A Simple Blood Test Warns of Possible Cardiometabolic Complications for Children With Obesity
Scientists from the University of Copenhagen have detected lipid biomarkers in children and teenagers with obesity that indicate an increased risk of developing type 2 diabetes, liver and heart disease as adults. A one-year lifestyle intervention lowered the levels of these lipid biomarkers, which demonstrates the importance of early intervention for children with obesity.
KEY FINDINGS: Scientists from the University of Copenhagen have detected lipid biomarkers in children and teenagers with obesity that indicate an increased risk of developing type 2 diabetes, liver and heart disease as adults. A one-year lifestyle intervention lowered the levels of these lipid biomarkers, which demonstrates the importance of early intervention for children with obesity.
BACKGROUND: The number of children and teens with obesity is increasing worldwide, with over 250 million expected to be affected by 2030. It is a major public health crisis, as children with obesity risk developing insulin resistance, fatty liver, and high blood pressure, which may lead to diseases such as cardiovascular disease, type 2 diabetes and liver disease, later in life.
DETAILS: Scientists think these diseases can be triggered by changes in the body's lipids -- a wide range of fats and oils in the body including triglycerides and cholesterol that serve many purposes including energy storage and cellular signalling. But it is still not well understood how lipid species change in children with obesity, and how they are linked to early cardiometabolic complications.
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Now, scientists at the University of Copenhagen have discovered that lipid species linked to cardiometabolic disease in adults are strongly associated with cardiometabolic risk factors in children and teenagers with obesity. The findings could pave the way for tests that serve as an early warning system for cardiometabolic disease.
"Our study shows that the impact of cardiometabolic associated lipid species emerges early in life in children with obesity, particularly affecting liver function and glucose metabolism. These risk lipid species could potentially be explored further as biomarkers for diagnosing or predicting cardiometabolic risk in children at high risk, offering new insights for early detection and intervention," says Postdoc Yun Huang from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, and co-first author of the study in Nature Medicine.
Early intervention reverses cardiometabolic disease risk
The scientists made their discoveries by drawing on the HOLBAEK Study biobank of more than 4,000 children with and without obesity. at the Children's Obesity Clinic at Holbaek Hospital. Together with scientists at Steno Diabetes Center Copenhagen, they harnessed powerful mass spectrometry technology to map hundreds of individual lipid species, each with distinct structures and functions, providing a detailed picture of lipid metabolism. By analyzing the differences in the lipid profiles of 958 children with overweight or obesity and 373 who had normal weight, they gained deep insight into obesity altered lipid profiles and their link to cardiometabolic risk, and the ability to detect excessive fat in the liver.
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Source: University of Copenhagen - The Faculty of Health and Medical Sciences (2024). A Simple Blood Test Warns of Possible Cardiometabolic Complications for Children With Obesity. ScienceDaily. 2024; Published: September 20, 2024. DOI: 10.1038/s41591-024-03279-x.
IL-17 Inhibitors Not Associated With Increased IBD Risk in Hidradenitis Suppurativa
A systematic review and meta-analysis of 24 studies found that inflammatory bowel disease events were rare among patients with hidradenitis suppurativa receiving IL-17 inhibitors. In randomized trials, new-onset IBD occurred in 0.23% of patients receiving IL-17 inhibitors versus 0% with placebo, with no significant difference between groups. The findings are reassuring but support continued monitoring because event numbers were low and reporting was inconsistent.
KEY FINDINGS: IBD events were uncommon among patients with HS receiving IL-17 inhibitors, and randomized trial data did not demonstrate a significant increase in IBD risk compared with placebo. The higher incidence observed in nonrandomized studies may reflect differences in patient populations, follow-up, or other sources of bias and should not be interpreted as evidence of causation. Because event numbers were low and reporting of IBD outcomes was inconsistent, continued monitoring remains important, particularly in patients with existing or suspected IBD. The findings support the use of IL-17 inhibitors in HS while emphasizing the need for further prospective data on gastrointestinal outcomes.
BACKGROUND: Interleukin-17 (IL-17) inhibitors are increasingly used to treat moderate to severe hidradenitis suppurativa (HS), but concern remains about their potential relationship with inflammatory bowel disease (IBD), particularly Crohn disease and ulcerative colitis. Because patients with HS already have an elevated background risk of IBD, it can be difficult to determine whether IBD events occurring during IL-17 inhibitor therapy are treatment-related or reflect the underlying disease. This systematic review and meta-analysis evaluated the incidence of IBD among patients with HS receiving IL-17 inhibitors and compared event rates with placebo in randomized clinical trials.
DETAILS: The investigators searched PubMed, Embase, and the Cochrane CENTRAL database from inception through November 2025. Twenty-four studies met the inclusion criteria, comprising 10 randomized clinical trials, 11 nonrandomized studies, and 3 case reports. Overall, the analysis included 3,015 patients with HS treated with an IL-17 inhibitor. Outcomes included new-onset IBD, worsening of preexisting IBD, IBD subtype, clinical features, and time to IBD onset.
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Across the 10 randomized clinical trials, new-onset IBD occurred in 6 of 2,572 patients receiving IL-17 inhibitors (0.23%) compared with 0 of 1,066 patients receiving placebo through week 16. The pooled risk difference was 0.002 (95% CI, -0.003 to 0.007), indicating no statistically significant difference between treatment and placebo groups.
In the nonrandomized studies, 7 new-onset IBD events were reported among 469 patients, corresponding to a crude incidence of 1.49%. The pooled incidence was 3.90% (95% CI, 2.30%-6.50%). Across randomized trials, long-term extension studies, and nonrandomized studies, 17 new-onset IBD cases and 4 IBD flares were reported.
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Source: Cutrona, M., Jolkovsky, E. L., Romanelli, S., et al. Inflammatory Bowel Disease and Interleukin-17 Inhibitors in Hidradenitis Suppurativa: A Systematic Review and Meta-Analysis. JAMA Dermatology. 2026; Published: September 9, 2026. DOI: 10.1001/jamadermatol.2026.3373.
Formononetin May Protect Against Anthracycline Cardiotoxicity Through Cardiac Metabolic Improvement
A preclinical study identified ERRa as an early metabolic regulator of anthracycline-induced cardiotoxicity, with its reduction occurring before overt cardiac dysfunction. Formononetin, an ERRa activator, improved cardiac metabolism and function in mouse and pig models while also enhancing doxorubicin's anticancer activity in breast cancer organoids. The findings suggest a potential dual-action strategy for protecting the heart during anthracycline therapy, but clinical studies are still needed.
KEY FINDINGS: The findings identify ERRα downregulation as an early and potentially causal component of anthracycline-induced cardiac injury. Formononetin improved cardiac energy metabolism and function in experimental models while retaining, and potentially enhancing, doxorubicin's anticancer activity in breast cancer organoids. The study therefore suggests that pharmacologic activation of ERRα could represent a future strategy for simultaneously addressing anthracycline cardiotoxicity and cancer treatment. However, the evidence remains preclinical, and clinical studies are required to determine whether these findings translate into cardioprotection in patients receiving anthracycline chemotherapy.
BACKGROUND: Anthracyclines such as doxorubicin are effective anticancer agents, but their use can be limited by anthracycline-induced cardiotoxicity (AIC). Early metabolic disturbances in cardiac muscle may contribute to the development of cardiac dysfunction. This study investigated the role of estrogen-related receptor α (ERRα), a regulator of cardiac energy metabolism, in AIC and evaluated whether pharmacologic activation of ERRα with formononetin could provide cardiac protection while maintaining anticancer activity.
DETAILS: The investigators used a porcine model of anthracycline cardiotoxicity to examine changes in ERRα over time and cardiomyocyte-specific gain- and loss-of-function mouse models to assess its functional role. Mechanistic experiments, including ChIP-qPCR, reporter assays, and microscale thermophoresis, were used to investigate how formononetin interacts with the ERRα pathway. Cardiac tissue from patients who had received chemotherapy was also examined, while human breast cancer patient-derived organoids were used to evaluate potential effects on tumor activity. ERRα expression was reduced in hearts from the porcine AIC model and in cardiac tissue from patients treated with chemotherapy. In pigs, the reduction occurred at the 6-week subclinical stage, before overt cardiac dysfunction developed. Increasing ERRα expression specifically in cardiomyocytes enhanced mitochondrial metabolic programs and fatty-acid oxidation and preserved systolic function after doxorubicin exposure, whereas ERRα reduction worsened metabolic dysfunction and cardiac impairment.
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Drug screening identified formononetin as a selective ERRα activator. In mouse and pig models, formononetin increased ERRα activity, improved cardiac mitochondrial metabolism, and reduced anthracycline-associated cardiac injury. Mechanistic experiments indicated that formononetin interacts with the ERRα/PGC-1α complex and promotes its stability, supporting activation of downstream metabolic pathways.
Importantly, formononetin also demonstrated anticancer activity in human breast cancer patient-derived organoids. Treatment with formononetin alone reduced organoid viability and proliferation, while combining formononetin with doxorubicin produced greater antitumor effects.
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Source: Wang, X., Ling, G., Wei, Y., et al. Natural ERRα Activator Formononetin Ameliorates Anthracycline Cardiotoxicity via Metabolic Improvement. Circulation Research. 2026; 139(7): e329042. Published: September 11, 2026. DOI: 10.1161/CIRCRESAHA.126.329042.
Accounting for Long-Term Consequences of Tuberculosis Strengthens the Case for Preventive Screening in New Immigrants
A Canadian modeling study found that including long-term illness and mortality after tuberculosis more than doubled the estimated health benefits of postarrival TB screening and preventive treatment among new immigrants. Incorporating these consequences reduced the projected cost from $235,088 to $100,742 CAD per QALY gained. The findings highlight the importance of considering the long-term burden of TB when evaluating prevention strategies.
KEY FINDINGS: The analysis suggests that excluding long-term illness, mortality, and healthcare costs after TB treatment can substantially underestimate the health value of TB prevention. In the modeled Canadian immigrant population, incorporating these consequences more than doubled the estimated QALY benefit of postarrival TB infection screening and preventive treatment and reduced the estimated cost per QALY by more than half. However, the findings depend on assumptions about the long-term effects of TB, and the investigators noted that some underlying associations may include residual confounding and that post-TB illness estimates are less certain.
BACKGROUND: Tuberculosis prevention strategies are commonly evaluated by considering acute TB disease and death, while longer-term consequences after successful treatment may be overlooked. These consequences can include persistent illness, increased mortality, and additional healthcare utilization. This study assessed how incorporating these longer-term effects would change estimates of the health benefits and cost-effectiveness of postarrival TB infection screening and preventive treatment among people newly immigrating to Canada.
DETAILS: The investigators developed a Markov microsimulation model representing a hypothetical cohort of 400,000 people immigrating permanently to Canada in 2025. The analysis compared the existing postarrival TB infection screening level of 0.5% with a modeled screening strategy reaching 68% of eligible new immigrants. The intervention targeted new permanent residents from countries with annual TB incidence >50/100,000 persons; individuals testing positive for TB infection were assumed to receive 4 months of daily rifampin as preventive treatment. Outcomes were projected over 25 years and included TB episodes, TB deaths, quality-adjusted life-years (QALYs), and TB-related healthcare costs. The model incorporated three post-TB consequences: increased mortality after TB treatment, persistent illness or disability, and excess healthcare costs. A total of 2,000 probabilistic simulations were performed to account for uncertainty in model parameters.
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When only acute TB consequences were considered under the current screening scenario, the model projected 927 (95% UR 764-1,123) TB cases, 30 (95% UR 24-36) TB deaths, and 312 (95% UR 241-386) QALYs lost over 25 years. Adding post-TB death increased estimated QALYs lost by 1.6-fold, while including post-TB illness increased them by 1.5-fold. When all three long-term consequences were incorporated, TB was projected to account for 657 (95% UR 479-876) QALYs lost, a 2.1-fold increase compared with considering acute consequences alone.
The expanded screening and preventive-treatment strategy produced 2.4-fold greater estimated QALY gains (95% UR 1.6-4.4-fold) and 2.2-fold more TB deaths averted (95% UR 1.6-3.0-fold) when all post-TB consequences were included. The estimated incremental cost-effectiveness ratio decreased from $235,088 to $100,742 CAD per QALY gained. In the model incorporating all post-TB consequences, 53% of simulations fell below a willingness-to-pay threshold of $100,000 per QALY, compared with 8% when only acute TB consequences were considered.
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Source: Ainiwaer, A., Uppal, A., Schwartzman, K., et al. Posttuberculosis Consequences on Tuberculosis Prevention Effectiveness and Cost-effectiveness among New Immigrants, Canada. Emerging Infectious Diseases. 2026; 32(9): 1421-1429. Published: September, 2026. DOI: 10.3201/eid3209.260473.
A Pragmatic SMART Study of Medication and CBT Sequencing in Pediatric Anxiety Disorders
Fluoxetine and exposure-based CBT showed broadly comparable improvement over 24 weeks. Among those remaining symptomatic, CBT followed by combination therapy showed the strongest overall improvement pattern.
KEY FINDINGS: In this pragmatic study of clinically complex and demographically diverse youths, fluoxetine and exposure-based CBT produced broadly comparable improvement in anxiety symptoms over 24 weeks. For patients who remained symptomatic after 12 weeks, adding the alternate treatment generally showed a tendency toward greater improvement than optimizing monotherapy, although the overall differences were small and did not establish combination therapy as superior on the primary outcome. The CBT→combination sequence produced the strongest overall pattern of improvement across anxiety severity and functional impairment measures. Treatment response also varied across racial and ethnic groups, with Non-Hispanic White youths showing greater benefit from fluoxetine-based treatment sequences on some parent- and youth-reported secondary outcomes, whereas racial and ethnic minority youths showed greater benefit from transition to combination therapy on selected measures.
BACKGROUND: Choosing between medication and cognitive-behavioral therapy (CBT) as the initial treatment for pediatric anxiety disorders, and determining how to proceed when symptoms persist, remains clinically challenging. This pragmatic randomized trial evaluated whether initiating treatment with fluoxetine or exposure-based CBT produced better outcomes and whether adding the alternate treatment was more effective than continuing the initial therapy when remission was not achieved after 12 weeks.
DETAILS: This 24-week, single-blind sequential multiple assignment randomized trial included 316 youths aged 8-17 years with DSM-5 anxiety disorders, significant anxiety symptoms, and functional impairment. Participants were initially randomized to 12 weeks of fluoxetine or weekly exposure-based "Coping Cat" CBT. Fluoxetine dosing ranged from 10 to 80 mg/day. Youths who did not achieve remission after 12 weeks were subsequently randomized to either optimization of their initial treatment or optimization plus addition of the other modality. Outcomes included youth- and parent-reported 41-item Screen for Child Anxiety Related Emotional Disorders (SCARED) scores and Childhood Anxiety Impact Scale (CAIS) scores. The study was conducted in primary care and community mental health settings and included youths with substantial sociodemographic disadvantage and co-occurring mental health conditions.
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Youth-reported SCARED scores decreased by 31.7% over 24 weeks, from 42.9 at baseline to 29.31 at study endpoint. Improvement did not differ significantly between initial fluoxetine and CBT, although CBT showed a nonsignificant numerical advantage, with a 24-week difference in mean group change of 1.45 (95% CI=-2.25, 5.16). Among participants who did not remit by week 12, combination treatment was not significantly superior to continued optimized monotherapy for youth-reported anxiety at week 24 (group difference in mean change from baseline: -2.74, 95% CI=-6.53, 1.05).
Exploratory analyses of treatment sequences found that CBT followed by combination therapy produced the greatest overall improvement across the primary and secondary outcomes, although youth-reported SCARED scores did not differ significantly between individual sequences at week 24. Parent-reported SCARED scores declined by 37.8%, from 38.9 to 24.2, over 24 weeks. Parent ratings showed faster improvement with initial fluoxetine at weeks 6 and 12, while youth-reported CAIS scores favored initial CBT by week 24. Reduced appetite was more frequent with medication during both treatment stages, occurring in 43.7% versus 32.3% during stage 1 (p<0.05) and in 17.3% with med→med, 3.6% with CBT→CBT, and 12.1% with combination treatment during stage 2 (p=0.013). Serious or unexpected adverse events were rare.
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Source: Peterson, B. S., West, A. E., Weersing, V. R., et al. A Pragmatic SMART Study of Medication and CBT Sequencing in Pediatric Anxiety Disorders: A Randomized Clinical Trial. American Journal of Psychiatry. 2026; 183(9): 668-681. Published: September, 2026. DOI: 10.1176/appi.ajp.20251037.
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