J. Clin. Med., Volume 15, Issue 11 (June-1 2026) – 409 articles

Background: Early assessment of myocardial injury severity at presentation remains challenging in acute myocardial infarction (AMI). Complete blood count (CBC)-derived inflammatory indices may provide accessible adjunctive biomarkers reflecting early systemic inflammatory activation associated with myocardial injury. This study evaluated the association and discriminative performance of CBC-derived inflammatory indices for presentation-time myocardial injury severity. Methods: This retrospective study included 252 patients with AMI. CBC-derived inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-lymphocyte × platelet ratio (NLPR), were calculated from blood samples obtained at presentation (0 h). Correlation analysis, multivariable linear regression, logistic regression, incremental model analysis, and receiver operating characteristic (ROC) analysis were performed to assess associations with high-sensitivity Troponin T (hs-Troponin T) levels and high myocardial injury, defined as the highest hs-Troponin T tertile. Results: Both log NLR and log NLPR showed significant positive correlations with log hs-Troponin T (ρ = 0.422 and 0.396, respectively; p < 0.001). In multivariable linear regression adjusted for clinical variables and AMI subtype, log NLR (B = 0.88, p < 0.001) and log NLPR (B =0.77, p < 0.001) remained independently associated with log hs-Troponin T. Incremental model analysis demonstrated significant increases in explanatory performance after addition of log NLR (ΔR² = 0.137) and log NLPR (ΔR² = 0.121, p < 0.001). In logistic regression, log NLR (adjusted OR 2.77, 95% CI 1.65–4.66) and log NLPR (adjusted OR 2.46, 95% CI 1.53–3.95) were independently associated with high myocardial injury. ROC analysis demonstrated modest improvement in discrimination after incorporation of inflammatory indices, with AUC increasing from 0.709 for the baseline clinical model to 0.778 with log NLR and 0.770 with log NLPR. Supplementary reclassification analyses demonstrated improved classification performance. Conclusions: CBC-derived inflammatory indices, particularly NLR and NLPR, were independently associated with presentation-time myocardial injury severity in patients with AMI, even after adjustment for AMI subtype. Although improvements in ROC-based discrimination were modest, supplementary reclassification analyses suggested incremental value beyond conventional clinical variables and AMI subtype. These findings support the potential utility of CBC-derived inflammatory indices for early assessment of myocardial injury during AMI presentation. Full article

Background: Obstetric anal sphincter injuries (OASIS) are a major cause of long-term maternal morbidity. Identification of risk factors is central to prevention strategies. Methods: A retrospective cohort study was conducted including all singleton, term, cephalic vaginal births over a four-year period (September 2018 to September 2022) at a UK tertiary maternity unit. OASIS was defined as third- or fourth-degree perineal tears according to RCOG criteria. Multivariable logistic regression analysis was used to identify independent predictors. A pre-specified sensitivity analysis restricted to nulliparous women was performed. Secondary outcomes included postpartum haemorrhage (PPH), defined as blood loss >1 L. Reporting follows the STROBE statement for cohort studies. Results: Among 9586 vaginal births, 270 OASIS cases were identified, corresponding to an incidence of 2.82%. Independent predictors included nulliparity (aOR 7.12, 95% CI 5.07–10.01), Asian ethnicity (aOR 3.50, 95% CI 2.55–4.81), shoulder dystocia (aOR 3.45, 95% CI 1.89–6.32), and birthweight ≥4000 g (aOR 1.85, 95% CI 1.16–2.95). Maternal age ≥35 years showed a borderline association (aOR 1.34, 95% CI 0.99–1.80, p = 0.056). Using forceps as the reference, ventouse (aOR 0.28, 95% CI 0.17–0.47) and spontaneous vaginal delivery (aOR 0.23, 95% CI 0.13–0.39) were associated with lower OASIS odds. Episiotomy (recorded as a binary variable) was associated with lower adjusted odds of OASIS (aOR 0.27, 95% CI 0.17–0.44). PPH occurred in 21.5% of women with OASIS versus 6.5% without (p < 0.001). Conclusions: OASIS risk is driven by a combination of maternal, fetal, and intrapartum factors. Selective mediolateral episiotomy was associated with lower adjusted odds of OASIS in this cohort, but this is an observational finding and does not constitute proof of a causal protective effect. It should be interpreted cautiously given the retrospective design, the recording of episiotomy as a binary variable without procedural detail, and the substantial potential for residual confounding by indication. The findings support targeted perineal protection strategies and selective rather than routine episiotomy use. Full article

Background: Axillary hidradenitis suppurativa (HS) often requires wide surgical excision and reconstruction. Thoracodorsal artery perforator (TDAP) flaps and split-thickness skin grafts (STSGs) are common options, but comparative long-term data are insufficient. Methods: In this single-center retrospective study, patients aged ≥ 17 years with Hurley stage II–III axillary HS underwent wide excision followed by TDAP flap or STSG reconstruction. Demographic variables, surgical characteristics, complications, recurrence, shoulder mobility, and dermatology-specific quality-of-life outcomes assessed using the Dermatology Life Quality Index (DLQI) were analyzed. Results: In total, 35 reconstructions were reviewed: TDAP (n = 15, 42.9%) and STSG (n = 20, 57.1%). Follow-up was longer for TDAP (28.53 ± 16.38 vs. 19.65 ± 28.06 months; p = 0.014). Mean defect size was 105.47 ± 26.29 cm² (TDAP) vs. 164.65 ± 77.99 cm² (STSG; p = 0.116). Both groups showed significant improvement in DLQI from preoperative to postoperative assessments (TDAP: +20.87; Graft: +18.50; both p < 0.0001), with no significant postoperative difference (p = 0.9608). Smokers had higher preoperative DLQI scores than non-smokers (+5.72; p = 0.0051), but postoperative outcomes were similar (p = 0.5908). Conclusions: Both reconstructions after wide axillary excision provided durable coverage, low complication rates, and significant improvement in quality of life. Incorporating patient-reported and functional outcomes into reconstructive planning may optimize surgical decision-making for axillary HS. Full article

Congenital pericardial agenesis (CPA) is a rare anomaly that is often considered a benign incidental finding but may present with nonspecific symptoms and mimic structural heart disease. Its clinical relevance remains incompletely defined, particularly regarding the distinction between a harmless anatomical variant and a clinically significant condition. We present a retrospective two-center case series of four patients with imaging-confirmed CPA, combined with a narrative review of the literature aiming to evaluate the clinical spectrum, diagnostic challenges, and management implications of CPA. The clinical presentation of our patients was heterogeneous, ranging from incidental findings to chest discomfort and dyspnea. In all cases, initial echocardiography suggested alternative diagnoses, including right ventricular cardiomyopathy, atrial septal defect, or pericardial disease, leading to diagnostic uncertainty. Definitive diagnosis was established using multimodality imaging, particularly cardiac magnetic resonance and computed tomography, which demonstrated characteristic features such as cardiac levoposition and interposition of lung parenchyma. Three patients had complete left pericardial agenesis and one had a partial defect. All patients were managed conservatively, without complications during follow-up. Full article

Purpose: To evaluate the real-world effectiveness of low-dose atropine in slowing myopia progression in European children and to contextualize axial elongation using an age- and race-adjusted epidemiological model. Methods: This retrospective, longitudinal cohort study included 76 children (mean age 8.7 ± 1.5 years) with myopia treated with atropine 0.01%, 0.025%, or 0.05% at a tertiary hospital in Madrid. Cycloplegic spherical equivalent (SE) and axial length (AL) were recorded at baseline and 12 months. Expected untreated AL elongation was estimated using a published meta-regression model. Observed and expected AL changes were compared using paired t-tests. Predictors of SE and AL progression were assessed using multiple linear regression including age, sex, baseline SE or AL, atropine concentration, adherence, ethnicity, and family history. Results: Mean SE progression was −0.08 ± 0.11 D per year, and mean AL elongation was 0.08 ± 0.23 mm per year. Expected untreated elongation was 0.36 ± 0.09 mm per year and significantly exceeded the observed elongation (p < 0.001), representing a 78% relative reduction (effect size Cohen’s d = −1.18). Older age (≥9 years) and more negative baseline SE were associated with greater SE progression (p < 0.05). Adverse effects and treatment tolerability were not systematically evaluated in this retrospective cohort. No significant differences were found across atropine concentrations, adherence levels, sex, ethnicity, or family history. The regression model for AL progression was not statistically significant. Conclusions: Low-dose atropine demonstrated real-world effectiveness in reducing myopia progression in European children. Axial elongation was markedly lower than epidemiological expectations, supporting low-dose atropine as a first-line therapy in routine clinical practice. Age and baseline refractive error were significant predictors of treatment response. Full article

Background: The factors contributing to physical inactivity in patients with asthma remain unclear. We aimed to explore the pulmonary and extra-pulmonary factors associated with physical activity (PA) in these patients, with stratification by activity intensity. Methods: Patient demographics, Charlson Comorbidity Index, lung function, bronchial and alveolar nitric oxide (NO) levels, six-minute walk test (6 MWT), and PA were cross-sectionally evaluated in healthy participants (n = 14) and patients with asthma (n = 29). The desaturation–distance ratio (DDR) was measured as an index derived from travel distance and desaturation levels during the 6 MWT. Results: Patients with asthma had significantly lower PA than healthy participants, regardless of activity intensity (≥2 metabolic equivalents [METs]: 198 min vs. 240 min, p < 0.05; ≥3 METs: 54 min vs. 86 min, p < 0.05; ≥4 METs: 10 min vs. 26 min, p < 0.01). Extra-pulmonary factors (age, comorbidities, and 6 MW distance) showed higher correlation coefficients with PA as activity intensity increased. Contrastingly, pulmonary factors (asthma severity, airflow limitation, and alveolar exhaled NO) showed lower correlation coefficients with PA as activity intensity increased. The DDR was negatively associated with active time across all activity intensities. Conclusions: Our findings suggest that aging and comorbidities are potential limiting factors for moderate-to-vigorous physical activity, whereas asthma severity and airway dysfunction restrict daily life in patients with asthma. Moreover, the DDR could facilitate detection of real-life physical inactivity in patients with asthma. Full article

Background/Objectives: Multimodal large language models (LLMs) are increasingly integrated into dental diagnostics. This study evaluated the ability of ChatGPT-4o and Gemini 3 Flash to visually identify endodontic instruments and assess their explanatory plausibility regarding instrument morphology. Methods: Standardized images of five endodontic file systems (Reciproc R25, Reciproc Blue, WaveOne Gold, MM One Shape, and XP-endo Finisher) were submitted to both models via their free tiers. Each image was evaluated 50 times per model (total n = 500) to assess both classification accuracy and response consistency. Visual recognition performance was measured using recall, precision, and F1-score, while the plausibility of morphological explanations was evaluated using a structured 3-point scale. Results: Gemini 3 Flash demonstrated significantly higher recognition performance compared to ChatGPT-4o (p < 0.001). The overall acceptable response rate was higher for Gemini 3 Flash (94.4%, [95% CI: 91.5–97.3%]) than for ChatGPT-4o (67.2%, [95% CI: 61.4–73.0%]; p < 0.001). Notably, Gemini 3 Flash showed strong performance in identifying complex instrument designs, whereas ChatGPT-4o exhibited marked limitations in recognizing certain non-standard geometries. Reliability analysis indicated higher consistency for Gemini 3 Flash (κ = 0.86, [95% CI: 0.81–0.91]) compared to ChatGPT-4o (κ = 0.51, [95% CI: 0.44–0.58]). Conclusions: Gemini 3 Flash outperformed ChatGPT-4o in both classification accuracy and consistency in this controlled visual identification task. While these findings highlight the potential of multimodal LLMs in endodontic workflows, their current performance variability limits direct, autonomous clinical application. Further validation under clinically realistic conditions is required before such systems can be considered reliable adjunctive tools. Full article

Background/Objectives: Traumatic duodenal diverticulum perforation is a rare, potentially fatal consequence of blunt trauma. Nonspecific symptoms and diagnostic challenges often delay recognition. This systematic review characterizes its clinical features, management, and outcomes. Methods: A systematic literature search covering 1960 to December 2025 identified eligible cases. Inclusion criteria were blunt trauma-related duodenal diverticulum perforations confirmed by imaging or surgery. Data were analyzed according to PRISMA 2020 guidelines. Results: Twenty-one cases were identified (mean age 62.9 years; sex ratio (M:F) 8:13). Primary injury mechanisms were traffic accidents (10 of 21) and falls from height (8 of 21). Most injuries involved the descending duodenum (D2; 17 of 21). Common presenting signs included abdominal pain (19 of 21) and epigastric tenderness (16 of 21). Computed tomography confirmed findings consistent with perforation in all scanned patients (17 of 17). Surgical management was employed in 20 of 21 patients, predominantly via manual (11 of 20) or stapled (9 of 20) diverticulectomy, with drainage applied in 18 of 20 operated cases. Complications occurred in 13 of 21 patients. Overall mortality was 4 of 21. Conclusions: Traumatic duodenal diverticulum perforation remains a life-threatening event requiring high clinical vigilance. The data collected suggest that early CT scanning and prompt surgical intervention may be associated with better treatment outcomes, although these conclusions should be treated with caution due to the small sample size. The protocol was registered in PROSPERO (CRD420261285658). Full article

Background: As survival after colorectal cancer (CRC) has improved, an increasing proportion of patients live beyond five years, making long-term outcomes increasingly relevant. In addition to cancer-related mortality, survivors remain at risk of death from other causes influenced by clinical and psychosocial vulnerabilities. Methods: We conducted a 10-year prospective cohort study including 838 patients with stage I–IV CRC treated in public hospitals in the Basque Country (Spain). Patients were recruited between November 2010 and December 2012 and followed for up to 10 years after surgery. Clinical, sociodemographic, lifestyle, and patient-reported outcomes were collected. Competing risk regression models (Fine-Gray) were used to estimate sub-distribution hazard ratios (sHRs) for CRC-specific and non-CRC mortality, stratified by tumor site and sex. Results: After 10 years, 40% of patients had died, with 66% of deaths attributable to CRC and 34% to other causes. CRC-specific mortality was mainly driven by tumor-related factors, including advanced stage (stage IV: sHR 7.18, p < 0.001) and residual disease after surgery (R1/R2: sHR 2.68; p < 0.001), with larger effect sizes observed in rectal cancer. In contrast, non-CRC mortality was associated with patient vulnerability, including age ≥75 years (sHR 3.57, p < 0.001), absence of adjuvant chemotherapy (sHR 5.59, p < 0.001), anemia, alcohol consumption, and poor functional status. Patients with rectal cancer and women reported poorer baseline quality of life. Sex-stratified analyses suggested differential patterns of vulnerability, with psychosocial and quality-of-life-related factors appearing more relevant in women, whereas lifestyle and clinical factors appeared more prominent in men. Conclusions: Long-term mortality in CRC reflects the interplay between tumor-related factors and patient vulnerability. Competing risk models allow a more accurate characterization of cause-specific outcomes and may help identify high-risk subgroups for tailored follow-up and management strategies. Full article

Background/Objectives: Lower-limb muscle quantity and quality may be associated with mobility performance, but the relationship between bioelectrical impedance analysis (BIA)-derived lower-limb indices and slow Timed Up and Go (TUG) performance remains insufficiently established. This cross-sectional study examined the associations of lower-limb muscle mass and phase angle (PhA) with TUG performance and explored ROC-derived values for slow TUG performance in 280 community-dwelling Japanese adults. Methods: Lower-limb muscle mass and segmental lower-limb PhA were measured using multifrequency segmental BIA and averaged across both legs. Multiple linear regression analyses were used to examine associations between TUG time and BIA-derived indices after adjusting for age and body size. Receiver operating characteristic analyses were performed for slow TUG performance, defined as TUG ≥ 9 s and ≥10.2 s, and Youden index-derived values were calculated as exploratory estimates. Results: Lower-limb PhA was independently associated with TUG performance across both body-size adjustment models, whereas lower-limb muscle mass was retained only in the model adjusted for BMI. For slow TUG performance, the lower-limb muscle mass-to-body weight ratio showed moderate discriminatory ability, with AUCs of 0.75 for TUG ≥ 9 s and 0.78 for TUG ≥ 10.2 s. Standardized lower-limb PhA showed AUCs of 0.65 and 0.64, respectively. The Youden index-derived standardized PhA value was Z = −1.04 for both TUG thresholds; however, these ROC-derived values were not internally or externally validated. Conclusions: Lower-limb BIA-derived indices, particularly segmental lower-limb PhA, were associated with TUG performance in community-dwelling Japanese adults. The ROC-derived values should be interpreted strictly as exploratory, hypothesis-generating estimates and should not be used for clinical screening or individual-level clinical decision-making without validation in larger independent cohorts. Full article

Background/Objectives: In Saudi Arabia, noncommunicable diseases (NCDs) are an increasing public health concern, with almost 70% of deaths related to chronic diseases. The study aimed to analyze 33-year trends in NCD risk factors and apply machine learning (ML) models to identify ecological associates of premature NCD-related mortality, sex-specific analyses and project trajectories to 2030. Methods: A longitudinal ecological time-series design which used WHO Global Health Observatory (GHO) NCD Indicators (1990–2022; select lipid indicators from 1980). Five supervised regression ML models—OLS, LASSO, Ridge, Random Forest, and Gradient Boosting—were trained with TimeSeriesSplit cross-validation (five folds) to preserve temporal order and prevent data leakage. A formal PELT changepoint algorithm confirmed trend breakpoints. Linear projections to 2030 were estimated with 95% prediction intervals. Results: Adult obesity increased by +20.6 percentage points (pp) over 33 years. Under a no-policy-change scenario, female obesity is projected at 50.3% by 2030 (95% PI: 50.0–50.5%). Premature NCD mortality declined by −5.9 pp. Under TimeSeriesSplit CV, all models yielded negative R², confirming LOOCV R² = 0.98 reflected shared time-trend artefacts; the ML component is reframed as descriptive feature-importance analysis. The obesity sex gap (female minus male) was the strongest ecological associate of premature NCD mortality. Diabetes treatment coverage showed a strong inverse ecological association (r = −0.913). Conclusions: NCD risk factors in Saudi Arabia are evolving in complex ways. Targeted interventions addressing sex-specific disparities and healthcare system performance are urgently needed to meet national and global NCD targets. Full article

Background: Ischemic cardiomyopathy (ICM) is characterized by heterogeneous structural remodeling that is not fully captured by conventional systolic metrics. How multidimensional structural echocardiographic information can improve pre-revascularization risk stratification remains unclear. Methods: In this retrospective study, 989 patients with ICM undergoing coronary angiography and revascularization were included in the derivation cohort, and 482 patients from an independent campus served as the validation cohort, with a median follow-up duration of 6.5 years. The primary endpoint was cardiovascular mortality. Eight routinely acquired pre-revascularization echocardiographic structural variables were analyzed. Unsupervised clustering identified structural clusters, and principal component analysis (PCA) was used to derive a structural risk score. Associations with cardiovascular mortality were assessed using the Cox proportional hazards model, and prognostic performance was evaluated by comparing individual echocardiographic predictors using Harrell’s C-index and time-dependent AUC analyses. Results: Three distinct structural clusters emerged, differing in chamber size, systolic function, pulmonary pressures, mitral regurgitation severity, and long-term cardiovascular mortality. The PCA-derived structural risk score, reflecting the dominant axis of remodeling and volume overload, showed association with cardiovascular mortality in the derivation cohort and remained independently predictive after multivariable adjustment. Compared with single echocardiographic parameters, both the structural clusters and the risk score demonstrated superior discriminative performance. In the validation cohort, the structural score again showed a consistent and independent association with cardiovascular mortality. Conclusions: Multidimensional structural echocardiographic assessment reveals clinically meaningful remodeling patterns and enables construction of a robust PCA-derived structural risk score. Both approaches provide prognostic information beyond individual echocardiographic measures and support more precise pre-revascularization risk stratification in patients with ICM. Full article

Background/Objectives: Early mortality after pediatric liver transplantation remains a clinical challenge, yet few studies have specifically addressed 30-day outcomes. Conventional pretransplant scores such as the age-appropriate MELD/PELD score were not designed for post-transplant risk prediction. We aimed to evaluate whether dynamic postoperative biomarker trajectories and novel composite ratios can identify high-risk patients. Methods: This single-center retrospective cohort study included 140 consecutive pediatric patients (<18 years) who underwent primary liver transplantation between 2015 and 2023. Patients were classified as deceased (≤30 days, n = 11) or survivors (>30 days, n = 129). PRISM-III, PELOD-2, and age-appropriate MELD/PELD scores were evaluated. Serial laboratory parameters were collected at pretransplant and at 0, 24, and 72 h. Delta (Δ) values and composite ratios—including lactate clearance, lactate-to-albumin ratio (LAR), INR×lactate product, platelet ratio, and fibrinogen/INR—were calculated. Penalized logistic regression (Firth method) was used for multivariate analysis. Internal validation was performed using bootstrap resampling (1000 iterations) and leave-one-out cross-validation (LOO-CV). Because two of the three components of the multivariable model (ΔINR, ΔALT) were derived from 72-h values, the model is best understood as a 72-h landmark risk model rather than as an immediate post-transplant early-warning tool. Results: The 30-day mortality rate was 7.9% (11/140), with central nervous system complications as the leading cause (36.4%). PRISM-III demonstrated excellent discrimination (AUROC 0.957; cut-off ≥ 14); the age-appropriate MELD/PELD score, a pretransplant tool not designed for post-transplant prediction, showed near-chance performance (AUROC 0.513; p = 0.576). A distinctive biomarker crossover pattern was observed: non-survivors had paradoxically lower pretransplant INR, ALT, and LAR values, but trajectories diverged sharply by 24 h. The INR×lactate product achieved an AUROC of 0.981 at 72 h. LAR at 24 h achieved 0.909, and lactate clearance at 0 → 72 h achieved 0.783. Postoperative hypernatremia emerged as a strong predictor (AUROC 0.884). In multivariate analysis, PRISM-III (OR 4.00), ΔINR (OR 3.28), and ΔALT (OR 3.46) were independent predictors (apparent AUROC 0.989). Internal validation confirmed model stability: bootstrap-corrected AUROC was 0.978; LOO-CV AUROC was 0.957 (sensitivity 90.9%, specificity 96.9%). Conclusions: Dynamic postoperative factors—rather than pretransplant disease severity—appeared more strongly associated with 30-day mortality after pediatric liver transplantation in this single-center exploratory analysis. The INR×lactate product, a novel two-variable composite, showed very high apparent discrimination (AUROC 0.981) and is proposed as a hypothesis-generating candidate marker requiring prospective external validation before any clinical use. The combined PRISM-III + ΔINR + ΔALT model (best understood as a 72-h landmark risk model, since two of its three components are defined at 72 h postoperatively) demonstrated robust internal validation performance (LOO-CV AUROC 0.957); however, given the small number of events (n = 11) and the absence of external validation, the model should be regarded as exploratory. Full article

Background: Programmed cell death protein-1 (PD-1) and its ligands, PD-L1 and PD-L2, constitute a central immune checkpoint pathway that regulates T-cell activity and tumor immune escape, while their relationship with STAT signaling remains incompletely understood in ccRCC. Methods: We analyzed 27 paired ccRCC and adjacent non-tumorous human kidney tissue samples. mRNA levels of PD-1, PD-L1, PD-L2, STAT1, and STAT3 were quantified by RT-qPCR. In addition, representative human ccRCC cell lines (CAKI-2 and A-498) were treated with IFN-γ to assess the time-dependent modulation of immune checkpoint molecules and STAT pathway activation. Results: PD-L1 and PD-L2 were significantly upregulated in tumor tissues compared with adjacent normal kidney tissue. Exploratory observation suggests grade dependent increase. Whereas PD-1 was predominantly downregulated, IFN-γ treatment induced a rapid transcriptional upregulation of PD-L1 and PD-L2 in RCC cell lines, with maximal protein accumulation observed at 72 h. STAT1, but not STAT3, exhibited dynamic induction following IFN-γ stimulation, showing temporal association with PD-L1 and PD-L2 upregulation, indicating cell-line-specific regulatory effects. Correlation analyses confirmed a strong correlation between PD-1 and its ligands, whereas STAT1 and STAT3 expression showed no direct association with PD-L1 or PD-L2 levels in cancer samples. Conclusions: Our findings demonstrate that PD-L1 and PD-L2 are frequently upregulated in ccRCC and dynamically regulated by IFN-γ/STAT1-dependent signaling. Our results provide additional insight into the mechanisms of immune escape and underscore the potential of integrated profiling of PD-1 ligands and STAT signaling to guide personalized immunotherapeutic strategies in ccRCC. Full article

Background: Carotid atherosclerosis is a recognised manifestation of systemic vascular disease, and its association with coronary artery disease (CAD) has been well described. However, previous studies have largely been conducted under conventional diagnostic conditions and have focused on carotid plaque, intima–media thickness, or simple present-versus-absent stenosis classifications, rather than duplex-derived haemodynamic markers across the spectrum of angiographic CAD burden. The COVID-19 pandemic and post-pandemic period changed referral patterns and created more variable cardiovascular presentations, including symptoms that could resemble or mask obstructive CAD. Therefore, we investigated whether the established association between carotid stenosis severity and CAD burden remains detectable in a diagnostically heterogeneous real-world cohort, and whether routinely available carotid duplex haemodynamic parameters provide a clinically relevant signal in this setting. Methods: This single-centre, cross-sectional study was performed as a carotid-focused secondary analysis of the BG Study cohort. We included 902 consecutive patients who underwent invasive coronary angiography between 2021 and 2023 and carotid duplex ultrasonography during the same hospitalisation. CAD burden was defined according to the number of major coronary vessels with ≥70% diameter stenosis and classified as no CAD, one-vessel, two-vessel, or three-vessel disease. Carotid duplex parameters included peak systolic velocities of the common, internal, and external carotid arteries, as well as ICA stenosis severity graded according to NASCET criteria. Associations with CAD burden were assessed using a staged statistical approach combining χ² tests, Kruskal–Wallis tests with post hoc pairwise comparisons, Spearman correlation, inverse probability weighting, and ordered logistic regression. Results: The prevalence of measured ICA stenosis of any grade and severe ICA stenosis increased with greater CAD burden (both p < 0.001). Median PSV values of the bilateral ICAs and ECAs differed significantly across CAD groups on global intergroup testing. Post hoc pairwise analyses showed that significant corrected differences were concentrated between patients without CAD and those with multivessel or three-vessel CAD, particularly for ICA stenosis measures and bilateral ECA PSV. Spearman analysis demonstrated weak but statistically significant correlations between carotid parameters and CAD burden (ρ = 0.085–0.134). After inverse probability weighting, covariate balance was achieved, with all post-IPW standardised mean differences being <0.01. In ordered logistic regression (OLR) analysis, patient-reported history of carotid stenosis (OR 2.25, 95% CI 1.38–3.67; p < 0.001), right external carotid artery PSV per 10 cm/s (OR 1.31, 95% CI 1.09–1.57; p = 0.004), left ICA PSV per 10 cm/s (OR 1.17, 95% CI 1.01–1.36; p = 0.034), and left ICA stenosis per 10% (OR 1.24, 95% CI 1.11–1.39; p < 0.001) were independently associated with higher CAD burden. Exploratory ratio-based analyses showed that the ECA/CCA PSV ratio was associated with CAD presence and higher CAD burden, whereas the ICA/CCA ratio showed weaker associations; neither ratio-based index outperformed absolute ECA PSV. Conclusions: In this carotid-focused secondary analysis of a pandemic-era angiography cohort, carotid stenosis severity and duplex-derived haemodynamic parameters were independently but modestly associated with increasing angiographic CAD burden. These findings support carotid duplex markers as adjunctive indicators of systemic atherosclerotic burden rather than standalone tools for CAD detection or treatment decision-making. Future validation in vascular surgery populations is warranted to determine whether routinely available carotid duplex parameters can contribute to targeted cardiovascular risk recognition before major vascular procedures. Full article

Background/Objectives: To develop and validate a multidimensional risk assessment scale for identifying patients at risk of peripheral venous catheter (PVC)-associated phlebitis. Methods: This methodological study followed a two-phase design. In Phase 1 (scale development), an initial item pool of 39 candidate items was generated from a focused literature review and refined using the Lawshe technique with 20 expert raters. Data were collected from 729 hospitalized patients, who contributed 1008 PVCs between February and September 2021. Because the scale items are catheter-level, the PVC was the unit of analysis: 502 PVCs (from 380 patients) were used for exploratory factor analysis (EFA), and 506 PVCs (from 349 patients) for confirmatory factor analysis (CFA). In Phase 2 (clinical application), the finalized scale was administered to a separate, independent cohort of 208 patients between September and October 2021 alongside the Infusion Nurses Society (INS) Phlebitis Scale. Reliability was assessed using the Kuder–Richardson 20 (KR-20) coefficient, and discriminative performance was evaluated with Receiver Operating Characteristic (ROC) curve analysis. Results: EFA and CFA confirmed a three-factor structure comprising 14 items distributed across Individual, Chemical, and Mechanical risk domains. The instrument demonstrated strong internal consistency (KR-20 = 0.823) and excellent discriminative accuracy (AUC = 0.898), with an optimal cut-off of 20.5 (sensitivity 87%, specificity 91%). All CFA fit indices met the conventional acceptability thresholds (χ²/df = 3.249; GFI = 0.943; AGFI = 0.914; CFI = 0.942; NFI = 0.919; IFI = 0.943; TLI = 0.925; RMSEA = 0.067). In Phase 2, scale scores correlated significantly with the INS Phlebitis Scale (r = 0.794, p < 0.001). Conclusions: The Risk Assessment Scale for PVC-Associated Phlebitis is a valid and reliable instrument with strong psychometric properties. It enables early identification of high-risk patients and supports targeted preventive strategies in clinical practice. Full article

Background: The optimal antiplatelet strategy after transcatheter aortic valve implantation (TAVI) in patients who do not require long-term oral anticoagulation remains debated. Randomized trial evidence supports single antiplatelet therapy (SAPT) over dual antiplatelet therapy (DAPT), yet real-world practice patterns and the magnitude of benefit in contemporary TAVI populations remain heterogeneous. Methods: We analyzed consecutive patients undergoing TAVI at a single tertiary center between April 2009 and April 2023 who were discharged on an antiplatelet regimen only. Patients on chronic oral anticoagulation were excluded. The exposure was defined by the discharge regimen (SAPT vs. DAPT), treated as a time-varying variable with person-time split at the documented date of any regimen change. The pre-specified efficacy endpoint was ischemic major adverse cardiovascular events (iMACE: death, stroke, or myocardial infarction); net adverse clinical events (NACEs) added major bleeding. The primary analysis was a time-varying Cox model adjusted for baseline variables. Sensitivity analyses included an intention-to-treat Cox model, a 6-month landmark Cox model, and an inverse-probability-of-treatment-weighted (IPTW) time-varying Cox model. Results: Of 662 eligible patients, 147 (22.2%) were discharged on SAPT and 515 (77.8%) on DAPT. Median follow-up was 34 months (IQR 14–52). During follow-up, 141 iMACE and 146 NACEs occurred. In the primary time-varying Cox model, the adjusted hazard ratio for DAPT versus SAPT was 1.28 (95% CI 0.81–2.04; p = 0.292) for iMACE and 0.71 (95% CI 0.44–1.14; p = 0.159) for NACE. None of the sensitivity models demonstrated a statistically significant difference between groups. Major bleeding was rare (six events; two SAPT, four DAPT). The 30-day landmark analysis showed no signal of an effect of regimen on late stroke (HR 1.12, 95% CI 0.39–3.12). Conclusions: In a contemporary real-world TAVI cohort, no statistically significant difference between SAPT and DAPT was observed for ischemic or net adverse clinical events. These findings demonstrate no ischemic disadvantage of SAPT compared with DAPT in real-world practice and are consistent with the randomized evidence base supporting SAPT as a reasonable default antiplatelet strategy after TAVI in patients without another antithrombotic indication. The bleeding endpoint was underpowered, and the expected bleeding advantage of SAPT could not be independently evaluated in this cohort. Full article

Placental examination is frequently performed following adverse fetal or neonatal neurologic outcomes to elucidate the cause or timing of injury. In practice, however, the placenta more often serves as a biologic archive of fetal stress, adaptation, and reduced physiologic reserve rather than a definitive record of injury. This review synthesizes current research linking placental pathology to perinatal brain injury, with emphasis on biological mechanisms and temporal interpretation. We examine how placental findings inform assessments of intrauterine stress, impaired placental or fetal perfusion, inflammation, and diminished placental reserve. Surrogate markers of fetal stress, including nucleated red blood cells and intrauterine meconium passage, provide contextual evidence regarding the duration and severity of intrauterine compromise but do not establish causality. Finally, we review acute circulatory disruption, chronic or intermittent impairment of fetal blood flow, umbilical cord-related pathology, and immune-mediated placental disorders that increase vulnerability to neurologic injury. Full article

Background/Objectives: Pregnancy is characterized by complex physiological, hormonal, and immunological changes that influence the oral environment and the microbial composition of the oral cavity. Emerging evidence suggests that maternal oral dysbiosis may be associated with systemic inflammatory responses and may potentially influence pregnancy outcomes. This systematic review aimed to evaluate the current clinical evidence regarding the association between maternal oral dysbiosis and adverse pregnancy outcomes, including preterm birth, low birth weight, and gestational complications. Methods: A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library was conducted for studies published between January 2013 and September 2025. Observational studies and clinical trials examining the relationship between maternal oral dysbiosis or periodontal pathogens and pregnancy outcomes in pregnant women were included. Study selection was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines, and the review was prospectively registered in PROSPERO (CRD420261383855). Data were extracted on the study design, population characteristics, microbiological assessment methods, and reported pregnancy outcomes. Ten studies met the inclusion criteria of this review. Results: Seven of the ten included studies reported significant associations between the increased prevalence of periodontal pathogens, including Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia, and adverse pregnancy outcomes, particularly preterm birth and low birth weight (LBW). Several studies have identified oral bacterial DNA in placental tissues, supporting the potential hematogenous microbial translocation pathways. However, heterogeneity in microbiological assessment techniques and study designs limits the comparability of the findings. Conclusions: Current evidence suggests that maternal oral dysbiosis may be associated with the inflammatory pathways linked to adverse pregnancy outcomes. Further prospective studies and standardized microbiome analyses are required to clarify the role of the oral microbiome in maternal and fetal health. Integrating oral health assessments into prenatal care may be an important strategy for improving maternal and neonatal outcomes. Full article

Background/Objectives: Athletes are characterized by distinct haemodynamic adaptations of the cardiovascular system, including descending aorta haemodynamics, that could influence the diagnosis of coarctation of the aorta. This study aims to evaluate the normal range for the maximum velocity of blood flow in the descending aorta (Vmax-AoDesc) and the predictors of Vmax-AoDesc in apparently healthy athletes without coarctation of the aorta. Methods: We examined 559 asymptomatic healthy athletes with an age of at least 12 years and a tricuspid aortic valve (420 males, age: 29 ± 14 years). We performed evaluations of athletic history, measurements of brachial systolic and diastolic blood pressure, cardiac and aorta ultrasonography and cardiopulmonary exercise testing. Forty athletes were reassessed after a median follow-up of 3.0 (IQR: 2.1) years. Results: The median Vmax-AoDesc was 1.29 (IQR: 0.28) m/s, with a maximum of 2.00 m/s. The Vmax-AoDesc could be independently predicted by age (β = −0.392, p < 0.001), ratio of systole/diastole (β = 0.095, p = 0.023), brachial systolic blood pressure (β = 0.251, p < 0.001), left ventricular stroke volume (β = 0.256, p < 0.001), ascending aorta diameter (β = −0.230, p < 0.001), aortic arch diameter (β = −0.111, p = 0.044) and descending aorta diameter (β = −0.103, p = 0.017). Age accounted for the greatest variability of Vmax-AoDesc (5.8%). Vmax-AoDesc correlated positively with h/week of endurance exercise training (rho = 0.182, p < 0.001) and oxygen uptake at second ventilatory threshold (rho = 0.299, p = 0.001). Vmax-AoDesc did not change significantly during follow-up (p = 0.438). The median change in Vmax-AoDesc was −0.05 (IQR: 0.18) m/s. However, when Vmax-AoDesc was adjusted for all the above-mentioned independent predictors of Vmax-AoDesc apart from age and systolic blood pressure, there was a reduction in adjusted Vmax-AoDesc during follow-up (p = 0.007), indicating a reduction in Vmax-AoDesc with aging. Conclusions: The upper limit of the normal range for Vmax-AoDesc was 2.00 m/s in athletes without coarctation of the aorta. Young age was the most important predictor for the measurement of high Vmax-AoDesc. There was an upregulation of Vmax-AoDesc in athletes with a greater volume of endurance exercise training. Full article

Background/Objectives: Ventilator-free days (VFDs) are a useful composite measure to assess both survival and duration of mechanical ventilation in critically ill patients. This study aimed to determine the factors associated with (VFDs) in neonates with persistent pulmonary hypertension of the newborn (PPHN) and to compare VFDs according to the etiology and severity of PPHN. Methods: We conducted a retrospective cohort study of neonates diagnosed with PPHN between 2013 and 2023. VFDs were defined as days alive and free of mechanical ventilation within the first 28 days. Severe-to-critical PPHN group was defined as an oxygenation index (OI) > 25. Results: Among 175 neonates, the median (interquartile range [IQR]) VFDs were 20 (9–23) days. The factors independently associated with fewer VFDs included maximum OI > 40 (adjusted hazard ratio [aHR] 3.5, 95% confidence interval [CI]: 2.49–4.9), receiving more than two inotropic drugs (aHR 2.27, 95% CI: 1.49–3.45), acute kidney injury (AKI) (aHR 1.54, 95% CI: 1.1–2.17), and ventilator-associated pneumonia (VAP) (aHR 3.42, 95% CI: 1.8–6.48). The median (IQR) number of VFDs in neonates with PPHN secondary to respiratory distress syndrome (RDS), pneumonia/sepsis, meconium aspiration syndrome, and transient tachypnea of the newborn were 16 (0–22), 17 (7–21), 22 (11–24), and 22 (15–24) d, respectively (p = 0.023). Neonates in the severe-to-critical group had markedly fewer VFDs than those in the mild-to-moderate group (8.5 vs. 22 d, p < 0.001). Conclusions: Infants with PPHN from RDS had the fewest VFDs. A maximum OI > 40, use of multiple inotropic agents, AKI, and VAP were associated with a low number of VFDs. Given the retrospective, single-center design, these findings are associative and hypothesis-generating, requiring prospective multi-center validation. Nonetheless, VFDs remain a comprehensive measure of both mortality and respiratory morbidity in this population. Full article

Background/Objectives: Approximately 17 million individuals worldwide experience stroke annually. Stroke-induced cerebral hypoxia or infarction can impair multiple cognitive domains. This study aims to monitor the cognitive abilities of patients with acute stroke through the intervention of electroencephalogram (EEG) devices. Methods: Patients from the neurology ward were invited to participate after obtaining study approval from the research ethics committees of a medical center in northern Taiwan. Participation was explained to the eligible individuals, and only those who met the criteria and signed the informed consent form were included. The participants were those who agreed to undergo 10 sessions of the EEG training. Ultimately, 30 valid samples were collected. The effectiveness of the intervention was analyzed using the pre- and post-test results of the Mini-Mental State Examination (MMSE) and Conners’ Continuous Performance Test (CPT3). Results: After 10 EEG intervention sessions, the patients showed significant differences in the pre- and post-test results of the MMSE and CPT3 (p = 0.0001 and p = 0.007, respectively). The EEG training suggests a possible association with changes in cognitive performance following stroke. Conclusions: EEG-based interventions may be potentially associated with cognitive improvement. The effects appeared similar across patient subgroups; however, given the pilot nature of this study and the absence of a control group, the findings should be interpreted cautiously. Further well-designed controlled studies are needed to confirm these preliminary observations and evaluate their clinical applicability. Full article

Background/Objectives: Due to the inherent rotational instability of the proximal fragment in unstable basicervical intertrochanteric (IT) fractures, the biomechanical effect of lag screw position may differ from that observed in typical unstable IT fractures. This study aimed to evaluate the influence of lag screw positioning on proximal fragment displacement and stress distribution after cephalomedullary nailing (CMN) in unstable basicervical IT fractures using finite element analysis. Methods: Twelve finite element models of unstable basicervical IT fractures fixed with a CM nail were constructed with lag screws placed in four anteroposterior (AP) positions (superior 5 mm, center, inferior 5 mm, and inferior 10 mm) and three axial positions (anterior, center, and posterior). The positional change of the proximal fragment and stress concentration on the nail construct were measured. Results: In this computational model, proximal fragment displacement and stress concentration, including peak von Mises stress and mean stress over a region of interest, increased as the lag screw was positioned more inferiorly on the AP view and more posteriorly on the axial view. Conversely, a relatively superior-anterior lag screw position was associated with the lowest proximal fragment displacement and reduced stress concentration on the nail construct and around the lag screw tip. Conclusions: Within the limitations of this finite element analysis using a single femoral model and axial loading condition, a relatively superior-anterior lag screw position was associated with more favorable biomechanical behavior compared with more inferior or posterior positions. These findings should be interpreted as hypothesis-generating biomechanical observations rather than direct clinical guidance. Full article

Background: The growing complexity and cost of oncohematological treatments has created an urgent need for standardized methodologies capable of enabling inter-institutional comparisons of healthcare expenditure within homogeneous patient groups. Cancer-related pharmaceutical costs vary substantially depending on tumour type, disease stage, and therapeutic approach, making cross-institutional benchmarking challenging due to heterogeneity in patient populations and clinical practice patterns. Therefore, integrating cost analysis with clinically meaningful patient stratification is essential to improve resource allocation and outcome evaluation. Methods: A multicentre working group comprising four tertiary hospitals in Madrid (Spain) was established to develop and preliminarily evaluate a novel classification system for adult oncohematological patients. A standardized methodology was designed to stratify patients into homogeneous groups (PATONCO categories) based on tumor location, therapeutic objective, and clinically relevant biomarkers. A cost indicator was defined as the average cost per patient per month for each PATONCO category. Data were extracted from pharmacy dispensing systems and analyzed using descriptive and inferential statistics, including Kruskal–Wallis and post hoc Dunn tests. Results: A total of 3659 patients were included (3168 oncology; 491 hematology), distributed across 62 programmes (54 oncology; 8 hematology). The PATONCOS tool enabled the identification and validation of a cost indicator (average cost/patient/month per category), allowing inter-hospital comparison. Significant differences in costs were observed across most high-prevalence categories, reflecting variability in drug selection within homogeneous patient groups, as documented by the differential use of specific therapeutic agents across centers. The model demonstrated its capacity to detect intra-group homogeneity and inter-group variability, improving the identification of high-cost patient subgroups and supporting benchmarking across centers. Conclusions: The PATONCOS tool provides a novel, clinically oriented stratification methodology that integrates pharmacotherapy, biomarkers, and disease stage with economic evaluation. This approach enables more accurate comparisons of oncology treatment costs between institutions and may support data-driven decision-making in resource allocation. Its implementation may contribute to more sustainable healthcare systems by aligning clinical practice with economic outcomes. Full article

Background: Fractures of the upper cervical spine are challenging to treat due to their proximity to critical neurovascular structures and the need for immediate, stable fixation. Open posterior fixation remains the standard but is associated with soft-tissue disruption and morbidity. Minimally invasive, navigation-assisted pedicle screw fixation represents a viable alternative for older populations, significantly reducing surgical morbidity and tissue trauma. The present study evaluates the accuracy, safety, and perioperative outcomes of minimally invasive navigated posterolateral C1–C2 fixation. Methods: We conducted a retrospective consecutive case review of 51 patients who underwent minimally invasive C1–C2 screw fixation between 2019 and 2024. All procedures were performed using intraoperative O-arm imaging and StealthStation S8 navigation. Screw placement accuracy was assessed using the Bredow modification of the Gertzbein–Robbins and Heary classifications. Perioperative data, including operative time, screw dimensions, radiation dose, complications, and hospital stay, were recorded. Results: Fifty-one patients were included in the study. A total of 212 screws were placed. According to Gertzbein–Robbins grading, 92.4% were Grade A, 6.6% were Grade B, and 1% were Grade C. According to Heary grading, 95% were Grade I and 5% were Grade III. No vertebral artery injuries, new neurological deficits, or intraoperative hardware failures occurred. The mean screw lengths were 33.2 mm (SD = 3.38 mm) (C1) and 32 mm (SD = 4.30 mm) (C2). The mean operative time was 128 min (SD = 52.95 min). The mean radiation dose was 629.16 mGy·cm² (SD = 372.2 mGy·cm²). One superficial wound infection occurred. The median postoperative NRS was 4 (IQR: 4–5). The mean hospital stay was 4.21 (SD = 3.77) days. Conclusions: Our findings demonstrate that the presented approach for C1–C2 fixation is a highly accurate and safe alternative to open posterior fixation for upper cervical fractures. Full article

Background: The prognostic relevance of classical clinicopathological factors in glioma may vary across World Health Organization (WHO) grades. We examined whether anatomical location, Ki-67, and treatment-related variables show grade-dependent associations with survival. Methods: We retrospectively included 429 patients with glioma treated at a single center between 2012 and 2024. Patients were stratified into WHO grade 2–3 gliomas (n = 129) and WHO grade 4 gliomas (n = 300). Overall survival was evaluated using Kaplan–Meier analysis and Cox proportional hazards models. Additional exploratory analyses were performed in cases with known IDH status with adjustment for IDH and MGMT status. Results: Median overall survival for the full cohort was 29.93 months, and survival differed significantly across WHO grades. In grade 2–3 gliomas, higher Karnofsky Performance Status, non-deep location, and lower Ki-67 were associated with better survival; deep/midline location and Ki-67 ≥ 30% remained independently associated with worse overall survival. Within non-deep grade 2–3 tumors, temporal location was associated with worse survival. In grade 4 gliomas, female sex, non-deep location, and receipt of radiotherapy were independently associated with better survival, whereas Ki-67 was not prognostic. In exploratory molecularly adjusted analyses, deep/midline location remained associated with worse survival across grades, whereas the prognostic effect of Ki-67 became unstable. Longer chemotherapy duration showed a trend toward improved survival in grade 4 gliomas. Conclusions: Classical clinicopathological factors show substantial grade-dependent prognostic heterogeneity in glioma. Anatomical location appears to be a relatively stable adverse prognostic factor across grades, including after partial molecular adjustment. In contrast, the prognostic relevance of Ki-67 was less robust after adjustment for IDH and MGMT and should be interpreted cautiously as an exploratory, molecular-context-dependent marker. Full article

Background/Objectives: Trauma triggers complex early immune responses. However, the relationship among trauma severity, changes in immune cell survival, and circulating inflammatory mediators remains unclear. This study compared early cell viability and death patterns in CD66b⁺ granulocytes, total T lymphocytes, and CD4⁺ and CD8⁺ T-cell subsets as well as inflammatory mediator levels between patients with non-severe and severe trauma. Methods: This single-center prospective observational study included 67 adult patients with trauma who were classified into non-severe and severe trauma groups according to the Injury Severity Score (ISS < 15 vs. ISS ≥ 15). Blood samples were obtained within 1 h of arrival at the emergency department. Flow cytometry was used to assess the viability, early apoptosis, late apoptosis, and necrosis in the leukocyte subsets. Serum concentrations of intercellular adhesion molecule-1 (ICAM-1), macrophage migration inhibitory factor (MIF), CD40 ligand (CD40L), and interleukin-1 receptor antagonist (IL-1ra) were measured using enzyme-linked immunosorbent assays. Results: The severe trauma group had a significantly lower proportion of early apoptotic CD66b⁺ granulocytes than the non-severe trauma group (2.9% [1.4–6.7] vs. 6.3% [3.7–10.9], p = 0.001), whereas the live, late apoptotic, and necrotic CD66b⁺ granulocyte fractions did not differ significantly between the two groups. Most T-cell death parameters were similar between the groups, although an exploratory increase in necrotic CD4⁺ T lymphocyte abundance was observed in the severe trauma group. IL-1ra levels were significantly higher in the severe trauma group than in the non-severe trauma group and were associated with ISS in both mediator-only and adjusted sensitivity regression analyses. Conclusions: Severe trauma was associated with reduced early apoptosis in the CD66b⁺ granulocyte compartment and elevated IL-1ra levels shortly after injury compared with non-severe trauma. These findings suggest that early immune alterations after severe trauma may involve compartment-specific granulocyte death patterns and counter-regulatory inflammatory responses rather than generalized changes across leukocyte populations. Full article

Cell replacement therapy is a promising investigational approach for Parkinson’s disease (PD), a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra. Although current PD therapies provide symptomatic relief, none halt or reverse disease progression. Early transplantation studies using fetal dopaminergic neurons provided proof of concept for PD cell replacement, with recent efforts focusing on pluripotent stem cell-derived dopaminergic progenitors that are now entering clinical testing. These strategies face challenges, however, including immune compatibility, tumorigenic risk, and the need for controlled differentiation and functional integration. Multi-lineage differentiating stress-enduring (Muse) cells are endogenous, non-tumorigenic pluripotent-like stem cells that home to sites of tissue injury and differentiate in response to the host microenvironment. A targeted literature search of PubMed and Scopus, however, did not identify prior reviews specifically addressing Muse cells in the context of PD, highlighting a gap in the literature. Here, we examine current limitations of established cell-replacement approaches and consider whether Muse cells may represent a mechanistically distinct cell source. Early clinical studies of Muse cell therapy in stroke and amyotrophic lateral sclerosis suggest an encouraging safety profile and preliminary signals of potential therapeutic benefit, although these findings are based on small, early-stage trials and require confirmation. The evidence supporting Muse cell therapy in PD is currently limited to a single preclinical animal study, supported by mechanistic in vitro findings and indirect evidence from other neurologic disease models; therefore, its relevance to PD remains to be established, and current evidence is insufficient to support conclusions regarding clinical efficacy. Together, these observations provide a rationale for further targeted preclinical investigation and support the systematic evaluation of Muse cells as a mechanistically distinct candidate for regenerative therapy in PD. Full article

Background/Objectives: Carotid perivascular adipose tissue (PVAT) density on computed tomography angiography (CTA) is a noninvasive surrogate marker of local vascular inflammation, but its relevance to stroke etiology in a homogeneous cohort of patients undergoing mechanical thrombectomy (MT) remains unclear. Methods: We retrospectively analyzed 146 consecutive patients with acute ischemic stroke treated with MT for acute middle cerebral artery (MCA) occlusion between May 2018 and August 2024. Baseline CTA was used to quantify carotid PVAT density with two 2–3 mm² circular regions of interest per internal carotid artery (ICA), placed ≥1 mm from the vessel wall. Measurements were performed bilaterally, and the ICA ipsilateral to the occluded MCA was defined as the stroke-side ICA. Etiology was classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) system and grouped as large-artery atherosclerosis (LAA), cardioembolism (CE), and other/undetermined (OD/UD). Interobserver agreement was assessed using the intraclass correlation coefficient. Results: The mean age was 72.21 ± 12.39 years; 83.6% of patients achieved successful recanalization (mTICI ≥ 2b), and 47.9% had a favorable 90-day outcome (mRS ≤ 2). In the LAA subgroup (n = 38), ipsilateral PVAT density was significantly higher (less negative) than contralateral PVAT density (−64.24 ± 11.74 vs. −78.22 ± 9.13 HU; p < 0.001). Ipsilateral PVAT density differed significantly across TOAST groups (ANOVA p = 0.004), being higher in LAA than in CE (Δ = 11.19 HU; p = 0.003) and OD/UD (Δ = 9.54 HU; p = 0.004). ROC analysis showed modest discrimination for LAA versus non-LAA stroke (AUC 0.67, 95% CI 0.58–0.75), with an optimal cutoff of −79 HU (sensitivity 92.1%, specificity 40.7%). In multivariable logistic regression, higher ipsilateral PVAT density was independently associated with LAA etiology (per 1-HU increase: OR 1.048, 95% CI 1.018–1.079; p = 0.0016). PVAT density was not associated with recanalization success or 90-day functional outcome. Conclusions: In patients with acute MCA occlusion undergoing MT, higher carotid PVAT density on the stroke side was independently associated with LAA stroke etiology but had limited value for predicting MT success or short-term clinical outcome. Full article