An elite Russian unit is escalating its use of drones in Donetsk, forcing the defenders to innovate.
Jillian Kay Melchior
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Tag: Blood
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Opinion | Ukraine at the Rubicon
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FBI affidavit details bloody attack aboard cross-country flight out of San Francisco
For roughly one minute, a Florida man unexpectedly rained blows upon an unsuspecting passenger aboard a cross-country flight heading from San Francisco toward Washington, D.C., on Monday afternoon, a federal agent alleged.
Blood from the victim, asleep at the time and unprepared for the vicious assault, splashed onto the sleeves of the suspect’s lime green windbreaker, an FBI special agent claimed in an affidavit filed in U.S. District Court for the Eastern District of Virginia. Stains splattered onto nearby seats, walls and windows as blood flew from the victim’s head and face, the agent wrote.
The victim’s screams ultimately saved him, as a bystander stepped in, subdued the attacker and held him at bay for the remaining three hours until the assailant was arrested upon landing, the agent alleged.
Florida resident Everett Chad Nelson faces federal assault charges in the incident. The victim’s name was not released.
A call to Nelson’s court-ordered public defender was not immediately returned. Nelson is due back in court Dec. 11.
The FBI received an alert from the Transportation Security Administration at 9:26 a.m. about a disturbance aboard a roughly five-hour United Airlines flight from San Francisco to Dulles Airport in Virginia.
Nelson was seated about four rows from the back of the 82-seat plane. He was returning to his seat after using the restroom at the front of the plane about two hours into the flight when he stopped at the 12th row.
The affidavit alleges that he “began physically attacking a sleeping male passenger by punching him repeatedly in the face and head until blood was drawn.”
The victim suffered bruises on his eyes and a gash on his nose, according to the FBI agent.
Another passenger eventually broke up the fight, according to the affidavit and United Airlines media relations. The victim was treated by a doctor aboard the plane.
Nelson was eventually moved to the front of the aircraft and monitored by the passenger who had earlier stopped him, according to the affidavit and United.
“Thanks to the quick action of our crew and customers, one passenger was restrained after becoming physically aggressive toward another customer,” United Airlines wrote in a statement.
United said the flight landed on time and was met by paramedics and law enforcement at the gate.
The Federal Aviation Administration said it was conducting its own investigation of the incident. Airlines have been besieged by unruly passengers this year, the FAA said, citing roughly 1,700 incidents to date.
Andrew J. Campa
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Video: About Our Investigation Into Cord Blood Banks
Some families pay thousands of dollars to store their children’s stem cells with the hope of a healthier future for them. But Sarah Kliff, an investigative health care reporter for The New York Times, explains that the cells are rarely useful and are sometimes contaminated.
Sarah Kliff, Claire Hogan and James Surdam
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Peter Pan & Pinocchio Join Winnie-the-Pooh in Becoming Slasher Baddies
Last year, a new horror franchise took flight with Pooh: Blood & Honey. With the iconic bear now in the public domain, the film turned Winnie and Piglet into a pair of grim slasher villains carving up a post-grad Christopher Robin and several university students. It went over about as well as expected, but did well enough financially to kick off both its own sequel and a larger universe—sorry, Poohniverse—for more public domain characters to get a horror treatment.
Blood & Honey 2 already dropped this year, so now we’re getting our first look at the whole “expanded universe” part of the thing. Per Variety, classic characters Pinocchio and Peter Pan are set to headline their own individual films, both of which are currently being sold at Cannes. Pinocchio: Unstrung takes the boy puppet will be welcomed into the Poohniverse “with a bang,” said director Rhys Frake-Waterfield, who also helmed the two Pooh movies. The film’s being pitched as a subversion of Carlo Collodi’s classic 1883 book, and one that’ll rely more on practical gore—one scene, according to Variety, will see the title character wear the skin of one of his victims to “feel like a real boy.”
Meanwhile, Peter Pan’s Neverland Nightmare puts Martin Portlock (Scream of the Wolf) in the title role, who’s gone and kidnapped Michael (Peter DeSouza-Feighoney), the younger brother of Wendy Darling (Megan Placito). She endeavors to save him with Tinkerbell’s (Kit Green) help, who in this universe is a heroin junkie convinced that it’s actually pixie dust. Once you’re done rolling your eyeballs, the cast is further filled by Charity Kase as Captain Hook, and the likes of Kierston Wareing, Nicholas Woodeson, Olumide Olorunfemi, and Teresa Banham in currently undisclosed roles.
Like the Marvel movies this is trying to emulate, Peter and Pin are getting solo movies to prepare them for a bigger future in the so-called Twisted Childhood Universe. Both characters will converge with Pooh and Piglet in Poohniverse: Monsters Assemble in 2025, which’ll also introduce the likes of Sleeping Beauty and the Mad Hatter. The TCU aims to keep on keeping on after the crossover, because a third Blood & Honey is locked in for 2026, while solo movies for Sleeping Beauty and Snow White are also said to be in the works. Yay?
At time of writing, Peter Pan’s Neverland Nightmare is set to release later this year after production wraps, while Pinocchio: Unstrung will release in 2025 ahead of Monsters Assemble.
Want more io9 news? Check out when to expect the latest Marvel, Star Wars, and Star Trek releases, what’s next for the DC Universe on film and TV, and everything you need to know about the future of Doctor Who.
Justin Carter
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Managing Stress and Cholesterol Levels for Better Heart Health – Aha!NOW
A healthy heart is imperative for better health. The heart requires a clear and constant blood supply to work efficiently. Both high stress levels and high cholesterol levels are detrimental as they restrict the blood supply to the heart. Moreover, there is a link between stress and cholesterol. Know more about this and how to manage their levels to keep your heart active and healthy. ~ Ed.
Stress and high cholesterol are two common health issues that often occur together. Research shows that there is a correlation between stress and cholesterol levels – stress can contribute to high cholesterol which can in turn cause stress. By understanding their connection and taking steps to manage both stress and cholesterol, you can improve your overall health and well-being.
The Impact of Stress on Cholesterol
Stress triggers our bodies to produce hormones like cortisol and adrenaline. These hormones trigger a “fight or flight” response, increasing blood pressure, heart rate, and blood sugar levels. Cortisol also signals the liver to produce more cholesterol. This reaction helped our ancestors survive immediate physical threats, but modern stress is often psychological and prolonged. Chronic stress keeps cholesterol production high, causing unhealthy LDL or “bad” cholesterol levels to rise.
High cholesterol doesn’t always cause noticeable symptoms. But over time, it can lead to a buildup of plaque in the arteries. This narrows the interior walls, restricting blood flow to the heart and brain. It increases the risk of heart attack, stroke, and other cardiovascular issues. Studies show that people with high stress often have elevated LDL cholesterol and triglyceride levels. Managing stress is key to maintaining healthy cholesterol levels and improving heart health.
The Effects of High Cholesterol on Mental Health
Just as stress negatively impacts cholesterol, high cholesterol can also trigger stress in a vicious cycle. High cholesterol is damaging to blood vessels everywhere, including those in the brain. Plaque buildup in cerebral arteries limits oxygen supply, which can impair cognitive skills. It also reduces the production of serotonin, an important neurotransmitter that regulates mood.
This disruption to blood flow and brain function can cause varied neuropsychiatric symptoms. People with high LDL cholesterol often report increased anxiety, irritability, and feelings of depression. There is also an increased long-term risk of dementia. For those already dealing with mental health issues, high cholesterol presents another challenge while exacerbating existing symptoms. Knowledge of how lifestyle habits affect both the mind and body empowers people to take control of their health.
8 Lifestyle Changes to Manage Stress and Cholesterol
The good news is that many of the same healthy lifestyle changes can target both high cholesterol and high stress levels. Here are some practical, evidence-based ways to reduce stress while improving cholesterol profiles:
Get Active
Regular exercise is one of the most effective stress relievers while also lowering LDL and raising HDL cholesterol. Aim for 30-60 minutes per day of activity like brisk walking, swimming, cycling, or rowing. Yoga and Pilates can also relax the mind and strengthen the heart.
Eat a Healthy Diet
Limit saturated fat, trans fats, and cholesterol by eating more vegetables, fruits, whole grains, legumes, fish, and lean protein. Be sure to get ample fiber, omega-3 fatty acids, antioxidants, and probiotics. Avoid excess sugar and salt. Limit alcohol, which stresses the liver and raises triglycerides.
Lose Excess Weight
Carrying excess body fat, especially around the abdomen, puts more stress on the heart and promotes inflammation. Losing even 5-10% of your body weight can significantly lower cholesterol while boosting mood.
Quit Smoking
Smoking damages blood vessels while increasing the risk of lung disease, cancer, and heart attack. Kicking the habit reduces stress and improves cholesterol.
Get Adequate Sleep
Lack of sleep is linked to higher cholesterol as well as increased cortisol production. Strive for 7-9 hours per night, going to bed and waking at consistent times to regulate your circadian rhythm.
Practice Relaxation Techniques
Meditation, deep breathing, Tai Chi, and yoga have proven benefits for psychological stress. They activate the parasympathetic nervous system to initiate a relaxation response, lowering blood pressure and cholesterol.
Manage Medications
If lifestyle changes aren’t enough, cholesterol and blood pressure medications may be needed. Anti-anxiety or antidepressant drugs can also help in some cases, but their effects should be monitored. Be sure to take any prescribed drugs regularly to reduce strain on the cardiovascular system.
Get Screened and See Your Doctor
Have your cholesterol levels tested regularly and get screened for heart disease risk. If the numbers are very high, your doctor may recommend more aggressive treatment. Discuss any mental health concerns as well so underlying causes can be addressed.
By relieving stress and keeping cholesterol levels in check, you can break the unhealthy cycle between mind and body. Caring for both is essential for improving heart health and enjoying a better quality of life.
When we talk about cholesterol and liver health, it is important to know that the liver plays a central role in regulating cholesterol levels and metabolism. It removes cholesterol from the bloodstream and excretes it into bile. The liver also synthesizes cholesterol for the production of cell membranes and hormones. When we consume foods high in cholesterol and saturated fats, the liver churns out more LDL particles, which elevate cholesterol further.
This extra burden on the liver also creates oxidative stress, compounding the negative effects. Supporting liver function through a healthy lifestyle is therefore important for maintaining normal cholesterol range and reducing cardiovascular risks.
Conclusion
Stress and high cholesterol often coincide, fueling each other in a destructive loop. By eating well, exercising, getting enough sleep, managing medications as needed, and implementing stress-reduction techniques, you can target both issues simultaneously. Caring for your mind and body together through a holistic approach helps relieve pressure on the heart while also enhancing mental health and wellbeing.
Addressing stress and cholesterol through positive lifestyle changes leads to improved physical and emotional health over the long term.
Over to you
How do you manage your heart health? What are your tips to keep the stress and cholesterol levels under control? Share them in the comments below.
Image credit: Freepik
Disclaimer: We’re not offering any medical advice here. These ideas are for educational and entertainment purposes only. Always seek a professional medical opinion from a physician of your choosing before making any medical decision. The information provided here is not intended to be a substitute to the advice given by your physician or another healthcare professional.
Disclaimer: Though the views expressed are of the author’s own, this article has been checked for its authenticity of information and resource links provided for a better and deeper understanding of the subject matter. However, you’re suggested to make your diligent research and consult subject experts to decide what is best for you. If you spot any factual errors, spelling, or grammatical mistakes in the article, please report at [email protected]. Thanks.
Emma Williams
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Fact check: Are COVID vaccine recipients ineligible to donate blood in NC?
If you have received a COVID vaccine, you are eligible to give blood – but you may have to wait before donating.
An ongoing national blood shortage could delay critical medical procedures, Dr. Nick Bandarenko, Duke Health’s medical director of transfusion services, told ABC11 last month.
“Surgery, transplant or accident in a car. Suddenly there’s a need for blood,” said Dr. Bandarenko. “The Red Cross is one of the major suppliers in our region. They’ve asked us to exercise conservation measures to make sure those who truly need blood will have it available.”
But despite the critical need for blood donors, there’s been some debate online about whether those who have received a COVID vaccine are eligible to donate.
“The American Red Cross is now asking blood donors if they ever received the Covid vaccine,” an X user posted last week. “If you answer Yes, they want you to call ahead to see if you’re still eligible. I thought the vax was ‘safe and effective’? What info are they hiding from us?”
Similar rumors have been spread on Facebook and TikTok, Snopes reported — but the claims concerning ineligibility are false.
If you have received a COVID vaccine, you are eligible to give blood — but in rare cases you may have to wait before donating.
Do I have to wait to give blood after getting vaccinated?
In most cases, there is no wait time to donate blood for those who received the COVID vaccine, according to the American Red Cross.
The Red Cross says those who received vaccines from the following manufacturers and are symptom-free do not have to wait to give blood:
However, if you got a vaccine from a manufacturer not listed above, or you don’t know what type of vaccine you received, you’ll have to wait two weeks before donating blood, according to the Red Cross.
How do I know which type of vaccine I received?
If you were vaccinated, you should have received a card or printout indicating which COVID vaccine you got, the Red Cross says.
The Red Cross encourages donors to bring those cards with them to their appointments.
Am I eligible to donate blood in NC?
In North Carolina, you must be at least 16 years old and weigh at least 110 pounds to donate blood, according to UNC Medical Center. Donors under 18 must have a signed parental consent form to donate blood on the day of donation.
“Donors should feel well and healthy on the day of donation and free of infectious diseases, including colds,” UNC Medical Center says.
Additional eligibility criteria may apply to individuals with certain medical conditions, or who are on medication, according to the Red Cross.
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Penis fibroblasts crucial for erection, underestimated.
Regular erections could be important for maintaining erectile function, according to a new study on mice published in Science by researchers at Karolinska Institutet. “We discovered that an increased frequency of erections leads to more fibroblasts that enable erection and vice versa, that a decreased frequency results in fewer of these cells,” says principal investigator Christian Göritz.
Newswise — In a new study on mice, researchers at Karolinska Institutet and Uppsala University in Sweden show that connective tissue cells called fibroblasts have a previously unknown and very important function in mediating erection.
“Fibroblasts are the most abundant cells in the penis of both mice and humans, but they have been neglected in research,” says Eduardo Guimaraes, researcher at the Department of Cell and Molecular Biology at Karolinska Institutet and first author of the paper. “Now we can show, using a very precise method called optogenetics, that they have a very important role in regulating blood flow in the penis, which is what makes the penis erect.”
The study shows that fibroblasts mediate erection by taking up the neurotransmitter noradrenaline, which leads to the widening of blood vessels in the penis. How effective this process is depends on the number of fibroblasts.
The body adapts
The researchers were also able to show that the number of fibroblasts in the penis is affected by the frequency of erections. The more frequent the more fibroblasts and vice versa; a lower frequency of erections reduced the number of fibroblasts.
“It’s not so strange really. If you exert yourself a lot, your body adapts. If you run regularly, it will eventually become easier to breathe while running,” says Christian Göritz, senior researcher at the Department of Cell and Molecular Biology at Karolinska Institutet, who led the study.
In terms of what conclusions can be drawn for humans from studies on mice, Christian Göritz says that in this case there are significant similarities.
“The basic mechanisms of erection are very similar in all mammals regarding anatomy, cell structure and so on,” he says. “However, there is one difference between humans and most mammals – they have a bone in their penis. This means that effective blood flow regulation is probably even more important for human reproduction.”
Fewer fibroblasts with age
Older mice had fewer fibroblasts in the penis, which was also reflected in lower blood flow. The ability to get an erection decreases with age also in humans, which could be partly due to fewer fibroblasts in the penis. The researchers therefore believe that it could be possible to train the ability to get an erection to counteract impotence in the same way as you can train your strength or fitness at the gym.
“This is not something we have shown in our study, so it is a bit speculative, but a reasonable interpretation is that it gets easier if you have regular erections,” says Christian Göritz.
He hopes that the new knowledge of the role of fibroblasts in erection may also lead to new treatments for erectile dysfunction.
The research was mainly funded by the Bertil Hållsten Foundation and the Knut and Alice Wallenberg Foundation. There are no reported conflicts of interest.
Facts: Erectile dysfunction, or impotence, affects between 5 and 20 per cent of all men, with the incidence increasing with age. Erectile dysfunction often negatively affects the quality of life and physical and psychosocial health, both for the patient and their family. Common risk factors, apart from age, are similar to those for cardiovascular disease: inactivity, obesity, hypertension, smoking, high cholesterol levels and metabolic syndrome. Source: Region Stockholm knowledge support Viss.nu.
Publication: “Corpora cavernosa fibroblasts mediate penile erection”, Eduardo Linck Guimaraes, David Oliveira Dias, Wing Fung Hau, Anais Julien, Daniel Holl, Maria Garcia-Collado, Soniya Savant, Evelina Vågesjö, Mia Phillipson, Lars Jakobsson, Christian Göritz. Science, online 8 February 2024, doi: 10.1126/science.ade8064.
Karolinska Institute
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ASH 2023 Tip Sheet From Sylvester Comprehensive Cancer Center
EMBARGOED
Newswise — Many physician-scientists and other researchers from Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine will be making oral or poster presentations or participating in panel discussions at the American Society of Hematology’s 2023 annual meeting in San Diego, Dec. 9-12.
Below is an EMBARGOED summary highlighting several presentations involving Sylvester physicians and other staff members.
Please note that all information is strictly embargoed until the date and time of each presentation.
Lymphomas
EMBARGOED UNTIL Monday, December 11, 2023: 5:45 PM, Grand Hall C
Presenting Author: Juan Pablo Alderuccio, MD, Sylvester Comprehensive Cancer Center
Intro: No standard-of-care exists for treatment of relapsed/refractory follicular lymphoma (FL) with worse prognosis in those demonstrating progression of disease within 24 months from frontline immunochemotherapy. Loncastuximab tesirine (loncastuximab) is an antibody-drug conjugate comprising a monoclonal antibody. The authors report results of a single-institution, investigator-initiated study evaluating this combination for the first time to treat FL. Conclusion: A limited duration program combining loncastuximab with rituximab in patients with FL is well tolerated and highly effective for high-risk patients or those with high disease burden.
EMBARGOED UNTIL Sunday, December 10, 2023: 5:00 PM
Presenting Author: Trent Wang, DO, MPH, Sylvester Comprehensive Cancer Center
Intro: There are limited reported outcomes of patients with large B-cell lymphoma (LBCL) who are infused with CD19 CAR-T cells while being in radiographic or metabolic complete remission (CR). The authors hypothesize that these patients in complete remission before CAR-T infusion may have favorable progression-free survival with lower toxicity.
Conclusion: CAR-T cell in LBCL patients who are CR after receiving two or more lines of prior therapy is a reasonable consolidation option, with a subset of patients remaining progression-free at two years. Their 9% rate of non-relapse mortality highlights the importance of continued follow-up.
EMBARGOED UNTIL Monday, December 11, 2023: 5:45 PM
Presenting Author: Jay Y. Spiegel, MD, FRCPC, Sylvester Comprehensive Cancer Center
Intro: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 CAR T-cell therapy that induces durable responses in patients with relapsed or refractory large B-cell lymphoma. The authors previously reported outcomes for axi-cell patients treated with standard-of-care therapy, including 42% who were ineligible for the ZUMA-1 trial. Now, they update outcomes for this cohort at 58 months.
Conclusion: This multicenter, retrospective study showed similar five-year results to the ZUMA-1 trial, despite including patients ineligible for that trial due to comorbidities. It supports the curative potential of axi-cel therapy but highlights the risk for non-relapse mortality in this group.
EMBARGOED UNTIL Saturday, December 9, 2023: 5 PM
Presenting Author: Jorge A. Florindez, MD, University of North Carolina School of Medicine
Sylvester Authors: Izidore S. Lossos, MD, and Juan Pablo Alderuccio, MD
Intro: Some patients with follicular or marginal zone lymphoma experience high-grade transformation (HGT) into diffuse large B-cell lymphoma. This study used population-based data to assess incidence and risk factors for HGT, post-HGT overall survival and lymphoma-specific survival across subtypes with treatment or surveillance as initial strategies.
Conclusion: Frontline treatment was associated with lower risk for HGT in follicular lymphoma, with advanced stage and female gender identified as risk factors. For other lymphomas, initial treatment neither diminished HGT risk nor improved survival afterward.
Myelodysplastic Syndromes/Neoplasms
EMBARGOED UNTIL Monday, December 11, 2023: 4:45 PM
Presenting Author: Luca Lanino, MD, Humanitas Clinical and Research Center, Milano, Italy
Sylvester Authors: Mikkael A. Sekeres, MD, Justin Taylor, MD and Stephen D. Nimer, MD
Intro: Significant discrepancies still exist between WHO and ICC classifications of myelodysplastic syndromes/neoplasms, despite their recent inclusion of gene mutations and chromosomal abnormalities to enhance diagnosis and clinical decision-making. These differences potentially cause inconsistent practices within the clinical setting. This study for the International Consortium for MDS adopted a data-driven model to develop a harmonization road map for these classifications.
Conclusion: The study demonstrated the value of this approach based on advanced statistical methods to generate harmonized MDS classifications.
EMBARGOED UNTIL Monday, December 11, 2023: 11:45 AM
Presenting Author: Justin Watts, MD, Sylvester Comprehensive Cancer Center
Intro: Bromodomain and extra-terminal (BET) proteins regulate expression of critical oncoproteins associated with myelofibrosis (MF) and other blood-cancer malignancies, including B-lymphoma-2. This ongoing Phase 1, dose-escalation study is evaluating the safety and tolerability of a BET inhibitor as monotherapy and in combination with ruxolitinib.
Conclusion: Monotherapy and combination therapy with ruxolitinib were generally well-tolerated, except for the largest monotherapy amount that caused two dose-limiting toxicities. Dose-finding for both therapies is ongoing to determine the recommended expansion dose.
EMBARGOED UNTIL Saturday, December 9, 2023: 5:30-7:30 PM, Halls G-H (San Diego Convention Center)
Senior Author: Justin M. Watts, MD, Sylvester Comprehensive Cancer Center (Presenting author is Jorge Cortes, MD, Georgia Cancer Center, Augusta)
Intro: Olutasidenib, a small molecule drug that targets a mutation involved in certain cancers and is approved for relapsed and refractory acute myeloid leukemia (AML), was studied in 22 patients with a specific type of myelodysplastic syndromes/neoplasms (MDS).
Conclusion: In this subgroup of patients in a Phase 1/2 study, the drug – used both alone and in combination with another drug – induced durable remissions in patients with intermediate-, high-, or very high-risk MDS, and the treatment had a tolerable and manageable safety profile.
EMBARGOED UNTIL Saturday, December 9, 2023: 5:30-7:30 PM, Halls G-H (San Diego Convention Center)
Senior Author: Mikkael A. Sekeres, MD, Sylvester Comprehensive Cancer Center (Presenter: Amy E. DeZern, MD, Johns Hopkins University)
Intro: Myelodysplastic syndromes (MDS) – disorders of blood cells in the bone marrow – may result from mutations in stem cells responsible for blood cell creation. Screening and monitoring of some diseases can be accomplished by assessing mutations in peripheral blood, from a basic blood draw, but because the ability to detect and monitor mutations involved with MDS and related conditions is less certain, guidelines often require invasive bone marrow evaluations instead.
Conclusion: This study, which included 36 patients, compared results from peripheral blood and bone marrow studies and found that peripheral blood can be used to reliably identify somatic (non-hereditary) mutations in patients with suspected or established MDS and related conditions.
EMBARGOED UNTIL Monday, December 11, 2023: 6-8 PM, Halls G-H (San Diego Convention Center)
Sylvester Co-Authors: Mikkael A. Sekeres, MD, and Namrata Sonia Chandhok, MD, Sylvester Comprehensive Cancer Center (Presenting Author: Jan Philipp Bewersdorf, MD, Memorial Sloan Kettering Cancer Center)
Intro: This multicenter analysis aimed to provide a better understanding of treatment options for patients with cancers of blood cells in the bone marrow – higher-risk myelodysplastic syndromes/neoplasms (HR-MDS). Two drugs, azacitidine and decitabine, both hypomethylating agents, or HMA, provide the foundation of mainstay, frontline treatments for HR-MDS, but they have not been compared directly in randomized trials.
Conclusion: This study, involving 1,223 patients, with 919 patients included in the survival analysis, found no significant difference in overall survival or overall responses between the two groups of patients treated with the drugs.
44 Altered RNA Export in SF3B1 Mutants Increases Sensitivity to Nuclear Export Inhibition
EMBARGOED UNTIL Saturday, December 9, 2023: 9:45 AM
First Presenter: Sana Chaudhry, Sylvester Comprehensive Cancer Center
Senior Author: Justin Taylor, MD, Sylvester Comprehensive Cancer Center
Intro: About half of MDS patients carry genetic alterations, known as somatic mutations, in spliceosome genes, with SF3B1 being the most commonly mutated one. However, no successful therapy exists to target this pathway. The authors hypothesized that XPO1 inhibition may preferentially affect these mutant cells via splicing, and that high-risk MDS patients with this mutation would have a better response to rational drug combinations with next-generation XPO1 inhibitors.
Conclusion: The study provides insight on the mechanisms behind the increased effectiveness of XPO1 inhibition in SF3B1-mutant MDS and leukemia patients. These findings also may contribute to development of potentially beneficial drug combinations.
Leukemias
EMBARGOED UNTIL Sunday, December 10, 2023: 4:30-5:45 PM, Room 6CF (San Diego Convention Center
Presenting Author: Justin M. Watts, MD, Sylvester Comprehensive Cancer Center
Description: This Education Session will review the transformation in AML therapy from traditional 7+3 for fit patients and hypomethylating agents for unfit patients to new standards of care and ongoing questions in the field. We will discuss the data regarding the development of hypomethylating agents plus venetoclax as the new standard of care for older patients and those not eligible for induction chemotherapy. There is growing interest in the use of HMA/Ven combinations for younger and fit patients and in specific subsets of AML; limited data in these patient populations and ongoing clinical trials will be reviewed. Resistance to HMA/Ven therapy remains a significant concern, and recent data regarding mechanisms of resistance and potential strategies to overcome ven resistance will be addressed. Given the FDA approval of several targeted agents in AML since 2017, there is a need to understand and optimize the use of these medications in combinations with traditional AML therapy. Questions regarding combinations, sequencing and management of toxicities will be discussed. Optimization of 7+3 chemotherapy in specific subsets of AML will be reviewed, including 7+3 based combinations with FLT3 inhibitors or gemtuzumab, as well as the use of CPX-351 in older patients with secondary AML and recent data in other AML patient populations.
EMBARGOED UNTIL Sunday, December 10, 2023: 6-8 PM, Halls G-H (San Diego Convention Center)
Senior Author: Justin M. Watts, MD, Sylvester Comprehensive Cancer Center (Presenter: Jorge Cortes, MD, Georgia Cancer Center, Augusta)
Intro: Olutasidenib, a small molecule drug approved for treatment of relapsed and refractory acute myeloid leukemia, targets a specific mutation that exists in these cancers. It is being studied in subsets of patients whose disease returned after treatment with stem cell transplant or the drugs ivosidenib (IVO) or venetoclax (VEN). The research team is conducting post-study analyses to better understand the response to olutasidenib in these poor-prognosis subgroups.
Conclusion: Olutasidenib alone or in combination with a drug called azacitidine may induce complete remissions in patients with this type of AMD or myelodysplastic syndromes/neoplasms (MDS) that was relapsing or refractory to VEN, IVO or even hematopoietic stem cell transplant. This supports further study in larger groups of difficult-to-treat patients.
EMBARGOED UNTIL Monday, December 11, 2023: 4 PM
Presenting Author: Esther Natalie Oliva, MD, U.O.C. Ematologia, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio Calabria, Italy
Senior Author: Mikkael A. Sekeres, MD, Sylvester Comprehensive Cancer Center
Intro: QuANTUM-First, a global, Phase 3 clinical trial evaluated the safety and effectiveness of the novel oral inhibitor quizartinib in combination with standard first-line and consolidation chemotherapy, and as a maintenance monotherapy for adults with acute myeloid leukemia (AML). While quizartinib showed clinically meaningful improvements in overall survival, an exploratory endpoint assessed its impact on patient-reported outcomes. The authors report the first longitudinal results of these outcomes.
Conclusion: Quizartinib showed improvement in overall survival without any detrimental impact on quality of life and symptoms when added to standard chemotherapy, followed by maintenance monotherapy in newly diagnosed AML patients.
Lung Cancer
2649 Predictors and Timing of Venous Thromboembolism in Lung Cancer
EMBARGOED UNTIL Sunday, December 10, 2023: 6-8 PM, Halls G-H (San Diego Convention Center)
Presenter: Thomas Plate IV, MD, Sylvester Comprehensive Cancer Center (all authors affiliated with Sylvester and/or University of Miami)
Intro: Venous thromboembolism (VTE), the blockage of a blood vessel by a clot, is a common complication in lung cancer, and physicians often prescribe blood thinners for prevention, but there’s uncertainty about true incidence, risk factors and effects of treatments with various subtypes of lung cancer. Sylvester researchers analyzed data from their tumor registry to identify patients diagnosed with lung cancer between 2018 and 2022 and assess venous thromboembolism events and related factors.
Conclusion: The retrospective study found an increased risk of VTE among patients treated for lung cancer and determined that the development of thrombosis was associated with a significantly decreased overall survival. Every subgroup of patients was at high risk of developing VTE. Statistical analyses showed that VTE and other factors including age, gender, cancer stage, and blood counts were significant predictors of death.
Myeloid Malignancies
EMBARGOED UNTIL Saturday, December 9, 2023: 5:30-7:30 PM, Halls G-H (San Diego Convention Center)
Senior Author: Justin Taylor, MD, Sylvester Comprehensive Cancer Center (Additional Sylvester co-authors: Namrata Sonia Chandhok, MD, [co-first author] and Justin M. Watts, MD) (Presenting author: Jan Philipp Bewersdorf, MD, Memorial Sloan Kettering Cancer Center)
Intro: Researchers at Sylvester and Memorial Sloan Kettering have studied the effects of an experimental drug, E7820, in patients with relapsing or refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) that result from mutations in certain genes. Preclinical data from their work shows a synergy between E7820 and a drug called venetoclax.
Conclusion: Based on preclinical data, the researchers plan to amend their current Phase 2 study to include a separate arm of E7820 in combination with venetoclax – a combination that has never been studied in human AML and MDS patients.
Multiple Myeloma
210 Efficacy and Safety of Daratumumab (DARA) Monotherapy in Patients with Intermediate-Risk or High-Risk Smoldering Multiple Myeloma (SMM): Final Analysis of the Phase 2 Centaurus Study EMBARGOED UNTIL Saturday, December 9, 2023: 3:15 PM, Harbor Ballroom (Manchester Grand Hyatt San Diego) Presenting Author: Ola Landgren, MD, Sylvester Comprehensive Cancer Center Intro: Smoldering multiple myeloma (SMM) is a precursor disorder to multiple myeloma (MM). Current guidelines recommend only active monitoring for SMM, with treatment beginning only when it progresses to MM, but therapeutic intervention at the earlier stage may help delay progression to MM. Investigators in this multicenter collaboration hypothesized that daratumumab (DARA), a monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, could delay progression of SMM to MM. Preliminary results of the Phase 2 CENTAURUS study were previously reported. Here, the researchers present the final analysis. Conclusion: Findings from the final analysis continue to demonstrate the clinical activity of DARA monotherapy in patients with intermediate- or high-risk SMM after a median follow-up of approximately seven years. No new safety concerns were observed.
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Sylvester Comprehensive Cancer Center
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Landscape for AML Patients Evolving Rapidly as Research Discoveries Advance New Treatments
Newswise — MIAMI, FLORIDA (EMBARGOED UNTIL DEC. 10, 2023, AT 7:30 P.M. ET) – The treatment landscape for acute myeloid leukemia (AML) is evolving rapidly, as research discoveries at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine and other academic cancer centers advance new, more effective therapies for this aggressive blood cancer.
“We’ve seen more progress during the past 10 years than the previous four decades combined,” said Justin M. Watts, M.D., Sylvester hematologist, associate professor of medicine, and Pap Corps Early Career Endowed Professor in Leukemia, “especially when it comes to treating older AML patients.”
Watts, who serves as chief of the leukemia section at Sylvester, will highlight new drugs, such as Venetoclax plus Azacitidine, and new targeted therapies resulting from research advances when he leads an educational session at ASH 2023, the annual meeting of the American Society of Hematology in San Diego, Dec. 9-12.
The session is designed to update community-based physicians who treat AML patients on current standards of care for using these new drugs sequentially or in triplet combinations with targeted inhibitors.
Background
Acute myeloid leukemia is a cancer characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood-cell production. It’s one of the most common leukemia types in adults, although it’s fairly rare, accounting for about 1% of all cancers.
It tends to afflict older adults, with 68 being the median age when first diagnosed, according to the American Cancer Society. Men are slightly more at risk than women.
Typically, AML patients have been treated with intensive chemotherapy and a bone-marrow or stem-cell transplant. Those therapies are generally more effective in people under age 60. “We can cure about 60% of younger patients now, which is significantly better than just two decades ago,” said Watts. “But older patients, depending on their fitness level, don’t usually tolerate these treatments and historically less than 10 percent were cured, but this is now pushing 30% with the advent of venetoclax plus azacitidine and targeted inhibitors.”
Until recently, next steps for these patients were limited to supportive care and blood transfusions, he added.
Targeted Therapies for Mutations
However, the outlook has improved, especially for older patients, with the emergence of new drugs and targeted inhibitors for the mutations driving AML, Watts says.
“AML is almost always driven by mutations acquired over time,” he explained. “That’s why the risk of AML increases as we age.”
Although there are hundreds of mutations that can cause this blood cancer, and most patients have more than one, there are five more common ones that are targetable: IDH1, IDH2, FLT3, NPM1 and MLL, Watts said. All of these now have approved therapies – or ones in development – thanks to ongoing research at Sylvester and other cancer centers.
The results are encouraging. “We’re seeing very promising results in our studies and trials, combining Venetoclax, Azacitidine and targeted therapies, often as frontline therapy for AML,” he noted.
Watts said the combination of Venetoclax and Azacitidine is producing good outcomes in about 52% of older patients, and the median survival is more than 2 years in these patients, with some patients living much longer.
Additionally, targeted therapies are proving effective, even in relapsed patients, and these treatments are also better tolerated than chemotherapy.
Now, researchers like Watts and his colleagues must determine the best way to combine venetoclax and targeted therapies to produce the best outcomes. “That includes designing clinical trials to help us identify the optimal combinations for the right patients with specific mutations,” he explained, “and determining when we stop therapy for patients in a long remission.”
On the Horizon
Watts said that up to 50% of AML patients have a mutation for which there is no current targeted therapy. “We have to expand our targeted therapies to treat AML patients with harder to target mutations,” he explained, citing TP53 and RAS mutations as two common pathways for treatment resistance. “We currently have few approved therapies that are effective for these patients, especially if they are older.”
Watts believes the future direction for AML treatment will involve targeted therapy combined with the “best backbone we have, possibly chemotherapy for younger patients or the drugs like venetoclax and azacitidine generating good results for older adults.”
One of the biggest things that may come into play is immunotherapy, he said. “I can see us getting the immune system more involved in treating these blood cancers, as it has done with solid tumors and lymphoma.”
Disclosures
Dr. Watts serves on the consulting/advisory boards of Rigel, Servier, Celgene/BMS, Daiichi Sankyo, Aptose and Ativarre. He receives research funding from Takeda, Immune Systems Key Ltd, and Rigel.
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Sylvester Comprehensive Cancer Center
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ASH: Targeted oral therapy reduced disease burden and improved symptoms for patients with rare blood disorder
Newswise — SAN DIEGO ― The targeted therapy bezuclastinib was safe and rapidly reduced markers of disease burden while also improving symptoms for patients with a rare blood disorder called nonadvanced system mastocytosis, according to results of the Phase II SUMMIT trial reported by researchers at The University of Texas MD Anderson Cancer Center.
The findings, presented today at the 2023 American Society of Hematology (ASH) Annual Meeting, demonstrate that all participants treated with bezuclastinib achieved at least a 50% reduction in markers of disease burden and 63% reported their disease symptoms eased within 12 weeks. That number increased to 78% after an additional eight weeks of treatment, at which time all patients also reported an improvement in pain symptoms.
“The era of targeted therapy offers hope, not just for alleviating symptoms but for getting to the root of the condition,” said principal investigator Prithviraj Bose, M.D., professor of Leukemia. “Bezuclastinib provides precision targeting without the typical central nervous system or bleeding side effects often associated with similar drugs.”
Systemic mastocytosis (SM) is a rare disease marked by the buildup of malignant mast cells in the bone marrow and other tissues. These high levels of abnormal mast cells can lead to a multitude of symptoms due to the release of chemicals called mediators. SM can range from non-advanced (NonAdvSM) to advanced disease (AdvSM), with symptoms that can include brain fog and skin rashes to gut issues and life-threatening anaphylaxis.
In up to 95% of patients, SM is driven by the KIT D816V gene mutation. Treatments targeting this mutated kinase have been used for AdvSM variants, but they are known to have off-target activity that can cause toxicities that restrict dosing and, therefore, limit efficacy.
There are two variants within NonAdvSM: indolent systemic mastocytosis (ISM) and smoldering systemic mastocytosis (SSM). ISM, which affects the majority of patients with SM, is characterized mostly by symptoms related to mast cell degranulation and mediator release. SSM is identified by a higher mast cell burden, marked by high levels of blood enzymes like serum tryptase, but without resulting organ damage.
Bezuclastinib is a potent type-1 tyrosine kinase inhibitor that blocks mutant KIT D816V activity while sparing other kinases, minimizing the potential for off-target side effects. In a separate, prior studies, the drug demonstrated minimal brain penetration in animals and no central nervous system toxicities in patients with AdvSM.
The first part of the SUMMIT trial followed 20 patients with NonAdvSM for a median duration of seven months. The majority were female (75%) with a median age of 50. Seventy-five percent of patients had the KIT D816V mutation, and all had moderate-severe symptoms. Patients were treated with either 100 or 200 mg of bezuclastinib or with placebo. All patients continued to receive their baseline anti-mediator treatments throughout the trial.
Researchers evaluated the efficacy of bezuclastinib through multiple patient-reported outcome measures and changes in markers of disease burden, such as serum tryptase, bone marrow mast cell percentage and KIT D816V mutation allele burden.
Patients who received the 100 mg dose experienced a median reduction in symptoms of 48.5% after 12 weeks. During this period, none of the patients in the placebo group reported significant improvement in their overall symptoms. However, after transitioning those patients to bezuclastinib treatment, 67% reported an improvement in their symptoms after four weeks.
After 20 weeks, more patients observed greater improvements in dermatological symptoms (78%), gastrointestinal symptoms (33%) and cognitive symptoms (33%) compared to the 12-week mark.
Adverse events generally were mild and reversible, with the most frequent being a change in hair color, nausea and peripheral edema. No serious adverse events related to bezuclastinib were reported in the 100 mg or 200 mg cohorts.
“This drug may offer great promise in the treatment of non-advanced systemic mastocytosis,” Bose said. “As we move forward, our aspiration is to optimize the dosage while maintaining a robust safety profile.”
To futher assess the drug’s efficacy in patients with NonAdvSM, next steps for the SUMMIT trial include comparing bezuclastinib against placebo once the optimal dose is determined. Part Ib of the trial will investigate 100mg and 150 mg daily doses that use a different formulation of the drug, and those results are expected in 2024, Bose explained.
The SUMMIT trial was sponsored by Cogent Biosciences. Bose reports relationships with Cogent Biosciences, GSK, Novartis, Karyopharm, AbbVie, PharmaEssentia, Jubilant, Morphic, Kartos, Telios, Disc, Jassen, Geron, Ionis, Incyte, Bristol Myers Squibb, Sobi, MorphoSys, Blueprint and Sumitomo. A full list of co-authors and disclosures can be found with the abstract.
Read this press release in the MD Anderson Newsroom.
University of Texas MD Anderson Cancer Center
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ASH: Novel menin inhibitors show promise for patients with advanced acute myeloid leukemias
Newswise — Two clinical trials led by researchers from The University of Texas MD Anderson Cancer Center demonstrated early positive results from novel therapies targeting menin for the treatment of relapsed or refractory acute leukemias with specific genetic alterations. Results from the studies were shared today in oral presentations at the 2023 American Society of Hematology (ASH) Annual Meeting. More information on all ASH Annual Meeting content from MD Anderson can be found at MDAnderson.org/ASH.
Menin inhibitor monotherapy reduces disease burden in majority of relapsed or refractory acute leukemia patients (Abstract 57) According to data from a Phase I trial led by Elias Jabbour, M.D., professor of Leukemia, the menin inhibitor JNJ-75276617 showed early clinical activity in patients with relapsed or refractory acute leukemias and genetic alterations in KMT2A or NPM1, which are associated with poor clinical outcomes.
Among 66 patients able to be evaluated after one month of treatment, JNJ-75276617 monotherapy reduced bone marrow disease burden in 71%, and 33 of those patients had a decrease in bone marrow blasts of more than 50%. Median time to first response was less than two months. Similar response rates were observed across patient groups with both genetic alterations.
“Patients with relapsed or refractory leukemias and KMT2A or NPM1 alterations often do poorly on currently available therapies, so there is a need to advance more effective options,” Jabbour said. “We are encouraged by the antileukemic activity of this monotherapy, which mimics what we saw in the preclinical setting.”
In the multi-center clinical trial, researchers took a stepwise approach in evaluating the safety and efficacy of JNJ-75276617, a potent and selective inhibitor of the interaction between the scaffolding protein menin and the methyltransferase KMT2A. Eighty-six patients who had acute leukemias with NPM1 & KTM2A genetic alterations were included in the trial.
Patients received the therapy orally on a 28-day cycle. Fifty-six percent of evaluable patients had AML with KMT2A alterations and 43% of evaluable patients had NPM1 alterations. The median age of trial participants was 63 years, while the median number of prior therapies was two.
Differentiation syndrome was the most common side effect in patients, but was overcome with step-up dosing. The trial is ongoing to determine the recommended Phase II dose.
The trial is sponsored by Janssen Pharmaceuticals. A complete list of collaborating authors and their disclosures can be found with the abstract.
Oral therapy combination shows promising results for advanced acute leukemias (Abstract 58) The Phase I/II SAVE trial, led by Ghayas Issa, M.D., assistant professor of Leukemia, combined the menin inhibitor revumenib with venetoclax and hypomethylating agent ASTX727, yielding encouraging responses in adult and pediatric patients with relapsed or refractory advanced acute myeloid leukemia (AML) with KMT2A or NUP98 rearrangements or NPM1 mutations.
The overall response rate among nine evaluable patients was 100%. Three patients achieved complete remission, one patient achieved complete remission with partial hematologic recovery, and three patients had complete remission with incomplete platelet count recovery. In addition, one patient had a partial response and one had a morphologic leukemia-free state. Measurable residual disease was undetectable in six of the patients.
“These advanced and acute leukemias often are very difficult to treat and currently have no approved targeted therapies. We believe these early results suggest this treatment will be highly effective in advanced leukemias,” Issa said. “This is our first look at an entirely oral combination therapy using menin inhibitors, and the results are very encouraging. If sustained in further trials, this could lead to a change in the standard of care for this patient population, with great potential to improve their quality of life.”
Revumenib is a potent, oral, selective inhibitor of the menin-KMT2A interaction. To date, nine patients aged 12 years and older have been enrolled in the trial. Of those, five patients had KMT2A rearrangements, three had NUP98 rearrangements and one had mutant NPM1. On average, patients had received three prior lines of therapy.
Side effects were manageable and consistent with previous studies. The trial is ongoing, with plans to establish the recommended Phase II dose and optimize delivery of the combination before enrolling patients in the Phase II cohort.
This investigator-initiated study was supported by Syndax and Astex. A complete list of collaborating authors and their disclosures can be found with the abstract.
Read this press release in the MD Anderson Newsroom.
University of Texas MD Anderson Cancer Center
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La explicación científica detrás de algunas reacciones extrañas del cuerpo
Newswise — EAU CLAIRE, Wisconsin — A diario, el cuerpo hace algunas cosas bastante extrañas e inusuales. A continuación, se incluyen algunas preguntas y respuestas que ofrecen la explicación científica de por qué suceden.
¿Por qué se arrugan los dedos de las manos en el agua?
Inicialmente, se pensaba que los dedos se arrugaban en el agua por los cambios en los líquidos que ocurren entre los tejidos y el agua en la que están inmersos. Expertos en evolución hallaron evidencia de que esto puede haber permitido a los seres humanos a agarrar mejor los objetos bajo el agua. A las personas con lesiones nerviosas en los dedos de las manos o de los pies generalmente no se les arrugan los dedos de la misma forma.
¿Por qué a veces siento un pulso en los oídos?
El pulso en los oídos puede deberse a diversos motivos. El tinnitus suele describirse como un timbre en los oídos, pero existe una variación en la que la persona siente y escucha el pulso en los oídos. Esto se denomina tinnitus pulsátil. Un aumento en la presión arterial o una obstrucción en el conducto auditivo puede ocasionar que la persona escuche el pulso. Otra causa puede ser una anomalía en las arterias próximas a los oídos. Este es un motivo para consultar con su equipo de atención médica.
¿Por qué tiritamos cuando hace frío?
Tiritar cuando hace frío es una manera de hacer temblar a los músculos para generar calor. El cuerpo siempre intenta mantener la temperatura lo más cercana posible a 98,6 grados (37 °C).
¿Por qué algunas personas estornudan cuando miran el sol?
Esto se conoce como reflejo del estornudo fótico. La explicación teórica detrás de esta reacción es la siguiente: el nervio óptico, que detecta un cambio en la luz, está ubicado cerca del nervio trigémino, que controla los estornudos. Un estornudo típico se produce por una irritación en la nariz, que activa al nervio trigémino y desencadena un estornudo. Al salir de una habitación a oscuras hacia un lugar con iluminación brillante, las pupilas se contraen. Este reflejo rápido se inicia en el nervio óptico y puede dar la sensación de irritación en la nariz, lo que genera el estornudo. No todas las personas tienen esta reacción, y no está claro por qué algunas la tienen y otras no.
¿Por qué siento una punzada en el costado al correr?
Las punzadas en el costado se ocasionan por la irritación del diafragma, un músculo que separa la cavidad pulmonar y la cavidad abdominal. Los corredores novatos o quienes incrementan el ritmo o la distancia tienen más probabilidades de sentir punzadas en el costado. En ocasiones, la causa es una respiración demasiado rápida o una alimentación inapropiada antes de correr. Si siente una punzada en el costado, disminuya la velocidad, estire los músculos del torso y concéntrese en respirar lenta y regularmente.
¿Por qué el párpado comienza a contraerse de repente?
La contracción del párpado se llama blefaroespasmo. Se desconoce la causa exacta, pero se suele atribuir a la fatiga, al consumo de cafeína y al estrés. Se recomienda estirar el músculo que se está contrayendo halándolo suavemente con la punta de los dedos en el área y descansar bien. En general, la contracción desaparece sola. Si la contracción dura más de un par de días o tiene dificultad para abrir el párpado, será necesario que lo vea un profesional de atención médica.
— Amy Rantala, M.D., atiende pacientes en Ortopedia y Medicina Deportiva en Eau Claire, Wisconsin.
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New Case Western Reserve University study finds diabetes drug may reduce risk for colorectal cancer
Newswise — CLEVELAND—A groundbreaking study by researchers at Case Western Reserve University suggests a class of medications used to treat type 2 diabetes may also reduce the risk of colorectal cancer (CRC).
The findings, published today (Dec. 7) in the journal JAMA Oncology, support the need for clinical trials to determine whether these medications could prevent one of the deadliest types of cancers. Eventually, the medications may also show promise in warding off other types of cancer associated with obesity and diabetes.
“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular anti-diabetic drugs, such as Metformin or insulin, at preventing the development of CRC,” said Nathan Berger, the Hanna-Payne Professor of Experimental Medicine at the Case Western Reserve School of Medicine and the study’s co-lead researcher.
Glucagon-like peptide-1 receptor agonists, or GLP-1 RAs, are medications to treat type 2 diabetes. Usually given by injection, they can lower blood-sugar levels, improve insulin sensitivity and help manage weight. They’ve also been shown to reduce the rates of major cardiovascular ailments.
Importantly the protective effect of GLP-1 RAs are noted in patients with or without overweight/obesity.
“To our knowledge,” said co-lead researcher Rong Xu, a professor at the School of Medicine, “this is the first indication this popular weight-loss and anti-diabetic class of drugs reduces incidence of CRC, relative to other anti-diabetic agents.”
Berger and Xu are members of the Case Comprehensive Cancer Center.
National health problem
Being overweight or obese or having diabetes are risk factors for increasing incidence of CRC and for making its prognosis worse.
The National Institutes of Health (NIH) defines being overweight and obese as an increase in size and amount of fat cells in the body above certain levels. These conditions are common nationally and are caused by several factors—among them diet, lack of sleep or physical activity, genetics and family history.
Healthcare providers use body mass index to measure body fat based on height and weight. Nearly 75% of adults ages 20 or older in the United States are either overweight or obese, and nearly 20% of children and teens ages 2 to 19 have obesity, according to the NIH.
Obesity is a chronic health condition that raises the risk for heart disease—the leading cause of death in the United States—and is linked to many other health problems, including type 2 diabetes and cancer.
The American Cancer Society estimates CRC is the third-leading type of cancer in both sexes, with 153,000 new cases per year. It is also the second-leading cause of cancer mortality with 52,550 deaths per year.
The study
Since GLP-1 RAs have been shown to be effective anti-diabetic and weight-loss agents, the researchers hypothesized they might reduce incidence of CRC.
Using a national database of more than 100 million electronic health records, the researchers conducted a population-based study of more than 1.2 million patients. These individuals had been treated with anti-diabetic agents from 2005-19; the CWRU team examined the effects of GLP-1 RAs on their incidence of CRC, as compared to those prescribed other anti-diabetic drugs.
Population-based research means matching as many people as possible with the same characteristics—sex, race, age, socio-economic determinants of health and other medical conditions—to accurately compare the drug’s effects.
Among 22,572 patients with diabetes treated with insulin, there were 167 cases of CRC. Another 22,572 matched patients treated with GLP-1 RAs saw 94 cases of CRC. Those treated with GLP-1 RAs had a 44% reduction in incidence of CRC.
In a similar comparison of 18,518 patients with diabetes treated with Metformin, compared to 18,518 patients with diabetes treated with GLP-1 RAs, had a 25% reduction in CRC.
“The research is critically important for reducing incidence of CRC in patients with diabetes, with or without overweight and obesity,” Berger said.
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(Initial data for this manuscript was developed last summer by Lindsey Wang and William Wang, Orange High School students whose work was sponsored by the Case Comprehensive Cancer Center and National Cancer Institute-funded Scientific Enrichment Opportunity/Youth Engaged in Science Program. Lindsey Wang is now a first-year undergraduate at Case Western Reserve in the pre-professional scholars program, planning to enroll at the Case Western Reserve School of Medicine.)
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Video shows deputies repeatedly punching man in headlock during violent arrest in East L.A.
Two Los Angeles County sheriff’s deputies put a man in a headlock and repeatedly punched him in the head outside his home in East Los Angeles, according to his family.
Deputies wrestled 34-year-old Alejandro Hernandez to the ground Monday, just before 4 p.m., and placed him in a headlock, according to his mother, Gabriela Ortega.
Hernandez’s family said he was washing his car outside his home when the confrontation began, but the Sheriff’s Department said he was walking in the street in the 3500 block of Floral Drive at the time. The deputies watched him move his hands toward his waistband similar to “someone who was possibly attempting to conceal something,” according to a Sheriff’s Department statement.
The deputies alleged they recognized Hernandez because of his prior history as a gang member and when they approached and searched him they “felt a firearm in his waistband,” according to the Sheriff’s Department.
Hernandez refused to be handcuffed, the Sheriff’s Department said, and that’s when the deputies forced him to the ground. The violent arrest was first reported by Fox 11 News.
In the cellphone video recorded by Ortega’s younger son, one deputy placed Hernandez in a headlock and pulled back his arm. Hernandez tried to pull the deputy’s arm off his neck, but the other deputy repeatedly punched and elbowed him in the head. Blood pooled on Hernandez’s face as the deputy continued to punch him and tried to get handcuffs on Hernandez’s wrist, according to the video. At one point during the encounter, a deputy pulled out a handgun from his holster and pointed it at a neighbor who approached Hernandez and the deputies, the video showed.
The deputies said they found a loaded 9-millimeter firearm inside Hernandez’s pants. He was arrested on suspicion of being an ex-felon in possession of a firearm and battery on a police officer. The department said Hernandez and the deputies were treated at a local hospital for their injuries.
“They’re saying that a police officer had blood. But it was my son’s blood,” Ortega said when reached by phone on Tuesday. “You could see in the video how he’s punching him so hard with his fist and elbow going back and forth. Of course he’s going to have blood.”
The department said the arrest and the deputies’ actions are under investigation.
“As with any use-of-force incident a comprehensive review will be conducted to determine if department policies and procedures were followed,” the Sheriff’s Department said in a news release.
Hernandez is an amputee, missing part of his leg, and spends most of his time at home, according to his mother. But she feels that because of his criminal record, law enforcement officers continue to harass him and her family. In a separate incident, sheriff’s deputies pulled over her husband because he didn’t have a license plate on the front of his vehicle. She said a deputy pointed a gun at her husband during that incident.
She feels the deputies who beat her son were going out of their way to target him.
“I want people to be held accountable for their actions. As a mother, that’s what I want and that’s what I’m going to fight for,” said Ortega, who was at work during the incident but saw the video footage later. “Just because you have a badge, you think that gives you the right and that you’re above the law?”
Hernandez remains in police custody, according to jail records, with no bail set.
Nathan Solis
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Cyberpunk 2077’s Incredible Turnaround Will Now Be Preserved Forever
Image: CD Projekt Red As Cyberpunk 2077 approaches its third anniversary, the beleaguered blockbuster is getting a send-0ff to immortalize its unlikely turnaround. CD Projekt Red announced an Ultimate Edition for the sci-fi RPG on November 21 that includes this year’s Phantom Liberty expansion and the massive 2.0 overhaul patch. There will even be a physical copy for PlayStation 5 and Xbox Series X/S owners.
Cyberpunk 2077: Ultimate Edition will come to “next-gen” consoles and PC on December 5, and give players the chance to experience the open world story and years of fixes and upgrades all in one place for $60.
“This new release is the perfect way to experience every story of the dark future; it also contains the free Update 2.0, which overhauled many of the game’s systems, introducing dynamic skill trees, high-octane vehicle combat, and enhanced enemy and police AI — as well as adding new weapons, vehicles, and clothes,” CDPR wrote in a press release.
Game of the Year editions became something of a joke in the industry many years ago, but if any release deserved to get repackaged that way, it’s Cyberpunk 2077. Once pulled from the PlayStation Store for being so busted on PS4, the game is now pretty close to what players had hoped for based on years of trailers and E3 hype. Phantom Liberty, starring Idris Elba as FIA sleeper agent Solomon Reed, is the type of high-quality expansion fans have come to expect from the studio behind The Witcher 3‘s Hearts of Stone and Blood and Wine DLC. The underlying gameplay has also markedly improved.
Read More: Phantom Liberty’s New Ending Is The Perfect Coda To Cyberpunk 2077
But the real significance of the new Ultimate Edition is that Cyberpunk 2077‘s definitive 2.0 version will now be the one included on physical discs for PS5 and Xbox Series X/S players. The Xbox version will even include the entire Phantom Liberty expansion incorporated into the base game. (PS5 owners will have to download it during installation.) That means that even in the actual year 2077, when the video game servers will have likely long since shut down, anyone who still has an ancient console and the Ultimate Edition disc will still be able to experience Cyberpunk 2077 in its complete form.
Lots of games have managed to engineer live service-style redemption arcs these days, but very few get to see them memorialized in physical form. Now if only the Netflix spin-off Cyberpunk: Edgerunners could get a physical release as well.
Ethan Gach
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More vampires need to play with their food
Even vampires deserve treats. One of the many sacrifices that people make in exchange for eternal life in vampire lore is flavor. They can only eat one thing for the rest of their elongated lives, and it’s a metallic, salty, sinister thing. We all know this. We accept this. But vampires shouldn’t have to give up texture, too. So, in 2013, filmmaker Jim Jarmusch was brave enough to create a vampire with the vision to turn that blood into something good to eat: Eve and her blood Popsicles in Only Lovers Left Alive.
As a millennial woman, I have consumed more than my fair share of vampire stories. I grew up entranced by Interview with the Vampire. Stephenie Meyer’s Twilight series of books and films fell into my lap right on the heels of another fantasy series that, er, need not be named. Then there was True Blood, The Vampire Diaries, binge-watching Buffy the Vampire Slayer on the then-new app Hulu. But just once has drinking blood ever looked appetizing to me. Once have I ever vanted to suck blood, and that’s thanks to Eve.
Jarmusch’s moody hangout comedy stars Tom Hiddleston and Tilda Swinton as vampires named Adam and Eve (don’t worry about it) who’ve been on-again-off-again spouses for centuries and reunite when Adam is in a particular state of ennui. He’s got a hookup at a local blood bank, so he doesn’t need to do any killing. But Eve gets experimental. In an effort to surprise and cheer Adam up, she freezes some O negative. Very refreshing, especially when you’re in “a hot spot,” she says. Now, Hiddleston enjoying “blood on a stick” is a finger-licking image by itself, but this is not that kind of thirst blog. Hand to Lilith, this is the first and only time I have felt represented on screen by a fictional vampire. This is exactly the type of thing I would do if I were undead. I love to eat Popsicles. I love to make Popsicles.
Have you ever been in a situation where you had limited ingredients in your house — because of money, college, a thunderstorm, or a pandemic, for example — and had to get creative in order to avoid eating the same thing every day? Imagine that plus immortality. Shouldn’t vampires be messing around in the kitchen in an attempt to spice up their lives, like, all the time? The titular cannibal on Hannibal enjoyed sanguinaccio dolce, an Italian pudding, with human blood instead of the traditional pig’s blood. You can’t tell me Lestat wouldn’t be into that.
Vampires are inventive, prolific even, in many ways. Across literature, film, and television, their fighting styles vary. They choose to spend their daytime hours in different ways. You can always count on a fictional vampire to experiment with fashion. But not food. Whether the story is romantic or horrifying or a bit of both, we usually see vampires feeding on fresh human blood by sucking directly from their victim’s neck, wrist if they’re polite, or femoral artery if they’re nasty. It can be scary or erotic, but never exactly tasty. If a vampire doesn’t want to kill, and we have plenty of sullen and brooding faces in popular culture, they’ll find more palatable methods. The immortal teenagers on The Vampire Diaries drink blood-filled IV bags like Capri-Suns. Baz in Rainbow Rowell’s Carry On series, Interview with the Vampire’s Louis de Pointe du Lac, and the “vegetarian” Cullen family in the Twilight series hunt animals. Still, they’re drinking from the source. There’s no sense of fun. There’s no flair.
I can think of some notable exceptions. On Buffy the Vampire Slayer, the vampire Spike alludes to enhancing his blood with burba weed for flavor and crushed-up Weetabix for texture. At least once in season 6 we see him doing it, so we know it wasn’t a dry joke (hard to tell with those Whedon types). What We Do in the Shadows has a little fun, too. The vampires can get high off the blood of people who are on drugs. They can mix blood with Bud Light and get drunk. Still, that’s not very elegant or inventive. I expect more from them.
Others just merit an honorable mention. The glamorous antagonist known only as the Countess in the 1985 sex comedy Once Bitten drinks a glass of blood with a celery stalk. Occasionally you’ll see vampires drink their blood from a red wine glass or a flask. Presentation is important, so I appreciate that. Amy Heckerling’s romantic comedy Vamps mixes it up by having Krysten Ritter stick a straw into the rat she’s draining. That’s (a) gross and (b) boring! And True Blood, of course, is built around a synthetic blood that vampires can buy bottled and drink “out” in society. However, many of the vampires on True Blood prefer the real thing and tend to drink it in the usual way. Russell will stick his hand into a human’s chest cavity and pull out their heart, but he apparently can’t be bothered to prepare his food.
Come on! Where are the foodie vampires? I know that Hollywood’s best and brightest can do better. What about blood foam? Blood soup is already a dish in many cuisines. There are lots of foods cooked with blood, like black pudding or coq au vin. Where’s the whipping, frying, curdling, and coagulating? Show me a vampire starting the day with a steaming cup of hot blood. I don’t see why you couldn’t make freeze-dried astronaut blood for an afternoon snack. If Popsicles are possible, why not a bloody shaved ice, slushie, or sorbet?
I don’t even think I’ve ever seen a vampire lick a rare steak. Let’s face it: Being a vampire looks fun! Except for drinking blood, of course. That can change. If vampire fiction is here to stay, we owe it to them to give them something good-looking to eat instead of just someone good-looking to eat.
Leah Marilla Thomas
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UTHealth Houston researchers awarded $2.6M NIH grant to study molecular pathways and potential strategies for treatment of myocardial ischemia and reperfusion injury
Newswise — A four-year, $2.6 million grant to study circadian rhythm and novel therapies to protect the heart during a heart attack or cardiac surgery has been awarded to UTHealth Houston by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.
Principal investigator Holger Eltzschig, MD, PhD, professor, and co-investigator Wei Ruan, MD, PhD, assistant professor, from the Department of Anesthesiology, Critical Care and Pain Medicine at McGovern Medical School at UTHealth Houston, are studying translational, pharmacologic, and interventional strategies targeting circadian rhythm and hypoxia signaling that could help patients who are experiencing a heart attack or undergoing open-heart surgery.
Previously published research in 2012 and 2021 by Eltzschig and Ruan showed that biological rhythms affect myocardial ischemia and reperfusion injury (IRI) severity. IRI can occur in the setting of a heart attack, open-heart surgery, or during circulatory arrest, where blood flow is temporarily cut off (ischemia). During this period, the affected heart tissues suffer from inadequate oxygen supply (hypoxia). Once the obstruction is removed and blood flow resumes (reperfusion), rather than bringing immediate relief, this sudden influx of blood can lead to additional stress and damage to the heart.
The previous research further indicated that larger infarctions or higher incidences of heart failure happen in patients with morning onset heart attacks rather than later in the day. This daytime variation of myocardial injury hints at a potential interaction between circadian rhythm and hypoxia signaling.
“My laboratory has been very interested in studying IRI for over two decades,” said Eltzschig, the John P. and Kathrine G. McGovern Distinguished University Chair and the director of the Center for Perioperative Medicine at McGovern Medical School. “We undertook an unbiased look to understand the molecular mechanisms of why there are differences in heart attacks in the early morning versus the late afternoon.”
In studies that led up to the current grant application, the team of scientists analyzed heart tissue samples from circadian rhythm-trained mice following heart attacks at different time points of the day. In addition, they analyzed samples derived from the left heart ventricle of patients undergoing cardiac surgery at different times of the day. They identified a highly differentially expressed gene, BMAL1, a core circadian transcription factor. The genetic deletion of BMAL1 in mouse hearts eliminates daytime variations in cardiac injury.
Natural protective molecules called hypoxia-inducible factors (HIFs) are activated due to a lack of oxygen and promote the adaptation to limited oxygen availability. In addition, HIFs limit excessive tissue inflammation in order to prevent further tissue damage. Specifically, researchers uncovered that HIF2A works together with BMAL1 in heart tissues to provide circadian-dependent heart protection.
With this grant, researchers will aim to understand how BMAL1 and HIF2A interact and their functional roles in modulating daytime variation of cardiac injury. High-resolution imaging techniques will be employed to study the molecular interactions between BMAL1 and HIF2A by Kuang-Lei Tsai, PhD, co-principal investigator and assistant professor, and postdoctoral researcher Tao Li, PhD, from the Department of Biochemistry and Molecular Biology at McGovern Medical School. They will further explore the possibility of targeting the BMAL1 and HIF2A pathways as therapeutic strategies to protect the heart from injuries during surgery.
“We are using data to see if the pathways and transcriptional regulations are occurring in patients undergoing cardiac surgery in the morning or the afternoon,” Eltzschig said.
The other co-principal investigator of the study is Jochen Daniel Muehlschlegel, MD, MMSc, MBA, professor and chair of the Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University. NIH Grant R01HL165748 funds this research.
University of Texas Health Science Center at Houston
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Enhancing cancer immunotherapy using modified CAR-T cells.
Newswise — CAR-T cell therapy is a last hope for many patients with blood, bone marrow or lymph gland cancer when other treatments such as chemotherapy are unsuccessful. A limiting factor of this otherwise very effective and safe therapy is that the cells used in the process quickly reach a state of exhaustion. Researchers at the University of Freiburg have now been able to prevent this exhaustion and thus significantly improve the effect of the therapy in a preclinical animal model. The new results have been published in the journal Nature Immunology.
Using the body’s own defences against cancer
CAR-T cells are one of the personalised cancer therapies and have been used in specialised centres in Europe since 2018. In this complex treatment, immune cells, or more precisely T cells, are taken from the blood of cancer patients, genetically engineered in the laboratory with a chimeric antigen receptor (CAR) and then re-administered. The receptor helps the T cells to identify and kill cancer cells. As a result, the therapy utilises the body’s own cells to permanently eradicate the cancer.A simplified T-cell receptor
The CAR functions like a sensor with which the T cell recognises characteristic surface features of cancer cells. The synthetic CAR consists in part of elements of the natural T cell receptor, but its structure is greatly simplified in comparison. The CAR has only one of the four different subunits that transmit the signals that trigger the activation of the immune response in unmodified T cells.“The CARs authorised by the drug authorities all use the so-called zeta chain, which triggers a particularly strong activation of the T cell as soon as the CAR binds to the surface of a cancer cell. Whether the other three signalling chains of the T-cell receptor – gamma, delta and epsilon – can also be used for CARs has not yet been investigated,” explains Prof. Dr Susana Minguet, who led the current study together with Prof. Dr Wolfgang Schamel. Both are members of the Cluster of Excellence CIBSS – Centre for Integrative Biological Signalling Studies at the University of Freiburg and are researching how the various subunits of the T cell receptor transmit signals in order to trigger an immune response.
For their current study, the researchers produced four types of CAR-T cells, each expressing a CAR with each of the four signalling subunits, and tested them in a mouse model of leukaemia. “Surprisingly, the zeta chain, the domain used in clinically applied CAR-T cells, showed a lower anti-tumour effect than the other three domains. These eliminated the cancer cells in the leukaemia model significantly better,” explains Schamel.
Strong activation is a downside
The researchers explain the result by the fact that although the zeta chain transmits a strong activating signal to the cell, this also quickly exhausts the cell. “It’s as if we were making the cells run an ultramarathon at maximum speed,” explains Minguet. In contrast, the delta chain, which showed the best efficacy in the current study, triggers an inhibitory signal parallel to the activation of the T cell. “This allows the immune cell to run at its optimum speed,” says Minguet.Results relevant to clinical research
“Our results show that CARs that use one of the other signalling domains instead of the zeta chain could mitigate or prevent the disadvantages of existing therapies with CAR-T cells,” summarises Schamel. The researchers conclude that the development of new CAR therapies should therefore consider strategies that can achieve a more balanced immune response.University of Freiburg
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Potato starch supplements could be solution to bone marrow transplant complications
BYLINE: Tessa Roy
Newswise — Experts at the University of Michigan Health Rogel Cancer Center have found a potential solution for preventing a common and dangerous complication in patients that receive stem cell transplants from a donor’s blood or bone marrow.
Approximately 18,000 people per year in the United States are diagnosed with life threatening illnesses, including blood cancers where a blood or bone marrow stem cell transplant from a donor is their best treatment option.
About 9,000 such transplants are performed yearly in the U.S.
When patients receive a stem cell transplant, they get a new immune system from the donor whose job is to attack cells that don’t belong there including cancer cells.
Sometimes, however, those donor immune cells (the graft) begin to see the patient’s own body (the host) as unfamiliar and foreign. As a result, the donor cells may attack the patient’s own organs and tissues, causing Graft versus Host Disease.
GVHD develops in up to half of patients who receive stem cell transplants from a donor’s blood or bone marrow. It can affect many parts of the body and can range from mild or moderate to more severe and even life threatening.
The way to prevent and treat GVHD is by using strong medicines to suppress the immune system which can cause patients to get infections which can also be life-threatening. Therefore, while bone marrow and blood stem cell transplants from a donor are lifesaving for many patients with various serious illnesses, the development of GVHD can cause injury or even death and the treatments available for GVHD are risky.
Previous research showed that the bacteria that normally live in the intestines and their products can affect whether or not GVHD happens after a transplant.
Researchers have found that a food supplement made from potato starch, when given to ten patients who received stem cell transplants from a donor, changed the products of intestinal bacteria in a way that could potentially prevent GVHD from happening.
“GVHD is a major limitation to the lifesaving capability of blood or marrow stem cell transplants. It is exciting to think of the prospect of potentially finding a simple, low-cost, and safe approach to mitigating this dangerous complication for patients who need a stem cell transplant, but researching this approach in more patients is still needed to confirm,” said Mary Riwes, D.O., assistant professor of internal medicine and medical director of the inpatient adult stem cell transplant unit of the Medical Directors Partnering to Lead Along with Nurse Managers program.
Investigators are currently enrolling more patients for a second phase of this study to determine whether taking potato starch will indeed result in less GVHD after stem cell transplant. Sixty patients undergoing a blood or bone marrow stem cell transplant from a donor who are ten years or older will be randomized to take potato starch or placebo starch in addition to taking all the usual medications for preventing GVHD with 80% receiving potato starch and 20% placebo starch. This phase II clinical trial will help researchers learn whether or not taking potato starch is an effective intervention for preventing GVHD.
More information about this Phase II trial can be found on Clinicaltrials.gov identifier: NCT02763033
Additional authors include Jonathan L. Golob, John Magenau, Mengrou Shan, Gregory Dick, Thomas Braun, Thomas M. Schmidt, Attaphol Pawarode, Sarah Anand, Monalisa Ghosh, John Maciejewski, Darren King, Sung Choi, Gregory Yanik, Marcus Geer, Ethan Hillman, Costas A. Lyssiotis, Muneesh Tewari and Pavan Reddy
Funding/disclosures: Thanks to the volunteers who participated in the study and the clinical and research staff of the University of Michigan Bone Marrow Transplant program. This work was supported by the National Heart, Lung, and Blood Institute (grant no. P01 HL149633, P.R., M.T., M.M.R.) which facilitated all bio sample analyses. The funder had no role in the design and analysis of the study. Resistant starch was purchased using institutional startup funds (M.M.R).
Paper cited: “Feasibility of a dietary intervention to modify gut microbial metabolism in patients with hematopoietic stem cell transplantation,” Nature. DOI: 10.1038/s41591-023-02587-y
Michigan Medicine – University of Michigan
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Why is Captain Laserhawk called a ‘Blood Dragon Remix,’ anyway?
Ubisoft and Netflix’s new animated series Captain Laserhawk: A Blood Dragon Remix has very little to do with the Far Cry game series, from which it draws part of its title. Viewers of the mixed-media show don’t need to know anything at all about Far Cry, or its strange, neon-infused spinoff from a decade ago. But series creator Adi Shankar said it would be “disingenuous” to not reference Far Cry 3: Blood Dragon, the 2013 video game that was a shocking aesthetic swerve in Ubisoft’s open-world survival adventure game.
Shankar said that calling his new mashup show, in which the worlds of Assassin’s Creed, Beyond Good & Evil, and the Tom Clancyverse collide, is him “paying homage, paying credit” to Far Cry 3: Blood Dragon.
“When you look at how important Far Cry 3: Blood Dragon was, it’s a seminal fucking piece of art,” Shankar said in an interview with Polygon. “At some point people are going to look back and say there were seminal things [in that game] that seeded this online art movement, which continues to grow. Blood Dragon was one of them. So this is me wanting to acknowledge that.”
Captain Laserhawk is more like a reverential cousin to Far Cry 3: Blood Dragon. Both pieces of media are set in dystopian futures, and steal liberally from ’80s-era influences: synthpop music, VHS tapes, video games, and effortlessly cool action stars. Far Cry 3: Blood Dragon’s hero was a mishmash of the T-800 Terminator and Kyle Reese wearing an NES Power Glove holding RoboCop’s hand cannon. Captain Laserhawk’s Dolph Laserhawk is similarly cybernetic, with a gun arm that evokes Mega Man’s Mega Buster or Samus Aran’s arm cannon.
There are clear similarities and distinct differences between the two Blood Dragons. Shankar described his show as “more of a vibe” as opposed to “adapting the ‘tome’ of Far Cry 3: Blood Dragon.” In fact, when Shankar’s show was first announced back in 2019, it was called Captain Laserhawk: A Blood Dragon Vibe.
Captain Laserhawk is “part of the same lineage” that the CRT-filtered, laser beam-slathered Far Cry game spinoff was, an aesthetic that has permeated through other works of art over the past decade. Shankar specifically namechecked Destiny 2, The Weeknd’s music videos, and the Duffer brothers’ Stranger Things as examples of contemporary works existing on the same creative lineage.
“It all just kind of organically happened via the internet and Blood Dragon was a seminal moment in that,” Shankar said.
And while the Far Cry 3 and Blood Dragon influences may be a small part of Shankar’s animated series, especially compared to how much Beyond Good & Evil influence it contains, there is some Far Cry at the show’s heart — and at its periphery.
“Well, you know [Far Cry 4’s] Pagan Min is in this, reinterpreted through a JoJo’s Bizarre Adventure lens,” Shankar said. And, he teased, “the universe is populated with other Far Cry characters. They exist, and you may not see them here, but they’re out there in the universe.”
Michael McWhertor
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