The failure of drugs such as SSRIs, used to treat depression, can be a result of genetic variations in patients. Variations within the gene that encodes the CYP2C19 enzyme results in extreme differences in the levels of escitalopram achieved in patients. Prescribing the dose of escitalopram based on a patient’s specific genetic constitution would greatly improve therapeutic outcomes. The study was conducted at Karolinska Institutet in association with researchers at Diakonhjemmet Hospital in Oslo.
Pharmaceutical treatment of depression commonly makes use of selective serotonin reuptake inhibitors (SSRIs) of which escitalopram is the most frequently administered clinically. However, escitalopram therapy is currently limited by the fact that some patients do not respond well to the drug, while others develop adverse reactions requiring discontinuation of treatment.
In order to individualise drug therapy, researchers are attempting to establish genetic biomarkers that can predict an individual’s response to drugs. In a recent study, it was discovered that variation in the gene encoding the enzyme responsible for escitalopram metabolism (CYP2C19) is very important in this respect. Individuals with a variant of the gene promoting increased enzyme expression had blood levels of escitalopram too low to impact the depression symptoms, whereas patients with a defective CYP2C19 gene reached drug levels which were too high. Overall, one third of the 2,087 study participants achieved escitalopram blood levels that were either too high or too low.
Interestingly, the researchers found that 30 per cent of the patients carrying gene variants causing excessive or inadequate enzyme levels switched to other drugs within one year, in contrast with only 10 to 12 per cent of patients carrying the common gene.
“Our study shows that genotyping of CYP2C19 could be of considerable clinical value in individualising doses of escitalopram so that a better all-round antidepressive effect could be achieved for the patients,” says Professor Magnus Ingelman-Sundberg at Karolinska Institutet’s Department of Physiology and Pharmacology who led the study together with Professor Espen Molden. “Because CYP2C19 is involved in the metabolism of many different SSRIs, the finding is also applicable to other types of antidepressants.”
Karolinska Instituteki.se/en/news/genetic-analysis-can-improve-depression-therapy

A blood test that measures the presence of heart-specific proteins called troponins is used by emergency clinics to diagnose myocardial infarction in patients with chest pain. For the past few years a newer laboratory method has been used at most hospitals in Sweden that is ten times more sensitive than the conventional troponin test. The high-sensitivity troponin test can discover heart attacks earlier so that treatment can commence, which is thought to improve the patients’ prognosis.
"But there is a lack of larger studies examining whether the high-sensitivity troponin test is of any significance for patients with newly diagnosed myocardial infarction in terms of survival or the risk of another heart attack," says study leader Dr. Martin Holzmann, associate professor of epidemiology at Karolinska Institutet’s Department of Medicine in Solna and physician at Karolinska University Hospital.
The study included all patients in Sweden who had had their first heart attack between 2009 and 2013. This gave a study population of almost 88,000 patients, 40,000 of whom had been diagnosed using the high-sensitivity troponin test and just over 47,000 using the conventional troponin test.
The researchers found that five per cent more myocardial infarctions were being diagnosed in hospitals that used the high-sensitivity troponin test. A year after the heart attack was registered there was no difference in mortality between the two groups, although the number of new heart attacks was lower in the group that had been diagnosed using the high-sensitivity troponin test.
"This surprised us," says Dr. Holzmann. "We didn’t think that the more sensitive test would affect the risk of future heart attacks."
The use of coronary angiography and balloon angioplasty was 16 and 13 per cent more common, respectively in the patients diagnosed with the high-sensitivity troponin test. In the USA, where the new test was not approved until 2017, there are fears that the more sensitive methods can entail a large increase in the number of examinations with no benefit to the patients.
"The increase we observed in our study was less than expected, which means that the high-sensitivity troponin test has enabled doctors to single out the patients who benefit from such intervention. We found no differences in medication between the two groups, so the differences in prognosis with fewer new heart attacks could be attributed to the fact that more coronary angiography and balloon dilation procedures have been performed on the right patients," says Dr. Holzmann, who also believes that the study supports the idea that the handful of hospitals in Sweden that still do not use the high-sensitivity troponin test should start to do so.

MedicalXpress
medicalxpress.com/news/2018-06-high-sensitivity-troponin-future-heart.html

EKF Diagnostics announces that its Stanbio Chemistry Procalcitonin (PCT) LiquiColor® assay has been FDA cleared and validated for use on Beckman AU 480, 680 and 5800 clinical chemistry analysers.  EKF is pleased to confirm the immediate availability of a user-defined application (UDA) for running this 10-minute test for bacterial infection and sepsis on these Beckman AU analysers.
PCT is a widely accepted marker for use in conjunction with other tests to quickly identify sepsis and monitor progression/severity over time. EKF’s PCT test is designed to be used on an open channel of most main brand clinical chemistry analysers, including Roche Cobas, Abbott Architect and Hitachi systems. Therefore, the availability of the user-defined  application (UDA) on Beckman AU analysers further increases the breadth of application of the LiquiColor PCT assay.   
Trevor McCarthy, Sales Manager, EKF Central Laboratory Products, EMEA/APAC said, “The news regarding the FDA clearance and Beckman AU analyser validated application for the PCT LiquiColor assay will bolster trust in the quality and reliability of our product.  Having EKF’s PCT assay validated on Beckman AU chemistry analysers allows us to provide a competitive alternative product for hospital labs and should open up new markets and opportunities for us to support improved and early detection of sepsis.”
The cost-effective, immunoturbidimetric assay, which features the use of monoclonal antibodies coated to latex particles, can determine PCT from just 20µL of serum and plasma specimens. Conveniently, the reagent set requires no reagent preparation and is designed to be used on open chemistry systems. It is available in a liquid-stable format, meaning that it can remain on-board a clinical chemistry analyser for up to four weeks.
PCT is a quick and effective adjunct marker in sepsis diagnosis which helps to differentiate between viral and bacterial infections, so enabling early administration of antimicrobial therapy. It is an important test, as the Surviving Sepsis Campaign (SSC) estimates that the incidence of sepsis is 3 per 1,000 worldwide. There has been a steady rise in the number of patients with sepsis; globally there are now over 18 million cases per year. Due to its high mortality, sepsis is a primary cause of death, accounting for over 60% of deaths per year in the developing world. It kills over 6 million new-borns and children each year and there are over 100,000 cases of maternal sepsis.
In addition to improving sepsis survival rates and improving antibiotic stewardship, studies have also shown that PCT testing reduces hospital costs and length of stay. For example, a recent large cohort study examined whether PCT testing helps to more effectively manage sepsis care. The study found that use of PCT testing on day one of admission into the ICU lead to an average of 1.2 fewer hospital days than patients who were not screened and saved an average of $2,759 (€2,337) on their total hospital costs. www.ekfdiagnostics.com

A discovery sheds light on how cancerous cells differ from healthy ones, and could lead to the development of new strategies for therapeutic intervention for difficult-to-treat cancers in the future.
An international team of investigators found a “stop sign”—a modified protein researchers named a PIP-stop—inside cells that are overused by cancerous cells that effectively prevents healthy ones from sorting material in the way they were designed to.
“We have discovered that breast cancer, leukaemia, lymphoma and neuroblastoma cells have too many PIP-stops. This would upset protein function, and opens up a new avenue for developing drugs that block PIP-stop formation by kinase enzymes,” said Michael Overduin, a University of Alberta cancer researcher and professor of biochemistry, who led the research project.
The team named the modification a PIP-stop because it stops proteins from interacting with lipid molecules called PIP.
Before making their discovery, the researchers first solved the 3-D structure of a sorting nexin protein, which is key to sorting proteins to their proper locations within the cell. Powerful magnets in the U.K. and in the National High Field Nuclear Magnetic Resonance Centre (NANUC), Canada’s national magnet lab based in Edmonton, were then used to detect signals from within individual atoms within the protein structure.
By focusing on the protein structure, the team was able to discover the PIP-stop and see how it blocked the protein’s function. The PIP-stop is a phosphate which is added to the protein surface that binds the PIP lipid, and normally controls how proteins attach to membranes.
Samples from cancer patients have too many PIP-stops, which could lead to the unregulated growth seen in tumour cells. Similar PIP-stops were found to be overused in a large number of other proteins involved in other cancer types, where they could also influence tumour growth.
“Our goal now is to design inhibitors for the overactive kinases that create PIP-stops, and to use this information to design drug molecules that block the progression of cancers, particularly those which lack effective treatments,” said Overduin.
University of Alberta Faculty of Medicine & Dentistrywww.folio.ca/medical-researchers-find-protein-that-marks-difference-between-cancer-and-non-cancer-cells/

A group of researchers from Mayo Clinic and Exact Sciences Corporation have completed a phase II study comparing a set of DNA markers to alpha fetoprotein as a method to test for liver cancer.
“We currently test for liver cancer using ultrasound and a blood protein marker called alpha fetoprotein,” says John Kisiel, M.D., a gastroenterologist at Mayo Clinic. “Unfortunately, these tests are not very sensitive for curable stage liver cancers, and most patients who need this testing do not have it easily available or [are] not able to receive it often enough to be effective.”
Dr. Kisiel and his colleagues developed a simple blood test using abnormal DNA markers that are known to exist in liver cancer tissues. They were able to confirm that the abnormal DNA markers were present in the overwhelming majority of blood samples that came from people with primary liver cancers. Simultaneously, these markers were absent in healthy individuals and individuals with cirrhosis of the liver but no evidence of tumours on their clinical follow-up.
“We were most excited that our DNA markers were able to detect more than 90 percent of patients with curable stage tumours,” says Dr. Kisiel. “This is the main reason why we think a DNA test will make difference, compared to currently available tests.” Dr. Kisiel says the next step will be to validate these markers in blood testing on much larger patient cohorts.

Mayo Clinic Cancer Center
newsnetwork.mayoclinic.org/discussion/mayo-clinic-researchers-take-a-step-closer-to-developing-a-dna-test-for-liver-cancer/