Search Results (8,241)

Posttraumatic Stress Disorder (PTSD) is characterized by disruptions in central nervous system functioning and existential crises, yet the mechanistic links between neurobiological processes and dimensions of life meaning and identity remain underexplored. The aim of this study was to examine the relationships between stress biomarkers (serotonin, cortisol, noradrenaline, and interleukin-12 [IL-12]) and existential attitudes (measured using the Life Attitude Profile (Revised) [LAP-R]) in mining rescuers, considering PTSD duration and participant age. This cross-sectional study included 92 men aged 18–50 years, divided into three groups: no PTSD (n = 28), PTSD ≤ 5 years (n = 33), and PTSD > 5 years (n = 31). Serum levels of four biomarkers and LAP-R scores across eight domains were evaluated. Statistical analyses employed nonparametric tests, including the Kruskal–Wallis test for overall group differences (with Wilcoxon r effect sizes for pairwise comparisons, Mann–Whitney U tests for post hoc pairwise comparisons, and Spearman’s rank correlations for biomarker–LAP-R associations. Age effects were assessed in two strata: 18–35 years and 36–50 years. Kruskal–Wallis tests revealed significant group differences (p < 0.001) for all biomarkers and most LAP-R domains, with very large effect sizes (r > 0.7) in pairwise comparisons for serotonin (control median: 225.2 ng/mL vs. PTSD ≤ 5y: 109.9 ng/mL, r = 0.86; vs. PTSD > 5y: 148.0 ng/mL, r = 0.86), IL-12 (control: ~8.0 pg/mL vs. PTSD ≤ 5y: 62.4 pg/mL, r = 0.86; vs. PTSD > 5y: ~21.0 pg/mL, r = 0.69), and LAP-R scales such as Life Purpose (control: 54.0 vs. PTSD ≤ 5y: 39.0, r = 0.78; vs. PTSD > 5y: 20.0, r = 0.86) and Coherence (control: 53.0 vs. PTSD ≤ 5y: 34.0, r = 0.85; vs. PTSD > 5y: 23.0, r = 0.86). The PTSD ≤ 5y group exhibited decreased serotonin, cortisol (median: 9.8 µg/dL), and noradrenaline (271.7 pg/mL) with elevated IL-12 (all p < 0.001 vs. control), alongside reduced LAP-R scores. The PTSD > 5y group showed elevated cortisol (median: ~50.0 µg/dL, p < 0.001 vs. control, r = 0.86) and normalized IL-12 but persistent LAP-R deficits. Older participants (36–50 years) in the PTSD ≤ 5y group displayed improved existential attitudes (e.g., Life Purpose: 47.0 vs. 27.5 in 18–35 years, p < 0.001), whereas in PTSD > 5y, age exacerbated biological stress (cortisol: 57.6 µg/dL vs. 36.1 µg/dL, p = 0.003). Spearman correlations revealed stage-specific patterns, such as negative associations between cortisol and Death Acceptance in PTSD > 5y (ρ = −0.49, p = 0.005). PTSD alters biomarker levels and their associations with existential dimensions, with duration and age modulating patient profiles. These findings underscore the necessity for integrated therapies addressing both biological and existential facets of PTSD. Full article

Background/Objectives: Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and total triiodothyronine (TT3) are biomarkers for evaluating thyroid function. Although hormone levels are affected by many biological and environmental factors, most laboratories use manufacturer-provided reference intervals (RIs) without considering these factors. Thus, in this study we assessed RIs for TSH, FT4, and TT3 in a Korean population, using a direct selection technique. Methods: Serum samples from patients without a history of thyroid disease, medication, family history, or antibody-positive test results were collected after a review of medical records. TSH, FT4, and TT3 levels were measured using the Cobas e801 analyzer (Roche Diagnostics GmbH, Mannheim, Germany) with dedicated reagents. RIs were then established using a non-parametric method, using values at the 2.5th and 97.5th percentiles as reference limits, which were then verified in a validation cohort. Results: A total of 618 subjects were enrolled in this study. Because the distribution of reference values for the four subgroups divided by sex and age (65 years) showed insignificant differences, combined RIs were determined, with the established RIs being 0.38–5.46 mIU/L for TSH, 12.28–22.40 pmol/L for FT4, and 0.94–2.32 nmol/L for TT3. When compared to manufacturer-claimed RIs, the Korean RI for TSH showed higher upper limits, while that for TT3 showed lower upper limits. Additionally, when newly established RIs were applied to the validation cohort, the rate of test-positive results decreased significantly. Conclusions: Significant differences in RIs for TSH and TT3 in the Korean population, compared to manufacturer-claimed values, highlight the need for population-specific RIs. Thus, interpreting the results for the Korean population requires caution, and Korean population-based RIs are necessary. Full article

The ovary is among the earliest organs to undergo age-related degeneration, limiting the reproductive potential of elite horses and constraining the growth of the equine industry. Follicular development during estrus is a key determinant of fertility, yet the molecular mechanisms underlying its decline, particularly at the level of specific ovarian cell types, remain poorly understood in equids. Here, we constructed a single-cell transcriptomic atlas to investigate ovarian changes in Kazakh horses. Using single-cell RNA sequencing (scRNA-seq), we profiled 112,861 cells from follicle-containing and follicle-absent ovaries, identifying nine distinct ovarian cell types and their subtypes, each with distinct gene expression signatures. Functional enrichment analyses revealed cell type-specific engagement in biological pathways, including ECM–receptor interaction, PI3K-Akt signaling, and oxytocin signaling. Gene expression patterns indicated tightly regulated processes of ovarian activation and cell differentiation. Notably, stromal cells exhibited high expression of ROBO2, LOC111770199, and TMTC2, while smooth muscle cells (SMCs) were marked by elevated levels of CCL5, KLRD1, and NKG7. Moreover, cell–cell interaction analyses revealed robust signaling interactions among SMCs, endothelial cells, neurons, and proliferating (cycling) cells. Together, these findings provide a comprehensive single-cell transcriptomic map of normal and abnormal ovarian states during estrus in Kazakh horses, offering novel insights into the cellular mechanisms of follicular development and identifying potential diagnostic biomarkers and therapeutic targets for ovarian quiescence in equids. Full article

Major depressive disorder (MDD) is a prevalent and disabling condition. Transcranial direct current stimulation (tDCS) may improve symptoms by modulating neuroplastic and inflammatory mechanisms. This randomized, double-blind, placebo-controlled trial will recruit adult outpatients with MDD showing residual symptoms despite at least four weeks of stable SSRI treatment. Participants will be randomized to active or sham add-on tDCS while continuing their antidepressant regimen. The intervention will consist of 15 sessions over 3 weeks, targeting the left dorsolateral prefrontal cortex (anode F3, cathode F4) at 2 mA for 30 min per session. The primary outcome is the reduction of depressive symptoms measured by the Hamilton Depression Rating Scale-17 (HDRS), with remission defined as HDRS-17 ≤ 7. Secondary outcomes include cognitive performance (attention, executive functioning, memory), serum biomarkers (BDNF, VEGF, NGF, NRG1, angiogenin, IGF1, IL-6, TNF-α), cortical excitability assessed by transcranial magnetic stimulation (motor threshold, silent period, intracortical inhibition/facilitation), and cerebral hemodynamics by transcranial Doppler sonography (blood flow velocity, pulsatility, resistivity). Assessments will occur at baseline, post-treatment, and 3- and 6-month follow-ups. This trial aims to evaluate the efficacy of adjunctive tDCS in MDD with residual symptoms and its biological correlates, bridging clinical improvement with electrophysiological and neurovascular mechanisms Full article

Background: Advanced heart failure (HF) carries high morbidity and mortality, and deterioration on the heart transplantation (HT) waiting list remains a major challenge. Intermittent outpatient levosimendan has been proposed as a bridge strategy, but the optimal regimen and its impact on peri-transplant outcomes remain uncertain. Within a personalized-medicine framework, we targeted a low-output/INTERMACS 3 phenotype and operationalized an adaptable, protocolized levosimendan pathway focused on perfusion/congestion stabilization to preserve transplant candidacy. Methods: We conducted a single-center, retrospective cohort study of 25 consecutive adults actively listed for HT between 2019 and 2024, treated with a standardized outpatient program of a 14-day interval of 6 h intravenous levosimendan infusions (target 0.2 μg/kg/min infusions) continued until transplant. Personalization in this program was operationalized through (i) phenotype-based eligibility (low CI and elevated filling pressures despite GDMT), (ii) predefined titration and safety rules for blood pressure, arrhythmias, and renal function, and (iii) individualized continuation until transplant with nurse-supervised monitoring and review of patient trajectories. Baseline characteristics, treatment exposure and safety, changes in hospitalizations and biomarkers, and peri-transplant outcomes were analyzed. Results: Patients were predominantly male (68%), with a mean age of 47.9 ± 17.5 years and severe LV dysfunction (LVEF 30.6 ± 9.8%). Median treatment duration was 131 days (IQR 60–241). No infusions required discontinuation for hypotension or arrhythmia, and no adverse events were directly attributed to levosimendan. Two patients (8%) died on the waiting list, both unrelated to therapy. During treatment, HF hospitalizations decreased significantly compared with the previous 6 months (48% vs. 20%, p = 0.033), renal function remained stable, and NT-proBNP trended downward. Of the 23 patients transplanted, two (9%) underwent urgent HT during decompensation. Post-transplant, vasoplegia occurred in 26% (n = 6 of 23), and 30-day mortality was 9% (n = 2 of 23). Conclusions: By defining the target phenotype, therapeutic goals, and adaptation rules, this study shows how a standardized but flexible outpatient levosimendan regimen can function as a personalized bridge strategy for low-output advanced HF. The approach was associated with fewer hospitalizations, stable renal function, and acceptable peri-transplant outcomes, and merits confirmation in multicenter cohorts with attention to patient heterogeneity and treatment effect refinement. Full article

Intestinal microbiota populations are constantly shaped by both intrinsic and extrinsic factors, including diet, environment, and host genetics. As a result, understanding how to assess, monitor, and exploit microbiome–host interplay remains an active area of investigation, especially in aquaculture. In this study, we analyzed the taxonomic structure and functional potential of the intestinal microbiota of European sea bass and rainbow trout, incorporating gilthead sea bream as a final reference. The results showed that the identified core microbiota (40 taxa for sea bass and 20 for trout) held a central role in community organization, despite taxonomic variability, and exhibited a predominant number of positive connections (>60% for both species) with the rest of the microbial community in a Bayesian network. From a functional perspective, core-associated bacterial clusters (75% for sea bass and 81% for sea bream) accounted for the majority of predicted metabolic pathways (core contribution: >75% in sea bass and >87% in trout), particularly those involved in carbohydrate, amino acid, and vitamin metabolism. Comparative analysis across ecological phenotypes highlighted distinct microbial biomarkers, with genera such as Vibrio, Pseudoalteromonas, and Paracoccus enriched in saltwater species (Dicentrarchus labrax and Sparus aurata) and Mycoplasma and Clostridium in freshwater (Oncorhynchus mykiss). Overall, this study underscores the value of integrating taxonomic, functional, and network-based approaches as practical tools to monitor intestinal health status, assess welfare, and guide the development of more sustainable production strategies in aquaculture. Full article

Background: This study aimed to evaluate the clinical effectiveness of dupilumab and its impact on CRSwNP and type 2 inflammatory biomarkers in patients with severe uncontrolled asthma, with or without comorbidities, within a real-life cohort. Methods: This was a single-center, prospective, and observational real-life study conducted at the Severe Asthma Unit of Germans Trias i Pujol University Hospital. The objective of this study was to assess the real-world response to dupilumab treatment in patients with severe asthma, with or without nasal polyposis, bronchiectasis, obesity, or switching from another biologic drug for their asthma. Results: The ACT score significantly increased (13.7 vs. 20.6; p = 0.001), while the number of exacerbations decreased (3.1 vs. 0.7; p = 0.005). Patients with CRSwNP showed an increase in the ACT score (13.1 vs. 19.8; p = 0.011) and a decrease in the number of exacerbations (3.0 vs. 1.3; p = 0.217). Patients with nasal polyps showed an increase in both SNOT22 (78.3 vs. 38.3; p = 0.013) and global VAS (8 vs. 4.2; p = 0.028). Patients with bronchiectasis receiving dupilumab showed an increase in the ACT score (12.7 vs. 21.3; p = 0.039) and a marked decrease in the number of exacerbations (2.8 vs. 0; p = 0.025). Obese patients treated with dupilumab showed an improvement in the ACT score (14.1 vs. 21.3; p = 0.044) and a decrease in the rate of exacerbations (3.2 vs. 1.3; p = 0.030). Patients with rhinoconjunctivitis receiving dupilumab showed an increase in the ACT score (13.4 vs. 19.1; p = 0.017) and a decrease in the number of exacerbations (3.3 vs. 0.8; p = 0.024). Conclusions: Dupilumab is a highly effective treatment for severe asthma, showing significant improvements in lung function, reductions in exacerbations, and enhanced quality of life for patients with and without nasal polyps. The results of this real-life study support dupilumab as a valuable addition to the therapeutic armamentarium for asthma, particularly for those with type 2 inflammation despite the presence of comorbidities such as bronchiectasis or obesity, or for patients in whom a previous biologic treatment failed. Full article

Background: Postoperative cognitive dysfunction (POCD) is a prevalent complication in elderly patients undergoing hip fracture surgery, often resulting in increased morbidity and prolonged rehabilitation. Biomarkers such as Neuron-Specific Enolase (NSE) and S100B protein have shown potential in detecting cerebral injury, yet their role in predicting long-term cognitive decline remains unclear. This study aimed to evaluate the association between biomarkers serum levels and the incidence of POCD in elderly patients undergoing proximal femur fracture surgery. Methods: A multicentric prospective observational study was conducted from January 2023 to February 2024, including 146 elderly patients with hip fractures treated surgically at ASL Bari and the University Orthopedic Department of Foggia. Biomarker levels of NSE and S100B were measured preoperatively (T0), at three days post-surgery (T1), and at one-year follow-up (T2). Cognitive function was assessed using the Pfeiffer Scale (PS) and the Mini-Mental State Examination (MMSE). Statistical analysis was performed using U Mann–Whitney tests and logistic regression to identify risk factors. Results: At three days post-surgery, 20.5% of patients exhibited POCD, with no significant differences in NSE and S100B levels compared to baseline. However, at one year, of the 96 patients investigated 37.9% of patients showed cognitive decline, with significantly elevated NSE (19.88 ± 4.03 μg/L) and S100B (1.86 ± 0.9 μg/L) compared to non-POCD patients (p = 0.01). Risk factors for long-term POCD included older age (OR: 1.24), diabetes mellitus (OR: 4.41), and lower baseline cognitive function (MMSE and PS scores, OR: 0.25 and 9.81, respectively). Conclusions: The study demonstrates that while early POCD is not associated with significant changes in NSE and S100B levels, their elevation at one-year follow-up suggests a possible correlation with chronic neuroinflammation and persistent neuronal damage. Preoperative cognitive impairment, advanced age, and diabetes mellitus are significant predictors of long-term cognitive decline. Incorporating biomarker evaluation and cognitive screening into perioperative management may enhance patient outcomes following hip fracture surgery. Full article

Background: Sarcoidosis is a systemic granulomatous disease with a highly variable clinical course, and distinguishing it from other diseases and predicting its prognosis can be challenging. In recent years, hematological and biochemical parameters have been investigated as potential biomarkers for assessing inflammation and predicting disease prognosis. This study aimed to evaluate the prognostic value of the lactate dehydrogenase-to-albumin ratio (LAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR). Methods: This retrospective, single-center study included 369 newly diagnosed patients with sarcoidosis who were admitted between January 2020 and October 2024. Sarcoidosis was diagnosed based on current ERS, ATS, and WASOG guidelines. At the 6-month follow-up, patients’ clinical courses were classified as regression, stable, or progression based on clinical, radiological, and pulmonary function tests. The predictive values of various hematological and biochemical parameters were analyzed using statistical methods, including binary logistic regression analysis and ROC analysis. Results: A total of 369 patients were included in the study. At the 6-month follow-up, 63.4% of patients showed regression, 21.4% had a stable course, and 15.2% showed progression. The progression group had a significantly higher LAR (5.26 [4.21–7.76]) compared to the stable/regression group (4.59 [3.82–5.86]) (p = 0.033). Additionally, baseline FVC% (OR, 0.97; p = 0.036) and the presence of dyspnea (OR, 3.08; p = 0.03) were identified as independent risk factors for disease progression. No significant associations were found between NLR, PLR, LMR, and serum ACE levels and the clinical course. The cutoff value of LAR for predicting disease progression was 4.87 (AUC: 0.605), with a sensitivity of 58.8% and specificity of 59.7%. Conclusions: Our study, which is the first to evaluate the prognostic value of LAR in sarcoidosis, identified this parameter as a significant indicator for the clinical course. The finding of significantly higher LAR levels in patients with disease progression suggests its potential as a prognostic biomarker. These results may help guide treatment and follow-up strategies, although further large-scale prospective studies are needed for validation. Full article

This narrative review synthesizes PubMed- and Scopus-indexed studies from 2020 to 2025, including preclinical animal models, prospective cohort studies, and level I and II randomized trials, to compare two leading biologic augmentation strategies: platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC). The review examines underlying mechanisms of action, delivery techniques, imaging biomarkers of graft maturation, patient-reported and functional outcomes, safety profiles, cost-effectiveness, and regulatory frameworks. PRP provides early anti-inflammatory and proangiogenic signaling, while BMAC delivers a concentrated population of mesenchymal stem cells and growth factors to the tendon–bone interface. Both modalities consistently enhance MRI-defined graft maturation, yet evidence of long-term functional or biomechanical superiority remains inconclusive. Emerging therapies such as peptide hydrogels, adipose-derived stem cells, and exosome delivery offer promising avenues for future research. Standardized protocols and large multicenter trials are needed to clarify comparative efficacy and inform personalized rehabilitation strategies. Full article

Background/Objectives: Transforming growth factor-beta (TGF-β) is a multifunctional cytokine involved in immune regulation, extracellular matrix turnover, and tissue repair. Its role in periodontitis remains controversial due to conflicting human studies. This systematic review addressed the PICO-based question: in adults with periodontitis (population), how does the expression and regulation of TGF-β isoforms (intervention/exposure) compare with healthy or post-treatment states (comparator) regarding clinical outcomes (outcomes)? Methods: A systematic search of PubMed and Scopus was conducted on 1 July 2025 for human studies published in English between 2010 and 2025. Eligible studies investigated TGF-β expression, function, or genetic regulation in periodontal tissues or biological fluids. Screening and quality appraisal were performed according to PRISMA guidelines, using design-specific risk-of-bias tools. The review protocol was prospectively registered in PROSPERO (CRD420251138456). Results: Fifteen studies met inclusion criteria. TGF-β1 was the most frequently analyzed isoform and was consistently elevated in diseased gingival tissue and gingival crevicular fluid, correlating with probing depth and attachment loss. Several studies reported post-treatment reductions in TGF-β, supporting its value as a dynamic biomarker. Additional findings linked TGF-β signaling to immune modulation, fibrosis, bone turnover, and systemic comorbidities. Evidence for TGF-β2 and TGF-β3 was limited but suggested isoform-specific roles in epithelial–mesenchymal signaling and scar-free repair. Conclusions: Current evidence supports TGF-β, particularly TGF-β1, as a central mediator of periodontal inflammation and repair, with promise as both a biomarker and therapeutic target. Standardized, isoform-specific, and longitudinal studies are needed to clarify its diagnostic and translational utility. Full article

Cardiorenal syndrome (CRS) reflects the intricate and bidirectional interplay between cardiac and renal dysfunction, commonly resulting in diagnostic uncertainty, therapeutic dilemmas and poor outcomes. While traditional biomarkers like serum creatinine (Cr) and natriuretic peptides remain widely used, their limitations in specificity, timing and contextual interpretation often hinder optimal management. This narrative review synthesizes the current evidence on established and emerging biomarkers in CRS, with emphasis on their clinical relevance, integration into real-world practice, and potential to inform precision therapy. Markers of glomerular filtration rate beyond creatinine—such as cystatin C—offer more accurate assessment in frail or sarcopenic patients, while tubular injury markers such as NGAL, KIM-1, and urinary L-FABP (uL-FABP) provide early signals of structural renal damage. The FDA-approved NephroCheck^® test—based on TIMP-2 and IGFBP7— enables risk stratification for imminent AKI up to 24 h before functional decline. Congestion-related markers such as CA125 and bio-adrenomedullin outperform natriuretic peptides in certain CRS phenotypes, particularly in right-sided heart failure or renally impaired patients. Fibrosis and inflammation markers (galectin-3, sST2, GDF-15) add prognostic insights, especially when combined with NT-proBNP or troponin. Rather than presenting biomarkers in isolation, this review proposes a framework that links them to specific clinical contexts—such as suspected decongestion-related renal worsening or persistent congestion despite therapy—to support actionable interpretation. A tailored, scenario-based, multi-marker strategy may enhance diagnostic precision and treatment safety in CRS. Future research should prioritize prospective biomarker-guided trials and standardized pathways for clinical integration. Full article

MicroRNAs (miRNAs) are small non-coding RNAs that play pivotal roles in post-transcriptional gene regulation, influencing development, differentiation, and disease pathogenesis. Since their discovery in 1993, miRNAs have been recognized for their evolutionary conservation and pleiotropic effects, with the 2024 Nobel Prize underscoring their significance in post-transcriptional regulation via the RNA interference (RNAi) pathway. This review synthesizes the complete life cycle of miRNAs—from transcription and processing to function and decay—emphasizing regulatory mechanisms and their implications in human diseases, particularly cancer. We discuss how epitranscriptomic modifications influence miRNA biogenesis and activity, explore their nuclear and mitochondrial functions, and address emerging challenges in miRNA-based therapeutics, including the expanding small RNA landscape such as tRNA-derived small RNAs (tsRNAs), and Argonaute (AGO)-independent activities. Despite hurdles such as modest multi-target effects, off-target interactions, and delivery challenges, miRNAs remain promising as both biomarkers and therapeutic agents, underscoring the need for sustained research to bridge preclinical insights with clinical applications. Full article

Background: Dupilumab, a monoclonal antibody targeting the IL-4/IL-13 receptor, has shown significant efficacy in improving asthma control and reducing exacerbations in patients with severe eosinophilic asthma. However, there is a lack of knowledge about real-world data on clinical remission rates and their predictors. Objective: This study aimed to evaluate clinical outcomes, remission rates, and predictive factors of remission in a real-life cohort of patients with severe eosinophilic asthma treated with dupilumab. Methods: We conducted a retrospective, bicentric, observational study including 52 patients with severe eosinophilic asthma treated with dupilumab. Clinical, functional, and biomarkers were assessed at baseline, 6 months, and 12 months. Statistical analyses included logistic regression to identify independent predictors of clinical remission. Results: After 12 months of treatment, 48.2% of patients achieved clinical remission. Dupilumab significantly improved asthma control and lung function (including FVC and FEF_25–75), reduced exacerbation rates, and maintenance therapy. High blood eosinophil levels (>490 cells/µL), high FeNO levels (>25 ppb), a history of CRSwNP, and better baseline FEV1 were associated with asthma remission. Conversely, obesity (BMI > 30) and related comorbidities (such as GERD, OSAS, and hypertension) and bronchiectasis were associated with a lower likelihood of remission. Multivariate analysis confirmed higher baseline FEV1 (OR 2.94; IC 1.13–7.6), positive history of CRSwNP (OR 8.03; IC 1.41–45.5), and higher baseline blood eosinophils (OR 1.003 IC 1.001–1.006) as independent predictors of clinical remission. Conclusions: These results are in line with the known effectiveness of dupilumab in severe eosinophilic asthma and identified a history of CRSwNP, higher baseline FEV1, and elevated blood eosinophils as key predictors of clinical remission. These findings may contribute to a more personalized approach to treatment selection, emphasizing the importance of comorbidity assessment together with type 2 inflammation biomarkers. Further prospective studies are needed to validate these results. Full article

Therapeutic plasma exchange (TPE) is increasingly recognized as a critical escalation therapy for managing acute multiple sclerosis (MS) relapses refractory to high-dose corticosteroids. Neuropathological and clinical evidence implicate humoral immune mechanisms, particularly autoantibodies, immune complexes, and complement activation, as key pathogenic drivers in a subset of MS attacks, notably those consistent with immunopathological pattern II. By removing these circulating immune effectors, TPE provides a rational strategy to dampen inflammation and promote neurological recovery. This review integrates current mechanistic insights with clinical efficacy data and practical implementation strategies for TPE in corticosteroid-refractory MS. Evidence from randomized controlled trials and observational cohorts demonstrates moderate-to-marked functional improvement in 40–60% of patients, with the greatest benefit observed when therapy is initiated within 14 days of symptom onset and cases demonstrating active inflammatory lesions on MRI. Predictors of a favorable response include younger age, short disease duration, severe syndromes involving optic nerve, brainstem, or spinal cord, and CSF markers of intrathecal B-cell activity. Although TPE is generally well tolerated in experienced centers, its broader adoption of TPE is limited by variability in access, institutional protocols, and provider familiarity. Standardization of treatment algorithms, validation of predictive biomarkers, and incorporation into streamlined clinical pathways are critical to maximizing its clinical impact. Future priorities include comparative trials against alternative escalation therapies, biomarker-guided patients’ selection, and comprehensive health-economic evaluations. Taken together, current evidence and recommendations from major neurology and apheresis societies support TPE as a valuable therapeutic modality capable of significantly improving relapse outcomes in appropriately selected MS patients. Full article