Search Results (208)

Animal venoms are complex biochemical secretions rich in highly potent and selective bioactive molecules, including peptides, enzymes, and small organic compounds. Once associated primarily with toxicity, these venoms are now recognized as a promising source of therapeutic agents for a wide range of medical conditions. This review provides a comprehensive analysis of the pharmacological potential of venom-derived compounds, highlighting their mechanisms of action, such as ion channel modulation, receptor targeting, and enzyme inhibition. Successful venom-derived drugs like captopril and ziconotide exemplify the translational potential of this biological arsenal. We discuss therapeutic applications in cardiovascular diseases, chronic pain, cancer, thrombosis, and infectious diseases, as well as emerging peptide candidates in clinical development. Technological advancements in omics, structural biology, and synthetic peptide engineering have significantly enhanced the discovery and optimization of venom-based therapeutics. Despite challenges related to stability, immunogenicity, and ecological sustainability, the integration of AI-driven drug discovery and personalized medicine is expected to accelerate progress in this field. By synthesizing current findings and future directions, this review underscores the transformative potential of animal venoms in modern pharmacotherapy and drug development. We also discuss current therapeutic limitations and how venom-derived compounds may address unmet needs in specific disorders. Full article

Background/Objectives: Erysipelas is an acute bacterial skin infection, particularly affecting the lower limbs, with a tendency to recur. Despite its clinical importance, data on demographic and epidemiological risk factors, as well as factors influencing hospitalization, remain limited. This study aimed to analyze the epidemiological and clinical characteristics of patients hospitalized with primary and recurrent erysipelas, focusing on risk factors contributing to disease onset, recurrence, and prolonged hospitalization. Methods: A retrospective single-center analysis was conducted on 239 patients hospitalized for erysipelas at the Department of Dermatology, Pediatric Dermatology, and Oncology at the Medical University of Lodz. Data collected included demographics, lesion location, laboratory markers, comorbidities, and hospitalization outcomes. Statistical analyses were performed to assess associations between risk factors, disease recurrence, and hospitalization duration. Results: The majority of erysipelas cases (85.4%) involved the lower limbs, with a higher prevalence in men. Upper extremities were mostly affected in women, especially those who had undergone breast cancer surgery. Recurrent erysipelas accounted for 75.7% of cases. Most patients (89.1%) had at least one comorbidity, with hypertension, diabetes type 2 (DM2), and obesity being the most common. Higher white blood cell (WBC) count, obesity, atrial fibrillation (AF), and the need for enoxaparin administration were independently associated with prolonged hospitalization. Dyslipidemia was significantly associated with erysipelas recurrence (p < 0.05). Conclusions: Both primary and recurrent erysipelas are associated with specific risk factors. Recurrent erysipelas may be linked to components of metabolic syndrome, particularly obesity and dyslipidemia, which emerged as a significant risk factor in this study. Hospitalization length may be prolonged by inflammation markers (WBC and CRP) and comorbidities such as AF, obesity, or the need for enoxaparin in patients with elevated thrombosis risk. Further multicenter studies with larger cohorts are needed to assess the impact of demographics, biomarkers, metabolic disorders, and treatment strategies on erysipelas recurrence and outcomes. Awareness of these risk factors is essential for effective prevention, management, and recurrence reduction. Full article

Venous thromboembolism (VTE) represents a significant complication of cancer immunotherapy, with emerging evidence suggesting distinct pathophysiological mechanisms compared to traditional chemotherapy-associated thrombosis. This narrative review examines the epidemiology and pathogenesis of VTE in patients receiving immunotherapies for cancer including immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T-cell therapy, bispecific T-cell engagers (BiTEs), among others. Real-world studies demonstrate a wide range of VTE incidence rates in ICI recipients, with potential mechanisms including exacerbated underlying interleukin-8-mediated inflammatory pathways and consequent neutrophil extracellular trap (NET) formation. CAR T-cell therapy is associated with unique hemostatic challenges, including concurrent thrombotic and bleeding risks related to cytokine release syndrome. Current risk assessment tools show limited predictive utility in patients receiving immunotherapies for cancer, highlighting the need for novel stratification models. Future research priorities include developing immunotherapy-specific risk prediction tools, elucidating mechanistic pathways linking immune activation to thrombosis, and establishing evidence-based and tailored thromboprophylaxis strategies. As cancer immunotherapy continues to evolve, understanding and mitigating thrombotic complications remains crucial for optimizing patient outcomes. Full article

Gynecological malignancies (ovarian, endometrial, and cervical cancers), including disseminated intravascular coagulation (DIC), often provoke systemic coagulopathy. In recent years, tumor-derived, tissue factor–positive microparticles (TF⁺ MPs) have emerged as potent drivers of cancer-associated thrombosis and possibly DIC. These small (0.1–1 µm) membrane vesicles bud from cancer cell surfaces and carry procoagulant factors (phosphatidylserine and TF) on their surface. We review how TF⁺ MPs are generated by tumor cells and amplify the extrinsic coagulation cascade, potentially triggering DIC in patients with advanced gynecologic cancers. Clinical studies have linked el evated TF⁺ MP levels and activity to venous thromboembolism (VTE) in cancer, and small case series suggest dramatically high MP–TF activity in cancer-related DIC. We summarize evidence that TF⁺ MPs from ovarian tumors carry exceptionally high TF procoagulant activity (median ~80 pg/mL), and nearly all patients with cancer-associated VTE or DIC have MP–TF levels above normal. This review discusses diagnostic implications (e.g., measuring MP–TF activity as a biomarker) and treatment strategies (through the reduction in tumors, anticoagulation, and experimental TF inhibitors) in this setting. We also identify gaps in knowledge (standardized MP assays, prospective studies) and propose future directions (targeting MP formation or TF signaling). Two summary tables highlight recent studies of TF⁺ MPs in gynecologic cancer and their clinical outcomes. Illustrative figures depict the TF⁺ MP-triggered coagulation cascade and a conceptual framework for clinical management. Understanding TF⁺ MPs in gynecological cancer could improve the prediction and management of DIC and related thromboses. Full article

Thrombosis is a common complication in cancer patients, with a substantial impact on morbidity and mortality. Diffuse large B-cell lymphoma (DLBCL) and other aggressive lymphomas carry a high venous thromboembolism (VTE) risk. Extracellular vesicles (EVs) have gained attention in recent research as a new potential biomarker for VTE development. To determine the profile and association of EVs with VTE in patients with DLBCL, we conducted a prospective cohort study on 62 patients diagnosed with DLBCL. A total of 11 patients (17.7%) developed VTE. The concentrations of platelet-derived EVs (PEVs), E-selectin+ EVs, P-selectin+ EVs, tissue factor (TF)-positive/CD20+ EVs, TF−/CD19+ EVs, TF−/CD45+ EVs, and TF−/CD20+ EVs were significantly higher in DLBCL patients compared to healthy controls. In contrast, the concentration of TF− PEVs was significantly lower in DLBCL patients compared to healthy controls. No statistically significant differences were observed in the concentrations of the EV profiles among the DLBCL patients with and without VTE. Using Cox regression analysis, we found that none of the observed EV populations demonstrated an association with overall survival (OS). In conclusion, patients with DLBCL have elevated concentrations of distinct EV populations—in particular, PEVs, E-selectin EVs, P-selectin EVs, TF+/CD20+ EVs, and TF− DLBCL/B-cell EVs (CD19, CD20, CD45)—compared to healthy controls. DLBCL patients exhibit a specific EV profile, which is not significantly related to the risk of VTE and OS outcomes. Our data provide an intriguing insight into EV profiles in patients with DLBCL. Additional research is needed to elucidate these findings further. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but their association with thrombosis presents significant clinical challenges. Patients with cancer already exhibit elevated risks for venous thromboembolism and arterial thrombosis, with treatment modalities like chemotherapy further exacerbating this risk. Emerging evidence suggests that ICIs contribute to thrombotic events through multifactorial mechanisms, including immune dysregulation, T cell activation, endothelial dysfunction, elevated tissue factor expression, and impaired fibrinolysis. Additional risk factors such as obesity, smoking, prior thrombotic events, and combination ICI therapy further increase thrombosis susceptibility. The literature reports varying incidence rates of ICI-associated thrombosis, with some studies indicating comparable risks to chemotherapy, while others highlight higher rates, particularly during the initial treatment phase. Management aligns with standard protocols for cancer-associated thrombosis, using low-molecular-weight heparin or direct oral anticoagulants, though optimal treatment duration and the role of prophylactic anticoagulation require further investigation. This review provides a comprehensive overview of the mechanisms, incidence rates, and clinical management strategies of ICI-associated thrombosis, emphasizing the importance of proactive risk assessment to optimize patient outcomes. Full article

Direct oral anticoagulants (DOACs) have emerged as a preferred alternative to vitamin K antagonists (VKAs) for the prevention and treatment of thromboembolic disorders, offering improved safety, predictable pharmacokinetics, and ease of administration. Despite these advantages, their use in complex clinical scenarios presents significant challenges that necessitate individualized therapeutic strategies. This comprehensive review explores the efficacy, safety, and limitations of DOAC therapy in special populations, including patients with renal or hepatic impairment, obesity, cancer-associated thrombosis, and antiphospholipid syndrome. Additionally, we examine their role in uncommon thrombotic conditions such as superficial venous thrombosis, embolic stroke of undetermined source, upper extremity vein thrombosis, inferior vena cava thrombosis, pelvic vein thrombosis, and cerebral vein thrombosis. The pharmacokinetic variability of DOACs in renal and hepatic dysfunction requires caution to balance the bleeding and thrombotic risks. In obesity, altered drug distribution and metabolism raise concerns regarding appropriate dosing and therapeutic efficacy. Cancer-associated thrombosis presents a complex interplay of prothrombotic mechanisms, necessitating careful selection of anticoagulant therapy. Furthermore, the use of DOACs in antiphospholipid syndrome remains controversial due to concerns about recurrent thrombotic events. Finally, in some unusual scenarios like inferior vena cava, pelvic vein, and cerebral vein thrombosis, the use of DOACs has scarce evidence. This review aims to guide clinicians in optimizing anticoagulation management in challenging patient populations by synthesizing current evidence and providing practical recommendations. Full article

Venous thromboembolism (VTE) is considered the most common and potentially life-threatening cardiovascular complication in cancer and the second leading cause of death after cancer progression itself. In recent years, the steadily increasing rate of cancer-associated thrombosis (CAT) seems mainly related to amelioration in imaging techniques and the placements of central venous catheters (CVCs). The pivotal role of CVCs in the switch from hospital to home care is offset by its high thrombotic burden. The peripherally inserted central catheter (PICC) offers advantages (convenience, fast access, and cost-effectiveness) in comparison to centrally inserted devices (PORT), but increased thrombotic risk is reported. The aim of this narrative review was to offer a comprehensive overview of the existing literature about PICC-related thrombosis (PICC-VTE) by analyzing the current knowledge and related gaps. We further discussed advancements in insertion techniques, underscored the role of the novel PICC-PORT lines, and provided a “head-to-head” comparison among major guidelines on primary thromboprophylaxis. Full article

Background: Mycotic aneurysms of the subclavian artery are infrequent and pose significant diagnostic challenges, particularly in the context of recurrent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. The concomitant presence of upper extremity deep vein thrombosis (UEDVT) further complicates the management of bleeding risk and the necessity for anticoagulation therapy. Methods: This report discusses a 75-year-old male patient with a medical history of lung and skin cancer undergoing immunotherapy who presented with a swollen and painful right arm. Ultrasound examination identified deep vein thrombosis in the right axillary and basilic veins, and blood cultures confirmed MRSA infection. Subsequent imaging revealed bilateral subclavian artery aneurysms with contained ruptures involving previously placed stent grafts. Emergent endovascular interventions were performed to prevent catastrophic hemorrhage. Results: Despite the initial interventions, concerns regarding infected stent grafts persisted due to ongoing MRSA bacteremia and the presence of an endoleak. The complexity of balancing anticoagulation for DVT with the risk of aneurysm rupture necessitated the patient’s transfer to a tertiary care center for potential open surgical debridement. Conclusions: This case underscores the diagnostic and therapeutic challenges associated with the simultaneous occurrence of vascular infection, thrombosis, and aneurysmal pathology. Although emergency endovascular repair provided temporary hemostatic control, definitive management may require graft removal if stent infection is confirmed. Optimal care in such complex clinical scenarios demands a multidisciplinary approach and may necessitate advanced surgical interventions. Full article

Current research demonstrates the expanding therapeutic potential of heparin derivatives in oncology, extending beyond traditional anticoagulation mechanisms. This systematic analysis examines the structural characteristics, molecular mechanisms, and therapeutic applications of heparin-based compounds in malignancy treatment. The essential antithrombin binding pentasaccharide sequence has enabled development of specialized molecular variants, particularly fractionated heparins and their non-anticoagulant counterparts. These agents exert antineoplastic effects via multiple pathways, particularly through modulation of heparanase enzymatic activity and specific protein–glycosaminoglycan interactions. Evidence from pivotal clinical trials (FRAGMATIC, MAGNOLIA, GASTRANOX) confirms efficacy in managing cancer-associated thrombosis while indicating potential enhancement of chemotherapeutic outcomes. The preparation methods utilize enzymatic cleavage reactions and selective chemical derivatization to generate structurally modified heparins exhibiting unique molecular characteristics and biological activities. Analysis of the glycosaminoglycan analog dociparstat sodium reveals significant activity in myeloid malignancies, mediated by specific interference with CXCL12/CXCR4 signaling cascades. Significant challenges remain in manufacturing scale-up, analytical validation, and long-term safety assessment. Future studies must address dose optimization, combination strategies, and controlled clinical trials to determine the full therapeutic potential of these compounds in clinical oncology. Full article

Background: Patients with cancer often develop a prothrombotic state that can evolve into venous and arterial thrombosis, which is associated with poor clinical outcomes. Glioblastoma multiforme (GBM) is the most frequently associated with thrombosis, but the underlying causes of this prothrombotic state are poorly defined. Objectives: We designed a study to characterize the expression of coagulation factor X (FX) and its alternatively spliced transcripts in glioblastoma tissues surgically removed from patients and in clonal cell lines. Methods: The F10 mRNA and FX protein were quantified in tissues surgically removed from seven patients with glioblastoma (glioma grade 3–4) and those from non-tumor patients. Glioblastoma cells from three human clonal lines were examined for the expression and secretion of FX at baseline and after the cells were stimulated with lipopolysaccharide (LPS) or subjected to oxygen/glucose starvation in culture. PCR products were subjected to Sanger sequencing and amplicon sequencing to identify F10 isoforms and their ratios. A chromogenic assay was performed to assess FX activity. Results: Glioblastoma tissue and cell lines expressed high levels of the full-length and an alternatively spliced F10 mRNA. The latter produced a C-terminal truncated FX. The ratio of full-length to truncated F10 transcripts was significantly higher in normal brain tissues than in glioblastoma tissue. In cultured cells from the glioblastoma cell lines, FX was secreted to the conditioned medium and was active in cleaving a chemical substrate. The FX expression and secretion were upregulated in cells stimulated with LPS or subjected to oxygen/glucose starvation. Discussion: Glioblastoma cells synthesize and secrete FX that was active in promoting thrombin generation. These findings provide a new underlying mechanism to explain why glioblastoma patients are prone to developing thrombosis. Full article

Introduction: Venous thromboembolism (VTE) is a major cause of non-cancer-related mortality in cancer patients. Understanding how demographic factors and cancer types influence VTE risk is critical for developing prevention strategies. This study investigates the incidence of VTE in a large cancer patient population, focusing on gender, race, and differences between solid and hematological malignancies. Methods: Data from the National Inpatient Sample (NIS) database were used to identify cancer patients diagnosed with acute VTE. The patients were divided into those with solid and hematological cancers. Key demographic and clinical characteristics were collected, and patients were matched 1:1 using propensity scoring. Statistical analyses, including logistic regression, assessed VTE incidence and its associations with demographic and cancer type variables. A p-value of <0.05 indicated statistical significance. Results: Out of 1,233,832 cancer patients, 63,505 (5.1%) were diagnosed with acute VTE. Females had a higher VTE rate than males (5.5% vs. 4.8%, p < 0.001). Racial disparities showed Black patients with the highest incidence (6.4%), followed by White patients (5%). Patients with solid malignancies exhibited a significantly higher incidence of VTE compared to those with hematological malignancies (5.4% vs. 4.1%; p < 0.001), with lung cancer and non-Hodgkin lymphoma mostly associated with VTE. Conclusions: This study identifies demographic and cancer-specific differences in VTE risk, emphasizing the need for personalized prevention. High-risk groups, including those with solid tumors, females, and Black patients, may benefit from targeted strategies to reduce the burden of VTE and improve cancer outcomes. Full article

The local expression of coagulation-related genes defines the tumor coagulome. The tumor coagulome plays a pivotal role in cancer-associated thrombosis (CAT) and hemostatic complications, such as venous thromboembolism (VTE), which are frequent in patients with advanced/metastatic cancer. Genomic analyses of human tumors, such as skin cutaneous melanoma (SKCM), have unveiled the complexity of the metastatic trajectories. However, no study to date has focused on the metastatic coagulome along these trajectories. Using bulk-tumor and single-cell analyses of primary SKCM, metastastic samples and circulating tumor cells (CTCs), we explored the coagulome of SKCM along metastatic progression. We identified consistent changes in the coagulome of SKCM metastases compared to primary tumors and observed metastatic site specificity. Compared to other metastatic sites, lung metastases of SKCM had a specific coagulome with a higher expression of F3, encoding Tissue Factor. Single-cell analyses were used to chart the inter- and intra-tumor heterogeneity and characterize the metastatic coagulome of SKCM. We found that a subpopulation of CTCs from SKCM expressed high levels of platelet genes, suggesting the contribution of CTC–platelet interactions to the CTC coagulome. These findings highlight the dynamic properties of the metastatic coagulome and its link to cancer progression. Full article

Resting sinus tachycardia is frequently encountered in cancer patients. It affects a wide variety of cancer patients and is associated with distressing symptoms. Cancer-associated resting sinus tachycardia varies in its underlying mechanism. It can stem from the tumor burden or the side effects of chemotherapy/radiotherapy, or it can be secondary to paraneoplastic syndrome or the sequalae of cancer itself (infection, anemia, thrombosis, etc.). The clinical significance of resting sinus tachycardia extends beyond mere symptomatology, as it can potentially indicate severe complications which may facilitate or exacerbate a new or underlying cardiovascular dysfunction. Therefore, this necessitates thorough diagnostic tools to discern the underlying cause and tailor appropriate management strategies, whether pharmacological, non-pharmacological, or conservative. While resting sinus tachycardia has been extensively investigated in the context of cardiovascular disease, its underlying etiology, clinical implication, prognostic value, and treatment options remain vague in the context of cancer. This review aims to explore the topic of resting sinus tachycardia in cancer patients through delving deeper into its underlying mechanism, presenting the current evidence on its effect on cancer-independent cardiovascular and all-cause mortality, as well as providing some insight into the currently available treatment options. It will also propose therapeutic interventions and strategies aimed at optimizing cancer patient care. Lastly, it will highlight research gaps which need to be addressed further, as future research is needed to refine the diagnostic criteria, develop targeted therapies, find alternative cardioprotective/cardio-neutral chemotherapy options, and establish evidence-based guidelines to improve outcomes in this vulnerable patient population. Full article

Background: The purpose of this article is to overview the clinical significance of left supraclavicular adenopathy and review the etiology of inferior vena cava (IVC) thrombosis, starting from a presentation of a rare case of renal cell carcinoma (RCCs) with Xp11.2 translocation involving TFE3 gene fusion. This article also aims to review the literature to understand the characteristics of this rare type of renal tumor. Renal cell carcinoma (RCC) associated with Xp11.2 translocation/gene fusion TFE3 is a rare subtype of kidney cancer that was classified in 2016 as belonging to the family of renal carcinomas with MiT gene translocation (microphthalmia-associated transcription factor). The prognosis for these kidney cancers is poorer compared to other types. Methods: We present a case of a 66-year-old man with Virchow–Troisier adenopathy during physical examination, which raises the suspicion of infra-diaphragmatic tumor. The echocardiography highlighted a heterogeneous mass in the right cardiac cavities, and the abdominal ultrasound exam revealed a solid mass at the upper pole of the left kidney. Results: Following computed tomography, magnetic resonance imaging, PET-CT, and histopathological and immunohistochemical examinations, the patient was diagnosed with renal carcinoma with Xp11.2 translocation and TFE3 gene fusion. Conclusions: IVC thrombosis is often associated with neoplastic disease due to the procoagulant state of these patients, the most common malignancies related to IVC thrombosis being represented by RCCs (38%), genitourinary cancers (25%), bronchus and lung cancers, retroperitoneal leiomyosarcoma, and adrenal cortical carcinoma. Imaging methods play a crucial role in differential diagnosis, allowing for the localization of the primary tumor and assessment of its characteristics. Full article