BackgroundPostoperative delirium (POD) is a common complication following transcatheter aortic valve replacement (TAVR) and is associated with adverse outcomes in older patients. Frailty, a multidimensional geriatric syndrome, has been increasingly recognized as a potential risk factor for POD. However, existing evidence remains inconsistent. This meta-analysis aimed to evaluate the association between frailty and POD after TAVR.MethodsA systematic search of PubMed, Embase, and Web of Science was conducted from inception to January 22, 2026. Cohort studies evaluating the association between preprocedural frailty and POD after TAVR were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model accounting for the influence of potential heterogeneity.ResultsTen cohort studies involving 7,702 patients were included. Frailty was present in 2,062 (26.8%) patients, and 786 (10.2%) developed POD. Pooled analysis showed that frailty was significantly associated with an increased risk of POD after TAVR (OR: 2.17, 95% CI: 1.60–2.95; I2 = 55%). The association was stronger in studies with sample size ≥ 500 compared with < 500 (OR: 2.74 vs. 1.38; p for subgroup difference < 0.001). The effect estimates were consistent across subgroups stratified by study design, age, sex, frailty assessment methods, follow-up duration, analytic models, and study quality (all p for subgroup difference > 0.05). Notably, studies using CAM-ICU to diagnose POD showed a stronger association than those using DSM criteria or other methods (OR: 3.60 vs. 1.56 and 2.53; p = 0.006). Meta-regression identified sample size as a significant source of heterogeneity (p = 0.02).ConclusionsFrailty is associated with an increased risk of POD after TAVR. These findings highlight the importance of frailty assessment for perioperative risk stratification and support targeted strategies to prevent delirium in high-risk patients undergoing TAVR.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420261352173.
Associations between serum tumor necrosis factor-alpha, hippocampal-prefrontal-ventricular volumes, and clinical profiles in schizophrenia: a biomarker and neuroimaging study in North Sumatera, Indonesia
IntroductionSchizophrenia is a neurodevelopmental disorder with systemic inflammation that is thought to play a role in its pathophysiology. The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) has been reported to be dysregulated in individuals with schizophrenia, but its relationship with brain volume changes remains inconsistent. This study aimed to analyze differences in TNF-α levels and brain volume (hippocampus, prefrontal cortex, and lateral ventricles) and their correlations in schizophrenia patients compared to healthy controls.MethodsThis analytical cross-sectional investigation was conducted on 50 schizophrenia patients and 50 healthy Batak controls at the Prof. M. Ildrem Provincial Mental Hospital, Medan. Serum TNF-α levels were measured by ELISA, while brain structure volume was measured by 1.5 T MRI and analyzed using AnalyzePro software.ResultsTNF-α levels in the schizophrenia group were significantly lower (3.35 pg/dl) than in the control group (16.90 pg/dl). No significant differences in hippocampal and prefrontal cortex volume were found between the groups. However, lateral ventricle volume was significantly larger in schizophrenia. Correlation analysis showed a weak negative relationship between TNF-α and prefrontal cortex volume only in the schizophrenia group.DiscussionThe finding of low TNF-α in schizophrenia supports the complexity of immune dysfunction in schizophrenia, which may be influenced by medication or disease phase. Consistent ventricular enlargement reinforces previous neuroanatomical findings. The association of TNF-α with the prefrontal cortex only within the schizophrenia cohort indicates a specific interaction between inflammation and brain morphology in this patient population.ConclusionsThe findings support TNF-α dysregulation in schizophrenia, albeit at lower levels. Lateral ventricular enlargement was consistently found, while changes in hippocampal and prefrontal cortex volume may be more subtle in this population. The negative correlation between TNF-α and the prefrontal cortex in schizophrenia suggests a potential role for inflammation in the pathology of this brain region.
Baseline working memory was associated with improvement in psychological quality of life in patients with persistent depressive symptoms: a prospective observational study
BackgroundCognitive dysfunction is prevalent in patients with depressive symptoms and contributes to impaired quality of life (QOL) and functional outcomes. However, the prognostic significance of specific cognitive domains for long-term outcomes remains unclear in patients with persistent depressive symptoms.MethodsIn this prospective observational study, 119 patients completed the detailed examination program in routine clinical care. Of these, 84 patients with persistent depressive symptoms provided consent for study participation and met the eligibility criteria for inclusion in the present study, including completion of the baseline assessment with the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV). The diagnostically heterogeneous cohort included patients with major depressive disorder/dysthymia as well as bipolar and related disorders. The World Health Organization Quality of Life Instrument, Short Version (WHO-QOL-26) and the World Health Organization Disability Assessment Schedule 2.0 were assessed at baseline, three, and six months; 60 participants provided 3-month follow-up data and 50 provided 6-month follow-up data. Primary hierarchical regression analyses were exploratory and conducted using complete-case data.ResultsAt baseline, participants exhibited relatively higher verbal ability and lower processing speed compared to normative data. While no significant group-level improvement in QOL was observed over six months and functioning did not improve overall, the WHODAS 2.0 standardized total score was temporarily higher at 3 months than at baseline. In exploratory analyses of complete cases, higher baseline working memory was significantly associated with greater improvement in the psychological domain of the WHO-QOL-26 at six months (β = 0.40; ΔR² = 0.14; p < 0.01). No other cognitive domains showed such associations.ConclusionsWorking memory was associated with subsequent improvement in psychological well-being and may represent a candidate prognostic marker in patients with persistent depressive symptoms. Given the exploratory nature and modest sample size, these findings require replication in larger, diverse populations.
Precision diagnosis model for treatment-resistant depression integrating serum metabolomics and clinical risk factors
ObjectiveThis study aimed to construct a high-efficiency dual-modal diagnostic model for treatment-resistant depression (TRD) by integrating serum metabolomics and clinical risk factors, and explore its metabolic pathological mechanisms.MethodsA total of 93 major depressive disorder (MDD) patients (53 TRD, 40 non-TRD) were enrolled for a single-center retrospective study. Serum untargeted metabolomics and clinical baseline data were collected, with differential metabolites and clinical risk factors screened by statistical analysis and multi-step machine learning to identify core features. Five machine learning algorithms were compared to build unimodal and random forest-based dual-modal diagnostic models, and KEGG pathway enrichment analysis was performed.Results3 core clinical risk factors (medical history, HDL, FBG) and 8 core metabolic biomarkers were identified. The dual-modal model achieved AUC 0.996 (training) and 0.911 (validation), outperforming unimodal models. Differential metabolites were mainly enriched in lipid (44.8%) and amino acid (23.9%) metabolism. Fibrinopeptide A516, 12-HETE and the three clinical factors were core driving features.ConclusionThe dual-modal model has high diagnostic efficiency for TRD. TRD is associated with endocannabinoid system hypofunction and metabolic imbalance, which provides an objective diagnostic tool and new insights for TRD mechanism research and therapy development.
ESMR: a process framework for calibration dynamics across psychosomatic and psychiatric phenomena
The brain can be modeled as a generative system that predicts bodily and environmental input and reduces mismatch through updating and action. From this perspective, stress is treated not as prediction error per se, but as a condition in which mismatch persists without sufficient recalibration. Health is therefore defined not as the absence of symptoms, but as the preservation of recalibrability, whereas psychopathology is conceptualized as the progressive fixation of recalibration failure. This paper proposes ESMR as a four-layer, two-timescale process framework for comparing psychosomatic conditions, psychiatric disorders, and psychosis-level phenomena in terms of partially shared failures of recalibration rather than as a single disease continuum. ESMR distinguishes E (Embodied Constraints), S (Salience Calibration), M (Metacognitive Model Revision), and R (Reality-Grounding Interface) across learning (L) and development (D). Development is treated not merely as slower accumulation of prior learning, but as change in the biological, representational, and self-regulatory architecture that alters both what forms of recalibration are possible and the background conditions under which learning can be taken up. A central distinction is that M concerns whether corrective information can be converted into updating, whereas R concerns whether already understood correction can be adopted as self-relevant reality under embodied, practical, and interpersonal constraints, with downstream transfer treated as a consequence rather than part of the R core. The framework predicts layer-specific cross-signatures rather than a single undifferentiated burden effect and outlines a staged empirical program using framing, disconfirmation, reality-grounding, and embodied/interoceptive tasks. ESMR is offered as a revisable, clinically oriented intermediate framework rather than a completed computational model.
AI-guided redesign of laboratory-evolved reverse transcriptases enhances prime editing
Nature Biotechnology, Published online: 21 May 2026; doi:10.1038/s41587-026-03149-6
A computational redesign strategy improves evolved prime editors.
Integrating public health into house design
Nature Medicine, Published online: 21 May 2026; doi:10.1038/s41591-026-04413-7
Housing is not just a backdrop to health, but a powerful intervention. A study now shows that redesigning the home environment can improve child health outcomes, but success requires community co-design and solutions for cost and scalability.
Resetting autoimmune disease with CAR cell therapies
Nature Medicine, Published online: 21 May 2026; doi:10.1038/s41591-026-04430-6
This Review surveys the fast-developing landscape of CAR T cells in autoimmune disease from both a technological and clinical standpoint, exploring the concept of deep B cell depletion and immune ‘reset’.
Foamy microglia link oxylipins to disease progression in multiple sclerosis
Nature Neuroscience, Published online: 21 May 2026; doi:10.1038/s41593-026-02302-3
Foamy microglia are associated with multiple sclerosis progression, linking phagocytosis, altered lipid metabolism (oxylipins) and lysosomal stress to nonclassical neuroinflammation and disease severity, highlighting potential therapeutic targets.
STAT+: RFK Jr.’s screen time warning
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MAHA is mad about this Trump win
When Sen. Bill Cassidy (R-La.) lost his primary, MAHA rejoiced. Not so with Rep. Thomas Massie, the Kentucky Republican who lost against a Trump-backed challenger.