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A new study published in the journal of BMC Cardiovascular Diabetology showed that in patients with critically sick ischemic stroke (IS), increased triglyceride glucose-body mass index (TyG-BMI) is substantially linked to an increased risk of short-term all-cause mortality.

Focal neurological dysfunction and cerebral tissue necrosis are hallmarks of ischemic stroke, which is usually caused by insitu thrombotic events or the embolization of atherothrombos from proximal artery sources. Moreover, the most frequent causes of ischemic stroke attributable to other causes include hematological illnesses, such as essential thrombocythemia, polycythemia vera, and thrombotic thrombocytopenic purpura, which can also present as acute ischemic stroke.

Calculated by multiplying fasting triglyceride and fasting glucose levels, the triglyceride-glucose index is a simple and accurate surrogate diagnostic for evaluating insulin resistance (IR), which is associated with IS. In order to fill up current research gaps and provide more accurate biomarker references for therapeutic applications, this study, which is based on the eICU database, examines the connection between the TyG-BMI and 28-day mortality in critically ill IS patients.

The effects of the TyG-BMI on 28-day hospital and intensive care unit mortality were examined using multivariate Cox regression models. To investigate the nonlinear association between the TyG-BMI and 28-day mortality, restricted cubic splines (RCS) were used. K-M curves were used to compare the results of the various TyG-BMI groups. Furthermore, subgroup and interaction analyses were conducted to confirm the results’ resilience.

The mean age of the 1,362 severely sick IS patients that were included was 68.41 ± 14.16 years, and 47.50% of them were male. The high TyG-BMI group had substantially greater ICU and 28-day hospital mortality, according to multivariate Cox regression analysis. The TyG-BMI and 28-day inpatient mortality had a nonlinear positive connection, according to RCS analysis.

There was a 37.3% rise in 28-day hospital mortality for every 1 standard deviation (SD) increase in TyG-BMI below the inflection point of TyG-BMI = 380.37, and an 87.9% decrease in 28-day hospital mortality for every 1 SD increase in TyG-BMI beyond 380.376. The P value for the log-likelihood ratio test is 0.004. The TyG-BMI showed a strong positive linear connection in RCS for 28-day ICU mortality. Overall, among critically sick IS patients in the US, an elevated TyG-BMI is substantially associated with a higher risk of short-term all-cause mortality. 

Reference:

Ouyang, Q., Xu, L., & Yu, M. (2025). Associations of triglyceride glucose-body mass index with short-term mortality in critically ill patients with ischemic stroke. Cardiovascular Diabetology, 24(1). https://doi.org/10.1186/s12933-025-02583-1

The molecular mechanism behind why heart attacks can vary in severity depending on the time of day has been uncovered by researchers at UTHealth Houston, potentially paving the way for innovative treatments that align with the natural circadian rhythm.

The study’s findings were published in Nature.

Previous research has shown that the severity of heart damage after an acute myocardial infarction, or heart attack, varies depending on the time of day, with morning attacks resulting in more significant damage and worse outcomes. However, the reasons behind these variations have remained unclear.

“If you have a heart attack in the morning, you are more likely to have fatal arrhythmias, heart failure, and you’re more likely to die from it. The question we asked is ‘Why?’” said Holger Eltzschig, MD, PhD, senior author, and chair and professor of the Department of Anesthesiology, Critical Care and Pain Medicine at McGovern Medical School at UTHealth Houston.

Researchers identified an interaction between two proteins, BMAL1 and HIF2A, as the key factor underlying time-of-day differences in the severity of heart injury following a heart attack. BMAL1 is a core circadian rhythm protein, responsible for regulating biological processes like sleep-wake cycles, metabolism, and hormone release. HIF2A helps the body adapt to hypoxia — low oxygen levels — by stimulating red blood cell production, promoting the growth of new blood vessels, and enhancing cell survival under low-oxygen conditions.

Heart attacks occur when blood flow to the heart is blocked and the muscle begins to die from lack of oxygen. Researchers discovered this interaction between BMAL1 and HIF2A regulated how heart cells in mice responded to low oxygen levels after a heart attack, modulating the heart’s response to injury.

In the preclinical study, researchers found that heart attacks that occurred around 3 a.m. resulted in greater damage to the heart, including larger infarct size and increased risk of heart failure. Heart attacks that occurred at 3 p.m. were less severe, and the heart was better able to adapt to low oxygen levels and promote efficient healing.

The research also revealed that the proteins BMAL1 and HIF2A target a specific gene, amphiregulin (AREG), which plays a vital role in regulating the extent of heart damage throughout the day. By targeting the BMAL1 and HIF2A-AREG pathway with drugs, researchers found they could provide significant protection to the heart, especially when treatments were timed to align with the body’s circadian phase.

According to Eltzschig, future clinical trials must evaluate whether aligning treatments with the body’s internal clock can enhance patient outcomes.

“This discovery opens up new avenues for treating heart attacks by considering the timing of drug administration,” said Eltzschig, who is John P. and Kathrine G. McGovern Distinguished University Chair at McGovern Medical School. “Our findings highlight the potential to use targeted drugs toward those proteins to reduce the severity of heart attacks when administered at specific times. Similarly, patients undergoing cardiac surgery may benefit from such drugs, like the hypoxia-inducible factor activator vadadustat, when given before their operation.”

The research team included Kuang-Lei Tsai, PhD, assistant professor, and Tao Li, PhD, a postdoctoral researcher and co-first author, from the Department of Biochemistry and Molecular Biology at McGovern Medical School. Using high-resolution cryo-electron microscopy, they were able to reveal the detailed structural interactions between BMAL1 and HIF2A to support future drug development targeting the BMAL1-HIF2A complex. This work provided the first direct molecular evidence of their complex formation and offered critical insights that could guide the development of new therapeutic strategies, Eltzschig said.

Reference:

Ruan, W., Li, T., Bang, I.H. et al. BMAL1–HIF2A heterodimer modulates circadian variations of myocardial injury. Nature (2025). https://doi.org/10.1038/s41586-025-08898-z

Cervical cancer screening guidelines in the U.S. recommend that most women can discontinue routine screening at age 65 after receiving two consecutive negative cotests, which involve concurrent human papillomavirus (HPV) and Papanicolaou (Pap) tests. However, empirical data on cancer and mortality risks for this demographic group remain sparse. A decision analytical comparative modeling study was conducted to estimate risks of cervical cancer and associated mortality for women who meet the exit criteria. Recent study utilized four distinct models from the Cancer Intervention and Surveillance Modeling Network (CISNET) and validated them against published data on cervical intraepithelial neoplasia grade 3 (CIN3) risks from a Kaiser Permanente Northern California (KPNC) cohort.

Model Outcomes and Analysis

With attention to both age-conditional and cumulative risks of cervical cancer and cancer death, the models generated outcomes for women aged 65, 70, 75, 80, and 85 years. Following the harmonized guidelines established in 2012, which reaffirmed the exit criteria based on adequate screening, the analysis sought to delineate cancer risks for those who had shown consistent negative results.

Microsimulations and Findings

The models involved microsimulations calibrated using U.S. epidemiologic data and facilitated comparisons of cancer risk under various screening histories. The findings highlighted that the 3-year risk for CIN3 for two consecutive negative results ranged from approximately 0.035% to 0.038%, marginally exceeding published bounds from the KPNC cohort, while the 5-year risks aligned within the accepted confidence interval, reflecting an estimated incidence of 0.075% to 0.083%.

Age-Conditional Risks Evaluation

In evaluating age-conditional risks, results indicated that, while the risks were generally low across both groups, lower age-conditional risks of cervical cancer and mortality were projected for those with comprehensive screening histories compared to those with only the two negative results when exiting screening. However, one of the models (Policy1-Cervix) produced a discrepancy, predicting higher risks in certain age brackets, suggesting variability among models stemming from different assumptions about cancer progression pathways.

Cumulative Risk Projections

Cumulatively, risks of cervical cancer by age 85 were projected to be between 0.026% and 0.081%, with mortality risks also being low (ranging from 0.005% to 0.038%). Interestingly, scenarios applying lower sensitivity for cytology tests and increased HPV incidence showed a slight escalation in these risks, underscoring the complexity of HPV theory in relation to cervical cancer risk. The present findings represent the first comprehensive estimates pertaining to this specific subset of older women and reaffirm the consequential role of rigorous screening in risk management. Despite the study’s insights, limitations were noted, including potential demographic disparities in the KPNC population and constraints surrounding various screening cessation criteria. Future guidelines should consider a broader spectrum of screening cessation strategies given the persistent uncertainties surrounding HPV incidence among aging cohorts. The analysis advocates for an intricate balance between minimizing cancer risks and evaluating screening-related harms and benefits, especially in the context of competing health concerns that accompany aging women. Continued surveillance of HPV prevalence should be prioritized to inform evolving cervical screening recommendations.

Key Points

– Cervical cancer screening in the U.S. allows most women to stop routine screening at age 65 after two consecutive negative HPV and Pap tests, but data on cancer and mortality risks for this age group is limited. A comparative modeling study aimed to fill this knowledge gap.

– The study employed four models from the Cancer Intervention and Surveillance Modeling Network (CISNET) to evaluate cancer and mortality risks in women aged 65 to 85, using data from a Kaiser Permanente Northern California cohort for validation.

– Microsimulations demonstrated that the 3-year risk for cervical intraepithelial neoplasia grade 3 (CIN3) after two negative tests was between 0.035% and 0.038%, with 5-year risks falling within acceptable confidence intervals, estimated at 0.075% to 0.083%.

– Age-conditional risks revealed that women with comprehensive screening histories exhibited lower cervical cancer and mortality risks compared to those who had only the necessary two negative results. However, one of the models predicted higher risks for certain age groups, indicating variability in model outcomes based on different cancer progression assumptions.

– Cumulative risk projections indicated a cervical cancer risk by age 85 of 0.026% to 0.081%, with associated mortality risks ranging from 0.005% to 0.038%. Increased HPV incidence and lower sensitivity in cytology tests were associated with slight increases in these risks.

– The study acknowledged demographic disparities in the data and the need for future guidelines to account for varied screening cessation strategies, emphasizing the importance of balancing cancer risk reduction with the assessment of screening-related benefits and harms in aging populations. Ongoing monitoring of HPV prevalence is crucial for adapting cervical screening recommendations.

Reference –

Shalini L Kulasingam et al. (2025). Estimated Cancer Risk In Females Who Meet The Criteria To Exit Cervical Cancer Screening. *JAMA Network Open*, 8. https://doi.org/10.1001/jamanetworkopen.2025.0479.

A new study published in the journal of BMC Pulmonary Medicine showed that dyspnea (mMRC score 1.67), symptom load (CAT score 10.24), and exacerbations were considerably greater in frail patients with chronic obstructive pulmonary disease (COPD).

Frailty is a multifaceted condition marked by a build-up of physiological deficiencies that lead to a loss of functional, cognitive, and physical reserves. A person is more susceptible to health stresses, including falls, hospital stays, and acute flare-ups of chronic illnesses, when frailty is present and worsens. 

Despite the underlying causes of frailty are many, they share characteristics with those of COPD, including endocrine dysregulation, decreased muscle mass and function, and chronic systemic inflammation. To learn more about the relationship between frailty and clinical outcomes for individuals with COPD, Mathew Cherian and team conducted a systematic review and meta-analysis of the literature.

This study reviewed MEDLINE, Cochrane Central, EMBASE, CINAHL, and Web of Science for observational studies assessing the relationship between frailty and clinical outcomes in people with COPD. The included studies evaluated dyspnea, symptom load, health-related quality of life, exacerbations, hospitalization, or death between frail and non-frail patients, diagnosed COPD by spirometry, and employed a validated frailty assessment instrument. 

7 of the 16 studies which represented a total of 5903 individuals were included in the meta-analyses out of the 1,385 identified studies. 50% of the included studies employed the Fried Frailty Phenotype assessment. Pooled estimates showed that frail individuals with COPD experienced increased dyspnea ratings, a greater burden of symptoms, and more COPD exacerbations during the previous year when compared to non-frail individuals. Frail vs. non-frail COPD patients had a higher mortality risk, according to the biggest research with the longest follow-up duration.

Overall, the patients who are frail have higher rates of hospitalizations, exacerbations, symptom load, and dyspnea when compared to COPD patients who are not weak. Frailty should be seen as a therapeutic feature because it is a strong predictor of outcomes for individuals with COPD.

Reference:

Cherian, M., Masoudian, P., Thavorn, K., Sandoz, J., Shorr, R., & Mulpuru, S. (2025). The impact of frailty on clinical outcomes among individuals with COPD: a systematic review and meta-analysis. BMC Pulmonary Medicine, 25(1), 146. https://doi.org/10.1186/s12890-025-03595-z

Resistance or muscle strengthening exercise, using weights or the body itself, may be the best type of exercise for tackling insomnia in older age, suggests a pooled data analysis of the available research, published in the open access journal Family Medicine and Community Health.

Aerobic exercise or a mix of strength, aerobic, balance, and flexibility exercises also seem to be effective, the analysis indicates.

Sleep quality tends to decline with age. And up to 1 in five older adults has insomnia, say the researchers. Poor quality sleep is not only linked to a range of serious health problems and cognitive impairment, but it also increases the likelihood of workplace underperformance and absenteeism, they add.

Previously published research suggests that exercise helps to alleviate the symptoms of insomnia, but it’s not clear which type of exercise might be most helpful.

In a bid to find out, the researchers scoured research databases for relevant clinical trials, published up to October 2022 that compared physical exercise with routine activities, usual care, other non-physical activity, or health education in people formally diagnosed with insomnia, using The Global Pittsburgh Sleep Quality Index (GPSQI).

The types of exercise covered by the studies included: aerobic, such as cycling, dancing, swimming, brisk walking, and gardening; resistance, such as using weights, push-ups, and planks; balance, such as step-ups, heel to toe walking; flexibility, such as gymnastics, yoga, and Pilates; and combination exercise encompassing a mix.

Twenty four studies, involving 2045 adults aged at least 60 (average 70), were included in the pooled data analysis. Most were carried out in Asia (56%), North America (16%), South America (16%), and Europe (12%). One in five were carried out in nursing homes.

Over half of the reported exercise intensity was mild to moderate and moderate, with average length of a session just over 50 minutes, and frequency around 2 to 3 times a week. On average, the exercise programmes lasted 14 weeks.

The pooled data analysis included only studies looking at combination exercise and aerobic exercise, because there weren’t enough studies covering the other exercise types.

This analysis showed that combined exercise significantly improved the GPSQI by 2.35 points while aerobic activity improved it by 4.35 points.

When the data were pooled using a network meta analysis–a statistical method that looks at several different ‘treatments’ and combines both direct and indirect effects-strength/resistance exercise was the most effective, improving the GPSQI by 5.75 points.

Aerobic exercise improved the GPQSI by 3.76 points, while combination exercise improved it by 2.54.

Of the comparators, sleep education was the most effective, although what this entailed wasn’t clearly defined in the included studies, and it still wasn’t as good as muscle strengthening/resistance exercise, the analysis showed.

The researchers caution that the design and methodology of the included studies varied considerably, and only a few looked at particular types of exercise. Several didn’t include any information on exercise intensity either.

Some exercises may prove challenging for older people because of restricted physical capabilities, suggest the researchers. But they nevertheless conclude that: “Exercise, particularly strengthening exercise and aerobic exercise, is beneficial for enhancing subjective sleep quality at a clinically significant level compared with normal activities.”

Reference:

Impact of different types of physical exercise on sleep quality in older population with insomnia: a systematic review and network meta-analysis of randomised controlled trials Doi: 10.1136/fmch-2024-003056.