The review, led by María José Correa-Méndez and colleagues at Pontificia Universidad Javeriana in Bogotá, Colombia, set out to map the landscape of adverse childhood experience screening in pediatric clinical care. Following the Joanna Briggs Institute methodology for scoping reviews and reporting against the PRISMA-ScR checklist, the team prospectively registered their protocol on the Open Science Framework before searching seven major databases, including MEDLINE, EMBASE, the Cochrane Library, LiLACS, PsycArticles, and CINAHL, along with gray literature. The search window ran from January 2012 to September 2025, capturing more than a decade of research on how clinics around the world have attempted to ask children and families about adversity.

The scale of the evidence base is striking. The researchers identified 8,173 records and, after independent screening by two reviewers, included 32 studies, reviews, guidelines, and policy statements that addressed screening among children aged 3 to 17 years in pediatric clinical settings. The included literature spanned quantitative, qualitative, and mixed-methods studies, reflecting the reality that implementing a sensitive screening program is as much a social and organizational challenge as a psychometric one. Data were extracted independently and synthesized through descriptive mapping and narrative synthesis, an approach suited to a field where the tools and processes vary so widely that a meta-analysis would be meaningless.

That heterogeneity emerged as one of the review’s central findings. The team identified 15 distinct adverse childhood experience screening tools in use in pediatric clinical practice, with completion times ranging from roughly 2 minutes to as long as 60 minutes, though most fell between 5 and 20 minutes. Studies differed not only in which instrument they deployed but in who served as the informant, whether a caregiver, an adolescent, or both; how responses were scored; and how the screening process was woven into the clinical encounter. Most of the research came from the United States, leaving clinicians and researchers elsewhere with little direct evidence about how screening performs in their own health systems and cultures.

The perceived benefits of screening were consistent across the literature. Clinicians and caregivers reported that structured screening enabled earlier identification of adversity, opened conversations that might otherwise never happen, and improved communication between families and providers. Screening also created concrete opportunities for timely referral to mental health or social services and for preventive care that could buffer the biological and psychological consequences of toxic stress. In the framing of trauma-informed care, the act of asking, when done sensitively, can itself be therapeutic, signaling to families that adversity is recognized and taken seriously rather than hidden or ignored.

The implementation strategies that supported these benefits were equally consistent. Successful programs invested in clinician training, so that providers felt competent and comfortable discussing sensitive topics; integrated screening questions into electronic health records, reducing friction and standardizing documentation; and built explicit linkages to mental health and social services, ensuring that a positive screen led somewhere rather than into a void. These three pillars, training, informatics, and referral infrastructure, appear repeatedly across the included studies as the practical machinery that turns a questionnaire into a functioning clinical pathway.

Yet the barriers documented in the review are formidable. Providers frequently cited limited training and time constraints within packed pediatric appointments. Follow-up pathways were often unclear, and community resources insufficient to respond to the volume of need that screening uncovered. Families and clinicians alike raised concerns about stigmatization and about the risk of labeling children with adversity without delivering adequate support, a scenario in which screening identifies harm but changes nothing for the child. Cultural fit emerged as a particularly acute problem in low- and middle-income countries, where tools developed in high-income settings may not map onto local family structures, social norms, or service landscapes.

The most consequential gap, however, is evidentiary. The review found that evidence linking adverse childhood experience screening to improved long-term health outcomes was scarce and inconsistent. This is a critical distinction for screening science: a test can be feasible, acceptable, and even accurate, but if detecting the condition does not translate into better health, universal screening cannot be justified. The authors conclude that current evidence is insufficient to support routine universal screening in pediatric settings or firm conclusions about long-term effectiveness, a sobering verdict for a practice that has been widely promoted in policy circles.

The review’s conclusions point toward a research and implementation agenda rather than an abandonment of the idea. The authors argue that implementation requires standardized, culturally adapted tools, clear care pathways, and adequate resources to respond to positive screens. Future studies should directly evaluate effectiveness, assess potential harms such as labeling and stigmatization, and develop context-appropriate screening models for settings with constrained resources and high social inequity. In other words, the field must move from proving that screening can be done to proving that doing it helps, and that it helps without causing collateral damage.

For pediatricians, the review offers a practical caution: before adopting a screening tool, clinics should consider whether they have the training, informatics, and referral capacity to respond to what they find. For researchers, it highlights the absence of long-term outcome data as the field’s defining weakness. And for policymakers, it underscores that screening without services risks becoming an empty gesture. The promise of identifying childhood adversity early remains real, and the biological rationale for early intervention is stronger than ever, but the new synthesis makes clear that the evidence required to make universal screening standard pediatric practice has not yet been built. Closing that gap, particularly in the low- and middle-income countries where the burden of childhood adversity is often greatest, is now the central task for this rapidly growing field.

Subject of Research: ACE screening in pediatric clinical settings

Article Title: Screening for adverse childhood experiences in pediatric clinical settings: a scoping review of tools, implementation strategies, and evidence gaps

Article References: Correa-Méndez, M. J., Vásquez-Ponce, M., Restrepo-Escudero, L., Díaz-González, V., Escobar, C., Franky-Escobar, I., Arango, I., Gómez, O. E., & González-Ballesteros, L. M. (2026). Screening for adverse childhood experiences in pediatric clinical settings: a scoping review of tools, implementation strategies, and evidence gaps. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07471-5

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07471-5

Keywords: adverse childhood experiences, ACE screening, pediatrics, scoping review, trauma-informed care, screening tools, child health, mental health, implementation barriers, BMC Pediatrics, Screening, adverse

Immune checkpoint inhibitors, or ICIs, have transformed the treatment of advanced cancer over the past decade. These drugs, which include antibodies targeting PD-1 and PD-L1, work by releasing the molecular brakes that tumors place on T cells. But the same immune activation that attacks cancer can also strike healthy tissue, producing immune-related adverse events, or irAEs. According to the literature, these occur in roughly 70 percent of patients receiving anti-PD-1 or PD-L1 therapy, with thyroid inflammation and skin toxicities among the most common.

For years, researchers have debated what these side effects mean for prognosis. Some studies report a positive association between irAEs and survival, while others find that certain irAEs are linked to worse outcomes and treatment interruption. The picture has remained murky, partly because most analyses lump all adverse events together rather than examining each one individually.

Now, a team of medical oncologists at Saglik Bilimleri University’s Prof. Dr. Cemil Tascioglu City Hospital in Istanbul has taken a more granular approach. In a retrospective study published in BMC Cancer, Mert Erciyestepe and colleagues analyzed data from 300 patients with metastatic malignancy treated between January 2020 and January 2024. Their goal was to dissect the relationship between individual irAEs and survival in patients receiving ICI treatment in first- and second-line settings.

The headline finding is striking. Patients who experienced any adverse event had a median overall survival of 25.0 months, compared with just 9.0 months in patients who developed no adverse events at all. The difference was highly statistically significant, with a p-value below 0.001. On the surface, this supports the conventional wisdom that side effects correlate with better outcomes.

But when the researchers broke the data down by specific adverse event, the story became far more nuanced. Patients who developed hypothyroidism had a median overall survival of 41.0 months, compared with 23.0 months in those who did not — a dramatic difference. Similarly, patients who experienced skin toxicity had a median overall survival of 48.0 months, the longest of any group examined. Both findings were statistically significant.

Not every adverse event was a good omen, however. Patients who developed elevated AST/ALT levels — a sign of liver inflammation — had significantly shorter survival, with a p-value of 0.015. Even more concerning, patients who developed pneumonitis, an inflammation of the lung tissue that is one of the most feared complications of checkpoint inhibitor therapy, had significantly shorter survival, with a p-value below 0.001. Meanwhile, the presence of mucositis, acute kidney injury, arthritis, adrenal insufficiency, and hypophysitis did not show any statistically significant difference in overall survival.

The researchers used standard survival analysis techniques to reach these conclusions. They employed the Kaplan-Meier method and log-rank tests to compare overall survival and progression-free survival between clinical groups, used independent t-tests for pairwise comparisons, and applied multivariate Cox regression to assess the risk of death across various clinical variables. This combination of approaches helps control for confounding factors that might otherwise distort the apparent relationship between adverse events and survival.

What might explain why some irAEs correlate with better survival while others correlate with worse? One possibility is that certain adverse events, like thyroid dysfunction and skin toxicity, reflect a broadly activated immune system that is also attacking the tumor. Hypothyroidism in particular is easily managed with hormone replacement, so it poses little threat to the patient while potentially serving as a biomarker of immune activation. In contrast, pneumonitis and hepatitis may reflect a dangerous loss of immune self-tolerance that forces treatment interruption, denying the patient the full benefit of therapy while simultaneously threatening vital organs.

The clinical implications are significant. If individual irAEs can serve as indicators of treatment response and survival, oncologists may be able to use them as real-time biomarkers, adjusting monitoring intensity and treatment strategy based on which side effects appear. A patient who develops hypothyroidism or a mild skin rash might be reassured that their immune system is engaged, while a patient who develops pneumonitis might warrant closer surveillance and more aggressive management. The authors suggest that survival can potentially be predicted by monitoring irAEs, though they caution that the number of studies on this subject remains relatively small.

Limitations of the study are worth noting. As a retrospective, single-center analysis of 300 patients, the findings may not generalize to all populations or treatment settings. The authors themselves call for larger, multicenter studies to confirm and extend their results. Still, the study adds an important layer of granularity to a controversial topic, moving the field beyond the simplistic question of whether adverse events are good or bad for survival. The answer, it turns out, depends on which adverse event — and that distinction could ultimately help clinicians make better decisions for their patients.

Subject of Research: Distribution of adverse effects of immune checkpoint inhibitors and their impact on survival: some with better but some with worse survival

Article Title: Distribution of adverse effects of immune checkpoint inhibitors and their impact on survival: some with better but some with worse survival

Article References: Erciyestepe, M., Afsar Satis, N., Ozturk, A. E., Dinc Sonusen, S., Aydin, O., & Erturk, K. (2026). Distribution of adverse effects of immune checkpoint inhibitors and their impact on survival: some with better but some with worse survival. BMC Cancer. https://doi.org/10.1186/s12885-026-16954-8

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16954-8

Keywords: Distribution, adverse, effects, immune, checkpoint, inhibitors, impact, survival, some, better, worse, scientific research

The research, published in BMC Cancer, was conducted by a team led by Thi Thu Thuy Nguyen of Hong Bang International University in Ho Chi Minh City, working with colleagues from Cho Ray Hospital and the Health Technology Assessment & Application Research Institute. The investigators performed a retrospective, cross-sectional analysis of all ADR reports related to anticancer drugs submitted to the Ho Chi Minh City Regional Drug Information and Pharmacovigilance Center between January 1 and December 31, 2023. Reports concerning drug quality problems and those not associated with anticancer drugs were excluded, leaving 291 reports for analysis. In Vietnam, where studies assessing the severity and preventability of ADRs using regional pharmacovigilance data have been scarce, the study fills an important evidence gap.

The technical backbone of the study rests on two internationally recognized assessment systems. First, the researchers used the World Health Organization–Uppsala Monitoring Centre (WHO-UMC) causality assessment system, a scale that classifies the likelihood that a suspected drug truly caused a reported reaction, ranging from unlikely through possible, probable, and certain. Only reports with a confirmed causal relationship were eligible for the next step. Second, the team applied the WHO Preventability method, known as the WHO P-method, which determines whether a reaction could have been avoided through actions such as respecting a documented drug history, avoiding therapeutic duplication, or adjusting doses for patient characteristics. This two-stage filtering is what allows pharmacovigilance scientists to separate genuine, unavoidable toxicities of powerful drugs from errors that better clinical practice might have caught.

The demographic picture that emerged is telling. Female patients experienced ADRs far more frequently than male patients, accounting for 212 of the 291 reports, or 72.9 percent, compared with 76 reports, or 26.1 percent, among men. The 40 to 64 age group dominated, representing 54.3 percent of cases, or 158 of 291 reports. This skew toward middle-aged women reflects both the epidemiology of cancer in Vietnam and the biology of the drugs involved. Agents such as carboplatin and paclitaxel, the two most frequently implicated drugs in the study, are mainstays of breast and gynecologic cancer treatment, and paclitaxel in particular is notorious for hypersensitivity reactions that occur more readily in female patients.

Of the 291 reports, causality assessment using the WHO scale confirmed a causal relationship between the suspected drug and the reaction in 253 reports, corresponding to 433 distinct drug–ADR pairs. These confirmed pairs were then evaluated for preventability, and the result was remarkable: only 2 reports, or 0.8 percent, were determined to be preventable. The vast majority of the confirmed reactions were classified as non-serious, accounting for 70.8 percent, or 179 of 253 reports. Nevertheless, a considerable proportion carried real clinical weight: 18.2 percent, or 46 reports, required hospitalization or prolonged a hospital stay, and 6.3 percent, or 16 reports, resulted in death. These figures underscore that even reactions deemed non-preventable can be devastating when the drugs involved are cytotoxic agents designed to kill dividing cells.

The two preventable cases deserve close attention because each represents a different, well-known category of avoidable harm. One involved cisplatin, a platinum-based chemotherapy drug, in a patient with a documented history of drug hypersensitivity. Administering a drug to a patient with a known allergy to it is precisely the kind of error that careful medication reconciliation and allergy documentation are designed to prevent. The other case involved epirubicin, an anthracycline agent, and was attributed to therapeutic duplication, meaning the patient received overlapping therapy that should not have been co-administered. Both scenarios fall squarely within the WHO P-method’s definition of preventability, which considers whether a reaction could have been avoided given the information available before the drug was given.

The most common anticancer drugs causing ADRs were carboplatin, implicated in 92 of the 433 drug–ADR pairs, or 21.2 percent, and paclitaxel, implicated in 87 pairs, or 20.1 percent. Carboplatin is a second-generation platinum compound whose dose is typically calculated using a formula based on kidney function, and its characteristic toxicities include myelosuppression, nausea, and thrombocytopenia. Paclitaxel, a taxane derived originally from the bark of the Pacific yew, is famous for infusion-related hypersensitivity reactions driven by the solvent Cremophor EL, as well as peripheral neuropathy and neutropenia. Both drugs are frequently combined in regimens for ovarian, breast, and lung cancers, which helps explain their prominence in the pharmacovigilance database.

Why does the preventability figure matter so much? In pharmacovigilance research, preventability estimates vary widely across settings and drug classes. Studies in general hospital populations have sometimes found that a third or more of ADRs are preventable, particularly those arising from prescribing errors, drug interactions, or failure to respect documented allergies. The very low preventability rate of 0.8 percent in this anticancer drug database suggests that most reactions to cytotoxic agents are intrinsic toxicities, predictable consequences of the drugs’ mechanisms of action rather than lapses in clinical judgment. This does not mean such reactions are unimportant; rather, it reframes the challenge. If most harm from chemotherapy is inherent to the drugs, then prevention must come from better supportive care, dose optimization, premedication, and monitoring, not simply from avoiding prescribing mistakes.

The study’s findings carry implications for how pharmacovigilance systems in low- and middle-income countries can inform patient safety. Vietnam’s regional drug information and pharmacovigilance centers collect spontaneous reports from hospitals across their catchment areas, and this analysis demonstrates that such databases can yield actionable characterizations of drug safety. The identification of preventable ADRs, even if rare, highlights the need for ongoing monitoring and evaluation to inform appropriate preventive strategies. The authors note that most anticancer drug–related ADRs in the study were non-serious, although a considerable proportion still resulted in hospitalization or death, and that the identification of preventable cases underscores the value of continuous surveillance in cancer treatment.

For patients and clinicians, the message is nuanced but ultimately reassuring in one respect and sobering in another. The reassuring part is that the overwhelming majority of confirmed reactions to anticancer drugs in this Vietnamese database were not the result of preventable errors; they were the expected, if unwelcome, consequences of drugs whose therapeutic power and toxic potential are two sides of the same coin. The sobering part is that a meaningful fraction of these reactions, nearly one in five, still sent patients to the hospital or extended their stays, and one in sixteen proved fatal. As cancer therapy evolves toward targeted agents and immunotherapies with their own distinctive safety profiles, the kind of systematic, database-driven preventability assessment exemplified by this study will remain an essential tool for distinguishing avoidable harm from the inherent price of treating cancer with drugs that attack the very machinery of cell division.

Subject of Research: Pharmacovigilance

Article Title: Preventability of adverse drug reactions to anticancer drugs: insights from the database of the Regional Drug Information and Pharmacovigilance Center

Article References: Nguyen, T. T. T., Nguyen, Q. B., Nguyen, T. K. U., & Do, H. Q. T. (2026). Preventability of adverse drug reactions to anticancer drugs: insights from the database of the Regional Drug Information and Pharmacovigilance Center. BMC Cancer. https://doi.org/10.1186/s12885-026-16459-4

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16459-4

Keywords: adverse drug reactions, anticancer drugs, pharmacovigilance, drug safety, cancer therapy, WHO-UMC causality assessment, preventability, adverse, drug, reactions, anticancer, drugs

The study, published in Current Psychology, surveyed 368 students at Koya University in the Hawler (Erbil) Governorate between April and May 2023. Participants were selected through a two-stage cluster sampling strategy designed to give every student an equal chance of inclusion. The researchers first divided the student population into five clusters based on dormitory blocks, then randomly selected rooms from the university’s Directory of Residential Halls using SPSS. All members of each chosen room were invited to participate, with the process continuing until an adequate sample was reached. Because the university had a higher proportion of female students at the time, the data collection aimed to include more female participants, who ultimately made up 59.2 percent of the final sample.

The results paint a sobering picture of childhood adversity in the region. More than half of participants, 56.8 percent, reported at least one ACE, while 12.8 percent reported four or more, indicating high cumulative exposure. Physical abuse was the most prevalent individual ACE at 31 percent, followed by emotional abuse at 27.7 percent, emotional neglect at 19 percent, household incarceration at 13.3 percent, and parental mental illness at 12.2 percent. One in ten participants reported experiencing childhood sexual abuse. Notably, the mean score for the abuse and neglect subtype was roughly double that of the household dysfunction subtype, suggesting that direct maltreatment was more common than family-level dysfunction in this sample.

The mental health burden among these young adults was equally striking. Nearly two in five students screened positive for PTSD, using the conservative 33-point cutoff on the PTSD Checklist for DSM-5, and 38.6 percent screened positive for generalized anxiety disorder on the GAD-7 scale. Mean perceived stress, measured on the Perceived Stress Scale, fell in the moderate range, with 72.3 percent of participants reporting moderate stress. Perhaps most alarming was the gap between symptom burden and formal care: only 4.62 percent of participants reported ever having been diagnosed with a mental disorder by a professional, pointing to widespread underdiagnosis and unmet need.

When the researchers fit multivariate logistic regressions adjusting for age, sex, year of study, and social support, each additional ACE was associated with a 26 percent increase in the odds of screening positive for generalized anxiety and a 36 percent increase in the odds of screening positive for PTSD. The subtype analysis revealed a novel pattern: each additional abuse and neglect ACE raised the odds of anxiety by 44 percent and PTSD by 55 percent, while each additional household dysfunction ACE was associated with a 49 percent increase in PTSD odds but showed no significant association with generalized anxiety. The researchers suggest that the relatively low prevalence of household dysfunction in the sample may have limited statistical power to detect an anxiety association, and that cultural norms, including strong taboos surrounding divorce, may contribute to underreporting of family difficulties.

Social support emerged as a powerful promotive factor across all models. Students with strong perceived social support, measured on the Oslo Social Support Scale, had 61 percent lower odds of screening positive for anxiety and 70 percent lower odds of screening positive for PTSD compared with those reporting poor support, all else equal. When adjusting for ACE subtypes, the protective associations remained robust, with strong support linked to 62 percent lower anxiety odds and 71 percent lower PTSD odds. The finding aligns with the main effects model of social support, which posits that direct promotive effects on well-being occur regardless of stress exposure, and resonates with the Health Outcomes from Positive Experiences framework, which emphasizes supportive relationships as key positive childhood experiences that foster resilience.

The prevalence of physical abuse in this sample exceeded the recent global pooled estimate of 18.2 percent but was consistent with the Middle East-specific estimate of 30.7 percent. Household incarceration also surpassed both global and regional pooled estimates. The researchers note that the broader pattern of findings generally aligned with the international literature, though a prior Iraqi study found physical neglect to be the most common ACE, a discrepancy the current team attributes partly to differences in sampling and translation methods. The Kurdistan Region’s long history of violence, including torture, displacement, genocide, the war against the Islamic State, and attacks by neighboring countries, likely compounds the mental health burden associated with early adversity.

The study employed culturally adapted instruments to ensure validity in the Kurdish context. The ACE questionnaire and Perceived Stress Scale were translated into the Sorani dialect of Kurdish using a forward-backward translation process, while the team used recently adapted Kurdish-Sorani versions of the Oslo Social Support Scale, GAD-7, and PCL-5 that had been piloted with Anfal Genocide survivors. Internal consistency was strong across measures, with Cronbach’s alpha reaching 0.93 for the PCL-5 and 0.89 for the GAD-7. Sensitivity analyses adjusting standard errors for clustering at the dormitory block level did not materially alter the primary results.

The findings carry significant implications for campus mental health planning and humanitarian practice. The high proportion of students screening positive for probable PTSD and anxiety suggests that university services in the Kurdistan Region may need substantially greater capacity for assessment, referral, and follow-up, capabilities the researchers note are currently lacking. Considering a history of adversity in routine assessment, provided it is done ethically and confidentially, may help contextualize students’ needs. Because social support was consistently associated with better outcomes, efforts to map and strengthen existing peer networks and student support structures may be reasonable components of broader well-being initiatives. In humanitarian settings, the results highlight the need to screen for ACEs and to protect and rebuild social connections for individuals and communities who have lost them.

The researchers acknowledge several limitations. The cross-sectional design precludes causal inference, the sample consisted exclusively of university students, and retrospective ACE reporting can introduce recall and reporting bias. The standard 10-item ACE measure may not fully capture adversity profiles salient in conflict-affected settings; the World Health Organization’s ACE International Questionnaire, for example, includes items on exposure to war and collective violence that could have been highly relevant to many participants. Future work would benefit from more contextually adapted measurement approaches that account for sociocultural factors and conflict-related exposures. Nevertheless, as the first study to explore the association between ACEs and mental health problems in the Kurdistan Region, the research provides a foundation for strategic planning among universities, humanitarian organizations, and other actors serving young adults in the region, underscoring the urgent need for greater mental health surveillance, expanded clinical screening, and investment in accessible psychosocial support.

Subject of Research: Mental Health

Article Title: Adverse childhood experiences, social support, and young adult mental health in the conflict-affected Kurdistan Region of Iraq

Article References: Hama-Amin, D. S., Bennouna, C., Vukovich, M. M., Mohammad, P. J., Muhammad Hussein, Y. W., Karim, B. M., Mohammed, V. A., Hussein, P. F., Hassan, S. N., & Hama Sharif, S. A. (2026). Adverse childhood experiences, social support, and young adult mental health in the conflict-affected Kurdistan Region of Iraq. Current Psychology, 45(20), Article 1621. https://doi.org/10.1007/s12144-026-10191-9

Image Credits: AI Generated

DOI: 10.1007/s12144-026-10191-9

Keywords: adverse childhood experiences, PTSD, generalized anxiety, social support, Kurdistan Region of Iraq, conflict-affected settings, university students, mental health, Adverse, childhood, experiences, social

The research team followed 284 patients with cervical cancer who underwent radical surgery followed by adjuvant concurrent chemoradiotherapy, a standard approach for women whose tumors show high-risk features after hysterectomy. Every blood abnormality observed during treatment was graded according to the Common Terminology Criteria for Adverse Events version 5.0, the widely used scale that ranks toxicity from grade 0 to grade 4. Patients were then divided into two groups: a mild group of 163 patients whose worst toxicity never exceeded grade 2, and a severe group of 121 patients who experienced grade 3 or grade 4 toxicity at some point during their course of therapy.

The single most striking finding was the behavior of lymphocytes, the white blood cells that include the T cells and B cells responsible for adaptive immunity. Lymphopenia occurred in 100.0 percent of patients, making it the only adverse event that touched every single participant in the study. More alarmingly, 37.67 percent of patients developed grade 3 or grade 4 lymphopenia, the levels at which infection risk climbs sharply and clinical attention becomes mandatory. Lymphopenia also arrived earlier than any other blood abnormality, with a median onset time of 16.5 days from the start of treatment, and it progressed to grade 3 or 4 severity at a median of just 25 days, meaning that by roughly the third or fourth week of a typical six-week course, more than a third of patients had already lost most of their circulating lymphocyte pool.

The broader spectrum of toxicity followed a predictable hierarchy of bone marrow sensitivity. Leukopenia, the general depletion of white blood cells, affected 93.66 percent of patients, while neutropenia, the loss of the neutrophils that form the first line of antibacterial defense, occurred in 74.65 percent. Anemia, the reduction of oxygen-carrying red blood cells, developed in 60.92 percent of patients, and thrombocytopenia, the loss of the platelets responsible for clotting, appeared in 21.83 percent. This pattern reflects the biology of pelvic irradiation combined with systemic chemotherapy: the rapidly dividing progenitor cells of the lymphoid lineage are the most vulnerable to DNA damage, followed by the granulocyte lineage, with the longer-lived red cells and platelets declining more slowly and less severely.

Using multivariable logistic regression to separate true independent risk factors from statistical noise, the researchers identified three factors that remained associated with severe hematological adverse events. Patients with FIGO stage IIB to IIIC disease, meaning locally advanced tumors that had spread beyond the cervix but not to distant organs, carried roughly double the odds of severe toxicity compared with earlier stages, with an odds ratio of 2.148 and a 95 percent confidence interval of 1.271 to 3.628. A history of neoadjuvant chemotherapy given before surgery independently increased the odds by 2.438-fold, with a confidence interval of 1.156 to 5.141, plausibly because the marrow had already been stressed before chemoradiotherapy began. The most powerful predictor, however, was a dosimetric measure of radiation exposure: when the volume of pelvic bone marrow receiving at least 40 gray, known as V40, reached 41 percent or more, the odds of severe toxicity jumped 7.389-fold, with a confidence interval of 3.712 to 14.710.

The pelvic bone marrow finding carries particular technical significance for radiation oncology. The flat bones of the pelvis, including the ilium, sacrum, and pubic bones, harbor a substantial reservoir of active hematopoietic marrow, and conventional radiation fields designed to cover lymph node drainage regions inevitably pass through these bones. When more than 41 percent of the pelvic marrow volume absorbs at least 40 gray, the progenitor cells within that exposed volume are effectively knocked out, and the remaining unirradiated marrow must compensate for the entire blood supply. The sevenfold increase in severe toxicity risk at this threshold suggests that V40 could serve as a practical planning constraint, guiding physicists and physicians to spare marrow volume during intensity-modulated treatment design in the same way they already constrain doses to the kidneys, bowel, and spinal cord.

The clinical consequences of severe toxicity were substantial and measurable. Compared with the mild group, patients in the severe group experienced longer durations of hematological adverse events and significantly higher rates of chemotherapy delay, chemotherapy dose reduction, and radiotherapy interruption. These disruptions matter because the effectiveness of concurrent chemoradiotherapy depends on maintaining treatment intensity: delaying or weakening the systemic component can compromise the short-term response. Indeed, the 3-month complete response rate was lower in the severe group than in the mild group, at 70.3 percent versus 82.8 percent, a difference that reached statistical significance with a P value of 0.012. Severe lymphopenia was also associated with a higher incidence of infection during treatment and with a higher pretreatment neutrophil-to-lymphocyte ratio, an inflammatory marker that may itself reflect a marrow already skewed toward stress before therapy commenced.

The connection between severe lymphopenia and infection deserves particular emphasis in the context of cancer treatment. Lymphocytes are not merely passive casualties of therapy; they are the cells that coordinate immune defense against bacterial, viral, and fungal pathogens, and they also participate in antitumor immune surveillance. When more than a third of patients lose their lymphocyte pool to grade 3 or 4 depletion within the first month of treatment, the clinical team must weigh the risk of opportunistic infection against the need to keep the treatment schedule intact. The finding that severe lymphopenia correlated with a higher pretreatment neutrophil-to-lymphocyte ratio hints that patients with a pre-existing inflammatory or stress profile may be more vulnerable to profound depletion once chemoradiotherapy begins, offering a potential blood-based screening tool that could be calculated from routine complete blood counts before the first fraction of radiation is delivered.

The study’s retrospective design and single-center cohort of 284 patients mean that the findings require validation in larger, prospective, and multi-institutional populations before they can be translated directly into clinical guidelines. Nevertheless, the authors argue that the practical implications are clear: early risk assessment before treatment begins, deliberate optimization of pelvic bone marrow dosimetry during radiation planning, and individualized supportive management, including growth factor support and prophylactic antimicrobial strategies for high-risk patients, may together reduce the burden of severe hematological toxicity. As concurrent chemoradiotherapy remains a cornerstone of adjuvant therapy for cervical cancer worldwide, identifying which patients will tolerate the full course and which will need treatment modification is a step toward preserving both the safety and the effectiveness of one of the most important regimens in gynecologic oncology.

Subject of Research: Spectrum and influencing factors of hematological adverse events associated with postoperative adjuvant concurrent chemoradiotherapy for cervical cancer

Article Title: Spectrum and influencing factors of hematological adverse events associated with postoperative adjuvant concurrent chemoradiotherapy for cervical cancer

Article References: Zhang, Z., Wu, T., Du, Y., Tian, W., Gong, S., Li, Z., & Xiao, Z. (2026). Spectrum and influencing factors of hematological adverse events associated with postoperative adjuvant concurrent chemoradiotherapy for cervical cancer. BMC Cancer. https://doi.org/10.1186/s12885-026-16900-8

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16900-8

Keywords: Spectrum, influencing, factors, hematological, adverse, events, associated, postoperative, adjuvant, concurrent, chemoradiotherapy, cervical

B/F/TAF is a three-drug coformulation that combines bictegravir, an integrase strand transfer inhibitor, with emtricitabine and tenofovir alafenamide, two antiretroviral agents that work through complementary mechanisms. The regimen is considered exceptionally potent, with a high genetic barrier to resistance and reduced renal and bone toxicity compared with older tenofovir formulations. However, as B/F/TAF has become a mainstay of antiretroviral therapy for people living with HIV across diverse populations, its long-term safety profile in real-world settings has remained incompletely characterized. The new study set out to address this gap by systematically mining post-marketing surveillance data accumulated since the drug’s approval.

The researchers extracted adverse event reports from the FAERS database covering the period from the first quarter of 2018 through the first quarter of 2025, including only those reports in which B/F/TAF was identified as the primary suspected drug. After applying the FDA’s official deduplication guidelines to remove duplicate records arising from quarterly data updates, the team retained 6,816 unique case reports encompassing 13,853 individual adverse events. All reported events were mapped to version 27.0 of the Medical Dictionary for Regulatory Activities, the standardized coding system used to classify adverse drug reactions across regulatory agencies worldwide.

To detect safety signals, the team employed four complementary disproportionality algorithms: the reporting odds ratio, the proportional reporting ratio with chi-square statistics, the Bayesian confidence propagation neural network, and the multi-item gamma Poisson shrinker. This combination of frequentist and Bayesian approaches enhances the robustness of signal detection, as each method calculates whether a particular drug-event pair is reported more frequently than would be expected by chance. A signal was considered valid only when specific statistical thresholds were met, such as the lower bound of the 95 percent confidence interval for the reporting odds ratio exceeding one, or the empirical Bayesian geometric mean exceeding two.

The analysis revealed that the highest number of reports fell under the category of injury, poisoning and procedural complications, with 1,792 cases, followed by general disorders and administration site conditions with 1,726 cases, and investigations with 1,499 cases. Only two system organ classes met all four disproportionality criteria simultaneously: congenital, familial and genetic disorders, and pregnancy, puerperium and perinatal conditions. At the level of individual preferred terms, the most frequently reported events were weight increase with 408 cases, product dose omission with 242 cases, and maternal exposure during pregnancy with 202 cases. The strongest signals by reporting odds ratio were viral load increased at 160.14, CD4 lymphocytes decreased at 124.60, and immune reconstitution inflammatory syndrome at 88.12.

Notably, the researchers emphasized that several of the strongest signals likely reflect treatment response rather than drug toxicity. Viral load increased and CD4 lymphocytes decreased are routine monitoring parameters in HIV care, and their high reporting odds ratios likely arise because clinicians report these values when treatment targets are not met, rather than because B/F/TAF directly causes virologic or immunologic deterioration. Similarly, immune reconstitution inflammatory syndrome represents a pathology of immune recovery following viral suppression, in which the reconstituted immune system mounts inflammatory responses against opportunistic pathogens. The team stressed that these pharmacovigilance signals should be distinguished from confirmed adverse drug reactions and interpreted as hypothesis-generating rather than causal.

The metabolic signals identified in the analysis corroborate growing concerns regarding integrase strand transfer inhibitor-associated complications. Weight increase and diabetes mellitus both generated robust signals, consistent with a recent META-INSTI analysis of FAERS data that reported elevated reporting odds ratios for hyperglycemia, new-onset diabetes, and weight gain with bictegravir. However, long-term phase 3 trial data and real-world cohort studies suggest that weight gain is most pronounced in the first year of treatment and in individuals with more advanced HIV disease at baseline, supporting a return-to-health hypothesis rather than a purely drug-driven effect. The renal signal represented by blood creatinine increased reflects the known renal tubular effect of tenofovir alafenamide without necessarily indicating glomerular injury, consistent with the established renal safety profile of this prodrug formulation.

Pregnancy-related signals emerged as particularly noteworthy in the analysis. Maternal exposure during pregnancy, foetal exposure during pregnancy, and spontaneous abortion all demonstrated robust signal generation, and the pregnancy and congenital disorder system organ classes were the only two to meet all four disproportionality criteria. The researchers noted that preliminary pharmacokinetic data support once-daily B/F/TAF without dose adjustment during pregnancy, and available pregnancy outcome data have not shown congenital malformations above the background rate. The spontaneous abortion signal warrants attention but must be interpreted in context, as it may reflect reporting of drug exposure during pregnancy rather than a causal association with pregnancy loss. The team called for continued vigilance and robust pregnancy registries to better characterize the reproductive safety profile of the regimen.

The analysis of time-to-onset data revealed that adverse signals cluster early in treatment but also emerge late. Among 2,064 reports with documented onset times, representing 30.28 percent of all case reports, the median time to onset was 60 days. The first month of therapy alone accounted for 37.94 percent of all reported events, followed by 12.45 percent in the second month and 7.27 percent in the third month. This early clustering underscores the first 90 days of therapy as a critical window for intensified safety monitoring. Importantly, 17.49 percent of events were reported after one year of treatment, challenging the assumption that safety surveillance can be relaxed after the initial phase. Long-term vigilance should focus on metabolic and cardiovascular risks requiring periodic glucose, lipid, and risk-score monitoring, as well as hepatobiliary events that may occur at varying times after initiation or withdrawal.

The researchers acknowledged several limitations inherent to FAERS-based analyses. Confounding by indication, concomitant medications, prior regimen switches, and the higher baseline prevalence of comorbidities among people living with HIV may all influence reported outcomes. Reporting bias may preferentially capture more clinically significant or novel events, and the absence of a comparator group precludes determination of whether observed signals are specific to B/F/TAF or reflect class effects of integrase inhibitors. Additionally, valid onset dates were available in only 30.28 percent of reports, potentially introducing selection bias into the time-to-onset analysis. Despite these constraints, the study provides a comprehensive real-world safety assessment of one of the most widely used antiretroviral regimens globally, reinforcing the necessity of longitudinal pharmacovigilance as B/F/TAF continues to serve an increasingly diverse and aging population of people living with HIV.

Subject of Research: A real-world pharmacovigilance study of FDA adverse event reporting system events for bictegravir/emtricitabine/tenofovir alafenamide

Article Title: A real-world pharmacovigilance study of FDA adverse event reporting system events for bictegravir/emtricitabine/tenofovir alafenamide

Article References: Liu, Y., Zhang, L., Li, X., & Zhao, H. (2026). A real-world pharmacovigilance study of FDA adverse event reporting system events for bictegravir/emtricitabine/tenofovir alafenamide. Frontiers in Pharmacology, 17, Article 1945154. https://doi.org/10.3389/fphar.2026.1945154

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1945154

Keywords: real-world, pharmacovigilance, adverse, event, reporting, system, events, bictegravir, emtricitabine, tenofovir, alafenamide, scientific research

The elevated odds of adverse outcomes in pregnancies occurring years before an SLE diagnosis aligns with a broader body of evidence indicating that the pathogenic processes underlying lupus begin long before patients meet classification criteria. Autoantibodies such as antinuclear antibodies, anti-double stranded DNA, and antiphospholipid antibodies can circulate for years, and in some cases more than a decade, before the emergence of characteristic clinical symptoms. During this preclinical window, low-grade inflammation, endothelial dysfunction, and immune complex formation may already be operative, and each of these mechanisms has plausible links to the placental and vascular pathology that underlies preeclampsia, fetal growth restriction, and pregnancy loss. The persistence of elevated risk even in pregnancies occurring more than five years before diagnosis, as seen in this cohort, suggests that subclinical immune dysregulation is not merely a transient precursor but a sustained biological state with real consequences for reproductive health.

Placental pathology offers one framework for understanding these associations. In established SLE, adverse pregnancy outcomes are frequently attributed to a combination of placental insufficiency, antiphospholipid antibody-mediated thrombosis, and complement activation at the maternal-fetal interface. Antiphospholipid antibodies in particular are known to bind trophoblast surfaces, interfere with normal placentation, and trigger complement-mediated inflammation that can culminate in early pregnancy loss or later-onset preeclampsia. If these antibodies or related immune disturbances are present during the preclinical phase of lupus, they could plausibly exert similar effects before any diagnosis is made. The study’s inclusion of antiphospholipid antibody status among the measured immunologic variables reflects this mechanistic reasoning, although the retrospective design means that the timing of antibody acquisition relative to individual pregnancies could not always be established with certainty.

The demographic composition of the cohort deserves attention when interpreting the findings. With more than four-fifths of participants self-identifying as Black and nearly a third residing in areas of high social vulnerability, the study captures a population that bears a disproportionate burden of both lupus incidence and poor pregnancy outcomes in the United States. Black women develop lupus at younger ages, experience more aggressive disease courses, and face higher rates of preeclampsia, preterm birth, and fetal demise compared with white women, even after accounting for socioeconomic factors. Structural determinants of health, including differential access to prenatal care, exposure to chronic stress, and environmental exposures, may compound the immunologic risks documented here. The use of an area-based social vulnerability measure in the analysis acknowledges this reality, and the fact that elevated pre-diagnosis risk persisted after adjustment suggests that the association is not fully explained by socioeconomic disadvantage alone, although residual confounding cannot be excluded in an observational design of this kind.

The methodological choice to use generalized estimating equations is well suited to this dataset, given that many participants contributed multiple pregnancies and outcomes within a single individual are correlated. By accounting for this within-person clustering, the analysis avoids the inflated precision that would result from treating repeated pregnancies as independent observations. The comparison strategy, anchoring risk estimates to ANA-positive controls rather than only ANA-negative controls, is also informative, because it isolates the contribution of evolving disease from the contribution of autoantibody positivity per se. The finding that ANA-positive and ANA-negative controls did not differ meaningfully in adverse outcome rates strengthens the conclusion that the excess risk among pre-diagnosis pregnancies stems from the underlying disease process rather than from serologic status alone.

Several limitations temper the interpretation of these results. The single-center design, drawing on a cohort established at one academic medical center, may limit generalizability to populations with different demographic and clinical profiles. The retrospective ascertainment of pregnancy histories, gathered through in-person interviews supplemented by electronic medical record review, introduces the possibility of recall bias, particularly for outcomes such as early spontaneous abortion that may not have been medically documented. The timing of autoantibody measurement relative to individual pregnancies was not standardized, meaning that some participants classified as ANA-positive controls may have seroconverted after their pregnancies, while some pre-diagnosis pregnancies may have occurred before any detectable autoimmunity. Classification of pregnancies by their temporal relationship to diagnosis also depends on the accuracy of the recorded diagnosis date, which itself may lag the true clinical onset of disease. Despite these constraints, the internal consistency of the dose-response-like pattern across the spectrum lends credibility to the central finding.

From a clinical standpoint, the results support the idea that pregnancy may serve as a sentinel opportunity for identifying women at risk of developing lupus. Pregnant women routinely engage with the health system through prenatal visits, laboratory testing, and ultrasound monitoring, creating multiple touchpoints where subtle signs of emerging autoimmunity could be recognized. Women who experience unexplained adverse pregnancy outcomes, particularly recurrent losses, severe or early-onset preeclampsia, or unexplained fetal growth restriction, are already sometimes evaluated for antiphospholipid syndrome and other rheumatologic conditions. The present findings suggest that such evaluations may be worthwhile even when the adverse outcome occurred years before any rheumatologic symptoms appear, and that a history of adverse pregnancy outcomes could be considered a potential marker within the preclinical lupus spectrum warranting longitudinal follow-up.

For rheumatologists and obstetricians caring for women with known SLE, the markedly elevated odds of adverse outcomes after diagnosis, roughly threefold in this cohort, reinforce established guidance that pregnancies in lupus patients should be planned when disease is quiescent and managed with coordinated multidisciplinary care. Hydroxychloroquine, low-dose aspirin, and careful monitoring of renal function and serologic activity are among the interventions with evidence for improving outcomes in this population. The lower median number of pregnancies observed among women after diagnosis may reflect both counseling about contraceptive choices and disease-related subfertility or pregnancy loss, underscoring how a lupus diagnosis reshapes reproductive trajectories.

Future research directions follow naturally from these findings. Prospective studies that measure autoantibodies and inflammatory markers serially before and during pregnancy could clarify whether specific immunologic signatures predict adverse outcomes within the preclinical window. Mechanistic work examining complement activation, type I interferon signaling, and placental pathology in pre-diagnosis pregnancies could illuminate the biological pathways involved. Additionally, investigating whether early intervention during the pre-SLE phase, such as hydroxychloroquine initiation in ANA-positive individuals with concerning features, could mitigate pregnancy risk represents a compelling question for clinical trials. Finally, replicating these results in more diverse cohorts and in centers serving different populations would establish whether the pre-diagnosis risk gradient is a general feature of lupus natural history or is modified by demographic and social context.

In sum, this study adds to a growing recognition that systemic lupus erythematosus is not a disease with a discrete onset but rather the culmination of a prolonged period of immune dysregulation with clinically meaningful consequences. The demonstration that pregnancy outcomes are compromised years before diagnosis, while isolated autoantibody positivity remains benign, refines the concept of the pre-SLE state and offers a practical framework for risk stratification. For women of childbearing age with lupus in their families, unexplained adverse pregnancy outcomes, or evolving autoimmunity, these findings argue for heightened vigilance and for viewing the reproductive years as both a window of vulnerability and an opportunity for earlier detection.

Subject of Research: Adverse pregnancy outcome associations among women prior to a diagnosis of systemic lupus erythematosus

Article Title: Adverse pregnancy outcome associations among women prior to a diagnosis of systemic lupus erythematosus

Article References: English, J. A., Wolf, B. J., & Kamen, D. L. (2026). Adverse pregnancy outcome associations among women prior to a diagnosis of systemic lupus erythematosus. Frontiers in Lupus, 4, Article 1806496. https://doi.org/10.3389/flupu.2026.1806496

Image Credits: AI Generated

DOI: 10.3389/flupu.2026.1806496

Keywords: lupus, pregnancy, autoimmunity, ANA, preeclampsia, preterm birth, reproductive health, rheumatology, Adverse, outcome, associations, women

Tens of millions of people worldwide remain at risk of chronic arsenic exposure, including populations in Bangladesh, India, Pakistan, Taiwan, Vietnam, Mexico, China, Argentina, Chile, and the United States. Drinking contaminated well water remains the most important route of exposure in many settings, although diet can become a dominant source once water is controlled. Rice and rice-based products contribute measurable inorganic arsenic intake, and the European Union, Taiwan, and the United States have established regulatory limits for inorganic arsenic in rice, with stricter thresholds for infant foods. Brown rice generally contains higher arsenic concentrations than polished white rice, because arsenic accumulates in the outer husk layers.

Interpreting arsenic biomarkers is complicated by seafood, which contains mostly organic arsenic species such as arsenobetaine that are considered of low toxicity and rapidly excreted. Nevertheless, seafood consumption can elevate urinary arsenobetaine and dimethylarsinate, muddying the use of total urinary arsenic as a proxy for inorganic exposure in seafood-consuming populations. Urinary arsenic speciation, which separates inorganic arsenic and its methylated metabolites monomethylarsonic acid and dimethylarsinic acid, offers a more informative metric. In a long follow-up cohort from an arsenicosis-endemic area, low-to-moderate exposure was associated with urothelial tract cancers, with susceptibility signals concentrated among individuals with lower primary methylation index or higher secondary methylation index, indicating that the body’s capacity to methylate arsenic shapes disease risk.

A striking translational advance is an artificial intelligence-based, noninvasive tool that estimates arsenic exposure from standardized photographs of the hands and feet. The algorithm leverages cutaneous stigmata such as hyperkeratosis patterns to classify exposure categories, potentially enabling scalable screening where laboratory testing is limited. This matters because arsenic leaves visible fingerprints on the skin: palmoplantar hyperkeratosis and variegated pigmentation are clinical hallmarks of chronic poisoning, and arsenic-associated skin cancers are distinguished from classical UV-related skin cancers by their multiplicity and their predilection for sun-spared skin.

The skin serves as a sentinel organ for both exposure and immune disruption. Arsenic is classified by the International Agency for Research on Cancer as a Group 1 carcinogen, yet it is often considered a weak mutagen, acting predominantly at the promotion rather than initiation stage of chemical carcinogenesis. After decades of exposure, skin cancers and keratosis may precede internal cancers of the bladder, lung, and liver, making cutaneous lesions an early surrogate indicator of systemic risk. The observation that only a subset of exposed individuals develop cancers or vascular disease suggests that host factors, including immune responses, modulate susceptibility. In patients with arsenic-associated cancers, the in vivo delayed-type hypersensitivity response, which depends on antigen-presenting cells and T cells, is impaired, and in blackfoot disease, anti-endothelial cell IgG antibodies drive endothelial proliferation and VEGF-dependent angiogenesis.

Experimental evidence reveals how arsenic differentially affects immune cell types. Arsenic selectively induces Fas-dependent apoptosis of Th2 lymphocytes, mobilizes epidermal Langerhans cells, the professional antigen-presenting cells of the epidermis, and polarizes Th1 responses in arsenical cancers. Macrophages from exposed individuals show reduced adhesion capacity and impaired phagocytosis, while monocytes from exposed children produce less superoxide anion and nitric oxide. Cytokine signatures are context-dependent: in a mouse epicutaneous sensitization model, arsenic elevated IFN-γ and IL-12 secretion, supporting Th1 polarization, but in humans with arsenic-induced skin lesions, stimulated T-cell proliferation is dose-dependently impaired with reduced IFN-γ, TNF-α, and IL-2 output. Population studies in Bangladesh reported elevated circulating type 2 cytokines, eotaxin, and IgE in exposed individuals with skin lesions, while ex vivo stimulation assays showed broader cytokine suppression, indicating that steady-state serum signatures and stimulated T-cell capacity can diverge by disease stage.

Innate inflammatory pathways emerge as a consistent theme. Subchronic arsenic exposure activates the AIM2 inflammasome in human keratinocytes and mouse skin, leading to caspase-1 activation and increased IL-1β and IL-18 production. Analyses of human skin samples in arsenic-related pathology have reported increased IL-6 and IL-17 levels with progressive increases across worsening skin-damage severity, while functional T-cell assays from exposed individuals have reported decreased IL-10 secretion. Dose-response relationships appear non-linear: within low-to-moderate exposure ranges, several studies support dose-related shifts toward innate immune activation and systemic inflammation, with West Bengal women exposed to 11–50 μg/L arsenic in groundwater showing increased monocyte CD14 expression, NF-κB signaling, and elevated circulating TNF-α, IL-6, IL-8, and IL-12 alongside reduced IL-10. At higher cumulative exposures or in patients with established arsenic-associated cancers, evidence points toward adaptive immune suppression, particularly impaired T-cell responsiveness.

Perinatal exposure represents a critical window for immune programming. In a Taiwanese birth cohort with 15-year follow-up, prenatal heavy metal exposure including arsenic was associated with cord blood IgE levels and distinct IgE trajectory patterns in relation to atopic diseases. Prenatal inorganic arsenic exposure was also linked to higher risk of atopic dermatitis in young children, and a U.S. cord-blood study showed that maternal arsenic levels were inversely associated with cord-blood T helper memory cells. Prenatal co-exposure to other metals may further modify risk; a study from China reported that prenatal co-exposure to higher levels of arsenic and thallium contributed substantially to the combined risk of allergic rhinitis. These findings highlight developmental immunotoxicology as a frontier for integrating arsenic exposure, cutaneous immunology, and allergic disease risk across the life course.

Genetic and epigenetic susceptibility further shape individual risk. TIMP3 promoter polymorphisms were associated with increased susceptibility to arsenic-induced skin cancer in an exposed cohort, with in silico analyses suggesting allele-specific transcription factor binding effects that influence matrix metalloproteinase activity and tissue architecture. Arsenic methylation capacity, repeatedly implicated in differential disease risk, is itself coupled to inherited variation: AS3MT haplotype status has been associated with DNA methylation and expression of multiple genes near AS3MT, illustrating how germline variation can shape the epigenetic context for exposure response. The review’s authors propose that integrating genotype, methylation indices, immune phenotyping, and clinical outcomes could operationalize risk stratification, while water mitigation, which has been associated with a reduced burden of arsenic-related cancers in Taiwan with substantial age-cohort effects, remains the cornerstone of primary prevention. Because cancer risk persists for years to decades after exposure reduction, targeted long-term surveillance of previously exposed communities, combined with scalable phenotyping tools and precision prevention strategies, offers the most promising path forward for the tens of millions still living with arsenic’s invisible immune legacy.

Subject of Research: Immune dysregulation as a mechanism linking chronic arsenic exposure to cancers and allergic disease

Article Title: Immune perturbation in arsenic-induced adverse health effects and cancers

Article References: Hong, C.-H., Yu, S., Wang, S.-L., Yu, H.-S., & Lee, C.-H. (2026). Immune perturbation in arsenic-induced adverse health effects and cancers. Journal of Cutaneous Immunology and Allergy, 9, Article 16386. https://doi.org/10.3389/jcia.2026.16386

Image Credits: AI Generated

DOI: 10.3389/jcia.2026.16386

Keywords: arsenic, immune dysregulation, skin cancer, environmental toxicology, allergic disease, biomonitoring, perinatal exposure, genetic susceptibility, Immune, perturbation, arsenic-induced, adverse

The research team, led by Marina Leonor Pinheiro and Olga Cunha of the University of Minho in Portugal, together with Marta Sousa and Rui Abrunhosa Gonçalves, focused on a group that has long been underrepresented in psychopathy research. Most of what scientists know about the developmental roots of psychopathic traits comes from studies of men, even though women constitute a growing share of the incarcerated population and display distinct patterns of offending, trauma exposure, and emotional functioning. Psychopathy itself is not a monolith. Contemporary models, including the widely used four-facet structure, distinguish between an interpersonal facet marked by manipulation and superficial charm, an affective facet defined by shallow emotion and lack of remorse, a lifestyle facet characterized by impulsivity and irresponsibility, and an antisocial facet reflecting a history of rule-breaking and criminal behavior.

Participants in the study, whose average age was just under 39 years, completed a battery of validated self-report instruments. The ACEs Scale captured the accumulated weight of childhood adversity, from physical and emotional abuse to living in a household marked by substance misuse or mental illness. The Benevolent Childhood Experiences Scale, developed specifically to measure the positive side of the developmental ledger, assessed the presence of supportive figures, safe surroundings, and comforting memories that can counterbalance harm. Adult attachment was measured with the Adult Attachment Scale–Revised, which yields three dimensions: anxiety about abandonment, comfort with closeness, and trust in others. Psychopathic traits were assessed with the Self-Report Psychopathy Scale–Short Form, allowing the researchers to examine both total scores and the individual facets separately.

The results confirmed the central association that decades of prior work had predicted. Adverse childhood experiences were positively associated with psychopathic traits overall, and the connection was particularly strong for the lifestyle and antisocial facets, the dimensions most closely tied to impulsive, unstable, and rule-violating behavior. In other words, women who reported more cumulative adversity in childhood were more likely to display the behavioral patterns of psychopathy that contribute directly to criminal careers and institutional misconduct. This facet-specific pattern matters theoretically, because it suggests that early trauma may shape the behavioral expression of psychopathy more powerfully than its emotional or interpersonal core.

Equally revealing was what the researchers found when they turned the lens toward positive childhood experiences. These benevolent early experiences were negatively associated with the lifestyle facet of psychopathy, meaning that women who recalled more supportive and nurturing childhood environments reported lower levels of impulsivity and irresponsibility in adulthood. The finding aligns with a rapidly expanding body of literature on what some researchers have called counter-ACEs, the idea that positive experiences can accumulate their own protective momentum and promote adaptive functioning even in the presence of significant adversity. Prior studies have linked positive childhood experiences to better adult mental health, stronger relationships, and reduced psychopathology across general and justice-involved populations.

But the study’s most ambitious test, and its most sobering result, concerned the interplay between these early experiences and adult attachment. Drawing on attachment theory, which holds that early caregiver relationships form internal working models that guide close relationships across the lifespan, the researchers hypothesized that the protective effect of positive childhood experiences might depend on a woman’s adult attachment profile. Secure attachment, characterized by low anxiety, comfort with closeness, and trust in others, could plausibly amplify the benefits of a benevolent childhood, while attachment insecurity could erode them. Using moderated moderation analyses, a statistical technique capable of detecting three-way interactions in which two moderators jointly condition the strength of an association, the team tested this possibility for each attachment dimension.

The verdict was negative. After applying false discovery rate correction, a stringent statistical safeguard against spurious findings when multiple tests are conducted, none of the hypothesized three-way interactions between adverse experiences, positive experiences, and any of the three attachment dimensions reached significance. Attachment anxiety, comfort with closeness, and trust in others did not condition the relationship between childhood adversity and psychopathic traits in this sample. The protective role that the researchers predicted for positive childhood experiences, in other words, was not amplified or diminished by adult attachment patterns among these incarcerated women. The authors interpret this as evidence that the hypothesized buffering mechanism may be more complex than attachment theory alone can explain, or that it may operate differently in forensic populations than in community samples.

The null findings carry real scientific weight. Interaction effects are notoriously difficult to detect and replicate, and recent methodological work has shown that developmental moderation hypotheses often fail to reproduce across cohorts and domains. By reporting their corrected non-significant results transparently, the Portuguese team contributes to a more honest map of where protective factors do and do not matter. The findings suggest instead a simpler picture: adverse and positive childhood experiences each show direct, facet-specific associations with psychopathic traits, and any protective effect of benevolent experiences appears not to hinge on how securely or insecurely these women attach to others as adults. For clinicians working in women’s prisons, the practical implication is that trauma history remains a critical risk marker, particularly for impulsive and antisocial behavior, while positive childhood experiences may merit attention as an independent, albeit modest, protective signal.

The study also highlights the broader case for trauma-informed care in correctional settings, an approach that recognizes the prevalence of childhood victimization among incarcerated women and integrates that understanding into assessment, treatment, and institutional policy. Because the design was cross-sectional and relied on retrospective self-reports, the researchers caution that causal direction cannot be established and that memory biases may influence reported adversity. The sample, drawn from Portuguese prisons, may not generalize to other cultural contexts. Still, as one of the few studies to examine ACEs, positive childhood experiences, attachment, and psychopathy simultaneously in women, the work opens a clear path forward: longitudinal designs and larger samples will be needed to determine whether benevolent early experiences truly inoculate against psychopathic outcomes, and under what relational conditions that protection takes hold.

Subject of Research: The relationship between adverse childhood experiences and psychopathic traits in incarcerated women, examining the moderating roles of positive childhood experiences and adult attachment.

Article Title: Adverse Childhood Experiences and Psychopathic Traits in Women: An Exploratory Study of the Moderating Role of Positive Childhood Experiences and Attachment

Article References: Pinheiro, M. L., Sousa, M., Gonçalves, R. A., & Cunha, O. (2026). Adverse Childhood Experiences and Psychopathic Traits in Women: An Exploratory Study of the Moderating Role of Positive Childhood Experiences and Attachment. Journal of Child & Adolescent Trauma. https://doi.org/10.1007/s40653-026-00971-7

Image Credits: AI Generated

DOI: 10.1007/s40653-026-00971-7

Keywords: adverse childhood experiences, positive childhood experiences, psychopathic traits, attachment, incarcerated women, childhood trauma, moderated moderation, forensic psychology, Journal of Child & Adolescent Trauma, resilience, Adverse, Childhood