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Tag: NEJM

  • About 22 high school age adolescents died each week from overdoses in 2022, driven by fentanyl-laced prescription pills

    About 22 high school age adolescents died each week from overdoses in 2022, driven by fentanyl-laced prescription pills

    BYLINE: Enrique Rivero

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    About 22 high school age adolescents died each week from overdoses in 2022, driven by fentanyl-laced prescription pills

    Newswise — An average of 22 adolescents 14 to 18 years of age died in the U.S. each week in 2022 from drug overdoses, raising the death rate for this group to 5.2 per 100,000– driven by fentanyl in counterfeit pills, new research finds.

    Adolescent overdoses had more than doubled among this group between 2019 and 2020, and have since intensified to such an extent that the death count equals a high school classroom each week, and is now the third largest cause of pediatric deaths behind firearm-related injuries and motor vehicle collisions. 

    The increase is, however, not due to more illicit drug use – which has in fact fallen over the years; for example, excluding cannabis, the rate of any illicit drug use among just 12th graders had fallen from about 21% to 8% in the 20 years since 2002. Instead, the increase is the result of drugs becoming deadlier due to fentanyl, which is increasingly found in counterfeit oxycodone, benzodiazepines and other prescription pills that fall into the hands of adolescents.

    But educators, physicians, and mental health practitioners can be instrumental in helping to stem this tide through pointed questions and guidance about drug use and the dangers that counterfeit pills present, the researchers write in a paper published in the New England Journal of Medicine. In addition, policymakers can focus on “hotspot” counties, most in western states, with particularly high overdose deaths.

    “Teenagers are likely to be unaware of just how high-risk experimenting with pills has become, given the recent rise in counterfeit tablets” said study co-author Joseph Friedman, a researcher at UCLA. “It’s often impossible to tell the difference with the naked eye between a real prescription medication obtained from a doctor and a counterfeit version with a potentially deadly dose of fentanyl. It’s urgent that teenagers be given accurate information about the real risks, and strategies to keep themselves and their friends safe.” 

    The researchers found that adolescent overdoses were occurring at double the national average in Arizona, Colorado and Washington State between 2020 and 2022. They identified 19 hotspot counties – that is, those with at least 20 overdose deaths and death rates higher than the national average, with Maricopa County in Arizona and Los Angeles County having the most fatal overdoses at 117 and 111, respectively, during this period. 

    The other 17 counties are Orange County, California (61 deaths), Cook County, Illinois (56), San Bernardino County, California (54), King County, Washington (52), Riverside County, California (41), San Diego County, California (36), Tarrant County, Texas (35), Clark County, Nevada (31), Kern County, California (30), Pima County, Arizona (29), Adams County, Colorado (25), Denver County, Colorado (24), Jackson County, Missouri (24), Santa Clara County, California (24), Bernalillo County, New Mexico (23), Davidson County, Tennessee (21), and Marion County, Indiana (21). 

    In addition, American Indian and Alaska Native adolescents had 1.82 times the overdose rates of whites between 2020 and 2022. And adolescents are overall likelier to use the pill form of the drug rather than powder, which was previously the main fentanyl source. For instance, while 0.3% of high school seniors in 2022 reported using heroin, which comes in powder form, 5% reported nonmedical use of prescription pills the same year.

    The researchers provide the following recommendations to combat these trends:

    • Pediatricians, other primary care physicians, and mental health practitioners should ask their adolescent patients if they or their peers were approached either in person or via social media about buying pills, or if they have used them without prescriptions
    • Educators, along with parents, can discuss with adolescents the dangers associated with counterfeit pills; these efforts should be especially prioritized in hotspot locations
    • Clinicians, educators and parents can highlight the Safety First curriculum that emphasizes abstinence from drugs and provides information about risk reduction for those who do experiment with drugs, such as where to find and how to use the overdose-reversal agent naloxone
    • Finally, naloxone should be available in schools, which should also adopt “no-questions-asked” pill-disposal programs as well as provide anonymous mechanisms such messaging services that students can use to ask about counterfeit pills and substance use without risk of punishment or embarrassment.

    “Fentanyl has rapidly become a leading cause of death in American teens,” said Dr. Scott Hadland, chief of adolescent medicine at Mass General for Children and senior author on the paper. “Policymakers, clinicians, families and communities need to partner together to address this worsening public health threat.”

    University of California, Los Angeles (UCLA), Health Sciences

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  • New study shows promising evidence for sickle cell gene therapy

    New study shows promising evidence for sickle cell gene therapy

    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.

    University of Chicago Medical Center

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  • Weight loss drug helps heart failure patients with obesity.

    Weight loss drug helps heart failure patients with obesity.

    Newswise — Amsterdam, Netherlands – 25 Aug 2023: Semaglutide improves heart failure-related symptoms and physical function and results in greater weight loss compared with placebo in patients with heart failure with preserved ejection fraction (HFpEF) and obesity, according to late breaking research presented in a Hot Line session today at ESC Congress 2023.1

    Approximately half of patients with heart failure in the community have HFpEF.2 Most patients with HFpEF are overweight or obese, and growing evidence suggests that obesity and excess adiposity are not simply comorbidities, but may play a pivotal role in the development and progression of HFpEF.3 Patients with obesity-related HFpEF have an especially high burden of debilitating symptoms (shortness of breath, exertional intolerance, swelling/oedema) and physical limitations, which collectively result in a poor quality of life.4,5 Few treatment options are available, and there are no approved therapies specifically targeting the obesity phenotype of HFpEF.

    Semaglutide is a potent glucagon-like-peptide-1 receptor agonist which has previously been shown to produce substantial weight loss in people with overweight and obesity.6 The STEP-HFpEF trial tested the hypothesis that treatment with semaglutide can significantly improve symptoms, physical limitations and exercise function, in addition to weight loss, in patients with HFpEF and obesity.7

    STEP-HFpEF was a randomised, double-blind, placebo-controlled trial conducted at 96 sites in 13 countries in Asia, Europe, North America and South America. The trial included patients with HFpEF (left ventricular ejection fraction ≥45%), body mass index (BMI) ≥30 kg/m2, heart failure symptoms and functional limitations (New York Heart Association functional class II–IV and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score [KCCQ-CSS] <90 points).

    Participants were randomly assigned in a 1:1 ratio to once-weekly subcutaneous semaglutide 2.4 mg or placebo for 52 weeks. The trial had two primary endpoints: change from baseline to week 52 in 1) KCCQ-CSS, a gold standard measure of heart failure-related symptoms and physical limitations; and 2) body weight. Confirmatory secondary endpoints included change in 6-minute walk distance (6MWD – a validated measure of exercise function); a hierarchical composite endpoint of death, heart failure events and change in KCCQ-CSS and 6MWD; and change in C-reactive protein (CRP – a measure of inflammation).

    The trial included 529 patients. The median age was 69 years and 56.1% were women. The median body weight and BMI at baseline were 105.1 kg and 37.0 kg/m2, respectively. At baseline, patients had a substantial degree of heart failure-related symptoms, physical limitations and poor exercise tolerance: 66.2% were NYHA class II and 33.8% were NYHA class III–IV; the median KCCQ-CSS was 58.9 points; and the median 6MWD was 320 meters.

    The trial met both primary endpoints and all confirmatory secondary endpoints. The mean change in KCCQ-CSS from baseline to week 52 was 16.6 points with semaglutide versus 8.7 points with placebo (estimated treatment difference [ETD]: 7.8 points, 95% confidence interval [CI] 4.8 to 10.9; p<0.001). The mean change in body weight from baseline to week 52 was -13.3% with semaglutide versus -2.6% with placebo (ETD: -10.7%, 95% CI -11.9% to -9.4%; p<0.001).

    Regarding secondary endpoints, the mean change in 6MWD was 21.5 meters for semaglutide versus 1.2 meters for placebo (ETD: 20.3 meters, 95% CI 8.6 to 32.1; p<0.001). For the hierarchical composite endpoint, semaglutide produced more wins than placebo (win ratio 1.72, 95% CI 1.37 to 2.15; p<0.001). The mean change in CRP was -43.5% and -7.3% with semaglutide and placebo, respectively (estimated treatment ratio 0.61, 95% CI 0.51 to 0.72; p<0.001).

    In terms of exploratory endpoints, the change in NTproBNP at 52 weeks was -20.9% and -5.3% for semaglutide versus placebo (estimated treatment ratio 0.84, 95% CI 0.71 to 0.98). One patient in the semaglutide group and 12 in the placebo group experienced an adjudicated event of heart failure hospitalisation or urgent visit (hazard ratio 0.08, 95% CI 0.00 to 0.42). Serious adverse events were reported in 35 (13.3%) and 71 (26.7%) participants with semaglutide and placebo, respectively (p<0.001).

    Principal investigator Dr. Mikhail Kosiborod of Saint Luke’s Mid America Heart Institute, Kansas City, US said: “In patients with HFpEF and obesity, treatment with semaglutide 2.4 mg produced large improvements in symptoms, physical limitations and exercise function, reduced inflammation, and resulted in greater weight loss and fewer serious adverse events as compared with placebo. To our knowledge, this is the first trial of a pharmacologic agent to specifically target obesity as a treatment strategy for HFpEF, and the magnitude of the benefits we observed is the largest seen with any agent in HFpEF. This will likely have a significant impact on clinical practice, especially since there is a dearth of efficacious therapies in this vulnerable patient group. We believe that these findings should also change the nature of the conversation about the role of obesity in HFpEF, as the STEP-HFpEF results clearly indicate that obesity is not simply a comorbidity in patients with HFpEF but a root cause and a target for therapeutic intervention.”

     

    References and notes

    1STEP-HFpEF will be discussed during Hot Line 1 on Friday 25 August at 11:15 to 12:15 CEST in room Amsterdam.

    2Dunlay SM, Roger VL, Redfield MM. Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2017;14:591–602.

    3Borlaug BA, Jensen MD, Kitzman DW, et al. Obesity and heart failure with preserved ejection fraction: new insights and pathophysiological targets. Cardiovasc Res. 2023;118:3434-3450.

    4Reddy YNV, Lewis GD, Shah SJ, et al. Characterization of the obese phenotype of heart failure with preserved ejection fraction: a RELAX trial ancillary study. Mayo Clin Proc. 2019;94:1199–

    1209.

    5Reddy YNV, Rikhi A, Obokata M, et al. Quality of life in heart failure with preserved ejection fraction: importance of obesity, functional capacity, and physical inactivity. Eur J Heart Fail. 2020;22:1009–1018.

    6 Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384:989-1002.

    7Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Design and baseline characteristics of STEP-HFpEF program evaluating semaglutide in patients With obesity HFpEF phenotype. JACC Heart Fail. 2023;S2213-1779(23)00245-7.

    European Society of Cardiology

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  • AI Transformation of Medicine: Why Doctors Are Not Prepared

    AI Transformation of Medicine: Why Doctors Are Not Prepared

    Newswise — BALTIMORE, August 5, 2023–As artificial intelligence systems like ChatGPT find their way into everyday use, physicians will start to see these tools incorporated into their clinical practice to help them make important decisions on diagnosis and treatment of common medical conditions. These tools, called clinical decision support (CDS) algorithms, can be enormously helpful in helping guide health care providers in determining, for example, which antibiotics to prescribe or whether to recommend a risky heart surgery. 

    The success of these new technologies, however, depends largely on how physicians interpret and act upon a tool’s risk predictions – and that requires a unique set of skills that many are currently lacking, according to a new perspective article published today in the New England Journal of Medicine that was written by faculty in the University of Maryland School of Medicine (UMSOM). 

    CDS algorithms, which make predictions under conditions of clinical uncertainty, can include everything from regression-derived risk calculators to sophisticated machine learning and artificial intelligence-based systems. They can be used to predict which patients are most likely to go into life-threatening sepsis from an uncontrolled infection or which therapy has the highest probability of preventing sudden death in an individual heart disease patient. 

    “These new technologies have the potential to significantly impact patient care, but doctors need to first learn how machines think and work before they can incorporate algorithms into their medical practice,” said Daniel Morgan, MD, MS Professor of Epidemiology & Public Health at UMSOM and co-author of the perspective. 

    While some clinical decision support tools are already incorporated into electronic medical record systems, health care providers often find the current software to be cumbersome and difficult to use. “Doctors don’t need to be math or computer experts, but they do need to have a baseline understanding of what an algorithm does in terms of probability and risk adjustment, but most have never been trained in those skills,” said Katherine Goodman, JD, PhD, Assistant Professor of Epidemiology & Public Health at UMSOM and co-author of the perspective.

    To address this gap, medical education and clinical training need to incorporate explicit coverage of probabilistic reasoning tailored specifically to CDS algorithms. Drs. Morgan, Goodman, and their co-author Adam Rodman, MD, MPH, at Beth Israel Deaconess Medical Center in Boston, proposed the following:

    1. Improve Probabilistic Skills: Early in medical school, students should learn the fundamental aspects of probability and uncertainty and use visualization techniques to make thinking in terms of probability more intuitive. This training should include interpreting performance measures like sensitivity and specificity to better understand test and algorithm performance.
    2. Incorporate Algorithmic Output into Decision Making: Physicians should be taught to critically evaluate and use CDS predictions in their clinical decision-making. This training involves understanding the context in which algorithms operate, recognizing limitations, and considering relevant patient factors that algorithms may have missed.
    3. Practice Interpreting CDS Predictions in Applied Learning: Medical students and physicians can engage in practice-based learning by applying algorithms to individual patients and examining how different inputs affect predictions. They should also learn to communicate with patients about CDS-guided decision making.  

    The University of Maryland, Baltimore (UMB), University of Maryland, College Park (UMCP) and University of Maryland Medical System (UMMS) recently launched plans for a new Institute for Health Computing  (IHC). The UM-IHC will leverage recent advances in artificial intelligence, network medicine, and other computing methods to create a premier learning health care system that evaluates both de-identified and secure digitized medical health data to enhance disease diagnosis, prevention, and treatment. Dr. Goodman is beginning a position at IHC, which will be a site that is dedicated to educating and training health care providers on the latest technologies. The Institute plans to eventually offer a certification in health data science among other formal educational opportunities in data sciences. 

    “Probability and risk analysis is foundational to the practice of evidence-based medicine, so improving physicians’ probabilistic skills can provide advantages that extend beyond the use of CDS algorithms,” said UMSOM Dean Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor. “We’re entering a transformative era of medicine where new initiatives like our Institute for Health Computing will integrate vast troves of data into machine learning systems to personalize care for the individual patient.”

    University of Maryland School of Medicine

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  • Dialysis exercise improves health, study says

    Dialysis exercise improves health, study says

    Newswise — Patients who engage in light exercise while undergoing dialysis are physically fitter and are admitted to hospital less frequently than those who do not. These are the findings of a large-scale study conducted by a consortium led by the Technical University of Munich (TUM). The researchers believe that exercise programs should be offered to dialysis patients as standard.

    Around 558,000 people in the United States have such severely impaired kidney function that they require dialysis several times per week. In Germany, about 80,000 people regularly undergo dialysis. Many also suffer from additional health issues such as diabetes and heart disease. “The limitations imposed by these diseases, and the time required for dialysis, often mean that those affected engage in little physical exercise. We wanted to change that,” says Martin Halle, Professor of Preventive and Rehabilitative Sports Medicine at TUM, who headed up the study.

    Personalized exercise plans

    Approximately 1,000 patients at 21 dialysis centers in Germany took part in the study, which has been published in the New England Journal of Medicine – Evidence. “We mounted one of the world’s largest studies on physical activity in the context of specific diseases,” says Martin Halle. Data from health insurance providers was consulted to ensure that the participant pool was representative of dialysis patients in Germany in terms of aspects such as age, gender and overall health.

    Over a twelve-month period, half of the study participants completed accompanied exercise sessions at least once and ideally three times per week alongside their dialysis, while others were subject only to medical monitoring. These sessions included 30 minutes of endurance training with a bed-cycle ergometer and a further 30 minutes of exercises with weights, resistance bands and balls. The exercises were tailored to each patient’s ability.

    Improvements in standardized testing

    After a year, the health of the study’s active participants had improved significantly. This included completing more repetitions in a one-minute sit-to-stand test and walking further in six minutes than at the start of the study. In the control group, these values were even lower at the end of the study period than at the outset.

    “This type of standardized testing may admittedly not appear to be particularly reflective of everyday life,” says Martin Halle. “However, the results demonstrate tangible improvements in quality of life and autonomy. For example, the participants were able to stand up from a chair at home without assistance, which was not always the case beforehand.” There are other signs of the training program’s positive effects: participants who completed regular training sessions spent an average of two days in hospital during the study, compared to an average of five days for the control group.

    Low costs per training unit

    “To my mind, the results speak for themselves,” says Martin Halle. “We were able to improve the participants’ health and also reduce the costs to the healthcare system with relatively little outlay.” The researchers’ figures suggest that the costs for personalized training would be around €25 per session per person.

    The DiaTT (Dialysis Training Therapy) consortium submitted the final report to the Federal Joint Committee (Gemeinsamer Bundesausschuss – G-BA), which had financed the study through its Innovation Fund (Innovationsfonds). This committee will ultimately determine whether this training is offered to all dialysis patients with statutory health insurance. “I hope our exercise program will become standard in statutory health insurance in Germany,” says Martin Halle. “The benefits will likely also apply to patients in other countries. However, the best approach for a broad implementation has to be found for each society.”

    The study participants will continue to be monitored in future to help researchers learn more about the effects of exercise over the long term. “Our study shows how important it is to adopt a holistic view of health, especially when it comes to elderly and infirm patients”, says Martin Halle. “While high-tech medicine is important, it can only achieve its full potential in combination with other fields, such as preventive medicine.”

    Publication:

    K. Anding-Rost, G. von Gersdorff, P. von Korn, G. Ihorst, A. Josef, M. Kaufmann, M. Huber, T. Bär, S. Zeißler, S. Höfling, C. Breuer, N. Gärtner, M.J. Haykowsky, S. Degenhardt, C. Wanner and M. Halle, for the DiaTT Study Group. “Exercise during Hemodialysis in Patients with Chronic Kidney Failure.” NEJM Evidence (2023). DOI: 10.1056/EVIDoa230005

    Technical University of Munich

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  • Major step forward reduces mortality in kidney failure patients

    Major step forward reduces mortality in kidney failure patients

    Newswise — Mortality in patients with kidney failure has been found to be 23% lower among those treated with high dose haemodiafiltration compared to those treated with high flux haemodialysis, according to new research from the CONVINCE consortium led by University Medical Center Utrecht.

    The study, published today in the New England Journal of Medicine, is the first international, randomised trial to compare the two treatments. The findings indicate that wider use of high dose haemodiafiltration would have clear benefits for patients.

    Chronic kidney disease is a leading global health problem that affects an estimated 830 million people globally. When the kidneys can no longer do their job, dialysis is used to clean the blood by removing waste products, a function normally performed by the kidneys themselves. Around four million people are on dialysis worldwide.

    Haemodialysis is the most common form of dialysis used in the treatment for kidney failure1. Though it has improved over the years, it is not good at removing larger molecules from the blood. Haemodiafiltration is a newer technology that can remove larger molecules, but it is not suitable for all patients due to the fact that it requires a higher blood flow rate to be effective. Previous studies have failed to conclusively prove that one method is more effective than the other.

    The CONVINCE trial has been led by researchers at UMC Utrecht together with collaborators at University College London (UCL), Charité Universitätsmedizin Berlin, University of Bari, The George Institute for Global Health and Imperial College London, along with dialysis providers Fresenius Medical Care, Diaverum and B. Braun Avitum. It is the first multinational, randomised trial to compare high-flux haemodialysis and high-dose haemodiafiltration, with the aim of clarifying which method is superior.

    At 61 centres in eight European countries, a total of 1,360 patients were randomised, with 683 treated with high-dose haemodiafiltration and 677 treated with high-flux haemodialysis three times a week.

    During a median follow-up of 30 months, all-cause mortality was 21.9% among those treated with high-flux haemodialysis, compared to 17.3% for those treated with high-volume haemodiafiltration. This 4.6% difference represents a 23% reduction in the risk of death.

    Lead investigator, Professor Peter Blankestijn (UMC Utrecht), said: “Our results show clear survival benefits for using haemodiafiltration over haemodialysis to treat kidney failure, akin to a 23% reduction in all-cause mortality. My hope is that haemodiafiltration can become the new standard.”

    Professor Matthias Rose (Charité University, Berlin), a senior author of the study and expert in patient-reported outcomes, said: “In addition to clinical events, patient perception and thus reported outcomes are very important.  We are currently performing in-depth analyses of the extensive data on patient-reported outcomes that have been collected in the CONVINCE study, with results expected later this year.”

    While haemodialysis is standard treatment in most countries, haemodiafiltration is less widely used in some places and is not used at all in places like the US. Most modern dialysis machines can perform either method, which would make a switch to haemodiafiltration relatively easy.

    Professor Andrew Davenport (UCL Medicine and the Royal Free Hospital), a senior author of the study, said: “During my career I’ve watched new treatments emerge for many diseases, from diabetes to cancer, but we haven’t seen the same advances in the treatment of chronic kidney disease. This study proves that targeting different molecules through haemodiafiltration has clear benefits for patients. I would say that this is the first major step forward in many years and is good news for kidney disease patients and their families.”

    The CONVINCE study was exclusively supported by the European Commission Research & Innovation, Horizon 2020, Call H2020-SC1-2016-2017 under the topic SC1-PM-10-2017: Comparing the effectiveness of existing healthcare interventions in the adult population (grant no 754803).

    University College London

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  • UC San Diego Scientists Find Treatment for Severe Genetic Skin Disorder

    UC San Diego Scientists Find Treatment for Severe Genetic Skin Disorder

    Newswise — In a true example of bench-to-bedside science, researchers at UC San Diego have identified the cause of a rare skin disorder, disabling pansclerotic morphea, and swiftly identified a treatment that dramatically improved patients’ symptoms. 

    The scientists discovered that the patients have an overactive version of a protein called STAT4, and that the drug ruxolitinib improved patients’ rashes and ulcers. 

    The results were published in the New England Journal of Medicine.

    DOI: 10.1056/NEJMoa2202318

    University of California San Diego

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  • UM School of Medicine Researchers Chart Path Forward on Developing mRNA Vaccines for Infections Beyond COVID-19

    UM School of Medicine Researchers Chart Path Forward on Developing mRNA Vaccines for Infections Beyond COVID-19

    Newswise — BALTIMORE, April 6, 2023 – After helping to develop and test new mRNA technologies for COVID-19 vaccines, University of Maryland School of Medicine (UMSOM) researchers and scientists are turning their attention to utilizing this innovative technology to ward off other infectious diseases like malaria and influenza. Last month, UMSOM faculty in the Center for Vaccine Development and Global Health (CVD) launched a new clinical trial to investigate the use of mRNA technologies to create a vaccine against malaria. CVD Director Kathleen M. Neuzil, MD, MPH, FIDSA also provided commentary in the nation’s leading medical journal on the feasibility of using mRNA to develop a universal influenza vaccine that could eliminate the need for seasonal shots.

    The huge success of mRNA vaccines to combat COVID-19 has opened up a new era in vaccine development, offering the potential for faster, more efficient, and more effective vaccine production. In an editorial commenting on a new study published last week in the New England Journal of Medicine (NEJM), Dr. Neuzil, who is also the Myron M. Levine, MD, Professor in Vaccinology at UMSOM, wrote, “the application of mRNA technology to influenza vaccines would permit the design of vaccines that incorporate mRNAs matched to multiple influenza strains, a rapid adaptive response to virus evolution, and the manufacture of combination vaccines that include influenza and noninfluenza proteins, which would facilitate delivery to populations.”

    Dr. Neuzil pointed to more than 20 studies underway or in the planning stages to test novel influenza vaccines utilizing this technology. She commented on a recent animal study published in Science, which tested an mRNA vaccine against all 20 known influenza virus subtypes. The study found that the single vaccine can provide protection against different strains of the influenza virus by simultaneously inducing antibodies against multiple antigens, which she said suggests that an mRNA vaccine against influenza is “feasible” but that “careful attention to safety evaluations will be critical.”During the COVID-19 pandemic, Dr. Neuzil led the team that launched the first clinical trial in the U.S. to test the Pfizer and BioNTech mRNA vaccine against COVID-19.

    CVD researchers also recently launched a new clinical trial investigating an mRNA-based vaccine for malaria. This phase 1, first-in-human study will aim to determine whether the vaccine is safe and its potential for efficacy against one of the world’s most deadly parasitic illnesses.

    “Many scientists who study malaria have long been invested in developing vaccines to prevent malaria deaths and disease, and the COVID-19 pandemic advanced the mRNA vaccine platform that can readily be adapted for other illnesses,” said Matthew Laurens, MD, MPH, Professor of Pediatrics and Medicine at UMSOM’s Center for Vaccine Development and Global Health (CVD) and Coordinating Investigator for the BioNTech mRNA malaria vaccine trial. “As this is the first study to test this novel mRNA-based vaccine in humans, we are hopeful we’ll see promising results that may be life changing for children who are at highest risk of death, severe disease, and inferior school performance due to malaria.” 

    Study participants ages 18 to 55 will receive three total injections of a vaccine made by BioNTech SE, or a placebo, over six months. The study is expected to be completed in September 2024. Investigators will carefully track how well the participants tolerate the injection and monitor any reactions that might occur. Importantly, participant immune responses will be measured after vaccination.

    There were 247 million malaria cases and 619,000 deaths reported worldwide in 2021 alone, which is a 9 percent increase from 2019 before the pandemic. Public health experts contend new strategies are urgently needed to achieve the United Nation’s sustainable development goal of 90 percent reduction in malaria incidence and mortality by 2030. Scientists have tried for decades to develop a highly effective malaria vaccine without much success.

    The current study’s mRNA approach – and other recent research investigating monoclonal antibodies for malaria — represent a promising advances to reduce malaria morbidity and mortality.

    The first vaccine against malaria (RTS,S/AS01) was approved by the World Health Organization in October 2021, and it provides modest protection against malaria. Unfortunately, it is in short supply and thus additional vaccines are urgently needed.

    In 2022, UMSOM researchers published findings from a study that showed a three-dose regimen of a whole-parasite vaccine against malaria – called Plasmodium falciparum sporozoite (PfSPZ) vaccine – demonstrated safety and efficacy when tested in adults living in Burkina Faso, West Africa, an area highly endemic for malaria.

    “Instead of relying on inactivated microbes to trigger an immune response, mRNA vaccines use mRNA to teach our cells how to make a protein, or piece of a protein, that resembles a microbe’s protein,” said UMSOM Dean Mark Gladwin, MD, who is also Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor at UMSOM. “This foreign protein triggers a human immune response against the microbe. The mRNA vaccine platform has several advantages in terms of stimulating a more robust immune response and enabling quick adaptation and scalability to new strains or variants that emerge during pandemics.”

    About the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine

    For over 40 years, researchers in the Center for Vaccine Development and Global Health (CVD) have worked domestically and internationally to develop, test, and deploy vaccines to aid the world’s underserved populations. CVD is an academic enterprise engaged in the full range of infectious disease intervention from basic laboratory research through vaccine development, pre-clinical and clinical evaluation, large-scale pre-licensure field studies, and post-licensure assessments. CVD has created and tested vaccines against cholera, typhoid fever, paratyphoid fever, non-typhoidal Salmonella disease, shigellosis (bacillary dysentery), Escherichia coli diarrhea, nosocomial pathogens, tularemia, influenza, coronaviruses, malaria, and other infectious diseases. CVD’s research covers the broader goal of improving global health by conducting innovative, leading research in Baltimore and around the world. Our researchers are developing new and improved ways to diagnose, prevent, treat, control, and eliminate diseases of global impact, including COVID-19. In addition, CVD’s work focuses on the ever-growing challenge of antimicrobial resistance.

    About the University of Maryland School of Medicine

    Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world — with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research.  With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding.  As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System (“University of Maryland Medicine”) has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies.  In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2021, the UM School of Medicine is ranked #9 among the 92 public medical schools in the U.S., and in the top 15 percent (#27) of all 192 public and private U.S. medical schools.  The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu

    University of Maryland School of Medicine

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  • خبراء السرطان في مايو كلينك يسلطون الضوء على التقدم المحرز في علاج الورم النقوي المتعدد

    خبراء السرطان في مايو كلينك يسلطون الضوء على التقدم المحرز في علاج الورم النقوي المتعدد

    Newswise — مدينة روتشستر، ولاية مينيسوتا— يشارك دكتور سكندر العوضي، دكتور في الطب، اختصاصي الدَّمَويات والأورام في مركز مايو كلينك الشامل لعلاج للسرطان تفاصيل حول تطورات جديدة توصلت إليها الأبحاث ستفضي إلى نتائج أفضل لمرضى الورم النقوي المتعدد.  

    الورم النقوي المتعدد هو نوع غير شائع نسبيًا من أنواع سرطان الدم التي تصيب نخاع العظم. رغم أنه لا يوجد علاج نهائيًا للمرض، إلا إنه يمكن التعامل معه بالعلاجات المتاحة مثل الأدوية، والعلاج الكيميائي، والإشعاع، أو حتى بزراعة نخاع العظم للمساعدة في إطالة جودة حياة المرضى.  

    يشارك دكتور العوضي في قيادة فريق من الباحثين في مايو كلينك لتجربةعلاج مستقبلات المستضد الخيمرية، والتي تسمى أيضًا علاج الخلايا التائية ذات مستقبلات المستضد الخيمرية (CAR-T cell)، لعلاج المرضى المصابين بالورم النقوي المتعدد، وتطوير أدوية جديدة لاستهداف الواسِمات السرطانية المختلفة مثل مستضد نضج الخلايا البائية وغيره.  

    يقول دكتور العوضي “التطورات في الأدوية والعلاجات الجديدة لعلاج الورم النقوي في حالة تطور وتغير مستمرين. وإنه لوقت باعث على الحماسة لإجراء أبحاث على أدوية السرطان لاكتشاف علاجات جديدة ستمنح الأمل لمرضى السرطان.”  

    إن علاج مستقبلات المستضد الخيمرية هو أحدث علاج مناعي للسرطان يحتوي على خلايا تائية مُعدّلة وراثيًا لاستهداف واسِمات الخلايا السرطانية تحديدًا، ولتنشيط الجهاز المناعي للتعرف على الخلايا السرطانية والقضاء عليها.  

    في دراسة نُشرت مؤخرًا في في مجلة نيو إنجلاند الطبية، والتي شاركت فيها مايو كلينك، قارن الباحثون نتائج علاج مستقبلات المستضد الخيمرية بنتائج نُظُم العلاج القياسية المتوفرة حاليًا لدى المرضى الذين عولجوا سابقًا من الورم النقوي المتعدد والذين عاودهم المرض بعد الشفاء منه. وقاس الباحثون معدلات البقاء على قيد الحياة التي خلت من تقدّم المرض، وهي الفترة التي يتعايش فيها المريض مع المرض خلال العلاج وبعده، ولكن دون أن يتفاقم المرض.  

    وأشارت الدراسة أنه بإجراء متابعة تفقدية بمتوسط 18.6 شهرًا، بلغ متوسط البقاء على قيد الحياة دون تقدّم المرض لدى المجموعة التي تلقت علاج مستقبلات المستضد الخيمرية 13.3 شهرًا، مقارنة بمتوسط بلغ 4.4 شهور فقط لدى المجموعة التي عولجت بنُظُم العلاج القياسية.  

    يضيف دكتور العوضي قائلاً: “تشير هذه النتائج إلى أننا نمضي في الطريق البحثي الصحيح الذي سيحدث تغييرًا في الممارسة العلاجية والتي ستقدم علاج مستقبلات المستضد الخيمرية في مرحلة مبكرة من علاج المرضى الذين عاودتهم الإصابة بالورم النقوي المتعدد — والذي أتمنى أن يصبح معيار الرعاية في المستقبل.”  

    يواصل باحثو مايو كلينك اختبار أدوية جديدة تستهدف الورم النقوي المتعدد حيث تقود فرق متخصصة التجارب السريرية مستخدمين طرق علاج مستقبلات المستضد الخيمرية الحديثة. يشمل ذلك استخدام العلاجات الجاهزة وعلاج مستقبلات المستضد الخيمرية في وقت مبكر من رحلة العلاج المرضى.  

    يوجد حاليًا ما يزيد عن 40 تجربة سريرية متاحة في مايو كلينك لمرضى الورم النقوي المتعدد. 

    ### 

    نبذة عن مايو كلينك 
    مايو كلينك هي مؤسسة غير ربحية تلتزم بالابتكار في الممارسات السريرية والتعليم والبحث وتوفير التعاطف والخبرة لكل مَن يحتاج إلى الاستشفاء والرد على استفساراته. لمعرفة المزيد من أخبار مايو كلينك، تفضَّل بزيارة شبكة مايو كلينك الإخبارية.  

    جهة الاتصال الإعلامية: 

    Mayo Clinic

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  • Eradicating Polio Will Require Changing the Current Public Health Strategy

    Eradicating Polio Will Require Changing the Current Public Health Strategy

    Newswise — Baltimore, MD, March 6, 2023— The recent public health emergency declarations in New York and London due to polio infections and detection of the virus in these cities’ wastewater strongly indicate that polio is no longer close to being eradicated.

    Now, four members of the Global Virus Network (GVN) proposed changes in global polio eradication strategy to get the world back on track to one day eliminating polio’s threat. Authors of the recommendations included University of Maryland School of Medicine Institute of Human Virology’s Director and Co-Founder Robert C. Gallo, MD, The Homer & Martha Gudelsky Distinguished Professor in Medicine, and Co-Founder and Chair of the Scientific Leadership Board of GVN; two of the world’s most prominent poliovirus experts, Konstantin Chumakov, PhD, DSci, Adjunct Professor at the George Washington University and the University of Maryland, and Stanley Plotkin, MD, Scientific Advisor of the Coalition for Epidemic Preparedness Innovations (CEPI); and GVN’s President Christian Bréchot, MD, PhD, Professor of University of South Florida.

    They suggested that eradication is possible only through ensuring the highest possible vaccination coverage worldwide and maintaining it indefinitely. Vaccination policies must be tailored individually for different regions of the world and use both the polio vaccine made of inactivated virus (in combination with other vaccines), as well as improved novel oral polio vaccines that use live, weakened virus. The experts also urged reconvening a scientific group advising the World Health Organization on poliovirus eradication that can respond as needed and adapt policies in the face of newer data or public health emergencies. 

    The infectious disease experts published their views in a perspective in the New England Journal of Medicine on February 16, 2023.

    The Global Polio Eradication Initiative (GPEI), which formed 34 years ago, aimed for a goal of polio eradication by 2000. This group developed the original polio eradication plan and formed a scientific advisory group, which was later disbanded before the projected goals were reached. According to the authors, this led to some decisions that were not based of solid science, including no longer immunizing against one of the three kinds of poliovirus while a weaker version of this poliovirus was still present in communities. The resulting resurgence of poliovirus circulation continues until this day, and the virus reappeared in the U.K., U.S., and other countries after decades when it thought to be eradicated.

    “The Initiative based their guidelines on the strategy that was used to eradicate smallpox. However, poliovirus is trickier in that for every person paralyzed by infection, hundreds have no symptoms at all, meaning the virus can silently circulate in communities without anyone knowing it,” said Dr. Gallo. “It was premature to assume that plans would run their course smoothly. These recent outbreaks confirm the need for an active scientific advisory group that can council, mobilize, and adjust the polio eradication plan in real-time as needed.”

    Over the last few decades, there has been an increase in global travel, which can allow infections to migrate from developing nations where they are more common to communities in industrialized nations where they can spread undetected becoming the greatest danger to the unvaccinated and people with weakened immune systems.

    With most people in the U.K. and the U.S. vaccinated against polio, how did this recent outbreak in two major international cities happen? As with other viruses once thought rare in more developed countries, such as measles or mumps, some communities chose not to vaccinate. Also, the nature of the polio vaccines in industrialized nations may have allowed asymptomatic infections to circulate undetected for a while now. 

    There are two main types of polio vaccines: the injectable version uses noninfectious virus particles to generate immunity (IPV) or the oral polio vaccine (OPV) that uses a live, weakened version of the virus.

    “The injectable ‘killed’ polio vaccine protects from paralysis, but unlike the live version it does not generate robust immunity in the intestinal tract needed to prevent virus circulation. This means that asymptomatic cases can circulate in vaccinated individuals. So then, why do we use not the live version instead?” said Dr. Chumakov. “The live, attenuated version can revert to virulence (a more an infectious version) and spread to people who are unvaccinated or who have compromised immune systems and occasionally cause paralytic disease. In fact, mutated versions of the oral polio vaccine are what are currently circulating in London and New York. It’s a Catch-22, but there may be a way out: recently a new version of the vaccine was developed that does not convert to virulent vaccine-derived poliovirus. In combination with the injectable polio vaccine, this novel oral polio vaccine can become an effective tool to safely create comprehensive immunity that can stop the spread of the disease.”

    The current polio eradication planned for phasing out the live, oral polio vaccines three years after the last wild or natural poliovirus case is documented, replacing it with the injectable polio vaccine. 

    “As history has recently shown us with COVID vaccines, just because we would like these vaccines to be available, it does not mean they will be. There may be a scramble and the richer countries will secure vaccines before the others,” said Dr. Plotkin. “Therefore, we at the GVN propose that the group institute a policy change not based solely on milestones, but rather whether there is an appropriate supply to compensate for the increased demand. Better yet, incorporate a strategy for ensuring there will be available injectable polio vaccines to support the world supply when the time comes.”

    Once the world converts entirely to injectable vaccines, the GEPI’s plan was to remove all polio vaccines ten years after this transition.

    “The biggest problem in the way of polio eradication is to do it safely through the combined use of inactivated and live oral vaccines. The former would prevent paralysis from both wild and vaccine-derived poliovirus, whereas the latter would eventually prevent circulation of both forms of poliovirus and paralysis,” said Dr. Bréchot. “The vaccine industry is capable of making both if they are given the order to do so.”

    About the Global Virus Network (GVN)

    The Global Virus Network (GVN) is essential and critical in the preparedness, defense, and first research response to emerging, exiting, and unidentified viruses that pose a clear and present threat to public health, working in close coordination with established national and international institutions. It is a coalition comprised of eminent human and animal virologists from 71 Centers of Excellence and 9 Affiliates in 40 countries worldwide, working collaboratively to train the next generation, advance knowledge about how to identify and diagnose pandemic viruses, mitigate and control how such viruses spread and make us sick, as well as develop drugs, vaccines, and treatments to combat them. No single institution in the world has expertise in all viral areas other than the GVN, which brings together the finest medical virologists to leverage their individual expertise and coalesce global teams of specialists on the scientific challenges, issues, and problems posed by pandemic viruses. The GVN is a non-profit 501(c)(3) organization. For more information, please visit https://gvn.org/. Follow us on Twitter at @GlobalVirusNews

     

     

    Global Virus Network

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  • Adding antipsychotic med to antidepressant may help older adults with treatment-resistant depression

    Adding antipsychotic med to antidepressant may help older adults with treatment-resistant depression

    BYLINE: Jim Dryden

    Newswise — For older adults with clinical depression that has not responded to standard treatments, adding the drug aripiprazole (brand name Abilify) to an antidepressant they’re already taking is more effective than switching from one antidepressant to another, according to a new multicenter study led by Washington University School of Medicine in St. Louis.

    Aripiprazole originally was approved by the FDA in 2002 as a treatment for schizophrenia but also has been used in lower doses as an add-on treatment for clinical depression in younger patients who do not respond to antidepressants alone.

    The new findings are published March 3 in The New England Journal of Medicine and are to be presented that same day by Eric J. Lenze, MD — principal investigator and head of the Department of Psychiatry at Washington University — and colleagues at the annual meeting of the American Association for Geriatric Psychiatry in New Orleans.

    Many people with clinical depression don’t respond to medications used to treat the condition. Consequently, some doctors switch such patients to different antidepressants in the pursuit of finding one that works, while other physicians may prescribe another class of drugs to see if a combination of medications helps.

    Both strategies have been recommended by experts as options for older adults with treatment-resistant depression. However, the new study was designed to help determine which strategy is most effective. Augmenting an antidepressant with aripiprazole helped 30% of patients with treatment-resistant depression, compared to only 20% who were switched to another solo antidepressant, results of the study show.

    “Often, unless a patient responds to the first treatment prescribed for depression, physicians follow a pattern in which they try one treatment after another until they land on an effective medication,” said Lenze, the Wallace and Lucille Renard Professor and the study’s corresponding author. “It would be beneficial to have an evidence-based strategy we can rely on to help patients feel better as quickly as possible. We found that adding aripiprazole led to higher rates of depression remission and greater improvements in psychological well-being — which means how positive and satisfied patients felt — and this is good news. However, even that approach helped only about 30% of people in the study with treatment-resistant depression, underscoring the need to find and develop more effective treatments that can help more people.”

    Treatment-resistant depression is no more or less common in older people than younger people, but because it seems to accelerate cognitive decline, identifying more effective ways to treat it is very important.

    Lenze, along with colleagues at Columbia University, UCLA, the University of Pittsburgh and the University of Toronto, studied 742 people, ages 60 and older, with treatment-resistant depression, meaning their depression had not responded to at least two different antidepressant medications.

    The researchers evaluated strategies commonly used in clinical practice to help alleviate treatment-resistant depression in older patients and designed the study to have two distinct phases. In the first phase, 619 patients, each of whom was taking an antidepressant such as Prozac, Lexapro or Zoloft, were randomly divided into three groups. In the first group, patients remained on whatever antidepressant drug each already was taking but also received the drug aripiprazole (Abilify). A second group also continued taking antidepressants but added bupropion (brand names Wellbutrin or Zyban), and a third group tapered off of the antidepressant each had been taking and switched to bupropion entirely.

    Over the course of 10 weeks, the participants received biweekly phone calls or in-person visits with study clinicians. At these visits, the medications were adjusted according to the individual patient’s response and side effects. The researchers found that the group that experienced the best overall outcomes was the one in which patients continued with their original antidepressants but added aripiprazole.

    The researchers also anticipated that some people in the study wouldn’t respond to the various treatments, so they added a second phase that included 248 participants. In this phase, patients taking antidepressants such as Prozac, Lexapro and Zoloft were treated with lithium or nortriptyline — medications that were widely used before those other, newer antidepressants were approved more than two decades ago. Rates of alleviating depression in the study’s second phase were low, about 15%. And there was no clear winner when augmentation with lithium was compared with switching to nortriptyline.

    “Those older drugs also are a bit more complicated to use than newer treatments,” Lenze explained. “Lithium, for example, requires blood testing to ensure its safety, and it’s recommended that patients taking nortriptyline receive electrocardiograms periodically to monitor the heart’s electrical activity. Since neither lithium nor nortriptyline were promising against treatment-resistant depression in older adults, those medications are unlikely to be helpful in most cases.”

    But even the best treatment strategy — adding aripiprazole to an antidepressant — was not markedly successful for many older patients with treatment-resistant depression.

    “This really highlights a continuing problem in our field,” said senior author Jordan F. Karp, MD, professor and chair of the Department of Psychiatry at the University of Arizona College of Medicine – Tuscon. “Any given treatment is likely to help only a subset of people, and ideally, we would like to know, in advance, who is most likely to be helped, but we still don’t know how to determine that.”

    Lenze emphasized that overall, antidepressants are highly helpful for the majority of people suffering from clinical depression. At least half of all people with depression feel much better after they begin taking the first medication they try. And almost half of the remainder not helped by a first drug improve when switched to a second drug, But that leaves a sizeable group with clinical depression that does not respond to two treatments.

    The problem is particularly difficult in older adults, many of whom already are taking several medications for other conditions such as high blood pressure, cardiac issues or diabetes,” Lenze said. “So switching to new antidepressants every few weeks or adding other psychiatric drugs can be complicated. In addition, because depression and anxiety in older adults may accelerate cognitive decline, there’s an urgency to find more effective treatment strategies.

    “There definitely is something that makes depression harder to treat in this population, a population that’s only going to keep getting larger as our society gets older,” he added.

    Lenze EJ, et al. Trial of antidepressant augmentation vs. switching in treatment-resistant geriatric depression. The New England Journal of Medicine, March 3, 2023.

    The study was funded by a grant from the Patient-Centered Outcomes Research Institute (PCORI), grant TRD-1511-33321. No in-kind support was received from pharmaceutical companies. Other funding was provided by the Taylor Family Institute for Innovative Psychiatric Research at Washington University School of Medicine. Other support came from the National Center for Advancing Translational Sciences and the National Institute of Mental Health of the National Institutes of Health (NIH). Grant numbers: 5RO1 MH114980, K24 AT009198, R01 MH114981. Additional funding provided by the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto.

    About Washington University School of Medicine

    WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,800 faculty. Its National Institutes of Health (NIH) research funding portfolio is the third largest among U.S. medical schools, has grown 52% in the last six years, and, together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,800 faculty physicians practicing at 65 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Children’s hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.

    Washington University in St. Louis

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  • UCLA Health tip sheet: Pesticides & Parkinson’s symptoms; Gender-affirming hormones improve mental health; Body composition & cardiovascular disease

    UCLA Health tip sheet: Pesticides & Parkinson’s symptoms; Gender-affirming hormones improve mental health; Body composition & cardiovascular disease

    UCLA Health Tip Sheet Feb. 21, 2023

    Below is a brief roundup of news and story ideas from the experts at UCLA Health. For more information on these stories or for help on other stories, please contact us at [email protected].

    Body composition, not BMI, may signal risk for cardiovascular disease  Body mass index has long been a measure of a person’s risk of developing cardiovascular disease, but body composition and its role in the disease have not been well studied. In a new study, UCLA researchers predicted higher fat mass would be linked to higher levels of coronary artery calcification (CAC) — a marker of subclinical cardiovascular disease – and higher fat-free mass would be linked to lower levels of CAC. Using computed tomography scans and bioelectrical impedance analysis to study CAC and body composition in 3,129 non‐Hispanic Whites, Blacks, Hispanics, and Chinese patients, the researchers unexpectedly found that higher fat-free mass and, to a lesser extent, higher fat mass were linked to high levels of CAC. The researchers cautioned that bioelectrical impedance analysis could not identify the quality of fat or fat-free mass. Given these findings, the researchers say measuring body composition rather than using BMI to assess obesity may be a better approach to evaluating cardiovascular disease risk. Read the study published Feb. 8, 2023 in the Journal of the American Heart Association.

    Bariatric surgery reduces risks of hospitalization for heart failure Bariatric surgery has been found to reverse the ill effects of diabetes and may be protective against obesity-related cancers. Because obesity rates are on the rise across the globe, UCLA researchers set out to study other health benefits weight loss surgeries confer, in particular the link between the procedures and acute heart failure hospitalizations. After analyzing data from the Nationwide Readmissions Database from 2016 to 2019, the researchers found bariatric surgery was associated with lower odds of being hospitalized with acute heart failure. Among patients hospitalized with acute heart failure, prior bariatric surgery was associated with lower risks of death, prolonged ventilation, and acute renal failure. Beyond the health benefits, those who had undergone surgery stayed one fewer day in the hospital and incurred about $1,200 less in hospital costs compared to age matched cohorts. Read the study in Surgery for Obesity and Related Diseases. 

    Pesticides may also worsen Parkinson’s symptoms: While researchers have consistently found an association between pesticide exposure and higher risk of developing Parkinson’s disease, there has been little study of whether such exposure can accelerate the course of the disease. In a new study of 53 pesticides associated with Parkinson’s onset, researchers led by UCLA assistant professor of neurology Kimberly Paul, PhD, identified 10 pesticides that are associated with faster progression of motor and non-motor symptoms. Furthermore, exposure to six of those pesticides was associated with worsening of multiple endpoints researchers measured. Two pesticides, copper sulfate (pentahydrate) and MCPA (dimethylamine salt), were associated with all three endpoints measured: motor function, cognitive function, and depressive symptoms. Read the study in the journal Science of the Total Environment.

    Repurposing an old drug for a rare disease: A drug used to treat epilepsy, retigabine, may help manage episodic attacks of paralysis in patients with the rare inherited muscle disease Hypokalemic Periodic Paralysis (HypoPP), according to a new study that tested retigabine in genetically engineered mice. There’s a strong need to identify new HypoPP treatments since existing ones only improve symptoms in about half of patients and have considerable side effects. HypoPP is often marked by reduced potassium levels in the blood during episodes of muscle weakness. While it was known that retigabine affects a potassium channel that plays an important role in the heart and brain, the channel wasn’t previously known to exist in skeletal muscle. However, the new study led by Dr. Stephen C. Cannon, chair of the physiology department at the UCLA David Geffen School of Medicine, found that retigabine helps stabilize the membrane potential of skeletal muscle, thereby protecting against attacks of muscle weakness. Read the study, published online Jan. 30, in the journal Brain.

    Women treated with thrombectomy for pulmonary embolism fare worse A new study led by UCLA researchers analyzed the different outcomes in men and women with a pulmonary embolism who are treated by a percutaneous pulmonary artery thrombectomy- a procedure in which a catheter is placed in a patient’s lung to dissolve or remove a blood clot. After analysis of a national cohort of US patients from an inpatient claims-based database, researchers reported that women had higher rates of procedural bleeding, vascular complications, and needed more blood transfusions compared to men. They also found that women had higher in-hospital death rates and were more likely to go a nursing home or an assisted living facility instead of returning home after discharge. Given these disparities in outcomes, study authors are calling for more sex-based research. Read the study in the January 1, 2023 issue of CHEST. 

    A new clue about Parkinson’s progression The transmission of misfolded proteins in the brain is a key mechanism for the progression of various neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease. Chao Peng, PhD, an assistant professor of neurology, found a novel mechanism that regulates the transmission of one of these pathological proteins, misfolded alpha-synuclein, which leads to disease progression in Parkinson’s. This mechanism is the discovery that many modifications that a cell makes in these proteins alter their ability for transmission in the brain and disease progression. This discovery not only provides critical insights into disease mechanism but also facilitates the development of novel therapy for neurodegenerative diseases. Read the study, published Jan. 23, in Nature Neuroscience.

    Urban heat islands, redlining and kidney stones The persistent rise in kidney stone prevalence in recent decades has prompted much speculation as to the causes. There has been some discussion about the effect of heat on nephrolithiasis. A review of recent data suggests that heat may play a role in stone formation on a large scale and among African-Americans in particular. A new UCLA-led study led by Dr. Kymora B. Scotland states that African-Americans are the race/ancestry group with faster rates of increasing incidence and prevalence of kidney stones. Researchers also found that urban heat islands in the United States have resulted in part from the effects of redlining, a practice of systematic segregation and racism in housing that led to the development of neighborhoods with substantial disparities in environmental conditions. Dr. Scotland and her team hypothesize that the increased temperatures experienced by residents in redlined communities, many of whom are African American may contribute to the 150% increase in the prevalence of kidney stones in African Americans in recent decades. Read the study in the January 1, 2023 issue of Current Opinion in Nephrology and Hypertension.

    Gender-affirming hormones tied to mental health for transgender youth Transgender and nonbinary teens who receive gender-affirming hormones experience improvement in body satisfaction, life satisfaction and less depression and anxiety than before treatment. These findings are according to newly-published research by a four-site prospective, observational study and co-authored by Marco A. Hidalgo, PhD. Dr. Hidalgo is a clinical psychologist and Associate Clinical Professor of Medicine at the David Geffen School of Medicine at UCLA. Read the study published January 19, 2023 in the New England Journal of Medicine.

    University of California, Los Angeles (UCLA), Health Sciences

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  • McMaster-led trial reduces COVID-19 hospitalization risk with single injection

    McMaster-led trial reduces COVID-19 hospitalization risk with single injection

    Newswise — Hamilton, ON (Feb. 9, 2023) – A team led by McMaster University researchers Gilmar Reis and Edward Mills has discovered that a single injection of pegylated interferon lambda (lambda) can successfully treat COVID-19 in people early in the disease.

    They say that one dose of lambda injected under a patient’s skin was more effective than any currently available treatment for early COVID and avoids the potential problems of patient adherence to drug treatment regimens.

    The findings were published in The New England Journal of Medicine on Feb. 9.

    “This discovery allows us to enter a new era where you can have pan-virus interventions against a range of diseases,” said Mills, a professor of the Department of Health Research Methods, Evidence, and Impact (HEI).

    Reis, an associate professor of the HEI, said, “Pegylated interferon lambda is a safe drug, and it is a single treatment approach.”

    “Lambda is not virus-specific as it works on all the different COVID-19 variants, and it probably also has a role to play in combatting other respiratory viruses such as influenza. We are beginning a study now of lambda for influenza.”

    Researchers tested lambda’s effectiveness using a randomized placebo-controlled trial involving adults with COVID-19 from both Canada and Brazil, who freely volunteered for the study. A total of 931 people received lambda and 1,018 received a placebo. Eighty-three per cent of the trial participants were vaccinated. Researchers ran the lambda trial from June 2021 to March 2022.

    Lambda works by activating the immune system’s antiviral defences against COVID-19 viruses invading the airways. Among the mostly vaccinated trial participants, lambda significantly reduced the need for hospitalization or emergency room visits compared to the placebo.

    “This could save tens of thousands of lives,” said Mills.

    Reis said, “The ultimate aim would be using it in combination with Paxlovid, but that needs to be evaluated in a clinical trial setting.”

    The lambda research falls under the ongoing TOGETHER trial, which Reis and Mills have led since June 2020. The ongoing platform study has evaluated multiple potential COVID-19 treatments during the pandemic. Potential treatments are always evaluated against a placebo.

    The TOGETHER platform has to date evaluated 14 different potential treatments, including lambda, since it was first launched in June 2020.

    External funding for the study was provided by FastGrants and the Rainwater Charitable Foundation. The lambda used in the trial was provided for free by Eiger BioPharmaceuticals.

    The McMaster researchers involved with the trial were Gilmar Reis, Edward Mills, Paula McKay, Sheila Sprague, Lehana Thabane and Gordon Guyatt.

    The study was done in partnership with Jordan Feld at University Health Network (UHN) and Professor Jeffrey Glenn at Stanford University. 

     

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    Editors:  

    A photo of Peginterferon Lambda can be found here: https://macdrive.mcmaster.ca/d/36d0184ee87a4513baf3/

    Credit: UHN

     

    McMaster University

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  • UNC Health Provider Ushers in First FDA-Approved Medication for Eosinophilic Esophagitis

    UNC Health Provider Ushers in First FDA-Approved Medication for Eosinophilic Esophagitis

    Newswise — Eosinophilic esophagitis (EoE) is an allergic condition of the esophagus that is on the rise throughout the United States. Patients with the condition typically have inflammation throughout their esophagus and trouble swallowing food – known as dysphagia.

    Without proper treatment, the lining of the esophagus becomes fibrous, and the passage becomes so narrowed, or strictured, that food can lodge in the esophagus, requiring medical attention.

    Historically, obtaining treatment has been difficult for U.S. physicians. There is one approved treatment for EoE in several other countries, but it is not available for use in the United States.

    This left physicians to rely on food elimination diets, off-label treatments, such as stomach acid reducers or asthma steroid medications (which are swallowed to coat the esophagus rather than inhaled), and stretching the esophagus with dilation during endoscopy. However, for many patients these methods were either not available or may not have been very effective.

    To fulfill this need, Evan Dellon, MD, MPH, a professor of medicine at the UNC School of Medicine and director of the Center for Esophageal Diseases and Swallowing, worked with colleagues on a clinical trial that led to approval of dupilumab for treatment in adults and adolescents with eosinophilic esophagitis.

    The drug was approved by the United States Food and Drug Administration in May 2022 based on a three-part, phase 3 clinical trial. The results of which were published in the New England Journal of Medicine in late December.

    “This study was designed to be a pivotal study for drug approval,” said Dellon, who was both the co-lead and corresponding author on the study. “Dupilumab was approved for eczema several years ago, and then was approved for asthma, and then for chronic rhinosinusitis with nasal polyposis. Eosinophilic esophagitis is now its fourth indication.”

    Scientifically speaking, EoE is caused by an accumulation of white blood cells, called eosinophils, in the esophagus – a place where they are not normally located. Typically, eosinophils can be found in the stomach, small bowel, and colon, where they are involved in fighting off parasites and infections. But when eosinophils are abnormally present in the esophagus, they release toxic chemicals, causing swelling, irritation, and ultimately the formation of scar tissue.

    Dupilumab is an antibody that blocks, or inhibits, a receptor called interleukin (IL)-4 receptor alpha. As a result, allergic factors IL-13 and IL-4, which are important in the inflammation that EoE patients experience, are suppressed when the receptor is blocked. This kind of drug cannot be taken orally; instead, it is injected under the skin once a week.

    The clinical trial was funded and sponsored by Regeneron Pharmaceuticals, the developer of dupilumab, and recruited 321 patients who were at least 12 years of age and weighed at least 40 kg (88 pounds), had a documented diagnosis of EoE through an endoscopic biopsy, and had not responded to eight weeks of high-dose stomach acid reducer therapy. The patients were separated into different groups to determine dosing and the overall effectiveness in resolving their symptoms and eosinophilic inflammation in the esophagus.

    The study had three parts. In part A, patients were randomized to either weekly dupilumab dosing or weekly placebo shots for 24 weeks. In part B, patients were randomized to one of two dose groups (weekly or every-other-week dupilumab) or to placebo, again for 24 weeks. Patients who completed parts A and B could continue on to part C, where they received open label dupilumab. This allowed the study of two different doses, as well as treatment up to 52 weeks.

    The study successfully met its pre-specified co-primary endpoints. Researchers witnessed a reduction in the eosinophil counts via esophageal biopsy (termed “histologic response”), as well as significant improvement in symptoms of dysphagia. In addition, there was better endoscopic healing with the medication than with placebo. Symptoms were only observed to improve more than placebo with the weekly dose than with a biweekly dose, so the medication was ultimately approved for once-weekly use.

    “In addition to the improvements with the eosinophil counts and symptoms, we also saw that the overall histologic severity, which includes all aspects of inflammation and pathologic changes in the biopsy improved with the Dupilumab,” said Dellon. “There was also evidence of normalization of the molecular changes associated with EoE. In basically every way disease activity was measured in this study, we saw improvements with dupilumab.”

    Because prior treatment guidelines were published prior to the FDA-approval of dupilumab, providers are still working out when it should be used for EoE in clinical practice. For example, should it be reserved for use after attempting other treatments first or should it be provided to patients who have more severe disease features. Dellon believes that initially most doctors will prescribe the therapy for their more severe patients who weren’t responding to prior therapies.

    “All of the patients in this study were non-responsive to proton pump inhibitors,” said Dellon, “So at the present time, this medicine should probably not be used as first-line treatment in most patients, and we are waiting for more data for how dupilumab would work in newly diagnosed EoE patients who have never been treated before.”

    To provide some guidance for use of dupilumab in clinical practice, Dellon worked with colleagues and the American College of Allergy, Asthma, and Immunology to develop what is known as a “yardstick”, which has just been published in the journal Annals of Allergy, Asthma, and Immunology. Essentially, this is a rapid communication that helps doctors choose the best course of treatment, given the patient’s individual situation, clinical severity, and prior treatments, while more formal treatment guidelines are under development.

    About the Center for Esophageal Diseases and Swallowing

    The Center for Esophageal Diseases & Swallowing (CEDAS) at the University of North Carolina at Chapel Hill is an exceptional team of professionals that is committed to providing quality healthcare and access to the newest technology and treatment for Barrett’s Esophagus, Eosinophilic Esophagitis, Gastroesophageal Reflux Disease, esophageal motility disorders, and other related conditions.

    About UNC School of Medicine  The UNC School of Medicine (SOM) is the state’s largest medical school, graduating more than 180 new physicians each year. It is consistently ranked among the top medical schools in the US, including 5th overall for primary care by US News & World Report, and 6th for research among public universities. More than half of the school’s 1,700 faculty members served as principal investigators on active research awards in 2021. Two UNC SOM faculty members have earned Nobel Prize awards. 

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    University of North Carolina Health Care System

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  • Sotorasib shows clinically meaningful activity in KRAS G12C-mutated advanced pancreatic cancer

    Sotorasib shows clinically meaningful activity in KRAS G12C-mutated advanced pancreatic cancer

    Newswise — In the Phase I/II CodeBreaK 100 trial, the KRAS G12C inhibitor sotorasib achieved meaningful anticancer activity with an acceptable safety profile in heavily pretreated patients with KRAS G12C-mutated metastatic pancreatic cancer, according to researchers at The University of Texas MD Anderson Cancer Center.

    The results of the trial, published today in the The New England Journal of Medicine, indicate an objective response rate of 21.1% and a median time-to-response of 1.5 months, with 84% of patients experiencing disease control. Median progression-free survival was 4 months and overall survival was 6.9 months.

    “These are encouraging early data because they point toward establishing that KRAS inhibitors can work in pancreatic cancers, which have been difficult to crack from a targeted therapy standpoint,” said principal investigator David S. Hong, M.D., professor of Investigational Cancer Therapeutics. “We look forward to data from larger trials as we continue working to bring much-needed new therapies to these patients.”

    The KRAS protein is part of a normal signaling pathway regulating growth and proliferation of cells, but activating mutations in KRAS drives abnormal growth in cancer. KRAS mutations are especially common in pancreatic cancers, occurring in about 90% of patients, while KRAS G12C mutations are present in 1-2% of cases.

    Sotorasib is a small-molecule inhibitor that irreversibly binds the mutant KRAS G12C protein to lock it in an inactive state. In 2021, this targeted therapy was approved by the Food and Drug Administration for the treatment of KRAS G12C-mutated metastatic non-small cell lung cancer, based on previous data from another cohort of this study.

    The pancreatic cancer cohort enrolled 38 patients with metastatic disease and a median of two prior lines of therapy. The median age of participants was 65.5, 76.3% were men and 55.3% had stage IV disease at initial diagnosis.

    All patients experienced treatment-emergent adverse events, the most common of which were abdominal pain (36.8%), diarrhea and nausea (23.7% each). Treatment-related adverse events were reported in 42.1% of patients, of which 15.8% were grade 3. The most frequently occurring grade 3 toxicities were diarrhea and fatigue (5.3% each). No adverse events resulted in discontinuation of treatment.

    According to Hong, these results may be a harbinger of success for other drugs in the pipeline targeting mutant KRAS that could potentially benefit far greater numbers of patients.

    “It’s gratifying to see results like this, since targeting mutant KRAS seemed virtually impossible just a few years ago. Still, we must continue our research efforts to make progress against other common KRAS mutations found in pancreatic and other cancer types,” Hong said. “Trials have recently begun on drugs targeting KRAS G12D, a much more common mutation in pancreatic cancer, as well as some pan-RAS therapies, which target multiple mutations.”

    This study was funded by Amgen. The work was also supported in part by the National Institutes of Health (P30 CA008748, P30 CA016672, 1UL1 TR003167), the Cancer Prevention and Research Institute of Texas (RP150535), and the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy at MD Anderson. A full list of authors and their disclosures can be found in the paper here.

    University of Texas M. D. Anderson Cancer Center

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  • NEJM study: Researchers Discover Hidden Genetic Anomaly Behind Common Late-Onset Cerebellar Ataxia

    NEJM study: Researchers Discover Hidden Genetic Anomaly Behind Common Late-Onset Cerebellar Ataxia

    Hello –This new scientific discovery, published today in the New England Journal of Medicine, should interest you for coverage. Below, please find link to full press release.

    Co-Senior Author Dr. Stephan Zuchner and Co-Primary Author, Dr. Matt Danzi, with the University of Miami are available for interviews.  Broll and high rez photos are also available.

    Full press release

    A copy of the study can be found here.

     

     

     

     

     

    University of Miami Health System, Miller School of Medicine

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  • Experimental Cancer Therapy Shows Success in More Than 70 Percent of Patients in Global Clinical Trials

    Experimental Cancer Therapy Shows Success in More Than 70 Percent of Patients in Global Clinical Trials

    Newswise — New York, NY (December 10, 2022) — A new therapy that makes the immune system kill bone marrow cancer cells was successful in as many as 73 percent of patients in two clinical trials, according to researchers from The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.

    The therapy, known as a bispecific antibody, binds to both T cells and multiple myeloma cells and directs the T cells—white blood cells that can be enlisted to fight off diseases—to kill multiple myeloma cells. The researchers described this strategy as “bringing your army right to the enemy.”

    The success of the off-the-shelf immunotherapy, called talquetamab, was even seen in patients whose cancer was resistant to all approved multiple myeloma therapies. It uses a different target than other approved therapies: a receptor expressed on the surface of cancer cells known as GPRC5D.

    Talquetamab was tested in phase 1 and phase 2 trials. The phase 1 trial, which was reported in The New England Journal of Medicine (NEJM), established two recommended doses that were tested in the Phase 2 trial. The results of the Phase 2 trial were reported at the American Society of Hematology annual meeting on Saturday, December 10. The study participants had all been previously treated with at least three different therapies without achieving lasting remission, suggesting talquetamab could offer new hope for patients with hard-to-treat multiple myeloma.

     “This means that almost three-quarters of these patients are looking at a new lease on life,” said Ajai Chari, MD, Director of Clinical Research in the Multiple Myeloma Program at The Tisch Cancer Institute and lead author of both studies. “Talquetamab induced a substantial response among patients with heavily pretreated, relapsed, or refractory multiple myeloma, the second-most-common blood cancer. It is the first bispecific agent targeting the protein GPRC5d in multiple myeloma patients.”

    Nearly all patients with myeloma who receive standard therapies continually relapse. Patients who relapse or become resistant to all approved multiple myeloma therapies have a poor prognosis, so additional treatments are urgently needed. This study, while an early-phase trial designed to detect tolerability and find a safe dose, is an important step in meeting that need.

    This Phase 1 clinical trial enrolled 232 patients at several cancer centers across the world between January 2018 and November 2021. Patients received a variety of doses of the therapy either intravenously or injected under their skin; future studies will focus on doses only administered under the skin either weekly or every other week

    The efficacy and safety findings in the phase 1 study were validated in the phase 2 trial presented at ASH. The phase 2 trial included 143 patients treated on a weekly dose and 145 patients treated at a higher biweekly dose.

    The overall response rate in these two groups was about 73 percent, Dr. Chari said. The response rate was maintained throughout various subgroups examined, with the exception of patients with a rare form of multiple myeloma that also extends to organs and soft tissues. More than 30 percent of patients in both groups had a complete response (no detection of myeloma-specific markers) or better, and nearly 60 percent had a “very good partial response” or better (indicating the cancer was substantially reduced but not necessarily down to zero).

    The median time to a measurable response was approximately 1.2 months in both dosing groups and the median duration of response to date is 9.3 months with weekly dosing. Researchers are continuing to collect data on the duration of response in the group receiving 0.8 mg/kg every other week and for patients in both dosing groups who had a complete response or better.

    Side effects were relatively frequent, but typically mild. About three-quarters of patients experienced cytokine release syndrome, which is a constellation of symptoms including fever that is common with immunotherapies. About 60 percent experienced skin-related side effects such as rash, about half reported taste changes, and about half reported nail disorders. The researchers said very few patients (5 to 6 percent) stopped talquetamab treatment because of side effects.

    The response rate observed in the study, which Dr. Chari explained is higher than that for most currently accessible therapies, suggests talquetamab could offer a viable option for patients whose myeloma has stopped responding to most available therapies, offering a chance to extend life and benefit from other new and future therapies as they are developed.

    These trials were sponsored and funded by Janssen.

      

    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, over 400 outpatient practices, nearly 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 7,300 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. We are consistently ranked by U.S. News & World Report‘s Best Hospitals, receiving high “Honor Roll” status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children’s Hospital among the country’s best in several pediatric specialties. The Icahn School of Medicine at Mount Sinai is one of three medical schools that have earned distinction by multiple indicators: It is consistently ranked in the top 20 by U.S. News & World Report‘s “Best Medical Schools,” aligned with a U.S. News & World Report “Honor Roll” Hospital, and top 20 in the nation for National Institutes of Health funding and top 5 in the nation for numerous basic and clinical research areas. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.

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

    Mount Sinai Health System

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  • New Onset Chronic Kidney Disease in People with Diabetes Highest Among Ethnic, Racial Minorities

    New Onset Chronic Kidney Disease in People with Diabetes Highest Among Ethnic, Racial Minorities

    Newswise — New onset chronic kidney disease (CKD) in people with diabetes is highest among racial and ethnic minority groups compared with white persons, a UCLA-Providence study finds.

    The study, published as a letter to the editor in the New England Journal of Medicine, found that new onset CKD rates were higher by approximately 60%, 40%, 33%, and 25% in the Native Hawaiian/Pacific Islander, Black, American Indian/Alaska Native, and Hispanic/Latino populations, respectively, compared to white persons with diabetes.

    Although high CKD incidence in diabetes persists, the rate declined from 8% of the overall diabetes population in 2015-2016 to 6.4% in 2019-2020”.

    “The results of our study constitute a call to action to institute directed, targeted efforts aimed at deliberately shifting the trajectory of persistently high rates of diabetes-related CKD and kidney failure that disproportionately affect racial and ethnic minority groups,” said co-author Dr. Susanne Nicholas, associate professor of medicine in the division of nephrology at the David Geffen School of Medicine at UCLA and chair of the UCLA Nephrology Racial and Health Equity Committee. “The first step should be to increase the rates of screening and detection of CKD in individuals with diabetes.”

    Researchers from the Geffen School, Providence, and the Centers for Disease Control and Prevention tracked 654,549 adults with diabetes from 2015 through 2020 using electronic health records from Providence Health and UCLA Health, two large not-for-profit health systems serving the Western United States.

    The prevalence of kidney failure requiring dialysis or transplant more than doubled to nearly 800,000 persons in the United States between 2000 and 2019, with diabetes as the leading cause. The rate of new onset of CKD in people with diabetes was previously unknown, yet the value of such incidence data is vital for identifying high-risk populations, determining the effectiveness of interventions, and assessing the effects on health care delivery and public health responses. Even more striking, less than 10% of patients with early stage kidney disease are aware of having CKD at this stage in its progression, when therapies are most effective. 

    “Given the rapidly growing population with diabetes in the United States and the corresponding high rates of kidney failure, the persistently high incidence of CKD marked by racial and ethnic disparities is troubling,” said lead author Dr.  Katherine Tuttle, executive director for research at Providence Inland Northwest Health and professor of medicine at the University of Washington. “Inclusive strategies for prevention, detection, and intervention are needed to reduce CKD risk in people with diabetes.”

    Additional study authors are Dr. O. Kenrik Duru and Dr. Keith Norris of UCLA; Cami Jones, Kenn Daratha, Dr. Radica Alicic, and Joshua Neumiller of Providence; and Nilka Ríos Burrows, Alain Koyama, and Dr. Meda Pavkov of the Centers for Disease Control and Prevention.

    University of California, Los Angeles (UCLA), Health Sciences

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  • New mitochondrial disease identified in identical twins

    New mitochondrial disease identified in identical twins

    Key Takeaways

    • In a set of identical twins, investigators have discovered a disease that affects the mitochondria, or the specialized compartments within cells that produce energy
    • Unlike in other mitochondrial diseases, mitochondria were hyperactive in these cases, so that even though the siblings had a high intake of calories, their body weights remained very low

    Newswise — BOSTON – In a set of identical twins, investigators led by researchers at Massachusetts General Hospital (MGH) and Children’s Hospital Philadelphia (CHOP) have identified a mitochondrial disease not previously reported.

    Diseases that affect mitochondria—specialized compartments within cells that contain their own DNA and convert the food we eat into energy needed to sustain life—typically interfere with mitochondrial function, but in these two patients, mitochondria were hyperactive.

    So, as reported in the New England Journal of Medicine, even though the siblings were eating far more calories than needed, their body weights remained very low.

    “This is a highly unusual mitochondrial phenotype. There are more than 300 rare genetic mitochondrial diseases, and nearly all of them are associated with an interruption of mitochondria,” says senior author Vamsi K. Mootha, MD, a Professor of Systems Biology and Medicine at MGH.

    Genome sequencing revealed a mutation in an enzyme called the mitochondrial ATP synthase, which is required by cells to generate the energy storage molecule ATP.

    Experiments indicated that this mutation creates “leaky” mitochondria that dissipate energy—a process called mitochondrial uncoupling.

    “We propose a new name—mitochondrial uncoupling syndrome—that presents with hypermetabolism and uncoupled mitochondria,” says Mootha. “These cases are very important for the field of rare disease genetics, mitochondrial biology, and metabolism.”

    The authors note that additional studies on mitochondrial uncoupling syndromes may provide insights into differences in energy metabolism in the general population.

    “These twins represent the first disorder of mitochondrial uncoupling where we have been able to find the genetic cause,” said Rebecca D. Ganetzky, MD, an attending physician in Mitochondrial Medicine program at CHOP and co-author of the study.

    “By discovering that pathogenic variants in the ATP synthase itself can cause mitochondrial uncoupling, these twins may be the first identified patients in a whole class of diseases of mitochondrial coupling.”

    Additional co-authors include Andrew L. Markhard, BA, Irene Yee, BS, Sheila Clever, MSc, Alan Cahill, PhD, Hardik Shah, MS, Zenon Grabarek, PhD, and Tsz-Leung To, PhD.

    This work was supported by the National Institutes of Health and others.

    About the Massachusetts General Hospital

    Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of “America’s Best Hospitals.” MGH is a founding member of the Mass General Brigham healthcare system.

    Massachusetts General Hospital

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  • ACS comments on European study on colonoscopies published in New England Journal of Medicine

    ACS comments on European study on colonoscopies published in New England Journal of Medicine

    Newswise — CHICAGO (October 11, 2022): The American College of Surgeons (ACS) is aware of a European study examining colonoscopy in Sweden, Poland, Norway, and the Netherlands, “Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death,” published this week in the New England Journal of Medicine1 that may seem to call into question the effectiveness of colonoscopy screening.

    Although the ACS recognizes global discrepancies in cancer screening recommendations across countries, the ACS remains committed to supporting U.S. evidence-based recommendations and practices based on decades of research, including the use of colonoscopy to screen for colorectal cancer.

    “As an evidence-based and educational organization of surgeons, it is clear that patient outcomes are vastly improved when cancer is detected early,” said ACS Executive Director & CEO, Patricia L. Turner, MD, MBA, FACS. “The value and importance of colonoscopies in preventing and detecting colorectal cancer cannot be overstated, and current U.S. guidelines are based on decades of research in the United States showing that routine screenings with colonoscopy can save lives.”

    “We recognize that this study is generating a lot of attention and could have the effect of discouraging some from getting life-saving colonoscopy screenings. We firmly stand behind the science that has unequivocally demonstrated the benefits of these screenings,” said Heidi Nelson, MD, FACS, Medical Director of the ACS Cancer Programs. As the Emeritus Fred C. Andersen Professor for the Mayo Foundation and consultant for Mayo Clinic’s division of colon and rectal surgery, Dr. Nelson is internationally renowned for her research in the field of colon and rectal cancer. “Significant work has gone on to optimize the reliability and accuracy of the colonoscopy test, both in terms of optimizing bowel preparations performed in advance of the procedure and the specialized training of the clinicians who perform the procedure. The evidence and data are abundantly clear that screenings with colonoscopies save lives. The bottom line is that people should continue to follow their doctors’ recommendations on colonoscopy screening.”

    Excluding skin cancers, colorectal cancer is the third most common cancer diagnosed in the United States, according to the American Cancer Society.2 Since the 1990s, national guidelines have supported the use of colonoscopies to screen for colorectal cancer.3 The procedure – in which a tube-like instrument with a light and video camera is inserted into the rectum to visualize abnormalities – can not only detect early cancers but can also prevent colorectal cancer through the removal of polyps, which can take 10-15 years to turn into cancer. 

    Moreover, colonoscopy has been recognized as an effective and reliable preventive health practice by the federal government. In 2000, the law expanded Medicare coverage to beneficiaries who were not considered high risk for colon cancer.4 Today, the American Cancer Society currently recommends that people at average risk of colorectal cancer start regular screening at age 45 through either a colonoscopy or a stool-based test.

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    1 Bretthauer M, Løberg M, Wieszczy P, et al. Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death,  New Engl J Med, 2022 Oct 9. doi:10.1056/NEJMoa2208375

    2 American Cancer Society Guideline for Colorectal Cancer Screening: https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html

    3 Trends in Screening for Colorectal Cancer -United States, 1997 and 1999: https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5009a2.htm

    4 Moore KJ, Medicare Expands Preventive Screening Benefits, Fam Pract Mang. 2001; 8(6):16: https://www.aafp.org/pubs/fpm/issues/2001/0600/p16.html

     

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    About the American College of Surgeons  

    The American College of Surgeons (ACS) is a scientific and educational organization of surgeons that was founded in 1913 to raise the standards of surgical practice and improve the quality of care for all surgical patients. The College is dedicated to the ethical and competent practice of surgery. Its achievements have significantly influenced the course of scientific surgery in America and have established it as an important advocate for all surgical patients. The College has more than 84,000 members and is the largest organization of surgeons in the world. “FACS” designates that a surgeon is a Fellow of the American College of Surgeons.   

     

     

    American College of Surgeons (ACS)

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