A Systematic Review and Meta-Analysis.

[Posted 23/Jan/2026]

AUDIENCE: Psychiatry, Family Medicine

KEY FINDINGS: Results of this systematic review and meta-analysis suggest that depressive disorders, anxiety disorders, PTSD, and sleep disorders were associated with an increased risk of ACS. Particularly, PTSD and sleep disorders emerged as significant risk factors for ACS, indicating the potential impact of sleep quality on cardiovascular outcomes. Future research addressing these limitations could provide more nuanced insights into the association between mental health and ACS.

BACKGROUND: Aim of this study is to estimate the association of ACS among patients with mental disorders, as compared with patients without mental disorders.

DETAILS: Study screening was performed in duplicates with conflicts resolved upon consensus. Inclusion criteria were as follows: (1) observational or randomized study, (2) measured association with ACS (incident events, risk ratio, odds ratio, hazard ratio [HR]), and (3) investigated any clinical mental disorder (based on DSM and International Classification of Diseases) before ACS events. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Data extraction was performed in duplicate and resolved on consensus. Data were quantitatively synthesized through random-effects meta-analysis. The National Institutes of Health Study Quality Assessment Tools were used to assess the quality of included studies. Studies were analyzed from January 1966 to October 2021. Among 3616 initially identified studies, 25 full-text articles met inclusion criteria with 22,048,504 participants of median (IQR) age 48.0 (34.5-56.1) years, with 13 019 897 males (59.1%). Depressive disorder (HR, 1.40; 95% CI, 1.11-1.78; P = .01; Grading of Recommendations Assessment, Development, and Evaluation [GRADE] certainty = very low), anxiety disorder (HR, 1.63; 95% CI, 1.40-1.89; P < .001; GRADE certainty = low), sleep disorder (HR, 1.60; 95% CI, 1.22-2.10; P < .001; GRADE certainty = low), and posttraumatic stress disorder (PTSD; HR, 2.73; 95% CI, 1.94-3.84; P < .001; GRADE certainty = moderate) were associated with increased risk of ACS. Bipolar (HR, 1.48; 95% CI, 0.47-4.61; P = .28; GRADE certainty = very low) and psychotic (HR, 0.97; 95% CI, 0.01-178.30; P = .06; GRADE certainty = very low) disorders were not significantly associated with increased risk of acute myocardial infarction, although they had similar point estimates to some other mental disorders.

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Source: Gupta, A., Tejpal, T., Seo, C., et al. Mental Disorders as a Risk Factor of Acute Coronary Syndrome: A Systematic Review and Meta-Analysis. JAMA Psychiatry.. Published: January 14, 2065. DOI: 10.1001/jamapsychiatry.2025.4253.

[Posted 2/Sep/2026]

AUDIENCE: Hematology, Oncology

KEY FINDINGS: In this phase II study, azacitidine, venetoclax, and gilteritinib produced high remission rates and encouraging long-term survival in patients with newly diagnosed FLT3-mutated AML who were unfit for intensive chemotherapy. The 3-year RFS and OS rates were 43% and 46%, respectively, although outcomes were less favorable in patients with FLT3-ITD mutations and baseline RAS pathway mutations. Most evaluable relapses were FLT3-negative, suggesting that resistance may involve mechanisms beyond persistent FLT3-mutated disease. Dose or duration reductions were frequently required during consolidation, primarily reflecting the challenge of managing myelosuppression. Randomized studies are needed to establish the role of this triplet regimen relative to current standard approaches.

BACKGROUND: Relapse after frontline azacitidine and venetoclax remains a major challenge in patients with FLT3-mutated acute myeloid leukemia (AML), with relapse often associated with expansion of FLT3-mutated clones. This phase II study evaluated the long-term efficacy and safety of adding the FLT3 inhibitor gilteritinib to azacitidine and venetoclax in adults with newly diagnosed FLT3-mutated AML who were considered unfit for intensive chemotherapy.

DETAILS: Thirty patients with newly diagnosed FLT3-mutated AML were treated with the azacitidine, venetoclax, and gilteritinib triplet regimen. The median age was 71 years, and 22 (73%) patients had FLT3-ITD mutations. Fourteen patients (47%) proceeded to allogeneic hematopoietic stem cell transplantation in first remission. The median follow-up was 41.5 months.

The complete remission or complete remission with incomplete hematologic recovery rate was 96%. Eleven patients (37%) subsequently relapsed, and among evaluable relapses, the FLT3 mutation was no longer detectable in 67%, indicating that relapse mechanisms were not necessarily driven by persistent FLT3-mutated disease.

The median relapse-free survival (RFS) was 23.4 months and median overall survival (OS) was 29.7 months. At 3 years, RFS was 43% and OS was 46%. Among patients with FLT3-ITD-mutated AML, median RFS and OS were 17.0 months and 21.8 months, respectively, with 3-year RFS and OS rates of 32% and 36%. Baseline RAS pathway mutations were associated with poorer outcomes.

Survival outcomes were similar regardless of whether patients underwent allogeneic hematopoietic stem cell transplantation in first remission. Among patients receiving at least one consolidation cycle, 68% required a reduction in the dose or duration of at least one study drug, highlighting the need to manage treatment-related myelosuppression during prolonged therapy.

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Source: Short, N. J., Kantarjian, H. M., Daver, N., et al. Long-Term Outcomes of Azacitidine, Venetoclax and Gilteritinib in Newly Diagnosed FLT3-Mutated AML. Blood Advances.. 2026; 10(17): 5743–5750. Published: May 27, 2026. DOI: 10.1182/bloodadvances.2026019841.

[Posted 2/Sep/2026]

AUDIENCE: Hematology, Oncology

KEY FINDINGS: In this phase II study, azacitidine, venetoclax, and gilteritinib produced high remission rates and encouraging long-term survival in patients with newly diagnosed FLT3-mutated AML who were unfit for intensive chemotherapy. The 3-year RFS and OS rates were 43% and 46%, respectively, although outcomes were less favorable in patients with FLT3-ITD mutations and baseline RAS pathway mutations. Most evaluable relapses were FLT3-negative, suggesting that resistance may involve mechanisms beyond persistent FLT3-mutated disease. Dose or duration reductions were frequently required during consolidation, primarily reflecting the challenge of managing myelosuppression. Randomized studies are needed to establish the role of this triplet regimen relative to current standard approaches.

BACKGROUND: Relapse after frontline azacitidine and venetoclax remains a major challenge in patients with FLT3-mutated acute myeloid leukemia (AML), with relapse often associated with expansion of FLT3-mutated clones. This phase II study evaluated the long-term efficacy and safety of adding the FLT3 inhibitor gilteritinib to azacitidine and venetoclax in adults with newly diagnosed FLT3-mutated AML who were considered unfit for intensive chemotherapy.

DETAILS: Thirty patients with newly diagnosed FLT3-mutated AML were treated with the azacitidine, venetoclax, and gilteritinib triplet regimen. The median age was 71 years, and 22 (73%) patients had FLT3-ITD mutations. Fourteen patients (47%) proceeded to allogeneic hematopoietic stem cell transplantation in first remission. The median follow-up was 41.5 months.

The complete remission or complete remission with incomplete hematologic recovery rate was 96%. Eleven patients (37%) subsequently relapsed, and among evaluable relapses, the FLT3 mutation was no longer detectable in 67%, indicating that relapse mechanisms were not necessarily driven by persistent FLT3-mutated disease.

The median relapse-free survival (RFS) was 23.4 months and median overall survival (OS) was 29.7 months. At 3 years, RFS was 43% and OS was 46%. Among patients with FLT3-ITD-mutated AML, median RFS and OS were 17.0 months and 21.8 months, respectively, with 3-year RFS and OS rates of 32% and 36%. Baseline RAS pathway mutations were associated with poorer outcomes.

Survival outcomes were similar regardless of whether patients underwent allogeneic hematopoietic stem cell transplantation in first remission. Among patients receiving at least one consolidation cycle, 68% required a reduction in the dose or duration of at least one study drug, highlighting the need to manage treatment-related myelosuppression during prolonged therapy.

Copyright © Skyscape. All rights reserved.

Source: Short, N. J., Kantarjian, H. M., Daver, N., et al. Long-Term Outcomes of Azacitidine, Venetoclax and Gilteritinib in Newly Diagnosed FLT3-Mutated AML. Blood Advances.. 2026; 10(17): 5743–5750. Published: May 27, 2026. DOI: 10.1182/bloodadvances.2026019841.

[Posted 1/Sep/2026]

AUDIENCE: Internal Medicine, Neurology, Cardiology

KEY FINDINGS: Common age-related somatic diseases appear to be more consistently associated with cerebrovascular injury, brain atrophy, and neuronal loss than with amyloid or tau pathology. These findings suggest that the relationship between systemic disease and dementia may involve multiple non-AD pathways rather than a direct effect on classical AD pathology. The review highlights the importance of recognizing mixed dementia and considering systemic health when evaluating brain aging and cognitive decline.

BACKGROUND: Several common age-related somatic diseases are associated with an increased risk of dementia, but the neuropathological pathways underlying these associations remain incompletely understood. This narrative review examined evidence linking heart disease, type 2 diabetes, kidney disease, liver disease, lung disease, and anemia with brain pathology, including Alzheimer's disease (AD)-related amyloid and tau pathology and non-AD changes such as neuronal loss, brain atrophy, cerebrovascular lesions, neuroinflammation, and non-AD proteinopathies.

DETAILS: The authors conducted a PubMed search for human studies investigating associations between somatic diseases and brain pathology using postmortem examinations, brain imaging, or cerebrospinal fluid biomarkers. The available evidence was qualitatively synthesized and graded according to its strength. The review specifically evaluated whether common systemic diseases were associated with AD-related pathology or with other forms of brain injury that may contribute to cognitive impairment and dementia.

Across the conditions examined, the strongest and most consistent associations were between somatic diseases and global neuronal loss or brain atrophy, as well as cerebrovascular lesions. In contrast, associations between somatic diseases and amyloid or tau deposition were limited and inconsistent. The review found no systematic studies examining neuroinflammation or non-AD proteinopathies in relation to somatic diseases.

Overall, the available evidence suggests that systemic diseases may contribute to brain damage predominantly through non-AD mechanisms, particularly cerebrovascular injury and diffuse neuronal loss, rather than by directly driving the characteristic amyloid and tau pathology of AD. The authors emphasize that these processes may contribute to the complex combination of pathologies frequently underlying dementia in older adults.

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Source: Grande, G., Valletta, M., Gasparini, F., et al. Brain pathology in relation to somatic diseases: Exploring the body–brain crosstalk. Journal of Internal Medicine. 2026; 300(3): 223–237. Published: June 2, 2026. DOI: 10.1111/joim.70119.

[Posted 27/Aug/2026]

AUDIENCE: Psychiatry, Pediatric

KEY FINDINGS: Across five experimental studies, AI educational services were associated with greater guilt, lower perceived value, and, in several conditions, less willingness to recommend the approach compared with direct parental engagement. The findings indicate that reluctance to use AI for children's education may be linked less to perceptions of AI capability and more to the belief that educating one's children is a parental responsibility. The study also suggests that framing AI use as necessary because of an individual's limitations, or demonstrating that other parents use AI services, may improve positive WOM toward these services.

BACKGROUND: Artificial intelligence (AI) educational services are increasingly positioned as tools that can assist children with learning and tutoring. However, the decision to use these services may be influenced by more than their perceived educational capability. This research examined how choosing AI educational services rather than direct parental involvement affects guilt, perceived value, and willingness to recommend the approach to others. Across five experimental studies, the investigators also examined whether perceived parental responsibility, intrinsic reasons for using AI, and conformity influence these responses.

DETAILS: The research used experimental designs comparing parental engagement with AI educational services across homework and writing-tutoring scenarios. Study 1a included 191 participants after exclusion of 9 cases; Study 1b included 200 participants; Study 2 included 200 participants; Study 3 included 390 participants; and Study 4 included 400 participants. Participants were recruited through the Credamo online platform.

In Study 1a, participants who considered using AI educational services reported greater guilt and assigned a lower monetary valuation than those who personally tutored their children. Mean guilt scores were 2.74 (SD 1.81) with AI educational services versus 2.09 (SD 1.58) with parental engagement (t=2.67, p=.008). Mean valuation was 1219.31 (SD 1154.32) versus 2097.99 (SD 2217.96), respectively (t=3.41, p=.001).

Study 1b reproduced these findings without using pictures and after accounting for parental status. Guilt was higher with AI educational services than with parental engagement (5.23 [SD 2.94] vs 3.79 [SD 2.47]; F(1, 198)=14.07, p<.001, η^p₂=.07). Valuation was lower with AI educational services (1219.62 [SD 1581.27] vs 2494.11 [SD 2530.90]; F(1, 198)=18.24, p=.001, η^p₂=.08).

Study 2 extended the analysis to willingness to recommend the educational approach. Participants using AI educational services reported greater guilt, lower valuation, and lower word-of-mouth (WOM) intentions than participants engaging in education themselves. Among participants with children, guilt means were 3.09 (SD 2.35) for AI educational services and 2.32 (SD 2.31) for parental engagement (F=4.18, p=.043, η^p₂=.03). Valuation was 477.83 (SD 547.20) versus 968.14 (SD 780.09), respectively (F=21.14, p<.001, η^p₂=.12), while WOM was 7.83 (SD 1.65) versus 8.23 (SD 1.41) (F=4.77, p=.030, η^p₂=.03).

Perceived responsibility for children's education emerged as an important explanatory mechanism. Attribution scores among participants with children were 6.27 (SD 2.50) in the AI condition and 8.79 (SD 0.86) in the parental-engagement condition (F=87.92, p<.001, η^p₂=.36). Mediation analysis showed that attribution significantly mediated the relationship between educational approach and guilt, valuation, and WOM, with effects of 0.6116, -183.9280, and -0.8910, respectively.

Study 3 demonstrated that the reason for choosing AI could alter the pattern of WOM responses. When participants lacked the ability to tutor their children, those using AI educational services reported greater positive WOM than those personally tutoring their children: 7.60 (SD 1.47) versus 6.76 (SD 2.29), p=.006. In the control condition, the pattern was reversed, with WOM scores of 7.36 (SD 1.90) for AI educational services and 7.86 (SD 1.23) for parental engagement (p=.04).

Study 4 found that social conformity also influenced WOM. Overall, WOM was lower with AI educational services than with parental engagement: 7.59 (SD 2.19) versus 8.30 (SD 1.10) (F(1, 396)=17.23, p.001, η^p₂=.04). When participants were given information that other parents were using AI educational services, the difference was no longer statistically significant (7.88 [SD 1.94] vs 8.24 [SD 1.23], p=.133). Without such conformity information, WOM was significantly lower for AI educational services (7.29 [SD 2.39] vs 8.36 [SD 0.94], p<.001).

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Source: Shao, A., Lu, Z., Liu, S. Q., et al. Demystifying the mist: Why do individuals hesitate to accept AI educational services?. British Journal of Psychology. 2026; 117(3): 932-956. Published: August, 2026. DOI: 10.1111/bjop.70040.

A population-based cohort study in Sweden and Norway.

[Posted 17/Aug/2026]

AUDIENCE: Neurology, Psychiatry

KEY FINDINGS: In this large Nordic population-based cohort, paternal valproate monotherapy during spermatogenesis was not significantly associated with neurodevelopmental disorders in offspring compared with paternal lamotrigine or levetiracetam monotherapy. Findings were consistent across dose-response analyses and among fathers with epilepsy. The results do not support an increased neurodevelopmental risk from paternal valproate exposure, although limitations inherent to registry-based observational research remain.

BACKGROUND: Valproate is an effective antiseizure medication, but its established teratogenic effects with maternal exposure have led to regulatory restrictions for women of reproductive potential. Concerns about possible paternal effects on offspring neurodevelopment have also prompted precautionary recommendations for men. This study evaluated whether paternal valproate use during spermatogenesis was associated with neurodevelopmental disorders (NDDs) in offspring.

DETAILS: This population-based cohort study used nationwide Swedish and Norwegian health registries. It included singleton live births at >=22 completed gestational weeks between 1 January 2007 and 31 December 2020 in Sweden and between 1 January 2010 and 31 December 2018 in Norway. After exclusions, 4681 children in Sweden and 1572 children in Norway were included for analysis.

The analysis compared children whose fathers received valproate monotherapy during spermatogenesis with children whose fathers received lamotrigine or levetiracetam monotherapy. Outcomes included NDDs, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability (ID), and disorders of psychological development. Analyses were adjusted for relevant parental and child characteristics, including parental age, psychiatric diagnoses, psychotropic medication use, epilepsy diagnosis, and, in Sweden, parental education and maternal cohabitation/marital status.

The study specifically examined paternal antiseizure medication exposure during spermatogenesis, corresponding to the approximately 3 months before conception. Dose-response analyses and analyses restricted to fathers with epilepsy were also conducted.

Among the children included in the primary comparison, 2051 were born to fathers who used valproate monotherapy during spermatogenesis. No significant association was identified between paternal valproate exposure and NDDs compared with paternal lamotrigine or levetiracetam exposure. The findings remained consistent in dose-response analyses and when the analysis was restricted to fathers with epilepsy.

During follow-up in Sweden, 406 children were diagnosed with an NDD, including 287 with ADHD, 140 with ASD, 55 with ID, and 79 with disorders of psychological development. In Norway, 60 children were diagnosed with an NDD, including 35 with ADHD, 13 with ASD, 5 with ID, and 26 with disorders of psychological development.

For ASD, the pooled adjusted hazard ratio was 1.29 (95% CI 0.89 to 1.85). The study authors noted that point estimates were slightly above 1.0 in some analyses but did not reach statistical significance.

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Source: Razaz, N., Soderling, J., Tomson, T., et al. Risk of Neurodevelopmental Disorders Associated With Paternal Use of Valproate During Spermatogenesis. Journal of Neurology, Neurosurgery & Psychiatry. 2026; 97-8: 671-679. Published: August, 2026. DOI: 10.1136/jnnp-2025-337441.

[Posted 6/Aug/2026]

AUDIENCE: Oncology, Ob/Gyn

KEY FINDINGS: This study demonstrates that gut microbiome imbalance may contribute to HR+ breast cancer progression through systemic metabolic and inflammatory mechanisms. Dysbiosis-associated elevation of primary bile acids was shown to promote mammary inflammation and tumor dissemination through PGE2 signaling. Clinical database analyses further suggested that bile acid pathway modulation, including bile acid sequestrant use, may be associated with improved survival outcomes in metastatic disease. These findings highlight the potential importance of microbiome-derived metabolites in cancer biology and future precision oncology strategies.

BACKGROUND: Breast cancer metastasis remains a major clinical challenge, particularly in hormone receptor-positive (HR+) tumors, which represent the most common metastatic breast cancer subtype. Emerging evidence suggests that alterations in the gut microbiome may influence systemic inflammation and cancer progression. This study investigated whether commensal dysbiosis alters bile acid metabolism and contributes to mammary gland inflammation and HR+ breast tumor dissemination.

DETAILS: Researchers evaluated the relationship between gut microbiome alterations, bile acid signaling, inflammation, and breast cancer progression using experimental models and human genomic and clinical datasets. Metabolomic profiling demonstrated increased primary bile acids in dysbiotic microbiomes. Additional mechanistic studies using bile acid sequestration and supplementation approaches examined how altered bile acid levels influenced mammary inflammation and tumor dissemination.

The investigators further analyzed The Cancer Genome Atlas (TCGA) data to evaluate associations between bile acid-related signatures, insulin resistance, prostaglandin E2 (PGE2) signaling, and survival outcomes in patients with HR+ breast tumors. Electronic health record data from the Epic Cosmos database were also examined to assess associations between bile acid sequestrant use and outcomes among patients with metastatic disease.

Commensal dysbiosis increased primary bile acid levels by disrupting microbial bile acid metabolism. Elevated primary bile acids promoted mammary gland inflammation and enhanced HR+ breast tumor dissemination through a prostaglandin E2 (PGE2)-dependent pathway.

TCGA analysis demonstrated that gene signatures related to bile acids, insulin resistance, and PGE2 signaling were associated with reduced survival in patients with HR+ tumors. In complementary clinical data analysis, bile acid sequestrant use was associated with longer restricted mean survival time among patients with metastatic disease.

These findings identify gut microbiome–bile acid signaling as a potential biological pathway linking intestinal dysbiosis with breast cancer progression and suggest that modulation of bile acid pathways may represent an area for future therapeutic investigation.

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Source: Putelo, A. M., Bajgai, S., Poblete, M. K., et al. Commensal Dysbiosis Alters Primary Bile Acid Signaling to Drive Mammary Gland Inflammation and Breast Tumor Dissemination. Cancer Research. 2026; Published: June 2, 2026. DOI: 10.1158/0008-5472.CAN-25-4466