Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become the most common chronic liver disease in childhood, paralleling the global increase in pediatric obesity and metabolic dysfunction. Once considered a benign condition, pediatric MASLD is now recognized as a heterogeneous and potentially progressive disease that may advance from simple steatosis to steatohepatitis, fibrosis, and, rarely, cirrhosis, with lifelong hepatic and cardiometabolic consequences. Its pathogenesis is multifactorial, involving insulin resistance, adipose tissue dysfunction, chronic low-grade inflammation, genetic and epigenetic susceptibility, environmental factors, and alterations in the gut microbiome. Most affected children are asymptomatic, and diagnosis is often prompted by elevated liver enzymes or incidental imaging findings. Noninvasive tools, including ultrasonography, elastography, serum biomarkers, and emerging multi-omics approaches, are improving disease detection and risk stratification, although liver biopsy remains the reference standard in selected cases. Lifestyle modification, including dietary optimization, increased physical activity, and gradual weight reduction, remains the cornerstone of management, while pharmacological therapies are still under investigation in pediatric populations. The marked variability in disease susceptibility; progression; and treatment response underscores the need for a personalized medicine approach. Integrating clinical characteristics with genomic, epigenomic, metabolomic, and microbiome data may enable early identification of high-risk children, more accurate prognostic assessment, and individualized preventive and therapeutic strategies. Early detection and multidisciplinary care involving pediatricians, hepatologists, endocrinologists, dietitians, and families may help reduce disease progression and the risk of long-term hepatic and cardiometabolic complications. This review summarizes current evidence on the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of pediatric MASLD, with a particular emphasis on precision diagnostics, biomarker discovery, and personalized therapeutic approaches. It also discusses current challenges and future directions for implementing personalized medicine to improve outcomes and reduce the lifelong burden of pediatric MASLD.
Background: Flexor tendon rupture is a rare but potentially disabling complication following minimally invasive treatment of Dupuytren’s disease. This meta-analysis compared rupture incidence after collagenase Clostridium histolyticum (CCH) injection and percutaneous needle fasciotomy/aponeurotomy (PNF/PNA). Methods: PubMed, MEDLINE, and Embase were systematically searched for randomised trials, cohort studies, clinical trials, and case series reporting complications after CCH or PNF for Dupuytren’s disease. Case reports and secondary evidence were excluded from incidence calculations, although reference lists of reviews were screened for eligible primary studies. Flexor tendon rupture events and study denominators were extracted as reported. Pooled incidence was estimated using random-effects proportional meta-analysis with logit transformation and continuity correction. Separate pooled estimates were generated for CCH and PNF, followed by subgroup comparison. Results: Forty-one studies were included. Across eligible studies, 68 flexor tendon ruptures were identified, including 62 after CCH and 6 after PNF. Ruptures most commonly involved the flexor digitorum profundus, affected the small finger, and occurred early, with a median time to rupture of 8 days, where reported. Fourteen PNF cohorts comprising 6058 treated units reported 6 ruptures, producing a pooled incidence of 0.32% (95% CI: 0.18–0.55%) with no observed heterogeneity. Twenty-nine CCH cohorts comprising 60,949 treated units reported 62 ruptures, producing a pooled incidence of 0.83% (95% CI: 0.42–1.64%) with substantial heterogeneity. Subgroup comparison demonstrated a higher pooled rupture incidence following CCH than PNF. Conclusions: Flexor tendon rupture is uncommon after both CCH and PNF. Characterisation of anatomical and treatment-related patterns of rupture may support more individualised risk counselling and treatment selection in Dupuytren’s disease. Future studies are required to develop clinically meaningful risk-stratification strategies.
Prompt diagnosis and treatment of sepsis and septic shock is crucial due to the persistently high rates of morbidity and mortality associated with the disease. Recently, research efforts have focused on identifying novel biomarkers that would detect, classify, and assess the severity of sepsis in a timely manner, thereby allowing for expeditious and precise treatment of sepsis and septic shock. Among these biomarkers, proenkephalin (PENK) has gained considerable attention. Accordingly, this narrative review aims to consolidate current evidence on the clinical utility of PENK in patients with sepsis and septic shock, with emphasis on its role as a biomarker of renal dysfunction and as a predictor of sepsis-associated acute kidney injury (AKI) and mortality in both the emergency department (ED) and intensive care unit (ICU) settings.
Tracheal intubation in patients at risk of acute hypoxemic respiratory failure (AHRF) carries a high risk of life-threatening desaturation, and the choice of peri-intubation oxygenation strategy critically influences patient safety. This narrative review synthesizes current evidence on non-invasive oxygenation techniques—high-flow nasal oxygen (HFNO), non-invasive ventilation (NIV), and their combination—across the pre-oxygenation, apneic, and awake-intubation phases of airway management. We examine the physiological mechanisms underlying each modality, appraise landmark randomized trials and meta-analyses (including PREOXI, OPTINIV, and OPTIMASK), and address disease-specific considerations in chronic obstructive pulmonary disease, heart failure, interstitial lung disease, severe obesity, obstructive sleep apnea, and obstetric, pediatric, and trauma populations. The evidence supports a phenotype-driven hierarchy rather than a single dominant technique: NIV—optionally combined with HFNO for apneic oxygenation—is preferred in severely hypoxemic critically ill patients, whereas HFNO alone is adequate for many moderately hypoxemic or non-hypoxemic patients. Progressive hypercapnia limits apneic oxygenation, particularly in chronic CO₂ retainers, underscoring the value of continuous CO₂ monitoring. Persistent under-implementation of NIV-based pre-oxygenation reveals a gap between evidence and practice. Individualized, physiology-guided oxygenation—aligned with the goals of personalized peri-procedural medicine—offers the greatest potential to reduce peri-intubation morbidity.
Background: Temporomandibular disorders (TMD) comprise a heterogeneous group of musculoskeletal conditions that may manifest during childhood and adolescence. However, standardized information regarding TMD-related clinical findings in pediatric populations remains limited because of methodological heterogeneity and the inconsistent application of validated diagnostic protocols. Objective: The aim of this study was to characterize clinical findings related to temporomandibular disorders in schoolchildren and to explore their potential contribution to individualized assessment strategies within the framework of personalized pediatric oral healthcare. Methods: A multicenter cross-sectional study was conducted in 1052 schoolchildren recruited from participating educational institutions. All participants underwent a standardized clinical examination that included assessment of masticatory muscle tenderness, temporomandibular joint tenderness, joint sounds, pain intensity, and perceived stress using an adapted pediatric DC/TMD protocol. Categorical variables were summarized as frequencies, percentages, and 95% confidence intervals (95% CIs). Associations between categorical variables were evaluated using Pearson's chi-square test, and multivariable logistic regression was performed to identify factors independently associated with pain. Results: Pain during clinical examination was identified in 111 participants (10.6%; 95% CI: 8.8-12.6%), whereas temporomandibular joint sounds and myofascial pain were detected in 1.4% and 0.3% of participants, respectively. Most pain was classified as mild, and the masseter muscle was the most frequently affected anatomical site. Increasing age and female sex were independently associated with pain. Compared with children aged 4-6 years, participants aged 10-12 years (adjusted OR = 9.61; 95% CI: 2.22-41.51) and 13-16 years (adjusted OR = 35.49; 95% CI: 8.59-146.61) showed significantly greater odds of pain. Female participants also demonstrated higher odds of pain than males (adjusted OR = 7.49; 95% CI: 3.68-15.21; all p < 0.05). Conclusions: Clinically detectable TMD-related findings were generally uncommon among schoolchildren aged 4-16 years and were predominantly mild and muscular. Increasing age and female sex were independently associated with pain, emphasizing the importance of demographic factors in the early clinical expression of TMD. Standardized pediatric clinical examination protocols may facilitate early identification of TMD-related findings and support preventive strategies during childhood and adolescence. These findings support the implementation of individualized clinical assessment strategies for early identification of children at risk of temporomandibular disorders, contributing to personalized preventive and therapeutic approaches in pediatric oral healthcare.
Background: Imeglimin is a novel oral antidiabetic agent that improves mitochondrial function and glucose metabolism in patients with type 2 diabetes mellitus (T2DM). Its effects on liver enzymes remain unclear. We investigated the effects of imeglimin on hepatic biomarkers, particularly γ-glutamyl transpeptidase (γ-GTP), and the reversibility of these changes after treatment discontinuation. Methods: This post hoc analysis of the prospective INFINITY Study included 25 patients with T2DM who completed 6 months of imeglimin treatment followed by a 3-month withdrawal period. Clinical parameters were averaged within predefined 3-month study phases. Changes during treatment and after discontinuation were analyzed. Results: Imeglimin significantly improved glycemic control. The geometric mean γ-GTP decreased from 36.2 (27.1-48.4) U/L during the Baseline Phase to 31.1 (23.5-41.1) U/L during the Late Treatment Phase (p < 0.05). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) also showed downward trends, although these changes were not statistically significant. During the Withdrawal Phase, γ-GTP returned to 35.6 (26.4-48.5) U/L (p < 0.05 vs. Late Treatment Phase). Patients with baseline γ-GTP >50 U/L showed larger but non-significant changes. Changes during treatment and after discontinuation were inversely correlated (r = -0.480, p = 0.015). Only total cholesterol correlated with γ-GTP during both treatment (r = 0.554, p = 0.005) and withdrawal (r = 0.450, p = 0.024). Conclusions: γ-GTP levels showed a significant decrease during imeglimin treatment and increased during the post-treatment observation period in patients with T2DM. Exploratory analyses identified an association between changes in γ-GTP and total cholesterol; however, these findings should be interpreted cautiously and require confirmation in prospective studies with prespecified endpoints.
Introduction: Gastrojejunal anastomosis (GJA) stricture is an important complication after laparoscopic Roux-en-Y gastric bypass (LRYGB). The impact of suture material on stricture rate when performing a hand-sewn GJA is not well established. Methods: This is a retrospective analysis of a prospectively maintained database that includes 882 patients who underwent primary or revisional LRYGB with a minimum 12-month follow-up. We compared two consecutive groups of patients who underwent hand-sewn gastrojejunal anastomosis: group 1 (n = 426), utilizing a multifilament non-absorbable/absorbable suture combination (silk/Vicryl®), whereas group 2 (n = 456) received an absorbable monofilament suture (Monocryl®). The primary outcome was the incidence of symptomatic GJA stricture, defined as an inability to pass a 10 mm gastroscope associated with dysphagia, vomiting, or food intolerance. Results: The symptomatic stricture rate was significantly lower in group 2 (0.7% vs. 6.8%; p < 0.001). On multivariate analysis, the use of monofilament sutures was a stronger protective factor (OR 0.09; 95% CI 0.03-0.30; p < 0.001), whereas revisional surgery was associated with an increased risk of symptomatic stricture (OR 2.61; 95% CI 1.05-6.50; p = 0.03). Type 2 diabetes mellitus and gender were not independent predictors. One-year weight loss was similar between patients who developed symptomatic strictures (and required dilations) and those who did not (p > 0.05). Conclusion: The use of absorbable monofilament sutures for hand-sewn GJA in LRYGB reduces the risk of symptomatic stricture without compromising weight loss outcomes. These findings support a personalized suture strategy, especially in high-risk patients undergoing revisional surgery.
Background/Objectives: Prolonged postoperative air leak (PAL) remains one of the most common complications after lung resection, significantly affecting postoperative recovery and healthcare utilization. While several preoperative risk factors have been identified, reliable intraoperative predictors are still lacking. This study aimed to evaluate whether intraoperative ventilator-derived parameters—volume decay (Vol-Decay) and pressure decay (Pres-Decay)—are associated with the development of PAL following uniportal video-assisted thoracic surgery (VATS) lung resection. Methods: We conducted a single-center study including 277 consecutive patients undergoing uniportal VATS lung resection for neoplastic disease between May 2023 and April 2024. At the end of the surgical procedure, intraoperative Vol-Decay and Pres-Decay were measured using the mechanical ventilator under standardized conditions. PAL was defined as an air leak persisting for more than 5 days within 30 days after surgery. Univariate and multivariate analyses were performed to identify independent predictors of PAL, and the optimal Vol-Decay cut-off was determined using Youden’s index. Results: PAL occurred in 18 patients (6.5%). At univariate analysis, higher smoking exposure, lower FEV1, lower FEV1/FVC ratio, and higher Vol-Decay were significantly associated with PAL. At multivariable analysis, only FEV1 (p = 0.013) and Vol-Decay (p = 0.038) remained independent predictors. The optimal Vol-Decay cut-off was 22 mL (AUC 0.64), with high specificity (0.94) but low sensitivity (0.34). Patients with Vol-Decay > 22 mL showed a significantly higher incidence of PAL compared to those with lower values (27.3% vs. 4.7%). Conclusions: Intraoperative Vol-Decay represents a simple, objective, and reproducible parameter associated with the development of prolonged air leak after uniportal VATS lung resection. Its measurement may enable real-time risk stratification and support personalized intraoperative decision-making, potentially guiding targeted corrective strategies. Further prospective multicenter studies are warranted to validate these findings and confirm their clinical applicability.
Circadian rhythms regulate key biological processes central to cancer biology, including cell cycle control, DNA repair, metabolism, immune function, and drug pharmacokinetics. Experimental models consistently demonstrate marked time-of-day differences in the efficacy and toxicity of chemotherapy, targeted agents, and immunotherapies. Clinical studies of chronomodulated chemotherapy—particularly with fluoropyrimidines, platinum compounds, and anthracyclines—show reproducible reductions in treatment-related toxicity, while effects on survival outcomes remain variable and often sex dependent. Emerging clinical evidence also suggests that timing of immune checkpoint inhibitor administration may influence progression-free and overall survival across several tumor types. However, translation into routine oncology practice has been limited by interindividual variability in circadian phase, tumor-specific disruption of clock function, lack of validated biomarkers, and logistical constraints of time-specific drug delivery. Advances in circadian phenotyping, wearable monitoring, and adaptive dosing technologies now offer feasible pathways toward individualized, biology-driven treatment timing. This narrative review critically evaluates mechanistic, preclinical, and clinical evidence for chronotherapy across oncological treatment modalities and examines challenges and opportunities for its integration into precision cancer care.
Background: Familial hypercholesterolemia (FH) is associated with accelerated atherosclerosis and an increased risk of cardiovascular disease. Aims: To evaluate circulating biomarkers of inflammation and atherosclerosis in patients with clinically suspected FH stratified according to the Dutch Lipid Clinic Network (DLCN) criteria. Methods: This cross-sectional study included 80 patients (mean age, 53.4 [13.2] years; 58% women) receiving maximally tolerated lipid-lowering therapy (statins ± ezetimibe). Serum concentrations of lipoprotein-associated phospholipase A2 (Lp-PLA2), tumor necrosis factor-α (TNF-α), apolipoprotein B (ApoB), oxidized low-density lipoprotein (oxLDL), and monocyte chemoattractant protein-1 (MCP-1) were measured. Participants were classified as definite FH (DLCN score > 8; n = 45) or non-definite FH (DLCN score ≤ 8; n = 35). Biomarker concentrations were analyzed according to the above subgroups and sex. Results: Patients with definite FH had significantly higher serum Lp-PLA2 concentrations (62.2 [33.8] vs. 46.5 [19.9] ng/mL; p = 0.03) and TNF-α concentrations (6.94 [4.53] vs. 4.51 [2.93] pg/mL; p = 0.02) compared to non-definite FH, whereas ApoB, oxLDL, and MCP-1 concentrations did not differ significantly between the subgroups. Women had significantly higher TNF-α concentrations compared to men (6.57 [4.74] vs. 4.60 [2.20] pg/mL; p = 0.04) with no differences among other cytokines. Conclusions: Patients with definite FH exhibited persistently higher circulating Lp-PLA2 and TNF-α concentrations despite maximally tolerated lipid-lowering therapy, suggesting ongoing activation of specific inflammatory pathways. These findings support further investigation of Lp-PLA2 and TNF-α as candidate biomarkers for cardiovascular risk assessment in FH.
Background/Objectives: Polyetheretherketone (PEEK) implants are increasingly being used for mandibular reconstruction and augmentation, yet predicting the resulting facial soft tissue changes remains challenging. Accurate pre-operative prediction of soft tissue deformation is essential for surgical planning and patient counselling. To the best of our knowledge, this study presents the first application of a computational model for predicting three-dimensional facial soft tissue deformation induced by PEEK implants. Methods: Four patient cases with pre-operative and post-operative cone-beam computed tomography scans were analysed. A mass tensor model was employed to predict soft tissue changes based on the pre-operative soft tissue shape, mandibular anatomy, and the designed PEEK implant. Model accuracy was quantified by comparing predicted outcomes to post-operative scans using landmark-based analysis of chin and jaw positions, as well as surface distance mapping, with a mean error below 2 mm adopted as the criterion for clinically acceptable accuracy. Results: Landmark-based analysis revealed a mean absolute error of 0.9 ± 0.8 mm between the predicted and actual positions. The mean surface distances were 1.3 mm for the jaw-chin region and 1.0 mm for the entire facial region. Conclusions: These results demonstrate the potential of a computational approach for real-time prediction of facial soft tissue changes following PEEK implant placement, achieving clinically relevant accuracy at the cohort level, with a tendency towards under-prediction and one case exceeding the threshold.
Pain is a leading cause of morbidity and healthcare utilization in sickle cell disease (SCD), and opioids remain central to treating vaso-occlusive and chronic pain. Yet opioid response varies widely, raising the question of whether pharmacogenetic testing should inform opioid prescribing. Our review examined the PubMed literature on pharmacogenomics and opioid efficacy in SCD. We focus on CYP2D6 as the clearest current pharmacogenetic signal for codeine and tramadol, and assess SCD-specific implementation studies, preemptive testing, and African pharmacoequity. The current evidence supports targeted CYP2D6-informed prescribing in selected contexts rather than universal testing for all opioids, while highlighting the need to integrate genotype with pain phenotype, drug-drug interactions, liver function, and clinically grounded implementation studies, and better characterize African and African-ancestry pharmacogene variation.
Background: Diabetes mellitus affects over 500 million people worldwide, yet many machine learning prediction models remain difficult to interpret, limiting their clinical applicability. This study proposes an explainable machine learning framework integrating the Marine Predators Algorithm (MPA) for hyperparameter optimization with SHAP-based explainability to diabetes prediction. Methods: Logistic Regression (LR), Random Forest (RF), and MPA-optimized XGBoost were evaluated using a publicly available Kaggle diabetes dataset of approximately 100,000 records. Statistical significance was assessed using Wilcoxon signed-rank tests with Bonferroni correction for fold-wise cross-validation results, while McNemar’s and DeLong’s tests were employed for paired comparison of independent test-set predictions and ROC-AUC values, respectively. Performance was assessed using accuracy, precision, recall, F1-score, specificity, ROC-AUC, and Brier score. SHAP was used to provide global and local model explanations. Results: The MPA-optimized XGBoost model achieved the highest performance, with 96.72% accuracy, 97.70% precision, 95.70% recall, 96.71% F1-score, and 99.56% ROC-AUC, significantly outperforming LR and RF (p < 0.001). The model demonstrated good calibration with a Brier score of 0.0262. SHAP analysis identified HbA1c level, blood glucose level, and age as the most influential predictors, while interaction analysis indicated a synergistic relationship between HbA1c and blood glucose. Conclusions: The proposed framework demonstrated strong predictive performance and interpretable model behavior on the publicly available diabetes dataset used in this study. These findings indicate the potential of MPA-based optimization combined with SHAP explainability for supporting transparent machine learning research in diabetes prediction. However, additional external validation using independent clinical datasets is required before considering the framework for clinical decision support or real-world deployment.
Introduction: Sarcopenia and frailty are emerging independent risk factors for cardiovascular disease. Sarcopenia represents a decline in function associated with reduced muscle mass. Frailty, defined as a phenotype or the multiple stress model, is associated with weakness and a decline in organ reserve with vulnerability to disease. Frailty and sarcopenia may overlap and have shared clinical risk factors including age and malnutrition. Methods: We performed a literature review of published studies on frailty and sarcopenia with respect to cardiovascular risk factors and body composition. Results: Studies demonstrated that obese sarcopenic or obese frail subjects had a higher prevalence of cardiovascular risk factors such as hypertension, diabetes mellitus, dyslipidaemia, smoking and sedentary lifestyle, which was highly associated with cardiovascular disease. On the other hand, anorexic malnourished frail participants with unintentional weight loss or sarcopenic subjects without obesity had a low prevalence of cardiovascular risk factors, which was less associated with cardiovascular disease. Conclusions: Obesity appears to play a crucial role in mediating the cardiovascular risk of both sarcopenic and frail patients.
Objectives: To assess whether muscle morphology and metabolism can inform personalised care in ventral hernias and to define which parts of a proposed postoperative remodelling model are supported by direct evidence. Methods: We conducted a structured narrative review of PubMed/MEDLINE, Scopus and Web of Science from 1 January 2010 through 30 April 2026. Two authors selected 38 publications. Evidence was classified as direct when generated in ventral or incisional hernia cohorts and indirect when drawn from inguinal hernia, transplantation, geriatric, oncological, animal or general muscle studies. No quantitative synthesis was undertaken. Results: Direct studies document lateral muscle displacement, impaired abdominal wall function, inconsistent associations between low muscle mass and clinical outcomes, and CT-derived increases in muscle cross-sectional areas after transversus abdominis release (TAR). The evidence for anterior abdominal wall myosteatosis, biomarker-guided care and the three proposed remodelling trajectories remains largely indirect. In a 37-patient TAR series, the median rectus abdominis cross-sectional area increased by 16.1% (IQR 11.4-27.0%); muscle function and metabolic recovery were not measured. Conclusions: Routine CT can yield muscle area, attenuation and intermuscular adipose tissue measures without further imaging. No anterior abdominal wall-specific thresholds or biomarker cut-offs have been validated, so these measures should not determine current treatment in isolation. Prospective studies should test whether combined imaging, functional and clinical phenotyping improves the selection of prehabilitation and follow-up.
Background: Polymyalgia rheumatica (PMR) is a clinically heterogeneous inflammatory disorder in which conventional acute-phase reactants may inadequately reflect the complexity and biological variability of disease activity. Precision medicine approaches integrating multidimensional clinical and laboratory data may offer a more comprehensive characterization of inflammatory phenotypes. This study investigated whether the combined assessment of cytokine profiles, routine laboratory biomarkers, ultrasound findings, and clinical variables could improve disease activity stratification in PMR. Methods: A total of 103 consecutive patients with PMR were retrospectively analyzed. Disease activity was assessed using the PMR Activity Score (PMR-AS) and, for exploratory purposes, dichotomized according to the cohort median (≥11 vs. <11). Group differences were evaluated using non-parametric statistical methods. The multidimensional structure of the dataset was explored through Spearman correlation analysis, principal component analysis (PCA), and unsupervised clustering. Predictive models, including logistic regression, random forest, and gradient boosting, were developed to evaluate the potential contribution of integrated analytical approaches to patient stratification. Results: The study cohort included 103 patients (63.1% female), with a median age of 76 years (IQR 71-81); 57 patients (55.3%) presented PMR-AS ≥11. Patients with higher disease activity exhibited significantly increased levels of CRP, fibrinogen, platelet count, IL-6, serum amyloid A (SAA), and myeloid-related protein (MRP), together with a higher prevalence of joint effusion and Power Doppler positivity. Among the evaluated biomarkers, SAA demonstrated the strongest correlation with disease activity (Spearman ρ = 0.878; p < 0.001). Multivariate predictive modeling showed high discriminative performance, with random forest achieving the highest cross-validated AUC (0.934), whereas gradient boosting demonstrated the best overall accuracy (0.883). Unsupervised clustering analysis identified a subgroup characterized by a more pronounced inflammatory signature associated with higher PMR-AS values. Conclusions: These findings support the concept that disease activity in PMR may be more effectively represented through an integrated multidimensional inflammatory profile rather than isolated biomarkers. The combined evaluation of routine laboratory parameters, cytokines, and imaging features may contribute to more refined patient stratification within a precision medicine framework. Although exploratory, these results highlight the potential value of advanced data integration strategies for supporting biologically informed disease characterization in PMR, while underscoring the need for external validation before translation into clinical practice.
Background: Although cardiovascular disease (CVD) significantly impacts the quality of life of millions of patients worldwide, the high costs of developing new drugs and conducting clinical trials for CVD hinder therapeutic development in this field. Repurposing approved drugs, of which the safety has already been tested can significantly reduce the time and cost required for treating CVD. From the perspective of pharmacology, repurposed drugs are selected to specifically target CVD patients carrying the matching drug targets, enabling tailored, personalized intervention. In the context of drug repurposing, therapeutic target mapping is a process used to assess the enrichment of molecules that can be affected by a drug in order to produce a therapeutic effect. Methods: This narrative review summarizes the workflows and challenges of performing therapeutic target mapping to assess the potential of repurposing existing drugs for treating CVD. We also share our perspective of how retrospective studies of human specimens can contribute to therapeutic target mapping based on experience from the Bruce McManus Cardiovascular Biobank (BMCB), a large explanted heart biobank located in Vancouver, Canada. The literature we discuss was identified by non-systematic searches of PubMed, using search terms “human-derived specimens”, “drug repurposing”, and “cardiovascular disease”. We reviewed articles from 2012 to 2026 and prioritized studies conducted after 2019 to discuss recent advances in the field. Conclusions: Human specimens of high molecular quality are needed for evaluating the enrichment of drug targets in CVD. Therapeutic target mapping in diseased cardiovascular tissue requires integrated expertise from medical, translational, and applied sciences to identify suitable human specimens for molecular phenotyping, and to design hypothesis-driven approaches to validate the drugs suggested for repurposing.
Background/Objectives: Chronic non-specific low back pain (CNLBP) is a leading cause of disability worldwide. Although several randomized trials have evaluated treatment effectiveness, less attention has been given to the responsiveness of outcome measures used to assess clinical change. This study aimed to evaluate the internal and external responsiveness of commonly used outcome measures in individuals with CNLBP. Methods: This study is a secondary analysis of a randomized controlled trial. Participants were analyzed as active and placebo groups and assessed at baseline, post-intervention, and follow-up. Internal responsiveness was evaluated using standardized mean differences (SMD) and standardized response means (SRM). External responsiveness was assessed using anchor-based approaches, including correlations with the Global Rating of Change Scale (GRCS) and receiver operating characteristic (ROC) curve analysis. Results: Outcome measures demonstrated moderate to high internal responsiveness, with large effect sizes observed for pain intensity (NRS) and quality of life (EQ-5D-3L). However, external responsiveness was limited, with all instruments presenting area under the curve (AUC) values below 0.70. The Bournemouth Questionnaire showed the highest discriminative performance among the instruments. Conclusions: The evaluated instruments were sensitive to detecting change at the group level but showed limited ability to discriminate clinically meaningful improvement at the individual level. These findings support the use of combined outcome measures to improve clinical interpretation and decision-making in CNLBP.
Background/Objectives: Non-small cell lung cancer (NSCLC) remains associated with high mortality, frequent late-stage diagnosis, biological heterogeneity, and recurrence after treatment. Although molecular and immunohistochemical biomarkers have transformed treatment selection, there remains a need for accessible, repeatable, and clinically practical circulating biomarkers that may support prognosis and post-treatment monitoring. This review discusses prolactin (PRL) as a candidate supplementary biomarker in NSCLC, with particular emphasis on its biological rationale, potential prognostic relevance, and possible role in personalized risk stratification after systemic therapy. Methods: This narrative review summarizes current evidence on established biomarkers in NSCLC, the physiology and regulation of PRL, PRL/PRLR signaling in cancer biology, mechanisms of PRL dysregulation in lung cancer, and available clinical observations concerning PRL alterations in NSCLC. Particular attention is given to the distinction between prognostic and predictive biomarkers, longitudinal monitoring, pituitary involvement, immune checkpoint inhibitor-related endocrine effects, and biological, pharmacological, and analytical confounders affecting PRL interpretation. Results: Current evidence suggests that PRL may be biologically relevant in NSCLC through its involvement in pathways related to cell proliferation, survival, angiogenesis, invasion, epithelial-mesenchymal transition, immune modulation, and possible therapy resistance. Clinical observations indicate that altered PRL levels may occur in advanced disease, pituitary involvement, systemic inflammation, stress, or during anticancer and supportive treatment. However, PRL lacks cancer specificity and is influenced by multiple confounders, including circadian rhythm, stress, endocrine disorders, macroprolactin, cachexia, medications, and assay variability. Available clinical data remain limited and are largely derived from small studies or case-based evidence. Conclusions: PRL should not currently be considered a standalone diagnostic, predictive, or treatment-selective biomarker in NSCLC. Its most realistic potential role is as a supplementary circulating marker within multimarker prognostic and monitoring models. Prospective validation with standardized sampling, assay procedures, and confounder adjustment is required before clinical implementation.
Background: Venous closure devices (VCDs) are being increasingly used after femoral venous access to facilitate recovery, but their comparative efficacy and safety versus manual compression or figure-of-eight suture remain uncertain. Because femoral venous access management is influenced by patient-related and procedural factors, VCDs may contribute to a more personalized postprocedural recovery strategy. Objective: Evaluation of the impact of VCDs on procedural recovery and vascular complications in patients undergoing cardiac procedures via femoral venous access. Methods: We systematically searched PubMed, Embase, and CENTRAL through to April 2025 for randomized controlled trials (RCTs) comparing VCDs with manual compression and/or figure-of-eight suture. Primary efficacy outcomes were time to hemostasis (TTH), time to ambulation (TTA), time to discharge (TTD), and time to discharge eligibility (TTDe). Safety outcomes were major and minor vascular complications. Risk of bias was assessed with RoB 2, and certainty of evidence assessed with GRADE. Random-effects models were used to pool standardized mean differences (SMDs) or risk ratios (RRs) with 95% confidence intervals (CIs). Results: Seven RCTs (n = 948) were included. VCDs use significantly reduced TTH (SMD: -1.00; 95% CI: -1.57 to -0.42) and TTA (SMD: -1.50; 95% CI: -2.42 to -0.58). TTD showed a non-significant trend favoring VCDs (SMD: -0.99; 95% CI: -2.13 to 0.15), while TTDe was consistently shorter with VCDs across three trials. Major vascular complications were rare and similar between groups (RR: 0.41; 95% CI: 0.09-1.89). Minor vascular complications were significantly reduced with VCDs (RR: 0.42; 95% CI: 0.22-0.79). Conclusions: In patients requiring femoral venous access for interventional cardiology procedures, VCDs improve time to hemostasis and ambulation and reduce minor vascular complications without increasing major events. These findings support VCDs as an effective and safe strategy for venous closure.
