A new study led by researchers at UC San Francisco and Kaiser Permanente has identified genetic predictors of normal prostate-specific antigen (PSA) levels in healthy men, which could be used to improve the accuracy of PSA-based prostate cancer screening tests.
Until recently, PSA tests for prostate cancer were considered an exemplar of successful early cancer detection leading to improved treatment outcomes. But over the past five years, a series of studies has suggested that the tests are not sensitive enough: frequent false positives lead to too many unnecessary medical procedures, and false negatives give men a false sense of security. In 2012, the test was given a ‘D’ rating by the U.S. Preventive Task Force, and the test is no longer covered by some insurers.
‘In the few years that PSA testing has become less popular, the use of the test has declined and the number of prostate cancer diagnoses has dropped,’ said John Witte, PhD, a UCSF professor of epidemiology and biostatistics and of urology, and co-senior author of the new study. ‘Disturbingly, some of the cases that are detected are now being diagnosed at a later stage, making successful treatment less likely. It’s a big conundrum for the field.’
One of the problems with current PSA tests is that they are a one-size-fits-all measurement of a protein that men naturally produce at different levels. The new genome-wide association study – led by Witte and co-senior author Stephen K. Van Den Eeden, PhD, a research scientist at Kaiser Permanente Division of Research and professor of urology at UCSF – suggests that the PSA test could regain its place in cancer prevention by factoring in genetic variations that affect the amount of PSA different men naturally produce.
Key to the study was Kaiser Permanente’s rich and comprehensive long-term dataset. The study included 28,503 men from the Kaiser Permanente cohort and 17,428 men from additional replication cohorts, in the aggregate representing nearly half a million PSA tests going back to the 1990s.
‘The unique setting of Kaiser Permanente allowed us to link every man in the study to our electronic clinical data and determine not just that they had a test, but also the level and frequency of testing over many years,’ said Van Den Eeden.
Using this large and rich study population, Witte’s group was able to identify 40 genetic regions, or loci, that together predict nearly 10 percent of normal variation in PSA levels in men who do not have cancer.
The authors also determined that the rest of the genomic sites studied in the paper explained an additional 32 percent of normal PSA variation, though the study was not sensitive enough to identify the specific genetic loci responsible for this additional variation. The results suggest that even more genetic predictors of PSA levels are likely to be uncovered by future studies, the authors said.
Understanding a given patient’s genetic predisposition to high PSA could allow physicians to better evaluate test results to predict the patient’s actual risk of prostate cancer, according to Witte, either by normalizing the results of PSA screens based on each individual’s natural PSA levels or by adjusting the threshold used to determine if a test result should trigger further testing, such as a prostate biopsy.

UC San Francisco (UCSF) http://tinyurl.com/yct5sks5

Researchers at the University of Texas at Dallas have developed a wearable diagnostic biosensor that can detect three interconnected, diabetes-related compounds — cortisol, glucose and interleukin-6 — in perspired sweat for up to a week without loss of signal integrity. The team envisions that their wearable devices will contain a small transceiver to send data to an application installed on a cellphone.
"Type 2 diabetes affects so many people. If you have to manage and regulate this chronic problem, these markers are the levers that will help you do that," said Dr. Shalini Prasad, professor of bioengineering in the Erik Jonsson School of Engineering and Computer Science. "We believe we’ve created the first diagnostic wearable that can monitor these compounds for up to a week, which goes beyond the type of single use monitors that are on the market today."
Prasad and lead author Dr. Rujute Munje, a recent bioengineering PhD graduate, describe their wearable diagnostic biosensor that can detect three interconnected compounds — cortisol, glucose and interleukin-6 — in perspired sweat for up to a week without loss of signal integrity.
"If a person has chronic stress, their cortisol levels increase, and their resulting insulin resistance will gradually drive their glucose levels out of the normal range," said Prasad, Cecil H. and Ida Green Professor in Systems Biology Science. "At that point, one could become pre-diabetic, which can progress to type 2 diabetes, and so on. If that happens, your body is under a state of inflammation, and this inflammatory marker, interleukin-6, will indicate that your organs are starting to be affected."
Last October, Prasad and her research team confirmed they could measure glucose and cortisol in sweat. Several significant advances since then have allowed them to create a more practical, versatile tool.
"We wanted to make a product more useful than something disposable after a single use," Prasad said. "It also has to require only your ambient sweat, not a huge amount. And it’s not enough to detect just one thing. Measuring multiple molecules in a combinatorial manner and tracking them over time allows us to tell a story about your health."
One factor that facilitated their device’s progress was the use of room temperature ionic liquid (RTIL), a gel that serves to stabilize the microenvironment at the skin-cell surface so that a week’s worth of hourly readings can be taken without the performance degrading over time.
"This greatly influences the cost model for the device — you’re buying four monitors per month instead of 30; you’re looking at a year’s supply of only about 50," Prasad said. "The RTIL also allows the detector to interface well with different skin types — the texture and quality of paediatric skin versus geriatric skin have created difficulties in prior models. The RTIL’s ionic characteristics make it somewhat like applying moisturizer to skin."
Prasad’s team also determined that their biomarker measurements are reliable with a tiny amount of sweat — just 1 to 3 microliters, much less than the 25 to 50 previously believed necessary.

ScienceDaily
www.sciencedaily.com/releases/2017/06/170623131515.htm

A study describes a new treatment pathway for antibiotic resistant bacteria and infectious diseases with benefits for patients and healthcare providers.

Researchers from the University of Birmingham and Newcastle University found that the unusual approach of removing antibodies from the blood stream reduced the effects of chronic infections, the requirement for days spent in hospital and the use of antibiotics.

In this study, the team identified two patients with bronchiectasis who suffered with chronic Pseudomonas aeruginosa infections that were resistant to many antibiotics; a 64-year-old male, diagnosed with bronchiectasis aged fifteen, and a 69-year-old female who had bronchiectasis from childhood.

Bronchiectasis is a disease that leads to permanent enlargement of the airways in the lung and affects over 300,000 patients in the UK. Symptoms are debilitating for patients, and typically include a chronic cough, shortness of breath, coughing up blood, and chest pain. Bronchiectasis often affects patients beyond the age at which lung transplantation is possible.

Chronic Pseudomonas aeruginosa lung infections commonly occur in patients suffering from bronchiectasis. Pseudomonas aeruginosa is a common bacterium that can cause disease and is known as a multidrug resistant pathogen, recognised for its advanced antibiotic resistance mechanisms and association with serious illnesses.

The patients volunteered to be part of an explorative treatment that built on previous findings from the research group in 2014.

Professor Ian Henderson, Director of the Institute of Microbiology and Infection at the University of Birmingham, explained:

‘These patients had an excess of a particular antibody in the bloodstream. In contrast to the protective effect normally associated with antibody, in these patients the antibody stopped the immune system killing the Pseudomonas aeruginosa bacterium and this worsened the patients’ lung disease. Perhaps counter-intuitively, we decided to remove this antibody from the bloodstream and the outcomes were wholly positive.’

Dr Tony De Soyza, Bronchiectasis service lead, Newcastle Upon Tyne Hospitals Trust and Senior Lecturer at Newcastle University, explained:

‘We needed a brand new way of tackling this problem. Working with kidney and immunology experts, we used a process known as plasmapheresis that is somewhat like kidney dialysis. The plasmapheresis involved the removal, treatment, and return of blood plasma from circulation, and was done 5 times in a week in order to remove antibody from the patients. We then replaced antibodies with those from blood donations. This treatment restored the ability for the patients’ blood to kill their infecting Pseudomonas.’

University of Birmingham www.birmingham.ac.uk/news/latest/2017/03/antibiotic-resistant-bacteria.aspx

The fight against skin cancer just got a new weapon. For years, melanoma researchers have studied samples that were considered uniform in size and colour, making them easier to examine by more conventional means. But melanomas don’t always come in the same shape and hue; often, melanomas are irregular and dark, making them difficult to investigate. Now, researchers at the University of Missouri have devised a new tool to detect and analyse single melanoma cells that are more representative of the skin cancers developed by most patients. The study outlines the new techniques that could lead to better and faster diagnoses for the life-threatening disease.

‘Researchers often seek out the types of cancerous cells that are homogenous in nature and are easier to observe with traditional microscopic devices,’ said Luis Polo-Parada, an associate professor of medical pharmacology and physiology and an investigator at Mizzou’s Dalton Cardiovascular Research Center. ‘Yet, because the vast amount of research is conducted on one type of cell, it often can lead to misdiagnosis in a clinical setting.’

The team that included Gary Baker, an assistant professor of chemistry in the MU College of Arts and Science and Gerardo Gutierrez-Juarez, a professor and investigator at the University of Guanajuato in Mexico, decided to supplement an emerging technique called photoacoustic (PA) spectroscopy, a specialized optical technique that is used to probe tissues and cells non-invasively. Current systems use the formation of sound waves followed by the absorption of light which means that the tissues must adequately absorb the laser light. This is why, up until now, researchers have focused only on strong-light-absorb cells melanoma cells, Polo-Parada said.

The team modified a microscope that was able to merge light sources at a range conducive to observing the details of single melanoma cells. Using the modified system, human melanoma and breast cancers as well as mouse melanoma cells were diagnosed with greater ease and efficiency. The team also noted that as the cancer cells divided, they grew paler in colour but the system was able to detect the newer, smaller cells as well.

‘Overall, our studies show that by using modified techniques we will be able to observe non-uniform cancer cells, regardless of their origin,’ Polo-Parada said. ‘Additionally, as these melanoma cells divide and distribute themselves throughout the blood, they can cause melanomas to metastasize. We were able to observe those cancers as well. This method could help medical doctors and pathologists to detect cancers as they spread, becoming one of the tools in the fight against this fatal disease.’

University of Missouri munews.missouri.edu/news-releases/2017/0504-fighting-cancer-new-microscopic-technique-could-help-detect-diagnose-metastatic-melanomas/

A new University of Alberta study showed that around-the-clock care from senior physicians helped reduce major complications in cardiac surgery patients as compared to receiving care from resident physicians. The study examined the results of more than 3,000 Alberta patients at the University of Alberta Hospital and Mazankowski Alberta Heart Institute.  Around-the-clock care from senior physicians helped reduce major complications in cardiac surgery patients as compared to receiving care from resident physicians, according to a new University of Alberta study.
Researchers found that patients who received 24/7 intensivist physician care had a seven per cent lower risk (26% vs 19%) of experiencing major complications and a nearly-four per cent lower chance (5.3% vs 1.6%) of cardiac surgical intensive care unit (ICU) readmission. Patients also experienced less time receiving mechanical ventilation and fewer surgical postponements.
The study examined the results of more than 3,000 Alberta patients at the University of Alberta Hospital and Mazankowski Alberta Heart Institute. Half were cared for at night by resident physicians over a seven-year period (2006-2013), with the other half cared for by dedicated in-house intensivist physicians over a period of 17 months (2013 and 2014).
“There have previously been large studies [examining this issue in general ICU units] and they have not found any benefit to taking residents away or adding staff physicians,” said study author Marc Benoit, a fellow in cardiology at the University of Alberta. “But we thought the cardiac ICU here might be different because the patients are more complex. Someone with a heart transplant who is sick is different than a standard hospital patient.”
“With more senior staff in-house at night, people were taken off the ventilators faster and we think there probably was more attention to detail for infection prevention. That is a possible explanation.”
Benoit stressed the findings were observational and that it cannot definitively be said that the change in staffing model was responsible for the outcomes. While the findings seem to support the use of senior physicians in specialized cardiac surgery ICUs, Benoit also notes that each hospital has unique circumstances and that careful thought needs to be put into the staffing of each of them.
“When looking at this issue of nighttime staffing, we need to consider the patient population. So maybe it’s not beneficial to keep senior physicians in-house in every single ICU, but it might be in some more complex units,” said Benoit.
“It is worth thinking about. Staffing patterns and care models can have very important effects on patient outcomes.”

University of Alberta
www.ualberta.ca/medicine/news/2017/july/improving-cardiac-icu-outcomes-through-specialized-24-7-care