Low-dose aspirin may help new mothers cut preterm birth risk

Daily low-dose aspirin, from as early as the sixth week of pregnancy through the 36th week, may lower the risk of preterm birth among first-time mothers, suggest the results of a clinical trial which involved women from several low and middle-income countries, including India.

The study, published in the journal The Lancet, involved more than 11,000 women.

The results showed that women taking daily low-dose aspirin were 11 per cent less likely to deliver before the 37th week of pregnancy, compared to those given a placebo.

"Our results suggest that low-dose aspirin therapy in early pregnancy could provide an inexpensive way to lower the preterm birth rate in first-time mothers," said study author Marion Koso-Thomas of the US National Institutes of Health's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

Preterm birth is the most common cause of infant death and the leading cause of long-term neurological disability in children.

According to the study authors, advances in newborn care have improved survival for preterm infants, but this care is limited or unavailable in many parts of the world.

Earlier studies have suggested that low-dose aspirin may reduce the risk of preterm birth and pre-eclampsia, a potentially life-threatening blood pressure disorder of pregnancy.

However, these studies were not large enough to statistically determine the therapy's effectiveness in reducing preterm birth.

The researchers enrolled 11,976 women with a first-time pregnancy from seven sites in India, Pakistan, Zambia, Democratic Republic of the Congo, Guatemala and Kenya.

Roughly half were assigned at random to receive 81 milligrams of aspirin daily; the other group received a daily placebo. Women were included in the study only if they maintained a pregnancy for more than 20 weeks.

Preterm birth (before 37 weeks) occurred in 11.6 per cent of the women who took aspirin and in 13.1 per cent of the women who took the placebo.

Similarly, birth before 34 weeks (early preterm delivery) occurred in 3.3 per cent of the aspirin group and 4 per cent of the placebo group (a 25 per cent reduction).

Women in the aspirin group also had a lower rate of perinatal mortality (stillbirth or newborn death in the first seven days of life), compared to the placebo group (45.7 per 1,000 births vs 53.6 per 1,000 births).

The risk of high blood pressure disorders of pregnancy at term did not differ significantly between the groups.

The low cost and safety of low-dose aspirin therapy suggests that it could be easily adapted for wide-scale use, suggested the study authors.

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Study finds improvements in survival rates for all cancers in young adults

A new study in the Journal of the National Cancer Institute, published by Oxford University Press, finds improvements in five-year survival rates for all cancers in young adults. For some cancers, however, there has been little improvement since the 1970s.

Over the past several decades, treatment of cancer in adolescents and young adults (people between age 15 and 39) has evolved significantly, leading to steady improvements in estimated survival rates.

Researchers here found that, among 282,969 five-year young adult cancer survivors, five-year mortality (from five through ten years after diagnosis) from all causes decreased from 8.3% among those diagnosed in 1975-1984 to 5.4% among those diagnosed in 2005-2011. However, for specific cancer types, including colorectal, bone, sarcomas, cervical/uterine, and bladder, there was little improvement in mortality over time. Researchers here found some reduction in late mortality in Hodgkin lymphoma, non-Hodgkin lymphoma, leukemia, central nervous system tumors, melanoma, breast cancer, and kidney cancer.

Some of the most obvious improvements in mortality over time were observed among young adult survivors of hematologic malignancies and central nervous system tumors, cancer types that are also predominant among children and have therefore been the focus of considerable cancer research in recent decades. Notably, the mortality rate among five-year young adult leukemia survivors dropped from over 25% to less than 5% between patients treated in the late 1970s and early 1980s and those treated more recently. Reductions in mortality over were also pronounced for survivors of lymphomas and central nervous system tumors, cancer types with some of the highest mortality rates. These findings show the impact of new treatments for patients with these cancers.

Although improvements in mortality rates have been more dramatic for children and older adults with cancer, findings from these reports indicate that early survival among young adults has improved steadily over the past several decades. Reported five-year survival gains likely reflect, in large part, the impact of advances in therapy for several of the most common cancers in young adults.

 It is important that we monitor trends in survival not only among recently diagnosed patients, but also among survivors who are several years beyond their initial cancer diagnosis. There have been substantial improvements over the past several decades for five-year survivors, though some cancer types have not shared in these improvements. Survivors of these cancer types may therefore be priority groups for efforts to improve long-term surveillance to reduce late mortality from cancer among adolescents and young adults."      Chelsea Anderson, paper's lead author. 

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Administering immunotherapy alongside chemoradiation for advanced NSCLC appears to be safe and tolerable

Research from Rutgers Cancer Institute of New Jersey shows administering the immunotherapy drug pembrolizumab together with chemotherapy given at the same time as radiation treatment (chemoradiation) is safe and tolerable as a first-line therapy for patients with stage 3 non-small cell lung cancer (NSCLC). The work, stemming from a multi-center phase 1 clinical trial led by Rutgers Cancer Institute, is published in the February 20 online edition of JAMA Oncology.

"Locally advanced NSCLC accounts for 20 to 25 percent of all new diagnoses of NSCLC, with five-year overall survival rates of between 25 to 30 percent when standard therapy is given. Current standard treatment in which an immunotherapy drug is administered after chemoradiaton offers a 57 percent progression-free survival rate compared to 43.5 percent when chemoradiation is given alone. Our team wanted to examine the safety and tolerability of the immunotherapy drug pembrolizumab when administered concurrently with chemoradiation, as we've learned from first-line treatment of stage 4 disease that we see better patient outcomes the earlier immunotherapy is given," shares Rutgers Cancer Institute radiation oncologist Salma Jabbour, MD, who is the lead and corresponding author of the current work.

Typically, the human body's immune system recognizes abnormal cells in the body and destroys them. Cancer cells frequently create proteins (PD-L1, programmed cell death ligand-1) on the cell surface that act as signals to turn off this part of the immune system. Pembrolizumab is a drug approved by the Food and Drug Administration to treat melanoma and other forms of cancer that targets PD-1 receptors, which act as a signaling 'switch.' Pembrolizumab blocks this action and turns the 'switch' back on, allowing the immune system to recognize cancer cells as foreign and attack them.

For a 27 month period between 2016 and 2018, 23 participants were enrolled (52 percent were women; median age 69 years). Five cohorts evaluating different timing and dosing of pembrolizumab combined with chemotherapy (carboplatin and paclitaxel weekly) and definitive radiation therapy (60 Gy in 2 Gy/day x 30 fractions) for unresectable, locally advanced, stage 3 disease were examined. Median follow-up time was 16 months.

Results show the combined treatment is feasible and well tolerated with a 12-month progression-free survival of 69.7 percent. Clinical benefit accounted for 94.6 percent at a median of 12.6 months. Of 19 evaluable patients (those who received 2 or more cycles of pembrolizumab) for response, the best response to therapy was a partial response seen in 73.7 percent, followed by 15.8 percent with a complete response, and 5.3 percent with stable disease. Local progression occurred in one patient, and of the six who developed metastatic disease, the median time to metastatic disease was 14.7 months. While there was an increased rate of pneumonitis, the authors note that patients with this form of lung inflammation responded to high-dose steroid treatment.

 This study demonstrates that the combination of immunotherapy with chemoradiation has the potential to improve cure rates for patients with stage 3 non-small cell lung cancer."   Dr. Salma Jabbour, professor of radiation oncology at Rutgers Robert Wood Johnson Medical School

Given the risk of pneumonitis when pembrolizumab is given with chemoradiation, the authors note further evaluation of the treatment combination through clinical trials is warranted, where careful radiation design to limit key lung parameters and biomarkers can be implemented. They add study limitations include the small sample size and limited follow-up duration.

For a 27 month period between 2016 and 2018, 23 participants were enrolled (52 percent were women; median age 69 years). Five cohorts evaluating different timing and dosing of pembrolizumab combined with chemotherapy (carboplatin and paclitaxel weekly) and definitive radiation therapy (60 Gy in 2 Gy/day x 30 fractions) for unresectable, locally advanced, stage 3 disease were examined. Median follow-up time was 16 months.

Results show the combined treatment is feasible and well tolerated with a 12-month progression-free survival of 69.7 percent. Clinical benefit accounted for 94.6 percent at a median of 12.6 months. Of 19 evaluable patients (those who received 2 or more cycles of pembrolizumab) for response, the best response to therapy was a partial response seen in 73.7 percent, followed by 15.8 percent with a complete response, and 5.3 percent with stable disease. Local progression occurred in one patient, and of the six who developed metastatic disease, the median time to metastatic disease was 14.7 months. While there was an increased rate of pneumonitis, the authors note that patients with this form of lung inflammation responded to high-dose steroid treatment.

    This study demonstrates that the combination of immunotherapy with chemoradiation has the potential to improve cure rates for patients with stage 3 non-small cell lung cancer."

    Dr. Salma Jabbour, professor of radiation oncology at Rutgers Robert Wood Johnson Medical School

Given the risk of pneumonitis when pembrolizumab is given with chemoradiation, the authors note further evaluation of the treatment combination through clinical trials is warranted, where careful radiation design to limit key lung parameters and biomarkers can be implemented. They add study limitations include the small sample size and limited follow-up duration.


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Protein therapy could improve outcomes following heart attack

Heart disease remains the largest killer in Australia and around the world. A new study has shown that a protein therapy- recombinant human platelet-derived growth factor-AB (rhPDGF-AB) - could improve outcomes following heart attack.

After a heart attack, scar tissue forms and this negatively affects heart function. Now, researchers from The Westmead Institute for Medical Research (WIMR) and the University of Sydney found that, infusing rhPDGF into subjects that have had heart attacks improves the quality of the scar, leads to the formation of new blood vessels in the heart, and reduced rates of dangerous heart arrhythmia (irregularities of heart rhythm that can cause sudden death).

This study was in a pre-clinical large animal model.

The discovery publishes today in the leading journal Science Translational Medicine.

Corresponding author who led the research team, Associate Professor James Chong, said:

    This is an entirely new approach with no current treatments able to change scar in this way.

    By improving cardiac function and scar formation following heart attack, treatment with rhPDGF-AB led to an overall increase in survival rate in our study.

    While the treatment did not affect overall scar size, importantly we found that rhPDGF-AB led to increased scar collagen fibre alignment and strength. This improved heart function after the heart attack.

Our collaborator Professor Richard Harvey,from the Victor Chang Cardiac Research Institute, had previously shown that the protein can improve heart function in mouse models following heart attack.

This project has been developed over more than 10 years and we now have compelling data in two species for the effectiveness of this treatment."

Following heart attack, the heart muscle is damaged, causing thick scar tissue to form. This can limit the heart's ability to function efficiently, and can increase the risk of heart failure, and sudden cardiac death.

Current treatments aim to restore blood and the oxygen supply to the heart as quickly as possible to reduce scarring. While this improves clinical outcomes, up to a quarter of patients experiencing their first heart attack will develop heart failure within one year.

Associate Professor Chong said: "While we have treatment protocols in place, it's clear that there is an urgent, unmet need for additional treatments to improve patient outcomes particularly after large heart attacks.

"Heart disease is the leading cause of death in Australia. It is thought that more than 400,000 Australians have had a heart attack at some stage in their lives and that there is roughly one heart attack every 10 minutes. Through our research, we have the opportunity to change the negative impact of these statistics.

"Some further animal studies are required to clarify safety and dosing. Then we can start looking towards clinical trials in humans very soon. rhPDGF-AB is clearly a promising therapeutic option, and could potentially be used alongside existing treatments to improve heart attack patient outcomes and survival rates.

"We now hope to further investigate the treatment, including whether it could be used in other organ systems impacted by scar tissue, such as the kidneys."

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13-Year Old Finds a Way to Treat Pancreatic Cancer

When it comes to pancreatic cancer, survival rates are extremely low. Statistics show that around 9% of people with pancreatic cancer survive for five years, and only around 1% survive for 10 years. And these stats haven't improved significantly in the past 40 years either. However, one 13-year-old, 8th grader  from Portland, Oregon, Rishab Jain is determined to change these statistics with his AI-based tool, PCDLS Net, which improves pancreas tracking during radiotherapy. Jain also won the 2018 Discovery Education 3M Young Scientist Challenge, before he started high school. 

But how did he get started? "It all started in the summer of 2017 when I went to visit my brother in Boston, and there I learned about some research that was happening, and the surprisingly low statistics about pancreatic cancer, like its survival rate." In light of this, he created an artificial intelligence-based tool called PCDLS Net to improve pancreas tracking during a treatment called radiotherapy for pancreatic cancer. 
Currently, pancreatic cancer is detected in quite a late stage, so by then, doctors use radiotherapy to help treat it, but most of the time, it is not effective enough. This inspired Jain to do some research on this. "Because I am a big programmer, and I like artificial intelligence, so I wondered if I could combine my knowledge in the two areas to help solve the problem, and I created an artificial intelligence-based tool called PCDLS Net to improve pancreas tracking during a treatment called radiotherapy for pancreatic cancer."
Jain contacted over 253 doctors and got 30 replies from leading experts from institutions at cancer centers and around the world. 

What makes surgery for the pancreas even more complicated is that it is very hard for the human eye to detect. This poses a big problem to radiologists and oncologists who have to find the pancreas and apply the radiation treatment. "other organs such as the stomach and liver that may cover the area, and also, it's right below the lungs causing it to move during some of the treatments. It's also very hard to reach in. It's right in the center of the abdomen next to the spinal cord... It's sometimes detailed as a mushy or angry organ because of its position in the body," he says. 

This is where Jain's invention comes into play. "My tool can be run to find where exactly the pancreas is in one of these CT or MRI slices and output this result instantaneously." He adds "currently, doctors have to apply sometimes a seven-millimeter overlay around the pancreas of radiation, and this can affect millions of healthy cells, so my tool is able to reduce that area to around four millimeters, so that saves millions of healthy cells and can improve patient quality of care." 
Jain says that he has detailed a five-year plan about how he want to globally commercialize his tool, PCDLS Net, improving pancreatic cancer survival rates. "I envision partnering with a hospital as well as 3M to work and create my tool as an add-on, and for this, I'll need to conduct clinical testing, so I want to gain FDA and IRB approval. So I want to continue pursuing medicine and engineering as I grow up, so for my undergraduate degree, I'm thinking about becoming a biomedical engineer," he concludes.

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Drug for Alzheimer's may also treat Chagas disease

Memantine, a drug used to treat Alzheimer's, can also prove effective in treating Chagas, a tropical disease, a new study has found.

The drugs currently used to treat Chagas disease, have serious side effects and limited use in those with chronic disease. However, researchers have found that memantine can diminish the number of parasites in mice infected with Chagas disease, and also increase the survival rate of the animals.

Chagas can be divided into acute and chronic phases, with the clinical phase causing heart, esophagus or intestinal symptoms.

The two drugs that have been used to treat Chagas for the last 50 years -nifurtimox and benznidazole are highly effective in the acute phase but used sparingly in the chronic phase due to serious side effects that occur with long-term treatment.

Researchers, in this work, studied memantine, which works on the central nervous system of animals but has also been shown to kill protozoa.

They first studied the effect of different concentrations of memantine on cultured macrophages -- a type of white blood cell -- that were infected with T. cruzi. Next, they tested the drug in T. cruzi-infected mice.

They found that memantine reduced the number of T. cruzi-infected macrophages in a dose-dependent way; more drug led to a greater reduction in the infection.

In mice with Chagas disease, memantine lowered levels of the parasite by 40 per cent and increased survival rates from 7.5 per cent to 12.5 per cent.

Not only this, but the mice treated with memantine also had 35.3 per cent lower parasite levels in their hearts compared to control animals.

"All these findings point memantine as an interesting starting point for the development of an optimized alternative therapy for Chagas disease," the researchers suggested.



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