Background: Brush biopsy is a minimally invasive method for early detection of oral squamous cell carcinoma (OSCC). Enhanced accuracy for clinical utility depends on analysis of the whole cell population and automated cohort classifications. Aim: This study aims to delineate OSCC, high-grade dysplasia (HGD), and low-risk lesions (LRLs) by profiling single-cell level alterations using multiplexed flow cytometry. Methods: Brush-biopsy samples were analyzed from patients with LRL, HGD, and OSCC. Flow cytometry analysis was standardized to ascertain cell distribution, heterogeneity, and epithelial cell content. Markers were used for epithelial cell (Pan-Cytokeratin [Pan-CK]/propidium iodide [PI]) and atypical cell (Sambucus–Nigra–Agglutinin-1 [SNA-1]/polyadenosine diphosphate-ribose polymerase inhibitor [PARPi-FL]) delineation. In addition, scatter properties and molecular-equivalence fluorescence (MEF) values of markers were analyzed for cohort classification. Results: Brush-biopsy samples from OSCC/HGD patients showed heterogeneity in the percentage of Pan-CK+ve/PI+ve cells. Significant variation in MEF values of SNA-1/PARPi-FL/PI delineated the OSCC cohort (area under the curve > 0.85). Furthermore, the markers in combination with scatter properties delineated OSCC (multivariate logistic regression; sensitivity: 90%, specificity: 82%). The analysis of the forward-scatter height-to-area ratio delineated HGD from low-risk lesions by capturing the morphology-based cellular differences. Conclusions: These results suggest that a flow cytometry-based analysis of brush-biopsy samples may serve as an adjunct tool for risk stratification of oral lesions. Relevance for patients: This study provides evidence towards the application of flow cytometry as an objective, quantitative adjunct to conventional cytology, and improves early detection and risk stratification of oral lesions using a minimally invasive sampling method, thereby supporting timely clinical decision-making and patient management.
Background: Alzheimer’s disease (AD) is a debilitating neurodegenerative disease and the main cause of age-related dementia. The incidence and financial burden of this brain disorder are expected to increase significantly in the coming decades. Establishing a definitive diagnosis of AD is a long and costly process involving multiple clinical assessments and a range of imaging and laboratory tests. Aim: This review investigates the potential application of Fourier-transform infrared (FTIR) spectroscopy in the diagnosis and screening of AD in the elderly, highlighting the advantages and limitations of this optical diagnostic method compared with those currently used in clinical practice. Additionally, this review examines the utility of FTIR spectroscopy in the differential diagnosis between AD and closely related neurodegenerative diseases. Conclusion: FTIR spectroscopy-based analysis of blood plasma possesses attractive properties to qualify as a promising screening and diagnostic test for AD. It can also be a potential tool for differentiating between AD and dementia with Lewy bodies with relatively high accuracy. This vibrational spectroscopic technique overcomes many, if not most, of the limitations associated with the laboratory and imaging methods used for AD diagnosis. Relevance for patients: Early detection of AD can be of immense benefit to patients, their caregivers, and society as a whole. It enables patients to plan their lives while retaining full decision-making capacity. It also allows patients to start appropriate treatment early in the disease course, which can delay their need for healthcare services.
Background: Hemifacial spasm (HFS) is a chronic and disabling movement disorder commonly affecting older adults. Although botulinum toxin (BoNT) is an established treatment, standardized and multidimensional assessments of severity remain limited. Aim: This study evaluates the therapeutic efficacy of the HFS Severity Score (HFSS), a newly developed scale incorporating five symptom domains, and compares its responsiveness with that of the Jankovic Rating Scale (JRS). Methods: This retrospective study included 18 patients aged 65 years or older who were treated with 10 units of BoNT. HFSS and JRS were assessed at baseline and 4 weeks post-injection by two blinded neurosurgeons. Inter-rater reliability (intraclass correlation coefficient [ICC]) and internal consistency (Cronbach’s α) were calculated. Pre–post differences were evaluated using the Wilcoxon signed-rank test. Convergent validity was examined using Spearman correlation between baseline HFSS and JRS. Responsiveness was assessed using change–score correlations and standardized response means (SRMs). Scatter plots were generated to visualize relationships between the scales. Results: Mean HFSS improved significantly from 9.39 to 3.72 (p <0.001), with all subdomains showing improvement. Baseline HFSS and JRS demonstrated a strong correlation (ρ = 0.82, p <0.001), while ΔHFSS and ΔJRS showed a weaker association (ρ = 0.32), reflecting a floor effect in post-treatment JRS scores. SRM scores indicated high responsiveness for HFSS (1.73) and JRS (1.54), while the ICC (0.91) and Cronbach’s α (0.85) confirmed excellent reliability. No adverse events were observed. Conclusion: BoNT treatment is effective and well-tolerated in older adults with HFS. HFSS is a reliable, multidimensional, and highly responsive tool that complements existing scales and enhances clinical assessment. Relevance for Patients: Older adults with HFS may achieve symptom relief with BoNT. HFSS provides a comprehensive metric that can enhance personalized care and reduce reliance on medication.
Background: Pulmonary embolism (PE) is a major global health concern and the third leading cause of cardiovascular mortality in the U.S. There are various treatment options available for the treatment of intermediate-to-high risk acute PE, including catheter-based treatments, surgical embolectomy, and systemic thrombolysis. Objective: To perform a systematic review and Bayesian network meta-analysis (NMA) comparing the safety and efficacy of advanced therapies in patients with intermediate-to-high risk acute PE. Methods: We searched PubMed/Medline, Embase, and Scopus for relevant studies published until August 30, 2024, and performed a Bayesian NMA to synthesize direct and indirect evidence using the Bayesian inference Using Gibbs Sampling to conduct a Network meta-analysis package in R. Results: Of 1,586 studies, 47 met the inclusion criteria, of which 45 were non-randomized. A total of 267,695 acute intermediate-to-high risk PE patients were included in the analysis, receiving one of five advanced interventions: ultrasound-assisted thrombolysis (USAT), standard catheter-directed thrombolysis (sCDT), catheter-based embolectomy, surgical pulmonary embolectomy (SE), or systemic thrombolysis. USAT had the lowest risk of short-term (94.11), long-term mortality (94.67), major bleeding (90.38), and risk of blood transfusions (91); sCDT had the lowest risk of intracranial hemorrhage (86.2), and SE had the lowest risk of any bleeding (99.37) and gastrointestinal bleeding (87.46) based on Surface Under the Cumulative Ranking values. Conclusion: In our study, USAT offers significant short- and long-term mortality benefits with the lowest risk of major bleeding and transfusion requirements, while sCDT is ideal for patients at high-risk for intracranial hemorrhage. Relevance for patients: Among catheter-based therapies for acute intermediate-to-high-risk PE, USAT offered the best clinical and safety outcomes.
Background: The blood-brain barrier (BBB) is an intricate structure of the vascular endothelium that regulates trafficking required for cerebral homeostasis via tightly regulated influx and efflux transport mechanisms. It also performs a critical function in mediating communication between the periphery and the central nervous system (CNS). The BBB is designed to maintain a precisely regulated microenvironment conducive to normal neuronal activity. The development of in vitro BBB models has been driven by the need for a fast, reliable, and cost-effective tool to study the complexities of the BBB and to screen potential CNS drugs. Aim: This review provides readers with a concise yet comprehensive introduction to the fundamental histology of the BBB. This background is essential for interpreting model design constraints and limitations in BBB simulation. Following that, we thoroughly examine in vitro models, providing a comprehensive analysis of their applications and the equations used to assess specific BBB parameters. Relevance for patients: From a translational and clinical perspective, in vitro models of the BBB have the potential to provide novel insights into brain pathophysiology under adverse conditions, including brain tumors, traumatic injuries, strokes, and neurodegenerative disorders, and ultimately aid in the discovery of effective treatment strategies.
Background: Viral elements, such as human papillomavirus (HPV), Epstein–Barr virus (EBV), endogenous retroviruses (e.g., human endogenous retrovirus K), and bacteriophages, are known to regulate oncogenic signaling. To assess the ability of patient-level virome activity and host-pathway disruption to predict patient survival, we developed a Trans-Kingdom Signaling Index (TKSI). Methods: We examined 320 patients with HPV-positive head and neck squamous cell carcinoma, HPV-positive cervical cancer, and EBV-positive stomach adenocarcinoma. Viral features, including HPV E6/E7, virome modules, phage CpG DNA, phage structural proteins, and viral double-stranded RNA, along with tumor RNA sequencing data, were analyzed using single-sample Gene Set Enrichment Analysis on six host pathways: nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), cGAS–STING, p53, MYC, EMT, and PD-L1. A coupling matrix (K) was constructed to connect viral modules to host pathways, and TKSI was calculated, normalized, and dichotomized into TKSI-high and TKSI-low. Results: TKSI values followed an approximately normal distribution and stratified survival independent of tumor type. Patients with high TKSI exhibited lower overall survival (median overall survival 18.2 vs. 29.4 months) and an adjusted hazard ratio of 1.6 (log-rank p=0.018). TKSI–survival associations were robust, with bootstrapped 95% confidence intervals supporting these findings. Observed virome–host interactions corresponded to known mechanisms, including HPV-mediated suppression of p53, EBV microRNA-mediated PD-L1 expression, human endogenous retrovirus K-mediated activation of MYC, and phage CpG–TLR9–NF-κB. Conclusion: Virome–host interactions significantly influence cancer prognosis and signaling. TKSI integrates viral and host mechanisms to improve risk stratification. Relevance for patients: TKSI-derived virome–human quantification enhances patient stratification and may guide the development of virome-responsive biomarkers for precision oncology.
Background: Guillain–Barré syndrome (GBS) causes acute flaccid paralysis and long-term motor and functional deficits, often necessitating prolonged, multidisciplinary rehabilitation. In recent years, rapid advances in biomedical and digital technologies have broadened the therapeutic landscape for neurorehabilitation; however, their use and methodological quality in GBS have not yet been comprehensively reviewed. Objective: This scoping review systematically maps and synthesizes emerging rehabilitation technologies in GBS, grouping them into five clusters: robotics, electrical/biofeedback therapies, virtual and telerehabilitation, augmented reality/sensor-based systems, and hybrid/interactive platforms. It integrates both primary studies (n = 18) and systematic reviews (n = 3) to assess outcome trends (motor recovery, functional independence, and secondary measures such as quality of life, usability, and engagement) and to evaluate methodological quality using the Joanna Briggs Institute’s critical appraisal tools. Relevance for patients: The mapping of technologies demonstrated consistent improvements in motor recovery and functional outcomes among GBS survivors, especially with robotic and electrical/biofeedback therapies. High-quality evidence (≥ 80% “Yes”) predominated in this area, supporting the safe and effective integration of technology-based rehabilitation. The review highlights the clinical relevance of engineering-assisted, interactive strategies that foster adaptive, personalized recovery and enhance patient engagement throughout long-term neurorehabilitation.