The first app and score to determine the one-year risk of a liver transplant patient dying or being hospitalized for a heart attack or other cardiovascular complication has been developed by Northwestern Medicine scientists.
“Knowing the patient’s risk is critical to help prevent the frequent cardiac complications that accompany liver transplant surgery and to determine which patients are likely to survive the transplant,” said Dr. Lisa VanWagner, an assistant professor of medicine and preventive medicine at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician.
Liver transplant surgery is among the highest-risk cardiac surgery. Unique blood flow changes occur in patients with end-stage liver disease. And during a liver transplant, massive changes in blood volume and adrenaline surges affect heart function.
“Identifying persons who are at highest risk may mean restricting transplantation so that we maximize the benefit of scarce donor organs to persons who have a lower risk of a cardiac event and are more likely to survive the stress of a liver transplant,” VanWagner said.
In those who are at higher risk, evaluation and consultation with a multidisciplinary team of physicians can help manage a wide array of cardiac conditions related to liver transplant patients.
The new app and method to establish risk is called the Cardiovascular Risk in Orthotopic Liver Transplantation (CAR-OLT). It’s intended for use in those ages 18 to 75 with liver disease who are undergoing evaluation for liver transplantation.
The app is both web-based (e.g., you can search the calculator and use it online) or you can download the app through a smartphone (iTunes or Google Play stores).
Prior to the new Northwestern risk-scoring method, physicians used several risk tools that had been developed in a non-liver transplant population. One such tool, the revised cardiac risk index, is no better at predicting cardiac risk in this population than flipping a coin (50 percent of the time the score predicts accurately, but 50 percent of the time it predicts inaccurately), VanWagner said.
The CAR-OLT method is thus the first liver transplant-specific risk tool for cardiac risk in liver transplant candidates.

Northwestern University
news.northwestern.edu/stories/2017/july/predicting-heart-events-after-liver-transplant/
 

Columbia University researchers have developed a personalized algorithm that predicts the impact of particular foods on an individual’s blood sugar levels. The algorithm has been integrated into an app, Glucoracle, that will allow individuals with type 2 diabetes to keep a tighter rein on their glucose levels-the key to preventing or controlling the major complications of a disease.

Medications are often prescribed to help patients with type 2 diabetes manage their blood sugar levels, but exercise and diet also play an important role.

‘While we know the general effect of different types of food on blood glucose, the detailed effects can vary widely from one person to another and for the same person over time,’ said lead author David Albers, PhD, associate research scientist in biomedical informatics at Columbia University Medical Center (CUMC). ‘Even with expert guidance, it’s difficult for people to understand the true impact of their dietary choices, particularly on a meal-to-meal basis. Our algorithm, integrated into an easy-to-use app, predicts the consequences of eating a specific meal before the food is eaten, allowing individuals to make better nutritional choices during mealtime.’

The algorithm uses a technique called data assimilation, in which a mathematical model of a person’s response to glucose is regularly updated with observational data-blood sugar measurements and nutritional information-to improve the model’s predictions, explained co-study leader George Hripcsak, MD, MS, the Vivian Beaumont Allen Professor and chair of biomedical informatics at Columbia. Data assimilation is used in a variety of applications, notably weather forecasting.

‘The data assimilator is continually updated with the user’s food intake and blood glucose measurements, personalizing the model for that individual,’ said co-study leader Lena Mamykina, PhD, assistant professor of biomedical informatics at Columbia, whose team designed and developed the Glucoracle app.

Glucoracle allows the user to upload fingerstick blood measurements and a photo of a particular meal to the app, along with a rough estimate of the nutritional content of the meal. This estimate provides the user with an immediate prediction of post-meal blood sugar levels. The estimate and forecast are then adjusted for accuracy. The app begins generating predictions after it has been used for a week, allowing the data assimilator to learn how the user responds to different foods.

The researchers initially tested the data assimilator on five individuals using the app, including three with type 2 diabetes and two without the disease. The app’s predictions were compared with actual post-meal blood glucose measurements and with the predictions of certified diabetes educators.

For the two nondiabetic individuals, the app’s predictions were comparable to the actual glucose measurements. For the three subjects with diabetes, the app’s forecasts were slightly less accurate, possibly due to fluctuations in the physiology of patients with diabetes or parameter error, but were still comparable to the predictions of the diabetes educators.

‘There’s certainly room for improvement,’ said Dr. Albers. ‘This evaluation was designed to prove that it’s possible, using routine self-monitoring data, to generate real-time glucose forecasts that people could use to make better nutritional choices. We have been able to make an aspect of diabetes self-management that has been nearly impossible for people with type 2 diabetes more manageable. Now our task is to make the data assimilation tool powering the app even better.’

Columbia University newsroom.cumc.columbia.edu/blog/2017/04/27/diabetes-app-forecasts-blood-sugar-levels/

“How long do I have, doctor?” For many cancer patients, following the initial shock of their diagnosis, thoughts quickly turn to estimating how much precious time they have left with family and friends or whether certain treatments could prolong their life.
While current methods of estimating mortality can be crude, patients with bowel cancer could soon more accurately predict their chances of survival, thanks to a new web calculator developed by academics at The University of Nottingham and medical software company ClinRisk Ltd.
The new tool, which can be accessed by doctors and patients alike, is intended to help people make more informed decisions around treatment and manage expectations following diagnosis.
Research to test the accuracy of the new calculator has shown that the tool can reliably predict both absolute survival rates for men and women with colorectal cancer.
The calculator also allows patients to update their mortality risk based on how long they have survived following a diagnosis of cancer.
The tool was developed by Professors Julia Hippisley-Cox and Carol Coupland in the University’s School of Medicine using the QResearch database, which gathers patient data from approximately 1500 general practices across England through EMIS Health’s clinical computer systems.
Professor Hippisley-Cox said: “Current methods of estimating survival tend to be unreliable and sometimes patients can be given a fairly misleading and unnecessarily gloomy prognosis based only on the grade and stage of their cancer, only to find that in reality they live much longer than these crude predictions when other information is taken into account.
“The good news is that this new calculator which doctors and patients can access will offer a far more realistic estimate. We understand that not everyone will want to do this, of course, but some patients are very keen on this approach so it’s an individual choice.”
Current methods of predicting survival are based on simple averages based only on age or the grade and stage of the cancer in the wider population.
The new tool looks at a range of additional risk factors including the patient’s, smoking history, body mass index, family history, other illnesses and treatments such as aspirin or statins as well as other information including whether they have had surgery or treatments such as chemotherapy to deliver a far more personalised prognosis.
The team used information from more than 44,000 patients from 947 practices to develop separate equations for men and women aged between 15 and 99 years old when diagnosed with bowel cancer.
They then tested the equations by using them retrospectively to predict the outcome at one year, five years and 10 years after diagnosis for 15,214 bowel cancer patients from 305 different GP practices and 437,821 colorectal cancer patients from the national cancer registry.
The results indicated that the team has devised strong models for the prediction of cancer survival outcomes.
They were also able to provide conditional survival estimates which show how mortality risks change over time, which are particularly important among patients where the initial prognosis is poor due to late stage disease.

University of Nottingham
www.nottingham.ac.uk/news/pressreleases/2017/june/new-web-calculator-to-more-accurately-predict-bowel-cancer-survival.aspx

Researchers from LSTM’s Research Centre for Drugs and Diagnostics (RCDD) have found a way of significantly reducing the treatment required for lymphatic filariasis and onchocerciasis from several weeks to seven days. By targeting Wolbachia, a bacterial symbiont that the filarial parasites need to live, the team has discovered a drug synergy that enables effective treatment over a shorter time.
Lymphatic filariasis (LF), which can cause elephantiasis or hydrocele, swelling of the limbs or scrotum and onchocerciasis, also known as river blindness, affect millions of people in some of the world’s poorest communities. Both are caused by filarial parasites for which the bacterial symbiont Wolbachia is essential for development. Filarial Neglected Tropical Diseases are prioritised for elimination, in line with fulfilment of the 2030 United Nations Sustainable Development Goals. A consensus of expert opinion, including the WHO, and major donors, USAID and UK DFID, considers that successful implementation of a macrofilaricidal (curative) or permanent sterilising drug would greatly accelerate the end game elimination of lymphatic filariasis and onchocerciasis. Traditional treatment for these conditions require repetitive, long-term mass drug administrations, and although targeting the symbiont with doxycycline has proved clinically effective, it is programmatically challenging due to the long treatment time and exclusion of pregnant women and children.
In a new paper researchers provide proof-of-concept of a radical improvement to the targeting of Wolbachia via a drug synergy between the anthelmintic drug albendazole and antibiotics. LSTM’s Professor Mark Taylor is senior author on the paper. He said: “As part of the A·WOL programme, we have screened all registered drugs for anti-Wolbachia activity, which has allowed us to look at repurposing existing and registered drugs against these debilitating conditions. The combination of an antibiotic and the anti-worm drug albendazole provided the greatest surprise when they acted synergistically to reduce the treatment time from weeks to days, opening up the opportunity to scale-up this approach at the community level.”
The team believe that their work is of immediate public health importance because the drugs that have been used, rifampicin and albendazole, are already registered. “These drugs can be tested in infected people as soon as possible,” continued Professor Taylor.
The first author on the paper, LSTM’s Dr Joe Turner, added, “the discovery of drug synergy between a common anthelmintic and different classes of antibiotics is also exciting because even more potent synergism may be evident when we combine with our next generation, ‘designer’ anti-Wolbachia drugs currently in development as part of the A·WOL programme. Potentially, we may be in a position to reduce curative treatment time frames down to five days or less for filariasis, with better acceptability and reduced costs for patients and local health systems”
Liverpool School of Tropical Medicine
www.lstmed.ac.uk/news-events/news/new-combination-therapy-of-registered-re-purposed-drugs-dramatically-shortens-anti

Clinicians today have an arsenal of more than 200 drugs at their disposal for treating a range of cancers — 68 drugs were approved between 2011 and 2016 alone. But many chemotherapeutic agents pose stubborn challenges: they cause serious side effects because they kill healthy cells in addition to cancer cells; some forms of cancer develop resistance to drugs; and many such chemotherapies, being poorly water-soluble, demonstrate low bio-availability resulting in sub-optimal drug delivery to cancer cells.
A potential solution lies in the synergistic combination of a chemotherapeutic drug with engineered genetic material designed to neutralize the malevolent genes conferring resistance to that drug, among other functions.
While there are numerous examples of synthetic dual gene and drug delivery vehicles, new hybrid materials developed in the lab at the NYU Tandon School of Engineering use easily modifiable proteins to deliver a chemical one-two punch: they combine a lipid “container” for transfection — the transportation of cargo past a cell membrane — and an easy-to-make protein capsule that can bind both small chemotherapeutic molecules and nucleic acids.
Developed by a team led by NYU Tandon Associate Professor of Chemical and Biomolecular Engineering Jin Kim Montclare — who also serves as an Affiliate Professor of Chemistry at NYU’s College of Arts and Sciences, and an Affiliate Professor of Biomaterials at NYU College of Dentistry, as well as being affiliated with SUNY Downstate as a Professor of Biochemistry — the hybrid lipid-protein material, called a lipoproteoplex, comprises both a coiled supercharged protein macromolecule and a commercially available transfection agent called Lipofectamine 2000.
Lipoproteoplex allows researchers to swap out a supercharged protein or lipid component and any number of siRNA to address a specific cell line and type of drug.
Because the researchers engineered the protein macromolecule with extensive positive charges on the surface and a hydrophobic core, it can be easily festooned with negatively charged short interfering RNA (siRNA) — a powerful tool for suppressing genes that invoke drug resistance and propagate disease states —while also serving as an efficient, and toxicity reducing, carryall for the hydrophobic chemotherapeutic agent doxorubicin.
In research published, the team details how the lipoproteoplex exposed to samples of the MCF-7 breast cancer cell line delivered more doxorubicin to target cells than did Lipofectamine 2000 alone, resulting in a substantial decrease in MCF-7 cell viability. They also demonstrated that the hybrid macromolecule was highly successful at siRNA transfection, silencing the gene by 60 percent.
Montclare said a key benefit of the new lipoproteoplex is ease of modification, an asset to researchers studying cells whose genetically invoked behaviour changes over time and differs by cell line and patient. Rather like a system of mix-and-match components, the lipoproteoplex allows researchers to swap out a supercharged protein or lipid component and any number of siRNA to address a specific cell line and type of drug.
“Unlike other pursuits at producing dual gene and drug delivery systems, this approach doesn’t require tedious chemical synthesis procedures; rather we can biosynthesize any variant of the supercharged protein,” she said. “This allows for substituting different siRNA molecules and chemotherapeutic drugs to suit lab needs.”

New York University Tandon School of Engineering
engineering.nyu.edu/press-releases/2017/08/09/researchers-nyu-tandon-create-new-biomaterial-delivers-drug-gene-silencer