Uveitis Risk Higher in Children with Early-Onset Atopic Dermatitis, Study Finds

Taiwan: A new large-scale cohort study published in JAMA Ophthalmology has revealed that children with early-onset atopic dermatitis (AD) may be at a significantly higher risk of developing pediatric uveitis, an inflammatory eye condition that can lead to vision complications if left untreated. Traditionally linked to skin-related issues, AD is now being associated with ocular inflammation, adding a new dimension to its clinical understanding.

The study found that children with early-onset AD had nearly twice the risk of developing uveitis (hazard ratio [HR] 1.92) compared to those without AD, independent of autoimmune conditions or dupilumab use. The risk was even greater in severe cases, with a more than threefold increase in likelihood (HR 3.64). These findings highlight the need for regular ophthalmologic monitoring in children with AD to enable early detection and management of uveitis.

Uveitis, which affects the uveal tract of the eye, can present with symptoms such as eye pain, redness, blurred vision, and light sensitivity. In some cases, it may be asymptomatic, particularly in children, making early detection and routine screening critical. Left untreated, chronic uveitis can lead to complications such as cataracts, glaucoma, or even permanent vision loss.

Against the above background, Yung-Yu Chu, Department of Ophthalmology, Chi Mei Medical Center, Tainan, Taiwan, and colleagues aimed to assess the likelihood of pediatric uveitis in children with early-onset atopic dermatitis relative to a matched control group.

For this purpose, the researchers conducted a cohort study using electronic health records from the TriNetX network, analyzing data from January 1, 2004, to December 14, 2024. Children with early-onset AD were compared to matched controls without AD, excluding those with prior uveitis. Propensity score matching was used to balance baseline characteristics. Using ICD-10 codes to identify AD cases, the primary outcome measured was the hazard ratio for developing pediatric uveitis. Cox proportional hazards models were employed to assess the risk, with all analyses completed on December 14, 2024.

The study led to the following findings:

  • After matching, 114,889 patients were included in each cohort, with a mean follow-up of 6.0 years in the AD group and 6.6 years in the control group.
  • The mean age at inclusion was approximately 0.5 years for the AD cohort and 0.6 years for the control cohort; 56.4% in the AD group and 56.9% in the control group were male.
  • The AD cohort showed a higher risk of developing pediatric uveitis compared to controls (94 [0.08%] vs 58 [0.05%]; HR, 1.92).
  • Sensitivity analysis excluding dupilumab users showed an elevated risk (HR, 1.77).
  • A similar increased risk was seen in patients without autoimmune conditions (HR, 1.52).
  • Children with severe AD had a significantly higher risk of developing pediatric uveitis compared to those with nonsevere AD (HR, 3.64).

The cohort study found that children with early-onset atopic dermatitis face a higher risk of developing pediatric uveitis, regardless of autoimmune conditions or dupilumab use.

“The findings highlight the importance of considering regular ophthalmologic monitoring in this population to enable early detection and timely management of uveitis,” the authors concluded.

Reference:

Chu Y, Sung C, Lin Y, et al. Risk of Developing Pediatric Uveitis Among Patients With Early-Onset Atopic Dermatitis. JAMA Ophthalmol. Published online April 03, 2025. doi:10.1001/jamaophthalmol.2025.0366

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GLP-1RA significantly reduces dementia and cognitive impairment in diabetic patients: JAMA

A new study published in the Journal of American Medical Association showed that glucagon-like peptide-1 receptor agonists (GLP-1RAs)-based glucose-lowering treatment was linked to reduction in dementia or cognitive impairment.

A risk factor for dementia, diabetes is thought to be responsible for around 5% of the population-attributable percentage of dementia cases. Also, diabetes increases the incidence of ischemic stroke, which may function as a mediator in the relationship between diabetes and vascular dementia.

The effectiveness of glucose-lowering medication in preventing incident dementia is unknown, despite the knowledge that diabetes is a risk factor for dementia. Thus, to ascertain whether cardioprotective glucose-lowering therapy (sodium-glucose cotransporter-2 inhibitors (SGLT2is), GLP-1RAs, metformin, and pioglitazone) was linked to a lower risk of dementia or cognitive impairment, as well as among the primary dementia subtypes, this study was carried out.

Studies published between the database’s creation and July 11, 2024, were found by searching the PubMed and Embase databases. This study shortlisted randomized clinical trials that compared cardioprotective glucose-lowering treatment with controls who reported dementia or a change in cognitive scores.

Based on data from phase III randomized clinical studies, medication classes that are suggested by recommendations for decreasing cardiovascular events were referred to as cardioprotective glucose-lowering treatments. Independent evaluations of the inclusion criteria were conducted, and disagreements were settled by consensus. 

12 trials evaluating SGLT2is, 10 trials evaluating GLP-1RAs, and 1 trial evaluating pioglitazone (no trials of metformin were found) were among the 26 randomized clinical trials (N = 1,64,531 participants) that reported the incidence of dementia or cognitive impairment. The mean (SD) age of the trial participants was 64.4 (3.5) years, and 57,470 (34.9%) of them were female.

Overall, there was no significant correlation seen between cardioprotective glucose-lowering medication and a decrease in dementia or cognitive impairment. GLP-1RAs, but not SGLT2is, were linked to a statistically significant decrease in dementia all medication classes. Overall, this meta-analysis revealed that glucose lowering with GLP-1RAs reduced all-cause dementia, even if cardioprotective glucose-lowering treatments were not linked to an overall decrease in the same.

Source:

Seminer, A., Mulihano, A., O’Brien, C., Krewer, F., Costello, M., Judge, C., O’Donnell, M., & Reddin, C. (2025). Cardioprotective glucose-lowering agents and dementia risk: A systematic review and meta-analysis: A systematic review and meta-analysis. JAMA Neurology. https://doi.org/10.1001/jamaneurol.2025.0360

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Individualized Antibiotic Duration in Febrile UTI tied to recurrence risk among children: Study

According to a new research, in children with febrile urinary tract infections, an individualized antibiotic regimen—stopping 3 days after clinical improvement—increased the risk of recurrence compared to the standard 10-day course. However, it reduced overall antibiotic use and associated side effects. With further research, this approach may be suitable for select pediatric cases.

The optimal antibiotic duration for febrile urinary tract infection (UTI) in children remains uncertain. We aimed to assess whether individualised treatment was non-inferior to standard 10-day treatment in terms of recurrent UTI and superior in reducing overall antibiotic exposure. INDI-UTI was a pragmatic, open-label, multicentre, randomised, controlled, non-inferiority trial conducted at eight Danish hospitals. Children aged 3 months to 12 years who were febrile (≥38°C), within 24 h of treatment start, and with significant growth of uropathogenic bacteria were randomly assigned (1:1) using a web-based module with randomly permuted blocks to individualised or standard 10-day treatment. Main exclusion criteria included known urinary tract abnormalities, complicated medical history, bacteraemia, and elevated serum creatinine. The individualised group stopped treatment 3 days after adequate clinical improvement (ie, absence of fever, flank pain, and dysuria), with a minimum treatment duration of 4 days. The primary outcomes were recurrent UTI within 28 days after treatment cessation (non-inferiority margin 7·5 percentage points) and total antibiotic days within 28 days of treatment initiation (superiority assessment). No sample size calculation was performed for the assessment of total antibiotic days. Safety was assessed in all included patients. Main analyses were done in the intention-to-treat population. Between March 28, 2022, and March 3, 2024, 694 patients were assessed for eligibility and 408 patients were randomly assigned to individualised (n=205; median antibiotic duration 5·3 days [IQR 4·8 to 6·5]) or standard 10-day treatment (n=203; 10·0 days [10·0 to 10·0]). Median age was 1·5 years (IQR 0·7 to 5·4), and there were 326 (80%) female and 82 (20%) male participants. Recurrent UTI within 28 days occurred in 23 (11%) of 205 patients in the individualised group and 12 (6%) of 203 patients in the standard 10-day group (difference 5·3 percentage points, one-sided 97·5% CI –∞ to 11·1, pnon_inferiority=0·24). Total antibiotic days within 28 days were 6·0 (IQR 5·3 to 7·5) in the individualised group and 10·0 (10·0 to 10·0) in the standard 10-day group (median difference –4·0 days [97·5% CI –4·5 to –3·7], p<0·0001). The incidence rate of antibiotic-related adverse events within 28 days was 6·8 per 100 patient-days in the individualised group and 11·1 per 100 patient-days in the standard 10-day group (rate ratio 0·61 [95% CI 0·47 to 0·80], p=0·0003). Serious adverse events occurred in 17 (8%) of 205 patients in the individualised group and 15 (7%) of 203 patients in the standard 10-day group (difference 0·9 percentage points [95% CI –4·6 to 6·5], p=0·79). Children with febrile UTI assigned to individualised treatment duration had an increased risk of recurrent UTI (by 5·3 percentage points) but reduced antibiotic use and fewer adverse event days within 28 days compared with those assigned to standard 10-day treatment. These findings highlight the potential of individualised treatment strategies to reduce antibiotic exposure and associated harms in most children with febrile UTI, supporting antimicrobial stewardship goals. Further research is needed to identify those requiring 10-day treatment to avoid compromising care for most children with febrile UTI who respond well to shorter durations. Copenhagen University Hospital Rigshospitalet Research Fund, Innovation Fund Denmark, and Greater Copenhagen Health Science Partners.

Reference:

Efficacy and safety of individualised versus standard 10-day antibiotic treatment in children with febrile urinary tract infection (INDI-UTI): a pragmatic, open-label, multicentre, randomised, controlled, non-inferiority trial in Denmark

Sethi, Naqash Javaid et al. The Lancet Infectious Diseases, Volume 0, Issue 0

Keywords:

Individualized, Antibiotic, Duration, Febrile, UTI, recurrence, risk, among, children, Study, Sethi, Naqash Javaid

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Cannabidiol therapy could reduce symptoms in autistic children and teenagers: Study

New research presented at the 2025 European Congress of Psychiatry reveals that the use of cannabidiol (CBD) cannabis extract can lead to meaningful benefits and improve the behaviour of children and adolescents with autism spectrum disorder (ASD). ASD affects approximately 1 in 100 children around the world and symptoms can include difficulty interpreting language, difficulty expressing emotions, and repetitive behaviour and routines.

The meta-analysis included randomised, placebo-controlled trials on the efficacy or safety of CBD cannabis extracts in children and adolescents with ASD. Three studies were used in total with 276 participants with a mean age of 10.5, ranging in age from 5 to 21. The dosage of CBD cannabis extract started at 1 mg/kg per day and was titrated up to 10 mg/kg.

Key findings from the study include:

• CBD cannabis extract use shows moderate improvements in social responsiveness and small yet notable reductions in disruptive behaviours.

• CBD cannabis extract significantly enhanced social responsiveness and reduced disruptive behaviour.

• The use of CBD cannabis extract has a favourable safety profile as it did not increase adverse events compared to placebo

• There were no significant differences between adverse events in CBD cannabis extract versus placebo

Lara Cappelletti Beneti Branco, Lead Investigator, São Camilo University Center, University of São Paulo, said: “The global population prevalence of ASD diagnosis amongst children and adolescents is growing, but many treatment pathways are not effective. It is promising to see the effect of CBD cannabis extract on the study participants. However, there still needs to be considerable focus on further research with larger trials to clarify its efficacy and safety in managing ASD.”

Professor Geert Dom, EPA President, said: “ASD can be extremely frustrating for all involved; parents of children and adolescents with the disorder, the treating clinicians and of course the children and adolescents themselves. A large part of this frustration is down to finding a viable treatment option that works to reduce symptoms. It is with delight that we see the results of this meta-analysis and we hope to see further research into this so we can move towards a solution to the unmet need within this community”.  

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New evidence links microplastics with chronic noncommunicable diseases

Tiny fragments of plastic have become ubiquitous in our environment and our bodies. Higher exposure to these microplastics, which can be inadvertently consumed or inhaled, is associated with a heightened prevalence of chronic noncommunicable diseases, according to new research being presented at the American College of Cardiology’s Annual Scientific Session (ACC.25).

Researchers said the new findings add to a small but growing body of evidence that microplastic pollution represents an emerging health threat. In terms of its relationship with stroke risk, for example, microplastics concentration was comparable to factors such as minority race and lack of health insurance, according to the results.

“This study provides initial evidence that microplastics exposure has an impact on cardiovascular health, especially chronic, noncommunicable conditions like high blood pressure, diabetes and stroke,” said Sai Rahul Ponnana, MA, a research data scientist at Case Western Reserve School of Medicine in Ohio and the study’s lead author. “When we included 154 different socioeconomic and environmental features in our analysis, we didn’t expect microplastics to rank in the top 10 for predicting chronic noncommunicable disease prevalence.”

Microplastics-defined as fragments of plastic between 1 nanometer and 5 millimeters across-are released as larger pieces of plastic break down. They come from many different sources, such as food and beverage packaging, consumer products and building materials. People can be exposed to microplastics in the water they drink, the food they eat and the air they breathe.

The study examines associations between the concentration of microplastics in bodies of water and the prevalence of various health conditions in communities along the East, West and Gulf Coasts, as well as some lakeshores, in the United States between 2015-2019. While inland areas also contain microplastics pollution, researchers focused on lakes and coastlines because microplastics concentrations are better documented in these areas. They used a dataset covering 555 census tracts from the National Centers for Environmental Information that classified microplastics concentration in seafloor sediments as low (zero to 200 particles per square meter) to very high (over 40,000 particles per square meter).

The researchers assessed rates of high blood pressure, diabetes, stroke and cancer in the same census tracts in 2019 using data from the U.S. Centers for Disease Control and Prevention. They also used a machine learning model to predict the prevalence of these conditions based on patterns in the data and to compare the associations observed with microplastics concentration to linkages with 154 other social and environmental factors such as median household income, employment rate and particulate matter air pollution in the same areas.

The results revealed that microplastics concentration was positively correlated with high blood pressure, diabetes and stroke, while cancer was not consistently linked with microplastics pollution. The results also suggested a dose relationship, in which higher concentrations of microplastic pollution are associated with a higher prevalence of disease. However, researchers said that evidence of an association does not necessarily mean that microplastics are causing these health problems. More studies are required to determine whether there is a causal relationship or if this pollution is occurring alongside another factor that leads to health issues, they said.

Further research is also needed to determine the amount of exposure or the length of time it might take for microplastics exposure to have an impact on health, if a causal relationship exists, according to Ponnana. Nevertheless, based on the available evidence, it is reasonable to believe that microplastics may play some role in health and we must take steps to reduce exposures, he said. While it is not feasible to completely avoid ingesting or inhaling microplastics when they are present in the environment, given how ubiquitous and tiny they are, researchers said the best way to minimize microplastics exposure is to curtail the amount of plastic produced and used, and to ensure proper disposal.

“The environment plays a very important role in our health, especially cardiovascular health,” Ponnana said. “As a result, taking care of our environment means taking care of ourselves.”

Reference:

New evidence links microplastics with chronic disease, American College of Cardiology, Meeting: American College of Cardiology’s Annual Scientific Session.

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Hyperbaric Oxygen Therapy and Conservative Approach Effectively Manage Severe MRONJ: Case Report

Japan: Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with the prolonged use of antiresorptive medications prescribed for osteoporosis and cancer treatment. It is characterized by persistent inflammation, necrotic bone exposure, and the formation of intraoral or extraoral fistulas. While surgical intervention is often beneficial, patients with MRONJ—many of whom have other serious conditions—may not always be suitable candidates for extensive surgical procedures.

A recent case report published in the Cureus journal highlights the successful management of an advanced case of medication-related osteonecrosis of the jaw (MRONJ) using hyperbaric oxygen (HBO) therapy in combination with conservative treatment.

An 81-year-old male with a history of prostate cancer and bone metastases developed extensive MRONJ after receiving denosumab therapy for nearly three years. The patient, who had been on a standard regimen of 120 mg subcutaneous denosumab every four weeks, presented with significant mandibular bone exposure, an extraoral fistula, and radiographic evidence of sequestration. Given his overall health condition and the preferences of his family, conservative treatment was chosen over extensive surgical intervention.

The treatment strategy involved a combination of antimicrobial therapy, regular oral irrigation, and HBO therapy. The patient was prescribed oral amoxicillin (750 mg/day) for 60 days and underwent 20 HBO therapy sessions on an outpatient basis. Each HBO session included controlled compression, a steady pressure maintenance phase, and gradual decompression using a specialized hyperbaric oxygen chamber. The therapy’s goal was to enhance oxygen supply to the affected area, facilitating the healing process.

Following HBO therapy, imaging revealed increased separation of the necrotic bone. To improve oral hygiene and aid sequestrum removal, the patient underwent a minor surgical procedure—saucerization—under local anesthesia. Histopathological analysis confirmed the presence of bacterial colonies and granulation tissue, further supporting the MRONJ diagnosis.

Post-saucerization, the patient continued with antimicrobial therapy and regular oral irrigation at a dental care unit. Nine months later, follow-up imaging showed further sequestrum separation, prompting a sequestrectomy under local anesthesia. Over the next two years, the remaining necrotic bone naturally detached, with no recurrent infections or worsening symptoms. Though an extraoral fistula persisted, there were no signs of active infection.

This case emphasizes the potential benefits of HBO therapy and conservative management in treating advanced MRONJ. The patient maintained his quality of life while managing the condition by avoiding extensive surgery. The findings also suggest that discontinuing denosumab could play a role in MRONJ resolution. Continued collaboration between medical and dental teams further contributed to positive patient outcomes.

This report highlights a non-invasive treatment alternative that may be particularly beneficial for elderly patients or those with significant comorbidities.

“MRONJ is a challenging condition that often necessitates extensive surgical intervention. However, this case report demonstrates the successful management of an elderly patient with advanced MRONJ through conservative treatment and hyperbaric oxygen therapy, avoiding invasive procedures,” wrote Tougo Tanabe and colleagues from the Department of Oral Diagnosis and Medicine, Hokkaido University, Sapporo, Japan.

“The findings also suggest that discontinuing denosumab may facilitate recovery. Additionally, continued medical collaboration was crucial in preserving the patient’s ability to use dentures and maintaining overall quality of life,” they concluded.

Tanabe T, Kimura T, Sakata K, et al. (February 18, 2025) Medication-Related Osteonecrosis Successfully Treated With Hyperbaric Oxygen Therapy and Conservative Treatment: A Case Report. Cureus 17(2): e79213. DOI 10.7759/cureus.79213

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Surgery Improves Long-Term Survival in Kidney Failure Patients with Acute Cholecystitis: Study

Researchers have identified in a new study that patients with renal failure undergoing chronic kidney replacement therapy (KRT), such as dialysis or kidney transplantation, are at high risk of postoperative complications. The results indicate that while surgery is at increased risk of early complications, it is linked with better survival at 12 months. The study was conducted by Dharmenaan and colleagues published in the Journal of Hepato-Biliary-Pancreatic Sciences.

A bi-national population cohort study was done with the assistance of Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry data and jurisdictional hospital admission data. All incident and prevalent patients receiving chronic KRT between 2000 and 2015 were included in the study. Those patients diagnosed with acute cholecystitis were identified by using the International Classification of Diseases (ICD) and divided into two groups based on whether or not they underwent cholecystectomy and how they were managed nonoperatively. Comorbidity-adjusted Cox models were used to examine 30-day and 12-month mortality between groups.

Key Findings

  • Of 46,779 patients receiving chronic KRT, 1,520 presented initially with acute cholecystitis in emergency.

  • Nonoperative management was provided to 87% of patients, while the rest were subjected to cholecystectomy.

  • 30-day mortality rates between the surgery and nonoperative groups were comparable (5.4% vs. 5.1%, p =0.83).

Surgery was linked to higher risks of nonfatal complications, such as:

  • Cardiovascular complications (OR 2.08, 95% CI 1.13–3.81)

  • ICU admission (OR 3.51, 95% CI 2.41–5.10)

  • Blood transfusions (OR 2.29, 95% CI 1.60–3.27)

  • 12-month survival was increased significantly in the surgery group (HR 0.61, 95% CI 0.43–0.87) compared to nonoperatively treated patients.

  • Increased 30-day readmission was observed in the nonoperative group (17.6% vs. 12.5%, p = 0.44).

The study authors concluded that patients with kidney failure undergoing chronic KRT who undergo an operation for acute cholecystitis have better 12-month survival rates when compared to nonoperative management patients. These observations point toward the necessity of individualized treatment protocols and vigilant monitoring to maximize patient benefit.

Reference:

Palamuthusingam, D., Hawley, C. M., Pascoe, E. M., Johnson, D. W., Sivalingam, P., Wood, S. T., Palamuthusingam, P., Jose, M. D., & Fahim, M. (2025). Operative and nonoperative management of acute cholecystitis in patients on chronic kidney replacement therapy. Journal of Hepato-Biliary-Pancreatic Sciences. https://doi.org/10.1002/jhbp.12133

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Hearing loss linked to heightened heart failure risk, suggests study

Hearing loss is linked to a heightened risk of developing heart failure, with the psychological distress caused by the impairment taking a key role in the observed association, finds a large long term study, published online in the journal Heart.

Hearing loss is increasingly common, particularly as people age, while the prevalence of heart failure is also on the rise, affecting around 64 million people worldwide, note the researchers.

While impaired hearing is associated with an increased risk of cardiovascular disease, principally, it is thought, as a result of the resulting social detachment, no study has comprehensively examined the association between objectively measured hearing ability and the risk of developing heart failure.

In a bid to plug this knowledge gap, the researchers mined the data of 164,431 participants from the UK Biobank, 4369 of whom wore hearing aids. None had heart failure to begin with. The average age of participants was 56, and 89,818 (around 55%) were women.

Their hearing ability was objectively measured using the validated Digit Triplets Test and the speech-reception-threshold (SRT). Participants (160,062) who didn’t wear hearing aids were categorised into three groups according to their performance on the DTT: normal (140,839; 88%); insufficient (16,759;10.5%); and poor (2464; 1.5%).

Comprehensive background information on current health, lifestyle, and psychosocial factors was collected via questionnaires.

Social isolation was assessed using a composite definition in the UK Biobank derived from scores (1-3) for the number of people living in the household, frequency of friend or family visits, and leisure or social activities. Those with a score of 2 or 3 were classified as socially isolated.

Psychological distress was assessed using a four-item version of the Patient Health Questionnaire (PHQ-4), with a score ranging from 0 to 12. Neuroticism, a depression-related personality trait, was assessed using 12 questions from the Eysenck Personality Questionnaire-Revised Short Form.

The development of heart failure among those who were not genetically predisposed to the condition was identified through medical records and death certificates during an average follow up of 11½ years.

During this period, 4449 (nearly 3%) of the participants developed heart failure. SRT levels were significantly positively associated with the risk of developing the condition in participants who didn’t wear hearing aids.

Compared with those with normal hearing, the adjusted heightened risks of developing heart failure were 15% and 28%, respectively, for insufficient and poor hearing, and 26% for hearing aid use.

The associations between SRT levels and heart failure risk were stronger in those without coronary heart disease or stroke at the start of the study.

SRT levels were significantly positively associated with social isolation, psychological distress, and neuroticism among those who didn’t wear hearing aids. And these factors had a substantial role in the observed associations in participants who didn’t wear hearing aids, accounting for 3%, 17%, and 3%, respectively, of the heightened risk of heart failure development.

When the scores for social isolation, psychological distress, and neuroticism were combined among those who had full data on these factors, the total mediating effect was just over 9%.

This was less than the sum of the mediating effects of each individual factor, which amounted to 19.5%, suggesting overlap and interaction between these three factors, say the researchers.

This is an observational study, and as such, can’t establish cause and effect. And data on hearing were collected only at the start of the study, while the participants in the current study were mainly of European descent and healthier than the UK general population, they acknowledge.

But there are plausible biological explanations for their findings, they say. “The rich distribution of capillaries in the…cochlea and the high metabolic demand of the inner ear may render these regions more sensitive to systemic vascular disorders rather than just local circulatory issues,” they suggest.

“Therefore, hearing impairment may reflect vascular health and serve as an early and sensitive predictor of cardiovascular disease, including [heart failure],” they add.

“Of note, both the participants who used hearing aids and those with poor hearing had a similarly significant increase in the risk of incident [heart failure], suggesting that while hearing aids can improve auditory function, they may not address the underlying vascular issues that contribute to the risk of [heart failure],” they continue.

And they explain: “Because hearing problems can lead to difficulties in speech comprehension and poor engagement in social activities, people with hearing impairment are more likely to experience social isolation, psychological distress, anxiety and depression than people without hearing impairment.

“These psychological factors may increase the activity of the sympathetic nervous system and the hypothalamic-pituitary adrenal axis, and enhance inflammation and oxidative stress, thereby accelerating atherosclerosis, increasing peripheral stress, and promoting the development of cardiac remodelling.”

The findings highlight the importance of integrating hearing health assessments into broader cardiovascular risk evaluation frameworks, they conclude. And strengthening psychological intervention in people with hearing impairment may be key to curbing the risk of heart failure, they suggest.

Reference:

https://heart.bmj.com/lookup/doi/10.1136/heartjnl-2024-325394

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Overproduction of fHbF and inadequate heme defence may contribute to foetal distress, suggests study

Authors evaluated the occurrence of cell free haemoglobin in
the foetal circulation of severe early-onset foetal growth pregnancies, and
measured the autologous heme-handling capacity, to determine whether they are
linked to foetal vascular biometry, indicative of survival risk. Foetal growth
restriction (FGR) represents a failure of a foetus to meet its genetically
determined growth potential. Being born small is associated with stillbirth and
a host of vascular, neurodevelopmental and endocrine conditions in later life,
including, hypertension, diabetes, stroke, coronary artery disease, renal injury
and cognitive impairment. Increased extracellular haemoglobin in plasma has
been implicated in numerous diseases, and vascular dysregulation conditions.
Pertinently, high free haemoglobin overcomes the sequestering capacity of plasma
defences, with deleterious sequalae affecting vascular health.

There is excess free fHbF in FGR neonatal cord blood at late
preterm or term gestations. Authors have also demonstrated that fHbF increases
fetoplacental vascular resistance by sequestering nitric oxide (NO), promoting
matrix damage to the placental stroma, compromising placenta barrier function.
They also reported compromised effects of fHbF on placental endothelial
junctions in the pro-inflammatory and pro-angiogenic effects. The circulating
scavengers, haptoglobin, hemopexin and alpha-1-microglobin (A1M) protect
against fHbF. These endogenous substances are pleiotropic, but within the
context of this study, bind fHbF to protect against the sequestration of
endothelial-derived nitric oxide and prevent fHbF from binding to the
inflammation-evoking TLR4 receptor which is strongly expressed in the placenta,
which activates to elicit expression of numerous inflammatory cytokines
placental in a primary trophoblast cell line. Normally, small amounts of fHbF
are efficiently handled by these systems with limited impact on vascular
function. However, in haemolytic conditions, where there is increased
erythrocyte turnover, including megaloblastoma, excess free Hb occurs, either
oversaturating existing defences, or leading to their compensatory upregulation.

Authors hypothesised that fHbF is elevated in cases of
early-onset FGR, with reduced heme scavenging, and is associated with clinical
features of foetal blood flow redistribution. Previous observations in PE have
demonstrated sexual dimorphism in response to biological challenges, which they
further explored in early-onset FGR.

It was a prospective study severe early-onset foetal growth
restriction pregnancies with close clinical management (estimated foetal weight
(EFW)< 3rd centile and<600 g at 20–26+6weeks; N=20). Temporal foetal
vascular obstetric biometry was recorded. Cord blood fHbF and key
heme-scavenger defences were measured and compared with normal term births
(N=26) and births with late-onset FGR (N=12).

fHbF was elevated in early-onset FGR compared with normal
pregnancy: 0.437(0.337/0.753) mg/mL; and 0.098 (0.045/0.264) mg/mL,
respectively (p<0.0001); whilst hemopexin was downregulated in early-
(p<0.001) and late-onset FGR (p<0.0001), compared to normal pregnancy:
36(14/81) μg/mL, 25(19/40) μg/mL, and 155(132/219) μg/mL, respectively; median
(interquartile ranges).

Early-onset FGR male foetuses had higher HbF compared with
the normal males: 0.710(0.433/0.857) mg/ mL; (p<0.001); 0.099(0.043/0.246)
mg/mL, respectively; median (interquartile ranges).

In early-onset FGR, ratios of mid-cerebral artery and
umbilical artery pulsatility indices correlated positively with heme-scavenger
levels (hemopexin and a heme-handling composite measure: p<0.05, r=0.672;
and p<0.01, r=0.620; respectively), indicating lower levels are associated
with cerebral vascular redistribution.

These heme handling measures also positively correlated with
gestational age at delivery (r=0.713 and r=0.642, respectively, p<0.01,
both) and birthweight (r=0.742, p<0.001; and r=0.523, p<0.05;
respectively).

Fetal cord plasma had significantly higher levels of fHbF in
the EVERREST cohort compared to normal pregnancy delivered at term. Authors
reported significant cord plasma reductionsn hemopexin in both FGR groups
compared to the normal group; being 4–6 times lower in the early- and
late-onset groups, respectively, with an apparent inverse relationship to the
heme load.

To give further strength to the calculation of heme handling,
they derived a composite calculation for each sample. Using this measure,
authors found that earlyonset FGR foetal plasma had a lower score than normal
term samples (p0.0001), more significant than for late-onset FGR(p<0.05). Overall,
they did not show any difference between absolute A1M levels in controls and
FGR groups, though the inclusion of A1M in the aforementioned composite measure
strengthened the separation between early- and late FGR cases.

The haptoglobin heme-defence, was below the level of detection
in all groups using a manual ELISA method (AbCam, ab219048 Human Haptoglobin
SimpleStep ELISA Kit) and by an automated immunoassay analyser method. Two
significant sexual dimorphism findings related only to males: (i) the foetal
plasma fHbF level was higher in early FGR pregnancies than occurred normally at
term; and (ii) matched by an equally significant reduction in hemopexin.

Authors have demonstrated that fHbF is overrepresented in
the severest cases of early onset FGR, with a consequential overwhelming of
heme defences, a scenario linked to poor foetal vascular performance, severe
foetoplacental insufficiency, and preterm delivery. In the early-onset FGR
group, sex-specific variations in response to fHbF and heme appear to exist
with female foetuses displaying higher MCA PI values and a greater proportion
of female foetuses showing MCA/UA ratios in excess of 1, a clinical threshold
below which is associated with increased stillbirth risk. Among this group they
also observed a tendency for female foetuses to have higher hemopexin levels
and more active heme handling profiles

Source: Adam Brook, Georgia Baynes,
Jonathan Scargill; BJOG: An International Journal of Obstetrics &
Gynaecology, 2025; 0:1–11 https://doi.org/10.1111/1471-0528.18104

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Protein in the nose provides information about COPD, reports research

Early diagnosis of COPD, chronic obstructive pulmonary disease, increases the quality of life of the patient and the efficacy of available treatments. Researchers at Karolinska Institutet in Sweden have now shown that material from nasal lavage provides a basis for assessing COPD. The study, which has been published in the Journal of Allergy and Clinical Immunology, could lead to a simple diagnostic method for early assessment of COPD.

Chronic obstructive pulmonary disease (COPD) affects ten percent of the population and is the fourth most common cause of death in the world. The disease is mainly caused by smoke from biomass and the patient group is very heterogeneous in terms of symptoms and prognosis.

This means that the medical needs vary greatly, while today’s examination methods are neither sufficient nor useful for assessing the large number of patients. Therefore, simple and safe methods that work at the individual level are needed.

Immune cells in the nose

Researchers at Karolinska Institutet and Karolinska University Hospital have now shown that elevated levels of the protein interleukin-26 (IL-26) in the nose of smokers with and without COPD can be used to assess patients with an early phase of the disease.

IL-26 is a so-called cytokine that is important for cell communication in the immune system. An interesting property of IL-26 is that this cytokine has a direct inhibitory effect on bacteria and viruses.

Cytokines can influence inflammation and immune responses, and IL-26 has previously been linked to various inflammatory diseases, including COPD. In COPD, the levels of IL-26 in the lower respiratory tract have been shown to be elevated.

In the current study, the researchers have focused on understanding how IL-26 is produced in the nose of smokers and what the levels say about the individual COPD patient.

“We have discovered that IL-26 is produced in greater amounts in the nose of smokers with COPD compared to non-smokers, while smokers without COPD showed a tendency towards increased levels. This suggests that IL-26 may be an important factor in the inflammatory process underlying COPD,” says the study’s first author Julia Arebro, researcher at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and physician at Karolinska University Hospital.

A simple nasal lavage

The study included 50 research participants; active habitual smokers with and without COPD, as well as a control group of healthy non-smokers. Patients with other lung diseases were excluded from the study.

Among other things, the study participants underwent a simple nasal lavage so that the researchers could analyse the presence of IL-26 in the nose. The measured levels were found to reflect inflammation of the lower respiratory tract but also symptoms and other clinical findings in COPD.

“This opens up an easier way to characterise COPD patients without having to examine their lower airways with methods that are resource-intensive and involve medical risks,” says Julia Arebro.

New treatment strategies

The study also shows that T cells, a type of white blood cell in the immune system, are involved in the production of IL-26 in the nose.

“Our results support that IL-26 contributes to the chronic inflammation that is typical for COPD. This may open up for new treatment strategies that target IL-26 to reduce inflammation and improve the quality of life for patients with COPD,” says Anders Lindén, professor at the Institute of Environmental Medicine, Karolinska Institutet, and senior physician at Karolinska University Hospital who has led the research team behind the study.

The study was conducted in patients with mild to moderate COPD. In a next step, the researchers are planning a similar study on COPD, but in later stages. If future work confirms current results, the researchers believe that the method for easily estimating patients with COPD can be implemented within the next few years.

Reference:

Julia Arebro, Nikolaos Pournaras, Patricia Ramos-Ramírez, Nasal production of IL-26 involving T cells in smokers with and without COPD, Journal of Allergy and Clinical Immunology, DOI: https://doi.org/10.1016/j.jaci.2025.03.017.

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