Myelofibrosis belongs to a group of chronic blood cancers known as myeloproliferative neoplasms, in which the bone marrow overproduces different types of blood cells. In myelofibrosis specifically, the spongy interior of the bone that manufactures blood cells develops fibrotic scar tissue, progressively impairing its ability to produce enough healthy blood cells. The disease is rare, with estimates suggesting that up to six people per 100,000 are living with it. Despite its low prevalence, myelofibrosis carries serious consequences: individuals face an elevated risk of transformation to acute myeloid leukemia, as well as disease-related complications including enlargement of the spleen, the organ that helps fight infection and filter blood, and the development of blood clots.

For much of the modern treatment era, clinicians have relied on a relatively limited therapeutic arsenal. JAK inhibitors, a class of drugs that modulate signaling pathways driving the disease, can reduce spleen enlargement and ease other symptoms, and they remain the mainstay of pharmacologic management. The only potentially curative option, however, is allogeneic stem cell transplant, a procedure in which a patient’s faulty blood-forming cells are replaced with healthy stem cells from a donor. Because myelofibrosis is rare and its course can be unpredictable, approaches to treatment have historically varied substantially among clinicians, a problem the new guidelines were designed to address by synthesizing available evidence into practical, actionable recommendations.

Among the most consequential recommendations is extended molecular testing at diagnosis. Genetic profiling helps identify high-risk mutations that can inform prognosis and guide treatment selection, allowing clinicians to stratify patients more precisely than clinical criteria alone. The guidelines also call for early transplant consultation for higher-risk individuals who are receiving and responding to JAK inhibitors, a recommendation that reflects the delicate timing calculus of transplantation: referring too late can mean losing the window in which a patient is well enough to undergo the procedure, while referring patients who will never need it exposes them to unnecessary risk.

The guidance takes a nuanced position on JAK inhibitor use depending on disease risk. For lower-risk individuals with disease-related symptoms, the guidelines support the use of these agents to improve quality of life. Conversely, for higher-risk individuals without disease-related symptoms, the recommendations advise avoiding JAK inhibitors, a stance that underscores a central tension in myelofibrosis care: symptom relief must be weighed against disease control and the pursuit of curative intent in patients whose biology portends aggressive disease. This risk-adapted framework is one of the clearest signals the panel has sent about how personalized the management of this cancer should become.

Anemia receives dedicated attention in the guidelines, covering strategies for managing low blood counts that arise either from myelofibrosis itself or from JAK inhibitor therapy. Anemia is among the most burdensome manifestations of the disease, contributing to fatigue, transfusion dependence, and diminished survival, yet evidence for its optimal management has remained fragmented. By consolidating guidance in this area, the panel aims to give clinicians a more consistent framework for a problem that routinely complicates long-term treatment.

Another notable recommendation concerns low-dose aspirin for patients carrying the JAK2 V617F mutation, the most common genetic alteration in myelofibrosis. Because these patients face an elevated risk of blood clots, the guidelines address whether aspirin therapy can meaningfully reduce thrombotic complications in this specific molecular subgroup. The inclusion of a mutation-specific recommendation illustrates how deeply genetic testing now permeates the management of myeloproliferative neoplasms, extending beyond diagnosis and prognosis into preventive care.

Guideline panel chair Brady Stein, MD, professor of medicine at Northwestern University’s Feinberg School of Medicine, emphasized the practical intent behind the effort. According to Stein, the recommendations address questions that routinely come up for clinicians and patients managing myelofibrosis, and the hope is that they will enable hematologists to more confidently deliver better care to their patients. He also acknowledged that important gaps in evidence remain, expressing hope that the questions the panel asked can help set a future research agenda to further improve care for patients with this disease.

Indeed, the guidance explicitly identifies several areas where more research is needed. These include enhancing the prediction of which patients will benefit from specific treatments, establishing better approaches to myelofibrosis-related anemia, and clarifying the optimal timing for transplant. Each of these gaps reflects a broader challenge in rare-disease medicine: with limited patient populations, randomized trials are difficult to mount, and evidence often accrues slowly. By articulating a research agenda alongside its clinical recommendations, the panel has effectively mapped the frontier for the next generation of myelofibrosis studies.

For patients, the practical message is that the guidance clinicians use for treating myelofibrosis has changed. The new ASH guidelines emphasize individualized care based on a patient’s symptoms, spleen enlargement, anemia, genetic testing results, transplant eligibility, and personal preferences. Patients may want to ask their care team whether extended molecular testing is appropriate for them, whether a JAK inhibitor may help with symptoms or spleen enlargement, how anemia should be managed, and whether they should be referred for a stem cell transplant consultation. For those with the JAK2 V617F mutation, the guidelines also address the use of low-dose aspirin to help prevent blood clots. Additional resources, including snapshots, visual summaries, and teaching slides, are available through the Society’s website, offering patients and clinicians alike a shared foundation for navigating a disease that has long demanded more certainty than the evidence could provide.

Subject of Research: Clinical practice guidelines for the management of myelofibrosis, a rare bone marrow cancer

Article Title: ASH issues new recommendations to improve myelofibrosis care

Article References: ASH issues new recommendations to improve myelofibrosis care. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: myelofibrosis, American Society of Hematology, Blood Advances, JAK inhibitors, stem cell transplant, molecular testing, JAK2 V617F, anemia, aspirin, myeloproliferative neoplasm, clinical guidelines, hematology

The conclusion matters because older adults are precisely the population in which any chemopreventive effect would be most valuable. Cancer incidence rises steeply with age, and the majority of cancer diagnoses in high-income countries occur in people over 65. If a safe, inexpensive, widely available medication could meaningfully blunt that risk, the public health implications would be enormous. The new summary, formatted as a Bottom Line Summary intended to distill evidence for practicing clinicians, cuts against that hope. Its patient-facing message is blunt: for those age 65 and older, taking a low dose aspirin every day does not lower cancer risk.

To understand why the field arrived at this point, it helps to trace the arc of the aspirin hypothesis. Aspirin, or acetylsalicylic acid, works by irreversibly inhibiting cyclooxygenase enzymes, thereby suppressing production of prostaglandins and thromboxane. That mechanism explains its classic effects on pain, fever, inflammation, and platelet aggregation, and it also supplied a plausible biological route to cancer prevention. Chronic inflammation is a recognized contributor to tumor development, and prostaglandin signaling has been implicated in processes ranging from cell proliferation to angiogenesis. Epidemiologists observed that people who took aspirin regularly appeared to have lower rates of colorectal cancer in particular, and randomized trials designed to test aspirin for cardiovascular prevention began to report, on longer follow-up, apparent reductions in cancer incidence and mortality among those assigned to the drug.

That evidence base, however, was never as clean as the headlines suggested. The randomized trials that generated the most optimistic findings were generally designed and powered to detect cardiovascular events, not cancer, and their cancer results emerged from post hoc analyses with varying durations of follow-up. Observational studies, for their part, are vulnerable to confounding: people who take aspirin regularly differ in many ways from people who do not, including in health-seeking behavior, access to care, and screening rates. When the evidence was assembled systematically, the signal weakened. A 2020 updated systematic review and subgroup meta-analysis of 29 randomized clinical trials of long-term aspirin use for primary cancer prevention, cited in the new summary, examined the totality of trial data and found that the hoped-for protective effect was not consistently supported across cancer types, populations, and doses.

Large randomized trials provided some of the most decisive tests. The ASCEND study, published in the New England Journal of Medicine in 2018, randomized more than 15,000 people with diabetes to aspirin or placebo and found that while aspirin reduced serious vascular events, it also increased major bleeding, and it did not produce the kind of broad benefit that would justify routine use. The JPAD trial in Japanese patients with type 2 diabetes and its ten-year observational follow-up, also published in 2018, examined aspirin’s effects in a diabetic population and found no evidence of a cancer chemopreventive benefit. These trials, conducted in populations at elevated vascular risk who might have been expected to benefit most, consistently failed to demonstrate that low-dose aspirin prevents cancer, while repeatedly confirming its capacity to cause bleeding.

The bleeding issue is central to any risk-benefit calculation. Aspirin’s inhibition of platelet function is permanent for the lifespan of each platelet, and because platelets circulate for roughly a week to ten days, even low doses produce a sustained anti-hemostatic effect. In younger and middle-aged adults this translates into a modest but real excess of gastrointestinal hemorrhage and, less commonly, hemorrhagic stroke. In older adults the risk is amplified: age-related changes in the gastric mucosa, higher prevalence of Helicobacter pylori infection and other comorbidities, greater use of interacting medications such as anticoagulants and nonsteroidal anti-inflammatory drugs, and increased frailty all raise the likelihood that bleeding will be serious rather than merely inconvenient. A prevention strategy that offers no cancer benefit while adding bleeding risk to a 75-year-old is, on its face, difficult to defend.

Professional bodies have been moving in this direction for several years. In the United States, the Preventive Services Task Force in recent guidance narrowed its recommendation on aspirin for primary cardiovascular prevention, declining to recommend initiation in adults 60 and older and suggesting that any decision to start aspirin in adults 40 to 59 at high cardiovascular risk should be individualized. The cancer-prevention rationale, once a secondary argument in favor of aspirin, has largely fallen away as trial evidence accumulated. The new Bottom Line Summary consolidates that shift for the specific question of cancer prevention in older adults, aligning clinical guidance with the randomized evidence rather than with the earlier observational enthusiasm.

The summary also illustrates the value of the evidence-based medicine approach it represents. Rather than relying on mechanistic plausibility or on the accumulated weight of observational associations, Burke and Wheeler, with the SGIM Evidence-Based Medicine Task Force, distilled the randomized trial evidence into a single actionable conclusion. The authors report no funding related to the submission and no conflicts of interest, and the work was reviewed through the SGIM EBM Subcommittee. In a field where enthusiasm for a cheap intervention can outpace the data, such structured syntheses serve as a corrective, translating complex and sometimes contradictory trial literature into guidance that a busy primary care clinician can apply directly in the examination room.

For patients, the practical takeaway is straightforward. People aged 65 and older should not start taking daily low-dose aspirin with the expectation of preventing cancer, and those who are taking it for that purpose have grounds to discuss stopping with their physician. Aspirin retains clear, well-established roles, including in the treatment of pain and fever and in the secondary prevention of cardiovascular events in people who have already had a heart attack or ischemic stroke, where its benefits demonstrably outweigh its risks. What the accumulating evidence has removed is the justification for aspirin as a general-purpose preventive pill in healthy older people. The once-promising idea that a daily tablet could ward off both heart attacks and cancer has, for the older population, been narrowed by the data: the cancer-prevention half of that promise has not survived rigorous testing, and the decision to take aspirin should rest on individualized assessment of cardiovascular benefit against bleeding risk, not on the hope of avoiding a cancer diagnosis.

Subject of Research: Low-dose aspirin for primary cancer prevention in older adults

Article Title: EBM BLS: Low Dose Aspirin Does Not Reduce the Risk of Cancer in Older Adults

Article References: Burke, H. B., & Wheeler, S. G. (2026). EBM BLS: Low Dose Aspirin Does Not Reduce the Risk of Cancer in Older Adults. Journal of General Internal Medicine. https://doi.org/10.1007/s11606-026-10876-8

Image Credits: AI Generated

DOI: 10.1007/s11606-026-10876-8

Keywords: aspirin, cancer prevention, chemoprevention, older adults, geriatrics, primary prevention, evidence-based medicine, randomized trials, bleeding risk, Journal of General Internal Medicine, ASCEND trial, risk-benefit

The study enrolled 334 patients who had suffered what the researchers classify as high-risk non-disabling ischemic cerebrovascular events, abbreviated HR-NICE. This category covers transient ischemic attacks and minor strokes that do not leave patients disabled but carry a high probability of recurrence. The danger window is brutally short: the risk of another vascular event is highest within the first days and weeks after the initial episode, which is precisely when early neurological deterioration tends to strike. Patients were enrolled within 24 hours of symptom onset — a demanding logistical requirement that reflects how rapidly the therapeutic window closes. Once enrolled, they were randomly assigned in a one-to-one ratio to one of two dual antiplatelet regimens: low-dose ticagrelor at 60 milligrams twice daily plus aspirin, or clopidogrel plus aspirin.

The logic behind the comparison rests on a well-known weakness of clopidogrel. The drug is a prodrug, meaning it must be converted by liver enzymes into its active form before it can inhibit platelets. The critical enzyme, CYP2C19, is encoded by a gene that varies widely between individuals. People carrying so-called loss-of-function alleles — a variant that is especially common in East Asian populations, affecting a majority of Chinese patients — convert clopidogrel poorly or not at all. For these patients, standard clopidogrel-based therapy offers substantially weaker platelet inhibition, and previous studies have linked poor clopidogrel response to early neurological deterioration after acute ischemic stroke. Ticagrelor, by contrast, is a reversible P2Y12 receptor antagonist that does not require metabolic activation, so its antiplatelet effect is essentially independent of CYP2C19 genotype.

This pharmacological distinction has already reshaped stroke care in China. The CHANCE-2 trial, published in the New England Journal of Medicine in 2021, showed that in patients carrying CYP2C19 loss-of-function alleles, ticagrelor plus aspirin outperformed clopidogrel plus aspirin in preventing recurrent stroke within 90 days. But CHANCE-2 required rapid genotyping to identify carriers — a capability that many hospitals, particularly in resource-limited settings, simply do not have. The new trial was designed with this gap in mind. Rather than genotyping patients and treating only those with the resistant variant, the investigators asked a more pragmatic question: does low-dose ticagrelor beat clopidogrel in an unselected HR-NICE population, where a large proportion of patients would be expected to carry loss-of-function alleles?

The answer was a clear yes. Early neurological deterioration within seven days — defined as an increase of at least two points on the National Institutes of Health Stroke Scale, or a one-point increase in the motor subscore compared with baseline — occurred in 10.8 percent of patients receiving ticagrelor plus aspirin, compared with 22.2 percent of those receiving clopidogrel plus aspirin. That corresponds to a relative risk of 0.55, with a 95 percent confidence interval of 0.33 to 0.92 and a p-value of 0.023. In plain terms, the ticagrelor regimen roughly halved the odds that a patient’s neurological condition would worsen in the critical first week. The trial used an intention-to-treat analysis, the most conservative approach, and its open-label design with blinded endpoint adjudication means that while treating physicians knew which drugs patients received, the researchers assessing outcomes did not — a design that minimizes bias in the primary result.

The benefits extended well beyond the first week. At 90-day follow-up, 92.8 percent of patients in the ticagrelor group had achieved an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin Scale, the standard measure of post-stroke disability. In the clopidogrel group, the figure was 80.8 percent — a statistically significant difference, with a relative risk of 1.13 and a p-value of 0.002. The rate of major ischemic vascular events within 90 days also trended in favor of ticagrelor, at 6.6 percent versus 10.8 percent, though this difference did not reach statistical significance (relative risk 0.54; p = 0.085), likely reflecting the relatively small number of events in a trial of this size.

Just as important as the efficacy signal was the safety profile, because the perennial concern with intensified antiplatelet therapy is bleeding. Dual antiplatelet regimens walk a narrow line: they must suppress platelet aggregation enough to prevent clot propagation and recurrence, but not so much that spontaneous hemorrhage becomes a hazard. In this trial, any bleeding events occurred in 6.0 percent of the ticagrelor group versus 4.2 percent of the clopidogrel group — a difference that was neither statistically significant (p = 0.563) nor clinically alarming, particularly since all bleeding events in both groups were classified as mild. Rates of adverse events overall (12.6 percent versus 10.2 percent) and serious adverse events (0.6 percent versus 1.8 percent) were similarly balanced between the groups. The low 60-milligram twice-daily dose of ticagrelor, rather than the 90-milligram dose used in cardiac patients, appears to be the key to achieving potent platelet inhibition while keeping bleeding in check.

The trial’s design details reinforce the credibility of these findings. It was registered prospectively with the Chinese Clinical Trial Registry in February 2023, conducted across multiple centers, and approved by the ethics committee of the First Affiliated Hospital of Dalian Medical University, with all patients or their legal representatives providing written informed consent. The investigators adhered to the Declaration of Helsinki and Good Clinical Practice guidelines. The primary endpoint — early neurological deterioration — is a mechanistically meaningful outcome, because it captures the dynamic process of thrombus growth and new clot formation in the vulnerable cerebral circulation, rather than merely counting later recurrent strokes. By targeting this early window, the regimen intervenes at the moment when platelet-rich thrombi are most actively propagating.

Why does the result matter globally, and not only in China? The CYP2C19 loss-of-function variant is most prevalent in East Asian populations, but it is common elsewhere too, and clopidogrel resistance is a recognized problem wherever the drug is used. Moreover, the trial’s most practical implication is precisely that it does not require genotyping. The authors conclude that the regimen may provide a safe and effective alternative antiplatelet strategy for preventing early neurological deterioration in institutions lacking rapid genotyping facilities — a description that fits the majority of stroke centers worldwide. A physician confronting a patient with a high-risk minor stroke or TIA can start low-dose ticagrelor plus aspirin immediately, without waiting for genetic test results that may take days or simply be unavailable.

Cautions remain, as they always do with a single trial. The study was conducted in China, the sample size of 334 patients is modest, and the open-label design, while mitigated by blinded endpoint assessment, cannot eliminate all performance bias. The trend toward fewer ischemic vascular events at 90 days did not reach statistical significance, and longer-term outcomes beyond three months were not assessed. Broader international replication, ideally in populations with different baseline risks and genetic backgrounds, would strengthen the evidence base. Still, the magnitude of the effect on early deterioration — the single most feared event in the days after a minor stroke — combined with a clean bleeding profile, makes this one of the more consequential antiplatelet findings in recent stroke research. For patients in the fragile hours after a warning stroke, a cheap, widely available, genotype-independent drug combination that halves the risk of getting worse is exactly the kind of pragmatic advance that changes clinical practice.

Subject of Research: Low-dose ticagrelor plus aspirin versus clopidogrel plus aspirin for preventing early neurological deterioration after high-risk non-disabling ischemic cerebrovascular events

Article Title: Low-dose ticagrelor combined with aspirin for preventing early neurological deterioration in patients with high-risk non-disabling ischemic cerebrovascular events: a multicenter, prospective, randomized, open-label, clinical trial

Article References: Liu, J., Cao, H., Wang, M., Jiao, Y., Zhou, R., Tang, Y., Chen, R., Liu, X., Shen, J., Li, D., Tian, W., Gong, X., Zhang, B., Liu, Y., & Ji, X. (2026). Low-dose ticagrelor combined with aspirin for preventing early neurological deterioration in patients with high-risk non-disabling ischemic cerebrovascular events: a multicenter, prospective, randomized, open-label, clinical trial. Journal of Neurology, 273(10), Article 568. https://doi.org/10.1007/s00415-026-14094-4

Image Credits: AI Generated

DOI: 10.1007/s00415-026-14094-4

Keywords: ticagrelor, aspirin, clopidogrel, early neurological deterioration, minor stroke, transient ischemic attack, dual antiplatelet therapy, CYP2C19, randomized clinical trial, stroke prevention, P2Y12 inhibitor, functional outcome

Lynch syndrome arises from inherited mutations in DNA mismatch repair genes, leaving affected individuals with a significantly elevated lifetime risk of colorectal cancer as well as several other malignancies. For this population, prevention is not an abstract concept but a daily reality shaped by intensive surveillance programs, genetic counseling, and difficult decisions about risk-reducing interventions. The scientific case for aspirin in this context has been building for years. The landmark CAPP2 study demonstrated that acetylsalicylic acid can significantly reduce the long-term risk of colorectal cancer in people with Lynch syndrome, using a comparatively high daily dose of 600 milligrams. That evidence positioned aspirin as one of the few chemopreventive agents with robust data in a hereditary cancer setting, offering a low-cost, widely accessible complement to regular colonoscopic surveillance.

The picture grew even more promising with the recently published international CaPP3 study, which suggests that a much lower dose of 100 milligrams daily could deliver a similar cancer-preventive effect while causing fewer side effects, and in particular fewer bleeding complications, which have long been the principal concern associated with long-term aspirin use. The prospect of a practical, better-tolerated regimen is significant for a group that must weigh preventive benefit against decades of continuous medication. Dr. Robert Hüneburg, corresponding author of the new study and a senior physician at Medical Clinic I at the UKB who also conducts research at the University of Bonn, urged measured interpretation of the dose comparison. Since the statistical criteria for formal equivalence between the two studies were not met in all analyses, he noted, the results should still be interpreted with some caution. However, he added, the CaPP3 findings suggest that 100 milligrams daily could be a practical and better-tolerated option for many patients.

Against this backdrop of evolving evidence, the Bonn team set out to measure how much of the science has actually reached clinical practice. The LYNX survey enrolled 539 people with Lynch syndrome from across Germany and was designed before the publication of the CaPP3 results, then conducted between December 2025 and February 2026. That timing matters for interpretation: the responses reflect the use of acetylsalicylic acid based on the scientific evidence available at the time of the survey, primarily the higher-dose CAPP2 findings. Hüneburg emphasized that future studies must show whether the new findings on lower dosages will contribute to acetylsalicylic acid being used more frequently for cancer prevention. In other words, the survey captures a snapshot of care under the old evidence regime, and the lower-dose data may yet shift the calculus for both physicians and patients.

What the survey revealed was not ignorance or apathy but a paradox. Awareness of established prevention measures among respondents was exceptionally high: about 97 percent were familiar with the specific screening recommendations for Lynch syndrome, and nearly all undergo regular colonoscopies. Adherence to surveillance, the cornerstone of Lynch syndrome care, is therefore excellent. Yet when it came to aspirin, the numbers collapsed. Only 10.4 percent of respondents reported currently taking acetylsalicylic acid, and just 6.9 percent of the entire group specifically used it for cancer prevention in the context of Lynch syndrome. For a population in which a well-studied, inexpensive preventive agent exists, those figures represent a profound gap between evidence and everyday care.

The reasons patients gave for avoiding aspirin were revealing. According to Dr. Anne-Sophie Layritz, co-first author of the study and an assistant physician at Medical Clinic I at the UKB, the main reasons cited were a lack of prior engagement with the topic, concerns about side effects, and uncertainty regarding the scientific evidence. Each of these barriers points to a different failure point in the care pathway. A lack of engagement suggests that the topic is simply not being raised consistently during counseling appointments. Concerns about side effects reflect legitimate worries about gastrointestinal bleeding that the lower-dose CaPP3 data may help address. Uncertainty about the evidence indicates that patients perceive the scientific picture as unsettled, a perception that clearer, more structured communication from care teams could correct. None of these barriers suggests resistance to prevention itself.

Indeed, the same survey documented remarkable enthusiasm for novel preventive approaches. About three-quarters of respondents could, in principle, imagine participating in a study on a preventive mRNA cancer vaccine, a technology that has moved from pandemic fame to the frontier of oncology. After receiving additional information about the concept, that proportion rose to about 80 percent. More strikingly, more than 92 percent stated that they would want to receive such a vaccine if it were approved in the future. A majority of participants also accepted the possibility of being assigned to a placebo group in such trials and the inherent risk of side effects, both of which are common sticking points in clinical trial recruitment. Nicola Reents, co-first author of the study representing SemiColon, said these results show just how great the interest is among those affected in innovative prevention options and in actively participating in research.

Taken together, the LYNX findings do not indicate any fundamental reluctance toward cancer prevention among people with Lynch syndrome. Instead, the authors describe a significant implementation gap between scientific evidence, medical counseling, and actual application. The community is demonstrably willing to embrace prevention, whether through established tools like colonoscopy or through future innovations like mRNA vaccines, but the translation of aspirin data into routine counseling has lagged. According to the authors, early, understandable, and structured information, together with an individualized assessment of benefits and risks, is crucial to closing that gap. As the lower-dose evidence matures, the window is open for care teams to revisit how chemoprevention is discussed, ensuring that patients receive balanced, up-to-date guidance rather than leaving aspirin’s potential benefits unexamined.

The collaborative design of the study itself offers a model for how such gaps might be bridged. Support from the centers of the German Consortium Familial Colorectal Cancer and the partnership with the self-help organization SemiColon were of central importance to the project, allowing the researchers to reach many affected individuals and to contextualize both the research questions and the results from the patients’ perspective. Reents of SemiColon served as a co-first author of the publication, an unusual and telling arrangement that embedded the patient voice directly into the research process. Hüneburg emphasized that the project is a very good example of research that is conducted not just about, but together with, those affected. For a condition in which lifelong engagement with prevention determines outcomes, that participatory approach may prove as consequential as any single clinical finding, pointing toward a future in which the evidence, the counseling, and the patient’s own informed decision finally align.

Subject of Research: Aspirin chemoprevention uptake among people with Lynch syndrome

Article Title: Aspirin rarely used for colorectal cancer prevention

Article References: Aspirin rarely used for colorectal cancer prevention. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: Lynch syndrome, colorectal cancer, aspirin, chemoprevention, CAPP2 study, CaPP3 study, cancer prevention, mRNA cancer vaccine, implementation gap, genetic predisposition, University Hospital Bonn, patient survey

Colorectal cancer is the third most frequently diagnosed cancer worldwide, with an estimated 1.8 million new cases each year. Randomized controlled trials have already shown that aspirin can reduce colorectal cancer incidence in certain populations, and the United States Preventive Services Task Force has recommended low-dose aspirin for primary prevention in adults aged 50 to 59 who carry a ten-year cardiovascular disease risk of at least 10 percent. Yet questions of long-term adherence, contraindications, and the sheer scale of the disease mean screening and surveillance will remain essential. That is why researchers are increasingly interested in novel biomarkers that could flag cancer risk earlier and more precisely, and epigenetic aging measures are among the most promising candidates.

Epigenetic clocks are mathematical models that estimate biological age from patterns of DNA methylation, the chemical tags that attach to DNA and switch genes on or off without altering the underlying sequence. The best-known clocks, developed by Steven Horvath and Gregory Hannum in 2013, capture aging signals that are largely independent of cell division. But cancer is intimately a disease of uncontrolled mitosis, and that is where a newer family of biomarkers comes in. Mitotic clocks, including EpiTOC, EpiTOC2, and MiAge, are designed to estimate the cumulative number of cell divisions a tissue has undergone. EpiTOC tracks methylation gains at CpG sites within Polycomb group target genes that are typically unmethylated in fetal tissue but accumulate methylation with age, effectively counting stem cell replication errors. EpiTOC2 goes further, estimating the total number of stem cell divisions in a tissue, while MiAge represents the lifetime tally of cell divisions and has been found universally accelerated across thirteen cancer types, including colon adenocarcinoma.

Previous work on this same cohort, published in 2020 by Noreen and colleagues, reported that long-term aspirin users showed deceleration of conventional epigenetic age measures, specifically the Hannum, Horvath, and PhenoAge metrics, in the proximal colon but not the distal colon. What that study could not answer was whether aspirin’s effect extended to cell proliferation itself. Because the widely used clocks capture aging signals independent of mitosis, it was possible that aspirin’s relationship with epigenetic aging was entirely proliferation-independent. The new study, led by Jamaji C. Nwanaji-Enwerem of Emory University and the University of California, Berkeley, together with Chijioke Nze and Andres Cardenas, set out to close that gap by applying three mitotic clocks to the same decade-spanning dataset.

The data came from a publicly available NCBI Gene Expression Omnibus dataset comprising DNA methylation profiles from healthy colon mucosa biopsies collected at two timepoints, baseline and a ten-year follow-up. The researchers analyzed 112 samples from 28 healthy Polish women, 11 of whom never used aspirin and 17 of whom were long-term users, defined as taking aspirin at least twice per week for at least two years. Three participants who crossed over from non-use to long-term use during the study were excluded to keep the longitudinal comparison clean. Each participant had provided both proximal, or cecal, and distal, or sigmoid, colon biopsies at both timepoints, allowing the team to examine whether effects differed along the length of the colon. Genome-wide methylation was profiled using the Illumina Infinium MethylationEPIC BeadChip, and the mitotic clocks were computed from the normalized methylation values using published R code.

The statistical approach was deliberately careful. Because the mitotic clocks correlate strongly with chronological age, the researchers calculated age-independent intrinsic rates by dividing each clock value by the participant’s age, then derived residuals from linear mixed effects models adjusted for body mass index, polyp status, and DNA methylation batch, with a random intercept for each participant to account for repeated measures. They then used paired Wilcoxon signed rank tests to compare baseline and follow-up values within each aspirin group. All three clocks correlated significantly with chronological age, with coefficients ranging from 0.41 to 0.63, and the clocks correlated strongly with one another, with r values above 0.79 in both colon regions and an especially tight relationship between EpiTOC and EpiTOC2 exceeding 0.99.

The headline result was unambiguous. In the proximal colon of long-term aspirin users, the intrinsic rates of all three mitotic clocks decelerated significantly over the ten-year period: EpiTOC by a median of 0.0004 DNAm units, EpiTOC2 by roughly 16 cell divisions, and MiAge by about 3 cell divisions, with P values of 0.008, 0.009, and 0.002 respectively. No such deceleration was observed in non-users. In the distal colon, only MiAge showed a significant deceleration among long-term users. When the researchers compared the ten-year changes between the two groups directly, long-term users showed more negative median differences in the proximal colon for all three clocks, though these between-group comparisons did not reach statistical significance, likely a consequence of the small sample size and the unpaired nature of that analysis.

The findings dovetail neatly with the earlier report of aspirin-linked deceleration of Horvath, Hannum, and PhenoAge measures in the proximal colon, and they suggest that cell proliferation may indeed be part of the mechanism by which aspirin influences epigenetic aging. The proximal-distal split is itself intriguing. The right and left colon differ in embryonic origin and in the molecular pathways that drive tumor initiation: mismatch repair mutations are more common in right-sided tumors, while chromosomal instability dominates on the left. Some chemopreventive interventions, including aspirin, appear more robust in the proximal colon. The authors argue that future epigenetic aging studies of colorectal cancer should routinely report colon location-specific results rather than pooling the two regions.

Beyond the aspirin story, the paper issues a broader call to standardize a young and somewhat fragmented field. The Horvath and PhenoAge clocks were built from roughly 8,000 and 10,000 samples respectively, whereas EpiTOC was developed from just over 650 samples, and MiAge and EpiTOC2 from around 4,000 and 3,000. Differences in training data may explain why different clocks show different sensitivity to biological processes, a pattern the authors have observed elsewhere, including in a study of simulated long-duration space travel where only PhenoAge deceleration remained statistically significant. They recommend that future colorectal cancer epigenetic studies include, at minimum, the traditional Hannum, Horvath, and PhenoAge measures alongside the mitotic clocks MiAge, EpiTOC, and EpiTOC2, to allow the field to converge on which markers best capture cancer-relevant biology and to enable meaningful meta-analyses.

The authors also urge caution on the social dimensions of epigenetic aging. Racial disparities in colorectal cancer are well documented, and one recent study reported epigenetic age acceleration in the right colons of African Americans alongside deceleration in European American peers. Yet when Devall and colleagues analyzed differentially methylated positions by race, 18.4 percent overlapped with markers of ancestry, and lifestyle and social factors were largely absent from the discussion. Given that epigenetic aging has been linked to diet, racial discrimination, neighborhood deprivation, and exposure to violence, the researchers recommend that future studies explicitly distinguish the effects of racism and social environment from ancestry itself. The study carries clear limitations: it was observational, involved only Polish women, lacked aspirin dose information, and adjusted for a limited set of covariates, so causality cannot be established, and immune-mediated mechanisms remain possible. Still, the convergence of three independent mitotic clocks on the same signal in the proximal colon of long-term aspirin users is a compelling hint that a century-old drug may be quietly slowing the cellular clockwork of the gut, and it sets a template for the larger, more diverse, and better standardized studies that must now follow.

Subject of Research: Epigenetic mitotic clock analysis of long-term aspirin use and colorectal cancer risk in healthy colon mucosa

Article Title: Long-term aspirin use and epigenetic mitotic clocks for cancer risk prediction: findings in healthy colon mucosa and recommendations for future epigenetic aging studies

Article References: Nwanaji-Enwerem, J. C., Nze, C., & Cardenas, A. (2021). Long-term aspirin use and epigenetic mitotic clocks for cancer risk prediction: findings in healthy colon mucosa and recommendations for future epigenetic aging studies. Epigenetics Communications, 1(1), Article 5. https://doi.org/10.1186/s43682-021-00004-4

Image Credits: AI Generated

DOI: 10.1186/s43682-021-00004-4

Keywords: aspirin, epigenetic clocks, mitotic clocks, colorectal cancer, DNA methylation, EpiTOC, EpiTOC2, MiAge, colon mucosa, chemoprevention, epigenetic aging, cancer risk prediction

The funding will support a one-year feasibility phase of the United States portion of a major international clinical trial designed to answer a deceptively simple question: is aspirin alone sufficient, or is a more intensive combination of blood-thinning medications the better approach for patients with SCAD? The study will be led by the Clinical Trial Center of Mount Sinai Fuster Heart Hospital and the Institute for Transformative Clinical Trials. If the feasibility phase succeeds, Mount Sinai will receive approximately $14 million over seven years from the NIH to launch the larger United States portion of the same trial, an investment that signals how seriously federal funders view the gap in evidence surrounding this disease.

The biological distinction at the heart of the trial is critical to understanding why it matters. In the typical heart attacks that dominate cardiology textbooks and clinical guidelines, the culprit is atherosclerosis — the gradual buildup of cholesterol-laden plaque inside the artery. When that plaque ruptures, platelets in the blood rush to the site and form clots that can completely block the vessel. Standard treatment after such an event relies heavily on antiplatelet medications, which make platelets less likely to stick together and form the clots that could cause a second attack. Decades of randomized trials in this patient population have established how aggressively such therapy should be applied.

SCAD, by contrast, is caused by a problem within the artery wall itself rather than by cholesterol buildup. A tear develops spontaneously in the layers of the vessel, and blood can accumulate within the wall, compressing the channel through which blood flows to the heart. Because the underlying pathology is fundamentally different, the rationale for applying the same intensive antiplatelet regimens is far less clear. Yet doctors have had no large, randomized trial conducted specifically in SCAD patients to guide them, and many of the treatments these patients receive today were developed and validated in entirely different populations. The result is a persistent uncertainty that affects treatment decisions made every day in emergency rooms and cardiac catheterization laboratories around the world.

The stakes are heightened by who SCAD affects. Roughly 80 to 95 percent of cases occur in women, most of whom are between 42 and 52 years old. Many have no traditional cardiovascular risk factors such as high cholesterol or diabetes, which means the condition often arrives without warning and can be mistaken for other causes of chest pain. Because SCAD disproportionately affects women at a relatively young age and without the traditional warning signs of heart disease, the researchers argue that identifying the optimal treatment is particularly important — the goal, as the trial’s leadership describes it, is to determine which treatment provides the best protection while exposing patients to the least unnecessary risk.

Roxana Mehran, MD, Mount Sinai Professor in Cardiovascular Clinical Research and Outcomes at the Icahn School of Medicine, is a Principal Investigator for the trial’s clinical coordinating center. Deepak L. Bhatt, MD, MPH, Director of Mount Sinai Fuster Heart Hospital and also a Principal Investigator of the clinical coordinating center, has emphasized that SCAD is a very different disease from the type of heart attack encountered most often, yet many treatments in use today were adopted from studies conducted in other patient populations. In his view, the trial offers an opportunity to generate the rigorous evidence that patients with SCAD and their physicians have long been waiting for — evidence that could finally place treatment of the condition on the same evidentiary footing as the care of more common heart attacks.

The trial itself, known as SCAD-ALIGN, has been designed to settle the antiplatelet question directly. It will compare a moderate antiplatelet strategy — aspirin alone for three months — against a more intensive strategy consisting of dual antiplatelet therapy for three months followed by nine months of single antiplatelet therapy. Researchers plan to enroll roughly 3,500 patients internationally, with approximately 500 of those in the United States across 60 sites. Participants will be evaluated for major cardiovascular outcomes, including cardiovascular death, myocardial infarction, recurrent SCAD, unplanned coronary revascularization, stroke, transient ischemic attack, and bleeding. That last outcome is especially important, because more aggressive blood thinning always carries an increased risk of hemorrhage, and the trial is structured to capture whether the intensive strategy’s potential benefits outweigh that hazard.

The scale of the effort reflects a fundamental challenge in studying rare diseases. SCAD is relatively uncommon, which means no single center or country can easily enroll enough patients to answer the question reliably. Alan Moskowitz, MD, Professor of Population Health Science and Policy at the Icahn School of Medicine and a Principal Investigator for the trial’s data coordinating center, has noted that the project brings together research networks and national funding organizations across multiple countries under one common study protocol. Annetine Gelijns, PhD, Chair of the Department of Population Health Science and Policy and a Principal Investigator for the data coordinating center, has added that the trial is expected to represent a novel model of international academic collaboration and to provide the first large-scale randomized evidence to help guide antiplatelet therapy in this patient population.

The collaborative architecture extends well beyond the United States. SCAD-ALIGN was endorsed by the Multinational Clinical Trials Initiative of the Global Cardiovascular Research Funders Forum, and the global collaboration includes investigators and funding organizations from the United States, Germany, the United Kingdom, Canada, the Netherlands, Denmark, Sweden, Spain, Australia, New Zealand, and other participating countries, with additional participation from centers in South America. Emilia Bagiella, PhD, Director of the Center for Biostatistics in the Department of Population Health Science and Policy and a Principal Investigator for the data coordinating center, has described this coordinated approach as intended to generate robust evidence for an important clinical question that affects women disproportionately and for which large-scale industry-sponsored research has been limited — a candid acknowledgment that commercial incentives have historically underserved conditions like SCAD.

For the patients and physicians who have navigated SCAD without the benefit of dedicated trial evidence, the launch of this feasibility phase marks a turning point. The condition’s rarity, its predilection for young and otherwise healthy women, and its fundamentally distinct mechanism have long combined to leave clinicians extrapolating from data that were never meant to apply to these patients. If the feasibility phase demonstrates that the international network can recruit and follow participants at the required scale, the full trial will proceed with the backing of approximately $14 million in NIH support over seven years, and the results could ultimately reshape treatment recommendations for SCAD patients worldwide — replacing inherited convention with evidence earned from the very population the disease affects most.

Subject of Research: An international randomized clinical trial comparing antiplatelet treatment strategies for spontaneous coronary artery dissection, a heart attack cause that predominantly affects young women.

Article Title: Mount Sinai awarded $2 million to launch international clinical trial on spontaneous coronary artery dissection

Article References: Mount Sinai awarded $2 million to launch international clinical trial on spontaneous coronary artery dissection. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: SCAD, spontaneous coronary artery dissection, Mount Sinai, NIH, clinical trial, antiplatelet therapy, aspirin, women's heart health, cardiology, SCAD-ALIGN, heart attack, dual antiplatelet therapy

The study, conducted by Özge Sönmez and Ahmet Emre Eşkazan of the Division of Hematology at Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, used a web-based questionnaire to probe how hematologists manage extreme thrombocytosis, the technical term for platelet counts that far exceed the normal range of roughly 150,000 to 450,000 per microliter. Fifty-six hematologists participated in the survey, which was supported by the Turkish Society of Hematology and approved by the local clinical studies ethics committee at Istanbul University-Cerrahpaşa. The authors set out to map real-world clinical behavior in a domain where evidence is thin, expert opinion varies widely, and the consequences of over-treatment or under-treatment can be serious for patients with essential thrombocythemia, one of the classical Philadelphia-negative myeloproliferative neoplasms.

The central finding concerns the platelet threshold at which physicians choose to intensify therapy. Cytoreductive treatment, which uses medications such as hydroxyurea to suppress platelet production in the marrow, was favored by 41.1 percent of respondents once platelet counts reached or exceeded 1000 × 10⁹ per liter, the celebrated million-platelet mark. But when the threshold was raised to 1500 × 10⁹ per liter, the proportion of hematologists opting for cytoreduction jumped to 83.9 percent. In other words, the million mark alone is not a universal trigger for action; it is a point of debate. Only when counts approach one and a half million does a strong majority of specialists converge on drug-based platelet lowering, a pattern that mirrors the cautious, risk-adapted philosophy embedded in contemporary myeloproliferative neoplasm guidelines.

Why does the million mark inspire such hesitation? The answer lies in the biology of extreme thrombocytosis. Very high platelet counts do not simply increase the risk of blood clots; paradoxically, they also raise the risk of bleeding. The mechanism is acquired von Willebrand disease, a condition in which the sheer excess of circulating platelets adsorbs and proteolytically cleaves von Willebrand factor, the adhesive protein that platelets and clotting depend on. As platelets multiply, they effectively devour their own hemostatic infrastructure, and the largest von Willebrand multimers disappear first. A patient with a platelet count of a million or more may therefore present with gastrointestinal bleeding or bruising rather than thrombosis, and giving aspirin to such a patient in the belief that high platelets mean high clot risk can precipitate dangerous hemorrhage.

This biological nuance explains the second pillar of the survey: laboratory assessment. A striking 78.6 percent of hematologists reported testing for von Willebrand factor ristocetin cofactor activity, abbreviated vWF:RCo, at the time of diagnosis of extreme thrombocytosis. This assay measures the functional capacity of von Willebrand factor to support platelet adhesion under shear stress, and it is the workhorse test for detecting the acquired form of the deficiency. The near-universal uptake of this test among survey respondents suggests that the field has internalized the lesson that platelet number alone is an unreliable guide to bleeding risk, and that documenting acquired von Willebrand disease is now considered a standard part of the initial evaluation when counts soar into the extreme range.

Aspirin decisions revealed an equally disciplined logic. In the presence of cardiovascular risk factors and in the absence of acquired von Willebrand disease, 91.1 percent of hematologists favored aspirin therapy for patients with platelet counts of at least 1000 × 10⁹ per liter, and 78.6 percent favored it at counts of at least 1500 × 10⁹ per liter. The slight decline at the higher threshold is telling: the very patients with the most extreme counts are also the most likely to harbor acquired von Willebrand disease, so the antiplatelet drug that protects one patient’s arteries becomes a hemorrhagic hazard for another. The survey thus captures, in numerical form, the delicate balancing act that defines extreme thrombocytosis management, where the same count can argue for and against the same drug depending on a single laboratory result.

When asked why they initiate cytoreductive treatment at all, respondents cited three goals with roughly equal frequency: prevention of thrombosis, prevention of bleeding, and control of symptoms such as headaches, erythromelalgia, and visual disturbances. This even distribution is itself informative. It shows that hematologists do not view cytoreduction solely as an anti-thrombotic strategy. Lowering the platelet count can restore von Willebrand factor levels and relieve bleeding, and it can also ameliorate the microvascular symptoms that plague many patients with essential thrombocythemia regardless of their thrombotic risk score. The therapeutic rationale, in practice, is tripartite, and the survey suggests that experienced clinicians weigh all three aims rather than fixating on any single one.

The most novel element of the report is its comparison with artificial intelligence. The authors posed the same clinical scenarios to AI programs and recorded the recommendations the models produced. The AI-generated advice supported von Willebrand testing, endorsed cytoreductive treatment particularly at platelet counts of 1500 × 10⁹ per liter or above, and generally recommended aspirin only for patients with counts of at least 1000 × 10⁹ per liter who did not have acquired von Willebrand disease. Across several clinical scenarios, the differences between the human specialists and the machine recommendations were few. The authors are careful to frame this comparison as exploratory, and they stop short of claiming that AI can substitute for clinical judgment, but the convergence is noteworthy at a time when large language models are being proposed as clinical decision aids.

The significance of this convergence deserves careful interpretation. On one hand, it suggests that the consensus positions in hematology, such as testing for acquired von Willebrand disease and reserving aggressive cytoreduction for the most extreme counts, are encoded deeply enough in the published literature that AI systems trained on that literature reproduce them faithfully. On the other hand, it raises the question of whether AI is genuinely reasoning or simply echoing the dominant patterns of its training data, including their blind spots. Where expert opinion is divided, as it clearly is at the million-platelet threshold where only about four in ten specialists opt for cytoreduction, an AI that confidently recommends a single course of action could flatten legitimate clinical nuance into false certainty. The survey’s exploratory design is a prudent acknowledgment of that risk.

For patients with essential thrombocythemia, the practical message of the study is reassuring in one respect and cautionary in another. Reassuring, because the management of extreme thrombocytosis appears to follow a coherent, biologically informed playbook: check von Willebrand function, tailor aspirin to its result, and reserve cytoreductive drugs chiefly for the most extreme counts or for patients with thrombosis, bleeding, or disabling symptoms. Cautionary, because the survey also exposes genuine variability at the margins, with more than half of specialists declining to treat at exactly one million platelets while others intervene. As Sönmez and Eşkazan conclude, extreme thrombocytosis itself remains an important driver of treatment decisions, particularly above 1500 × 10⁹ per liter, and the near-agreement between experienced hematologists and AI recommendations offers a provocative glimpse of a future in which algorithms may help standardize care, provided they are validated rigorously and deployed with the same humility that the survey’s authors bring to their own exploratory analysis.

Subject of Research: Clinical management of extreme thrombocytosis in essential thrombocythemia, comparing hematologist survey responses with artificial intelligence recommendations

Article Title: When platelets reach a million: insights from hematologists

Article References: Sönmez, Ö., & Eşkazan, A. E. (2026). When platelets reach a million: insights from hematologists. Annals of Hematology. https://doi.org/10.1007/s00277-026-07183-x

Image Credits: AI Generated

DOI: 10.1007/s00277-026-07183-x

Keywords: essential thrombocythemia, extreme thrombocytosis, platelets, cytoreductive therapy, acquired von Willebrand disease, aspirin, von Willebrand factor, myeloproliferative neoplasms, hematology, artificial intelligence, clinical survey, thrombosis

The scale of the problem is staggering. More than 650 active pharmaceutical ingredients and their metabolites have now been detected in the environments of over seventy countries, according to studies cited in the review. Pharmaceuticals reach rivers, lakes and groundwater through a web of pathways: human excretion via urine, sweat and saliva, improper disposal of unused medications down sinks and toilets, hospital effluent, veterinary drug residues in manure spread on fields, and even airborne diffusion of medicated dust from livestock facilities. Conventional wastewater treatment plants, designed to strip out organic matter and pathogens rather than trace drug molecules, routinely fail to eliminate these compounds, so they pass through facilities largely intact and re-enter the environment.

Aspirin, or acetylsalicylic acid, occupies a special place in this contamination story. Roughly 23 percent of the United States population, about 28 to 29 million people, takes it as a preventive measure against cardiovascular disease, and millions more use it for pain, fever and inflammation. Because the human body metabolizes only part of each dose, the remainder, along with the drug’s primary metabolite salicylic acid, flows into sewage systems. The review notes that aspirin’s persistence in water is compounded by its chemistry: in aqueous environments it readily hydrolyzes into salicylic acid and acetic acid, and its ionization state shifts with pH, producing a heterogeneous mixture of species with different affinities for any given treatment material.

The ecological consequences are subtle but serious. Chronic exposure to low concentrations of aspirin and its metabolites has been linked in laboratory studies to disrupted growth, reproduction and behavior in algae, invertebrates and fish, along with enzyme inhibition and oxidative stress. Salicylic acid released into waterways may interfere with photosynthesis in aquatic plants, weakening ecosystem dynamics from the base of the food web upward. The review also flags a less obvious casualty: microbial communities. Aspirin residues can alter microbial diversity and activity in natural waters and in the treatment plants themselves, potentially undermining sensitive processes such as nitrification and contributing to the broader crisis of antimicrobial resistance, since sub-therapeutic drug levels can promote horizontal transfer of resistance genes among bacteria.

Against this backdrop, the authors make the case for adsorption using agro-waste-derived materials as a treatment strategy that is simultaneously effective, economical and aligned with circular economy principles. Agricultural residues are abundant, essentially free at the point of generation, and rich in the lignocellulosic building blocks, cellulose, hemicellulose and lignin, that give them their capture power. Their surfaces carry hydroxyl, carboxyl and phenolic functional groups that bind pharmaceutical molecules through hydrogen bonding, electrostatic attraction, van der Waals forces and pi-pi stacking interactions between aromatic rings. Their hierarchical pore networks, ranging from micropores to macropores, provide both the surface area and the diffusion pathways needed to trap molecules of varying size and polarity.

The performance data compiled in the review are striking. Rice husk, characterized by Boehm titration, Fourier-transform infrared spectroscopy and point-of-zero-charge measurements, achieved a maximum Langmuir adsorption capacity of 47.03 milligrams of aspirin per gram at pH 2, while rice hull activated carbon removed 85.79 percent of the drug from contaminated water at pH 3.97 after 90 minutes. Spent tea leaf activated carbon, regenerated chemically with ethanol washing, retained 81.6 percent removal efficiency after six consecutive adsorption-regeneration cycles, down only marginally from 85.5 percent in the first cycle. Beyond aspirin, the review catalogs agro-waste successes against a pharmacopeia of contaminants: walnut shells capturing ibuprofen, pistachio nutshells outperforming carbon nanotubes for the antibiotic sarafloxacin, lotus leaves stripping norfloxacin, and functionalized banana stalks removing ciprofloxacin from solution.

The chemistry of why these materials work is now reasonably well understood. Oxygen-containing functional groups on the adsorbent surface form hydrogen bonds with aspirin and its metabolites, while graphitic carbon domains created during pyrolysis accommodate pi-pi electron donor-acceptor interactions with the drug’s aromatic ring. Solution pH governs everything: it determines the ionization state of aspirin, which has a pKa near 3.5, and the surface charge of the adsorbent relative to its point of zero charge, dictating whether electrostatic interactions are attractive or repulsive. Activation with chemicals such as phosphoric acid or potassium hydroxide, or physical treatments like steam and carbon dioxide activation, dramatically expands pore volume and surface area, while techniques such as grafting amine or carboxyl groups onto the biomass surface can tune selectivity toward specific pharmaceutical classes.

Crucially, the review does not stop at adsorption performance; it confronts the lifecycle question that often undermines green technologies. Spent adsorbents loaded with captured pharmaceuticals become hazardous waste in their own right, and improper disposal can simply re-release the contaminants, shifting pollution from the aqueous phase to the solid phase rather than eliminating it. The authors evaluate regeneration strategies in detail: chemical regeneration with acid, base or solvent washing restores capacity with minimal carbon loss; thermal regeneration breaks adsorbate bonds but consumes energy, emits carbon dioxide and degrades mechanical strength; microwave-assisted regeneration heats the carbon matrix internally, recovering more capacity with less energy and shorter process times; and emerging bio-regeneration uses microbial cultures to desorb and biodegrade captured pollutants, though it remains slow and dependent on the biodegradability of the adsorbed compound.

The review is equally candid about the risks embedded in competing recovery technologies. Chemical precipitation generates sludge and can leave residual reagents in treated effluent; membrane filtration suffers from fouling and high energy demands, particularly for reverse osmosis; advanced oxidation processes can produce toxic, stable transformation products and require specialized equipment; and ion exchange produces concentrated regenerant streams that must be carefully managed. Adsorption, by contrast, is simple to operate, inexpensive and generates fewer toxic byproducts, which is precisely why the authors argue it deserves priority for pharmaceutical remediation, provided the full chain from adsorbent preparation through regeneration to final disposal is managed responsibly.

What emerges is both a technical roadmap and a policy challenge. The authors call for life-cycle assessments to verify that agro-waste adsorbents genuinely outperform commercial activated carbon once preparation energy and chemical inputs are counted, for pilot-scale demonstrations of microwave-assisted regeneration at industrial scale, and for unified regulatory standards governing bio-based adsorbents and pharmaceutical discharge limits. They also emphasize prevention: drug take-back programs, greener pharmaceutical design, better hospital waste management and public education about proper medication disposal. If those pieces come together, the humble byproducts of rice milling, tea drinking and coffee brewing could become a cornerstone of sustainable water treatment, advancing clean water and sanitation goals while converting one waste stream into the solution for another.

Subject of Research: Use of agro-waste-based adsorbents for the removal, recovery and regeneration of aspirin pharmaceutical contamination in wastewater

Article Title: Agro-based wastes as sustainable alternatives for the removal of aspirin pharmaceutical: recovery, regeneration and risk assessments

Article References: Atunwa, B. T., Chan, S. Y. S., Tan, I. S., Lee, V. S., Tan, Y. H., & Lin, C.-W. (2026). Agro-based wastes as sustainable alternatives for the removal of aspirin pharmaceutical: recovery, regeneration and risk assessments. Advances in Industrial and Engineering Chemistry, 2(1), Article 2. https://doi.org/10.1007/s44405-026-00042-3

Image Credits: AI Generated

DOI: 10.1007/s44405-026-00042-3

Keywords: aspirin, agro-waste, adsorption, wastewater treatment, pharmaceutical pollution, activated carbon, rice husk, spent tea leaves, adsorbent regeneration, water remediation, emerging contaminants, circular economy