Tag: Hormone

  • Study reveals strong bidirectional relationship between perinatal depression and premenstrual disorders

    Study reveals strong bidirectional relationship between perinatal depression and premenstrual disorders

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    Women affected by premenstrual disorders have a higher risk of perinatal depression compared with those who do not, according to research published March 28th in the open access journal PLOS Medicine. The relationship works both ways: those with perinatal depression are also more likely to develop premenstrual disorders after pregnancy and childbirth. This study suggests that a common mechanism might contribute to the two conditions.

    Menstruating women experience cyclical hormone fluctuations through puberty, menstrual cycle, pregnancy and menopause. Some women have difficult to manage symptoms of low mood and depression during these fluctuations. Between a fifth and a third of women are reportedly affected by premenstrual disorders and 11% of mothers suffer perinatal depression -; depressive symptoms during pregnancy and up to 12 months after delivery.

    Qian Yang and colleagues at the Karolinska Institutet, Sweden and University of Iceland used the Swedish nationwide registers from 2001 to 2018 and identified 84,949 women with perinatal depression and 849,482 unaffected women. The researchers matched the women on age and calendar year, and further controlled for demographic factors, smoking, BMI, parity and history of psychiatric disorders. Among women with perinatal depression, almost 3% had premenstrual disorders before pregnancy compared with 0.6% of matched unaffected women. Women with perinatal depression were also twice as likely to report premenstrual disorders when the menstruation resumed after childbirth, compared to those unaffected by perinatal depression.

    The research sheds light on the association between the two conditions and supports a theory that they may share underlying biological mechanisms and/or risk factors. Understanding this association could help healthcare providers to better target support to women most likely to be affected.

    The authors add, “This study reveals a strong bidirectional relationship between perinatal depression and premenstrual disorders, using data from over 900,000 pregnancies. The findings suggest that both disorders may exist on a continuum, and emphasize the importance of recognizing these susceptibilities in clinical practice.

    Source:

    Journal reference:

    Yang, Q., et al. (2024) The bidirectional association between premenstrual disorders and perinatal depression: A nationwide register-based study from Sweden. PLOS Medicine. doi.org/10.1371/journal.pmed.1004363.

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  • Sweeteners do not increase hunger and help lower blood sugar, study finds

    Sweeteners do not increase hunger and help lower blood sugar, study finds

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    Replacing sugar with artificial and natural sweeteners in foods does not make people hungrier – and also helps to reduce blood sugar levels, a significant new study has found. 

    The double blind randomized controlled trial found that consuming food containing sweeteners produced a similar reduction in appetite sensations and appetite-related hormone responses as sugary foods – and provides some benefits such as lowering blood sugar, which may be particularly important in people at risk of developing type 2 diabetes. 

    The use of sweeteners in place of sugar in foods can be controversial due to conflicting reports about their potential to increase appetite. Previous studies have been carried out but did not provide robust evidence. 

    However, the researchers say their study, which meets the gold standard level of proof in scientific investigation, provides very strong evidence that sweeteners and sweetness enhancers do not negatively impact appetite and are beneficial for reducing sugar intake. 

    The trial was led by the University of Leeds in collaboration with the The Rhône-Alpes Research Center for Human Nutrition. It is the latest study to be published by the SWEET consortium of 29 European research, consumer and industry partners which is working to develop and review evidence on long term benefits and potential risks involved in switching over to sweeteners and sweetness enhancers in the context of public health and safety, obesity, and sustainability. It was funded by Horizon Europe. 

    Reducing sugar consumption has become a key public health target in the fight to reduce the rising burden of obesity-related metabolic diseases such as type 2 diabetes. 


    Simply restricting sugar from foods without substitution may negatively impact its taste or increase sweet cravings, resulting in difficulties sticking to a low-sugar diet. Replacing sugars with sweeteners and sweetness enhancers in food products is one of the most widely used dietary and food manufacturing strategies to reduce sugar intake and improve the nutritional profile of commercial foods and beverages.” 


    Catherine Gibbons, Lead Author, Associate Professor in the University of Leeds’ School of Psychology

    Principal investigator Graham Finlayson, Professor of Psychobiology in the University of Leeds’ School of Psychology, said: “The use of sweeteners and sweetness enhancers has received a lot of negative attention, including high profile publications linking their consumption with impaired glycaemic response, toxicological damage to DNA and increased risk of heart attack and stroke. These reports contribute to the current befuddlement concerning the safety of sweeteners and sweetness enhancers among the general public and especially people at risk of metabolic diseases. 

    “Our study provides crucial evidence supporting the day-to-day use of sweeteners and sweetness enhancers for body weight and blood sugar control.” 

    The study, which is the first of its kind, looked at the effects of consuming biscuits containing either sugar or two types of food sweetener: natural sugar substitute Stevia, or artificial sweetener Neotame on 53 adult men and women with overweight or obesity. 

    Until now, virtually all studies of the effects of sweeteners and sweetness enhancers on appetite and glycemia have been conducted using beverages as the vehicle. Few studies include volunteers with overweight or obesity and few have included volunteers of both sexes. 

    Most studies have only compared a single sweetener, mostly aspartame, with a control, and very few studies have examined the effect of repeated daily intake of a known sweetener or sweetness enhancer in the normal diet. 

    The new trial took place at the University of Leeds and the Rhône-Alpes Research Center for Human Nutrition (CRNH-RA), France between 2021 and 2022. Participants were all aged 18 to 60, with overweight or obesity. 

    The trial consisted of three two-week consumption periods, where participants consumed biscuits with either fruit filling containing sugar; natural sugar substitute Stevia, or artificial sweetener Neotame, each separated by a break of 14-21 days. Day 1 and day 14 of the consumption periods took place in the lab. 

    Participants were instructed to arrive in the lab after an overnight fast, a blood sample was taken to establish baseline levels of glucose, insulin and appetite-related hormones. They were also asked to rate their appetite and food preferences. 

    After consuming the biscuits, they were asked to rate how full they felt over several hours. Glucose and insulin levels were measured, as were ghrelin, glucagon-like peptide 1 and pancreatic polypeptide – hormones associated with the consumption of food. 

    The results from the two sweetener types showed no differences in appetite or endocrine responses compared to sugar, but insulin levels measured over two hours after eating were reduced, as were blood sugar levels. 

    SWEET project joint co-ordinator Professor Anne Raben, from the University of Copenhagen, Denmark, said: “The findings show that sweeteners are a helpful tool to reduce intake of added sugar without leading to a compensatory increase in appetite or energy intake, thereby supporting the usefulness of sweeteners for appetite, energy and weight management.” 

    Source:

    Journal reference:

    Gibbons, C., et al. (2024) Acute and two-week effects of neotame, stevia rebaudioside M and sucrose-sweetened biscuits on postprandial appetite and endocrine response in adults with overweight/obesity—a randomised crossover trial from the SWEET consortium. eBioMedicine. doi.org/10.1016/j.ebiom.2024.105005.

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  • Researchers identify increased brain tumor risk with specific contraceptive use

    Researchers identify increased brain tumor risk with specific contraceptive use

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    In a recent study published in BMJ, researchers evaluated the intracranial meningioma risk associated with progestogen use.

    Study: Use of progestogens and the risk of intracranial meningioma: national case-control study. Image Credit: fongbeerredhot/Shutterstock.comStudy: Use of progestogens and the risk of intracranial meningioma: national case-control study. Image Credit: fongbeerredhot/Shutterstock.com

    Background

    Meningiomas are primary central nervous system tumors that can compress nearby brain tissue, necessitating surgical decompression.

    Age, female sex, neurofibromatosis type 2, ionizing radiation exposure, and long-term usage of high-dose progestogens such as nomegestrol, chlormadinone, and cyproterone acetate are all risk factors for intracranial meningioma. Discontinuing these progestogens minimizes meningioma volume, avoiding surgery and its risks.

    However, meningioma risk related to other progestogens is uncertain, and there is no apparent link between exogenous female hormones and meningioma risk for hormonal contraceptives.

    Further, the evidence regarding hormone replacement therapy for menopause is conflicting. Discontinuing these progestogens minimizes meningioma volume, preventing surgery and related risks.

    About the study

    In the present observational and population-based study, researchers investigated whether certain progestogens increased intracranial meningioma risk and related delivery routes.

    The researchers analyzed data from France’s National Health Information System [i.e., Système National des Données de Santé (SNDS)]. Among 108,366 females, 18,061 residing in France and operating for intracranial meningioma from January 2009 to December 2018 were cases.

    The researchers matched each case to five control individuals by birth year and residence area (90,305 controls), excluding women with pregnancies commencing two years before hospitalization for meningioma surgery.

    Progestogens used included hydroxyprogesterone, progesterone, medrogestone, dydrogesterone, promegestone, medroxyprogesterone acetate, levonorgestrel, and dienogest. The administration routes investigated were oral, intramuscular, intravaginal, percutaneous, and intrauterine.

    The team defined progestogen use by one drug dispensation within 12 months before hospitalization (within three and five years for intrauterine levonorgestrel systems in doses of 13.50 mg and 52 mg, respectively).

    The researchers used the World Health Organization’s (WHO) Anatomical, Therapeutic, and Chemical (ATC) classification to define progestogen exposure. They used conditional logistic regressions to determine the odds ratios (OR) for analysis. Study covariates included residence, age, type 2 neurofibromatosis, and, for meningioma cases only, surgery year, tumor site, and grade.

    The team obtained adjuvant radiation data between three months before and six months after hospitalization. They also evaluated the patients for all-cause death two and five years after the hospitalization date and antiepileptic medicine use three years after surgery.

    In addition, they performed sensitivity analyses, stratifying the data by patient age, tumor location, and severity.

    Results

    The mean participant age was 58 years, and the most common tumor site was the skull base (56%). Most cases were benign (92%), with 5.8% atypical and 1.9% malignant tumors. Among the cases, 29% of women consumed antiepileptic medications after three years of surgery.

    Mortality rates were higher among cases than controls, with 2.8% of cases dying within two years and 5.3% within five years. Of 18,061 cases, 1.8% used oral or intravaginal progesterone, and 1.5% used spironolactone.

    0.9% used dydrogesterone, 0.9% used medroxyprogesterone acetate, 0.5% used percutaneous progesterone, 0.2% used medrogestone, 0.1% used dienogest, and 0.5% used promegestone.

    The team noted excess meningioma risk related to medrogestone use [42/18,061 cases (0.20%) vs. 79/90,305 control individuals (0.10%), OR 3.5], promegestone [83/18,061 (0.5%) vs. 225/90,305 (0.2%), OR 2.4], and medroxyprogesterone acetate [injectable route, 9/18,061 (0.05%) vs. 11/90,305 (0.01%), OR 5.6]. The excess meningioma risk was associated with progestogen use for ≥12 months.

    In contrast, there was no excess meningioma risk for dydrogesterone, progesterone, and levonorgestrel intrauterine medications. The team could not conclude hydroxyprogesterone or dienogest use due to the limited sample size of drug recipients.

    They observed a considerably elevated risk of intracranial meningioma for nomegestrol acetate [5.1% (925 cases) vs. 1.2% (1,121 controls), OR 4.9], cyproterone acetate [4.9% (891 cases) vs. 0.3% (256 controls), OR 19.2], and chlormadinone [3.5% (628 cases) vs. 1.0% (946 controls), OR 3.9], which were positive controls.

    The sensitivity analyses showed a high excess meningioma risk for the middle of the skull tumors (OR 8.3), with a slightly higher risk among women aged 45–54 years.

    The excess meningioma risk related to promegestone use was marginally higher among individuals aged above 65 years (OR 3.2) and for tumors in the middle or front of the skull (ORs of 3.0 and 3.2, respectively).

    Conclusions

    The study findings showed prolonged usage of medrogestone (oral, 5.0 mg), medroxyprogesterone acetate (injectable, 150 mg), and promegestone (oral, 0.10/0.50 mg) was associated with increased meningioma risk.

    However, there was no excess meningioma risk related to progesterone (oral, percutaneous, and intravaginal; 25, 100, and 200 mg), dydrogesterone (10 mg, combined with estrogen: 5, 10 mg), spironolactone (25, 50, 75 mg), and levonorgestrel (intrauterine, 13.5 mg and 52 mg) use.

    Future studies should investigate the relationship between progestogen duration and meningioma risk, broaden the topic to include dienogest and hydroxyprogesterone and evaluate meningioma risk with medroxyprogesterone acetate, a second-line injectable contraceptive infrequently used in France.

    Further research from nations with a larger population and vulnerable groups is required to improve understanding of the dose-response relationship of this medication.

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  • AI-based analysis uncovers two plant extracts with potential as GLP-1 agonist weight loss pills

    AI-based analysis uncovers two plant extracts with potential as GLP-1 agonist weight loss pills

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    Two plant compounds with potential as GLP-1 agonist weight loss pills have been identified in an AI (artificial intelligence)-based study, the European Congress on Obesity (ECO 2024) (Venice 12-15 May), will hear.

    Glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide and tirzepatide are highly effective at helping people lose weight. By mimicking the action of a hormone called GLP-1 and binding to and activating the GLP-1 receptor in cells, they reduce appetite and feelings of hunger, slow the release of food from the stomach and increase feelings of fullness after eating.

    There is, however, a need for alternatives, says Elena Murcia, of the Structural Bioinformatics and High-Performance Computing Research Group (BIO-HPC) & Eating Disorders Research Unit, Catholic University of Murcia (UCAM), Murcia, Spain.

    Although the effectiveness of current GLP-1 agonists has been demonstrated, there are some side-effects associated with their use – gastrointestinal issues such as nausea, vomiting, and mental health changes like anxiety and irritability. Recent data has also confirmed that when patients stop treatment they regain lost weight.


    In addition, most GLP-1 agonists are peptides – short chains of amino acids that can be degraded by stomach enzymes – and so they are currently more likely to be injected rather than taken orally.


    Drugs that aren’t peptides may have fewer side-effects and be easier to administer, meaning they could be given as pills rather than injections. Other recent research has highlighted two promising non-peptide compounds, TTOAD2 and orforglipron.


    These are synthetic and we were interested in finding natural alternatives.”


    Elena Murcia, of the Structural Bioinformatics and High-Performance Computing Research Group (BIO-HPC) & Eating Disorders Research Unit, Catholic University of Murcia

    Ms Murcia and colleagues used high-performance artificial intelligence (AI) techniques to identify non-peptide natural compounds that activate the GLP-1 receptor.

    “We focused on plant extracts and other natural compounds because they may have fewer side-effects,” says Ms Murcia. 

    Virtual screening was used to sift through more than 10,000 compounds to identify those that bound to the GLP-1 receptor.

    Next, further AI-based methods were used to look at how closely these bonds resembled those that occur between the GLP-1 hormone and its receptor. The 100 compounds that bound most similarly were then chosen for additional visual analysis, to determine whether they interacted with key residues – amino acids – on the receptor.

    Finally, a Venn diagram (a mathematical graph using overlapping circles) was compiled to identify the compounds with the highest potential as GLP1-R agonists.

    This resulted in a shortlist of 65 compounds, two of which, “Compound A” and “Compound B”, bound strongly to the key residues in a similar way to TTOAD2 and orforglipron. 

    Compound A and Compound B are derived from very common plants, extracts of which have been associated with beneficial effects on the human metabolism in the past. Further details of the plants and the compounds are being kept confidential until patents are granted. It is hoped both could be given in pill-form. The two compounds are now undergoing lab tests. 

    Ms Murcia says: “We are in the early stages of developing new GLP-1 agonists derived from natural sources. If our AI-based calculations confirmed in vitro and then in clinical trials, we will have other therapeutic options to manage obesity. 

    “Computer-based studies such as ours have key advantages, such as reductions in costs and time, rapid analysis of large data sets, flexibility in experimental design and the ability to identify and mitigate any ethical and safety risks before conducting experiments in the laboratory.

    “These simulations also allow us to take advantage of AI resources to analyze complex problems and so provide a valuable initial perspective in the search for new drugs.”

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  • Feedback loop involving estrogen linked to women’s higher propensity to nicotine addiction

    Feedback loop involving estrogen linked to women’s higher propensity to nicotine addiction

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    A newly discovered feedback loop involving estrogen may explain why women might become dependent on nicotine more quickly and with less nicotine exposure than men. The research could lead to new treatments for women who are having trouble quitting nicotine-containing products such as cigarettes.

    Sally Pauss is a doctoral student at the University of Kentucky College of Medicine in Lexington. She led the project.

    “Studies show that women have a higher propensity to develop addiction to nicotine than men and are less successful at quitting,” said Pauss, who is working under the supervision of Terry D. Hinds Jr., an associate professor. “Our work aims to understand what makes women more susceptible to nicotine use disorder to reduce the gender disparity in treating nicotine addiction.”

    The researchers found that the sex hormone estrogen induces the expression of olfactomedins, proteins that are suppressed by nicotine in key areas of the brain involved in reward and addiction. The findings suggest that estrogen–nicotine–olfactomedin interactions could be targeted with therapies to help control nicotine consumption.

    Pauss will present the research at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology, which will be held March 23–26 in San Antonio.

    Our research has the potential to better the lives and health of women struggling with substance use. If we can confirm that estrogen drives nicotine seeking and consumption through olfactomedins, we can design drugs that might block that effect by targeting the altered pathways. These drugs would hopefully make it easier for women to quit nicotine.”


    Sally Pauss, doctoral student, University of Kentucky College of Medicine

    For the new study, the researchers used large sequencing datasets of estrogen-induced genes to identify genes that are expressed in the brain and exhibit a hormone function. They found just one class of genes that met these criteria: those coding for olfactomedins. They then performed a series of studies with human uterine cells and rats to better understand the interactions between olfactomedins, estrogen and nicotine. The results suggested that estrogen activation of olfactomedins -; which is suppressed when nicotine is present -; might serve as a feedback loop for driving nicotine addiction processes by activating areas of the brain’s reward circuitry such as the nucleus accumbens.

    The researchers are now working to replicate their findings and definitively determine the role of estrogen. This knowledge could be useful for those taking estrogen in the form of oral contraceptives or hormone replacement therapy, which might increase the risk of developing a nicotine use disorder.

    The investigators also want to determine the exact olfactomedin-regulated signaling pathways that drive nicotine consumption and plan to conduct behavioral animal studies to find out how manipulation of the feedback loop affects nicotine consumption.

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  • After Appalachian hospitals merged into a monopoly, their ERs slowed to a crawl

    After Appalachian hospitals merged into a monopoly, their ERs slowed to a crawl

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    In the small Appalachian city of Bristol, Virginia, City Council member Neal Osborne left a meeting on the morning of Jan. 3 and rushed himself to the hospital.

    Osborne, 36, has Type 1 diabetes. His insulin pump had malfunctioned, and without a steady supply of this essential hormone, Osborne’s blood sugar skyrocketed and his body was shutting down.

    Osborne went to the nearest hospital, Bristol Regional Medical Center. He said he settled into a wheelchair in the emergency room waiting area, where over the next few hours he drifted in and out of consciousness and retched up vomit, then bile, then blood. After 12 hours in the waiting room, Osborne said, he was moved to an ER bed, where he stayed until he was sent to the intensive care unit the next day. In total, the council member was in the ER for about 30 hours, he said.

    Osborne said his ordeal echoes stories he’s heard from constituents for years. In his next crisis, Osborne said, he plans to leave Bristol for an ER about two hours away.

    “I want to go to Knoxville or I want to go to Roanoke, because I do not want to further risk my life and die at a Ballad hospital,” he said. “The wait times just to get in and see a doctor in the ER have grown exponentially.”

    Ballad Health, a 20-hospital system in the Tri-Cities region of Tennessee and Virginia, benefits from the largest state-sanctioned hospital monopoly in the United States. In the six years since lawmakers in both states waived anti-monopoly laws and Ballad was formed, ER visits for patients sick enough to be hospitalized grew more than three times as long and now far exceed the criteria set by state officials, according to Ballad reports released by the Tennessee Department of Health.

    Tennessee and Virginia have so far announced no steps to reduce time spent in Ballad ERs. The Tennessee health department, which has a more direct role in regulating Ballad, has each year issued a report saying the agreement that gave Ballad a monopoly “continues to provide a Public Advantage.” Department officials have twice declined to comment to KFF Health News on Ballad’s performance.

    According to Ballad’s latest annual report, which was released this month and spans from July 2022 to June 2023, the median time that patients spend in Ballad ERs before being admitted to the hospital is nearly 11 hours. This statistic includes both time spent waiting and time being treated in the ER and excludes patients who weren’t admitted or left the ER without receiving care.

    The federal government once tracked ER speed the same way. When compared against the latest corresponding federal data from 2019, which includes more than 4,000 hospitals but predates the covid-19 pandemic, Ballad ranks among the 100 hospitals with the slowest ERs. More current federal data is not available because the Centers for Medicare & Medicaid Services retired this statistic in 2020 in favor of other measurements.

    Newer data tells a similar story. The Joint Commission, a nonprofit that accredits health care organizations, collected this same measurement for 2022 from about 250 hospitals that volunteered the data, finding a median ER speed of five hours and 41 minutes — or about five hours faster than Ballad’s latest annual report.

    Ballad Health spokesperson Molly Luton said in an email statement that, by holding patients in the ER, where they are observed while waiting for a bed, Ballad avoids “overwhelming” its staff. Luton said ER delays are also caused by two nationwide crises: a nursing shortage and fewer admissions at nursing homes and similar facilities, which can create a backlog of patients awaiting discharge from the hospital.

    Luton added that Ballad’s ER time for admitted patients has dropped to about 7½ hours in the months since the company’s latest annual report.

    “On those issues Ballad Health can directly control, our performance has rebounded from 2022, and is now among the best in the nation,” Luton said.

    Luton also noted that Ballad performs better than or close to the national average on several other measurements of ER performance, including having fewer patients who leave without being treated. CMS data shows the national average is about 3%. Ballad reported 1.4% in its latest annual report.

    Osborne, the Bristol council member, attributed this statistic to Ballad’s monopoly.

    “Just because they aren’t leaving the ER doesn’t mean they are happy where they are,” he said. “It just means they don’t have anywhere else they could be.”

    Ballad’s big monopoly

    Ballad Health was formed in 2018 after state officials approved the nation’s biggest hospital merger based on a so-called Certificate of Public Advantage, or COPA, agreement. COPAs have been used in about 10 hospital mergers over the past three decades, but none has involved as many hospitals as Ballad’s.

    State lawmakers in Tennessee and Virginia waived federal anti-monopoly laws so rival hospital systems — Mountain States Health Alliance and Wellmont Health System — could merge into a single company with no competition. Ballad is now the only option for hospital care for most of about 1.1 million residents in a 29-county region at the nexus of Tennessee, Virginia, Kentucky, and North Carolina.

    The Federal Trade Commission warns that hospital monopolies lead to increased prices and decreased quality of care. To offset the perils of Ballad’s monopoly, officials required the new company to commit to a long list of special conditions, including dozens of quality-care metrics spelled out with specific benchmarks.

    In its latest annual report, Ballad improved on many quality-of-care metrics over the prior year, including several that the company prioritized, but still fell short on 56 of 75 benchmarks.

    ER time for admitted patients is one of those. The benchmark was set at three hours and 47 minutes in the original COPA agreement. Ballad met or nearly met this goal for three years, according to its annual reports. Then the ERs slowed.

    In 2022, Ballad reported a median ER time for admitted patients of about six hours.

    In 2023, it reported the same statistic at seven hours and 40 minutes.

    In the latest report, ER time for admitted patients had reached 10 hours and 45 minutes.

    CMS, which grades thousands of hospitals nationwide, warns on its website that timely ER care is “essential for good patient outcomes,” and that more time spent in the ER has been linked to higher complication rates and delays in patients getting pain medication and antibiotics.

    Ben Harder, chief of health analysis for U.S. News & World Report, said extensive ER times can be a symptom of slowdowns throughout a hospital, including in the operating room.

    “A long delay in getting patients admitted is both a risk in itself, in that a test may not get conducted as promptly,” Harder said. “But it’s also an indication that the hospital is backed up, and that there are problems getting patients moved from one unit to another.”

    Bill Christian, a spokesperson for the Tennessee Department of Health, said Ballad’s rising ER times had been “noted” but did not say if the agency had taken or was considering any action. Christian directed questions about Ballad’s latest stats to the company itself.

    ‘A nightmare for community members’

    Ballad has also fallen short — by about $191 million over the past five years — of its obligation to Tennessee to provide charity care, which is free or discounted care for low-income patients, according to health department documents and Ballad’s latest report. The health department waived this obligation in each of the past four fiscal years. Ballad has said it would ask for another this year.

    In a two-hour interview last year, Ballad CEO Alan Levine defended his company and said that because the Tri-Cities region could not support two competing hospital companies, the COPA merger had likely prevented at least three hospital closures. Levine attributed Ballad’s failure to meet quality benchmarks to the pressure of the covid pandemic and said charity care shortfalls were partly caused by Medicaid changes beyond Ballad’s control.

    “Our critics say, ‘No Ballad. We don’t want Ballad.’ Well, then what?” Levine said. “Because the hospitals were on their way to being closed.”

    Some residents see Ballad as a savior. John King, who runs a physical therapy clinic in the core of Ballad’s region, said at a public hearing last June that in multiple visits to Ballad ERs, including one for a stroke, he found their care to be quick and compassionate.

    “If it weren’t for Ballad Health, I literally would not be here today,” King said, according to a hearing transcript.

    Ballad’s failures to live up to the terms of the COPA agreement were detailed in a KFF Health News investigation last September, and the company faced a new wave of criticism in the months that followed.

    Local leaders in Carter County, Tennessee, in October debated but did not pass a resolution calling for Ballad to be better regulated or broken up. Tennessee Attorney General Jonathan Skrmetti, a Republican, said in an interview with the Tennessee Lookout published in November that Ballad must be constantly monitored in light of community complaints. Earlier this month, Tennessee state Rep. David Hawk (R-Greeneville), who represents a region within Ballad’s monopoly, called for Levine’s resignation, according to wjhl.com.

    In response, Ballad Health said in a statement it has “strong relationships with the majority of elected officials” in Carter County and welcomed scrutiny from the Tennessee attorney general. Ballad said Hawk’s “opinion certainly does not reflect our broader relationships” within the area. Tennessee lawmakers are also considering legislation to forbid future COPA mergers in the state, which Ballad said “risks putting more hospitals at risk for closure.”

    The bill was introduced by state Sen. Heidi Campbell (D-Nashville) and state Rep. Gloria Johnson (D-Knoxville), who is running for the U.S. Senate. Johnson said the bill would end Ballad’s protection from antitrust laws.

    “It’s just been a nightmare for community members out there,” Johnson said. “And they have no other option.”




    Kaiser Health NewsThis article was reprinted from khn.org, a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

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  • Genetic test can identify how patients with triple negative early-stage breast cancer will respond to immunotherapy

    Genetic test can identify how patients with triple negative early-stage breast cancer will respond to immunotherapy

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    Researchers have developed a genetic test that can identify how patients with triple negative early-stage breast cancer will respond to immunotherapy drugs. This means that patients who are unlikely to respond to these drugs can avoid the adverse side effects associated with them and can be treated with other therapies.

    Professor Laura van ‘t Veer told the 14th European Breast Cancer Conference that the latest results from the I-SPY2 trial suggest that the current standard of care for patients with triple negative breast cancer should be reconsidered.

    “Immunotherapy drugs can have very severe, irreversible adverse side effects, as observed in the I-SPY2 trial. The findings I’m presenting today should provoke a discussion about whether giving immunotherapy drugs to all patients with triple negative disease, which has recently become the standard of care in most countries, is the right strategy. Our research shows that it should be adapted so as to select only those patients who are very likely to benefit from this treatment. Patients who are unlikely to respond could then receive alternative therapies,” said Prof. van ‘t Veer, who is a Professor of Laboratory Medicine, Co-leader of the Breast Oncology Program and Director of Applied Genomics at the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, USA.

    The I-SPY2 trial was established in 2010 to find ways to screen new anti-cancer drugs and match them to specific biological markers in patients with breast cancer at high risk of early recurrence. Researchers developed an immune classifier, called ImPrint, composed of 53 genes, which can be used in the clinic to predict the likelihood of a patient responding to immunotherapies by looking at the biology of the patient’s tumor. It classifies tissue from patient biopsies into ‘likely responder’ or ‘likely non-responder’ to immunotherapy.

    Today, Prof. van ‘t Veer presented the results for an updated version of the classifier, ImPrintTN, refined to provide more accurate predictions for patients with triple-negative breast cancer – the type of breast cancer in which the cancer cells are not fuelled by either estrogen, progesterone or the HER2 protein.

    “Previously, we showed that gene expression signatures representing the active components of the immune system can predict the response to pembrolizumab – an immune-oncology drug that targets PD1, which is a protein on the surfaces of cells that plays a role in the immune system. Both patients with triple negative disease and also patients with hormone receptor positive breast cancer, who had not yet received treatment and whose tumours had this active immune biology, showed a significant, up to three times higher, pathologic complete response rate when treated with pembrolizumab,” she said.

    A pathologic complete response (pCR) is when the cancer shrinks and even disappears after drug treatment.

    She continued: “This classifier had a good performance across triple negative and hormone receptor positive breast cancers combined, and had very high positive predictive value for hormone receptor positive breast cancers, meaning that it identified those cancers that would likely respond to an immunotherapy.”

    “However, we noticed that the performance of ImPrint for triple negative breast cancers, where immune oncology drugs are now standard of care, was not yet good enough to identify patients in whom a ‘likely response’ to immunotherapy was so low that harm from serious side-effects would be higher than the benefit.

    “This new work now presents an update of the ImPrint classifier specifically for triple negative breast cancers, ImPrintTN. We found that it can predict patients who are unlikely to respond to immunotherapy, so that the harms from the treatment are greater than the benefit. This means it would be acceptable for them to forgo an immunotherapy drug in order to avoid the risk of these sometimes life-long irreversible adverse effects.”

    Out of 150 patients receiving immunotherapy in four arms of the trial and 128 patients in the control arm, receiving taxane and anthracycline chemotherapy, ImPrintTN identified 66% patients with triple negative breast cancer as being likely to respond to immunotherapy.

    Patients in the immunotherapy arms had been divided equally into two sets: a training and a test set, and the sets were also balanced so as to have an equal number of ‘responders’ and ‘non-responders’.

    In the independent test set, pCR rates were 71% compared to 22% in patients identified as unlikely to respond. When all five arms were combined (the test and the training sets), pCR rates were 74% in patients identified as likely to respond and 16% in those that ImPrintTN classified as unlikely to respond. This improves on the previous version of ImPrint where pCR rates were 38% among patients that it identified as unlikely to respond.

    In the control arm of the trial where patients had been treated with standard of care chemotherapies only, pCR rates were 30% among patients identified by ImPrint as ‘responders’ and 15% among ‘non-responders’.

    “The likelihood of an immunotherapy drug response for triple negative cancers that are ImPrint-positive, remains very high at 74%, while among patients that ImPrintTN identified as likely ‘non-responders’ the pCR rates for immunotherapy are now very low at 16% – low enough for the harm from immunotherapy drugs to outbalance the benefit in these patients,” said Prof. van ‘t Veer. “This is a clinically important improvement and suggests that ImPrintTN may help to inform prioritisation of immunotherapies versus other treatments for patients with triple negative breast cancer in order to best balance likely benefit versus the risk of serious and irreversible adverse effects. There is a subgroup of patients where the harm of these drugs outweighs the therapeutic benefit.

    “Once ImPrintTN has been validated further, immunotherapy drugs should only be given to patients with triple negative or HR positive disease who have a high likelihood of benefitting.”

    Professor Michail Ignatiadis from the Institut Jules Bordet in Brussels, Belgium, is Chair of the 14th European Breast Cancer Conference and was not involved in the research.

    It is increasingly appreciated that the ‘one size fits all’ approach is not optimal for the systemic treatment of patients with early triple negative breast cancer. The identification of biomarkers to identify patients that do not need neoadjuvant immunotherapy is an unmet medical need. The results presented today show that ImPrintTN is a promising such biomarker that, if further validated, can spare many women the short and long-term toxicity of these drugs.”


    Professor Michail Ignatiadis, Institut Jules Bordet in Brussels, Belgium

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  • Study highlights causal associations between gut microbes and hypothyroidism

    Study highlights causal associations between gut microbes and hypothyroidism

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    In a recent study published in Frontiers in Nutrition, researchers explored the association between the microbial community of the gut and hypothyroidism.

    Study: Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study. Image Credit: sdecoret/Shutterstock.comStudy: Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study. Image Credit: sdecoret/Shutterstock.com

    Background

    Hypothyroidism is a hormonal imbalance characterized by diminished thyroid gland activity and insufficient thyroid hormone synthesis, which can lead to heart disease, infertility, and poor brain development in children.

    It has a tremendous economic and social impact on the individuals impacted. Research has revealed that the gut microbiome might indirectly influence thyroid function, with studies indicating a drop in Prevotella in hypothyroid patients and an increase in Phascolarctobacterium, resulting in decreased bacterial diversity and richness.

    Gut microorganisms create short-chain fatty acids (SCFAs), which control thyroid cell expression and keep the intestinal barrier intact. Inadequate iodine consumption is a major cause of hypothyroidism, as the gut flora influences mineral absorption and enzyme activity in thyroid hormone production.

    However, the precise relationship between gut microbes and hypothyroidism is unknown due to historical case-control studies and confounding variables such as age, environment, nutrition, and lifestyle.

    Understanding the association between the intestinal microbiome and hypothyroidism requires extensive research into the underlying reasons and the development of novel therapeutic options.

    About the study

    The present two-sample and bidirectional Mendelian randomization (MR) researchers investigated whether gut microbes causally affect hypothyroidism development.

    The team analyzed summary statistical data from genome-wide association studies (GWAS) provided by the FinnGen [26,342 hypothyroidism cases of hypothyroidism with 59,827 controls; 16,378,441 single-nucleotide polymorphisms (SNPs)] and MiBioGen consortia (n = 18,430).

    They selected instrumental variables (IVs) from the MiBioGen consortium dataset, targeting SNPs related to gut microbial composition and gauging IV heterogeneity using Cochran’s Q statistics.

    The team used several techniques, including the weighted median, MR-Egger, simple model, weighted model, inverse variance weighted (IVW), and MR-PRESSO, to determine whether gut microbes are causally associated with hypothyroidism.

    They also performed reverse MR assessments for microbes that showed causal associations with hypothyroidism development in forward MR evaluation. For sensitivity analysis, they assessed horizontal pleiotropy and performed a leave-one-out analysis.

    The researchers analyzed the 16S ribosomal ribonucleic acid (rRNA) gene variable sites V1-V2, V3-V4, and V4 to assess gut microbial abundances and taxonomic classifications by direct-type taxonomic binning.

    They mapped microbiome quantitative trait loci (mbQTL) to detect genetic variants related to specific loci associated with gut bacteria. The researchers analyzed 119 taxa at the genus level, using 1,231 single-nucleotide polymorphisms as instrumental variables for assessment.

    Results and discussion

    In the IVW analysis, Akkermansia species (odds ratio 0.8), Ruminococcaceae UCG-011 isolate (odds ratio 0.9), Butyrivibrio species (odds ratio 0.9), and Holdemania species (odds ratio 0.9) exhibited protective effects against hypothyroidism.

    In contrast, Anaerostipes species (odds ratio 1.2), Intestinimonas species (odds ratio 1.1), and Ruminiclostridium species (odds ratio 1.2) were detrimental to hypothyroidism.

    Reverse MR estimates indicated no significant effects of hypothyroidism on the gut microbiome. Cochran’s Q statistics showed no significant heterogeneity among instrumental variables. The sensitivity analyses demonstrated the non-significant horizontal pleiotropy, and no SNPs considerably impacted the relationship between gut microbes and hypothyroidism.

    Akkermansia, a gut microbe that strengthens the intestinal lining, boosts the mucus layer and regulates the immune system, is a promising probiotic or live biotherapeutic product therapy. Its intestinal repair and immunomodulatory functions may provide new insights into hypothyroidism prevention and treatment.

    Butyrivibrio bacteria, which break down plant fibers and produce butyric acid, can generate SCFAs and promote intestinal well-being, which may be a significant factor in hypothyroidism.

    Holdemania is associated with several illnesses, including Parkinson’s disease and delirium. Hypothyroidism, characterized by reduced thyroid hormone levels, can lead to neuropsychiatric symptoms.

    Excessive alcohol consumption is associated with elevated levels of Holdemania in the gastrointestinal tract, reducing butyric acid concentration.

    The results indicated that anaerostipes, specialized anaerobes producing acetic and butyric acids, may contribute to hypothyroidism.

    The finding may be due to confounding factors like age, sex, ethnicity, dietary habits, and medications. Hypothyroidism can cause impaired gastrointestinal motility and overgrowth of intestinal flora, potentially altering Anaerostipes abundance during recovery.

    The study showed causal relationships between Akkermansia species and hypothyroidism, with increased Akkermansia inhibiting incidence and progression.

    The researchers identified probiotics like Akkermansia, Holdemania, Ruminococcaceae UCG-011, and Butyrivibrio that protect against hypothyroidism, while Intestinimonas, Anaerostipes, and Ruminiclostridium had contrasting effects. However, additional randomized clinical trials are required to elucidate precise mechanisms researchers can target for personalized therapies enhancing precision care.

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  • Dr. Abidemi Junaid on the Groundbreaking Vagina Chip

    Dr. Abidemi Junaid on the Groundbreaking Vagina Chip

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    In this insightful interview from SLAS 2024, we talk with Dr. Abidemi Junaid, a scientist at the Hansjörg Wyss Institute for Biologically Inspired Engineering at Harvard University. Junaid spearheads the development of the human Vagina Chip, a pioneering tool designed to study host-microbiome interactions in bacterial vaginosis and pave the way for biotherapeutic development and validation.

    With a rich background in biometrics, systems biomedicine, and pharmacology, Junaid’s interdisciplinary approach has culminated in the creation of a model that closely replicates the human vaginal environment. Here, Junaid shares insights into the challenges and triumphs of simulating the female reproductive system on a chip, the implications for women’s health research, and the future of biotherapeutic strategies beyond bacterial vaginosis. 

    Firstly, please introduce yourself and outline your career to date. More specifically, please provide us with an outline of the research you are presenting on a human Vagina Chip to study host-microbiome interactions in bacterial vaginosis for biotherapeutic development and validation here at SLAS.

    My name is Abidemi Junaid, and I am a scientist at Hansjörg Wyss Institute for Biologically Inspired Engineering at Harvard University. I lead the overall effort on the advancement of preclinical testing and modeling of the human reproductive tract using organ-on-chip technology.

    The reproductive health of a woman is strongly associated with a vaginal microbiome mainly composed of Lactobacillus species. In contrast, dysbiosis decreases this population and increases the diversity of anaerobic species, including pathogens, such as Garderenella vaginalis, as seen in bacterial vaginosis (BV).

    BV increases the risk of pre-term birth, miscarriages, and the chances of acquiring sexually transmitted diseases. Various therapeutic strategies are being explored to modulate the composition of the vaginal microbiome; however, there is no human-relevant preclinical model that faithfully reproduces the vaginal epithelial microenvironment for validation of potential therapeutics.

    At SLAS, I will describe our human Vagina Chip that is lined by hormone-sensitive, primary vaginal epithelium interfaced with underlying stromal fibroblasts, which sustains a low physiological oxygen concentration in the epithelial lumen.

    The Vagina Chip allows us to study a human model of the vaginal microbiome and develop new treatments for BV and other conditions that threaten women’s health.

    Firstly, for our readers, please could you tell us more about what organ-on-a-chip technologies are, and more specifically about the benefits of the human vagina chip compared to that of an animal model?

    Organs-on-chips (OoCs) are systems containing engineered or natural miniature tissues grown inside microfluidic chips. To better mimic human physiology, the chips are designed to control cell microenvironments and maintain tissue-specific functions.

    Animal models are of limited use in research to study host-microbiota interactions in the vaginal space because of the major physiological, anatomical, and microbial differences present in these models compared to the human vagina. The Vagina Chip replicates the human vaginal tissue microenvironment including its microbiome in vitro.

    Image Credit: Love Employee/Shutterstock.comImage Credit: Love Employee/Shutterstock.com

    How does the vagina chip technology simulate the unique environment of the female reproductive system, and what are its applications in women’s health research?

    The Vagina Chip supports the growth of healthy microbiome community on-chip, which is accompanied by maintenance of epithelial cell viability, accumulation of D- and L-lactic acid, maintenance of a physiologically relevant low pH, and down regulation of proinflammatory cytokines.

    The Vagina Chip can be used to better understand interactions between the vaginal microbiome and host tissues, as well as to evaluate the safety and efficacy of live biotherapeutics products.

    What is organ-on-a-chip technology?

    Your journey from biometrics to systems biomedicine and pharmacology is quite impressive. Could you share how your diverse academic background has influenced your approach to your current research on the human Vagina Chip?

    My interdisciplinary background has allowed me to apply various elements from engineering, chemistry, and biology in the further development of the human Vagina Chip to recapitulate the human vagina for biotherapeutic studies successfully.

    During my Ph.D., I learned how to use the high-throughput human microvessels-on-chips for screening patient samples and drug discovery. I was able to use these skills for studying microbes isolated from vaginal clinical swab samples in the Vagina Chip to mimic healthy and dysbiotic conditions.

    The Vagina Chip presents a novel approach to studying bacterial vaginosis (BV). Can you describe the initial challenges you faced in replicating the complex vaginal microenvironment on a chip?

    One of the initial challenges was getting the cells that we cultured in the Vagina Chip to differentiate and become stratified just like the human vagina. We were able to solve that by using homemade differentiation media and physiologically relevant dynamic flow of media in the system.

    Learn more about vaginal dysbiosis

    The study indicates that Lactobacillus-rich live biotherapeutic products (LBPs) can alleviate dysbiotic responses without eradicating G. vaginalis. How does this finding challenge or support existing theories about BV treatment?

    In a healthy vaginal microbiota, you a have high population of L. crispatus and very low population of G. vaginalis. Since we still see a high population of G. vaginalis after treatment with the LBP in our Vagina Chip, this indicates that additional treatment is needed to reduce the population of G. vaginalis and finally reach a healthy state.

    The Vagina Chip’s ability to correlate pro-inflammatory responses with untreated BV patient samples is intriguing. How do you envision this capability impacting the future of personalized medicine for reproductive health?

    There is growing recognition that taking care of women’s health is critical for the health of all humans, but the creation of tools to study human female physiology is lagging.

    We’re hopeful that this new preclinical model will drive the development of new treatments for BV as well as new insight into female reproductive health. Furthermore, this model will allow us to study individual patients from different ethnicities and develop therapies that is specific to each of them.

    You mention that further reduction in G. vaginalis numbers might produce a greater therapeutic effect. What strategies or modifications to the Vagina Chip are being considered to investigate this hypothesis?

    One of the strategies that we are trying is to treat the dysbiotic Vagina Chip with hydroxy-metronidazole and the LBP. Hydroxy-Metronidazole is an antibiotic that is commonly used to kill G.vaginalis in BV patients.

    However, treating with hydroxy-metronidazole alone can lead to recurrent BV. We hope that with the combination of hydroxy-metronidazole and LBP there is a lower chance of recurrence.

    Given the complexity of the vaginal microbiome and its impact on women’s health, how do you see your work influencing the development and validation of other biotherapeutic strategies beyond BV?

    Various therapeutic strategies are being explored to modulate the composition of the vaginal microbiome; however, there is no human model that faithfully reproduces the vaginal epithelial microenvironment for preclinical validation of potential therapeutics or testing hypotheses about vaginal epithelium-microbiome interactions.

    The Vagina Chip is a preclinical model of the human vaginal mucosa that can be used to understand better interactions between the vaginal microbiome and host tissues, as well as to evaluate the safety and efficacy of live biotherapeutics products. This will help us to predict how successful a biotherapeutic strategy would be in clinical trials.

    Finally, as someone at the forefront of organ-on-chip technology, what advice would you give to young scientists interested in entering this field, and what do you think are the most exciting possibilities on the horizon?

    The field of organs-on-chips is very interdisciplinary. So, I advise young scientists to explore research in various scientific areas and collaborate with people with different scientific backgrounds.

    I look forward to the time when we can fully use organ-on-a-chip technology to replace animal models. Moreover, this technology will be an important tool to decide whether a therapy should go to clinical trial.

    Where can readers find more information?

    About Abidemi Junaid, Ph.D. 

    Abidemi Junaid received his B.S. in Biometrics from Zuyd University of Applied Sciences, M.S. in Biomolecular Sciences from VU University, and Ph.D. in Systems Biomedicine and Pharmacology from Leiden University. His Ph.D. work was centered around the development of high-throughput human microvessels-on-chips for studying microvascular destabilization, infectious diseases, and metabolomics.

    He also worked on integrating mechanical fluid flow and biological and environmental sensing in organs-on-chips. Altogether, this enabled him to identify the impact of patient plasma on microvessels for clinical studies. As a Scientist at the Wyss Institute, he is working on advancing preclinical testing and modeling of the human immune system using organ-on-chip technology.

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  • The efficacy of the Mediterranean diet on health outcomes in adults with cancer

    The efficacy of the Mediterranean diet on health outcomes in adults with cancer

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    Cancer treatment is often associated with undue weight gain, mostly due to fat deposition. The Mediterranean diet (MED diet) may help support such patients during this period. A new study published in the European Journal of Clinical Nutrition explores the safety and benefits of this diet in adults with cancer, in addition to its feasibility in this population.

    Study: Mediterranean-style dietary interventions in adults with cancer: a systematic review of the methodological approaches, feasibility, and preliminary efficacy. Image Credit: Marian Weyo/Shutterstock.com
    Study: Mediterranean-style dietary interventions in adults with cancer: a systematic review of the methodological approaches, feasibility, and preliminary efficacy. Image Credit: Marian Weyo/Shutterstock.com

    Background

    Almost 20 million people today have received a cancer diagnosis, making it the leading cause of illness and death globally. The treatment of cancer is also associated with multiple adverse effects that cause rapid aging, trigger chronic metabolic aberrations, and reduce the quality of life.

    These side effects include early menopause, cognitive impairment, and cardiomyopathy, with persistent fatigue and weight loss. Such long-term ill effects could be mitigated by nutrition and exercise. Yet, there is little evidence to support the right nutritional pattern for such issues arising during or after cancer treatment.

    About the Mediterranean diet

    The MED diet has been long recognized as among the healthiest eating patterns. Compliance with this diet has been associated with reduced risk of many chronic illnesses, including type 2 diabetes and cardiovascular harm.

    This dietary pattern is characterized by a high consumption of fish, vegetables, legumes, nuts, fruits, and extra virgin olive oil, a moderate intake of dairy and red wine, with little added sugar, processed foods, and red meat. The antioxidant and anti-inflammatory profile of this diet have been thought to mediate its beneficial effects on cardiac and metabolic health.

    Previous evidence indicates that those on a MED diet have 22% and 13% lower odds of dying from prostate and breast cancer, respectively. This is very significant since the hormone treatment typically used in these cancers adversely affects the metabolic and body composition profile, increasing the risk of cardiometabolic disease.

    This group of patients has been shown to benefit from nutritional manipulation with exercise by reducing body fat and body weight. Yet, there is little systematic evidence to support the recommendation of a MED diet for adults with cancer. This prompted the current study.

    About the study

    A systematic review was undertaken, including 15 articles covering the MED diet intervention among this group of patients. Of these, ten included breast cancer patients, all women, and one mostly female breast cancer patients. The remaining included prostate cancer, acute myeloid leukemia, and lung cancer.

    In five of the studies, patients were being actively treated, while five were post-treatment studies. Three included patients who either had been or were being treated, with one starting within five years from the diagnosis.

    In most studies, the aim was to lose weight, but a few were aimed at lessening fatigue, reducing inflammatory mediator levels, enhancing the diet, or maintaining a stable weight. Energy restrictions at varying levels were applied for those who were obese or overweight. Others used strategies such as reduced portion size or consuming more satiating foods.

    What changes were observed?

    Most participants adhered closely to the MED diet compared to controls, at 64% to 96% completion rates. In six studies, the body weight of the MED diet participants decreased compared to that of the control group. In seven studies, the body mass index (BMI) decreased in the intervention group vs controls.

    A similar favorable change was reported in the body fat mass, though three also reported loss of lean mass.

    Multiple metabolic biomarkers and inflammatory markers were favorably affected, including decreased glucose markers, reduced cardiovascular markers including triglycerides and total cholesterol, increased high-density lipoprotein (HDL, ‘good cholesterol’), higher albumin levels, and reduced interleukin-8 (IL-8).

    The intervention was also associated with a higher quality of life and reduction in fatigue, as well as better emotional, physical, and cognitive health.

    What are the conclusions?

    The studies included in this review had widely varying study designs and MED diet content, making it difficult to provide a definitive recommendation to achieve these favorable outcomes. However, the safety and feasibility, as well as acceptability, of the MED diet as a nutritional intervention is established.

    The positive role of nutritionists in this type of intervention, with accompanying advice on nutritional value, cooking demos, and recipes tailored to individual clients, appears from the significantly higher adherence seen in such studies.

    Body weight reduction is particularly well supported by this diet with energy restriction, with overweight or obese subjects on hormone therapy or post-treatment for prostate or breast cancer losing up to 4 kg. Currently, evidence of the benefit of the MED diet is available only for women who have completed breast cancer treatment.

    Further studies need to be done to confirm that the MED diet will help prevent and manage chronic disease in this population of cancer survivors who are at high risk for such conditions. Approaches that protect or increase muscle mass but are compatible with this dietary pattern need to be explored.

    Confounding factors that may have mediated the improvement in cardiometabolic status and quality of life include frequent interactions with healthcare providers and other dietary components like green tea that have anti-inflammatory and antioxidant activity themselves. Careful documentation of the diet, adherence, and outcomes is necessary to rule out the role of such factors in preventing or managing chronic disease in future studies.

    Future longer term RCTs should focus on reducing the risk of, or managing, cardiovascular or metabolic disease after cancer treatment to improve the potential clinical implications of the MED-diet.”

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