Search Results (1,317)

Background/Objectives: Sodium–glucose cotransporter-2 (SGLT2) inhibitors have demonstrated cardiovascular benefits beyond glycemic control, yet the specific biological pathways potentially linking SGLT2 inhibitor exposure to cardiovascular outcomes after acute myocardial infarction (AMI) remain incompletely characterized. Two biologically plausible pathways, serum uric acid (SUA) reduction and renal functional preservation, have been proposed, but not directly compared in a unified analytical framework. This study aimed to explore whether associations between SGLT2 inhibitor exposure and recurrent post-AMI outcomes may be more strongly linked to SUA reduction and to renal functional changes, using a hypothesis-generating causal mediation analysis. Methods: This retrospective observational cohort study included 142 consecutive patients hospitalized for AMI who underwent percutaneous coronary intervention (PCI) during the index hospitalization, reflecting standard-of-care management for AMI in this tertiary center. Patients were categorized by SGLT2 inhibitor exposure (n = 57) vs. controls (n = 85). Both diabetic (47.2%) and non-diabetic (52.8%) patients were included. The primary endpoint was change in SUA (ΔUA); the secondary endpoint was myocardial infarction (MI) recurrence. Causal mediation analysis with nonparametric bootstrap simulation tested both mechanistic pathways. Results: SGLT2 inhibitor therapy was associated with significant SUA reduction (ΔUA = −0.99 mg/dL vs. +0.56 mg/dL in controls; p < 0.001), consistent across diabetic and non-diabetic subgroups and independent of AMI recurrence. Each 1 mg/dL decrease in SUA was associated with lower odds of recurrent MI in the initial model (β = −0.25; p = 0.041). However, after incorporation of renal functional change, the uric acid-mediated pathway lost significance (ACME p = 0.462), whereas the renal-mediated pathway remained significant (ACME p = 0.038). Serum creatinine change emerged as the strongest independent predictor of MI recurrence (β = 2.22; p = 0.015). Conclusions: The findings are more consistent with a renal-mediated pathway than with an independent uric acid-mediated pathway in explaining the observed associations between SGLT2 inhibitor exposure and recurrent post-AMI outcomes. These hypothesis-generating results from a retrospective design warrant prospective validation. Full article

Background: Current guidelines acknowledge that early discharge is not associated with late mortality and that in-hospital length of stay (LOS) of 48–72 h should be considered following successful primary percutaneous coronary intervention (PPCI) in low-risk patients. Recent studies have highlighted the safety of very early discharge after PPCI in highly selected low-risk patients; however, objective tools to guide discharge timing remain limited. The Index of Microcirculatory Resistance (IMR) offers a quantitative assessment of microvascular function and may help identify patients suitable for very early discharge. We aimed to evaluate the feasibility of using IMR to guide very early discharge in patients who underwent uncomplicated PPCI. Study design and objectives: The Safety of Early Discharge Using Index Microcirculatory Resistance in Patients with Acute Myocardial Infarction (SECURE) study is designed to assess the feasibility of using IMR, measured immediately following successful PPCI, to guide early discharge from hospital within 24 h. The SECURE study is a prospective, proof-of-concept, functional non-inferiority, single-centre, randomised, open-label trial to determine if patients with low IMR can be safely discharged when compared to standard discharge policy. The SECURE study will recruit 82 patients with low IMR following successful PPCI. Participants will be 1:1 randomised to either standard discharge timing or very early discharge (within 24 h). The left ventricle ejection fraction will be assessed using cardiac magnetic resonance imaging. A telephone follow-up at 3 months will be arranged. Clinical events are collected as secondary and exploratory safety endpoints. Conclusions: The SECURE study will provide proof-of-concept data about the feasibility of using IMR to guide very early discharge following PPCI. If successful, this study will provide data to plan for a larger study to determine the safety of this personalised approach. Full article

Background: In end-stage liver disease (ESLD), cardiovascular changes are frequent and relate to the presence of hyperdynamic circulation. In 2019, diagnostic criteria for cirrhotic cardiomyopathy (CCM) were updated to include tissue Doppler and speckle tracking imaging in defining left ventricle (LV) systolic and diastolic dysfunction. Evaluation of diastolic function remains challenging, with frequent indeterminate cases and emerging evidence of worse prognosis. The aim of the present study was to evaluate the prevalence of LV systolic and diastolic dysfunction in cirrhosis, in correlation with liver disease severity and potential prognostic implications. Methods: We performed an observational, retrospective, non-randomized, single-center study that included 99 cirrhotic patients evaluated for liver transplant (LT) in a tertiary center. Liver disease severity and complications were analyzed with survival and echocardiography data to determine potential correlations with prognosis. For statistical analysis, IBM^® SPSS^® Statistics version 20 (Chicago, IL, USA) was utilized. A two-sided p-value < 0.05 was considered statistically significant. Results: Left atrial (LA) volume index (r = 0.230, p = 0.022), LA reservoir strain (r = 0.291, p = 0.003), and LA contraction strain absolute value (r = 0.223, p = 0.027) positively correlated with the severity of liver disease expressed by MELD Na score. LA dilation (≥34 mL/m²) was the most common echocardiographic finding. It was present in 69.7% of patients, with one third having severe LA dilation (>45 mL/m²), which was associated with worse survival (log rank p = 0.019). LA contraction strain with an absolute value higher than 16% was also associated with worse survival (log rank p = 0.024). In multivariable Cox analysis, only MELD-Na and LA volume index remained independently associated with mortality. Diastolic dysfunction appeared more prevalent among the non-surviving patients irrespective of the diagnostic criteria used (p = 0.023 for American Society of Echocardiography 2016 criteria; p = 0.032 for CCM 2019 criteria). On binomial logistic regression, the presence of significant diastolic dysfunction (>grade 1) was associated with an increased probability of composite end-point of death or LT in the presence of liver disease severity confounders. The use of the LA stiffness index in discerning diastolic function in patients with standard inconclusive evaluation may warrant further investigation. Conclusions: Echocardiographic alterations, particularly LA enlargement, are associated with liver disease severity and clinical outcomes in ESLD. These findings are hypothesis-generating and suggest a potential role for echocardiography in risk stratification, warranting validation in larger prospective studies. Full article

Background: Early identification of patients at risk for adverse outcomes after cardiac surgery remains a major clinical challenge. While preoperative risk scores are widely used, the prognostic value of early postoperative ICU severity scores and functional performance measures has not been fully clarified. Methods: This prospective observational study included 195 patients undergoing cardiac surgery between 2018 and 2024. Predictive performance of EuroSCORE II, the SOFA score, the APACHE II score, Karnofsky performance status, handgrip strength, and phase angle was assessed for postoperative complications and mortality. Receiver operating characteristic (ROC) curves with 95% confidence intervals were calculated, and pairwise comparisons between ROC curves were performed. Major postoperative complications were analyzed using a composite endpoint including stroke, prolonged intubation, sepsis, and reoperation, excluding systemic inflammatory response syndrome (SIRS). Results: Major postoperative complications occurred in 46 patients (23.6%). For prediction of major postoperative complications, SOFA demonstrated the highest discrimination (AUC = 0.881, 95% CI 0.819–0.928), followed by APACHE II (AUC = 0.826, 95% CI 0.753–0.888) and EuroSCORE II (AUC = 0.695, 95% CI 0.602–0.785). In-hospital mortality occurred in 19 patients (9.7%). SOFA showed the strongest predictive performance (AUC = 0.915, 95% CI 0.851–0.968), followed by APACHE II (AUC = 0.869, 95% CI 0.781–0.939) and EuroSCORE II (AUC = 0.742, 95% CI 0.595–0.870). During follow-up, 54 patients (27.7%) died. Predictive performance was comparable between SOFA (AUC = 0.710, 95% CI 0.618–0.793), APACHE II (AUC = 0.695, 95% CI 0.606–0.782), and EuroSCORE II (AUC = 0.680, 95% CI 0.599–0.757). Conclusions: Early postoperative ICU severity scores, particularly SOFA and APACHE II, demonstrated strong predictive ability for major postoperative complications and in-hospital mortality following cardiac surgery and outperformed preoperative risk scores. Full article

Background: As life expectancy increases, a growing number of elderly patients are considered for curative hepatectomy for hepatocellular carcinoma (HCC). However, perioperative outcomes in elderly patients in the contemporary era of minimally invasive liver surgery remain incompletely defined. Methods: We retrospectively reviewed 277 consecutive patients who underwent elective curative hepatectomy for HCC between 2019 and 2023. Outcomes were compared using age thresholds of ≥75 and ≥80 years. The primary endpoints were 90-day mortality and major postoperative complications (Clavien–Dindo grade ≥ III). Multivariable logistic regression identified predictors of major complications. Results: Elderly patients had more comorbidities, whereas liver function, tumor characteristics, and extent of resection were comparable across age groups. Laparoscopic hepatectomy was performed more frequently in patients aged ≥80 years. Major complication rates and 90-day mortality were similar regardless of age, with no deaths among patients aged ≥75 or ≥80 years. Age ≥75 years, higher ALBI score, major comorbidities, and longer Pringle maneuver time were independently associated with major postoperative complications. Conclusions: Hepatectomy for hepatocellular carcinoma may be performed with acceptable short-term outcomes in carefully selected elderly patients, including octogenarians. Chronological age alone should not be considered an absolute contraindication to surgery, although findings should be interpreted with caution. Full article

Background/Objectives: Left ventricular ejection fraction (LVEF) typically improves after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis (SAS). However, the clinical significance and prognosis of patients presenting with supranormal LVEF (≥65%) remain poorly defined. This study aims to describe LVEF behavior, its relationship with mortality, and its effect on cardiac structure in this specific subgroup. Methods: A retrospective observational study was conducted at Hospital Clínico San Carlos (2008–2019), including SAS patients with pre-procedural supranormal LVEF. Patients were classified into two groups: those whose LVEF normalized (55–65%) and those whose LVEF remained supranormal. Demographic, clinical, and echocardiographic variables were collected at baseline and one-year follow-up. The primary endpoint was all-cause mortality at two years. Results: Out of 101 analyzed patients (mean age 82.8 years, 71.2% women), 71 (70.3%) experienced LVEF normalization at one year. Two-year mortality was 10% in the normalized group and 9.8% in the non-variable group, showing no significant difference. Regarding geometric characteristics, a trend toward left ventricular mass regression was observed only in the LVEF-normalized group (Delta −10; p = 0.062 vs. −8.4; p = 0.197). History of bleeding was the only variable showing a trend toward worse prognosis (p = 0.064). Conclusions: LVEF behavior one year after TAVI in patients with baseline supranormal function tends toward normalization. This change is not associated with differences in two-year mortality but is linked to a trend toward beneficial reverse cardiac remodeling. Full article

Background and Objectives: Overt perioperative stroke remains a feared complication of adult cardiac surgery. Diffusion-weighted magnetic resonance imaging (DWI-MRI) has revealed a more prevalent form of cerebral injury, termed silent stroke or silent brain injury (SBI). Covert ischemic lesions occur without focal neurological deficits but are increasingly associated with postoperative delirium, cognitive decline, and elevated long-term cerebrovascular risk. Despite growing recognition, the true burden, mechanisms, and clinical relevance of SBI remain incompletely integrated into perioperative practice. Materials and Methods: We performed a narrative review of the literature published between January 2000 and December 2025, identified through PubMed/MEDLINE and Scopus. Eligible studies included prospective and retrospective cohorts, randomized trials, systematic reviews, and meta-analyses involving adult patients undergoing coronary artery bypass grafting, valve surgery, or minimally invasive cardiac procedures, with or without cardiopulmonary bypass, and reporting MRI-detected ischemic lesions or validated surrogate markers of cerebral injury. Pediatric studies, transcatheter interventions, case reports, and non-English publications were excluded. Sixty studies met the inclusion criteria. Results: Silent stroke occurred more frequently than clinically apparent stroke, with new DWI-MRI lesions detected in approximately 20–60% of patients following cardiac surgery. Lesions were typically small, multifocal, and embolic in distribution, predominantly affecting cortical and watershed regions. Cardiopulmonary bypass-related factors, including aortic manipulation, cerebral microembolization, hemodilution, hypoperfusion, and impaired oxygen delivery, emerged as key contributors. Several studies demonstrated associations between SBI burden and postoperative delirium, early cognitive dysfunction, and functional decline. Perfusion-based neuroprotective strategies showed mechanistic benefit, although no single intervention conclusively prevented SBI. Conclusions: Silent stroke represents the most frequent form of neurological injury in adult cardiac surgery. Evidence suggests that these covert lesions reflect clinically meaningful cerebral injury, with potential short- and long-term consequences. Recognition of silent stroke as a relevant neurological endpoint supports a shift toward multimodal, perfusion-driven neuroprotective strategies and the routine incorporation of MRI-based outcomes in future cardiac surgical research. Full article

The brown trout (Salmo trutta) is a commercially and ecologically significant salmonid fish, yet its hepatic cellular and functional dynamics throughout the reproductive cycle remain poorly characterised, particularly in males. This study investigated seasonal and sex-specific liver plasticity across four reproductive stages: spawning capable (December), regressing (March), regenerating (July), and developing (November). We quantified mRNA and protein abundance of key oestrogen-responsive targets—vitellogenin (VtgA) and zona pellucida (ZP) proteins—alongside cell turnover markers, caspase 3 (Casp3) and proliferating cell nuclear antigen (PCNA). These molecular endpoints were integrated with stereological analyses to estimate hepatocyte, nuclear, and cytoplasmic volumes. Results revealed stage-dependent mobilisation and transient hepatic retention of reproductive proteins; females exhibited stronger vitellogenic signatures and more pronounced seasonal shifts than males. Although VtgA and ZP mRNA levels peaked during the developing and spawning-capable stages, males maintained low but consistent levels throughout the cycle, indicating constitutive hepatic oestrogen sensitivity. Regarding cell turnover, PCNA protein data indicated heightened proliferative activity during the spawning-capable and regressing stages. In contrast, while Casp3 mRNA levels remained stable across all stages, protein detection suggested a post-transcriptional increase in apoptotic signalling during the developing phase, consistent with controlled tissue remodelling rather than extensive cell loss. Stereological data confirmed enlarged hepatocyte and nuclear volumes during periods of high secretory and proliferative demand. Overall, these findings demonstrate significant stage-dependent and sex-specific plasticity in brown trout liver, providing a robust reference framework for ecological monitoring, endocrine disruption assessments, and studies of teleost reproductive physiology. Full article

Massage relieves stress and anxiety, but also helps to reduce musculoskeletal problems, decreasing tension, in all stages of life. For pediatric use, organoleptic properties, cosmetic safety and user acceptability of topical products are important given the higher frequency of irritative or allergic episodes in young skin. We evaluate for the first time the comprehensive cosmetic performance of Physiorelax Forte Plus natural formulation in cream, spray and roll-on applied regularly in healthy and active children/adolescents. 210 healthy volunteers were included (150 adults with sensitive skin and 60 children and adolescents [6–16 years]). This three-part, sequential, observational, non-comparative pilot design monitored user experience under real-world conditions: (I) Open-label testing to assess skin compatibility in adults (N = 60); (II) In-use testing in adults for cosmetic acceptability and safety over 14 days (N = 90); (III) In-use testing in children/adolescents for 14 days (N = 60). Outcomes were dermatological assessments for tolerability and user (and/or parents/caregiver(s)-reported) satisfaction/acceptability and perceived benefits. No control group or objective efficacy measures were included. Among pediatric participants, no cutaneous reactions were observed at application sites after 14 days of use. Proxy reporting about consumer satisfaction and acceptability for the range were generally high. Principal component analysis revealed a clear three-cluster structure (sensory, functional, practicality), with roll-on driving the strongest differentiation across items and spray aligning most closely with sensory attributes, while cream showed an intermediate functional profile. The Physiorelax Forte Plus range demonstrated a favorable cosmetic safety profile and consumer acceptability in pediatric use under real-world conditions. Findings are limited by the observational, unblinded design, absence of a control group, and reliance on subjectively reported outcomes; no clinical or pharmaceutical claims are implied. Future controlled studies incorporating objective dermatologic endpoints, benchmark products, and direct child/adolescent reporting are warranted. Full article

Background and Objectives: Medial unicompartmental knee arthroplasty (UKA) has emerged as an effective surgical option for isolated medial compartment osteoarthritis (OA), offering advantages in bone preservation, knee kinematics, and postoperative recovery compared with total knee arthroplasty (TKA). Although numerous studies have evaluated the mid- to long-term outcomes of UKA, reports focusing on cohorts with follow-up periods exceeding 10 years remain relatively limited. The purpose of this study was to analyze the long-term clinical and radiological results of medial fixed-bearing UKA using the Miller-Galante prosthesis. Methods: Sixty-eight patients who underwent UKA at a single institution with at least 10 years of follow-up were retrospectively reviewed. Clinical outcomes were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and knee range of motion (ROM). Radiological parameters including the hip-knee-ankle axis angle (HKA) and osteoarthritis (OA) grade using the Kellgren-Lawrence (K-L) grading system were evaluated. Implant survivorship was evaluated using Kaplan–Meier survival analysis. Results: A total of 68 patients were included with a mean age of 56.8 ± 7.5 years at surgery and a mean follow-up of 170.9 ± 37.3 months. Significant improvement in the WOMAC score was observed from 48.9 ± 17.2 preoperatively to 23.8 ± 27.7 at final follow-up (p = 0.002). The cumulative survival rates were 97.1% at 10 years and 84.8% at 15 years with conversion to total knee arthroplasty as the endpoint. Significant improvement in the HKA was observed from 172.5° ± 4.4° to 174.3° ± 4.8° postoperatively (p = 0.002), though residual varus alignment persisted. Progressive OA was observed in the lateral tibiofemoral and patellofemoral compartments (both p < 0.001) but showed no correlation with the WOMAC score. The failure group showed trends toward higher body mass index (BMI) and smaller preoperative HKA angle compared to the non-failure group. Conclusions: The long-term outcomes of medial fixed-bearing UKA using the Miller–Galante prosthesis were generally favorable, with significant functional improvement and acceptable implant survivorship. Although overall varus alignment was corrected, some residual varus deformity remained, and OA progression was observed in the lateral tibiofemoral and patellofemoral compartments over time. However, given the retrospective design and limited sample size, these findings should be interpreted with caution. Full article

Spinal cord injury (SCI) triggers a secondary injury cascade characterized by persistent innate immune activation, chronic neuroinflammation, and progressive tissue loss that limits functional recovery. Here, we evaluated a systemic combination treatment using propentofylline (PPF), a glial modulator, together with interleukin-4 (IL-4), a cytokine associated with repair-related myeloid responses. In vitro, PPF enhanced IL-4-dependent induction of arginase-1 (ARG1) in TNFα-primed BV2 microglia. In vivo, adult Fischer rats of both sexes received vehicle, PPF, IL-4, or combined PPF + IL-4 beginning within 1 h after moderate T8 contusive SCI and continuing daily for 14 days. Locomotor recovery was assessed longitudinally for 8 weeks, followed by histological and immunohistochemical analyses. Combined PPF + IL-4 treatment produced the greatest improvement in gross and skilled locomotor recovery compared with vehicle, or either monotherapy. At 8 weeks post-SCI, the combined therapy aligned with a reduction in chronic lesion-associated p-p38 MAPK, decreased pP65 NFkB (RelA) activation, increased expression of reparative factors ARG1 and CD206, as well as reduced lesion cavitation and trends toward greater gray and white matter preservation. Stratification of functional data by sex showed BBB improvements with combined PPF + IL-4 in both males and females after SCI. Together, these findings show that combined systemic PPF and IL-4 treatment was associated with improved functional recovery, reduced lesion cavitation, and changes in lesion-associated molecular and histological endpoints after SCI, supporting further preclinical investigation. Full article

The rapid emergence of New Psychoactive Substances (NPS), particularly pyrrolidinophenone derivatives, poses a significant challenge for public health and forensic toxicology. While their neuropharmacological profiles as dopamine transporter inhibitors are well-documented, their cardiac toxicity remains poorly understood. This study employs a multiparametric New Approach Methodology (NAM) using zebrafish embryos to integrate neurobehavioral and cardiotoxic endpoints for comparative hazard prioritization. We evaluated nine pyrrolidine-containing cathinones, including α-PVP, MDPV, α-PiHP, MDPiHP, α-D2PV, 3-Cl-, 4-Cl-, and 3,4-Cl-α-PVP, and 4-F-3-Me-α-PVP, on locomotor activity and cardiac rhythmicity using high-speed video microscopy and dynamic pixel analysis. Across the series, compounds induced concentration-dependent negative chronotropy and, in most cases, locomotor suppression. Crucially, we identified a functional dissociation between atrial rate control and atrioventricular (AV) conduction. The 3,4-dichloro substitution (3,4-Cl-α-PVP) was the most potent inducer of negative chronotropy (EC₅₀ = 52.6 μM), whereas 4-Cl-α-PVP exhibited a distinct pro-arrhythmic liability, increasing the incidence of 2:1 AV block. Time-course locomotor profiling indicated that α-PVP and chlorinated analogs were among the most potent behavioral modifiers. Using a Functional Safety Index (AV block EC₅₀/locomotor EC₅₀-like), we show that most compounds exhibit wide separations between neurobehavioral inhibition and severe conduction impairment, while specific substitutions, particularly para-chlorination, are associated with comparatively reduced functional separation between these endpoints within the assay. Overall, these data demonstrate that subtle structural changes within the pyrrolidinophenone scaffold can shape distinct arrhythmic phenotypes and functional safety profiles, supporting zebrafish-based integrated screening as a rapid platform for prioritizing emerging synthetic cathinones with comparatively higher cardiac liability within this experimental framework. Full article

Background: Retinal and optic nerve disorders are a leading cause of irreversible visual impairment worldwide. Advances in molecular genetics—including next-generation sequencing, genome-wide association studies, and gene-based therapeutic technologies—have reshaped understanding of both inherited and complex retinal diseases. However, translating genetic discovery into sustained clinical benefit remains biologically and practically constrained. Methods: A structured literature search was conducted using PubMed and Scopus to identify relevant studies published between 2015 and 2025. The search focused on molecular genetics, epigenetic modulation, mitochondrial biology, and translational applications in inherited retinal dystrophies and selected complex retinal diseases, prioritizing high-impact original research and systematic reviews addressing diagnostic innovation and therapeutic development. Results: Inherited retinal dystrophies represent the most advanced model of precision ophthalmology, with diagnostic yields approaching 70–80% in well-characterized cohorts. Gene augmentation and genome-editing strategies have demonstrated proof-of-concept efficacy, yet clinical benefit depends on residual cellular viability, delivery efficiency, and durability of expression. Emerging platforms include AAV-mediated gene transfer, in vivo CRISPR-based editing, RNA-directed splice modulation, and mitochondrial-targeted approaches. Persistent barriers include unresolved non-coding and structural variants, variant interpretation uncertainty, and endpoint selection in clinical trials. In contrast, complex retinal diseases such as glaucoma, age-related macular degeneration, and pathological myopia reflect polygenic susceptibility interacting with environmental and aging-related factors. Although polygenic risk scores refine probabilistic prediction, their utility is limited by ancestry bias and incomplete predictive performance. Epigenetic and mitochondrial mechanisms further modulate disease expression but remain largely non-actionable in routine practice. Conclusions: Retinal genetics has progressed from gene discovery to early therapeutic implementation. Future advances will depend on improved variant detection, functional validation, biomarker-guided staging, and integration of genomics with imaging and longitudinal modeling to achieve durable and equitable precision ophthalmology. Full article

Major depressive disorder (MDD) lacks reliable laboratory tests for diagnosis and treatment monitoring, underscoring the need for robust molecular readouts in blood. Beyond symptom-based classification, MDD can also be viewed as a condition involving impaired homeostatic regulation across stress-responsive, immune, metabolic, and neural systems. Consistent with this perspective, altered intron retention (IR) patterns have been observed in peripheral blood in depression-related and treatment-response contexts, supporting the translational relevance of this RNA-processing layer to mood disorders. A key observation underpinning this review is that IR can function as a reversible, intervention-responsive readout of physiological state. In a pre-symptomatic stress-like state in klotho mutant mice (a premature-aging model), widespread IR increases revert toward a healthy pattern upon treatment, suggesting that IR is embedded in a controllable homeostatic layer. Against the backdrop of limited cross-cohort transferability of differential gene expression (DGE) signatures, we propose that IR provides a mechanistically grounded biomarker layer because it reports regulated RNA processing states rather than context-fragile abundance endpoints. We operationalize IR as a post-transcriptional “throttle” on effective gene output, with increased IR/detained intron (DI) states acting as a reversible brake and decreased IR acting as an accelerator that increases translation-competent mRNA supply. Mechanistic exemplars across immune, metabolic, and neuronal systems (e.g., IFNG, OGT, MAT2A, neuronal activity-triggered intron excision, and intron detention-mediated stemness/differentiation switching in adult neural stem cells) show that defined inputs can switch IR/DI states to tune output kinetics. Integrating these findings, we propose an “Intron Retention Homeostat” (IR-Homeostat) model in which cells sense deviations from physiological set points and implement feedback control of gene output through switchable IR/DI regulation. This framework positions IR not only as a robust state readout for stratification, treatment response prediction, and pharmacodynamic profiling, but also as a tractable entry point to identify the molecular sensors and mediators that couple homeostatic signals to RNA processing control. Full article

Background/Objectives: The aim of this study was to assess whether preoperative pulmonary function testing (PFT) is related to postoperative complications after open thoracoabdominal aortic aneurysm (TAAA) repair. Methods: This study was conducted as a retrospective cohort analysis of 205 patients undergoing open TAAA repair (2006–2024) with preoperative spirometry and body plethysmography with at least one value available. Patients were classified by ventilation patterns: obstructive (n = 85, 45.2%), restrictive (n = 26, 14.1%), and hyperinflation (n = 56, 30.3%). Primary endpoints included in-hospital mortality, pulmonary complications (pneumonia, ARDS), and multi-organ outcomes. Associations were analyzed using chi-square and Spearman correlation tests and multivariable linear regression adjusted for age, smoking status, COPD, emergency operation, and time period. Results: Postoperative pulmonary complications occurred in 126 patients (61.5%), including pneumonia (46.8%) and ARDS (15.1%). Reduced vital capacity and FEV₁ expressed as a percentage of the lower limit of normal (%LLN) were related to postoperative pneumonia (p = 0.031 and p = 0.003) and ARDS (p = 0.038). Both obstructive and restrictive ventilation patterns were related to acute kidney injury after surgery (all KDIGO stage) (p = 0.044 and p = 0.043, respectively). Hyperinflation was related to atrial fibrillation (p = 0.039) and stroke (p = 0.034). FEV₁ < 2.0 L was related to increased mortality risk (p = 0.037), and FEV₁ < 1.5 L predicted acute kidney injury (p = 0.017), spinal cord ischemia (p = 0.035), and mortality (p = 0.023). Prolonged mechanical ventilation correlated with reduced preoperative lung function (VC %LLN ρ = −0.288, p = 0.002; FEV₁ %LLN ρ = −0.286, p = 0.001). During median follow-up of 6.35 years, patients in the highest FEV₁ quartile demonstrated substantially reduced long-term mortality (HR 0.27, 95% CI 0.10–0.73, p = 0.01). These associations between lower FEV₁ and VC (expressed as %LLN) with pneumonia, ARDS, in-hospital mortality, and prolonged ventilation remained significant after multivariable analysis. Conclusions: Preoperative pulmonary function assessment may help identify TAAA patients at increased risk of postoperative complications and mortality. Combining percentage-predicted spirometry, ventilation patterns, and hyperinflation markers may support individualized treatment selection, prehabilitation, and perioperative monitoring based on each patient’s specific risk profile. Full article