MYELODYSPLASTIC SYNDROME
New drug target for blood cancer
A study from Mount Sinai and UC San Diego shows how myelodysplastic syndrome (MDS), a rare blood cancer with a poor prognosis and no effective treatment, develops from cells altered by mutations affecting a cellular process called RNA splicing. These mutations produce an alternative version of the protein created by the gene GNAS that can be targeted by FDA-approved cancer treatments, making it a good target for MDS as well.
The study published in Cancer Discovery in October is the first of its kind, said Eirini Papapetrou, MD, PhD, a senior coauthor of the study and an associate professor of Oncological Sciences at the Tisch Cancer Institute. Papapetrou and colleagues have found that these mutations are present not only in diseases such as MDS, hematologic malignancies, and other tumors but also in other cancers-which could mean a broad application of the study findings.
Papapetrou stated that the discovery of GNAS "results in the activation of processes that would render the cancer cells vulnerable to MEK inhibitors." MEK inhibitors are drugs already approved by the FDA for the treatment of other cancers. "The discovery that we can try to use MEK inhibitors in this cancer is also a first, and our findings also support future drug development to target GNAS," said Papapetrou.
The researchers are in the process of creating a clinical trial designed to test MEK inhibitors, cancer drugs named for the protein they inhibit.
Gene Yeo, PhD, professor at UC San Diego School of Medicine, heads the study with Papapetrou. By integrating isogenic models of disease with cutting-edge RNA-omics to converge into a new target for MDS, Yeo said they can identify the targets as well as the driver of the disease. The team was able to show that MDS cells taken from the model and from patients with these mutations were sensitive to treatment with MEK inhibitors.
Researchers were able to investigate the mutations in a physiologic genetic context by employing stem cells in creating models of the mutation. They then turned the engineered cells into hematopoietic progenitor cells, the type of cells relevant in blood cancers, and conducted splicing and RNA binding analyses, Yeo explained.
Source: http://www.mountsinai.org/about/newsroom/2021/researchers-identify-new-drug-targ
STROKE AND ANEURYSMS
Safety of fibrinolytic therapy
A new study published in an online issue of Neurology, the medical journal of the American Academy of Neurology, finds that fibrinolytic drugs rarely cause the rupture of preexisting intracranial aneurysms. Currently, fibrinolytic drugs are not recommended for patients with strokes with an unruptured intracranial aneurysm, even as the same drugs have been prescribed as the main drug for most patients with strokes.
Conducted for over 15 years at a stroke center in Finland, the study examined the records of people who were diagnosed with a stroke and who were treated with fibrinolytic drugs. The study looked at how many of the participants had a preexisting unruptured aneurysm, and from that subgroup, examined how many people experienced hemorrhagic stroke or intracranial hemorrhage while in the hospital, caused by intracerebral aneurysm rupture after fibrinolytic therapy.
The study observed 3,953 participants, 132 of whom had at least one unruptured aneurysm. From a total of 155 unruptured aneurysms, the study classified 141 saccular and 14 fusiform aneurysms. After treatment with fibrinolytic therapy, the aneurysms ruptured and caused a hemorrhagic stroke in only three people, or 2.3%, all of whom had large aneurysms classified as fusiform basilar artery aneurysms. The three participants had also been treated with anticoagulation. Not one rupture was observed in all of the aneurysms classified as saccular.
The research also suggests that fibrinolytic therapy may be relatively safe even for larger unruptured saccular aneurysms, but recommends further considerations for those with large fusiform aneurysms, as to whom anticoagulation may increase the chances of aneurysm rupture.
"Our results suggest that fibrinolytic therapy may be relatively safe for people with acute ischemic stroke even if they have larger saccular aneurysms that have not ruptured," said study author Jyri Juhani Virta, MD, PhD, of the University of Helsinki in Finland in a press release.
"For people with large fusiform aneurysms, additional consideration should be taken regarding treatment as anticoagulation may increase the risk of aneurysm rupture."
He noted that their findings could make fibrinolytic therapy available to more patients, and thereby prevent more deaths or disability for those patients with acute ischemic strokes. However, one study limitation to consider was that large aneurysms were uncommon among the participants.
Source: http://www.aan.com/PressRoom/Home/PressRelease/4927
MALARIA
First malaria vaccine gets WHO recommendation
The World Health Organization (WHO) has approved the widespread use of the RTS,S/AS01 (RTS,S), the world's first malaria vaccine.
This recommendation comes after a nod from WHO global advisory bodies working on immunization and malaria to use the vaccine for comprehensive malaria control and malaria prevention in children living in regions with moderate to high malaria transmission such as sub-Saharan Africa.
Malaria is a fatal cause of childhood illness and death in sub-Saharan Africa, where more than 260,000 children under the age of 5 die from malaria every year. This new vaccine-to be administered in four doses in children age 5 months and older-acts against P. falciparum, the most deadly malaria parasite that is most prevalent in Africa.
"This is a historic moment. The long-awaited malaria vaccine for children is a breakthrough for science, child health and malaria control," said WHO Director-General Dr. Tedros Adhanom Ghebreyesus in a press release. "Using this vaccine on top of existing tools to prevent malaria could save tens of thousands of young lives each year."
The recommendation is based on the key findings of pilot vaccination programs launched in 2019 in Ghana, Kenya, and Malawi. These programs have administered over 2.3 million doses of the vaccine in these three African countries, indicating a favorable safety profile.
"For centuries, malaria has stalked sub-Saharan Africa, causing immense personal suffering," said Dr. Matshidiso Moeti, the WHO Regional Director for Africa. "We have long hoped for an effective malaria vaccine and now for the first time ever, we have such a vaccine recommended for widespread use. Today's recommendation offers a glimmer of hope for the continent which shoulders the heaviest burden of the disease and we expect many more African children to be protected from malaria and grow into healthy adults."
Source: http://www.who.int/news/item/06-10-2021-whorecommends-groundbreaking-malaria-vac
TOTAL KNEE ARTHROPLASTY
Cannabis use disorder linked with higher perioperative complications
Patients with cannabis use disorder undergoing total knee arthroplasty (TKA) experienced longer medical stays and higher costs and rates of medical complications, as opposed to a comparison cohort determined based on age, gender, coronary artery disease, diabetes mellitus, hyperlipidemia, obesity, and hypertension, says Rushabh Vakharia, MD of Maimonides Medical Center.
In a research presented at the American Academy of Orthopaedic Surgeons' Annual Meeting, Vakharia and colleagues employed a private payer database to identify patients with a history of cannabis use disorder who had TKA from January 1, 2008, to December 31, 2018, for end-stage osteoarthritis.
The 11-year randomized study looked at such dependent variables as the length of hospital stay, medical complications at the 90-day interval, 2-year prostheses-related complications, and the cost of care in the bundle era for 90 days, Vakharia explained in a press release. Vakharia also found that a history of cannabis use disorder meant greater risk for cardiopulmonary-related complications, respiratory failures, and thromboembolic complications. The study also noted higher rates of prostheses-related complications and higher care costs for both day-of-surgery and within the 90-day period.
Because the current science does not explain these findings, Vakharia stressed the need for larger prospective studies. In the absence of a more definitive explanation, Vakharia suggests that TKA surgeons take a multidisciplinary approach in the care of patients with cannabis use disorder, with the objective of mitigating the adverse events observed in the study. Recognizing that most patients with a history of cannabis use generally suffer from comorbidities, such as depression, anxiety, severe back pain, and other health disorders, Vakharia suggests that the mitigating measures may include optimizing patients prior to surgery and identifying underlying causes for cannabis use.
Source: http://www.healio.com/news/orthopedics/20210907/cannabis-use-disorder-linked-wit