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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Patients undergoing dialysis before transplantation have increased diabetic retinopathy risk: Study

A new study published in the Nature Scientific Reports showed that compared to kidney recipients who got preemptive transplants, individuals who experienced dialysis prior to transplantation are at a higher risk of developing long-term visual problems, including dry eye and diabetic retinopathy.

For individuals with end-stage renal disease, kidney transplantation is the only proven therapy option, and its success rate has grown over time. The patient survival has increased and the rejection rate has decreased thanks to improvements in surgical methods, immunosuppressive medications, and excellent postoperative care. Uremia, anemia, and oxidative stress are metabolic variables that might lead to ocular consequences from renal disease.

Furthermore, the link between alterations in the retinal microvasculature and microalbuminuria, a symptom of kidney glomerulus damage, raises the possibility that endothelial dysfunction is happening concurrently in the kidney and retinal blood vessels. Thus, this study evaluated the long-term ocular issues and determine the variables influencing these difficulties in dialysis and preemptive kidney transplant patients.

Nearly, 548 individuals who had a full ophthalmologic examination at least a year following kidney donation were included. Two groups of patients were created: Group 1 consisted of individuals who had previously had dialysis, and Group 2 consisted of those who had not. Hypertension and diabetes mellitus were identified as possible causes of retinopathy. Refractive error, intraocular pressure (IOP), best corrected visual acuity (BCVA), and results from dilated fundus and slit-lamp exams were among the data gathered.

Pterygium, corneal calcification, arcus lipoides, macular drusen, hypertensive retinopathy, central serous chorioretinopathy (CSC), diabetic retinopathy, pinguecula, lens opacity, and refractive error were among the ocular abnormalities that were noted. Every patient was receiving mycophenolate mofetil, calcineurin inhibitors, steroids, and mTOR inhibitors as part of maintenance immunosuppressive treatment.

A total of 291 patients in Group 2 (without dialysis) and 257 in Group 1 (with previous dialysis) were enrolled in the study. The groups’ requirements for myopic and hyperopic correction were comparable. Group 1 had a noticeably higher prevalence of dry eye. There were no discernible variations in the rates of glaucoma, cataract, pterygium, arcus lipoides, or pinguecula.

While other posterior segment findings, such as macular drusen, hypertensive retinopathy, and CSC, were similar between groups, diabetic retinopathy was considerably more prevalent in Group 1. The most common ocular problems were retinopathy, cataracts, and dry eye The patients who had previously had dialysis were much more likely to develop diabetic retinopathy and dry eye.

Overall, patients who had dialysis before transplantation were more likely to acquire and advance diabetic retinopathy than those who received preemptive transplantation.

Source:

Çetinkaya Yaprak, A., Avanaz, A., Erkan Pota, Ç., Arabacı Tur, K. T., & Yaprak, M. (2025). Long-term ocular complications after kidney transplantation. Scientific Reports, 15(1), 15222. https://doi.org/10.1038/s41598-025-99847-3

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Surgery in kids with mild sleep-disordered breathing tied to fewer doctor visits, meds

Surgical removal of enlarged tonsils and adenoids in children with mild sleep-disordered breathing (SDB) appears to significantly reduce the frequency of medical office visits and prescription medicine use in this group, according to a clinical study supported by the National Institutes of Health (NIH). The findings, published in JAMA Pediatrics, show that the surgery, called adenotonsillectomy, was tied to a 32% reduction in medical visits and a 48% reduction in prescription use among children with a mild form of the condition.

SDB refers to breathing disturbances during sleep that can range from loud snoring to occasional breathing pauses. About 6 to 17% of children in the United States have it, and for those with moderate to severe cases, adenotonsillectomy is a standard treatment commonly used. It can help reduce breathing problems, minimize behavioral issues, and also lower the risk of high blood pressure, full-blown sleep apnea, and other problems that may occur if the condition is left untreated. A recent NIH-supported clinical trial showed that for children with mild SDB, the surgery helped lower blood pressure and improve sleep and quality of life.

In the new study, researchers sought to determine whether adenotonsillectomy in comparison to watchful waiting (non-intervention) with supportive care is associated with fewer health care encounters and prescriptions. To find out, the researchers analyzed data from a randomized clinical trial that involved 459 children and adolescents with mild SDB who were recruited between 2016 and 2021 and followed for one year. The participants were ages 3 to 12 and were studied at seven academic sleep centers in the U.S.

During the trial, half the participants received an adenotonsillectomy, and the other half received supportive care without surgery, which included standardized education on healthy sleep and lifestyle and referral for untreated allergies or asthma. An analysis after the 12-month study period found 32% fewer health care encounters and 48% fewer prescriptions used among participants who underwent adenotonsillectomy, compared to those who did not undergo the surgery. For every 100 children, this equates to 125 fewer health care encounters and 253 fewer prescriptions-including for pain, skin, and respiratory medications — administered during the first year following surgery.

The reduced health care encounters included fewer office visits and outpatient procedures, particularly for sleep- and respiratory-related problems, but the mechanisms linking SDB treatment to health care outcomes are not clear.

Reference:

Bakker JP, Zhang F, Amin R, et al. Adenotonsillectomy and Health Care Utilization in Children With Snoring and Mild Sleep Apnea: A Randomized Clinical Trial. JAMA Pediatr. Published online March 17, 2025. doi:10.1001/jamapediatrics.2025.0023

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Optimizing One-Lung Ventilation: Prostaglandin E1 Advantage in Oxygenation and Safety, suggests study

In a recent study investigating the effects of prostaglandin E1 (PGE1) on reducing inspired oxygen concentration during one-lung ventilation (OLV), several key findings and outcomes were identified. The study included 120 patients undergoing thoracic surgery, randomly assigned to four groups receiving different FiO2 levels and PGE1 nebulization. The primary outcome was oxygenation during OLV, with secondary outcomes including inflammatory markers, postoperative complications, and hospital stay duration.

Results and Impacts of PGE1 Administration

The results showed that pre-OLV nebulization of PGE1 reduced the required FiO2 during OLV, leading to improved oxygenation and lower incidence of hypoxemia. The nebulized PGE1 groups exhibited delayed decreases in PaO2 and improvements in PaO2/FiO2 ratio compared to the control group. Furthermore, PGE1 inhalation resulted in lower Qs/Qt, reduced inflammatory cytokine levels, and improved clinical pulmonary infection scores. The study concluded that the combined impact of reduced FiO2 and PGE1 administration decreased the risk of hypoxemia and systemic inflammatory responses during OLV.

Importance of Lung Protection and Oxygenation Management

Additionally, the study highlighted the importance of lung protection and oxygenation management during OLV. Clear guidelines on optimal FiO2 levels during OLV are currently lacking, emphasizing the need for strategies to minimize oxidative stress while ensuring adequate oxygenation. The study findings supported the use of PGE1 to optimize oxygenation and reduce systemic inflammation by lowering FiO2 requirements during OLV.

Study Limitations and Recommendations for Further Research

However, the study also identified limitations that warrant further investigation. These include the need for larger sample sizes focused on postoperative complications, exploration of different PGE1 doses, and validation in populations with impaired lung function. Future studies should aim to explore long-term outcomes, diverse PGE1 doses, and the applicability of the recommended regimen across various patient populations.

Conclusive Findings on PGE1 Administration

In conclusion, the study demonstrated that pre-OLV PGE1 administration reduces the required FiO2 during OLV, leading to improved oxygenation, decreased hypoxemia risk, and lowered systemic inflammatory responses. This approach holds promise for optimizing patient outcomes during thoracic surgery by balancing oxygenation needs and minimizing oxidative stress-related complications associated with high FiO2 levels.

Key Points

– Pre-OLV nebulization of prostaglandin E1 (PGE1) reduced the needed FiO2 during one-lung ventilation (OLV), enhancing oxygenation and decreasing hypoxemia.

– Patients receiving PGE1 showed delayed decreases in PaO2, improved PaO2/FiO2 ratio, lower Qs/Qt values, reduced inflammatory cytokine levels, and better clinical pulmonary infection scores.

– Lung protection and oxygenation management during OLV are crucial, with the study underlining the lack of clear guidelines on optimal FiO2 levels.

– The study suggests that PGE1 administration can optimize oxygenation, lower systemic inflammation, and diminish hypoxemia risk by reducing FiO2 requirements during OLV.

– Study limitations include the need for larger sample sizes, exploration of different PGE1 doses, and validation in populations with impaired lung function.

– Conclusively, PGE1 administration pre-OLV holds promise in enhancing patient outcomes during thoracic surgery by balancing oxygenation requirements and minimizing complications related to high FiO2 levels.

Reference –

Lingxi Xing et al. (2025). The Impact Of Different Inspired Oxygen Concentrations Combined With Nebulized Prostaglandin E1 On Oxygenation In Patients Undergoing One-Lung Ventilation: A Randomized Controlled Trial. *BMC Anesthesiology*, 25. https://doi.org/10.1186/s12871-025-03081-3.

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Semaglutide and Liraglutide linked to Elevated Risk of Optic Nerve Damage in Seniors With Type 2 Diabetes: JAMA

USA: A recent research letter published in JAMA Ophthalmology has identified a potential link between certain glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and an elevated risk of nonarteritic anterior ischemic optic neuropathy (NAION) in older adults with type 2 diabetes. The study, led by Kin Wah Fung from the Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, found that semaglutide and liraglutide were particularly associated with higher risks among this drug class.

NAION is the second most frequent cause of vision loss due to optic nerve damage, with advanced age and long-standing type 2 diabetes recognized as major risk factors. Building on previous reports suggesting an association between semaglutide and NAION, the researchers conducted an extensive observational cohort study using data from Medicare enrollees aged 65 years and above who were prescribed antidiabetic medications between 2007 and 2021.

The study led to the following findings:

  • The study analyzed data from over 3.8 million patients with type 2 diabetes.
  • Around 15% of these patients received GLP-1 receptor agonists.
  • Semaglutide (4.9%) and liraglutide (4.2%) were the most commonly prescribed GLP-1 RAs.
  • During a median follow-up of 3.7 years, 0.2% of patients developed nonarteritic anterior ischemic optic neuropathy (NAION).
  • Use of GLP-1 RAs as a class was associated with a higher risk of NAION compared to other second-line antidiabetic drugs.
  • Semaglutide (HR 1.39) and liraglutide (HR 1.25) showed the strongest associations with NAION.
  • The median time between starting GLP-1 RA therapy and NAION diagnosis was 3.3 years.
  • Insulin use was linked to a higher risk of NAION compared with metformin only (HR 1.43).
  • Male sex, White race, and dual Medicare-Medicaid eligibility were associated with increased risk.
  • Rural residence and a history of diabetic retinopathy, chronic kidney disease, or obstructive sleep apnea were the additional risk factors.
  • The use of amiodarone, an antiarrhythmic medication, was also linked to elevated risk.
  • Age did not appear as a significant variable, likely due to the narrow age range of the cohort.

The findings reinforce earlier studies that flagged semaglutide as a potential risk factor for NAION, though the current analysis draws on a substantially larger patient base and a greater number of NAION cases. The researchers noted that excluding patients on metformin alone from the reference group was crucial to avoid overestimating the adverse effects of GLP-1 RAs, given that these individuals often have better glycemic control.

While the study provides important insights, the authors caution that certain limitations must be considered. These include reliance on diagnostic codes, the lack of precise data on the onset of type 2 diabetes before Medicare enrollment, and the restricted age range of participants, which may limit the applicability of findings to younger populations.

“Given the growing popularity of GLP-1 RAs for diabetes management and weight control, the researchers emphasize the need for further investigation into their ocular safety profile. They highlight that NAION, although rare, can result in permanent vision loss, making it essential for clinicians to weigh potential risks when prescribing these medications to older adults with type 2 diabetes,” the authors concluded.

Reference:

Fung KW, Baye F, Baik SH, McDonald CJ. GLP-1 RAs and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Older Patients With Diabetes. JAMA Ophthalmol. Published online July 31, 2025. doi:10.1001/jamaophthalmol.2025.2299

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FDA Approves First Vagus Nerve Stimulator for Rheumatoid Arthritis

SetPoint Medical’s vagus nerve stimulator has received FDA approval for treating moderate-to-severe rheumatoid arthritis (RA) in patients who do not respond to or cannot tolerate biologics or Janus kinase inhibitors. This marks the first electrical therapy approved for RA.

The SetPoint System is a first-of-its-kind neuroimmune modulation device for the treatment of adults living with moderate-to-severe RA who are not adequately managed by-or cannot tolerate-existing advanced RA therapies, such as biological and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs).

“The approval of the SetPoint System, the first-in-class neuroimmune modulation platform, represents a transformative milestone in the management of autoimmune diseases,” said Murthy V. Simhambhatla, Ph.D., CEO of SetPoint Medical. “We are committed to improving the health of people living with RA, and look forward to working with providers and payers to make our innovative therapy accessible to their patients. We plan to introduce the SetPoint System in targeted U.S. cities this year, followed by expansion across the country starting in early 2026.”

A Novel Therapy, Backed by Robust Clinical Research

More than 1.5 million Americans are living with RA, a chronic autoimmune disease in which the immune system mistakenly attacks healthy tissue, leading to joint pain, bone erosion, deformity, reduced mobility, and long-term disability. There is no cure for RA, and current treatment options are often limited by poor patient adherence and dissatisfaction. Only 25% of RA patients are satisfied with their therapy, and up to 50% discontinue their prescribed therapies within two years, largely due to inadequate or diminishing outcomes or intolerance to adverse effects.

The SetPoint System is an implantable, integrated neurostimulation device designed to deliver electrical stimulation to the vagus nerve, once daily, to activate the body’s innate anti-inflammatory and immune-restorative pathways. This groundbreaking therapy has the potential to transform the care for RA sufferers by offering a treatment option without immune-compromising risks.

FDA approval is supported by the results of the 242-patient randomized, double-blind, sham-controlled, RESET-RA study, that demonstrated the SetPoint System’s safety and efficacy in patients with moderately to severely active RA who had an incomplete response or intolerance to one or more biologic or targeted synthetic DMARDS.

“This is a landmark study in the treatment and care of rheumatoid arthritis,” said John Tesser, MD, FACP, FACR, MACR, a leading rheumatologist and national rheumatology principal investigator of the RESET-RA study. “The study met its primary efficacy endpoint of ACR20 at three months, with improvements observed in ACR response rates and disease activity metrics through 12 months of follow-up. 75% of patients in the study were free of biologic or targeted synthetic DMARDs at 12 months.”

The device placement procedure and stimulation therapy were well-tolerated, with a low rate of related serious adverse events (1.7%), and no observations of malignancies, major cardiac events, or serious infections related to the SetPoint Therapy.

“The approval of the SetPoint System highlights the potential of neuroimmune modulation as a novel approach for autoimmune disease, by harnessing the body’s neural pathways to combat inflammation,” said Mark Richardson, MD, PhD, Director of Functional Neurosurgery at Massachusetts General Hospital and Professor of Neurosciences at Harvard Medical School, and national surgical principal investigator in the RESET-RA study. “After implantation during a minimally invasive outpatient procedure, the SetPoint device is programmed to automatically administer therapy on a predetermined schedule for up to 10 years, simplifying care for people living with RA.”

The SetPoint System received Breakthrough Device Designation from the FDA, a program designed for technologies that offer potentially more effective treatment or diagnosis for debilitating diseases. The company is also planning to evaluate its platform for treatment of additional autoimmune indications, including multiple sclerosis and Crohn’s disease.

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Maternal Mortality and Analgesia: The Unseen Connection of Epidurals and Postpartum Hemorrhage, study finds

Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality globally, particularly affecting women with gestational hypertension due to their vulnerability to blood volume reduction. A recent retrospective cohort study analyzed the impact of epidural labor analgesia on blood loss within two hours post-delivery in this specific population, a critical period where up to 80% of total blood loss can occur.

Study Population and Methodology

The study included 1,903 participants who met the diagnostic criteria for gestational hypertension and were candidates for vaginal delivery. Data were meticulously collected from electronic medical records spanning nearly a decade. Comprehensive statistical analyses were performed using SPSS and R, encompassing both bivariate and multivariate logistic regression to explore associations with postpartum hemorrhage defined as blood loss of ≥300 mL. Results highlighted a prevalence of 16.9% of participants experiencing PPH of ≥300 mL. Multivariate logistic regression identified epidural analgesia as an independent risk factor for early postpartum hemorrhage (adjusted odds ratio (OR) = 1.30, 95% CI: 1.01–1.68, P = 0.039), alongside macrosomia and placental adhesion. In contrast, birth canal injury appeared protective against PPH. Notably, traditional risk factors such as age, BMI, and oxytocin use did not demonstrate significant associations with early blood loss. Prior studies have suggested that epidural analgesia does not increase PPH risk in non-hypertensive populations, raising questions about the unique pathophysiology associated with gestational hypertension. The mechanisms proposed include uteroplacental perfusion dysregulation due to vasospasm, which may impair uterine contractility, and potential disruptions to the vascular-coagulation pathway enhancing bleeding risk. Furthermore, the analysis reinforced previous findings where high BMI correlates with increased PPH risk. Critically, the definition of a ≥300 mL postpartum hemorrhage threshold was employed based on prior studies indicating its clinical relevance for early identification of PPH risk. However, the exclusive focus on the first two hours postpartum may overlook significant later blood loss, necessitating ongoing monitoring up to 24 hours.

Conclusions and Future Directions

The study concludes by calling for further prospective investigations to validate these findings and to optimize analgesic protocols to balance pain management with hemorrhagic risk in women with gestational hypertension, aiming to enhance maternal safety during childbirth.

Key Points

– Postpartum hemorrhage (PPH) is identified as the leading cause of maternal mortality worldwide, with heightened risk in women experiencing gestational hypertension due to susceptibility to substantial blood volume loss.

– A retrospective cohort study involving 1,903 women with gestational hypertension assessed the effect of epidural labor analgesia on blood loss within the first two hours post-delivery, a critical period for PPH occurrence. – Results showed a 16.9% prevalence of postpartum hemorrhage ≥300 mL, with multivariate logistic regression revealing that epidural analgesia (adjusted OR = 1.30, 95% CI: 1.01–1.68, P = 0.039), macrosomia, and placental adhesion were significant independent risk factors, while birth canal injury was protective.

– The investigation contradicted prior findings in non-hypertensive populations where epidural analgesia did not correlate with increased bleeding risk, suggesting a unique pathophysiological response in gestational hypertension that could affect uterine contractility and promote bleeding.

– The analysis reaffirmed that higher body mass index (BMI) is associated with increased PPH risk, accentuating the importance of considering obesity as a critical factor in monitoring bleeding risk during and after delivery.

– Recommendations emphasize the need for prospective studies to confirm these results and to refine analgesic strategies that effectively manage pain while minimizing hemorrhagic complications in patients with gestational hypertension, thereby improving maternal safety during labor.

Reference –

Weiguo Sun et al. (2025). Epidural Labor Analgesia Is A Potential Risk Factor For Increased Blood Loss Within Two Hours After Delivery In Women With Gestational Hypertension: A Retrospective Cohort Study. *BMC Pregnancy And Childbirth*, 25. https://doi.org/10.1186/s12884-025-07648-3.

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Womb lining problem identified as hidden cause of miscarriage in major UK study

Around one in six of all pregnancies are lost, mostly before 12 weeks, and each miscarriage increases the risk of another pregnancy loss. While the impact of embryo quality on miscarriage risk has been extensively studied, the endometrium (the womb lining) has largely remained a missing ‘black box’ in reproductive medicine.

In a study published today in Science Advances, researchers have uncovered a key piece of the miscarriage puzzle, tracing miscarriage risk back to a problem with the womb lining before pregnancy. This research offers a new scientific explanation as to why some women experience repeated pregnancy loss, even with healthy embryos.

“This is about identifying preventable miscarriages,” said lead author Warwick Medical School’s Dr Joanne Muter, whose work is funded by Tommy’s as part of its National Centre for Miscarriage Research. “Many women are told they’ve just had ‘bad luck’, but our findings show that the womb itself may be setting the stage for pregnancy loss, even before conception takes place.”

By analysing over 1,500 biopsies from more than 1,300 women, the team found that an essential biological process called the ‘decidual reaction’, which prepares the womb lining for pregnancy each month, often doesn’t progress properly in women with a history of miscarriage.

The endometrium’s role is to receive the embryo and support the development of the placenta throughout pregnancy. The decidual reaction transforms the womb lining into a supportive tissue for the embryo to implant. When it doesn’t fully activate or becomes dysregulated, it creates an unstable environment that, while still allowing embryos to implant, increases the risk of bleeding and early pregnancy loss.

Crucially, this isn’t random. The abnormal response in the womb lining, whether too weak or excessively strong, recurs across menstrual cycles for some women at a rate far greater than chance would predict. This suggests a consistent, measurable, and potentially preventable cause of miscarriage risk.

The research also shows that experiencing one miscarriage significantly makes it more likely that the womb lining will respond abnormally in future cycles, explaining why miscarriage often recurs.

Senior author Professor Jan Brosens, Professor of Obstetrics & Gynaecology at Warwick and UHCW NHS Trust and Scientific Director of the Tommy’s National Miscarriage Research Centre said: “It is well-established that chromosomal errors in embryos account for the rise in miscarriage rates in women older than 35 years. This study shows that each miscarriage increases the risk of an embryo implantation in an abnormal womb lining, regardless of age.

“Thus, the frequency of one of two events – abnormal embryo or abnormal decidual reaction – happening over hundreds of menstrual cycles determines the likelihood of miscarriage in each individual woman. Importantly, we now have the tools to screen for the risk of preventable miscarriage and to evaluate treatments that improve the womb lining before pregnancy.”

On the back of this research, the team has developed a diagnostic test to measure the molecular signals of a healthy or dysfunctional decidual reaction. The test is being piloted by UHCW NHS Trust at University Hospital, Coventry and has already supported the care of more than 1,000 patients.

Dr Jyotsna Vohra, Director of Research, Programmes and Impact at Tommy’s, said: “Far too often, women and birthing people who experience the trauma and devastation of recurrent miscarriage are left without answers.

“These findings from Tommy’s National Centre for Miscarriage Research pave the way not only for an explanation in some cases but more importantly for treatments that could prevent future pregnancy losses.”

One of the patients offered the new test, Holly Milikouris, says being given the opportunity to take part in the trial was life changing after she had experienced five miscarriages.

Holly’s diagnostic test revealed that her womb lining prepared poorly for pregnancy which had affected the development of her embryos. After undergoing treatment by Professor Brosens, she and her husband Chris went on to have two healthy children, three-year-old George and 17-month-old Heidi.

“My miscarriages were all ‘missed’, which means there were no symptoms to let us know there was a problem,” explained Holly, a civil servant from Cheshire. “We found out when I went for a scan and a grew to dread having scans.

“We felt lost and were beginning to accept that I might never successfully carry a pregnancy. The treatments that typically can help women who have experienced miscarriages hadn’t worked for us and each time we tried again we felt like we were rolling a dice with the baby’s life.

“Being given the opportunity to take part in this trial was life changing. For the first time the results of my biopsy were normal, and we went on to have not one, but two successful pregnancies. We will never be able to thank Professor Brosens enough and are hopeful that the results of this groundbreaking study will help many other families.”

Dr Tajnin Islam, a psychiatrist from Chester, had also experienced several failed pregnancies and felt she was running out of options with conventional methods before finding out about the clinic at University Hospital, Coventry. A test and biopsy carried out by Professor Brosens showed her womb lining also mounted a poor decidual reaction and after treatment she successfully retained a pregnancy.

Tajnin and her husband, a GP, now have a healthy 16-month-old son, Mivaan, who she describes as “a blessing.”

“I think this research and treatment is going to help a lot of women out there,” she said. “I’m over 40 and if I can have a baby then other women with my condition can also find the reason behind why they are having miscarriages and go on to have a baby. Thank you to Professor Brosens and the team.”

Current fertility diagnostics focus heavily on embryos, hormone levels, or genetic factors, often overlooking the role of the womb. This breakthrough positions the womb lining as a key player in early pregnancy health, opening new avenues for pre-conception care, personalised treatment, and emotional relief for patients who have long lived without answers.

Reference:

Joanne Muter et al. ,Stalling of the endometrial decidual reaction determines the recurrence risk of miscarriage.Sci. Adv.11,eadv1988(2025).DOI:10.1126/sciadv.adv1988.

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