Abstract: Objective: This study aimed to compare thromboangiitis obliterans (TAO) and diabetic peripheral vascular disease (DPVD), the two major causes of distal limb ischemia, within a single analytical framework. The comparison was not limited to practical biomarkers that could support differential diagnosis; it was based on multidimensional parameters that determine the clinical spectrum and prognosis. The two cohorts were systematically evaluated in terms of demographics and comorbidity burden, clinical presentation and limb involvement pattern, ulcer prevalence and localization, real-life treatment strategies (medical, endovascular, and surgical), and hard clinical endpoints (major/minor amputation, hospitalization, and all-cause mortality). DPVD was phenotyped according to the lesion level as isolated distal, isolated proximal, or multilevel. Within this framework, the isolated distal diabetic peripheral vascular disease (d-DPVD) subgroup was analyzed to determine how it differs from TAO in terms of clinical course, treatment patterns, and outcomes, despite the distal anatomical similarity. Methods: In this single-center retrospective cohort study, 120 non-diabetic patients who met the angiographic TAO criteria were compared with 395 patients with DPVD with infrapopliteal/pedal atherosclerotic involvement. The clinical characteristics, ulcer topography, treatment strategies, and outcomes were recorded. The discriminatory value of blood count and lipid-based inflammatory/atherogenic indices was evaluated using logistic regression and receiver operating characteristic (ROC) curve analyses. Additionally, a separate subgroup analysis was performed for the d-DPVD subgroup, which was considered the closest to the TAO phenotype in this study. Results: DPVD was characterized by older age, higher cardiometabolic comorbidity burden, and higher inflammatory and atherogenic indices than TAO. While ulcer prevalence was similar, the distribution differed: DPVD predominantly involved plantar/proximal ulcers in a single extremity, whereas TAO more frequently involved bilateral/multiple extremities and distal acral ulcers. Antiplatelet/statin use and revascularization were more common in patients with DPVD, and major amputation, all-cause mortality, and hospitalization rates were also higher. In multivariate analyses, age, cumulative smoking exposure, SIRI, and CRI-I distinguished DPVD from TAO independently. In the d-DPVD (isolated distal) subgroup, despite a similar distal anatomical distribution, the inflammatory/atherogenic burden and clinical risk were more unfavorable. Conclusion: TAO and DPVD are two distinct phenotypes with different pathobiologies and prognoses, despite similar distal ischemia presentations. Simple inflammatory and atherogenic composite indices, evaluated in conjunction with clinical/ulcer patterns, may support differential diagnosis and risk stratification in patients with PAD. However, prospective multicenter validation of these findings is required to confirm our results.

Abstract: Background/Objectives: Spread through air spaces (STAS) represents an aggressive invasion pattern in lung cancer and is associated with adverse oncologic outcomes. However, STAS is conventionally identified only after surgical resection, highlighting the need for reliable preoperative, noninvasive predictive approaches. Methods: In this retrospective study, patients who underwent surgical resection for lung cancer and had available preoperative ^18F-FDG PET/CT imaging were analyzed. Radiomic features were extracted from both intratumoral and peritumoral regions, the latter intended to reflect tumor microenvironment–related characteristics. Radiomic-only and clinicoradiomic models integrating clinical variables were developed using feature selection and multivariable modeling strategies, and their performance was evaluated using discrimination, calibration, and decision curve analyses. Results: Radiomic features derived from intratumoral metabolism and peritumoral tissue heterogeneity were associated with the presence of STAS. Integration of radiomic features with clinical parameters resulted in improved predictive performance compared with clinical models alone. The combined clinicoradiomic model demonstrated acceptable discrimination, calibration, and clinical utility across a range of threshold probabilities. Conclusions: Preoperative prediction of STAS in lung cancer is feasible using PET/CT-based radiomic analysis incorporating both intratumoral and peritumoral features. This noninvasive approach may provide biologically relevant information beyond anatomy-based assessment and supports further prospective validation of radiomic and clinicoradiomic models for STAS-oriented risk stratification.

Abstract: Background: Localized lower respiratory tract infection including unilobar and round pneumonia can be associated with hypoxia and oxygen requirements. This is unexplained. Hypothesis: Spread of fluid absorption inhibiting cytokines in the alveolar spaces of the inflamed lung is cause of hypoxia in localized lower respiratory tract infection by spread of CFTR dysfunction in alveolar epithelial cells to more areas including those not infected. Evidence supporting the hypothesis: There is no evidence of pulmonary shunting to explain hypoxia in localized pneumonia. Systemic inflammatory response syndrome (SIRS) related generalized increase in alveolar capillary barrier or pulmonary vasoconstriction not visible on a chest x-ray cannot explain the hypoxia detected. Testing the hypothesis: Confirmation of the hypothesis could be achieved using pulmonary MRI or high resolution CT to confirm spread of alveolar fluid accumulation from the localized pneumonia focus as opposed to generalized SIRS related pulmonary oedema together with cytokine and chloride measurement in bronchoalveolar lavage samples from the lung segments near the affected lung segment and unaffected contralateral lung. Ventilation/perfusion scintigraphy could investigate for involvement of vasoconstriction or microemboli from intravascular coagulation. Implications of a confirmation of the hypothesis: Should the posed hypothesis be confirmed adjuvant strategies including small molecule CFTR activators and CFTR activating combination of beta-agonists, phosphodiesterase inhibitors and steroids could be used to treat hypoxia.

Abstract: Background: Abrupt cessation of deep brain stimulation (DBS) in Parkinson’s disease (PD), most commonly due to implantable pulse generator (IPG) depletion, may lead to DBS withdrawal syndrome (DBS-WDS). However, withdrawal does not occur in all patients following stimulation cessation.Methods: We retrospectively analyzed 210 PD patients treated with DBS. Patients with documented stimulation cessation were evaluated for the presence of withdrawal syndrome based on clinical criteria. Demographic, disease-related, and treatment characteristics were assessed, with descriptive analysis of severe cases requiring intensive care.Results: DBS battery shutdown occurred in 28 patients (13.3%). Most patients did not develop withdrawal syndrome and experienced only transient motor worsening. Severe DBS-WDS requiring intensive care was rare, occurring in only three patients (1.4%). Battery shutdown alone did not predict withdrawal, and preoperative levodopa equivalent daily dose was not associated with withdrawal risk.Conclusions: DBS battery shutdown is usually not accompanied by withdrawal syndrome, and severe DBS-WDS is uncommon. Proactive battery management may help prevent this rare but serious complication.

Abstract:

Background: Intraoperative hypotension (IOH) is strongly associated with postoperative myocardial injury, acute kidney injury, and mortality. Current monitoring relies on reactive threshold alarms, often alerting clinicians only after hemodynamic compromise has occurred. We hypothesized that a machine learning (ML) approach utilizing engineered hemodynamic volatility features could predict IOH five minutes before its occurrence. Methods: A retrospective observational study was conducted using high-resolution intraoperative monitoring data from the VitalDB registry. The cohort included 1,750 adult patients undergoing non-cardiac surgery. We developed and compared three ML algorithms Logistic Regression (LR), Random Forest (RF), and Extreme Gradient Boosting (XGBoost) trained on physiological features including arterial pressure trends and rolling volatility indices. Performance was evaluated using the Area Under the Receiver Operating Characteristic Curve (AUROC) for discrimination and the Brier Score for calibration. Results: All models demonstrated robust predictive capability. The Random Forest model achieved the highest discrimination (AUROC 0.837), outperforming LR (0.824) and XGBoost (0.803). However, XGBoost demonstrated superior calibration with a Brier Score of 0.0825 (vs. 0.153 for RF), indicating more reliable probabilistic risk estimates. Feature importance analysis consistently identified hemodynamic volatility (rolling standard deviation of MAP) as the dominant predictor across all models. At the optimal threshold, the system demonstrated a sensitivity of 69.5% and specificity of 75.3%. Conclusions: We identified a trade-off between discrimination and calibration: Random Forest offers the best ranking for early warning, while XGBoost provides the most accurate risk probability. Crucially, hemodynamic instability was identified as a critical prodromal marker, suggesting that oscillatory variance precedes hypotension.

Abstract: Background/Objectives Nutritional risk is increasingly recognized as a relevant but under-assessed dimension of rheumatoid arthritis (RA), particularly in older adults managed in outpatient settings. Simple nutritional indices such as the Prognostic Nutritional Index (PNI) may help identify individuals at increased nutritional risk beyond conventional disease activity measures. This study aimed to characterize nutritional risk in older adults with RA using the Prognostic Nutritional Index, explore sex-specific patterns, and identify clinical associations of PNI variability, with complementary analyses focusing on high nutritional risk. Methods We conducted an observational cross-sectional study including 275 consecutive adults aged ≥50 years with RA attending routine follow-up at a tertiary rheumatology clinic. Nutritional risk was assessed using the PNI, calculated from serum albumin and total lymphocyte count, and analyzed primarily as a continuous variable and secondarily using established cut-off values. Clinical characteristics, inflammatory markers, body mass index, laboratory parameters, and patient-reported outcomes were recorded. Analyses were stratified by sex. Multivariable linear regression models were used to identify factors associated with PNI variability, and complementary logistic regression analyses were performed to explore factors independently associated with high nutritional risk (PNI < 40). Results More than half of the cohort (53.3%) exhibited PNI values compatible with nutritional risk. Men showed significantly lower PNI values than women, with a higher frequency of nutritional risk (61.5% vs. 49.7%, p < 0.01) and a markedly greater prevalence of high nutritional risk (18.0% vs. 5.0%, p < 0.001). Sex-specific association patterns were observed. In women, PNI showed only a weak inverse association with age. In contrast, in men, lower PNI values were associated with higher inflammatory burden, greater disease activity, lower body mass index, poorer mental health–related quality of life, and lower hemoglobin levels. In multivariable linear regression models restricted to men, hemoglobin emerged as the principal independent correlate of PNI. In complementary logistic regression analyses focusing on high nutritional risk (PNI < 40), hemoglobin remained the sole independent predictor (OR = 0.94, 95% CI 0.91–0.98; p < 0.01), supporting a robust association with clinically relevant nutritional risk. Conclusions Nutritional risk assessed by the PNI is common among older adults with RA and displays pronounced sex-specific patterns, with men showing a substantially higher burden of nutritional risk. The PNI captures a clinically relevant dimension of disease burden that extends beyond joint inflammation and traditional activity indices, supporting its use as a pragmatic nutritional screening tool in routine rheumatology practice.

Abstract: Huntington’s disease (HD) is characterized by progressive striatal atrophy and complex proteomic changes in the central nervous system. Using the ultrasensitive NULISA proteomic platform, we analyzed cerebrospinal fluid (CSF) from 88 persons with HD to dissect the biological correlates of gray matter loss. We identified a two-signal pattern of pathology. The first track, marked by the axonal damage protein Neurofilament Light (NEFL), showed a strong negative correlation with putamen volume (Pearson r = -0.53, p < 0.001), consistent with prior work supporting NEFL as a proxy for neurodegeneration and brain atrophy in HD. The second track was defined by a positive association between the immune regulator TNFRSF8 (CD30) and putamen volume (Pearson r = 0.36, p < 0.001), indicating a loss of putative immune-regulatory signal as atrophy progresses. TNFRSF8 was pre-specified for follow-up given its immune-regulatory role and interpretability in the context of immune dysregulation consistent with an immune-exhaustion-like profile. TNFRSF8 showed an independent association with striatal volume (Beta = 0.24, p = 0.008) after controlling for NEFL, CAG-Age-Product (CAP) score, and sex. These findings suggest that reduced immune-regulatory signaling is a distinct pathological correlate in HD, separable from general cytoskeletal damage, and warrants evaluation in longitudinal and interventional studies.

Abstract: Background/Objectives: Dilated (DCM) and hypertrophic cardiomyopathy (HCM) are common cardiomyopathies associated with heart failure. Electrocardiogram (ECG) screening before an echocardiogram could help streamline diagnosis, particularly in rural areas. Prior ECG machine-learning (ML) studies do not use open-source data when studying cardiomyopathy, and very few proprietary studies directly compare HCM and DCM or address ECG differences within obstructive (HOCM) and non-obstructive HCM (HNCM). Methods: Standard and vectorcardiogram-derived (VCG) ECG features were extracted from the MIMIC-IV-ECG database. The final cohort comprised 599 patients (HCM = 208 [HOCM = 99, HNCM = 53, unknown = 56], DCM = 391 [ischemic cardio-myopathy with left ventricular dilation = 250, non-ischemic = 141]). Logistic regression (LR) and extreme gradient boosting (XGBoost) with five-fold cross-validation separated HCM from ischemic cardiomyopathy with left ventricular dilation (DCM-I) and non-ischemic DCM (DCM-NI), and HOCM from HNCM. Results: Using the area under the receiver operating characteristic curve (AUC-ROC) as the performance metric, LR achieved high discrimination of HCM from DCM-I (0.92) and DCM-NI (0.90). However, differentiating HOCM from HNCM proved more difficult (XGBoost = 0.81; LR = 0.75). Both DCM subtypes (especially ischemic) showed lower QRS amplitudes and right-posterior ventricular gradient orientation; HCM displayed higher amplitudes and larger, more complex T-loops. Within HCM, HOCM had stronger leftward electrical activity and more dipolar to non-dipolar QRS energy after singular value decomposition. Conclusions: Using only open-access data, we demonstrate an interpretable ECG-based pipeline that discriminates cardiomyopathy and highlights distinct features. While detecting ob-struction remains difficult, ECG features provide measurable separation, supporting possible diagnostic screening and offering a reproducible framework for future studies.

Abstract: Background: Skin repair and wound healing are tightly regulated biological processes that require coordinated control of inflammation, redox balance, angiogenesis, and tissue remodeling. Natural extracts are increasingly investigated not as nonspecific bioactive mixtures, but as sources of chemically diverse phytochemicals capable of modulating defined molecular signaling pathways involved in skin repair. Methods: Representative botanical sources, including Aloe Vera, Centella asiatica, Curcuma longa, Calendula officinalis, and Panax ginseng, have been extensively studied in pre-clinical wound models, providing insight into how distinct phytochemical classes intersect with shared regulatory mechanisms. Results: Flavonoids, terpenoids, phenolic acids, alkaloids, and polysaccharides have been shown to influence inflammatory signaling, redox-sensitive pathways, growth factor-mediated responses, and cellular migration, thereby supporting phase-appropriate progression of wound healing. At the molecular level, modulation of pathways such as NF-κB, TGF-β, VEGF, and Nrf2 emerges as a recurring mechanistic theme, while excessive or poorly timed pathway activation is increasingly recognized as a source of impaired tissue quality or fibrotic risk. Advances in dermopharmaceutical formulation strategies, including hydrogels, nanoemulsions, and lipid-based carriers, have improved local delivery and stability of phytochemicals, but also introduced additional translational and regulatory constraints. Conclusions: This review provides a mechanism-driven and pharmaceutical-oriented synthesis of current evidence, highlighting how molecular specificity, temporal regulation, and formulation design collectively determine the therapeutic relevance of plant-derived extracts in skin wound healing.

Abstract: Reflexology is a complementary therapy based on the manual stimulation of reflex zones primarily located on the feet and hands. Its main therapeutic objective is to induce physiological responses aimed at functional regulation and the individual’s overall well-being. Contemporary practice is grounded in neurophysiological mechanisms of reflex action, linked to somatovisceral integration and modulation of the nervous system. From a historical perspective, the therapeutic stimulation of the hands and feet can be observed in various ancient medical systems, particularly in traditional Eastern practices such as Traditional Chinese Medicine and Ayurveda, where these techniques are used within energetic and empirical models of bodily balance. However, these antecedents do not constitute reflexology in the strict sense, as they lack a formulation based on anatomofunctional correspondences mediated by the nervous system. This article presents a critical narrative review of the historical and conceptual evolution of reflexology, analyzing its transition from traditional Eastern practices to its consolidation as a complementary therapy within modern Western medicine. The contributions of nineteenth- and early twentieth-century physiology are examined, together with the clinical input of specialists of that period, which enabled the structuring of a reproducible and clinically grounded discipline. Finally, contemporary neurophysiological evidence is integrated to support its therapeutic principles and its responsible inclusion within an integrative health care approach.

Abstract: Pancreatic cancer represents a major health issue with poor prognosis. There are several risk factors related to this important disease and their control may influence its burden. The radical treatment for pancreatic cancer remains the surgery and the use of minimally invasive approach is nowadays considered optimal. The aim of the study was to analyze the pancreatic cancer characteristics and the safety and feasibility of the minimally invasive approach in treating this type of cancer. We conducted a literature review in Pub-Med database using mesh-terms for pancreatic cancer and minimally invasive surgery focusing on the short-term outcomes of and long-term outcomes of MIS. We also reviewed the most relevant literature studying the epidemiology of the pancreatic cancer, risk factors, histopathology, resectability and surgical options, the use of preoperative biliary drainage, neoadjuvant and adjuvant treatment. The most revelant risk factors associated with pancreatic cancer are represented by age, sex, area of living, blood group, genetic factors and the presence of diabetes, human microflora, alcohol consumption, smoking, chronic pancreatitis, obesity. Minimally in-vasive approach for pancreatic cancer is associated with improved intraoperative and short-term postoperative outcomes such as: reduced intraoperative blood loss, faster functional recovery, lower postoperative pain, shorter hospital stay, but similar postop-erative morbidity and pancreatic fistula risk to the open approach. Regarding oncological results, minimally invasive approach provides optimal number of harvested lymph-nodes and R0 resection rates. Minimally invasive surgery for pancreatic cancer should be performed in high-volume, specialized centers with dedicated and experimented surgeons and for selected patients.

Abstract: Introduction: Orthobiologics such as Platelet-Rich Plasma (PRP) and Injectable Platelet-Rich Fibrin (i-PRF) have emerged as promising tools in regenerative medicine. However, the lack of methodological standardization and the still limited comparative characterization between these products represent significant barriers to their optimized clinical application. This comparative laboratory study aimed to characterize and differentiate PRP and i-PRF, focusing on their cellular composition, obtained volume, and concentration of Platelet-Derived Growth Factor (PDGF-BB). Materials and Methods: This study was conducted with 34 healthy individuals. Peripheral blood samples were collected from all participants. PRP was obtained using a modified double-spin centrifugation protocol, whereas i-PRF was prepared using a modified low-speed centrifugation technique. Cellularity (platelet and leukocyte counts), final produced volume, and PDGF-BB concentration were assessed using complete blood count analysis and enzyme-linked immunosorbent assay (ELISA), respectively. Statistical analysis was performed using Generalized Linear Models (GLM). Results: Both protocols resulted in significant increases in platelet and leukocyte concentrations compared to baselines values. PRP showed significantly higher platelet and leukocyte concentrations compared with i-PRF, as well as markedly higher PDGF-BB levels. In contrast, i-PRF yielded a substantially greater final volume and enabled a higher absolute delivery of total leukocytes, whereas PRP delivered a greater absolute number of platelets. Female Sex, presence of comorbidities, and increased abdominal circumference positively influenced product volume and cellular composition. Discussion: Although both PRP and i-PRF effectively concentrate blood-derived components, they present distinct biological profiles regarding cellularity, volume, and growth factor availability. These findings indicate that PRP and i-PRF are not interchangeable, and their clinical use should be guided by the target tissue, therapeutic mechanism, and evidence from randomized clinical trials.

Abstract: Systemic light-chain (AL) amyloidosis is a rare and incurable disease, classified under the category of plasma cell neoplasms and other diseases with paraproteins in the fifth edition of the World Health Organization classification of lymphoid tumors. This entity shares some similarities with multiple myeloma (MM), remarkably a bone marrow infiltration of clonal plasma cells. Moreover, one out of five newly diagnosed AL amyloidosis (NDAL) also fulfills the current diagnostic criteria for MM. A multidisciplinary therapy approach should be established, in which hematological therapy plays a crucial role. Anti-clonal therapy is the basis of hematological therapy, besides supportive therapy and emerging anti-fibrils therapy. In recent years, advances in the anti-clonal therapy of MM have progressively transferred to carefully selected patients with systemic AL amyloidosis, significantly improving outcomes in this rapidly changing field. This review aims to critically analyze the comparative evolution and evidence-based approach of anti-clonal therapy in NDAL vs. MM since the introduction of bortezomib. Participation in clinical trials remains the first option to consider in daily clinical practice.

Abstract: Objective: This systematic review aimed to evaluate the efficacy and safety of preoperative nutrition-based interventions on pre-, intra-, and postoperative outcomes in children undergoing cardiac surgical procedures. Methods: CENTRAL, MEDLINE, and EMBASE were systematically searched for interventional and observational studies comparing any nutritional preoperative intervention with a control or alternative strategy in pediatric patients undergoing cardiac surgery, up to July 2025. The main outcome was postoperative length of stay in the intensive care unit (ICU). The certainty of evidence was assessed using the GRADE approach. Results: Nineteen studies were included (8 randomized controlled trials [RCTs], 1 non-randomized trial, and 10 observational studies), evaluating heterogeneous interventions or exposures, including fatty acids, vitamin D supplementation, and structured preoperative nutritional protocols. Two RCTs demonstrated shorter ICU and hospital stays with extended preoperative nutritional support (2 weeks vs 1 week; n = 40; and 1 month vs no support; n = 80). Observational data indicated an association between preoperative nutritional support and reduced hospital length of stay (meta-analysis of 4 studies; n = 278) as well as fewer days to achieve full enteral feeding postoperatively (meta-analysis of 3 studies; n = 138). No significant difference in postoperative ICU stay was observed between groups (meta-analysis of 2 studies; n = 175). No intervention-related serious adverse events were reported. The overall certainty of evidence was very low. Conclusions: This systematic review provides very low–certainty evidence suggesting that preoperative nutrition-based interventions in children undergoing cardiac surgery are safe and may offer clinical benefits. Substantial heterogeneity across studies underscores the need for well-designed trials and standardized preoperative nutritional protocols.

Abstract: Sodium-glucose cotransporter 2 (SGLT2) inhibitors, widely used in the treatment of type 2 diabetes, have recently emerged as potential anticancer agents due to their effects on tumor metabolism and growth signaling pathways. This article presents a viewpoint on the growing body of preclinical evidence linking SGLT2 inhibition to antitumor activity, including reduced glucose uptake, AMPK activation, mTOR suppression, and cell cycle arrest. Agents such as canagliflozin, dapagliflozin, and empagliflozin have demonstrated efficacy across various cancer models, though clinical validation remains limited. We propose that SGLT2 inhibitors may offer a promising therapeutic strategy in metabolically active tumors, especially when guided by molecular profiling. While further research is needed, these findings support reconsidering the oncologic relevance of this drug class within a personalized medicine framework.

Abstract: Background The optimal treatment for unresectable intrahepatic cholangiocarcinoma (iCCA) remains uncertain. Hepatic arterial infusion chemotherapy (HAIC) aims to increase local drug concentration and tumor response. Methods Following PRISMA 2020 guidelines and PROSPERO registration (CRD420251128740), we searched major databases up to March 2025. Included: observational comparative studies of HAIC (alone or with immunotherapy) vs. systemic therapy in unresectable iCCA. Outcomes: OS, PFS, ORR/DCR, grade 3–4 AEs. Pooled estimates used random-effects REML with Hartung–Knapp adjustment. Results Thirteen observational studies (~1,200 patients; no RCTs) were included. HAIC significantly improved tumor response (ORR/DCR RR 2.74 and 1.25, 95% CIs 1.91–3.92 and 1.04–1.50) with non-significant trends favoring HAIC for survival (OS HR 0.66, 95% CI 0.28–1.54; PFS HR 0.59, 95% CI 0.30–1.15). Severe toxicity was comparable (RR 0.79, 95% CI 0.10–6.20; exploratory, k=2). Heterogeneity low (I² ≤1%). Conclusions This observational meta-analysis suggests HAIC is associated with superior tumor response and non-significant survival trends without excess severe toxicity versus systemic therapy in unresectable iCCA. These hypothesis-generating findings require confirmation by randomized trials.

Abstract: Older patients with unresectable locally advanced non-small cell lung cancer (NSCLC) frequently receive concurrent chemoradiotherapy (CCRT) with daily low-dose carboplatin; however, real-world data on its efficacy, safety, and prognostic factors remain limited. We aimed to retrospectively evaluate the clinical outcomes of this regimen and examined whether systemic inflammation-based indices predict prognosis in this setting. We reviewed 52 consecutive patients with locally advanced NSCLC treated with first-line CCRT using daily low-dose carboplatin at three Japanese institutions between April 2007 and December 2019. The median progression-free survival (PFS) and overall survival (OS) were 11.5 and 40.1 months, respectively. Twenty patients received durvalumab as maintenance therapy. In the overall cohort, multivariate analysis identified the Glasgow Prognostic Score (GPS) as an independent predictor of PFS. A GPS of 0–1 was also associated with a significantly longer OS in univariate analysis. CCRT with daily low-dose carboplatin provided durable disease control with acceptable toxicity in older patients with unresectable stage II/III NSCLC. The GPS appears to be a simple marker for PFS in this population and may aid in pretreatment risk stratification alongside histology and consolidation strategies.

Abstract: Background: Atrial fibrillation (AF) is a prevalent arrhythmia closely associated with cardiometabolic disorders and systemic inflammation. Epicardial adipose tissue (EAT), located in direct contact with the atrial myocardium, has emerged as a biologically active tissue involved in atrial remodeling through inflammatory, fibrotic, and electrophysiological mechanisms. The objective of this review is to summarize current translational and clinical evidence on the role of EAT in AF pathophysiology and to discuss its implications for diagnostic assessment, interventional management, and cardiometabolic therapeutic strategies. Methods: A narrative review of experimental, translational, and clinical studies was conducted using major biomedical databases. The literature was evaluated with a focus on mechanisms linking EAT to atrial remodeling, noninvasive imaging techniques for EAT characterization, echocardiographic and electroanatomical markers of atrial disease, outcomes of catheter ablation strategies, and pharmacological interventions targeting metabolic and inflammatory pathways. Results:The available evidence indicates that increased EAT volume and altered inflammatory activity are associated with atrial fibrosis, conduction abnormalities, and impaired atrial function, contributing to AF initiation and persistence. Multimodality imaging, including cardiac computed tomography and cardiac magnetic resonance, enables quantitative and qualitative assessment of EAT and supports clinical phenotyping. Clinical studies report an association between higher EAT burden and increased AF recurrence after pulmonary vein isolation, particularly in patients with persistent AF. Emerging cardiometabolic therapies, such as glucagon-like peptide-1 receptor agonists and dual GIP/GLP-1 agonists, have been shown to reduce EAT volume and inflammatory markers, although direct evidence linking these interventions to improved AF outcomes remains limited. Conclusions: EAT represents a relevant pathophysiological interface between metabolic disease and AF with potential clinical implications. Incorporating EAT assessment into routine evaluation may enhance risk stratification and support personalized AF management. Further prospective studies are required to define its role as a therapeutic target in clinical practice.

Abstract:

Introduction: Recent guidelines have emphasized the importance of early mobilization and rehabilitation of patients following cardiac surgery. However, studies on the optimal targets and prescription methods for phase I cardiac rehabilitation (CR) are lacking.Purpose: This study aimed to evaluate the feasibility and utility of an early phase 1 submaximal cardiopulmonary exercise test (CPET) using a recumbent ergometer in patients who have undergone cardiac surgery. Methods: Twenty ambulatory patients who underwent cardiac surgery between December 2021 and February 2023 were referred to the CR department on the fifth postoperative day, and a CR program was initiated. The program was conducted five times a week, with hour-long sessions consisting of warm-up exercises, resistance training, aerobic exercises, and a cool-down period. A recumbent ergometer-based submaximal CPET was performed approximately nine days after the surgery, prior to discharge. Participants initiated the test at 0 W, and the workload was increased by 20 W after 2 minutes. During the test, researchers evaluated parameters including estimated peak values of oxygen consumption (VO2), metabolic equivalents of task, respiratory exchange ratio (RER), blood pressure, heart rate (HR), and rating of perceived exertion (RPE). The grip strength test, 6-minute walk test (6MWT), Korean Activity Scale/Index (KASI), EuroQol-5 dimension (EQ-5D), and short-form 36-item health survey (SF-36) values were also measured prior to discharge. Results: Twenty patients (75% male, average age 62.50 ± 1.99 years) underwent CPET at a median of 9.0 (8.0; 12.5) days postoperative. The average exercise duration of the CPET was 411.75 ± 168.25 seconds. During the test, their estimated peak VO2 was 12.32 ± 0.75 ml/kg/min (corresponding to 46.65 ± 2.08% of VO2 max). The estimated peak RER was 1.01 (0.98–1.12), and the estimated peak RPE was 15.00 ± 0.51. Furthermore, the estimated peak HR was 111.8 ± 3.76 beats/min (equivalent to 70.95 ± 2.09% of age-predicted maximal HR). After adjustment for age and sex, significant positive correlations were observed between the estimated peak VO2 and 6MWT, squat endurance test, KASI, EQ-5D, and the physical component summary (PCS) of the SF-36 questionnaire. The 6MWT, squat endurance test, KASI, and PCS of SF-36 showed a correlation coefficient (r) of 0.522 (p=0.026), 0.628 (p=0.005), 0.586 (p=0.011), and 0.546 (p=0.019), respectively. No significant cardiac events, such as ST elevation/depression or hemodynamic instability, were observed during the test.Conclusion: Our findings suggest that performing recumbent ergometer-based CPET during early phase 1 CR is safe and feasible. These results highlight the potential of recumbent ergometer-based CPET as a valuable tool for guiding the appropriate prescription of early CR programs following hospital discharge in patients undergoing cardiac surgery.

Abstract: Justicia spicigera is a central medicinal plant in Mexican ethnomedicine, yet its therapeutic potential against prostate cancer remains largely unexplored. This study investigated the antiproliferative and pro-apoptotic effects of a 50% hydroalcoholic extract from the leaves and stems of J. spicigera on androgen-sensitive LNCaP prostate cancer cells. Phytochemical profiling via TLC and LC-MS putatively identified the bioactive flavonoid kaempferitrin within the complex extract. Biological assays, including MTT, trypan blue exclusion, and flow cytometry, revealed that the extract inhibits LNCaP proliferation in a distinct, dose-dependent manner. At a lower concentration (250 µg/mL), the extract exerted a primarily cytostatic effect by inducing significant G₀/G₁ cell cycle arrest without triggering immediate cell death. Conversely, higher concentrations (≥500 µg/mL) were potently cytotoxic, reducing cell viability to below 20% and inducing late apoptosis in approximately 58% of the population within 24 hours. These results validate the biological activity of J. spicigera in a prostate cancer model and suggest that the extract, or its constituent flavonoids could serve as a template for developing treatments that target both cell cycle checkpoints and programmed cell death.