ReportWire

Tag: Blood

  • UTHealth Houston researchers awarded $2.6M NIH grant to study molecular pathways and potential strategies for treatment of myocardial ischemia and reperfusion injury

    UTHealth Houston researchers awarded $2.6M NIH grant to study molecular pathways and potential strategies for treatment of myocardial ischemia and reperfusion injury

    [ad_1]

    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.

    [ad_2]

    University of Texas Health Science Center at Houston

    Source link

  • Enhancing cancer immunotherapy using modified CAR-T cells.

    Enhancing cancer immunotherapy using modified CAR-T cells.

    [ad_1]

    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.

    [ad_2]

    University of Freiburg

    Source link

  • Potato starch supplements could be solution to bone marrow transplant complications

    Potato starch supplements could be solution to bone marrow transplant complications

    [ad_1]

    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

    [ad_2]

    Michigan Medicine – University of Michigan

    Source link

  • Why is Captain Laserhawk called a ‘Blood Dragon Remix,’ anyway?

    Why is Captain Laserhawk called a ‘Blood Dragon Remix,’ anyway?

    [ad_1]

    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.

    Far Cry bad guy Pagan Min does make an appearance.
    Image: Netflix

    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.”

    [ad_2]

    Michael McWhertor

    Source link

  • Anesthesiologist-led blood management programs save hospitals significant amounts of blood and reduce costs with same or better patient outcomes

    Anesthesiologist-led blood management programs save hospitals significant amounts of blood and reduce costs with same or better patient outcomes

    [ad_1]

     

    Newswise — SAN FRANCISCO — Blood management programs that reduced or avoided transfusions saved a health system millions of dollars annually, with a return on investment of more than $7 for every dollar spent, while achieving the same or better outcomes, suggests research presented at the ANESTHESIOLOGY® 2023 annual meeting. 

    Over the past 10 years, the Johns Hopkins Health System established a comprehensive blood management program with two primary goals: 1) to reduce unnecessary transfusions across the five-hospital health system, and 2) to provide specialized care that avoids transfusions in patients who decline them. Together these efforts save blood and reduce costs, making more blood available for those who really need it, such as trauma patients. Transfusions are routinely used for emergencies and trauma, but also are needed in heart, transplant, hip or knee replacement, spine, vascular, liver and pancreatic surgery. Nonsurgical patients also need blood, for example those with cancer (leukemia, lymphoma), sickle cell anemia or gastrointestinal bleeding.

    “Since we are always dealing with blood shortages, doing more with less is critically important,” said Steven M. Frank, M.D., lead author of the study and professor in the Department of Anesthesiology and Critical Care Medicine at Johns Hopkins Medicine, Baltimore. “We like to say that blood saves lives when you need it, but only increases risks and costs when you don’t. Our results showed that a comprehensive blood management program can substantially help the bottom line — for every dollar spent, we received $7.50 in return.”

    Starting in 2012, two anesthesiologist-led, multidisciplinary blood management programs were run side by side. 

    • The Patient Blood Management Clinical Community program was designed to reduce unnecessary transfusions using several methods. The methods include evidence-based transfusion triggers, a “Why Give 2 When 1 Will Do?” single unit of blood transfusion campaign, and other anesthesiology-led before, during or after surgery measures of “keeping blood in the patient” such as using medications or intentionally lowering blood pressure to reduce bleeding and using smaller tubes to collect blood for lab tests. Over a 10-year period, the annual blood acquisition cost reduction was $2.9 million, a 10.9% decrease and a 9.6-fold return on investment.
    • The Center for Bloodless Medicine and Surgery program was designed to avoid transfusions entirely for those who don’t accept them, primarily Jehovah’s Witness patients. The program brings in revenue by attracting patients who are often turned down by other hospitals. Over 10 years, the program brought in approximately $5 million a year (after subtracting the direct cost of care), representing a 6.6-fold return on investment. 

    Clinical outcomes such as infection, blood clots, kidney injury, heart attack or stroke were the same before and after the Patient Blood Management Clinical Community program was instituted. Clinical outcomes were the same or better for the Center for Bloodless Medicine and Surgery program, as the incidence of hospital-acquired infection was significantly lower when transfusions were avoided. 

    “By reducing unnecessary medical procedures, we are actually doing more with less and providing higher value care,” said Dr. Frank. “Since clinical outcomes are either the same or better while giving less blood, the patients benefit from reduced risks and costs.”

    THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS

    Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific professional society with more than 56,000 members organized to advance the medical practice of anesthesiology and secure its future. ASA is committed to ensuring anesthesiologists evaluate and supervise the medical care of all patients before, during and after surgery. ASA members also lead the care of critically ill patients in intensive care units, as well as treat pain in both acute and chronic settings.

    For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at asahq.org. To learn more about how anesthesiologists help ensure patient safety, visit asahq.org/MadeforThisMoment. Join the ANESTHESIOLOGY® 2023 social conversation today. Like ASA on Facebook, follow ASALifeline on Twitter and use the hashtag #ANES23.

     

    # # #

     

    [ad_2]

    American Society of Anesthesiologists (ASA)

    Source link

  • Two easy fixes could reduce bleeding after cesarean delivery

    Two easy fixes could reduce bleeding after cesarean delivery

    [ad_1]

    Newswise — SAN FRANCISCO — Two simple solutions could help prevent severe bleeding (postpartum hemorrhage) after cesarean delivery, suggests research presented at the ANESTHESIOLOGY® 2023 annual meeting. As the leading cause of maternal mortality in the U.S. at the time of birth, postpartum hemorrhage is more common after cesarean deliveries than vaginal births.

    Both solutions help address uterine atony, which causes up to 80% of postpartum hemorrhage. Uterine atony is when, after delivery, the uterus remains soft and weak instead of contracting to compress the blood vessels that had been attached to the placenta. One solution involves infusing a medication to help the uterus contract after delivery. The other is an early warning system that prompts an assessment of how well the uterus is contracting after delivery to quickly alert the health care team when a woman is at risk for heavy bleeding and requires treatment.

    “Bleeding during a cesarean delivery is a high-stakes, high-risk situation, and when it occurs, the obstetrics and anesthesia teams must work together to rapidly prevent and treat ongoing bleeding,” said James Xie, M.D., lead author of the early warning study and clinical assistant professor of anesthesiology, perioperative and pain medicine at Stanford University, California. “Studies have shown that rapid recognition and management are essential to improving outcomes.”

    “The ultimate goal is to decrease maternal mortality and morbidity,” said Jessica Ansari, M.D., M.S., senior author for both studies and an obstetric anesthesiologist at Stanford University. “Recent estimates show a new mother dies of postpartum hemorrhage about every seven minutes, mostly in low-resource settings. If our findings can be confirmed in larger studies, it could transform the way we prevent and treat postpartum hemorrhage.”

    Calcium chloride infusion

    The researchers looked at using calcium chloride to help prevent bleeding in women with uterine atony because it is inexpensive, simple, safe and doesn’t require refrigeration like other treatments. Consequently, it can be used even in very low-resource settings, where women are much more likely to die from pregnancy-related bleeding. They found that calcium chloride reduced the amount of bleeding that patients experienced during their cesarean delivery by nearly a measuring cup (more than 200 mL).

    The double-blind, randomized, controlled trial included 120 women who required a cesarean delivery after labor with an oxytocin infusion (which increases contraction of the uterus during labor), placing them at much higher risk of suffering from uterine atony and bleeding after the birth. Researchers randomly assigned 60 women to receive 1-gram infusions of calcium chloride and 60 women to receive a placebo. The infusion was administered slowly after the baby was delivered, and the study was blinded, meaning the patients and their doctors were unaware if they received calcium or the placebo. Of the women who received the placebo, 57% had postpartum hemorrhage and 15% required a blood transfusion, while 40% of those who received calcium chloride had postpartum hemorrhage and 8.3% required a blood transfusion.

    The last Food and Drug Administration-approved drug to treat uterine atony was released in 1979.

    “New treatments to treat uterine atony are desperately needed,” said Alla Yarmosh, M.D., lead author of the study and clinical assistant professor in anesthesiology at Stanford University. “This is the first time an infusion of calcium chloride has been studied as a possible treatment to help the uterus contract after cesarean delivery and decrease bleeding in those patients. If our findings are confirmed by larger studies, it would be an easy technique for institutions to implement since anesthesiologists run infusions during surgery regularly.”

    Early warning system

    For the early warning study, researchers created an alert that pops up on the anesthesiologist’s electronic health record (EHR) module two minutes after the baby is marked as delivered, asking for a uterine score from 1-10. The anesthesiologist prompts the obstetrician to assess the uterine tone (by manually feeling it) and provide the score, which the anesthesiologist records. Scores of 6 or lower mean the uterus is not contracting well and the woman is at higher risk for postpartum hemorrhage.

    This real-time communication that a woman is at risk alerts the treatment team, which can then determine the best solution. Physicians can give the woman medications to help the uterus contract better or put stitches or balloons in the uterus to compress the vessels to prevent further bleeding, said Dr. Xie. They also can anticipate and prepare for hemorrhage, which can be addressed by giving the woman medications to stabilize blood clotting or ordering blood products to be ready for transfusion.

    The study assessed more than 1,000 consecutive cesarean deliveries by 70 different obstetricians over eight months. The uterine tone score was assessed three times for each patient and was documented reliably; two minutes after delivery (recorded 87% of the time), seven minutes after delivery (recorded 97% of the time), and 12 minutes after delivery (recorded 98% of the time). At 12 minutes, 179 women (18%) had scores of 6 or lower, meaning they were at higher risk for severe bleeding. Of those with scores of 6 or lower, 77% experienced hemorrhage, 46% experienced major hemorrhage and 25% needed a blood transfusion.

    “Our research shows that this simple scoring system is a very meaningful, easy way to ensure that if the uterus is contracting poorly and there is a risk of hemorrhage, it will be recognized by their health care team early,” said Dr. Xie. “In the future we can further refine models that predict when women are at high risk of bleeding around the time of delivery to help physicians be prepared to manage bleeding caused by poor uterine tone.”

    The United States has the highest maternal mortality rate among high-income countries.

    THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS

    Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific professional society with more than 56,000 members organized to advance the medical practice of anesthesiology and secure its future. ASA is committed to ensuring anesthesiologists evaluate and supervise the medical care of all patients before, during and after surgery. ASA members also lead the care of critically ill patients in intensive care units, as well as treat pain in both acute and chronic settings.

    For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at asahq.org. To learn more about how anesthesiologists help ensure patient safety, visit asahq.org/madeforthismoment. Join the ANESTHESIOLOGY® 2023 social conversation today. Like ASA on Facebook, follow ASALifeline on Twitter and use the hashtag #ANES23.

    [ad_2]

    American Society of Anesthesiologists (ASA)

    Source link

  • Make diagnosing serious geriatric diseases as easy as measuring blood sugar

    Make diagnosing serious geriatric diseases as easy as measuring blood sugar

    [ad_1]

    Newswise — In 2023, life expectancy in Korea will be 83.6 years, the third highest among OECD countries, and it is steadily increasing every year. As the proportion of the elderly population increases, the social cost of treating various geriatric diseases is also increasing rapidly, and there is a growing interest in early diagnosis of diseases. Among the various diagnostic methods, researchers are actively conducting research on measuring glutamine as an indicator of geriatric diseases by finding that the concentration of glutamine in the cells and blood of patients with serious diseases such as cancer, diabetes, and dementia is significantly changed compared to normal people.

    Dr. Seo, Moon-Hyeong of the Natural Product Research Center at the Korea Institute of Science and Technology (KIST), together with Dr. Park, Keunwan of the Natural Product Informatics Research Center, have developed a technology that can quickly and accurately measure glutamine concentrations without complicated measurement processes and expensive analytical equipment through the principle of ‘ligand-induced protein assembly’.

    Glutamine is an amino acid in the blood that is used by cells to synthesize proteins or as an energy source, and its rapid fluctuation in certain situations makes it a useful biomarker for the treatment and early diagnosis of disease. For this reason, researchers are actively studying glutamine metabolism in the body to diagnose metabolic and degenerative diseases, including cancer treatment by inhibiting the metabolism of glutamine, which is also a nutrient for cancer cells.

    Until now, the measurement of glutamine concentration in the body has relied on expensive specialized analytical equipment such as amino acid analyzers, which cannot measure changes in glutamine concentration in living cells in real time. In the case of relatively low-cost research kits, cumbersome pre-treatment processes such as protein removal in biological samples were required, resulting in long measurement times and low accuracy.

    The team developed a sensor protein for measuring glutamine based on the principle of “ligand-induced protein assembly” that can easily measure the concentration of glutamine in the blood. By separating a glutamine binding protein into two artificial proteins and then binding to the sample, and named it Q-SHINE by combining Q, the symbol for glutamine, and SHINE, which means brightly glowing. Experiments showed that the Q-SHINE sensor was highly selective, not responding to amino acids with similar structure such as glutamic acid and D-glutamine. The lowest concentration of glutamine that can be measured is 1 micromolar (µM, one millionth of a molar), which is 20 times lower than the enzymatic assay most commonly used in research kits. In addition, the sensor protein can be easily produced in E. coli, making it possible for a research kit to analyze glutamine concentrations at the same level as analytical instruments worth hundreds of millions of dollars.

    The team also used the Q-SHINE sensor to monitor changes in glutamine concentration in the cytoplasm and mitochondria of living cells in real time. In particular, by verifying the difference in glutamine concentration between cancer cells and normal cells, it is expected to speed up the development of anticancer drugs by inhibiting glutamine metabolism.

    “The Q-SHINE sensor developed by KIST will enable easy monitoring of glutamine concentration, similar to the self-monitoring of blood glucose by diabetics,” said Dr. Seo, Moon-Hyeong. “If used for glutamine metabolism research, it will greatly contribute to early diagnosis and identification of causes of severe geriatric diseases such as cancer, diabetes, and dementia, as well as development of cancer drugs that regulate glutamine metabolism.”

     

    ###

    KIST was established in 1966 as the first government-funded research institute in Korea. KIST now strives to solve national and social challenges and secure growth engines through leading and innovative research. For more information, please visit KIST’s website at https://eng.kist.re.kr/

    The research, which was supported by the Ministry of Science and ICT (Minister Lee Jong-ho) through the KIST Major Project and the Korea Research Foundation’s Excellent New Research Project, was published in the latest issue of the international journal Sensors and Actuators, B: Chemical (IF=8.4, top 0.8% in JCR).

    [ad_2]

    National Research Council of Science and Technology

    Source link

  • Prior infections and vaccinations affect COVID-19 mutation vulnerability, per study.

    Prior infections and vaccinations affect COVID-19 mutation vulnerability, per study.

    [ad_1]

    Newswise — A person’s immune response to variants of SARS-CoV-2, the virus that causes COVID-19, depends on their previous exposure – and differences in the focus of immune responses will help scientists understand how to optimise vaccines in the future to provide broad protection.

    A new study has found that people differ in how vulnerable they are to different mutations in emerging variants of SARS-CoV-2.

    This is because the variant of SARS-CoV-2 a person was first exposed to determines how well their immune system responds to different parts of the virus, and how protected they are against other variants.

    It also means that the same COVID-19 vaccine might work differently for different people, depending on which variants of SARS-CoV-2 they have previously been exposed to and where their immune response has focused.

    The discovery underlies the importance of continuing surveillance programmes to detect the emergence of new variants, and to understand differences in immunity to SARS-CoV-2 across the population.

    It will also be important for future vaccination strategies, which must consider both the virus variant a vaccine contains and how immune responses of the population may differ in their response to it.

    “It was a surprise how much of a difference we saw in the focus of immune responses of different people to SARS-CoV-2. Their immune responses appear to target different specific regions of the virus, depending on which variant their body had encountered first,” said Dr Samuel Wilks at the University of Cambridge’s Centre for Pathogen Evolution in the Department of Zoology, first author of the report.

    He added: “Our results mean that if the virus mutates in a specific region, some people’s immune system will not recognize the virus as well – so it could make them ill, while others may still have good protection against it.”

    The research, published today in the journal Science, involved a large-scale collaboration across ten research institutes including the University of Cambridge and produced a comprehensive snapshot of early global population immunity to COVID-19.

    Researchers collected 207 serum samples – extracted from blood samples – from people who had either been infected naturally with one of the many previously circulating SARS-CoV-2 variants, or who had been vaccinated against SARS-CoV-2 with different numbers of doses of the Moderna vaccine.

    They then analysed the immunity these people had developed, and found significant differences between immune responses depending on which variant a person had been infected with first.

    “These results give us a deep understanding of how we might optimise the design of COVID-19 booster vaccines in the future,” said Professor Derek Smith, Director of the University of Cambridge’s Centre for Pathogen Evolution in the Department of Zoology, senior author of the report.

    He added: “We want to know the key virus variants to use in vaccines to best protect people in the future.”

    The research used a technique called ‘antigenic cartography’ to compare the similarity of different variants of the SARS-CoV-2 virus. This measures how well human antibodies, formed in response to infection with one virus, respond to infection with a variant of that virus. It shows whether the virus has changed enough to escape the human immune response and cause disease.

    The resulting ‘antigenic map’ shows the relationship between a wide selection of SARS-CoV-2 variants that have previously circulated. Omicron variants are noticeably different from the others – which helps to explain why many people still succumbed to infection with Omicron despite vaccination or previous infection with a different variant.

    Immunity to COVID-19 can be acquired by having been infected with SARS-CoV-2 or by vaccination. Vaccines provide immunity without the risk from the disease or its complications. They work by activating the immune system so it will recognise and respond rapidly to exposure to SARS-CoV-2 and prevent it causing illness. But, like other viruses, the SARS-CoV-2 virus keeps mutating to try and escape human immunity.

    During the first year of the pandemic, the main SARS-CoV-2 virus in circulation was the B.1 variant. Since then, multiple variants emerged that escaped pre-existing immunity, causing reinfections in people who had already had COVID.

    “The study was an opportunity to really see – from the first exposure to SARS-CoV-2 onwards – what the basis of people’s immunity is, and how this differs across the population,” said Wilks.

    [ad_2]

    University of Cambridge

    Source link

  • Primary care intervention reduces hypoglycemia risk from type 2 diabetes overtreatment in older adults

    Primary care intervention reduces hypoglycemia risk from type 2 diabetes overtreatment in older adults

    [ad_1]

    Newswise — WASHINGTON—A newly published quality improvement study shows how a simple intervention by health care providers reduced the number of older adult patients with type 2 diabetes at risk for hypoglycemia (low blood sugar) by almost 50% and led to de-escalation of diabetes medications that cause hypoglycemia in 20% of patients.

    Twenty percent of Americans aged 65 and older have diabetes. This age group is particularly at risk for hypoglycemia because older people are often overtreated with insulin and other diabetes medications that can cause hypoglycemia. Severe hypoglycemia episodes in older adults can lead to adverse events such as falls, seizures, coma, and even death.

    Severe hypoglycemia from insulin and certain oral type 2 diabetes medications is the second most common adverse drug event resulting in emergency room visits and hospitalizations in older people with diabetes.

    “This study demonstrates that a low-cost clinical decision support tool, without the additional use of continuous glucose monitoring technology, can decrease the number of patients at high risk for hypoglycemia and reduce overtreatment with insulin and diabetes medications that cause hypoglycemia,” said study author Jeffrey B. Boord M.D., M.P.H., of Parkview Health System in Fort Wayne, Ind. Boord is the Chair of the Endocrine Society’s Hypoglycemia Prevention Initiative Steering Committee. “The patients in our study also reported significant reductions in the negative impact of hypoglycemia on their daily lives.”

    The study included 94 patients at risk of treatment-related hypoglycemia at Pottstown Medical Specialists in Pottstown, Pa. Physicians were trained on how to use a clinical decision support (CDS) tool to facilitate shared decision making with patients and improve health outcomes.

    During three clinic visits over 6 months, the clinicians used the tool to assess hypoglycemic risk, set individualized HbA1c (blood sugar level) goals, and reduce or discontinue the use of diabetes medications that can cause hypoglycemia.

    The use of the clinical decision support tool and shared decision making reduced the at-risk population by 46% and led to the discontinuation of hypoglycemic medications in 20% of participants. Patients also completed a validated patient-reported outcome tool (TRIM-HYPO) to evaluate the impact of non-severe hypoglycemic events on their daily lives. The patients reported improvements in their daily functioning, emotional well-being, diabetes management, sleep disruption and work productivity related to reduction in non-severe hypoglycemic events.

    “Because this intervention was so successful, we hope that our clinical decision support tool could be adopted for use in other primary care settings to lower the risk of hypoglycemia and improve the overall well-being of older adults with diabetes,” Boord said.

    The HypoPrevent study was part of a larger, multi-year joint effort by the Endocrine Society and Avalere Health, known as the Hypoglycemia Prevention Initiative, to determine best practices in primary care to reduce the impact of hypoglycemia on older (65+) people with type 2 diabetes who use medications that cause hypoglycemia and have a recent A1c <7%, both of which put them at increased risk of hypoglycemia.

    In conjunction with HypoPrevent, the Society formed a technical expert panel to develop quality measures—tools that help us measure or quantify healthcare processes, outcomes, patient perceptions and organizational structure—to reduce the risk of hypoglycemia in the outpatient setting. These performance measures are designed to help providers identify opportunities to improve patient care.

    For details about the initiative including an implementation guide for how to use the clinical decision tool and resources on the key role of the diabetes educator, visit: endocrine.org/hypoglycemia-prevention-initiative.

    The other authors of this study are Deborah A. Koehn of VCU Stony Point Women’s Health in Richmond, Va.; Kathleen Marie Dungan of The Ohio State University in Columbus, Ohio; Amisha Wallia of Northwestern University Feinberg School of Medicine in Chicago, Ill.; Deborah Otcasek Lucas of Avalere Health and BridgingCare LLC in Washington, D.C.; Robert W. Lash and Mila N. Becker of the Endocrine Society in Washington, D.C.; and Lawrence D. Dardick of David Geffen School of Medicine at UCLA in Los Angeles, Calif.

    The study was funded by Abbott Laboratories, Eli Lilly and Company, Merck, Novo Nordisk and Sanofi.

    The study, “Reducing Hypoglycemia From Overtreatment of Type 2 Diabetes in Older Adults: The HypoPrevent Study,” was published in the Journal of the American Geriatrics Society.

    # # #

    Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world’s oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.

    The Society has more than 18,000 members, including scientists, physicians, educators, nurses and students in 122 countries. To learn more about the Society and the field of endocrinology, visit our site at www.endocrine.org. Follow us on Twitter at @TheEndoSociety and @EndoMedia.

    [ad_2]

    Endocrine Society

    Source link

  • Unveiling Asthma’s Molecular Secrets: How Blood Molecules Influence Airway Processes

    Unveiling Asthma’s Molecular Secrets: How Blood Molecules Influence Airway Processes

    [ad_1]

    Newswise — New York, NY (September 20, 2023) – A new study by researchers at the Icahn School of Medicine at Mount Sinai has unraveled the intricate molecular interplay between systemic processes within the blood and localized processes within the airways of individuals with asthma.

    This pioneering research opens doors to potential novel treatments targeting specific molecules, with the aim of providing more effective relief for asthma patients. The research findings were published today in Genome Medicine.

    The study, which examined 341 participants comprising individuals with persistent asthma and non-asthmatic controls, used advanced transcriptomic sequencing techniques to analyze blood and nasal samples. Through this comprehensive approach, the researchers unveiled crucial molecules and processes that hold the key to understanding asthma better. Within the blood, the NK cell granule protein and perforin emerged as central players. In the nasal passages, the G3BP stress granule assembly factor 1 and InaD-like protein took on pivotal roles. Notably, the study underscored the profound influence of blood molecules on asthma by virtue of their effects on nasal molecules.

    Supinda Bunyavanich, MD, MPH, MPhil, the Mount Sinai Professor in Allergy and Systems Biology, Deputy Director of the Elliot and Roslyn Jaffe Food Allergy Institute, and a senior author of the study, highlighted the importance of this holistic approach: “Our findings represent a groundbreaking connection between systemic factors in the bloodstream and localized factors in the airways, working collaboratively to drive asthma. This discovery marks a significant stride towards understanding core mechanisms of asthma, transcending the conventional focus on only the airways.”

    However, Dr. Bunyavanich also sounded a note of caution, saying, “While these revelations provide invaluable insights into the molecular framework of asthma, it’s imperative to acknowledge that further research is needed before these breakthroughs can translate into immediate therapies.”

    Key Highlights:

    • The study offers an integrated perspective on the intricate relationship between systemic processes and airway-specific mechanisms in asthma.
    • Prominent blood molecules, including the NK cell granule protein and perforin, appear to exert their influence on asthma through their interactions with nasal molecules like the G3BP stress granule assembly factor 1.
    • The findings chart a path for future research endeavors, guiding the development of targeted asthma therapies that modulate these specific molecules.
    • Given that asthma affects millions globally, the implications of this research are far-reaching. This study paves the way for a deeper comprehension of the disease, instilling optimism for the emergence of more efficacious therapeutic strategies in the foreseeable future.

    For more details, read the full study in Genome Medicine.

    This study was funded supported by the National Institutes of Health grant R01 AI118833.

    Study details: Zhang L, Chun Y, Irizar H, et al. Integrated study of systemic and local airway transcriptomes in asthma reveals causal mediation of systemic effects by airway key drivers. Genome Medicine.

    Dr. Bunyavanich has no conflicts of interest to disclose.

     

    About the Mount Sinai Health System

    Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, more than 400 outpatient practices, more than 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

    Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,400 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. Hospitals within the System are consistently ranked by U.S. News & World Report‘s® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report‘s® “Best Hospitals” Honor Roll for 2023-2024.

    For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.

    [ad_2]

    Mount Sinai Health System

    Source link

  • Third Elaine Redding Brinster Prize Awarded for Development of Sickle Cell Disease Therapy

    Third Elaine Redding Brinster Prize Awarded for Development of Sickle Cell Disease Therapy

    [ad_1]

    Newswise — PHILADELPHIA—For his work discovering the basis for hemoglobin gene switching and applying those insights to develop a therapy for sickle cell disease and other blood diseases, the Institute for Regenerative Medicine at the University of Pennsylvania awarded Stuart Orkin, MD the third Elaine Redding Brinster Prize in Science or Medicine.

    Orkin’s research advanced the understanding of how the fetal hemoglobin gene— the main oxygen carrier protein in the human fetus—is silenced in adults. He also developed a therapy that re-activates the fetal gene for adult hemoglobin gene defects, which cause red blood cell diseases.

    “Dr. Orkin has beautifully illustrated how a career of basic science investigation into the mechanisms for gene regulation can be applied, in one’s own laboratory, to a method for combating devastating human diseases. Notably, his discovery of unexpected details in how the fetal hemoglobin gene is regulated suggested insights for a therapy, for which he availed of the latest gene editing technologies to develop a specific clinical application for sickle cell disease,” said Ken Zaret, PhD, director of Penn’s Institute for Regenerative Medicine and the Joseph Leidy Professor of Cell and Developmental Biology in the Perelman School of Medicine. “We are thrilled that Dr. Orkin is the third awardee of the Elaine Redding Brinster Prize.”

    The prize, supported by an endowment from the children of Elaine Redding Brinster, is awarded annually to a researcher whose singular discovery has made a unique impact on biomedicine. Each winner receives $100,000, a commemorative medal, and an invitation to present a ceremonial lecture at the University of Pennsylvania.

    Orkin will accept the prize on March 13, 2024, as part of the day-long Ralph L. Brinster Symposium at Penn’s Philadelphia campus. The symposium will feature eminent speakers from across the biomedical sciences, including Titia de Lange, PhD, of Rockefeller University; Carla Shatz, PhD, of Stanford University; Alejandro Sànchez Alvarado, PhD, of the Stowers Institute for Medical Research; and Marianne Bronner, PhD, of the California Institute of Technology.

    “I am very honored, and humbled, by recognition with the Brinster Prize. I hope that work of my laboratory will inspire others to pursue a career of fundamental discovery for the benefit of patients,” said Orkin, the David G. Nathan Distinguished Professor of Pediatrics, Harvard Medical School, and investigator with Howard Hughes Medical Institute.

    Orkin has been honored with several prestigious awards, including the Canada Gairdner International Award, the Gruber Foundation Prize in Genetics, the King Faisal Prize in Medicine, the Kovaleno Medal of the National Academy of Sciences, and the Harrington Discovery Institute Prize for Innovation in Medicine. Orkin is also a member of the U.S. National Academy of Medicine and National Academy of Sciences.

    Previous recipients of the Elaine Redding Brinster Prize include molecular biologist C. David Allis, PhD, and neurogeneticist Huda Zoghbi, MD.

    The Penn Institute for Regenerative Medicine is dedicated to researching cells and tissues with an eye toward turning the knowledge gained into new diagnostic and therapeutic techniques and tools. A member of the International Society for Stem Cell Research’s (ISSCR) Circle of Stem Cell Institute and Center Directors, the institute features faculty from five schools across the University of Pennsylvania and includes representation from Children’s Hospital of Philadelphia and the Wistar Institute.

     

    ###

     

    Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.

    The Perelman School of Medicine is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.

    The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

    Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.

    [ad_2]

    Perelman School of Medicine at the University of Pennsylvania

    Source link

  • Analysis Reveals Factors Associated With Patients With Sepsis Who Require Mechanical Ventilation

    Analysis Reveals Factors Associated With Patients With Sepsis Who Require Mechanical Ventilation

    [ad_1]

    Newswise — An analysis of 10 years of health data showed that risk factors for needing mechanical ventilation changed for patients with newly diagnosed sepsis as more time passed after onset. 

    In the study, 13.5% of patients with a new diagnosis of sepsis required initiation of mechanical ventilation. More than half of these patients required mechanical ventilation within the first 24 hours after sepsis onset, while initiation of mechanical ventilation occurred after 24 hours in 47.4% of patients.

    “Factors Associated With Initiation of Mechanical Ventilation in Patients With Sepsis: Retrospective Observational Study” examined 10 years of data from the University of Michigan Medical Center electronic health data warehouse. The analysis included adult patients with sepsis who were not receiving mechanical ventilation at sepsis onset. The study is published in American Journal of Critical Care (AJCC).

    Co-author Robert Freundlich, MD, MS, MSCI, is an associate professor, department of anesthesiology, and chief of the anesthesiology informatics research division at Vanderbilt University Medical Center, Nashville, Tennessee. The research was conducted during his research fellowship in critical care at the University of Michigan, Ann Arbor.

    “Requiring mechanical ventilation is often a pivotal point for patients with sepsis, and their risk of respiratory failure may vary with time,” he said. “Identifying patients at high risk and implementing targeted interventions in a timely manner has the potential to significantly improve outcomes.”

    A total of 35,020 patients met sepsis criteria, and 28,747 patients were eligible for inclusion after exclusion criteria were applied. The dataset spanned July 10, 2009, to Sept. 7, 2019.

    Of all eligible patients, 3,891 (13.5%) required mechanical ventilation within 30 days after sepsis onset. Of these, 2,046 (52.6%) required mechanical ventilation within 24 hours of diagnosis. Mechanical ventilation was subsequently initiated for 441 (11.3%) patients from one to two days after sepsis onset, and for 312 (8.0%) patients from two to three days following diagnosis. The remaining 1,092 (28.1%) experienced late respiratory failure or required mechanical ventilation three to 30 days after diagnosis.

    Patients requiring mechanical ventilation had higher baseline illness severity and a higher prevalence of 27 of the 35 comorbidities on the Elixhauser Comorbidity Index, which measures overall severity of comorbidities.

    They also had a higher in-hospital mortality rate (21%) than patients who did not require mechanical ventilation (7%). Further analysis revealed that of the patients who received mechanical ventilation before but not after sepsis onset, only 35 (4% of 822) died prior to hospital discharge.

    Factors that were independently associated with an increased likelihood that mechanical ventilation would be needed included race, systemic inflammatory response syndrome (SIRS) score, Sequential Organ Failure Assessment (SOFA) score and congestive heart failure. Risks decreased with time for the SOFA score and congestive heart failure and varied with time for four comorbidities and three culture results.

    The researchers recommend future proactive studies focus on the effects of fluid resuscitation and other processes of care on the need for mechanical ventilation in this patient population. The use of noninvasive ventilation and high-flow nasal cannula may also impact the need for intubation and mechanical ventilation and should be evaluated.

    To access the article and full-text PDF, visit the AJCC website at www.ajcconline.org.

    About the American Journal of Critical Care: The American Journal of Critical Care (AJCC), a bimonthly scientific journal published by the American Association of Critical-Care Nurses, provides leading-edge clinical research that focuses on evidence-based-practice applications. Established in 1992, the award-winning journal includes clinical and research studies, case reports, editorials and commentaries. AJCC enjoys a circulation of about 130,000 acute and critical care nurses and can be accessed at www.ajcconline.org.

    About the American Association of Critical-Care Nurses: For more than 50 years, the American Association of Critical-Care Nurses (AACN) has been dedicated to acute and critical care nursing excellence. The organization’s vision is to create a healthcare system driven by the needs of patients and their families in which acute and critical care nurses make their optimal contribution. AACN is the world’s largest specialty nursing organization, with about 130,000 members and nearly 200 chapters in the United States.

    American Association of Critical-Care Nurses, 27071 Aliso Creek Road, Aliso Viejo, CA 92656; 949-362-2000; www.aacn.org; facebook.com/aacnface; twitter.com/aacnme

    [ad_2]

    American Association of Critical-Care Nurses (AACN)

    Source link

  • New study shows promising evidence for sickle cell gene therapy

    New study shows promising evidence for sickle cell gene therapy

    [ad_1]

    New research published in the New England Journal of Medicine indicates that stem cell gene therapy may offer a promising, curative treatment for the painful, inherited blood disorder sickle cell disease (SCD).

    The findings from a new clinical trial, published August 31, add to the body of evidence supporting gene therapy as a treatment for sickle cell disease, which primarily impacts people of color.

    About 100,000 Americans have sickle cell disease, according to the U.S. Centers for Disease Control and Prevention. The condition, which can cause a lifetime of pain, health complications and expenses, affects one in 365 Black babies born in the U.S. and one in 16,300 Hispanic babies.

    Until recently, the only treatment options have been intensive bone marrow transplants from siblings or matched donors. But other curative therapies are now on the horizon. The University of Chicago Medicine Comer Children’s Hospital was one of three sites to enroll patients in the clinical trial, which tested a stem cell gene therapy to treat sickle cell disease.

    As part of the trial, researchers used CRISPR-Cas9 to edit specific genes in stem cells — the building blocks of blood cells — taken from each patient. The edits increased the cells’ production of fetal hemoglobin (HbF), a protein that can replace unhealthy, sickled hemoglobin in the blood and protect against the complications of sickle cell disease. The patients then received their own edited cells as therapeutic infusions.

    The therapy was the second for this disease to use CRISPR-Cas9 technology and the first to target a new genetic area and use cryopreserved stem cells with the hope of increasing access to such a treatment. Other gene therapy studies for SCD have used lentiviruses — a type of virus often modified and used for gene editing which remain in the cell long-term. No foreign material remains in stem cells edited with CRISPR-Cas9.

    Trial participants who received the CRISPR-edited stem cells reported a decrease in vaso-occlusive events, a painful phenomenon that occurs when sickled red blood cells accumulate and cause a blockage.

    “The biggest take-home message is that there are now more potentially curative therapies for sickle cell disease than ever before that lie outside of using someone else’s stem cells, which can bring a host of other complications,” said James LaBelle, MD, PhD, director of the Pediatric Stem Cell and Cellular Therapy Program at UChicago Medicine and Comer Children’s Hospital and senior author of the study. “Especially in the last 10 years, we’ve learned about what to do and what not to do when treating these patients. There’s been a great deal of effort towards offering patients different types of transplants with decreased toxicities, and now gene therapy rounds out the set of available treatments, so every patient with sickle cell disease can get some sort of curative therapy if needed. At UChicago Medicine, we’ve built infrastructure to support new approaches to sickle cell disease treatment and to bring additional gene therapies for other diseases.”

    As the scientific community continues to refine and expand the applications of gene therapy, the potential for curative treatments for diseases like sickle cell disease is becoming more of a transformative reality. The journey is ongoing, with the need for long-term follow-up and further research, but this study provides an encouraging glimpse into a future of effective genetic interventions.

    In the larger context of therapeutic development, LaBelle stressed the importance of the study’s contribution to the growing body of evidence supporting the viability of gene therapy as a treatment for sickle cell disease. Two other gene therapies for the disease are awaiting FDA approval this year.

    “The data from this trial supports bringing on similar gene therapies for sickle cell disease and for other bone marrow-derived diseases. If we didn’t have this data, those wouldn’t move forward,” he said.

    The study, “CRISPR-Cas9 Editing of the HBG1/HBG2 Promoters to Treat Sickle Cell Disease,” was published in NEJM in August 2023. Co-authors include Radhika Peddinti, along with researchers from St. Jude Children’s Research Hospital, Memorial Sloan Kettering Cancer Center, Novartis Institutes for BioMedical Research, Children’s Hospital Los Angeles, and IRCCS San Raffaele Hospital in Milan, Italy. The authors also acknowledged research coordinator Christopher Omahen and Amittha Wickrema, director of UChicago’s cell processing facility.

    [ad_2]

    University of Chicago Medical Center

    Source link

  • Microbiome-Directed Therapies for Undernutrition, Big Data for Precision Medicine, Health Equity, and More to Be Explored at 2023 AACC Annual Scientific Meeting & Clinical Lab Expo

    Microbiome-Directed Therapies for Undernutrition, Big Data for Precision Medicine, Health Equity, and More to Be Explored at 2023 AACC Annual Scientific Meeting & Clinical Lab Expo

    [ad_1]

    Newswise — ANAHEIM—At the 2023 AACC Annual Scientific Meeting & Clinical Lab Expo, laboratory experts will present cutting-edge research and technology that is shaping the future of clinical testing and patient care. From July 23-27 in Anaheim, California, the meeting’s 250-plus sessions will deliver insights on a broad range of timely healthcare topics. Highlights include discussions about addressing childhood undernutrition using microbiome-directed therapies, harnessing the power of big data to practice precision medicine, creating more equitable healthcare systems, improving cardiovascular care for women, and using genomic-modification strategies to treat sickle cell disease. 

    Microbiome-Directed Therapies for Childhood Undernutrition. Scientists are exploring whether disruptions to the normal development of the human gut microbiome—a collection of microbes in the gastrointestinal tract—could play a role in causing childhood undernutrition. In the meeting’s opening plenary, Dr. Jeffrey I. Gordon discusses the possibility of developing microbiome-directed therapies to address this devastating global health problem. Dr. Gordon is the 2023 Wallace H. Coulter Lectureship Awardee and founding director of The Edison Family Center for Genome Sciences & Systems Biology at the Washington University School of Medicine in St. Louis. 

    Practicing Precision Medicine from 700 Trillion Data Points. Over the past decade, researchers and clinicians have measured trillions of points of molecular, clinical, and epidemiological data that could be harnessed to improve disease diagnostics and therapeutics. In this plenary session, Dr. Atul Butte, chief data scientist at the University of California, San Francisco, highlights his center’s recent work on integrating electronic health records data from over 8 million patients and discusses how such big data could help providers to practice more precise medicine.

    Choosing Equity in Healthcare. The 2020 reckoning with racism in America had an intersectional impact on health, healthcare delivery, and medical education. Dr. Thea James, vice president of mission, associate chief medical officer, and co-executive director of the Health Equity Accelerator at Boston Medical Center, will share how one academic healthcare system approached an enterprise-wide transformation toward organizational equity. 

    Addressing Cardiovascular Disease in Women. Cardiovascular disease is the leading cause of death for U.S. women, yet the underrepresentation of women in medical research has led to pervasive sex-based gaps in knowledge and care delivery. In this plenary session, Dr. Nanette K. Wenger, professor of medicine in the division of cardiology at Emory University School of Medicine, calls for a cultural shift toward equity, including awareness campaigns that identify cardiovascular disease as the major health threat for women. 

    Advances in Curative Therapies for Sickle Cell Disease. In the meeting’s closing plenary, Dr. Mark C. Walters, chief of the hematology division and professor of pediatrics/hematology at the University of California, San Francisco, will discuss diverse new approaches for addressing sickle cell disease that apply genomic modifications to patients’ cells to elicit a therapeutic effect. He will present examples of both promising results and pitfalls, while also exploring how to ensure equitable access to these new therapies. 

    Additionally, at the Clinical Lab Expo, more than 900 exhibitors will display innovative technologies that are just coming to market in every clinical lab discipline. 

    “The 2023 AACC Annual Scientific Meeting program showcases the versatility of laboratory medicine professionals and the enormous impact they have on improving health and healthcare,” said AACC CEO Mark J. Golden. “From investigating promising therapies to translating data into better medicine to advancing equity in healthcare systems, our plenary speakers exemplify the pioneering vision and collaborative nature of the clinical laboratory community.”

    ______________________________________________________________________

    Session Information

    AACC Annual Scientific Meeting registration is free for members of the media. Reporters can register online here: https://www.xpressreg.net/register/aacc0723/media/landing.asp

     

    Microbiome-Directed Therapies for Childhood Undernutrition

    11001 Developing Microbiome-Directed Therapeutics for Treating Childhood Undernutrition

    Sunday, July 23

    5:00-6:30 p.m. U.S. Pacific Time

     

    Practicing Precision Medicine from 700 Trillion Data Points

    12001 Precisely Practicing Medicine from 700 Trillion Points of Data

    Monday, July 24

    8:45-10:15 a.m., U.S. Pacific Time

     

    Choosing Equity in Healthcare

    13001 Choosing Equity in Healthcare: An Organizational Transformation

    Tuesday, July 25

    8:45-10:15 a.m., U.S. Pacific Time

     

    Addressing Cardiovascular Disease in Women

    14001 Cardiovascular Disease in Women: Epidemiology, Awareness, Access, and Delivery of Equitable Health Care

    Wednesday, July 26

    8:45-10:15 a.m., U.S. Pacific Time

     

    Advances in Curative Therapies for Sickle Cell Disease

    15001 Advances in Curative Therapies for Sickle Cell Disease

    Thursday, July 27

    8:45-10:15 a.m., U.S. Pacific Time

     

    About the 2023 AACC Annual Scientific Meeting & Clinical Lab Expo

    The 2023 AACC Annual Scientific Meeting offers 5 days packed with opportunities to learn about exciting science from July 23-27 in Anaheim, California. Plenary sessions will explore microbiome-directed therapies for undernutrition, big data for practicing precision medicine, healthcare equity, cardiovascular disease in women, and promising sickle cell disease treatments.

    At the Clinical Lab Expo, more than 900 exhibitors will fill the show floor of the Anaheim Convention Center in Anaheim, California, with displays of the latest diagnostic technology, including but not limited to COVID-19 testing, artificial intelligence, point-of-care, and automation.

    About the Association for Diagnostics & Laboratory Medicine (ADLM) 

    Dedicated to achieving better health through laboratory medicine, ADLM (formerly AACC) brings together more than 70,000 clinical laboratory professionals, physicians, research scientists, and business leaders from around the world focused on clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management, and other areas of progressing laboratory science. Since 1948, ADLM has worked to advance the common interests of the field, providing programs that advance scientific collaboration, knowledge, expertise, and innovation. For more information, visit www.myadlm.org.

     

    [ad_2]

    American Association for Clinical Chemistry (AACC)

    Source link

  • At an event in California, a Brazilian health tech company presented its exclusive technology for blood tests with AI, delivering results within 30 minutes

    At an event in California, a Brazilian health tech company presented its exclusive technology for blood tests with AI, delivering results within 30 minutes

    [ad_1]

    Newswise — During the AACC – Annual Scientific Meeting & Clinical Lab Expo, held in Anaheim, California (USA) from July 23rd to 27th, the Brazilian health tech company Hilab, specializing in clinical analysis tests, participated in the congress alongside ABIMO – Brazilian Association of Medical Devices Industry. The company showcased innovative solutions for the healthcare industry, including two notable launches and the world’s only point-of-care Hemogram device capable of delivering a complete blood count with the assistance of AI and other technologies within 30 minutes.

    The Hilab Lens, the smallest point-of-care device for a complete blood count, represents a significant breakthrough in the field of digital microscopy. According to information from ANS- National Health Agency, this test is requested in nearly half of medical orders, as it can identify hundreds of diseases.

    The device works by healthcare professionals collecting a blood sample from the fingertip, similar to rapid glucose tests. The extracted sample is placed in a capsule and inserted into the device. The sample information is sent via the Internet of Things to the company’s central laboratory, where the test is verified first by Artificial Intelligence and then by a specialized healthcare professional in hematology. Finally, the test results are sent to the patient’s mobile phone via SMS and email, all within half an hour, while traditional methods take approximately 12 to 48 hours.

    Bernardo Almeida, an infectious disease physician, and Chief Medical Officer of Hilab, explains that “the complete blood count is so popular because it evaluates the quantity and quality of the main blood components, supporting the assessment and monitoring of acute infectious conditions, anemia evaluation, as well as assessing overall health. With the test’s ease and speed, medical professionals and patients can benefit from the prompt delivery of results in both routine and emergency cases.”

    The efficiency of the device was demonstrated through a pilot operation at the Brazilian hospital Erasto Gaetner, a reference institution for the clinical and surgical treatment of oncology patients in Curitiba (PR). Moreover, its theses were presented and validated in articles published by Nature, one of the most relevant scientific journals in the world. Today, the device is already in use in various healthcare facilities across the country, including occupational medicine companies, clinics, and other locations.

    Additionally, Hilab will introduce two new devices at the event: the Hilab Volt and the Hilab Wave. These compact devices will also operate remotely connected via the internet to the health tech’s central laboratory. The Hilab Volt functions based on electrochemistry and reads an electrode that selectively interacts with the sample, generating a useful analytical electrical signal. It will allow the evaluation of indices such as calcium, sodium, potassium, iron, and glucose, among others. The Hilab Wave operates through spectrophotometry, an optical analysis methodology that quantitatively measures the absorption of light by solutions, used for biological and physicochemical investigations. It enables dozens of tests, including phosphorus, magnesium, cholesterol, Vitamin D, and even the incidence of Malaria.

    “Participating in a scientific and international event of this magnitude reinforces Brazil’s ability to transform the healthcare sector using technology as an ally. For Hilab, as a Brazilian company, this is a particularly special and rewarding moment, marking a positive milestone in their history, indicating that they are on the right path by providing quality and innovative services that can address urgent healthcare access issues worldwide“, says Marcus Figueredo, CEO, and co-founder of Hilab.

    Certifications and Recognitions

    In 2016, the United Nations, in conjunction with DNV-GL, published a report called “Future of Spaceship Earth,” aiming to showcase companies that were creating technologies capable of achieving the Sustainable Development Goals (SDGs). Hilab was the only company from South America to be chosen and mentioned in the report.

    Hilab has also received recognition from the Global Entrepreneurship Competition in Barcelona, being among the 16 most promising ventures in the world. Moreover, it was the winner of the Med Tech Awards, a competition seeking companies with innovative solutions in the healthcare sector, organized by the British Government.

    Recently, the company was awarded the MIT Innovative Workplaces seal for its disruptive work in the healthcare sector. The certification from MIT Technology Review, the world’s largest ecosystem for content and innovation, measures the effectiveness of the startup’s innovation-related actions.

     

    About Hilab

    Hilab is a 100% Brazilian health tech founded in Curitiba with headquarters in Manaus, developing national devices and technologies for clinical analysis. Its innovative approach allows tests to be conducted using just a few drops of blood. Hilab’s disruptive model differentiates it from traditional laboratories, eliminating the need to transport biological samples. This innovative approach enables the delivery of results in a matter of minutes, providing a faster and more efficient experience for patients. The company employs an advanced technological platform that integrates Artificial Intelligence and the Internet of Things (IoT), enabling the digitization of tests from anywhere in the world, creating a decentralized laboratory.

    The company also offers the possibility of conducting tests in loco, without the need to send information remotely. Additionally, Hilab revolutionizes the patient experience by providing less uncomfortable and fingertip-based sample collection. With the use of innovative devices, Hilab simplifies the result delivery process, sending reports signed by healthcare professionals directly to the patient’s mobile phone within 30 minutes.

    [ad_2]

    2023 AACC Annual Scientific Meeting Press Program

    Source link

  • Atlantic Health System Cancer Care enrolls first patient in eastern US in groundbreaking non-Hodgkin lymphoma drug trial

    Atlantic Health System Cancer Care enrolls first patient in eastern US in groundbreaking non-Hodgkin lymphoma drug trial

    [ad_1]

    Newswise — MORRISTOWN, N.J. – JUNE 29, 2023 – Atlantic Health System Cancer Care is the only site on the east coast of the United States to enroll a patient in a new trial designed to test a groundbreaking approach to treating non-Hodgkin lymphoma. The patient enrolled received their first dose of the medication last week and is only the 20th patient in the country to receive this novel treatment.

    Developed by Caribou Biosciences, Inc., the medicine leverages chimeric antigen receptor (CAR) T-cell therapy, the practice of using modified versions of the body’s own T-lymphocyte immune cells to find, target and destroy cancer cells. However, unlike in traditional CAR T-cell therapies, where blood from the patient is withdrawn, then modified in a lab, and then infused back into the body, this medication is created using already donated blood, modified to match the patient, thus cutting down on the amount of time needed to prepare treatment and potentially resulting in a better match for the patient. The T-cells are modified using CRISPR genetic material editing technology.

    The treatment is provided at Atlantic Health System’s Morristown Medical Center in the Carol G. Simon Cancer Center by Mohamad Cherry, MD, Medical Director, Hematology/Oncology and Medical Director, Atlantic Cellular Therapy Program, and in partnership with the Translational Genomics Research Institute (TGen) of Phoenix, Arizona via the Breakthrough Oncology Accelerator, a pioneering research and clinical collaboration designed to improve patient access to the most innovative and sophisticated therapies for cancer.

    “Recent years have seen remarkable advancements in the ability to treat cancers of all types, but the next step in the treatment of blood cancers such as non-Hodgkin lymphoma may well be the groundbreaking, customized care we are researching as part of this trial,” said Dr. Cherry. “The ability to enter patients into treatment faster and with greater efficacy would be a tremendous win for patients and the physicians committed to helping them on their healing journey.”

    Atlantic Health System is already involved in a number of studies examining the amazing potential of CAR T-cell therapies treating leukemia and lymphoma.

    “The Atlantic Health System Cancer Care team is committed to providing extraordinary care to every patient in a way that is specific to that particular patient,” said Eric D. Whitman, MD, Medical Director, Atlantic Health System Cancer Care and Director, Atlantic Melanoma Center. “This exciting study holds the potential to craft even more tailored and specific medications and we are proud to be part of it.”

    This first-in-human trial involves non-Hodgkin lymphoma patients for whom initial treatment was unsuccessful or are experiencing a return of the disease. You can learn more about the study at the National Institutes of Health website for clinical trials.

    Visit the Atlantic Health System website to learn more about the exciting research underway in cancer care and other specialties.

    About Atlantic Health System Cancer Care

    Atlantic Health System Cancer Care offers an unparalleled network of cancer specialists and resources for more than 70,500 patients annually through its flagship Carol G. Simon Cancer Center at Morristown and Overlook medical centers, as well as its comprehensive oncology programs at Chilton, Hackettstown and Newton medical centers. With more than 250 cancer specialists and medical professionals, all five hospitals and Atlantic Medical Group have been recognized nationally for their role in advancing the fight against cancer.

    Atlantic Health System Cancer Care is the lead affiliate of Atlantic Health Cancer Consortium (AHCC) – the only New Jersey-based National Cancer Institute (NCI) Community Oncology Research Program (NCORP).  Atlantic Health System is affiliated with the Translational Genomics Research Institute (TGen) of Phoenix, Arizona, and together they have created the Breakthrough Oncology Accelerator, a pioneering research and clinical collaboration designed to improve patient access to the most innovative and sophisticated therapies for cancer.

    About Atlantic Health System

    Atlantic Health System is at the forefront of medicine, setting standards for quality health care in New Jersey, Pennsylvania and the New York metropolitan area. Powered by a workforce of 19,000 team members and 5,440 affiliated physicians dedicated to building healthier communities, Atlantic Health System serves more than half of the state of New Jersey including 12 counties and 6.2 million people. The not-for-profit system offers more than 400 sites of care, including its seven hospitals: Morristown Medical Center in Morristown, NJ, Overlook Medical Center in Summit, NJ, Newton Medical Center in Newton, NJ, Chilton Medical Center in Pompton Plains, NJ, Hackettstown Medical Center in Hackettstown, NJ, Goryeb Children’s Hospital in Morristown, NJ, Atlantic Rehabilitation Institute in Madison, NJ and through its partnership with CentraState Healthcare System in Freehold, NJ.

    The system includes Atlantic Medical Group, part of a physician enterprise that makes up one of the largest multispecialty practices in New Jersey with more than 1,600 physicians and advance practice providers. Joined with Atlantic Accountable Care Organization and Optimus Healthcare Partners they form part of Atlantic Alliance, a Clinically Integrated Network of more than 2,500 health care providers throughout northern and central NJ.

    Atlantic Health System provides care for the full continuum of health care needs through 24 urgent care centers, Atlantic Visiting Nurse and Atlantic Anywhere Virtual Visits. Facilitating the connection between these services on both land and air is the transportation fleet of Atlantic Mobile Health.

    Atlantic Health System leads the Healthcare Transformation Consortium, a partnership of six regional hospitals and health systems dedicated to improving access and affordability and is a founding member of the PIER Consortium – Partners in Innovation, Education, and Research – a streamlined clinical trial system that will expand access to groundbreaking research across five health systems in the region.

    Atlantic Health System has a medical school affiliation with Thomas Jefferson University and is home to the regional campus of the Sidney Kimmel Medical College at Morristown and Overlook Medical Centers and is the official health care partner of the New York Jets.

     ###

    [ad_2]

    Atlantic Health System

    Source link

  • Blood test aids in predicting lung cancer mortality risk

    Blood test aids in predicting lung cancer mortality risk

    [ad_1]

    Newswise — HOUSTON ― A blood-based test developed by researchers at The University of Texas MD Anderson Cancer Center can predict an individual’s risk of dying from lung cancer when combined with a personalized risk model.

    According to new data published today in the Journal of Clinical Oncology, a blood-based four-protein panel (4MP), when combined with a lung cancer risk model (PLCOm2012), can better identify those at high risk of dying from lung cancer than the current U.S. Preventive Services Task Force (USPSTF) criteria.

    These findings build upon previous MD Anderson research demonstrating the combination test more accurately determined who is likely to benefit from lung cancer screening than the USPSTF criteria.

    “This simple blood test has the potential to save lives by determining the need for lung cancer screening on a personalized basis,” said co-corresponding author Samir Hanash, M.D., Ph.D., professor of Clinical Cancer Prevention. “Given the challenges associated with CT as a frontline screening method for lung cancer and the fact that most individuals diagnosed with the disease do not meet current guidelines, there is an urgent demand for an alternative approach.”

    For this study, MD Anderson researchers analyzed pre-diagnostic blood samples from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, including 552 individuals who later developed lung cancer and 2,193 who did not. Of the 552 individuals diagnosed during the six-year study period, 70% (387) died from lung cancer.

    Using hazard ratios, the researchers assessed the relationship between the risk scores generated by the combination model (4MP + PLCOm2012) and the incidence of lung cancer death. The combination showed improved sensitivity, specificity and positive predictive value compared to the 2013 and 2021 USPSTF criteria for predicting lung cancer-specific mortality among individuals who smoked at least 10 pack-years (PYs).

    The USPSTF recommends that adults at elevated risk for lung cancer receive a low-dose CT scan each year, which was shown to reduce lung cancer deaths in the 2011 National Lung Screening Trial (NLST). The 2021 USPSTF criteria applies to adults aged 50 to 80 who have at least a 20 PY smoking history and currently smoke or have quit within the past 15 years.

    “For individuals who currently are not eligible for lung cancer screening, a positive test may help to identify those possibly at risk for lung cancer death,” said co-corresponding author Edwin Ostrin, M.D., Ph.D., assistant professor of General Internal Medicine. “We envision this as a tool that could be deployed worldwide, as the future of early detection of this disease.”

    Lung cancer causes an estimated 25% of cancer deaths. Early detection improves prospects of survival, but most countries do not screen for it. Fewer than half of all U.S. cases are among people who are eligible under USPSTF guidelines.

    While the blood test could be implemented as a lab-developed test in the near future, Food and Drug Administration (FDA) approval likely would require evaluation through a prospective clinical trial.

    Hanash is an inventor on a patent application related to the blood test. A complete list of co-authors and their disclosures is included in the paper.

    This study was supported by the National Institutes of Health and National Cancer Institute (U01CA194733, U01CA213285, U01CA200468, U24CA086368), the Cancer Prevention & Research Institute of Texas, Lyda Hill Philanthropies, and the Lung Cancer Moon Shot®, part of MD Anderson’s Moon Shots Program®.

    Read the full release on the MD Anderson Newsroom. 

     

    [ad_2]

    University of Texas MD Anderson Cancer Center

    Source link

  • توصلت أبحاث Mayo Clinic أن من يعانون من السُمنة المفرطة وأحد المتغيرات الجينية، عرضة أكثر للإصابة بارتفاع ضغط الدم

    توصلت أبحاث Mayo Clinic أن من يعانون من السُمنة المفرطة وأحد المتغيرات الجينية، عرضة أكثر للإصابة بارتفاع ضغط الدم

    [ad_1]

    Newswise — روتشستر ، مينيسوتا – تعتبر السمنة وما يرتبط بها من مشاكل في القلب والأوعية الدموية مصدر قلق كبير في جميع أنحاء العالم. وجدت دراسة أجرتها Mayo Clinic أن الأشخاص الذين يعانون من السمنة ولديهم متغير جيني معين معرضون بشكل متزايد لخطر الإصابة بارتفاع ضغط الدم. 

    مع السمنة ، يزداد خطر الإصابة بأمراض القلب والأوعية الدموية ، والتي تشمل السكتة الدماغية وفشل القلب الاحتقاني واحتشاء عضلة القلب. السمنة مرض متعدد العوامل ينتج عن اختلال توازن الطاقة. السمنة عامل خطر قابل للتعديل لأمراض القلب والأوعية الدموية. 

    وضحت ليزيث سيفينتس، دكتور في الطب “الباحثة في علم الجهاز الهضمي في Mayo Clinic “يتم التحكم في وزن الجسم من خلال مجموعة معقدة ومتعددة من التفاعلات بين العوامل الوراثية والعوامل البيئية. “تتراوح احتمالية الإصابة بالسُمنة الوراثية بين 40% إلى 70%، ولكن فقط 10% من حالات السُمنة المفرطة المبكرة تحدث بسبب جيني.” 

    تلك المتغيرات هي نتيجة لحدوث طفرات متنحية في الجينات المسؤولة عن مسار الليبتين والميلانوكورتين، وهو المسار المسؤول عن تنظيم تناول الطعام ووزن الجسم. وتعد هذه التغيرات الجينية الأكثر انتشارًا، حيث لوحظ وجودها في 6% من الأطفال و2.5% من البالغين الذي يعانون من السُمنة المفرطة المبكرة. 

    وفي برنامج الطب الدقيق للسُمنة التابع لـ Mayo Clinic، أرادت د. سيفينتس وزملاؤها دراسة الاختلافات بين عوامل الخطر للمرض القلبي الوعائي وبين الأمراض التي تصيب من يعانون من السُمنة المفرطة، سواءً كان لديهم المتغير الجيني أو لم يكن. ووضحت “بفهم تأثير هذه المتغيرات على صحة القلب والأوعية الدموية يمكننا مساعدة الأطباء لعلاج عوامل الخطر القابلة للتعديل في مرضى السُمنة المفرطة.” 

    لتحقيق ذلك، قام الباحثون بعمل دراسة مستعرضة على المشاركين في البنك الحيوي التابع لـ Mayo Clinic ممن يعانون من سمنة مفرطة. تم تعريف السمنة المفرطة على أنها زيادة مؤشر كتلة الجسم عن 40، أو الحاجة إلى إجراء جراحة علاج السُمنة بعد ثبوت وجود متغير جيني في مسار الليبتين والميلانوكورتين للمريض. يتكون الينك الحيوي التابع لـ Mayo Clinic من مجموعة من العينات الطبية والتي تشمل عينات الدم ومشتقاته، والمعلومات الطبية التي تبرع بها مرضى Mayo Clinic لاستخدامها في الأبحاث الطبية المستمرة. 

    تم تحديد 168 حامل للمتغير الجيني MC4R. ووجد الباحثون في مايو كلينك أن الحاملين لهذا المتغير كانوا أكثر عرضة للإصابة بارتفاع ضغط الدم، كما كان لديهم عدد أكبر من عوامل الخطر لأمراض القلب والأوعية الدموية مقارنة بغير الحاملين للمتغير الجيني وعددهم 2039. ووضح د. أندريس أكوستا، دكتور في الطب، الباحث الرئيسي في معمل الطب الدقيق للسُمنة “لم يؤثر العمر أو الجنس أو مؤشر كتلة الجسم -وكلها عوامل خطر لأمراض القلب والأوعية الدموية- على النتائج، وتوصلنا في النهاية إلى أن الحاملين للمتغير الجيني أكثر عرضة للإصابة بارتفاع ضغط الدم”. 

    مع ذلك، وتبعًا للنتائج، فالحاملين للمتغير الجيني MC4R ليسو أكثر عرضة للإصابة بالمرض القلبي الوعائي أو للوفاة، تبعًا للنتائج التي عُرضت في إحدى أبحاث مجلة “مايو كلينيك بروسيدنجز – Mayo Clinic Proceedings”. استكمل د. أكوستا، كبير الباحثين، قائلًا: “توقعنا وجود زيادة أكبر في ارتفاع ضغط الدم، لأن زيادة الوزن تنبئ بالإصابة بارتفاع ضغط الدم”. 

    وأعربت د. سيفينتس عن تفاجؤ الباحثين من عدم وجود علاقة ثابتة مع المرض القلبي الوعائي. ووضحت ” نظرًا لمدى تعقيد مسببات المرض القلبي الوعائي، فببساطة قد يكون هناك قدر ضخم من البيانات التي لم يتم قياسها في تحليلاتنا”. 

    تكمن أهمية هذا البحث بالنسبة للأطباء في إدراك أن مرضى السُمنة الذين أظهر تنميطهم الوراثي وجود متغيرات متباينة الزيجوت في مسار اللبتين والميلانوكورتين قد لا يكونون محميين من ارتفاع ضغط الدم كما كان يعتقد سابقًا. ووضحت د. سيفينتس “يحتاج هؤلاء المرضى إلى مزيد من الاهتمام بعوامل الخطر القابلة للتعديل لارتفاع ضغط الدم، بما فيها أنواع العلاج الفردية للسُمنة”. 

    قد يصاب الأفراد الحاملين للمتغير الجيني بالسُمنة منذ الطفولة، لكن لم يتم توثيق الفترة الزمنية في الورقة التي قدمها الباحثون في Mayo Clinic. نحتاج إلى أبحاث أخرى لتحديد مخاطر الإصابة طويلة المدى للسمنة وللمرض القلبي الوعائي في الحاملين للمتغير الجيني. 

    من بين قيود هذا البحث أن 90% من المشاركين في بنك الحيوي لـ Mayo Clinic من البيض، لذا لا يمكننا تعميم نتائج هذا البحث على الأعراق الأخرى. 

    تلقى بحث د. أكوستا الدعم من المعاهد الوطنية للصحة، ومن البنك الحيوي التابع لـ Mayo Clinic، وشركة Rhythm لدراسة الأنماط الجينية. لم يتم الإعلان عن أي تضارب في المصالح. يقدم مركز Mayo Clinic للطب الفردي الدعم للبنك الحيوي لـ Mayo Clinic. 

    يمكنكم الرجوع إلى الورقة البحثية للتعرف على القائمة الكاملة للمؤلفين، والتمويل وتضارب المصالح، والإفصاحات. 

    لمزيد من المعلومات، يمكنك الرجوع إلى مدونة مركز Mayo Clinic للطب الفردي.  

    ###   

     نبذة عن مايو كلينك للرعاية الصحية   مايو كلينك للرعاية الصحية، الموجودة في لندن، هي شركة فرعية مملوكة بالكامل لمؤسسة مايو كلينك، وهو مركز طبي أكاديمي غير هادف للربح. تُصنَّف مايو كلينك في المرتبة الأولى بين المستشفيات وفقًا لتقرير يو إس نيوز آند وورد ريبورت بسبب: جودة الرعاية. مايو كلينك للرعاية الصحية هي المدخل الرئيسي في المملكة المتحدة لتلك التجربة التي لا مثيل لها. تفضل بزيارة مايو كلينك للرعاية الصحية لمزيد من المعلومات.   

    [ad_2]

    Mayo Clinic

    Source link

  • Advancing bioprinting for functional blood vessels

    Advancing bioprinting for functional blood vessels

    [ad_1]

    Newswise — In this project volumetric bioprinting was for the first time successfully combined with melt electrowriting. This combines the speed and cell-friendliness of volumetric printing with the structural strength needed to create functional blood vessels. The study by the biofabrication lab of Regenerative Medicine Center Utrecht (RMCU) was published today in Advanced Materials.

    Volumetric printing is a technique that was pioneered for bioprinting by the RMCU biofabrication lab in 2019. It is a fast technique, which allows cells to survive the printing process. However, because this type of printing is done in cell-friendly gels, the resulting prints are structurally not very sound. This is a problem for blood vessels, which have to be able to withstand high pressures and bending. For this reason, a merger of volumetric bioprinting and melt electrowriting was pursued.

    Melt electrowriting is a highly accurate type of 3D printing that works by directing a narrow filament of molten (biodegradable) plastic. It’s able to produce intricate scaffolds that are mechanically strong and able to deal with force. The downside here is that they can’t be printed with cells in there directly, because of the high temperatures involved. Therefore, volumetric bioprinting was used here to solidify cell-laden gels onto the scaffolds.

    How to merge electrowriting with volumetric printing

    The process starts with the creation of a tubular scaffold using melt electrowriting. This is then submerged into a vial with photoactive gel and placed in the volumetric bioprinter. In principle, the laser of the printer can selectively solidify the gel that sits in, on and/or around the scaffold. “In order to get this right, we had to place the scaffold exactly center in the vial,” first author Gabriël Größbacher says. “Any deviation from the center would mean that the volumetric print would be off-set. But we managed to center it perfectly by printing the scaffold on a mandril that we fitted to the vial.”

    In this study, Größbacher and colleagues tested various thicknesses of the scaffold, which resulted in more or less strong tubes. Finally, they also tested various placements of the bioprinted gels. These could either be placed on the inner side of the scaffold, inside the scaffold itself or on the outside of it. By using two differently labeled stem cells, the team was able to print a proof of principle blood vessel with two layers of stem cells, and seeded epithelial cells in the center to cover the lumen of the vessel.

    From tubes to functional vessels

    The design could also allow for holes in the side of the print, giving the possibility for controlled permeability of the vessel for the blood to do its function. Finally, the researchers also created more complex structures like forked vessels, and even vessels with venous valves that were functional in maintaining a unidirectional flow.

    Größbacher: “This was a proof of principle study. What we now need to do is replace the stem cells with functional cells that are part of a real blood vessel. That means adding muscle cells and fibrous tissue around the epithelial cells. Our goal now is to print a functional blood vessel.”

    [ad_2]

    University Medical Center Utrecht

    Source link

  • Promising Phase III Results Give Hope to People Living with Myelodysplastic Syndromes

    Promising Phase III Results Give Hope to People Living with Myelodysplastic Syndromes

    [ad_1]

    Newswise — Amer Zeidan, MBBS, medical director of the hematology early therapeutics research program at Yale Cancer Center and associate professor of medicine (hematology) at Yale School of Medicine, will reveal new data at the American Society of Clinical Oncology (ASCO) annual meeting from a phase III study evaluating the efficacy of imetelstat in red blood cell (RBC) transfusion-dependent lower-risk myelodysplastic syndrome (LR-MDS) patients. Myelodysplastic syndromes(MDS) are a group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells. The study results demonstrate significant and clinically meaningful efficacy, representing a potential breakthrough in the treatment of anemic LR-MDS.

    Imetelstat, a telomerase inhibitor, was evaluated in patients who were heavily RBC transfusion-dependent LR-MDS and who were refractory or ineligible for erythropoiesis-stimulating agents (ESAs), but did not receive lenalidomide or hypomethylating agents (other drugs used to treat MDS). The phase III study, known as IMerge, enrolled a total of 178 patients. The findings from the study provide critical evidence supporting imetelstat’s efficacy and safety profile. These results are expected to have a substantial impact on future treatment strategies for patients diagnosed with LR-MDS.

    Dr. Zeidan, first and presenting author of the research at ASCO, answered questions on the study and its significance for patients living with MDS:

    Q: What is the significance of this study?

    A: “This is a very important study. Imetelstat is a first-in-class agent. It’s a first-in-class telomerase inhibitor, and this is the first time we have a phase III study of a drug in this class. We already completed the phase II study that was single arm that looked at a similar population of patients with lower risk MDS (myelodysplastic syndromes) who are heavily transfusion dependent, and the transfusion independence rate with the drug was around 40%. Transfusions in MDS are associated with increased risk of complications, increased risk of death, not to mention healthcare utilization and costs. So, trying to reduce transfusions and ideally make patients transfusion independent is a very important goal of treatment in patients with lower risk MDS.

    So the excellent activity of imetelstat in the phase II part of the study was taken to a phase III trial and what we have found in this study is what we actually expected based on the phase II trial: the transfusion dependence rate was much better with imetelstat compared to placebo, it was around 40% for an eight-week duration of transfusion dependence, the primary endpoint of the study, compared to 15% with a placebo; and most importantly, it was also durable. The median duration of transfusion independence for those who responded was more than 50 weeks. So clearly, a very positive study, very consistent with the phase II data. I think this drug could become an important option for patients.”

    Q: What are the key findings from the data? What will you highlight at ASCO?

    A: “During the ASCO presentation, we’ll discuss in detail, the efficacy of the drug in terms of transfusion independence, hematologic improvement, durability of response, but also looking within subgroups for patients based on the genetic profile. We will also discuss early signs of disease modification that we are seeing through reduction of variable allele frequency of important mutations that contribute to the pathogenesis of MDS. We’ll also discuss the side effect profile and how the interruption of therapy has led to, I think, a manageable and reversible side-effect profile, mostly in the setting of liver enzyme abnormalities and cytopenias (a medical condition where there are a low number of red blood cells).”

    Q: Are there other treatment options for this niche group of patients affected by this cancer?

    A: “Yes, so myelodysplastic syndromes have been renamed neoplasms by the World Health Organization, the most recent classification to emphasize that it’s a cancer. Many people think of MDS as an anemia or a pre-leukemia or a syndrome, but they are actually cancers. However, they differ in their severity. Patients in general are grouped into two big groups, lower risk and higher risk. In lower risk patients, those patients can live for years, but they have a lot of complications related to the low blood counts. That could be anemia, thrombocytopenia, or neutropenia, or a combination of these, but the most common use cytopenia is anemia. Anemia often is associated with reduced quality of life. The patient often needs regular transfusions. It’s also associated with significant complications and high risk of death, as well as issues related to needing to go to the clinic frequently, healthcare utilization costs. Correction of anemia is very important. Historically, the only treatment we had was erythropoiesis stimulating agents for patients with lower risk MDS. In recent years, other drugs have been approved like lenalidomide, as well as hypomethylating agents and luspatercept. However, the response to these drugs is limited, and at some point, the patient will progress and will need additional treatment. I think imetelstat potentially could fill a very important gap there because those patients are generally not going to be cured without a bone marrow transplant, which is not something that’s commonly done in MDS patients where the average age is in the early 70s. The goal is to try to improve quality of life in those lower risk MDS patients and make them transfusion independent as much as possible and that’s generally achieved by sequential therapy. So you go from one agent to the next, while trying to maintain quality of life keeping the patient out of the hospital and minimizing complications of the treatment itself.”

    Q: What is next in terms of research. What would you like done in future studies?

    A: “This is a very important question. I think the next step is going to be focusing more on how to increase the overall durability of response as well as increased the rate of response. And I think that’s going to be done by combining drugs. We have several active drugs now. So, figuring out how to combine them, and probably trying to treat patients earlier in their disease course will be important, so they don’t even get to the point of becoming transfusion dependent. Several of those studies I think are going to happen over the next few years. And of course, there are other drugs that are being studied in phase I and phase II trials. Some of those hopefully will also lead to benefit to patients so that if we cannot cure the disease, we can for most patients at least improve their quality of life, make transfusions as least as possible, and also make sure they are out of the hospital and having a good quality of life.”

    Q: What does the presentation at ASCO mean to you?

    A: “It’s one of the most gratifying moments for a clinical investigator when we hear a trial we worked on is positive. The reason why we do clinical trials is to help our patients. So have a positive trial and especially with an agent that you have worked on for years, and you have been very involved in the trial for a long time, not only in accruing patients, but also in the design and the conduct and oversight of the study and to have a trial being positive, especially for a randomized phase III trial, is a very good feeling, and the day when you hear that the results are positive is a day that you tend to remember for a very long time because what you have worked on did not only help your own patients, but hopefully if the drug gets approved, it’s going to help many patients that you have not directly interacted with, which is I think is the most important mission of any clinical research. We are the face of the trial as clinical investigators, but we have a huge team here at Yale. A lot of coordinators, clinical research nurses, regulatory staff, and our nurse practitioners – all of them have been very important to the conduct of the trial here at Yale. This was a global study that happened in many countries, many centers, and it’s a coordinated effort. So we are presenting the data on behalf of everybody and hoping that the regulatory review will be successful, and we have another option for our patients.”

    [ad_2]

    Yale Cancer Center/Smilow Cancer Hospital

    Source link