out in the USA and nine trials conducted outside of the USA. The five cardiac surgery trials carried out in the USA uniformly found no effect of vitamin C against post-operative AF. In contrast, the nine cardiac surgery trials conducted outside of the USA found a mean reduction of 44% in the incidence of post-operative AF and there was no heterogeneity between these nine trials. Five of the latter trials were carried out in Iran, two in Greece, one in Slovenia and one in Russia.
The single study on the recurrence of AF after a successful cardioversion, which was carried out in Greece, found that vitamin C decreased the risk of AF recurrence by 87%.
In the non-US cardiac surgery trials, vitamin C decreased the length of hospital stay by 12.6% and intensive care unit stay by 8.0%.
Some of the surgery patients in the non-US studies were administered vitamin C orally, whereas in others vitamin C was administered intravenously. The latter route leads to substantially higher levels of vitamin C in the blood, thus the effects of the two administration methods might differ.
Oral administration of vitamin C decreased the occurrence of post-operative AF by 73%, whereas intravenous administration decreased it by 36%. On the other hand, oral administration shortened the length of hospital stay by only 7% (0.4 days), whereas intravenous administration decreased it by 16% (1.5 days). Thus, the effect of intravenous vitamin C administration was greater for the length of hospital stay, but less for the occurrence of post-operative AF.
According to Drs. Hemilä and Suonsyrjä, “Vitamin C is a safe low-cost essential nutrient. Given the consistent evidence from the less wealthy countries, vitamin C might be administered to cardiac surgery patients, although further studies are needed to find out optimal protocols for its administration. However, there seems to be no rationale for further study of unselected patients in wealthy countries, but the effects of vitamin C for patients who have a particularly low documented level of vitamin C might still be worthwhile.”

ScienceDailyhttp://tinyurl.com/ydek9set

Administration of the amino acid D-serine, a dietary supplement, contributes to the improvement of the cognitive and motor capacity of a patient with a mutation that affects glutamate receptors
A translational, multicenter study carried out by research groups of the Bellvitge Biomedical Research Institute (IDIBELL), San Juan de Dios Hospital (HSJD), the University of Barcelona (UB), Clinic Hospital (IDIBAPS), the University of Vic (UVic), Santa Creu i Sant Pau Hospital (IIB Sant Pau) and the thematic area of Rare Diseases (CIBERER), has unveiled the potential of D-serine – a dietary supplement – to improve the neuronal function of a patient with a mutation of the glutamate receptors associated to atypical Rett syndrome with severe encephalopathy. This collaborative study, led by Dr. Xavier Altafaj (Neuropharmacology Unit, IDIBELL), opens a new range of therapeutic options for patients with mutations that affect glutamatergic neurotransmission. Likewise, this study has allowed to establish a unique and novel experimental approach that is currently being transferred to an ambitious project that aims to design predictive algorithms that lead to personalized treatments that can be quickly transferred to the clinical practice for other mutations that affect glutamatergic transmission.
"The story begins about three years ago, when Dr. Ángeles García-Cazorla, a neuropediatrician at San Juan de Dios Hospital and professor at the University of Barcelona, contacted us regarding one of his patients, who presented an atypical form of Rett syndrome with severe encephalopathy”, explains Dr. Xavier Altafaj, leader of the study and member of the Neuropharmacology Unit IDIBELL-UB, led by Dr. Francisco Ciruela. While assessing the exome of this patient,  the geneticists of San Juan de Dios (Dr. Judith Armstrong) identified a mutation that affects the coding gene for a subunit of glutamate receptors of the NMDA type. "Our research group is specialized in the study of these type of receptors, which in physiological conditions are associated with learning processes, memory, neurodevelopment and neuronal plasticity, and which are the main actors in excitatory transmission and neuronal function”, Altafaj adds.
The HSJD medical team and Dr. Altafaj’s group were interested in finding out whether the patient’s mutation could be responsible for for her disability to some extent. To do so, the team of Dr. David Soto (UB-IDIBAPS) carried out several functional studies that allowed them to prove that the mutation drastically reduces the activity of the glutamate channel. With these results, the group of Dr. Altafaj started a second battery of cellular, physiological and biochemical studies with the participation of Dr. Carles Sindreu (UB), Dr. Àlex Bayés (IIB Sant Pau) and Dr. Francisco Ciruela (IDIBELL-UB), to characterize the consequences of the loss of function of mutated receptors.
At the same time, computational studies conducted by Dr. Mireia Olivella (UVic) revealed that the mutation of the glutamate receptor sequence – potentially responsible for the patient’s symptoms – modified the receptor structure, decreasing the size of the canal’s pore and thus its affinity for glutamate, as it was subsequently validated at the experimental level. Glutamate is the main excitatory neurotransmitter of the central nervous system; Consequently, if the channel activity of this receptor is impaired, calcium intake could be reduced, leading to a clear decrease in neuronal function.
"Bearing everything in mind, we had two options," says Dr. Altafaj: "either we spent years designing a personalized drug or therapeutic approach to specifically correct the hypophysiologicality of the affected receptors, or we looked for an existing drug or compound able to increase the functionality of these receptors, forcing their activity and improving calcium intake. We were faced with a time-dependent situation, since neurodevelopmental processes are critical at the patient’s age, and consequently we went for the second option."
In order to be activated, NMDA receptors require the simultaneous presence of glutamate and the amino acids glycine or serine, which act as co-agonists. Knowing that glycine also acts on other types of receptors, IDIBELL researchers proposed to administer D-serine – an already commercialized dietary supplement, easy to administer and without side effects – to improve receptor activation and rebound glutamatergic transmission. In vitro studies in cell lines and primary cultures showed that D-serine supplementation enhanced the activity of mutated receptors. These results led Dr. Ángeles García-Cazorla, with the consent of the patient’s parents, to start a D-serine supplemented diet.
Follow-up of the patient by the Drs. Ángeles García-Cazorla and Anna López (HSJD showed that dietary supplementation with D-serine can be associated with significant improvements in the patient’s symptoms, both at a motor and cognitive level. "The patient is able to develop basic motor tasks that were unthinkable of at the beginning of the treatment, 17 months ago. We could say that the patient is connected to the outside world that surrounds her, and this represents a critical and unavoidable step towards establishing new neuronal connections", Dr. Altafaj describes.
The researchers are cautious but optimistic at the same time: "the results that we observe in the patient after a year and a half are very promising and we hope that she continues to improve, but we must also bear in mind that they are the consequence of a combined effort of several therapeutic interventions. In addition to treatment with D-serine, neuro-stimulation therapies have also been implemented and parents have been able to create a very positive development environment that is also contributing. However, prior experience with similar clinical cases had not shown improvements that significant, and in this sense this study makes us feel very optimistic and encourages us to keep following this direction. "

Bellvitge Biomedical Research Institute (IDIBELL),
www.idibell.cat/modul/news/en/1007/a-personalized-treatment-with-metabolic-therapy-improves-the-motor-and-communication-skills-of-a-patient-with-atypical-rett-syndrome
 

Multiple myeloma is a cancer of the plasma cells, which are white blood cells produced in bone marrow that churn out antibodies to help fight infection. When plasma cells become cancerous, they produce abnormal proteins, and the cells can build up in bone marrow, ultimately seeping into the bloodstream.

The disease is typically diagnosed through a bone marrow biopsy, in which a needle is inserted near a patient’s hip bone to suck out a sample of bone marrow – a painful process for many patients. Clinicians can then isolate and analyse the plasma cells in the bone marrow sample to determine if they are cancerous.
There is currently no way to easily detect plasma cells that have escaped into the bloodstream. Circulating plasma cells are not normally found in healthy people, and the ability to detect these cells in blood could enable doctors to diagnose and track the progression of multiple myeloma.

Now engineers at MIT have devised a microfluidic technique to capture and count circulating plasma cells from small samples of blood. The technique, which relies on conventional blood draws, may provide patients with a less painful test for multiple myeloma.

The group’s technique builds on a microfluidic design that was previously developed by George Whitesides, a professor of chemistry at Harvard University. Whitesides and his colleagues fabricated a small microchip, the channel of which they etched with repeating, V-shaped grooves, similar to a herringbone pattern. The grooves cause any fluid flowing through the microchip to swirl about in eddies, rather passing straight through. The cells within the fluid therefore have a higher chance of making contact with the floor of the device, as first shown by Memhmet Toner at Massachusetts General Hospital.

Researchers including Karnik have since reproduced this microfluidic design, coating the microchip’s floor with certain molecules to attract cells of interest.
In its latest work, Karnik’s team used the microfluidic herringbone design to capture circulating plasma cells. They coated the channels of a microchip, about the size of a glass slide, with CD138, an antibody that is also expressed on the membranes of plasma cells. The team then flowed small, 1-milliliter samples of blood through the device. The herringbone grooves circulated the blood in the microfluidic channels, where the antibodies, acting as tiny Velcro pads, grabbed onto any passing plasma cells while letting the rest of the blood flow out of the device.

Once the cells were isolated in the microchip, the researchers could count the cells, as well determine the kinds of antibodies that each cell secretes.
‘With the ease of a blood draw’
The researchers tested the device using blood samples from healthy donors as well as patients with the disease. After counting the number of cells captured in each sample, they observed very low numbers of circulating plasma cells in healthy samples – about two to five cells per milliliter of blood – versus substantially higher counts in patients diagnosed with multiple myeloma, of about 45 to 184 cells per milliliter.

MIT news.mit.edu/2017/myeloma-patients-biopsies-plasma-cells-blood-bone-marrow-0404

Using computed tomography (CT) to evaluate muscle health may help identify optimal treatments for older patients who fall and break their hips, a new study led by radiologists from UC Davis and Wake Forest Baptist medical centres has found.

The research specifically showed that decreased ‘core’ muscle that stabilizes the spine was associated with decreased survival times following hip fractures.

While CTs of core muscle have been used to predict patient outcomes, the new study is the first to use the imaging technology to link survival with hip fractures, a common cause of injury, hospitalizations and disability among older Americans.

Doctors could potentially use information about muscle loss, known as sarcopenia, to determine a patient’s level of frailty and guide treatment decisions, according to lead author Robert Boutin. A patient with favourable life expectancy, for instance, could be treated for hip fracture with total hip arthroplasty, resulting in lower reoperation rates, better hip function and better quality of life. In contrast, a patient with clinical and imaging features of frailty could benefit most from a simpler surgery.

‘As patients age, it becomes increasingly important to identify the safest and most beneficial orthopaedic treatments, but there currently is no objective way to do this,’ said Boutin, a UC Davis professor of radiology. ‘Using CT scans to evaluate muscles in addition to hip bones can help predict longevity and personalize treatment to a patient’s needs. We’re excited because information on muscle is included on every routine CT scan of the chest, abdomen and pelvis, so the additional evaluations can be done without the costs of additional tests, equipment or software.’

The study included nearly 300 people who were at least 65 years of age and treated for fall-related injuries at UC Davis Medical Center between 2005 and 2015. All were suspected of breaking their hips and received CTs to diagnose or rule out fracture.

The researchers evaluated the CTs with additional measurements of the size and density of lumbar and thoracic muscle alongside the spine. That information was then compared with mortality data from the National Death Index, a centralized database of death record information maintained by the U.S. Centers for Disease Control and Prevention.

The results showed that patients with better core muscle had significantly better survival rates over the duration of the 10-year study.

The study is especially important because most prior research on CTs of muscle has been in cancer patients and involved larger sample sizes, according to senior author Leon Lenchik.

‘The fact that we were able to predict survival in such a small group of non-cancer patients is truly remarkable,’ said Lenchik, professor of radiology at Wake Forest.

The authors hope their work will inspire additional studies of sarcopenia, which is epidemic worldwide, and research focused on improving orthopaedic treatments for older patients.

UC Davis Health www.ucdmc.ucdavis.edu/publish/news/newsroom/12046

MIT and Harvard Medical School researchers have devised a way to image biopsy samples with much higher resolution — an advance that could help doctors develop more accurate and inexpensive diagnostic tests.
For more than 100 years, conventional light microscopes have been vital tools for pathology. However, fine-scale details of cells cannot be seen with these scopes. The new technique relies on an approach known as expansion microscopy, developed originally in Edward Boyden’s lab at MIT, in which the researchers expand a tissue sample to 100 times its original volume before imaging it.
This expansion allows researchers to see features with a conventional light microscope that ordinarily could be seen only with an expensive, high-resolution electron microscope. It also reveals additional molecular information that the electron microscope cannot provide.
“It’s a technique that could have very broad application,” says Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT.
Boyden and his colleagues used this technique to distinguish early-stage breast lesions with high or low risk of progressing to cancer — a task that is challenging for human observers. This approach can also be applied to other diseases: In an analysis of kidney tissue, the researchers found that images of expanded samples revealed signs of kidney disease that can normally only be seen with an electron microscope.
“Using expansion microscopy, we are able to diagnose diseases that were previously impossible to diagnose with a conventional light microscope,” says Octavian Bucur, an instructor at Harvard Medical School, Beth Israel Deaconess Medical Center (BIDMC), and the Ludwig Center at Harvard, and one of the paper’s lead authors.
Boyden’s original expansion microscopy technique is based on embedding tissue samples in a dense, evenly generated polymer that swells when water is added. Before the swelling occurs, the researchers anchor to the polymer gel the molecules that they want to image, and they digest other proteins that normally hold tissue together.
This tissue enlargement allows researchers to obtain images with a resolution of around 70 nanometers, which was previously possible only with very specialized and expensive microscopes.
In the new study, the researchers set out to adapt the expansion process for biopsy tissue samples, which are usually embedded in paraffin wax, flash frozen, or stained with a chemical that makes cellular structures more visible.
The MIT/Harvard team devised a process to convert these samples into a state suitable for expansion. For example, they remove the chemical stain or paraffin by exposing the tissues to a chemical solvent called xylene. Then, they heat up the sample in another chemical called citrate. After that, the tissues go through an expansion process similar to the original version of the technique, but with stronger digestion steps to compensate for the strong chemical fixation of the samples.
During this procedure, the researchers can also add fluorescent labels for molecules of interest, including proteins that mark particular types of cells, or DNA or RNA with a specific sequence.
“The work of Zhao et al. describes a very clever way of extending the resolution of light microscopy to resolve detail beyond that seen with conventional methods,” says David Rimm, a professor of pathology at the Yale University School of Medicine, who was not involved in the research.

MIT
news.mit.edu/2017/microscopy-technique-could-enable-more-informative-biopsies-0717