Stem cells may help to stay strong in old age
Researchers have found how an unexpectedly high number of mutations in the stem cells of muscles impair cell regeneration.
As we grow older, our muscular function declines. So, according to the researchers, this discovery may result in new medication to build stronger muscles even when in old age.
For the study, published in the journal Nature Communications, researchers investigated the number of mutations that accumulate in the muscle’s stem cells (satellite cells).
“What is most surprising is the high number of mutations. We have seen how a healthy 70-year-old has accumulated more than 1,000 mutations in each stem cell in the muscle, and that these mutations are not random but there are certain regions that are better protected,” said co-author Maria Eriksson, professor at Sweden’s Karolinska Institutet.
The mutations occur during natural cell division, and the regions that are protected are those that are important for the function or survival of the cells. Nonetheless, the researchers were able to identify that this protection declines with age.
“We can demonstrate that this protection diminishes the older you become, indicating an impairment in the cell’s capacity to repair their DNA. And this is something we should be able to influence with new drugs,” said Eriksson.
The study was performed using single stem cells cultivated to provide sufficient DNA for whole genome sequencing.
“We achieved this in the skeletal muscle tissue, which is absolutely unique. We have also found that there is very little overlap of mutations, despite the cells being located close to each other, representing an extremely complex mutational burden,” the researcher noted.
Source: http://indianexpress.com/article/lifestyle/health/stem-cells-may-help-to-stay-strong-in-old-age-5077701/
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Bariatric surgery prolongs lifespan in obese
Obese, middle-age men and women who had bariatric surgery have half the death rate of those who had traditional medical treatment over a 10-year period, reports a study that answers questions about the long-term risk of the surgery.
The study was by Northwestern University Feinberg School of Medicine and the Clalit Research Institute in Israel, which has one of the highest rates of bariatric surgery in the world. It will be published Jan. 16 in JAMA.
“We showed that a long-term effect of bariatric surgery is a longer life for obese patients,” said study co-author Dr. Philip Greenland, professor of preventive medicine at Northwestern University Feinberg School of Medicine. “They had half the death rate, which is significant.”
The rate of death in individuals who did not have surgery was 2.3 percent compared to 1.3 percent in those who had surgery. The study compared 8,385 people who had the surgery (65 percent women and 35 percent men) to 25,155 who did not. In the U.S, the majority of people who have bariatric surgery are women.
The average age of a person in the study was 46 years old with a Body Mass Index (BMI) of 40, the equivalent of being 5 feet 7 inches tall and weighing 265 pounds. BMI is a measure of body fat based on weight in relation to height.
Previous studies looking at this question were indefinite because follow-up data was limited due to high costs and patients dropping out.
In addition, most people in Israel remain with the same HMO throughout their life, allowing researchers to track the same individuals for long periods of time.
The new results illuminate the real-world experience of patients having bariatric surgery. This study, based on electronic health records from an HMO in Israel, looked at detailed data on 33,540 obese individuals for up to a decade.
“Bariatric surgery is an increasingly frequent treatment for severe obesity,” said study co-author Laura Rasmussen-Torvik, an assistant professor of preventive medicine at Feinberg. “It’s highly effective in promoting weight loss but also invasive and can lead to short- and long-term complications. In order for patients and doctors to make the best-informed decisions about what weight loss strategies to pursue, they need to understand the true costs and benefits of the procedures.”
In 2011, 158,000 bariatric surgeries were performed in the U.S. and in 2016, 216,000 were performed, a 37 percent increase.
While the short-term benefits of weight loss surgery — such as weight loss and better control of diabetes and blood pressure — are well known, there is concern about complications from the surgery. Among the concerns are malabsorption of nutrients including vitamin deficiency, anemia and protein deficiency. But there was not a higher rate of anemia, vitamin or protein deficiency among those who had surgery in this study.
The study looked at three types of bariatric surgery compared to the usual care by a primary care physician, which may include dietary counseling and behavior modification. The surgery types included roux-en-Y gastric bypass (creating a pouch at the top of the stomach that limits the amount a person can comfortably eat and bypassing the first part of the small intestine), laparoscopic adjustable gastric banding (restricting the amount of food the stomach can hold with an adjustable band) and sleeve gastrectomy (reducing the size of the stomach).
“Surgery sounds like a radical approach to managing obesity, and a lot of people reject it because it seems like a risky thing to do, but it’s actually less risky to have the surgery,” Greenland said.
Source: https://www.sciencedaily.com/releases/2018/01/180116131257.htm
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Liver Cancer: A new method for identifying splicing biomarkers developed
Turns out, a new method has identified splicing biomarkers for liver cancer. According to a Cold Spring Harbor Laboratory-study, researchers have developed a method for identifying splicing-based biomarkers for the most common form of liver cancer, hepatocellular carcinoma (HCC).
The researchers, led by Professor Adrian Krainer, believed the method will be useful in other cancer types as well. Since, liver cancer is particularly diverse, genetically, and prone to relapse, identifying biomarkers that can predict disease progression is a critical goal in the fight against it.
“This study underscores the potential for learning how RNA splicing variants can contribute to cancer and points to these variants as potential biomarkers for cancer progression,” Krainer said. Splicing refers to a process in which an RNA message copied from information encoded in a gene is edited before it is able to serve as a blueprint for the manufacture of a specific protein.
A gene can give rise to multiple RNA messages, each resulting in a different protein variant, or “isoform.” Many diseases have been associated with errors or variations in the way that RNA is spliced. Errors or variations in splicing can lead to non-functional proteins or proteins with distinct or aberrant functions.
Recent studies have identified splicing irregularities in liver cancer cells. Led by researcher Kuan-Ting Lin, Krainer’s team developed a method that comprehensively analyzes all RNA messages made from a given gene. The team tested their splicing-variant detection method in HCC, by analysing RNA messages in HCC cells sampled from hundreds of patients.
They found that particular splicing isoforms of the gene AFMID correlated with very poor patient survival. These variants lead cells to manufacture truncated versions of the AFMID protein. These unusual versions of the protein are associated with adult liver cancer cells with mutations in tumour-suppressor genes called TP53 and ARID1A.
These mutations, the researchers hypothesised, are associated with low levels of a molecule called NAD+ that is involved in repairing damaged DNA. Restoring missing portions, called exons, to AFMID’s normal RNA message, they proposed, might raise NAD+ to normal levels, avoiding mutations in TP53 and ARID1A.
The team hopes to use small molecules called ASOs (antisense oligonucleotides) that can bind to RNA, to change the way AFMID’s RNA messages are spliced. Krainer’s team previously used this technique to correct errors in the splicing of the gene SMN2 as a way to treat spinal muscular atrophy (SMA).
Fixing AFMID splicing could lead to enhanced production of NAD+ and an increase in DNA repair. “If we can do this, AFMID splicing can become a therapeutic target and the source of a new drug for liver cancer,” Lin said.
Source: https://www.hindustantimes.com/health/liver-cancer-a-new-method-for-identifying-splicing-biomarkers-developed/story-AfcNZSQyt2KGi2BEoWvatM.html
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Be careful: Use of off-label drugs to treat retinal diseases can lead to vision loss
‘Off-label’ drug use is defined as use of a drug that has not cleared the necessary regulatory approval for specific diseases/ conditions and is therefore not an approved drug for the same.
There have been concerns about off-label drug use causing vision loss in the patients. Owing to multiple reports of vision loss and similar adverse events, experts have called out the heightened need for stringent patient safety guidelines to be formalised with immediate effect in India. Most of these adverse effects are being experienced by the patients with retinal diseases across the country, post alleged administration of off-label drug injections.
‘Off-label’ drug use is defined as use of a drug that has not cleared the necessary regulatory approval for specific diseases/ conditions and is therefore not an approved drug for the same. Allegedly, these drugs have not been approved for treating retinal diseases. In the above cases, vial of an off-label drug was prescribed and injected in patients, leading to bacterial infection in the eye. This infection, when left untreated, led to complete vision loss, as observed in these patients.
“Patient safety holds paramount importance in medical practice. Splitting of the same vial of the drug for multiple patients increases the risk of microbial infections and compromises the sterility of the drug. The recent incidents of vision loss experienced by retinal patients across the country were due to use of the same vial of an ‘off-label drug’ for multiple patients”, said Dr Sunandan Sood, Former HOD – Eye Department, Government Medical College and Hospital, Chandigarh. Sood continued, “In order to avoid such practices, policies focused on patient safety must be framed to ensure enforcement of stringent patient safety guidelines in the country”.
Current treatments for retinal diseases like Age-Related Macular Degeneration (AMD) and Diabetes Macular Edema (DME) are known to reduce the level of a protein called Vascular Endothelial Growth Factor (VEGF). This protein is responsible for abnormal blood vessel growth in the retina and macula. The drugs approved for the treatment of AMD and DME are anti-VEGF. Given the availability of efficacious anti-VEGF treatment options in the country, the use of an off-label drug without following proper procedures puts the patient safety at major risk.
Further stressing the adoption of stringent patient safety guidelines in India, Bejon Misra, Founder, Patient Safety and Access Initiative of India Foundation, a (PSM) India Initiative, said, “India is poised to provide a huge opportunity for patients to access quality medicines through the recently announced Pradhan Mantri Aushadi Parak Yojana (PM – APY). It, therefore, becomes crucial for pharmaceutical companies, medical practitioners and regulators to be more responsible towards patient safety and Quality Management Systems (QMS). Patient safety should be kept in mind and monitored judiciously on a drug-by-drug and administration basis and across all disease indications addressed by a particular drug.”
The World Health Organization (WHO) calls patient safety an endemic concern, recognizing that healthcare errors impact 1 in every 10 patients around the world. This number also includes adverse events due to drugs. The need of the hour for the pharma industry in India is to prioritise patient safety in addition to universal access to healthcare.
Source: https://www.hindustantimes.com/health/be-alert-use-of-off-label-drugs-to-treat-retinal-diseases-can-lead-to-vision-loss/story-OpZaU66qBqHkCVj1bNVIwJ.html
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A life-saving device in singapore help end-stage heart failure patients stay fit for a transplant until healthy organ is available
Left Ventricular Assiste Device (LVAD) in singapore help end-stage heart failure patients stay fit for a transplant until healthy organ is available.
It is an implanted mechanical-pump that can mean the difference between life and death for a person whose heart is too weak to effectively pump on its own.
“When there’s a failure in the heart’s left ventricular chamber, the device aims to assist its main function to pump the blood through out the body without any obstruction” said Dr. Lim Chong Hee, a cardiothoracic surgeon at mount elizabeth hospitals in singapore.
restricted supply of oxygenated-blood flow to the body from the heart due to left ventricular failure increase the risks of damaging other organs as well, explained Dr. Lim.
Eventually, this condition may lead to total heart failure or death.
Multple uses of LVAD
An LVAD can be used either as temporary or a permanent solution to sustain the cardiac muscles. Some patients may need it until they fully recover or a heart is available for transplant, while others have to keep it for life.
“The LVAD briefly restores the heart function,which gives time for the body to reverse any organ damages, allowing the patient to go for a transplant in a better shape” explained Dr. Lim.
He also recommended implanting LVAD transitorily to recover from various treatable cardiac conditions, such as viral infections.
“While the patient is undergoing therapy, the LVAD will assist the heart function for a period of time until it significantly improves & is able to effectively do its job, then the LVAD pump can be removed,” he said.
In some cases, terminally ill patients who are ineligible for a heart transplant can permanently use an LVAD, which improves their survival odds.
Some studies have revealed that using a permanent LVAD device doubled the one- year survival rate of the patients with end-stage heart failure if compared with drug treatments alone.
On top of that, LVADs can be implanted in young patients as well.
For example, one of Dr. Lim’s youngest patients was an 11-year-old boy who flew in from malaysia on the verge of losing his life from heart failure. His chances of recovery were very slim until Dr. Lim was able to implant an LVAD. After weeks, he recovered & was able to return home.
However, some patients are too young to receive an LVAD because of their limited chest size, so the device has to be implanted externally, forcing patients to be hospitalised until the pump can be removed.
How the procedure works
The device is attached to left ventricular chamber in order to pump blood to the heart’s main artery known as aorta – through an open heart surgery.
This device will have a small wire that passes through the abdominal wall & is attached to an external computer controller, a batter & another reserve pack.
Dr. Lim explained that the controller provides energy to the device through the wire & is used to maintain the pumping speed in the heart. It also records data to help monitor the device’s behaviour.
Patients are required to wear these external units at all times, sometimes on a belt or harness, outside the body. the bayyery has to be recharged everyday.
“Unfortunately, technology has not advanced yet to the points where all the units of an LVAD can be implanted inside the body,” acknowledged Dr. Lim.
Post-op recovery
A patient’s recovery prospect depends on the individual’s overall health conditions before entring the operating theatre, according to Dr. Lim.
“LVAD mainly protects the heart function, so patients with other health issues like kidney or liver failure face an increased risk of complications & a longer recovery time,” he said.
Most patients are required to stay in the hospital for a minimum of two weeks to recover from the surgery, while being closely monitered for potential health risks associated with the organ failures.
Before leaving the hospital, patients & their caregivers are trained to recognise any circumstances that may pose a concern at home like low blood flow or any signs of infections. Also, both caregivers & patients must learn how to clean the device.
“As you get it, you can do normal activities like driving or light sports,” explained Dr. Lim.
Source: Global Health magazine – Parkway hospitals singapore special edition
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Common knee surgery doesn’t help older adults
Many older adults are getting surgery to remove damaged cartilage in the knee even though these operations may not help ease pain or improve mobility in people over 65, a U.S. study suggests.
Researchers focused on a procedure known as arthroscopic partial meniscectomy, which involves shaving or cutting out damaged or torn tissue. Some previous research suggests younger patients with severely damaged cartilage may benefit from this operation, but it may not work any better than physical therapy for most people, especially when they’re over 65, researchers note in JAMA Surgery.
Despite the lack of benefit, more than 12,000 surgeons performed almost 122,000 of these procedures for patients insured by Medicare, the U.S. health program for people 65 and older, in 2015, the current study found.
“This study shows that it remains extremely common in older patients,” said senior study author Dr. Martin Makary, a surgery professor at Johns Hopkins School of Medicine in Baltimore.
“However, its benefit is limited to a small subset of patients who are usually younger,” Makary said by email.
In addition to the total number of partial meniscectomies, researchers also looked at how often operations involved just this procedure, and not additional work to repair damage to ligaments or cartilage.
Overall, about two-thirds of the operations involved this procedure alone, regardless of whether surgeons did a low or high volume of knee operations, the study found.
Among high-volume surgeons, 13 percent never did additional repair work when they performed arthroscopic partial meniscectomies, while 7 percent never performed this procedure on its own.
While researchers didn’t have data to explain why so many seniors are getting an operation that in all likelihood won’t help them, it’s possible that some doctors and patients aren’t yet aware of several randomized controlled experiments published in recent years showing a lack of benefit, researchers write.
Some surgeons and patients might be aware of this evidence, but disagree about the interpretation of the findings or think that their particular case might be an outlier where the procedure actually helps, the authors also write.
“Despite evidence, there is still a very strong belief by many surgeons and patients that the surgery is effective,” said Jonas Bloch Thorlund, a sports medicine researcher at the University of Southern Denmark who wasn’t involved in the study.
“Indeed, many patients do get better,” Thorlund said by email. “However, this is more likely due to placebo effect, natural remission, or a phenomenon called regression to mean (when people experiencing extreme pain before surgery report only average pain afterwards).”
The study wasn’t a controlled experiment designed to prove whether or how these operations might impact pain or mobility in older adults with knee problems.
Another limitation of the study includes the reliance on procedure codes in Medicare records, and the authors note in some cases patients might have other underlying issues or surgeons might be doing procedures for reasons not highlighted in the records.
Patients with degenerative meniscal tears, which can occur with osteoarthritis, may benefit from physical therapy, weight loss if needed and education on how to move to reduce pain, Thorlund said.
SOURCE: bit.ly/2Hkb5WF JAMA Surgery, online February 28, 2018.
URL: https://in.reuters.com/article/us-health-elderly-knee-surgery/common-knee-surgery-doesnt-help-older-adults-idINKCN1GL2TK
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