Category: 8. Health

A recent study has highlighted the intense impact of grief on individuals, demonstrating that the sorrow following the death of a loved one can significantly increase the risk of death over a decade.

The study, published in the journal Frontiers in Public Health, was conducted by researchers at Aarhus University in Denmark and followed 1,735 bereaved relatives for 10 years, revealing alarming statistics tied to the intensity of grief experienced, CNN reported.

The researchers categorised participants into “low” and “high” grief symptom groups. Their findings showed that 26.5% of those with high grief symptoms — characterised by emotional numbness, feelings of meaninglessness, and identity confusion — died during the study period.

In contrast, only 7.3% of those experiencing milder grief symptoms passed away.

“High levels” of grief were defined as experiencing more than half of the nine identified symptoms, including emotional numbness, feelings of meaninglessness, difficulty accepting the loss, and confusion over one’s identity.

Participants completed questionnaires at the study’s outset, then again six months and three years after their bereavement, providing a detailed picture of their emotional state.

The study also observed increased interaction with the healthcare system among those with high grief symptoms, noting higher use of antidepressant medication, mental health services, and primary care.

“Those with a high grief trajectory seem to be a vulnerable group of relatives already before the death, with need for special attention,” Nielsen told CNN via email.

“(They) may need additional support. They may experience distress and have difficulties coping with the situation,” she said, pointing to previous studies that have highlighted low socioeconomic status, poor self-reported health, and higher symptoms of depression and anxiety as all contributing to overwhelming grief.

While this study didn’t specify causes of death, its findings align with existing research on how traumatic loss impacts physical health.

Cardiologist Sian Harding, professor emeritus of cardiac pharmacology at Imperial College London, who was not involved in the research, highlighted the study’s crucial “longitudinal perspective”.

She noted that while an acute effect of bereavement on heart health is well-known, this study demonstrates a prolonged, damaging impact that can manifest as heart disease and other ailments.

“It was not a particular surprise to me that this particular form of stress, while prolonged, has a damaging effect on the body. It can come out particularly as heart disease, but other things as well,” said Harding.

This prolonged stress from grief can lead to elevated blood pressure, increased cortisol levels, a higher risk of diabetes, and poor mental health.

The well-established “broken heart syndrome” — also called stress-induced cardiomyopathy or Takotsubo cardiomyopathy — a sudden weakening of the heart muscle, is a prime example of acute stress’s physical toll.

Findings from the latest study suggest that healthcare workers “may be able to discover distressed relatives early in the patient’s illness trajectory and offer follow-up,” said Nielsen.

There are about 70 million baby boomers in the United States, many now over age 65. As people age, rates of cardiovascular and cerebrovascular diseases rise, leading to more use of blood thinners such as warfarin. At the same time, older adults face a higher risk of head injuries and brain bleeding, especially after falls.

Falls are the leading cause of injury and death in older adults, causing 38,000 deaths and 3 million emergency department visits in 2021. The health care cost for non-fatal falls in this group reached $80 billion in 2020, up sharply from 2015.

While anticoagulants protect against heart and vessel problems, they increase the risk of serious bleeding, particularly, brain hemorrhages after head trauma. It is widely believed that supratherapeutic warfarin activity increases the chance of brain hemorrhage after trauma. Current guidelines call for extra monitoring and repeat brain scans for patients on warfarin after head injuries.

Warfarin is considered especially challenging because maintaining safe blood-thinning levels – measured by the International Normalized Ratio (INR) – can be difficult. When INR is too high, bleeding risk rises significantly. Although many studies link high INR with increased bleeding risk, most have been small or limited.

To address a critical gap in emergency care, researchers at Florida Atlantic University’s Charles E. Schmidt College of Medicine conducted a new study to determine whether very high INR levels increase the risk of brain bleeding following a fall-related head injury in adults aged 65 and older who take warfarin. Conducted over one year at two Level I trauma centers in South Florida, the study examined 2,686 patients admitted to the emergency department due to a fall. Researchers compared outcomes between patients who were on warfarin before their injury and those who were not taking any blood thinners.

Results of the study, published in the American Journal of Emergency Medicine, found that being on warfarin, even at higher blood-thinning levels, did not significantly increase the risk of brain bleeding after blunt head trauma. In fact, patients with poorly controlled, low warfarin activity had the highest bleeding risk. This challenges common assumptions and underscores the importance of proper anticoagulation management rather than avoiding anticoagulants altogether.

Overall, about 11% of the patients studied experienced brain bleeding after head trauma. Among those not on blood thinners, about 6% had brain bleeds, compared to around 7% of patients on warfarin. Bleeding rates were similar between patients with INR levels above and below 3.0.

Notably, patients with lower-than-recommended INR levels had the highest rates of brain bleeding – nearly 20%. Those within or slightly above the therapeutic range had lower rates, and no brain bleeds occurred in patients with critically high INR levels (above 5).

Data from our study suggest supratherapeutic INR levels may not increase intracranial hemorrhage risk as much as we previously believed. This raises important questions about current emergency care protocols and how we monitor these patients. It’s critical to re-examine our approach to managing anticoagulation in older adults after head trauma to provide the safest, most effective care without unnecessary tests or hospital stays. It’s our hope that findings from our research will help improve patient outcomes while reducing health care costs.”

Richard Shih, M.D., senior author and professor of emergency medicine, FAU Schmidt College of Medicine

Researchers reviewed each patient’s medical history, physical exam findings, blood tests and CT scans, and followed up with phone calls and chart reviews two weeks after the injury to identify any delayed brain bleeding. The primary goal was to determine whether bleeding occurred within 14 days, confirmed by CT scans during the hospital stay. The study also looked at the type and severity of brain bleeds, patient outcomes, length of hospitalization, and survival rates.

“With clearer evidence on how blood-thinning levels impact outcomes, health care providers can develop more precise guidelines for follow-up care and monitoring – optimizing resources and improving patient management,” said Lisa Clayton, D.O., co-author and associate dean for graduate medical education and chair, FAU Department of Emergency Medicine. “In South Florida, where our older population is rapidly growing, this research is especially valuable. It could help emergency teams to make smarter, more balanced decisions that protect patients from serious complications without unnecessary interventions, advancing patient-centered care in a region facing this critical public health challenge.”

Study co-authors are Chelsea Caplan, first author and a medical student at the University of Miami Miller School of Medicine; Gabriella Engstrom, Ph.D., research assistant professor of emergency medicine; Mike Wells, Ph.D., research assistant professor of emergency medicine; Scott M. Alter, M.D., assistant dean for clinical research and associate professor of emergency medicine; and Joshua J. Solano, M.D., an associate professor of emergency medicine; all within the FAU Schmidt College of Medicine; Eric Bruno, M.D., University of Tennessee Health Science Center; and Timothy P. Buckley, M.D., an assistant professor of emergency medicine and quality improvement director, FAU Schmidt College of Medicine.

The research was supported by The Florida Medical Malpractice Joint Underwriting Association Grant for Safety of Health Care Services Grant RFA #2018-01, “Geriatric Head Trauma Short Term Outcomes Project (The GREAT STOP).”

A new drug candidate may work to prevent a common type of fatty liver disease.

The disease, metabolic dysfunction-associated steatotic liver disease (MASLD), sometimes leads to cirrhosis and liver cancer.

Linked to obesity and diabetes, MASLD affects 38% of adults and is believed to be caused by the spread of senescent cells in the liver.

Also called “zombie cells,” these cells have stopped functioning but continue to live, attacking the liver, spreading toxins, and setting the stage for a number of related liver diseases.

In a study in Nature Aging, the newly developed drug called 753b targets and degrades two proteins that senescent cells rely on to survive.

In mice, the drug successfully reduced the amount of fat and scar tissue built up in the liver caused by the senescent cells.

“Chronic fatty liver disease is a global problem,” says corresponding author Liya Pi, assistant professor of pathology at Tulane University School of Medicine.

“Not only did the drug selectively target senescent cells and slow the progression of MASLD, it also halted the development of associated liver diseases as well as hepatocellular carcinoma.”

Hepatocellular carcinoma is the most common form of liver cancer, and the study found that treatment with 753b actually reduced the size of liver tumors in mice with MASLD, as long as the cancer was not fully established.

The drug candidate is part of a broad class of senescent cell-targeting drugs called senolytics. Pi says that 753b shows promise due to its selectiveness in only targeting harmful senescent cells that are attacking the liver.

“This is the first study showing this compound having a high efficiency in senolytic clearance,” Pi says.

“More research is needed but hopefully this is a potential tool that patients can one day use to control this disease.”

The study was a collaboration between Tulane University, the University of Texas Health Science Center at San Antonio, and the University of Florida.

Source: Tulane University

This transcript has been edited for clarity. 

Akshay Jain, MD: Greetings from Chicago. I’m Akshay Jain, endocrinologist from Vancouver, Canada. Joining us at the ADA 85th Scientific Sessions today, we’ve got a very special guest, Dr Athena Philis-Tsimikas, who is the corporate vice president at Scripps in San Diego. Welcome. 

Athena Philis-Tsimikas, MD: Thank you so much. Happy to be here. 

Jain: Dr Philis-Tsimikas is one of the lead investigators of the QWINT trial, looking at new basal insulin efsitora alfa. What do you think is the need to have another new insulin? 

Philis-Tsimikas: It’s a good question, because we have so many amazing new drugs that have come out and that we’re seeing here at the ADA this year. Despite that, we know that there are over 800 million people with diabetes across the world, just recently published, and that means that there’s still going to be many people that require insulin.

We know that about 50%-25% of people will still, at some point, require insulin. I do think that insulin remains relevant, and we need to have new ways to deliver and really make it easier for people to take insulin. 

Jain: That makes sense. Despite all the new medications, insulin’s not going anywhere. It’s still going to be the backbone for many people requiring optimal diabetes management. Tell us about the QWINT program. What are the studies talking about, and what are they evaluating? 

Philis-Tsimikas: The QWINT programs are interesting and exciting. You said it’s a basal insulin, but it’s actually a once-weekly basal insulin. As opposed to the once daily that we’ve had for a long time and newer once dailies that were longer, this now takes us even longer. 

Insulin efsitora was tested in the QWINT trials. It was tested in people naive to insulin, people already on insulin, and in type 1 diabetes— so both type 2 and type 1 diabetes — and looking to see if it was noninferior to daily basal insulin and even if it was superior. 

Jain: That’s great. What did the study show? 

Philis-Tsimikas: I was the lead author on QWINT-3, which was a basal insulin switch trial. For people already coming in on basal insulin, we switched them to go to either efsitora or degludec. At the end of 26 weeks, we showed that it was noninferior. They had a lowering of their A1c from about 7.8% down to about 7%. It was noninferior. They did not show superiority, but what an amazing finding to know that you could take insulin just once a week and still get your A1c down to just below 7%.

Jain: Remarkable ability to drop the injection burden, going from 365 shots a year to just 52 shots a year. That’s really uplifting. Where I work in Canada, we’ve got access to insulin icodec, which is a once-weekly insulin, and that is also helping improve patient outcomes. We are moving forward with our ability to give basal insulin with fewer shots.

In your studies, were there any patient reported outcomes that were evaluated? 

Philis-Tsimikas: There were. We did look at satisfaction questionnaires. Satisfaction questionnaires came out better for those who were on once-weekly insulin efsitora. In addition, we also looked at patient safety, so we wanted to make sure that, while you’re getting to those better A1cs, do you really have no difference in hypoglycemia? It did show that — for combined nocturnal, both level 2 and level 3 outcomes — there was no difference in terms of the hypoglycemia rates. 

Jain: That’s a really important thing. One very interesting thing that I saw at the presentation yesterday on the QWINT-1 study is that they looked at level 1 hypoglycemia. Do you want to share some of the results with our audience about that? 

Philis-Tsimikas: Sure. QWINT-1 was a very interesting study because it gave a fixed dose of this basal once-weekly insulin at intervals of every 4 weeks. If you needed an incremental increase, it increased from 100 to 150, to 250, up to 400.

Despite having this fixed-dose adjustment, there was no increase in the level 1 or the level 2/level 3 combined hypoglycemia episodes. It’s interesting because in all the other trials of once-weekly insulin, level 1 with icodec and efsitora, both were slightly more elevated in those groups. It’s very interesting that in the fixed-dose implementation we did not see that difference. 

Jain: I think that’s remarkable. The safety is very important. It’s paramount. Also, it gives more confidence to primary care, especially those who are a little shy of starting insulin. 

Now, one thing that I’d love to talk to you about is the loading dose concept. This is not something that one is aware of when you are using daily basil insulin. Can you tell us about the need for doing this loading and what exactly the loading entails? 

Philis-Tsimikas: Right, absolutely. This was found in both the icodec and the efsitora studies that we did. Because this has a very long half-life and it takes a while to get up to a steady state, we do need to give a one-time only starting dose. 

With efsitora, it was three times what the calculated weekly dose was. You take your daily dose, multiply it by seven to get your weekly dose, and then by three for that one-time starting dose. Icodec was similar in that you had to take it times seven, but then one and a half times, so you gave a 50% extra dose.

That starting dose allows you to get up a little bit faster so that you don’t run higher blood sugars during that first 2-3-week time period. 

Jain: That’s excellent. The other very interesting thing that I saw about the QWINT-1 study was that 76% of individuals were able to get to a dose with this fixed-dose regimen without requiring more than 400 units a week. It doesn’t require too much for that flexible dosing aspect. Do you want to share a little bit more about that? 

Philis-Tsimikas: I think that was absolutely an interesting part. The fact that you can manage the majority of patients with just this one insulin injection once a week without having to then further titrate in a very detailed way that can be difficult for the patient and the provider, right? So, 76% of the time is remarkable. 

Jain: I think one thing to also note is that, as clinicians, we are always aware that it’s a marathon, not a sprint, right? Sooner or later, as long as you’re up-titrating, you’ll get to the target range.

With the QWINT-1 protocol, for the first month, you’re continuing to stay on 100 units. I think it’s important to reassure the patients that we will be going up in a gradual manner, so that they’re not too worried that the sugar’s not coming down that quickly.

Philis-Tsimikas: Absolutely. If you think about it, for someone who’s insulin naive, that’s where they’ve been running. It might not even make a difference for them. 

Jain: Exactly. 

Philis-Tsimikas: For someone who’s been on insulin that we’re switching over, that might make a little bit of a difference but certainly not for that insulin-naive population.

Jain: Any final pearls of wisdom that you want to give to our audience? 

Philis-Tsimikas: Maybe just that for our patients who were on the study, they were all incredibly happy to be able to convert over to this once-weekly dose. Many did not want to stop, and they’re all looking forward to seeing when once-weekly insulin will be available — in the United States, at least. I know you are lucky to have it in Canada and other places in Europe. We’re looking forward to it in the United States as well. 

Jain: Thank you so much for joining us, Dr Philis-Tsimikas. 

Philis-Tsimikas: Thank you so much. 

Results from a phase 1 first-in-human dose-escalation study (NCT04872166) evaluating BTX A51 revealed the agent’s tolerability with manageable adverse events, alongside suppressed MCL1 expression in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS).^1,2

Brian J. Ball, MD, and colleagues wrote in the study¹ that “10% (3 of 31) patients experienced a complete remission with incomplete count recovery (CRi). Specifically, these patients had RUNX1 mutations and the CR/CRi rate for RUNX1-mutated patients receiving BTX A51 at efficacious doses (11 mg or higher) was 30%.” The median duration of response was 1.9 months (range 1.5-2.5), though all 3 responding patients discontinued treatment after relapse.

Thirty-one patients were enrolled between January 13, 2025 through February 28, 2022, to receive oral doses of BTX A51 ranging from 1 mg to 42 mg 3 days a week. Dosing schedules varied: 1 mg was given 5 days per week for 21 days over a 28-day cycle; 3 mg, 5 mg, 8 mg, 11 mg, 21 mg, and 42 mg doses were administered 3 days per week for 21 days over a 28-day cycle; and a 21 mg dose was also explored 3 days per week for 28 days over a 28-day cycle. Patients remained on treatment for a median of 24 days, with a range of 3 to 135 days.

The primary end points were safety, maximum tolerated dose, and recommended phase 2 dose based on the incidence of dose-limiting toxicities (DLTs) during cycle 1. Secondary end points included estimated preliminary efficacy, overall and event-free survival, pharmacokinetics, and pharmacodynamics.

Of the 31 patients, 28 had R/R AML and 3 patients had high-risk R/R MDS. The median age was 75 years (range, 22–84) and the median number of prior lines of therapy was 2 (range, 1-8). Overall, 97% had received prior venetoclax (Venclaxta) and hypomethylating agents and 43% exhibited no response after 2 lines of induction chemotherapy.

The majority (55%) of patients were male, 3 patients had prior allogeneic hematopoietic cell transplantation, and 12 (38%) harbored RUNX-1–mutated tumors.

Overall safety showed that all patients had at least 1 treatment-emergent adverse event (TEAE) of any grade with the most common occurring in 10% or more patients were nausea (67%), emesis (63%), hypokalemia (53%), and diarrhea (40%). Reported TEAEs of grade 3 or higher were febrile neutropenia (33%), anemia (33%), thrombocytopenia, and hypokalemia (23% each).

Investigators determined that 1 patient experienced a DLT during cycle 1 and 1 patient developed a grade 3 elevation in alkaline phosphatase level at the 21 mg dose that resolved 4 days after holding treatment. Another patient experienced encephalopathy and grade 3 hepatic failure with elevations in aspartate aminotransferase, alanine transaminase, and bilirubin, resulting in discontinuation of the 42 mg dose.

Overall, there were 11 deaths among patients during the study treatment and within 28 days of the last dose. Five of these deaths were attributed to disease progression. Six deaths occurred in the absence of overt disease progression due to lung infection, cardiac arrest, intracranial hemorrhage, fungal infection, and septic shock.

The investigators also performed in-vitro and ex-vivo studies on AML cell lines and primary patient samples to evaluated antileukemic activity in patients with RUNX1 mutant and wild type. They observed a decrease in the expression of oncogenes such as MYC and MDM2.

“Importantly, this oncogene suppression, accompanied by the downregulation of the anti-apoptotic protein MCL1, led to the activation of p53 or DNA damage response and subsequent cleavage of caspase 3, thereby inducing leukemia cell apoptosis,” the investigators wrote in their paper.

These findings were modest but encouraging and the next steps will be exploring the agent in combination with azacitidine and with azacitidine and venetoclax (Venclexta).

REFERENCES:

1. Ball B, Xiao W, Borthakur G, et al. Phase I first-in-human dose escalation study of the oral casein kinase 1α and cyclin dependent kinase 7/9 inhibitor BTX-A51 in advanced MDS and AML. J Hematol Oncol. 2025 Jul 15;18(1):73. doi: 10.1186/s13045-025-01724-z.

2. Ball B, Xiao W, Borthakur G, et al. Phase I first-in-human dose escalation study of the oral casein kinase 1α and cyclin dependent kinase 7/9 inhibitor BTX-A51 in advanced MDS and AML. Preprint. Res Sq. 2024;rs.3.rs-4954060. Published 2024 Oct 15. doi:10.21203/rs.3.rs-4954060/v1

As we mark World Hepatitis Day, WHO calls on governments and partners to urgently accelerate efforts to eliminate viral hepatitis as a public health threat and reduce liver cancer deaths.

Every 30 seconds, someone dies from a hepatitis-related severe liver disease or liver cancer. Yet we have the tools to stop hepatitis.”

Dr. Tedros Adhanom Ghebreyesus, WHO Director-General

Viral hepatitis – types A, B, C, D, and E – are major causes of acute liver infection. Among these only hepatitis B, C, and D can lead to chronic infections that significantly increase the risk of cirrhosis, liver failure, or liver cancer. Yet most people with hepatitis don’t know they’re infected. Types B, C, and D affect over 300 million people globally and cause more than 1.3 million deaths each year, mainly from liver cirrhosis and cancer.

Hepatitis D now classified as carcinogenic

The International Agency for Research on Cancer (IARC) recently classified hepatitis D as carcinogenic to humans, just like hepatitis B and C. Hepatitis D, which only affects individuals infected with the hepatitis B, is associated with a two- to six-fold higher risk of liver cancer compared to hepatitis B alone. This reclassification marks a critical step in global efforts to raise awareness, improve screening, and expand access to new treatments for hepatitis D.

“WHO has published guidelines on testing and diagnosis of Hepatitis B and D in 2024, and is actively following the clinical outcomes from innovative treatments for hepatitis D,” said Dr Meg Doherty, incoming Director of Science for Health at WHO.

Treatment with oral medicine can cure hepatitis C within 2 to 3 months and effectively suppress hepatitis B with life-long therapy. Treatment options for hepatitis D are evolving. However, the full benefit of reducing liver cirrhosis and cancer deaths can only be realized through urgent action to scale up and integrate hepatitis services – including vaccination, testing, harm reduction, and treatment – into national health systems.

Latest data and progress

Encouragingly, the majority of low- and middle-income countries (LMICs) have strategic plans on hepatitis in place and progress in national hepatitis responses is increasing:

• in 2025, the number of countries reporting national hepatitis action plans increased from 59 to 123;
• as of 2025, 129 countries have adopted policies for hepatitis B testing among pregnant women, up from 106 reported in 2024; and
• 147 countries have introduced the hepatitis B birth dose vaccination, an increase from 138 in 2022.

However, critical gaps remain in service coverage and outcomes, as stated in the 2024 Global Hepatitis Report:

• testing and treatment coverage remain critically low; only 13% of people with hepatitis B and 36% with hepatitis C had been diagnosed by 2022;
• treatment rates were even lower – 3% for hepatitis B and 20% for hepatitis C – well below the 2025 targets of 60% diagnosed and 50% treated; and
• integration of hepatitis services remains uneven: 80 countries have incorporated hepatitis services into primary health care; 128 into HIV programmes and just 27 have integrated hepatitis C services into harm reduction centres.

  The next challenge will be to scale up the implementation of prevention, testing and treatment coverage. Achieving WHO’s 2030 targets could save 2.8 million lives and prevent 9.8 million new infections. With declining donor support, countries must prioritize domestic investment, integrated services, better data, affordable medicines, and ending stigma.

Forging new partnerships

To mark World Hepatitis Day, WHO is partnering with Rotary International and the World Hepatitis Alliance to strengthen global and local advocacy. This year’s campaign “Hepatitis: Let’s break it down“ demands action to confront the rising toll of liver cancer linked to chronic hepatitis infections. It also calls for decisive steps to dismantle persistent barriers – from stigma to funding gaps – that continue to slow progress in prevention, testing, and treatment.

Through a joint webinar and coordinated outreach, the partnership underscores the vital role of civil society and community leadership, alongside governments, in sustaining momentum and accelerating progress toward hepatitis elimination.

The presence of synthetic chemicals known as per- and polyfluoroalkyl substances (PFAS) may significantly raise the risk of developing type 2 diabetes (T2D) by causing metabolic disruptions.¹

The nested case-control study was published in eBioMedicine.

“PFAS are synthetic chemicals that resist heat, oil, water, and stains, and are found in countless everyday consumer products,” Vishal Midya, PhD, MStat, corresponding author and assistant professor of environmental medicine at the Icahn School of Medicine at Mount Sinai, said in a statement.¹ “Because they don’t break down easily, PFAS accumulate in the environment—and in human bodies. Our study is one of the first to examine how these chemicals may disrupt the body’s metabolism in ways that increase diabetes risk—particularly in diverse US populations.”

The researchers conducted an analysis within BioMe, a large, electronic health record-linked biobank of over 65,000 patients who have received primary care at Mount Sinai Hospital since 2007.² After excluding individuals with T2D at baseline, the team identified 180 incident T2D cases, which were equally distributed among Black, Hispanic, and White participants. Cases were matched by age, sex, and ancestry to 180 diabetes-free controls.

Using plasma samples collected approximately 6 years before diagnosis, the researchers measured levels of seven PFAS compounds and conducted untargeted metabolomic profiling.

The analysis found that each tertile increase in PFAS mixture exposure was associated with a 31% higher likelihood of developing T2D (OR, 1.31; 95% CI, 1.01-1.70), with perfluorooctane sulfonate contributing most strongly to this association. Several metabolites, including 5-hydroxytryptophan, glucoheptulose, and sulfolithocholylglycine, were linked to both higher PFAS exposure and increased odds of T2D, with the association involving sulfolithocholylglycine remaining statistically significant after correcting for multiple comparisons.

Pathway enrichment analysis revealed that PFAS exposure and T2D shared disrupted metabolic pathways, including glutamate metabolism, arginine and proline metabolism, and drug metabolism via cytochrome P450 enzymes.

However, the researchers acknowledged some limitations, including a small sample size that limited detection of sex- or ancestry-specific effects and the ability to assess newer short-chain PFAS. Because PFAS and metabolomic data were collected at the same time, causality could not be established. The researchers also noted that pathway analyses should be interpreted with caution due to database limitations and potential false discoveries. Lastly, residual confounding, such as diet or reproductive history, may also have influenced results.

Despite these limitations, the researchers believe the findings suggest a potential metabolic mechanism through which PFAS may influence diabetes risk.

“This research leverages an exposomics framework to characterize environmental impacts and associated metabolic alterations contributing to the development of type 2 diabetes in vulnerable US populations,” Damaskini Valvi, MD, PhD, MPH, senior author of this paper and associate professor of public health and environmental medicine at the Icahn School of Medicine at Mount Sinai, said in a statement.¹ “Findings can help us design more effective interventions for the early prevention of type 2 diabetes in the future, taking into account individuals’ exposures to environmental chemicals along with other well-known genetic, clinical, and lifestyle factors implicated in diabetes development. Mounting research suggests that PFAS are a risk factor for several chronic diseases, such as obesity, liver disease, and diabetes.”

References

1. “Forever chemicals” linked to higher risk of type 2 diabetes. Mount Sinai Health System. News release. July 20, 2025. Accessed July 29, 2025. https://www.newswise.com/articles/forever-chemicals-linked-to-higher-risk-of-type-2-diabetes

2. Midya V, Yao M, Colicino E, et al. Exposure to per- and poly-fluoroalkyl substances in association to later occurrence of type 2 diabetes and metabolic pathway dysregulation in a multiethnic US population. eBioMedicine. July 20, 2025. Accessed July 29, 2025. https://www.thelancet.com/journals/EBIOM/article/PIIS2352-3964(25)00282-8/fulltext

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Rapid at-home testing for skin cancer could now be possible, with researchers at the University of Michigan developing a silicone patch to do just that.

The ExoPatch, which contains star-shaped microneedles, successfully distinguished between melanoma and healthy skin in mouse skin tissue and pig skin samples, in a study funded by the National Institutes of Health. The research is published in Biosensors and Bioelectronics.

How the ExoPatch works

The ExoPatch features many microneedles, measuring just 0.6 mm long and at a width of less than 100 nanometers (0.0001 mm) at their tip.

“The star-shaped needles make puncture easier and less painful, but they are so small that they only go through the top-most layer of the skin, the epidermis, and do not draw blood,” explained Sunitha Nagrath, the Dwight F. Benton Professor of Chemical Engineering at U-M and the co-corresponding author of the study.

These microneedles are coated with a gel containing Annexin V, a protein that binds to exosomes from the interstitial fluid that fills the spaces between cells in the epidermis.

Once thought to be cellular “trash”, exosomes actually contain important DNA and RNA that play a role in cell-to-cell communication. Cancer cell exosomes can contribute to tumor spread, making their detection an early indicator of disease.

When applied to the skin for 15 minutes, the microneedles penetrate the epidermis without drawing blood. After removal, the patch is dissolved in an acidic solution to release the captured exosomes. A test strip dipped into this solution displays two lines if melanoma exosomes are present or one line if absent, functioning similarly to at-home COVID-19 tests.

Positive results in proof-of-concept tests

The ExoPatch was first tested on pig skin, chosen for its similarity to human skin. Imaging confirmed that the microneedles penetrated between 350 and 600 nanometers, within the epidermis but above the dermis. For scale, the human epidermis on the forearm is roughly 18,300 nanometers thick.

The device was then tested on mouse skin samples, half of which contained melanoma cells, in order to test whether the ExoPatch could capture melanoma exosomes from skin tissue.

After a 15-minute application window, the ExoPatch was removed and microscopy images were used to confirm that exosomes had been extracted using the microneedles. Following this, the ExoPatch was dissolved and processed as-intended with the test strips. 

The ExoPatch was found to have collected 11.5 times more exosomal protein from melanoma samples than from healthy tissue, with the test strips producing a line 3.5 times darker for melanoma-positive samples.

Future work

According to the researchers, the next step to move this technology forward is conducting a pilot study in humans, followed by a series of clinical trials. If successful, the ExoPatch could be a rapid advancement for at-home melanoma testing – allowing individuals to detect the most aggressive form of skin cancer early, without a biopsy or blood draw. 

“A fair-skinned person with moles must go to the doctor about every six months to send off a biopsy to see if they’re malignant or benign. With this test, they could instead test at home, get the results right away and follow up with a dermatologist for a positive result,” Nagrath said. 

The researchers also suggest that modifying the gel coating could potentially allow for the detection of exosomes associated with other cancers, including lung, breast, colon, prostate and brain cancer.

“This is the first patch designed to capture disease-specific exosomes from fluid under the skin. The potential applications are huge,” said Nagrath.

Reference: Smith SM, Kumari A, Marvar JP, Onukwugha NE, Kang YT, Nagrath S. Stellate silicon microneedles for rapid point-of-care melanoma exosome isolation and detection via a lateral flow assay. Biosens Bioelectron. 2025;285:117560. doi: 10.1016/j.bios.2025.117560

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In this study, we found that RDW is related to short- and long-term all-cause mortality in patients with AP and sepsis in the MIMIC-IV database. Cox regression analysis indicated that, even after adjusting for variables, RDW remained significantly related to the primary clinical outcomes, with the differences reaching statistical significance. In our sensitivity analysis restricted to patients without anemia, RDW remained significantly associated with 28-, 90-, and 365-day mortality in univariate Cox regression. However, this association lost statistical significance after adjustment for covariates in the multivariate model. This may be attributed to the reduced sample size in the non-anemic subgroup, which may have limited the statistical power to detect significant associations, particularly after adjustment for multiple covariates. However, further prospective studies with larger non-anemic populations are needed to validate these findings.

The RCS analysis in our study revealed specific turning points for RDW at 12.9%, 17.7%, and 17.7% for 28-, 90-, and 365-day mortality, respectively, suggesting a nonlinear association between RDW and mortality risk. Although we did not perform subgroup analyses based on these thresholds due to limited sample size, these values may hold important clinical significance. For instance, RDW levels exceeding 12.9% could serve as an early warning marker for clinicians to identify patients at increased risk of poor outcomes. Incorporating such thresholds into clinical protocols could potentially escalate care for high-risk patients. Moreover, these turning points may inform future risk stratification models and facilitate individualized prognostic assessments. Further prospective studies and multicenter cohorts are warranted to validate the prognostic utility and generalizability of these RDW thresholds. Establishing evidence-based cutoffs may ultimately support the integration of RDW into routine prognostic scoring systems for acute pancreatitis with sepsis.

Subgroup analyses revealed that both race and gender may modify the prognostic significance of RDW. The association between high RDW and long-term mortality was not significant in Black patients, in contrast to White and Other racial groups. This may reflect racial differences in baseline RDW distributions [25]. Additionally, the stronger association of RDW with short-term mortality in male patients raises the possibility of sex-based physiological or hormonal differences affecting erythropoiesis [26]. These findings suggest that RDW may be interpreted in the context of patient demographics.

In previous studies, RDW has been shown to be related to many diseases, such as ischemic stroke, carotid atherosclerosis, abdominal aortic aneurysm rupture, and cerebral embolism [12, 27]. Chen et al. [28] showed that in patients undergoing cardiac surgery, elevated RDW was associated with higher 28-day mortality. In addition, RDW is associated with a prognosis of cardiac arrest, heart failure, respiratory failure, and acute kidney injury [29,30,31,32]. Recent studies have also reported that RDW is associated with the prognosis of patients with COVID-19 and kidney failure [33, 34]. Moreover, RDW has been shown to serve as a prognostic marker in critically ill patients when used in combination with other clinical indicators [35].

In the study of He et al. [17], the AUC value of RDW for predicting in-hospital mortality of AP patients was lower than that of BISAP and SOFA. Our study demonstrated that the AUC for RDW was higher than that for SIRS and BISAP. RDW exhibited comparable or superior predictive performance relative to conventional scoring systems such as BISAP and SIRS, particularly in predicting long-term mortality. Although the AUC of RDW was lower than that of the SOFA score, this difference reached statistical significance only at 28 days and was not significant at 90 or 365 days. This suggests that RDW performs comparably to SOFA in predicting long-term mortality. However, these comparisons should be interpreted cautiously, as RDW is a single biomarker while these scores incorporate multiple clinical dimensions.

The possible mechanisms of occurrence in this study may be partly explained by the following three points. Firstly, AP is an acute inflammatory disease caused by auto-digestion of the pancreatic parenchyma; the pathogenesis involves activation of gastrointestinal enzymes, the kinin system, pancreas damage, and inflammation [36, 37]. In patients with sepsis, increased tissue kallikrein [38] may exacerbate endothelial hyperpermeability [38], which exacerbates the inflammatory response. Elevated levels of inflammatory cytokines and altered iron metabolism may lead to impaired erythropoiesis, leading to elevated RDW levels [39]. Secondly, one of the important pathogenesis of AP is pancreatic microcirculatory dysfunction [40]. When microcirculatory dysfunction is present, local hypoxia may be exacerbated, and the flow of RBC through the microvasculature may be impaired, leading to increased differences in red blood cell morphology, which may cause an elevated RDW [8, 41, 42]. Thirdly, chronic or persistent inflammation may lead to oxidative stress and nutrient imbalances, including increased utilization of intracellular iron and depletion of vitamin B12. These factors may suppress effective erythropoiesis and further contribute to variability in red blood cell morphology [9].

The advantage of this study is that RDW, as a single, easily accessible marker, can be used to predict clinical results in patients with AP and sepsis. Previously, BISAP, SIRS, and SOFA were key scores for assessing the prognosis of AP and sepsis, which have been demonstrated in several studies [21,22,23]. Our study showed that RDW retains strong predictive ability compared to BISAP and SIRS, and it performs similarly to SOFA in predicting long-term mortality. Many indicators have been used to predict the prognosis of AP in some recent literature. For example, serum lactate, triglyceride glucose- body mass index, and phosphorus-to-calcium ratio may be associated with the prognosis of AP [43,44,45]. Relying on a single index to determine the prognosis of a disease may be flawed. In the future, these indicators are expected to combine to determine the prognosis of a disease more comprehensively. This may provide clinicians with new insight to help them identify patients at risk for poor prognosis.

However, this study still has some limitations. First, this study is retrospective in nature. Although significant associations were observed, these findings should be interpreted as correlations rather than proof of causality. This limitation also impacts the clinical applicability of our results. RDW may serve as a useful prognostic indicator, but it should not yet be used in isolation to guide clinical decisions without prospective validation. Second, despite adjusting for a wide range of potential confounding variables in Model 3, residual confounding due to unmeasured variables remains a possibility. For instance, the MIMIC-IV database does not capture certain relevant factors such as inflammatory markers (e.g., procalcitonin, interleukins), nutritional status, or use of medications like protease inhibitors and somatostatin. In addition, some variables related to AP were excluded due to the excessive number of certain missing values in the database, including height, neutrophils, CRP, HbA1c, HDL, LDL, triglyceride, and TC. These factors can influence both RDW levels and patient prognosis. The absence of such data could potentially bias our results, either overestimating or underestimating the true relationship between RDW and mortality. Third, our study used only the first RDW measurement at ICU admission, which limits the ability to assess prognostic value from dynamic changes. Prior studies suggest that rising or persistently high RDW levels may indicate worse outcomes [46]. However, due to limited follow-up RDW data in MIMIC-IV, we could not analyze trends. Nevertheless, future prospective studies should incorporate serial RDW monitoring to evaluate temporal patterns and their prognostic value. Approaches such as modeling dynamic RDW values, slope-based change metrics, or incorporating time-dependent covariates in survival models may provide deeper insights into the dynamic prognostic utility of RDW in critically ill patients with AP and sepsis. Fourth, due to the limitations of the database itself, only patients enrolled in MIMI-IV were used in this study, and our study lacks external validation. To enhance the clinical applicability of our findings, future studies should perform external validation using independent cohorts from different countries, healthcare systems, or care levels (e.g., non-ICU settings, emergency departments, or general wards). In particular, patient populations such as those with acute pancreatitis without sepsis or sepsis alone could help evaluate the condition-specific utility of RDW. Approaches should include assessment of both calibration (agreement between predicted and observed outcomes) and discrimination (e.g., AUC) using the same cutoff values identified in our analysis. Fifth, our study exclusively focused on patients with AP and sepsis. We did not include patients with AP without sepsis, nor those with sepsis alone. This selection may have introduced a degree of selection bias and limits our ability to determine whether the prognostic value of RDW is specific to the co-occurrence of both conditions or also applicable when each occurs independently. Sixth, the study is subject to selection bias, as patients included in the MIMIC-IV database were not randomly selected but rather admitted based on clinical need and available data. This may have resulted in overrepresentation of patients with more severe conditions, which could affect the generalizability of our findings. Additionally, information bias may be introduced due to the reliance on clinical documentation and electronic health records, where misclassification or incomplete data may have occurred. Seventh, the retrospective application of Sepsis-3 criteria using electronic health record data presents inherent challenges. In retrospective datasets such as MIMIC-IV, infection is often inferred indirectly—via timing of antibiotics or culture orders—which may not fully reflect clinical judgment. Eighth, our study focused solely on all-cause mortality without distinguishing between specific causes of death. It may mask distinct associations between RDW and specific causes of death, such as infection-related, cardiovascular, or pancreatitis-associated mortality. Ninth, treatment heterogeneity among patients was not fully accounted for in our analysis. Certain treatments—such as blood transfusions, iron or vitamin supplementation, nutritional therapy, and organ support interventions (e.g., continuous renal replacement therapy, mechanical ventilation)—may alter RDW values or modulate inflammation and erythropoiesis, thereby indirectly influencing the relationship between RDW and clinical outcomes [16, 47,48,49,50]. Future prospective studies should aim to collect detailed treatment-related data and consider advanced statistical methods such as propensity score adjustment or stratified analysis to more accurately isolate the prognostic role of RDW from treatment effects. Tenth, our study may be subject to temporal bias due to the long data collection period (2008–2022) covered by the MIMIC-IV database. Over this time span, significant changes in the management of both acute pancreatitis and sepsis likely occurred, including updates in sepsis definitions (e.g., Sepsis-3 in 2016), improvements in early fluid resuscitation strategies, organ support protocols, and infection control practices. These clinical advancements could influence both mortality outcomes and the systemic inflammatory milieu, potentially affecting RDW values and their prognostic relevance. Moreover, technological improvements in hematologic analyzers over the years may have contributed to variability in RDW measurements. In this study, we did not perform stratified analyses by time periods due to sample size constraints and the lack of consistent treatment documentation. However, future studies should consider stratifying patients by admission year or implementing time-adjusted models to assess whether the predictive value of RDW is temporally stable or modified by evolving clinical practices. Furthermore, we conducted a post-hoc power analysis using G*Power to evaluate whether our total sample size (n = 759) was adequate for logistic regression analyses. Assuming OR = 1.2, α = 0.05, Pr = 0.17, and total sample size = 759, the analysis confirmed that our study had sufficient power to detect significant associations between RDW and mortality outcomes. However, when performing subgroup analyses, patients of Black race had relatively small sample sizes. Post-hoc analysis revealed that in this subgroup, the power of the test was below the 0.8 threshold, indicating a risk of type II error. Clinically, this implies that non-significant findings in these subgroups should not be interpreted as definitive evidence of no association between RDW and mortality. Rather, they reflect the need for cautious interpretation and underscore the importance of conducting future studies with larger and more diverse populations. Improving representation of underrepresented groups such as Black patients is essential to ensure that prognostic tools like RDW can be equitably applied across all patient populations.