Cancer immunotherapy linked to rare liver complication, study warns

A global study reveals that cutting-edge cancer immunotherapies, while lifesaving, carry a hidden risk: they may trigger cholestasis, a serious liver condition where bile flow stalls. Analyzing 634 patient reports from global drug-safety databases (FAERS and VigiBase), scientists found immunotherapy patients had a significantly higher risk of cholestasis than chemotherapy recipients. Those under 65 faced greater danger, and women developed symptoms weeks earlier than men (Median 1.17 vs. 1.90 months).

Anti-PD-1 drugs (e.g., pembrolizumab) and combination therapies posed the highest risk. In mice, combined anti-CTLA-4/anti-PD-L1 drugs caused severe bile duct injury. Molecular analysis linked the condition to disrupted bile acid metabolism and inflammation pathways.

“This isn’t about abandoning immunotherapies-they save lives,” stresses senior author Peng Luo, PhD, of Southern Medical University. “But we must monitor liver function aggressively, especially in the first month for women and young adults. Catching cholestasis early prevents irreversible damage.”

Surprisingly, cholestasis often occurred without classic hepatitis symptoms, suggesting routine liver tests alone may miss it. The team urges adding bile acid level checks to standard monitoring.

Reference:

Yan, Xinronga,†; Li, Zhengruib,†; Jiang, Aiminc,†; Chen, Jinghonga,†; Huang, Xufengd,e; Hajdu, Andrásd; Wong, Hank Z.H.f; Cheng, Quang,h,*; Zhang, Jiani,*; Lin, Anqia,*; Luo, Penga,*. Immunotherapy-induced cholestasis in cancer: insights from the two real-world pharmacovigilance databases of FAERS and vigiBase. International Journal of Surgery ():10.1097/JS9.0000000000002607, June 05, 2025. | DOI: 10.1097/JS9.0000000000002607.

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Study finds living in rural environments in first 5 years of life could be a risk factor for developing type 1 diabetes

New research to be presented at this year’s Annual Meeting of the European Association for the Study of Diabetes (EASD) in Vienna, Austria (15–19 September) suggests that living in a rural environment in the first five years of life could increase the risk of developing type 1 diabetes compared with living in urban environments.

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Study finds rising cannabis use among Black and Hispanic men with chronic illness

Cannabis use is gaining popularity in the United States, driven by growing legalization, public acceptance and diverse methods of consumption.

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The power of play in early childhood

Play is how young children make sense of the world. Whether with dolls, blocks, trains, or playdough, children use play to explore, experiment, and learn. In early childhood, it is essential that children have at least an hour of open-ended play each day, as recommended by research. During this time, they should be encouraged to ask questions, test ideas and engage in creative thinking. Play is not just fun — it is foundational. Play supports cognitive growth, language and communication skills, social and emotional development, physical coordination, creativity, and overall school readiness.

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Scientists identify shared biological roots of long COVID and chronic fatigue syndrome

In recent years, doctors and scientists are increasingly studying long-lasting illnesses that begin after someone recovers from an infection. Two of the most well-known examples are long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

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‘And’ vs. ‘Then’: What words in online reviews tell us about hospital visits

Can simple words like “and” or “then” in online reviews help health care providers learn about their patients’ experiences?

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Methylglyoxal Independently Contributes to Liver Fibrosis in Obesity: Study

A new study has determined that increased concentrations of methylglyoxal (MGO), a potent reactive byproduct of glucose metabolism, can independently cause the onset of liver fibrosis among obese individuals. The finding is consistent with mounting evidence indicating that MGO and similar compounds not only initiate inflammation and produce deleterious advanced glycation end products (AGEs), but also are key players in liver injury involved with metabolic dysfunction-associated steatotic liver disease (MASLD).

The research, which quantified plasma concentrations of MGO, glyoxal (GO), and 3-deoxyglucosone (3-DG), had significant correlations with severity of liver fibrosis, even in non-type 2 diabetic subjects. The study was conducted by Oluwatomisono I. and colleagues published in the journal of Diabetes Obesity and Metabolism.

264 severely obese subjects undergoing bariatric surgery were studied as part of the BARIA cohort. Among the participants, 22% had type 2 diabetes, 77% were female, the median age was 47 years (IQR: 39–54 years), and the median BMI was 39 kg/m² (IQR: 36–41 kg/m²). Plasma concentrations of MGO, GO, and 3-DG were measured in a research setting using ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Liver fibrosis was assessed by two different approaches: the non-invasive Fibrosis-4 (FIB-4) Index and direct liver histology score from biopsies.

Key findings

  • Plasma MGO levels were significantly increased in people with type 2 diabetes (median: 288 nmol/L; IQR: 257–334 nmol/L) versus those without diabetes (median: 238 nmol/L; IQR: 212–279 nmol/L). MGO also rose higher in men (267 nmol/L; IQR: 236–301 nmol/L) than in women (245 nmol/L; IQR: 214–288 nmol/L).

  • The same tendencies were seen for GO and 3-DG, suggesting that dicarbonyl stress is greater in men and people with diabetes.

  • Plasma concentrations of MGO, GO, and 3-DG were positively correlated with higher scores for FIB-4 Index, a very high correlation with liver fibrosis.

  • That is, correlation coefficients (rho) were 0.21 for MGO, 0.29 for GO, and 0.25 for 3-DG, and all were statistically significant (p < 0.05).

  • In multiple linear regression models controlling for several potential confounders (age, sex, BMI, smoking status, alcohol intake, hypertension, insulin resistance, HbA1c, and fasting glucose), the relationship between MGO and the FIB-4 Index continued to hold strong.

This study highlights dicarbonyl stress especially from methylglyoxal as a significant and independent contributor to liver fibrosis in obese individuals, even in the absence of diabetes.

Reference:

Akinrimisi, O. I., Koning, M., Scheijen, J. L. J. M., Meijnikman, A. S., Sindhunata, D. P., Bruin, S., van de Laar, A., Franken, R., Acherman, Y., Gerdes, V. E. A., Nieuwdorp, M., Schalkwijk, C. G., & Hanssen, N. M. J. (2025). Higher plasma dicarbonyl levels are associated with liver fibrosis in obese individuals. Diabetes, Obesity & Metabolism. https://doi.org/10.1111/dom.16643

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Waist Circumference Linked to Higher Mortality Risk in Menopausal Women: Study

A study published in Annals of Internal Medicine has revealed that menopausal women with larger waist circumference faced a higher risk of death across all body mass index (BMI) categories. Researchers emphasized that waist circumference is a simple and cost-effective measure for assessing health risks. The study was conducted by Aaron K. and fellow researchers.

BMI has been a widely used standard measure to evaluate obesity-related health risk for many years. It does not, however, measure fat distribution, particularly abdominal fat, which is more directly associated with chronic disease and mortality. In 2020, a consensus statement suggested BMI-specific WC cut points in an attempt to further stratify risk. The purpose of this study was to determine whether the use of these WC cut points in BMI categories would enhance prediction of 10- and 20-year mortality risks.

The analysis used data from 139,213 postmenopausal women 50 to 79 years old, sampled between 1993 and 1998, with follow-up through 2021. Patients were split into a development cohort (n = 67,774) and two external validation cohorts:

  • Validation Cohort 1 (n = 48,335), supplemented with overweight and obese women

  • Validation Cohort 2 (n = 23,104), with women from varied and geographically remote U.S. centers

Height, weight, and waist circumference were assessed at recruitment. Participants were stratified into five BMI groups:

  • Normal weight (18.5–<25 kg/m²)

  • Overweight (25–<30 kg/m²)

  • Obesity-1 (30–<35 kg/m²)

  • Obesity-2 (35–<40 kg/m²)

  • Obesity-3 (≥40 kg/m²)

Each of the BMI groups was also stratified according to WC cutpoints:

  1. ≥80 cm for normal weight,

  2. ≥90 cm for overweight,

  3. ≥105 cm for obesity-1,

  4. ≥115 cm for obesity-2 and 3.

Key findings

  • During a median follow-up of 24 years, 69,297 women died.

  • Normal BMI but increased WC: HR = 1.17 (95% CI, 1.12–1.21)

  • Overweight with increased WC: HR = 1.19 (CI, 1.15–1.24)

  • These risks were comparable to women with obesity-1 and normal WC: HR = 1.12 (CI, 1.08–1.16)

  • Obesity-1 with increased WC: HR = 1.45 (CI, 1.35–1.55)

  • This risk was comparable with those with obesity-3 and normal WC: HR = 1.40 (CI, 1.28–1.54)

  • For Validation Cohort 1, WC addition increased c-statistics by 0.7% (from baseline to 61.3%) and continuous NRI by 20.4% (CI, 17.3–23.6%) at 10 years.

  • For Validation Cohort 2, there was a 12.3% improvement in risk stratification (CI, 8.5–16.0%) but no consistent improvement in discrimination.

  • The results at 20 years were comparable to those at 10 years, suggesting long-term applicability of these measures.

In this big cohort of postmenopausal women, categorizing BMI by waist circumference thresholds modestly enhanced prediction of mortality risk, especially for women with greater abdominal fat. These data argue in favor of routine incorporation of waist circumference into assessment of obesity and cardiovascular risk in older women.

Reference:

Aragaki, A. K., Manson, J. E., LeBlanc, E. S., Chlebowski, R. T., Tinker, L. F., Allison, M. A., Haring, B., Odegaard, A. O., Wassertheil-Smoller, S., Saquib, N., Masaki, K., Harris, H. R., Jager, L. R., Bea, J. W., Wactawski-Wende, J., & Anderson, G. L. (2025). Development and validation of body mass index-specific waist circumference thresholds in postmenopausal women : A prospective cohort study: A prospective cohort study. Annals of Internal Medicine, ANNALS-24-00713. https://doi.org/10.7326/ANNALS-24-00713

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Study highlights the severity of acute necrotizing encephalopathy in kids with the flu: Study

For most children, influenza (flu) usually means unpleasant symptoms like a fever, sore throat, and achy muscles. But for a small subset of kids, the flu can trigger a rare but serious complication called influenza-associated acute necrotizing encephalopathy (ANE). This form of brain inflammation typically occurs in response to a virus — such as those that cause the flu-and can lead to lasting neurological problems and brain damage. Now, findings of a multicenter study, published today in JAMA, led by Molly Wilson-Murphy, MD, and Rachel Walsh, MD, in Boston Children’s Neuroimmunology Center suggest that ANE is often fatal in these children-despite intensive treatment.

Revealing the risks of influenza-associated ANE

During the 2024-5 U.S. flu season, clinicians at large pediatric centers reported an increased number of children with influenza-associated ANE. This anecdotal rise in cases prompted Wilson-Murphy and her colleagues at Stanford University and elsewhere to collect data on pediatric patients who had been diagnosed with ANE between 2023 and 2025.

After analyzing data on 41 patients from 23 U.S. pediatric hospitals, the team found that influenza-associated ANE carried a high risk of morbidity and mortality. Although most children were previously healthy and didn’t have a significant medical history prior to diagnosis, Wilson-Murphy and her colleagues found that influenza-associated ANE had a 27 percent mortality rate. Those patients died within an average of just three days of exhibiting symptoms, typically from brain herniation.

Of the 30 children who survived influenza-associated ANE, several still experienced neurological difficulties such as epilepsy three months later. Likewise, just 43 percent had regained the ability to walk unassisted.

“While rare, ANE is potentially devastating and can progress very quickly. It is incredibly important for providers to be able to recognize ANE and to act immediately, as rapid treatment may save lives and minimize long-term difficulties,” says Wilson-Murphy. “Vaccination may be important in helping to prevent ANE.”

Vaccination remains key

In addition to shedding light on the severity of influenza-associated ANE, the study highlights the importance of vaccinating children against the flu. Of the 41 patients included in the review, only six had received an age-appropriate flu vaccine for the season during which they developed influenza-associated ANE. Only one of the 11 children who died had received a flu shot. These findings support those from previous research, including a large Japanese epidemiologic study, which showed that mass vaccination of school-aged children significantly reduced death from influenza-associated encephalopathy, likely through decreased community transmission.

Along with the role of flu vaccination in prevention, Wilson-Murphy and her colleagues point to the importance of prompt diagnosis and treatment of influenza-associated ANE. Because death occurred quickly in fatal cases, rapid, intense management of the condition — including neuroprotective critical care and immunotherapy — is key.

“There is still so much we have yet to learn about ANE, but we hope this study has helped raise awareness and pave the way for more surveillance and recognition and, ultimately, to advances in treatment,” says Wilson-Murphy.

Reference:

Influenza-Associated Acute Necrotizing Encephalopathy (IA-ANE) Working Group. Influenza-Associated Acute Necrotizing Encephalopathy in US Children. JAMA. Published online July 30, 2025. doi:10.1001/jama.2025.11534.

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Dapagliflozin reduced mortality risk in aortic stenosis patients undergoing TAVI: Study

A new study published in The New England Journal of Medicine showed that daily dapagliflozin dramatically reduced the risk of death or deteriorating illness among patients with heart failure (HF) at one year following transcatheter aortic valve implantation (TAVI).

Since patients with valvular heart disease have been mostly excluded from randomized studies of the medicine, dapagliflozin (Farxiga; AstraZeneca), an SGLT2 inhibitor, has not yet been explicitly evaluated in TAVI. It is advised in heart failure regardless of ejection fraction. Additionally, TAVI patients are often older, and studies prefer to exclude this demographic. Thus, this study by Sergio Raposeiras-Roubin and colleagues to evaluate the function of dapagliflozin in TAVI.

This randomized, controlled study was carried out in Spain to assess the effectiveness of dapagliflozin (10 mg once day) in comparison to standard treatment alone for aortic stenosis patients receiving TAVI. Each patient had a history of heart failure along with at least one of the following conditions: diabetes, left ventricular systolic dysfunction, or renal insufficiency. At one year of follow-up, the main outcome was a composite of mortality from any cause and worsening heart failure, which was defined as hospitalization or an urgent visit.

Following TAVI, a total of 637 patients were randomly allocated to receive standard therapy alone, and 620 patients were randomly assigned to take dapagliflozin; 1222 patients were included in the primary analysis after exclusions.

Nearly, 91 patients (15.0%) in the dapagliflozin group and 124 patients (20.1%) in the standard-care group experienced a primary-outcome event. 55 patients (8.9%) in the standard-care group and 47 patients (7.8%) in the dapagliflozin group died from any cause. In 9.4% and 14.4% of the patients, respectively, heart failure worsened. The dapagliflozin group experienced a substantially higher incidence of genital infection and hypotension.

Overall, the effectiveness of dapagliflozin in the TAVI group emphasizes that these patients do not have a normal heart even when the outflow blockage has been relieved. When compared to conventional treatment alone, dapagliflozin significantly reduced the incidence of mortality from any cause and worsening of heart failure in older persons with aortic stenosis receiving TAVI who were at high risk for heart-failure events.

Source:

Raposeiras-Roubin, S., Amat-Santos, I. J., Rossello, X., González Ferreiro, R., González Bermúdez, I., Lopez Otero, D., Nombela-Franco, L., Gheorghe, L., Diez, J. L., Baladrón Zorita, C., Baz, J. A., Muñoz García, A. J., Vilalta, V., Ojeda-Pineda, S., de la Torre Hernández, J. M., Cordoba Soriano, J. G., Regueiro, A., Bordes Siscar, P., Salgado Fernández, J., … Ibáñez, B. (2025). Dapagliflozin in patients undergoing transcatheter aortic-valve implantation. The New England Journal of Medicine. https://doi.org/10.1056/nejmoa2500366

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