News
Zika and Birth Defects: The Evidence Mounts
The National Institutes of Health (NIH) provides an evidence based blog that describes growing support for connecting the recent rise of birth defects in Central and South America with the parallel spread of the Zika virus. Several studies have been funded by NIH to investigate this correlation and the potential for casual effect.
Two major pieces of evidence:
1) the Zika virus can kill human neural progenitor cells which give rise to the cerebral cortex and can cause microcephaly, and
2) a group of pregnant women infected by the virus had significantly more rates of microcephaly in the fetus.
Further concerns over the impact of the Zika virus, have shown in The New England Journal of Medicine article (88 healthy pregnant woman enrolled in the study, 72 were confirmed to be infected):
Of the Zika-infected women, almost a third had developing babies that showed signs of very serious abnormalities by ultrasound.
- 5 babies showed growth restrictions with or without microcephaly.
- 7 had other abnormalities of the central nervous system.
- 7 babies showed abnormally low levels of amniotic fluid or blood flow to the brain or umbilical cord.
- Two babies in the study were stillborn just weeks before their due dates.
These and the other studies mentioned in the article strengthen the case that the Zika virus is behind the rise of microcephaly.
CardioBrief: Theranos ignored red flags on blood clotting test
In a new report from the Wall Street Journal, Theranos has been accused of reporting potentially inaccurate results for the monitoring and therapy adjustment considerations for patients taking warfarin (Coumadin). The blood test for 81 patients over a six month period has been called into question due to evidence that suggests the tests were run even though erratic results from quality control checks were identified. Information provided by the Centre of Medicare and Medicaid Services’ (CMS) inspectors found ‘deficient practices’ in five categories of lab tests that posed immediate threat to patients. In the allegations, the company has also been reported to have used expired reagents in certain prothrombin time tests and lacked the proper qualified staffing model for their quality control program. Beth Waldron, an anticoagulation expert from the University of North Carolina in Chapel Hill stated, "Anticoagulants are the most common medication to cause adverse events for good reason… Too little drug in the body can cause clotting while too much can cause bleeding and both these extremes bring potentially fatal consequences. Warfarin is a finicky drug which requires daily vigilance by patients like myself to ensure a good outcome. The anticoagulant effect of warfarin is highly influenced by diet, lifestyle and concomitant medications. This is why the PT/INR test is so vital...it tells us how we're doing given all these influences, at staying within the optimal blood thinning target range and it guides our dosage adjustments accordingly." Theranos continues to work to rectify their current situation under great scrutiny of the media.
First human vaccine trial for most widespread species of malaria
Of the five malaria parasites species that attacks humans, Plasmodium falciparum and Plasmodium vivax cause the most deaths and is most widely spread, respectively. Walter Reed Army Institute of Research has investigated the P. vivax malaria vaccine in 30 immunized human volunteers. Using three levels of the vaccine dose and a control group, the volunteers were infected by mosquitos with malaria. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use. Published in the PLOS Neglected Tropical Diseases, the results identified that the vaccine was well tolerated and immunogenic but did not prevent malaria infection. However, it did significantly delay the parasitemia in 59% of the participants albeit small compared to the control group (examination of blood smears). Although the results have negative indications for the vaccine’s use, the study did provide valuable information on how to improve it and develop the next-generation version as stated by Lt. Col. Robert Paris, M.D., Director of the U.S. Military Malaria Research Program.
Hematology
Choosing Wisely endorsements give ASH opportunity to ‘make a difference’ beyond hematology
The Choose Wisely campaign is designed to create national dialogue on reducing unnecessary and wasteful medical tests, treatments and procedures. Representatives from the American Society of Hematology (ASH) have identified profession-specific items for questions on cost and potential harm that can be reduced in alignment with the campaign goals. For the current year, a new philosophy was used and the endorsement of 5 recommendations proposed by other specialties was adopted to decrease health profession silos. Lisa Hicks, MD, MSc, FRCPC, Assistant Professor of medicine at University of Toronto, hematologist at St. Michael’s Hospital and chair of the ASH Choosing Wisely Task Force, told HemOnc Today. “There is overlapping expertise and shared care models throughout medicine. We really felt that the way for us to crack the nut of overutilization was through collaboration. We wanted to leverage the work that had been done by others and share it with our community.”
The ASH-endorsed recommendations include:
- Do not routinely order thrombophilia testing for patients undergoing a routine infertility evaluation;
- Do not perform repetitive complete blood count and chemistry testing in the face of clinical and lab stability; and
- Do not transfuse red blood cells for iron deficiency without hemodynamic instability
For more details on these recommendations be sure to click on the article.
Cellular protein plays important role in aggressive childhood cancer
Published in the Journal of Clinical Investigations, UCLA scientist have been able to describe how cellular proteins contribute to the B-acute lymphoblastic leukemia (B-ALL), the most common cancer in children and a difficult one to treat. The research team catalogued the proteins in B-ALL and mixed lineage leukemia (MLL; which leads to B-ALL), and compared the analysis to identify which proteins had higher prevalence rates. The IGF2BP3 protein ‘stood out’ and it was uncovered that it regulates various RNA messages causing MLL and potentially leading to B-ALL. Further research indicated that IGF2BP3 “binds to and stabilizes hundreds of leukemia-promoting RNA messages and consequently increases how much protein is made, resulting in an environment that is conducive to leukemia cell growth.” When the protein was removed from leukemia cells decreased disease promoting messages. Continued efforts are underway to examine the protein's role in other cancers and determine drug models. As indicated in their abstract, “our data suggest that IGF2BP3-mediated targeting of oncogenic transcripts may represent a critical pathogenetic mechanism in MLL-rearranged B-ALL and support IGF2BP3 and its cognate RNA-binding partners as potential therapeutic targets in this disease.”
Microbiology
Researchers develop MALDI-TOF method for detecting vancomycin-resistant MRSA
The identification of vancomycin intermediate S. aureus (VISA) in the clinical laboratory depends on standard susceptibility testing, which takes at least 24 hours to complete after isolate 37 subculture, whereas heterogeneous VISA (hVISA) are not routinely detected in clinical labs . University of Washington researchers have developed a MALDI-TOF mass spec-based method for detecting vancomycin non-susceptible methicillin-resistant Staphylococcus aureus (MRSA). Published in the Journal of Clinical Microbiology, the approach marks a step forward for efforts applying mass spectrometry to the detection of antibiotic resistance and provides a more rapid method of detecting VISA and hVISA organisms. Using a support vector machine, they correctly identified 100% of VISA and 97% of VSSA isolates 49 with an overall classification accuracy of 98%. Addition of hVISA into the model 50 resulted in 76% hVISA identification, 100% VISA identification, and 89% VSSA 51 identification, for an overall classification accuracy of 89%.
Research
The elusive blood test for depression
Researchers have found numerous biomarkers associated with depression, but the statistical significance of each of these in isolation has not been strong enough to make a diagnosis, according to Richard Shelton, MD, Charles B. Ireland Professor and vice chair of research in the department of psychiatry at the University of Alabama at Birmingham School of Medicine. By combining the results from the measurement of many of these analytes, however, scientists are beginning to create tests that could potentially wield real predictive power. In a combined pilot (n = 79) and replication (n = 77) study and a larger follow-up confirmation study (n = 154), this research team showed that a panel of nine serum biomarkers and a prediction algorithm could differentiate between depressed and non-depressed individuals. Known as MDDScore, the test demonstrated a sensitivity and specificity both >90%, and holds the distinction of being one of the few biomarker-based assays for depression whose effectiveness has been validated in a replication study. The nine biomarkers it measures are associated with changes observed during major depression that take place in the neurotrophic, metabolic, inflammatory, and hypothalamic-pituitary-adrenal axis pathways. Using the pattern of these biomarkers’ concentrations as well as body-mass index, the algorithm then calculates a score on a scale of 1 to 9 that is adjusted for sex indicating the probability that a patient has depression.
Children to receive umbilical cord blood in world first cerebral palsy trial
"Unfortunately we hear of many Australian children with (cerebral palsy) and their families travelling overseas to receive unregulated stem cell treatments at great cost," said Professor Iona Novak , Head of Research at the Cerebral Palsy Alliance Research Institute. "This study, using cord blood which has been stored under Australian government-regulated conditions, is an important first step towards potentially improving treatment." In the world’s first medical trial and conducted at the Royal Children's Hospital in Melbourne, children with cerebral palsy will be infused with umbilical cord blood. Children aged 1 to 10 with cerebral palsy will receive infusions of cord blood rich in stem cells, which have the ability to develop into other cells in the body and help repair the system. "We are excited about this Australian trial commencing and the promising future of this much-talked about treatment," Stewart said. "I encourage other families to store their children's cord blood." Keep an eye out as results develop from this two year study!
Procedure allows kidney transplant from any donor
Researchers from Johns Hopkins are now able to transplant kidney organs from any donor, irrespective of their compatibility, which is saving more lives that the traditional long-term dialysis treatment while waiting for a donor match. The desensitization technique uses external filtration of antibodies from the patient’s blood. After the patient’s immune system regenerates new antibodies, the new set have been shown to be less likely to attack the transplant organ. In an eight-year study evaluating this technique in 1025 recipients, the study has shown higher survival benefits compared to those who remained on the waiting list. By the end of the study, 76.5% of those who had received the incompatible transplant were still alive, compared to 43.9% of those patients who were still on the waiting list. Although the exact mechanism behind this technique has not been fully revealed, great interest has been spark and scientists and clinicians are highly anticipating more information. “For the first time, we have definitively shown that incompatible live donor kidney transplantation provides almost twice the survival of a patient’s next best option,” said Dorry Segev, professor of surgery at Johns Hopkins.
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