Background: Genetic variants within the 17q21 locus and epigenetic modifications regulating immune function have been associated with childhood asthma, yet reported effect sizes vary across studies due to methodological heterogeneity and differences in study design. Objectives: To systematically synthesize evidence on genetic and epigenetic markers associated with childhood asthma using a two-level random-effects meta-analysis integrating published meta-analyses and independent cohort studies. Methods: PubMed/MEDLINE and Embase were searched for studies published in English between 2011 and 2024. Eligible studies included pediatric populations with asthma or wheeze phenotypes assessing predefined genetic (ORMDL3, GSDMB) or epigenetic (AHRR, FOXP3, CpG loci) markers and reporting odds ratios (ORs) or sufficient data for their derivation. Risk of bias was assessed using established quality criteria for observational studies. Quantitative synthesis was performed using a two-level random-effects model with restricted maximum likelihood estimation. Results: Six studies comprising 51,235 children met the inclusion criteria. The overall pooled estimate demonstrated a significant association between molecular markers and childhood asthma (pooled OR = 1.45; 95% confidence interval (CI) 1.30-1.61). Subgroup analyses showed comparable effects for meta-analytic data (OR = 1.39; 95% CI 1.24-1.56) and cohort studies (OR = 1.47; 95% CI 1.31-1.64). Genetic markers yielded a pooled OR of 1.38 (95% CI 1.21-1.56), while epigenetic markers showed a pooled OR of 1.48 (95% CI 1.27-1.73). Heterogeneity in asthma definitions, methylation platforms, and limited representation of non-European populations may affect generalizability. Conclusions: This systematic review and two-level meta-analysis provides robust evidence that both genetic and epigenetic variations contribute to childhood asthma susceptibility and supports integrative multi-omic approaches for early-life risk stratification.
Background/Objectives: Perioperative neurocognitive disorders (PNDs), including delirium and postoperative cognitive dysfunction, affect 10-50% of elderly surgical patients and are associated with increased morbidity and mortality, as well as substantial healthcare costs. Despite their clinical significance, the underlying mechanisms remain incompletely understood and effective interventions are limited. This narrative review synthesizes current evidence on the pathophysiology, risk factors, and management strategies for PNDs. Methods: We conducted a comprehensive literature review of peer-reviewed publications addressing PND epidemiology, mechanisms, assessment, and interventions. Key databases were searched for studies published through 2025, with emphasis on systematic reviews, meta-analyses, and landmark clinical trials. Results: PND represents a spectrum of cognitive impairments with multifactorial etiology involving neuroinflammation, neurotransmitter imbalances, and blood-brain barrier dysfunction. Advanced age, pre-existing cognitive impairment, and surgical factors constitute major risk domains. Validated assessment tools including the Confusion Assessment Method (CAM) and 4AT enable systematic detection. Multicomponent non-pharmacological interventions demonstrate 30-40% delirium reduction, while pharmacological prevention shows limited efficacy. Emerging evidence links perioperative delirium to accelerated long-term cognitive decline and increased dementia risk. Conclusions: PND represents a significant public health challenge requiring systematic attention in aging surgical populations. Evidence-based multicomponent interventions should be integrated into routine perioperative care pathways. Future research must elucidate mechanistic pathways linking acute delirium to chronic cognitive impairment and develop targeted therapies to preserve cognitive health in surgical populations.
Background/Objectives: To evaluate the clinical and MRI characteristics of benign solitary schwannomas of the extremities, compare pre- and postoperative neurological symptoms, and identify preoperative and intraoperative risk factors for postoperative complications. Methods: A retrospective review was conducted on 47 patients with histopathologically confirmed benign solitary schwannomas of the extremities who underwent surgical excision. Demographic data, MRI characteristics (tumor volume, perilesional edema, and degenerative changes such as cystic components or intratumoral hemorrhage), fascicular relationship, and use of tru-cut biopsy were recorded. Pre- and postoperative neurological symptoms were compared. Univariate logistic regression analysis was performed to identify factors associated with postoperative complications. Results: The mean age was 38.6 ± 15 years, and the mean follow-up period was 109.8 ± 65.1 months. Lesions were predominantly located in the upper extremity (65.9%), with a mean volume of 9.6 ± 4.8 cm3; perilesional edema and/or degenerative changes were present in 53.1% of cases. Postoperative complications occurred in 19.1% of patients, with intrafascicular involvement being a significant predictor (OR = 5.4, p = 0.037) and a positive preoperative Tinel's sign showing a trend toward significance (OR = 4.2, p = 0.084). Tumor volume, perilesional edema, degenerative changes, tru-cut biopsy, and anatomical location were not significantly associated with complications. At final follow-up, pain remission was 82.1%, and paresthesia improvement was 63.6%. Conclusions: Intrafascicular involvement was associated with postoperative complications in univariate analysis, whereas preoperative MRI characteristics, biopsy, and Tinel's sign showed no predictive value for postoperative risk.
Background/Objectives: Persistent strength deficits and psychological impairments may compromise return to sport (RTS) after anterior cruciate ligament reconstruction (ACLR). We investigate the relationship between thigh muscle isokinetic strength recovery at six months after ACLR and long-term psychological outcomes related to RTS in competitive male soccer players. Methods: Sixty male soccer players who underwent primary ACLR with bone-patellar tendon-bone autograft were retrospectively analyzed. Isokinetic testing of quadriceps and hamstrings was performed one week before surgery and six months post-surgery at 90°/s and 180°/s. Limb symmetry index (LSI) was calculated both pre- and post-operatively. At long-term follow-up (mean ≈ 4 years after RTS), athletes completed questionnaires assessing RTS status, ACL re-injuries, sport-related perceptions, and kinesiophobia using the Tampa Scale for Kinesiophobia (TSK). Statistical analyses were conducted to explore associations between post-operative LSI and TSK scores and to compare psychological and neuromuscular outcomes between athletes with and without ACL re-injury. Results: Absolute quadriceps and hamstring peak torque values significantly increased from pre- to post-surgery, with quadriceps strength deficits persisting only in the operated limb. However, quadriceps LSI significantly decreased post-operatively, while hamstring LSI remained stable. Pearson correlation analysis revealed a weak positive association between post-operative quadriceps LSI at 90°/s and TSK scores (r = 0.34). Overall, RTS rate was 91.7%, but a second ACL injury occurred in 18.2% of athletes. No significant differences were observed between re-injured and non-re-injured athletes in TSK scores or post-operative LSI values at either angular velocity (all p > 0.29). High kinesiophobia (TSK ≥ 37) was present in 56.7% of the cohort at long-term follow-up. Conclusions: Despite significant strength gains, quadriceps limb symmetry worsened six months after ACLR, with deficits confined to the operated limb, suggesting persistent neuromuscular inhibition. These physical deficits coexist with long-term kinesiophobia despite high RTS rates. The weak associations between strength symmetry and psychological outcomes highlight the multifactorial nature of RTS and support the need for an integrated physical, psychological, and neuro-cognitive approach to rehabilitation and RTS decision-making.
Background: Augmented reality (AR) and mixed reality (MR) promise to enhance anatomical understanding, spatial orientation, and workflow in cardiac surgery. Their clinical adoption remains limited and the translational path is incompletely defined. Methods: A PubMed search was conducted by two independent reviewers from database inception through July 2025 and identified peer-reviewed, English-language articles describing peri- or intra-operative AR/MR applications in cardiac surgery. Relevant clinical, preclinical, technical, and review articles were selected for inclusion based on scope and content. Given the narrative approach and heterogeneity across studies, findings were synthesized qualitatively into application domains. Results: Fourteen studies were included. Five domains emerged: (1) preoperative planning and patient-specific modelling-MR enhanced spatial orientation and planning for minimally invasive and valve procedures; (2) intraoperative navigation and visualization-AR improved targeting and interpretation with preclinical overlay errors ≈ 5 mm; (3) physiological/functional guidance-thermographic AR detected ischemia in vivo with strong correlation to invasive thermometry; (4) robotic integration and workflow optimization-AR-guided port placement and stepwise robotic adoption supported the feasibility of totally endoscopic CABG; (5) AR-based early rehabilitation. Conclusions: Early clinical and preclinical evidence supports AR/MR feasibility and utility for visualization and orientation in cardiac surgery. Priorities include deformable, motion-compensated registration, ergonomic integration with robotic platforms, and multicentre trials powered for operative efficiency and patient outcomes.
Background/Objectives: Postoperative atrial fibrillation (POAF) is a common and serious complication after coronary artery bypass grafting (CABG), leading to increased morbidity and healthcare utilization. Although systemic inflammation is a well-established driver of POAF pathogenesis, no composite preoperative inflammatory biomarker has been validated for risk stratification in this population. This study aimed to evaluate the novel Inflammatory Burden Index (IBI)-the first composite biomarker combining acute-phase (C-reactive protein, CRP) and chronic cellular (neutrophil-to-lymphocyte ratio, NLR) inflammation-as a preoperative predictor of POAF after CABG. Methods: In this large retrospective cohort study, we included 3481 consecutive patients who underwent isolated CABG at a high-volume cardiac center between 2019 and 2024. Preoperative IBI was calculated as CRP (mg/dL) × NLR. The primary outcome was new-onset POAF within the first 7 postoperative days, confirmed by continuous telemetry on 12-lead ECG. Predictive performance was assessed using multivariable logistic regression, receiver operating characteristic (ROC) curve analysis (area under the curve, AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and internal validation via bootstrapping (1000 resamples). Results: POAF developed in 866 patients (24.9%). Patients with POAF exhibited significantly higher preoperative IBI levels (39.4 ± 18.6 vs. 26.3 ± 16.7, p < 0.01). In multivariable analysis adjusted for age, hypertension, left atrial diameter, and other clinical covariates, IBI emerged as a strong independent predictor of POAF (adjusted OR 1.041, 95% CI 1.036-1.046, p < 0.01). The IBI alone demonstrated moderate-to-good discriminative performance (AUC 0.72, 95% CI 0.70-0.74), significantly outperforming the Systemic Immune/Inflammation Index (SII; AUC 0.61, DeLong test p < 0.001) and providing superior reclassification (NRI 0.150, IDI 0.032) and model fit (lower AIC). Combining IBI with established clinical risk factors further improved predictive accuracy (combined AUC 0.74, specificity 72.4%). Tertile-based stratification revealed a clear graded relationship with POAF incidence (low IBI: 16.6%, medium: 21.3%, high: 35.1%; p = 0.02). Notably, the medium IBI stratum (11.18-25.44) displayed the highest discriminative power (AUC 0.87, 95% CI 0.85-0.88), with bootstrap validation confirming model stability (minimal bias, robust 95% CI). Conclusions: This study establishes the preoperative Inflammatory Burden Index (IBI) as the first validated composite inflammatory biomarker independently associated with POAF following CABG. Its superior performance over existing indices (SII), graded risk stratification, and peak accuracy in the moderate inflammation window highlight its potential for personalized preoperative risk assessment and targeted perioperative intervention strategies.
Background: Robot-assisted partial nephrectomy (RAPN) can be done using either a three-arm or four-arm configuration. However, the evidence comparing the perioperative, functional, and oncological outcomes between these two approaches is inconsistent. Therefore, we aimed to quantitatively compare the outcomes of three-arm versus four-arm RAPN. Methods: A comprehensive search of multiple databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane, was conducted, adhering to the PRISMA guidelines. Studies comparing three-arm and four-arm RAPN were included. Continuous outcomes were assessed using mean differences (MD), and dichotomous outcomes were evaluated using risk ratios (RR). The ROBINS-I tool was used to determine the risk of bias. Results: Five studies that met the selection criteria were included in the final review and analysis. The pooled analyses demonstrated no significant difference in estimated blood loss, warm ischemia time, transfusion rates, overall complications, major complications, or positive surgical margins between the three-arm and four-arm RAPN. Although the initial primary analysis showed a shorter length of stay within the three-arm RAPN technique, the sensitivity analysis did not reflect this finding. Conclusions: The three-arm and four-arm RAPN demonstrated comparable perioperative, functional, and oncologic outcomes. As both techniques appear to be effective, the choice of configuration may be decided by the institutional resources, case complexity, and the surgeon's preference.
Cardiac pacing has undergone a significant transformation in the last decade. Leadless pacing (LP), once only a conceptual idea stemming from the early interest in eliminating lead-related complications of transvenous pacemakers, has now become a reality in clinical practice. Since the introduction of the first human single-chamber asynchronous leadless ventricular pacing in 2012, atrioventricular-synchronized single- or dual-chamber leadless pacing systems have been approved for clinical use since 2020. Leadless cardiac resynchronization therapy (CRT) has shown optimistic results in case series and awaits its full utility in real-world clinical practice. With the successful feasibility study of leadless conduction system pacing, we are eagerly awaiting long-term safety and efficacy data on a large scale. Another important frontier is the development of self-rechargeable LP, which may be an ideal pacemaker for the future and may reduce the burden of multiple device replacements as batteries near the end-of-service. Totally extravascular percutaneous leadless pericardial micro-pacemaker system implantation is under development. In this state-of-the-art review, we examine the evolution of cardiac pacing, emphasizing the development and utility of LP to meet maximum physiological pacing needs, optimize atrioventricular synchrony and cardiac resynchronization, and broaden its indications.
Background: Building on the validation of the Your Memory test for mild cognitive impairment in English speakers, this study adapted and validated the Memory Test for Mild Cognitive Impairment (TYM-MCI) for older Spanish-speaking adults, highlighting its potential utility for the early detection of amnestic mild cognitive impairment and cognitive profiles associated with increased risk of dementia. Methods: A total of 151 independently functioning adults aged 60 or older (Barthel Index 9-10) completed the TYM-MCI, the Addenbrooke's Cognitive Examination-Revised (ACE-R-Ch), the Mini-Mental State Examination, and the original TYM. Analyses included ROC curves, correlation matrices, and principal component analysis (PCA). Results: The TYM-MCI exhibited strong psychometric properties (Cronbach's α = 0.832; sensitivity = 81.7%; specificity = 47.8%). The optimal cut-off score was ≥24.5/30. Scores between 19 and 24.5 suggested probable mild cognitive impairment (MCI). Conclusions: The episodic memory components of this test are key cognitive features relevant to the modification and monitoring of early cognitive decline and are straightforward to administer. Notably, the TYM-MCI specifically assesses both visual and verbal episodic memory. It can be used alongside other assessments, such as the ACE-R or MMSE, to support the clinical evaluation of cognitive functioning in older adults. Clinically, it provides an early assessment and follow-up in individuals presenting with memory complaints, contributing to timely clinical decision-making in the context of cognitive decline.
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