Search Results (21,453)

Background and Objectives: Severe COVID-19 frequently fulfills Sepsis-3 criteria and is characterized by thrombo-inflammation and endothelial injury. We evaluated whether a bedside endothelial activation index (EAI = D-dimer/fibrinogen) identifies biologically distinct phenotypes and relates to interleukin-6 (IL-6) response after therapeutic plasma exchange (TPE), and whether baseline IL-6 predicts a ≥50% IL-6 reduction. Methods: Retrospective single-center ICU cohort of adults with SARS-CoV-2 infection, sepsis-related organ dysfunction, and ≥1 TPE session (n = 51). Patients were stratified by median EAI (low vs. high). Outcomes included peri-procedural biomarker/physiology changes (post–baseline), IL-6 responder status (≥50% reduction), correlations with IL-6 reduction (%), and multivariable predictors of response. Results: Compared with low EAI (n = 25), high EAI (n = 26) had higher baseline D-dimer (6.2 vs. 2.2 µg/mL) and lower fibrinogen (2.9 vs. 7.1 g/L) (both p < 0.001). Low EAI showed larger CRP decreases (ΔCRP −84.0 vs. −2.3 mg/L; p = 0.001) and larger fibrinogen falls (Δ −3.1 vs. −0.4 g/L; p < 0.001), while high EAI had larger D-dimer decreases (Δ −2.5 vs. −0.6 µg/mL; p = 0.004) and a modest SOFA improvement (Δ −0.3 vs. +0.1; p = 0.026). IL-6 responders (n = 20) had higher baseline IL-6 than non-responders (365.2 vs. 47.1 pg/mL; p < 0.001). Baseline IL-6 independently predicted response (per doubling: OR 1.94, 95% CI 1.27–2.95; p = 0.002), while age reduced odds (OR 0.91/year, 95% CI 0.84–0.99; p = 0.032). IL-6 reduction correlated with ΔCRP (ρ = −0.41; p = 0.003) and ΔPaO₂/FiO₂ (ρ = 0.37; p = 0.01). Conclusions: EAI stratifies distinct thrombo-inflammatory patterns around TPE, while baseline IL-6 is the dominant predictor of achieving large IL-6 reductions. To emphasize the novelty and clarify the study objective, this exploratory analysis used a phenotype-stratified framework to test whether a simple bedside endothelial activation index could enrich biological response assessment to adjunctive TPE. The prespecified primary outcome was achievement of a ≥50% IL-6 reduction after completion of the TPE course; secondary outcomes included peri-procedural biomarker, oxygenation, SOFA, and ICU endpoints. Full article

Background and Objectives: Coronavirus disease 2019 (COVID-19) is characterized by excessive inflammatory responses, including the so-called cytokine storm, which contributes substantially to morbidity and mortality in hospitalized patients. The vagus nerve, through the cholinergic anti-inflammatory pathway, represents a theoretically attractive therapeutic target for modulating systemic inflammation. Vagus nerve stimulation (VNS) has emerged as a potential adjunctive treatment for COVID-19, with several randomized controlled trials (RCTs) investigating its efficacy on inflammatory biomarkers and clinical outcomes. The quality of this evidence base has not been rigorously evaluated. This systematic review critically appraises all available RCT evidence for VNS in hospitalized COVID-19 patients. Materials and Methods: We systematically searched PubMed, Scopus, Cochrane (CENTRAL), and Web of Science from database inception to January 2026, for RCTs evaluating any form of VNS (invasive, non-invasive, cervical, or auricular) in hospitalized patients with confirmed acute COVID-19. Two reviewers independently screened titles, abstracts, and full texts according to pre-specified eligibility criteria. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, with assessments initially performed using multiple artificial intelligence tools and subsequently validated by the authors in accordance with PRISMA 2020 guidelines. Given substantial heterogeneity and high risk of bias, narrative synthesis was performed rather than meta-analysis. Also, GRADE assessment was performed. Results: From 437 records identified, six RCTs comprising 221 patients met the inclusion criteria. Five trials (83%) were rated as high risk of bias, primarily due to inadequate blinding, substantial baseline imbalances, significant missing data and extensive multiple testing without statistical correction. The single double-blind trial with a credible sham control (Rangon et al.) found null results across all outcomes, including clinical progression, ICU transfer, and mortality, while the five “high” risk-of-bias trials generally reported positive findings on various inflammatory markers and clinical outcomes. One trial (Corrêa et al.) measured heart rate variability as a direct indicator of vagal activation and found no change despite claiming anti-inflammatory effects, contradicting the proposed mechanism of action. Significant cognitive findings from an interim analysis (Uehara et al., n = 21) disappeared in the larger completed trial (Corrêa et al., n = 52), providing empirical demonstration of false positive findings in small, underpowered studies. Conclusions: Currently available evidence supporting the use of VNS for acute COVID-19 remains scarce; however, the physiological rationale remains sound, although the absence of reliable target engagement markers in the included studies limits confidence in this treatment method. Large-scale, double-blind, sham-controlled trials are required before VNS can be firmly recommended for COVID-19 management. Full article

Background/Objectives: Asthma affects millions of patients worldwide and impacts their quality of life, particularly among children. Colonisation or an imbalance within natural resident microbiota may drive inflammatory responses in asthma; antibiotic resistance genes (ARGs) have also been investigated in asthma microbiome studies. However, research on the association between airway microbiota and ARGs remains limited. Therefore, we elucidated functional-level characterisation at the level of ARGs, virulence factors, and active pathways among a paediatric asthma cohort relative to a healthy control. Methods: Overall, 29 children with asthma and 20 control subjects were enrolled, and 3 swabs (2 nasal and 1 oropharyngeal) were obtained from each participant. Genomic DNA was extracted and sent for shotgun sequencing, after which bioinformatic analysis was conducted to remove human reads and analyse the microbiota pattern in the samples. The abundance of antibiotic resistance genes was evaluated along with the distribution of virulence genetic markers. Functional investigation of the most prevalent metabolic pathways was also performed. Results: Upper airway microbiome functional capacity varied by anatomical location, with oropharyngeal communities exhibiting greater metabolic breadth than nasal communities, suggesting the sample source to be the dominant factor shaping gene content, pathway profiles, and community structure. Asthma-related functional differences were modest, and no biological pathways remained significant following false discovery rate correction. Enrichment of antimicrobial resistance genes was observed, particularly those conferring resistance to β-lactams, macrolides, and tetracyclines. Conclusions: Different anatomical niches exhibit differential activities, and further exploration in this direction could aid in the development of diagnostic and therapeutic biomarkers for asthma. Full article

Background: The pain experienced by people with fibromyalgia (FM) is thought to be the result of altered nociceptive processing, impaired descending inhibition and reduced tolerance to physical load. However, the relationship between the amount of exercise and pain reduction remains unclear. Methods: This study synthesized randomized controlled trials of exercise interventions for FM to quantify the combined analgesic effects of different types of exercise. A secondary aim was to standardize exposure using metabolic equivalent of task (MET)-based metrics and examine the association between cumulative intervention dose (MET·h) and analgesic response (Hedges’ g) across intervention arms. Following the PRISMA guidelines, a search was conducted in PubMed for randomized controlled trials published up to 31 December 2025. After screening and a full-text assessment, 15 trials were included. The protocols were converted into MET-defined intensity and weekly MET·min exposure, and the cumulative dose was calculated as the total MET·h accrued over the intervention period. Random-effects models were used to estimate the pooled effects within modality subgroups. Results: Across modalities, exercise was associated with reductions in pain, with effects typically falling within the small-to-moderate range. Larger improvements were observed in structured or supervised programs. The dose-response scatter plot showed wide variability across the dose range, with overlapping confidence intervals. An exploratory fourth-degree polynomial fit explained limited variance (R² = 0.1615) and did not indicate a monotonic dose-response pattern. This suggests that cumulative workload alone is a weak proxy for therapeutic response. Conclusions: Based on these findings, a pain-responsive algorithm combining weekly Visual Analogue Scale (VAS), ΔVAS and Talk Test thresholds was implemented as a preliminary online calculator to support the prescription of exercise tailored to symptoms. Full article

The common metabolic disorder, lactose intolerance, is often treated with oral lactase enzyme supplements, which can frequently cause gastrointestinal instability. This work utilizes Malbranchea cinnamomea’s AA9 lytic polysaccharide monooxygenase (LPMO) to target β-lactose (β-lactose) in an investigation of a new enzymatic approach for lactose breakdown. Potential possibilities for lactose breakdown are AA9 LPMOs, copper-dependent enzymes that oxidatively cleave glycosidic bonds in polysaccharides. We employed a combined in silico method that incorporated molecular docking, density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. Docking studies revealed that β-lactose formed hydrogen bonds with key residues SER100, ASN54, and ARG56, exhibiting a greater binding affinity (−5.4 kcal/mol) toward LPMO compared to the control citric acid (−4.9 kcal/mol). Upon DFT analysis, (LPMO) showed excellent stability and appropriate reactivity for enzyme interaction. The higher stability of the LPMO-β-lactose complex was highlighted by MD simulation over 100 ns, which showed lower root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values, greater structural compactness, and reduced solvent accessibility when compared to the control. These collective findings suggest that β-lactose interacts efficiently with the AA9 LPMO active site, supporting its potential as a novel enzymatic target for lactose degradation. This computational study provides a theoretical foundation for developing alternative therapeutic strategies for lactose intolerance, though further in vitro and in vivo investigations are required to validate these findings. Full article

Background/Objectives: Doxorubicin is an anthracycline chemotherapeutic agent widely used in the treatment of breast cancer. However, its clinical utility is limited by the drug’s resistance development, low oral bioavailability, and dose-dependent side effects. The semi-essential amino acid, L-arginine, has gained attention as a potential adjuvant that could improve the drug distribution and cytotoxic effectiveness of chemotherapeutics. This study aimed to explore the multifunctional effect of L-arginine on the intestinal absorption and anti-breast cancer activity of doxorubicin. Methods: The rabbit in situ intestinal perfusion technique was employed to investigate the membrane transport parameters of doxorubicin both in the absence and presence of L-arginine. Furthermore, the effect of L-arginine on the cytotoxic activity of doxorubicin against breast cancer cells (MCF-7) was assessed using the MTT assay. Results: Co-perfusion of L-arginine with doxorubicin enhanced the fraction of doxorubicin absorbed, with a recorded 4.3-fold enhancement in the jejuno-ileum and a 1.5-fold enhancement in the colon segment. In MCF-7 cells, co-treatment with L-arginine resulted in a significant potentiation of doxorubicin cytotoxicity. At L-arginine concentrations of 10 μM and 50 μM, the recorded IC₅₀ decreased from 41.3 μM to 8.2 μM and to 22.1 μM, respectively. The superior efficacy of 10 μM L-arginine compared to 50 μM reflected a biphasic concentration-dependent response. Conclusions: L-arginine modulated two critical aspects of doxorubicin efficacy, intestinal absorption and cytotoxic activity. The biphasic response emphasizes the importance of L-arginine dose optimization. These findings support the potential of L-arginine as a safe adjuvant for developing oral doxorubicin formulations. This approach can reduce the dose-related toxicity of doxorubicin and improve therapeutic outcomes. Full article

Background/Objectives: Retinoblastoma represents the most common intraocular malignancy in childhood; however, the clinical applicability of mitomycin C (MMC) is restricted by dose-dependent ocular toxicity. Consequently, the development of pharmacological strategies that sensitize tumor cells to MMC while allowing dose reduction remains an unmet therapeutic objective. In this context, quercetin, a bioactive flavonoid with pleiotropic anticancer properties, has emerged as a potential chemosensitizing agent. Methods: Human retinoblastoma cell lines Y79 and WERI-Rb1 were exposed to MMC and quercetin, administered either individually or in fixed-ratio combinations. Cytotoxic responses were quantified through dose–response modeling and IC₅₀ determination following 24 and 48 h of treatment. Drug–drug interactions were quantitatively characterized using the Chou–Talalay combination index (CI) approach and isobologram analysis. Cell cycle distribution was assessed by propidium iodide (PI)-based flow cytometric analysis to evaluate treatment-associated alterations in cell cycle progression. Apoptotic cell death was assessed by Annexin V-FITC/PI flow cytometry, while transcriptional modulation of genes associated with apoptosis, cell cycle regulation, and oxidative stress (BAX, BCL-2, TP53, CASP3, CDKN1A, and HMOX1) was evaluated by qRT-PCR. Modulation of tumor-supportive signaling was examined by measuring VEGF and IL-6 secretion. Translational relevance was further investigated using a three-dimensional (3D) tumor spheroid model, and the functional contribution of reactive oxygen species (ROS) was interrogated through N-acetyl-L-cysteine (NAC) rescue experiments. Results: Quercetin significantly enhanced the cytotoxic activity of MMC in both retinoblastoma cell lines, with CI values below 1 across IC₅₀–IC₉₀ effect levels, indicating a synergistic pharmacological interaction. PI–FACS analysis revealed that combined MMC and quercetin treatment induced a pronounced accumulation of cells in the G2/M phase, consistent with cell cycle arrest, with a more marked effect observed in Y79 cells compared with WERI-Rb1 cells. Combination treatment resulted in a pronounced increase in apoptotic cell populations compared with single-agent exposure and triggered a coordinated pro-apoptotic transcriptional response, characterized by increased expression of BAX, TP53, CASP3, CDKN1A, and HMOX1, alongside suppression of BCL-2 and a marked shift in the BAX/BCL-2 ratio. Concurrently, VEGF and IL-6 secretion were significantly reduced, reflecting attenuation of pro-angiogenic and pro-inflammatory signaling. Notably, synergistic cytotoxicity was maintained in 3D tumor spheroids, where combined treatment induced spheroid shrinkage, architectural disruption, and reduced viability. NAC pretreatment diminished ROS accumulation and partially restored cell viability, indicating that oxidative stress contributes to, but does not solely account for, the observed synergistic cytotoxic effect. Conclusions: Collectively, these findings indicate that quercetin appears to function as an effective chemosensitizing adjuvant to MMC in retinoblastoma models, through transcriptional changes consistent with p53-associated apoptotic signaling at the transcriptional level, G2/M cell cycle arrest, and partial involvement of ROS-related cellular stress responses, along with suppression of tumor-supportive signaling pathways. The preservation of synergistic activity in 3D tumor spheroids supports the potential preclinical relevance of this combination. However, these findings are based on transcriptional and phenotypic analyses and should be interpreted as hypothesis-generating, requiring further validation through protein-level and in vivo studies before translational application. Full article

Background: In multicultural healthcare systems such as the Italian one, migrant children may experience dental care as particularly stressful because linguistic and cultural barriers can limit communication, emotional expression, and understanding of the clinical setting. Aim: Understanding the emotional experience of migrant children during dental visits is essential for improving clinical management in pediatric dentistry and orthodontics within multicultural contexts. Because linguistic barriers often limit verbal communication, this study aimed to explore children’s mental representations, emotional states, and perceptions of the dental environment through drawing and to evaluate the clinical implications for communication and therapeutic collaboration. Methods: This qualitative study was conducted in Italy between 2016 and 2025 and analyzed 50 drawings produced by 50 foreign-born migrant children aged 6–13 years, recruited through an educational cooperative in Piacenza. Most participants originated from developing countries and had limited proficiency in Italian, frequently showing a marked “experience gap” in drawing ability that interfered with normative developmental stages described by Lowenfeld. The analysis focused on spatial organization, line quality, color use, posture, interpersonal distance, and representation of the clinical environment, integrating graphic competence assessment with emotional interpretation. Results: Younger children commonly depicted rigid lines, essential settings, and oversized dental unit lamps, whereas older children increasingly represented threatening or disproportionate instruments, aggressive dentists, and omission of the patient figure. Around age 10, drawings became more detailed and colorful, although symbols of closure, such as locked doors, persisted. In adolescents, representations polarized between rich, coherent scenes and extremely essential drawings dominated by fear, rigidity, minimal environments, and symbols of constraint. The findings suggest that drawing may represent a valuable non-verbal clinical and communicative resource for exploring migrant children’s emotional experience of dental care and for identifying signs of anxiety and vulnerability that may not emerge through verbal interaction alone. Conclusions: These findings support the value of a culturally sensitive dental approach integrating drawing, visual aids, multilingual educational materials, and play-based strategies to reduce communication barriers and improve cooperation in migrant children receiving pediatric dental and orthodontic care. Full article

Background/Objectives: This study evaluates the efficacy of hypoglossal nerve stimulation as an alternative intervention for pediatric patients with obstructive sleep apnea (OSA) unresponsive to standard therapies and examines the uniformity of therapeutic outcomes across different patient cohorts. Methods: An extensive systematic search was performed across four principal databases (PubMed, EMBASE, Cochrane Library, and Web of Science) utilizing keywords associated with pediatric OSA and hypoglossal nerve stimulation, encompassing studies up to July 2025 that provided objective polysomnographic metrics (e.g., apnea-hypopnea index [AHI] values) to enable the quantitative assessment of pre- and post-intervention effects in children. The primary outcome measured was the ratio of means (ROM), determined from pre–post data in single-group studies, with summary estimates obtained using the fixed-effects model. Results: The systematic review included nine eligible studies with a total of 140 pediatric subjects, the majority of whom were adolescents with Down syndrome. AHI meta-analysis outcomes indicated a marked improvement in OSA severity, yielding an overall ROM of 0.57 [95% confidence interval: 0.49–0.65]. The therapeutic benefit demonstrated a high degree of uniformity across cohorts, as indicated by minimal statistical heterogeneity (I² = 16%, p = 0.30). Funnel plot assessment showed no statistically significant evidence of systematic publication bias. Conclusions: Current evidence suggests that hypoglossal nerve stimulation therapy is a safe, effective, and valuable alternative for pediatric OSA patients who do not respond to conventional therapies. Full article

Background/Objectives: Pulmonary arterial hypertension (PAH) is a rare but life-threatening disease that presents particular therapeutic challenges in children. It is characterized by pulmonary vasoconstriction and vascular remodeling, leading to right ventricular strain and eventually right heart failure. Although advances in pharmacotherapy have improved outcomes, treatment options remain limited. This review aims to evaluate the potential role of sotatercept, a novel fusion protein recently approved for adult PAH, and to assess the translatability of adult data to the pediatric population. Methods: A narrative synthesis of preclinical studies and randomized controlled trials was conducted to summarize the current evidence on sotatercept. In addition, pathophysiological, developmental, and therapeutic differences between adult and pediatric PAH were critically examined to assess relevance and applicability to younger patients. Results: Clinical trials in adults (PULSAR, STELLAR, ZENITH, HYPERION) confirm sotatercept’s efficacy on background therapy, with significant reductions in pulmonary vascular resistance, improvements in 6 min walk distance, enhanced right ventricular function, and risk reductions in clinical worsening events. However, extrapolation to pediatric PAH faces challenges including etiological differences (e.g., PAH-CHD predominance, PPHN in infants), age-inappropriate endpoints (e.g., 6MWD infeasible in young children), variable growth-related pharmacokinetics, and compensatory RV physiology delaying overt failure. Safety concerns are manageable in adults but raise pediatric-specific alarms: activin inhibition’s theoretical tumorigenic potential (dual tumor suppressor/promoter role), pubertal/fertility disruption (FSH suppression, gonadal maturation delay), and skeletal growth interference—unproven clinically yet demanding long-term monitoring. The ongoing MOONBEAM trial will provide initial pharmacokinetic/safety data in children. Conclusions: Sotatercept represents a promising, first-in-class therapeutic option for PAH with the potential to transform disease management. Nevertheless, dedicated pediatric studies are crucial to confirm safety, efficacy, and appropriate dosing and to define its role in the long-term treatment of children with PAH. Full article

The growing interest in harnessing natural compounds for health and medical applications underscores the necessity for innovative approaches to decipher their mechanisms of action. Among diverse strategies, non-probe-based methods for identifying the molecular targets of compounds represent one of the frontiers in drug discovery. This review focuses on an array of non-probe techniques for unveiling interactions between natural molecules and biological targets. The advantages and limitations of label-free protein target identification schemes suitable for lysed cells and living cells are analyzed. High-throughput target screening methods and their role in facilitating a holistic understanding of compound–target interactions are summarized. Based on comprehensive evaluation and comparison, this review aims to provide guidelines for selecting appropriate non-probe strategies to accelerate the characterization of the therapeutic potential of natural compounds. Full article

Background: Sialylation, a key terminal glycosylation modification, plays a pivotal role in tumor progression and immune evasion. The sialyltransferase ST3GAL4 is implicated in individual cancers, but its pan-cancer landscape and systemic associations remain undefined. Methods: We performed an integrated multi-omics analysis using transcriptomic, proteomic, genomic, DNA methylation, and tumor microenvironment datasets from TCGA, CPTAC, GTEx, and other public resources. Immune associations were evaluated via TIMER2.0 and TISIDB. Experimental validation included immunofluorescence staining for ST3GAL4 protein in human tumor specimens. Results: ST3GAL4 exhibited pervasive, lineage-specific dysregulation across cancers. Elevated expression correlated with adverse prognosis, genomic instability, and specific RNA modification patterns. Tumor microenvironment analyses revealed significant associations: ST3GAL4 expression positively correlated with cancer-associated fibroblast and endothelial cell infiltration but was inversely associated with cytotoxic T-cell abundance. Functional enrichment implicated ST3GAL4 within glycosphingolipid metabolism and glycan biosynthetic pathways. In experimental models, its expression demonstrated context-dependent modulation following cytokine stimulation and immunotherapy. Immunofluorescence confirmed tumor-specific protein expression and its spatial co-occurrence with stromal and immune cell markers. Conclusion: This multi-omics study delineates a comprehensive pan-cancer atlas of ST3GAL4, establishing its association with aggressive tumor behavior, an immunosuppressive microenvironment, and core glycosylation pathways. These findings position ST3GAL4 as a potential cross-tumor node linking sialylation to immune evasion, providing a rationale for future mechanistic and therapeutic exploration. Full article

Background/Objectives: Ginger has a long history as both a culinary and medicinal plant and is widely recognized in traditional medicine for its ability to promote health and well-being. The principal bioactive compounds of ginger are present in fresh and dried forms and have been largely studied for their therapeutic potential. These compounds exhibit a wide range of biological activities mediated through various mechanisms. Advances in nanotechnology have enabled the development of innovative delivery systems, thereby enhancing the bioavailability and therapeutic efficacy of ginger-derived compounds in modern medical applications. Methods: A comprehensive literature review was conducted to evaluate the characteristics of ginger and its potential role in disease prevention. Relevant studies were identified through the main research databases, publication screening, manual reference checks, and author consensus was conducted. Results: This narrative review provides an overview of the therapeutic potential of bioactive compounds in ginger for the management and prevention of cardiovascular, arthritis, neurodegenerative, and gastrointestinal diseases, with particular emphasis on the molecular mechanisms. In addition, their potential anti-aging properties are extensively discussed. The evidence reported is predominantly preclinical (in vitro and in vivo models), with more limited and heterogeneous clinical data. Recent studies have also highlighted the role of artificial intelligence (AI) in accelerating the discovery and evaluation of bioactive agents with therapeutic relevance across diverse biological systems. Conclusions: This review highlights the emerging applications of ginger extracts in human health and suggests their applications in both traditional medicine and contemporary drug discovery. Full article

Introduction: University students are vulnerable to psychological distress due to the academic and social demands of this life stage. Mindfulness and self-compassion are effective and adaptable strategies in an academic environment that promote emotional regulation and psychological well-being. This study aims to conduct a systematic review and meta-analysis to evaluate the combined impact of mindfulness- and self-compassion-based interventions (MBSCIs) on psychological distress. It will also analyze their role as predictors of therapeutic change, as well as the moderating influence of sociodemographic and contextual factors. Method: We systematically searched PubMed, Scopus and Web of Science for randomized controlled trials (RCTs) and single-group pre-post trials investigating the effect of MBSCI on anxiety, depression and stress in college students. Studies were combined using the inverse variance method in a random effects model. Additional subgroup and meta-regression analyses were performed, and risk of bias was assessed. The review was pre-registered (PROSPERO registration number: CRD420251003822). Results: Our review included 49 studies with a total of 5043 participants (3721 in the intervention group, and 1322 in the control group). The results provide relevant evidence on the efficacy of MBSCI in the university population, especially in reducing symptoms of stress, anxiety, and depression. The effect sizes observed were moderate-to-large for stress and small-to-moderate for anxiety and depression, supporting their clinical usefulness in university educational settings. However, these findings should be interpreted with caution, as no included study achieved low risk of bias, and heterogeneity was moderate-to-high across most outcomes. Conclusions: The results suggest that MBSCI could alleviate psychological distress in university students. However, these results are limited by some methodological issues (risk of bias, heterogeneity, lack of follow-ups, poor standardization). It would be advisable to integrate these practices into the university curriculum as workshops or complementary activities. Further studies are needed to confirm their effectiveness and explore sustained effects and differences according to individual characteristics. Full article

Background/Objectives: Pulmonary embolism (PE) is a major cause of cardiovascular mortality, particularly in high-risk cases complicated by hemodynamic instability. Systemic thrombolysis is the recommended treatment in such settings; however, the coexistence of thrombocytopenia represents a major therapeutic challenge due to concerns regarding bleeding risk. Evidence guiding thrombolytic therapy in thrombocytopenic patients with PE is limited. This study aimed to present a representative case and review the available literature addressing thrombolysis in PE complicated by thrombocytopenia. Methods: A qualitative review of published case reports was conducted using the PubMed and Scopus databases, and articles describing adult patients with objectively confirmed PE, documented thrombocytopenia, and treatment with thrombolytic therapy were included. Eight case reports met the inclusion criteria, and the clinical characteristics, severity markers, platelet dynamics, treatment strategies and outcomes were analyzed and compared with the reported case. Results: Most of the reported patients presented with high-risk pulmonary embolism, defined by hemodynamic instability, including shock or cardiac arrest. Thrombolysis was frequently administered despite platelet counts below conventional thresholds. Platelet levels at the time of thrombolysis varied widely, including cases of severe thrombocytopenia. Clinical and hemodynamic improvement was observed in most of the cases, while major bleeding complications were infrequent. The reported case demonstrated successful systemic thrombolysis with rt-PA in a postpartum patient with suspected heparin-induced thrombocytopenia and high-risk PE, without hemorrhagic events. Conclusions: Available evidence suggests that thrombolytic therapy may be a viable life-saving option in carefully selected thrombocytopenic patients with high-risk pulmonary embolism. Therapeutic decisions should prioritize clinical severity and hemodynamic status over platelet count alone, emphasizing individualized, multidisciplinary risk–benefit assessment. Full article