Microwave Thermal Ablation for Breast Cancer in Africa: A Pioneering Case Report Utilizing TATOpro.

The adoption of minimally invasive treatments for early-stage breast cancer is increasing. Microwave thermal ablation (MWA), a minimally invasive technique, has been studied for treating small breast cancer lesions. However, long-term evidence on its efficacy as a sole treatment is limited, as most studies combine MWA with other therapies and post-treatment surgical excision. This report details the case of an 83-year-old African patient who declined surgery and systemic therapies, opting for MWA using the TATOpro system as the sole treatment for contralateral breast cancer with axillary lymph node metastasis. The report includes a one-year follow-up, assessing disease recurrence with MRI and ultrasound. The findings highlight MWA's potential as an innovative and efficacious breast cancer treatment, emphasizing the need for adaptable strategies in oncology.

Hybrid argon plasma coagulation for the treatment of Barrett's esophagus: A prospective, multicenter study.

BACKGROUND: The incidence of Barrett's esophagus (BE) in China is lower compared to the Western populations. Hence, studies conducted in the Chinese population has been limited. The current treatment options available for BE treatment includes argon plasma coagulation (APC), radiofrequency ablation and cryoablation, all with varying degrees of success. AIM: To determine the efficacy and safety of HybridAPC in the treatment of BE. METHODS: The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment. These procedures were performed by seven endoscopists from different tertiary hospitals. The duration of the procedure, curative rate, complications and recurrent rate by 1-year follow-up were recorded. RESULTS: Eighty individuals were enrolled for treatment from July 2017 to June 2020, comprising of 39 males and 41 females with a median age of 54 years (range, 30 to 83 years). The technical success rate of HybridAPC was 100% and the overall curative rate was 98.15%. No severe complications occurred during the operation. BE cases were classified as short-segment BE and long-segment BE. Patients with short-segment BE were all considered cured without complications. Thirty-six patients completed the one-year follow-up without recurrence. Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment. The mean duration of the procedure was 10.94 ± 6.52 min. CONCLUSION: Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up, especially in cases of short-segment BE. This technique could be considered as a feasible alternative ablation therapy for BE.

Effect of CNT Oxidation on the Processing and Properties of Superacid-Spun CNT Fibers.

Spinning fibers from carbon nanotube (CNT)/superacid dispersions has emerged as a promising strategy for industrial-scale production of high-performance CNT fibers (CNTFs). The oxygen content and types of functional groups on CNT surfaces significantly influence dispersion, assembly processes, and fiber properties. In this study, Tuball-SWCNTs were purified and oxidized at varying levels. The dispersion behavior of CNTs with different oxidation levels in chlorosulfonic acid was systematically observed, and the mechanical properties of fibers spun from these dispersions were compared. By adjusting the dispersion concentration, highly oriented CNTFs were produced with a specific strength of 1.03 N/tex, a tensile strength of 1.59 GPa, and an electrical conductivity of 3.58 MS/m. Further investigations indicated that oxygen-containing functional groups decrease the coagulation rate, increasing the maximum draw ratio during spinning and improving CNT alignment in the fibers. Molecular dynamics simulations demonstrated that these functional groups (-OH, -COOH) enhance load transfer between CNTs through hydrogen bonding. This specific strength is the highest achieved using Tuball-SWCNTs for superacid-spun fibers, surpassing previous works due to the oxidation-controlled coagulation rate, enhanced fiber orientation, and improved load transfer via hydrogen bonding. This study provides insights for designing and optimizing high-performance CNTFs.

Assessment of short-term results of thrombosuction during primary percutaneous coronary intervention in patients with acute myocardial infarction.

Aim: The study investigated the short-term outcomes of thrombosuction during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction. Materials & methods: The study consisted of 57 patients who underwent primary or rescue PCI. The effect of thrombosuction on thrombolysis in myocardial infarction (TIMI) flow, failure to restore blood flow in the target vessel, and occurrence of mortality were reviewed in patients. Results: Thrombosis was performed in 45.61% of patients. Thrombosuction during PCI resulted in significant incremental TIMI-flow changes in this group of patients compared with patients who did just PCI. In 86.6%, these changes were three-degree and the initial TIMI-flow has changed from 0 to 3. Conclusion: The number of patients who underwent rescue PCI was higher than the smaller number of individuals who underwent thrombosuction.

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Pilot Assessment of Platelet Thrombus Area and Contractile Force in Pediatric Congenital Heart Surgery Patients Using a Microfluidic Device.

OBJECTIVES: This work was designed to evaluate maximum platelet contractile force and thrombus area before and after cardiopulmonary bypass (CPB) in pediatric patients having congenital heart disease (CHD) surgery using a microfluidic device. DESIGN: A prospective cohort study was designed. SETTING: The work took place at an academic medical center. PARTICIPANTS: Twenty pediatric CHD patients ≤8 years of age with expected CPB time >30 minutes were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood was collected at baseline and post-CPB. Maximum platelet contractile force and thrombus area were evaluated in vitro using a microfluidic device (ATLAS PST). Post-CPB samples were supplemented with recombinant von Willebrand factor (rVWF) to explore the impact on contractile force and thrombus area. At baseline, the maximum thrombus area was 0.06 (0.05, 0.07), and the maximum force was 123.3 nN (68.4, 299.5). Linear mixed-effects regression models showed that the maximum thrombus area was larger post-CPB and post-CPB + rVWF compared with pre-CPB (estimated coefficient [Est] = 0.04, p = 0.002; Est = 0.09, p < 0.001, respectively). The maximum thrombus area was also larger post-CPB + rVWF compared with post-CPB (Est = 0.04, p = 0.001). Force was higher post-CPB + rVWF compared with pre-CPB (Est = 173.32, p = 0.044). CONCLUSIONS: In pediatric CHD patients, microfluidic testing demonstrated that platelet thrombus area increased slightly after CPB, while platelet contractile force did not change. In vitro addition of rVWF further increased thrombus area, suggesting augmentation of primary hemostasis. Microfluidic assessment of platelet contractile force and thrombus area in pediatric CHD patients appears feasible and can demonstrate changes after CPB. Further studies are needed to determine its accuracy, clinical utility, and normal values for pediatric patients.

Sheehan's Syndrome in a Patient With Factor XI Deficiency.

Sheehan's syndrome (SS) is a condition characterized by panhypopituitarism that generally occurs after an episode of postpartum bleeding. There are certain hypotheses regarding the development of SS in the postpartum period. Coagulation factor abnormalities have been reported to be associated with SS. Associated hypothyroidism and hypocortisolism have been found to cause coagulation abnormalities. After the correction of the hypothyroidism and hypocortisolism, there is a gradual correction of the coagulation abnormality. In our case, a middle-aged woman presented with recurrent episodes of hospital admission because of generalized weakness and fever. She was found to have a biochemistry profile suggestive of hypopituitarism with preserved gonadal function. Her hemogram was normal, but the coagulogram showed a prolongation of activated partial thromboplastin time with a near-normal prothrombin time. She was evaluated and found to have factor XI deficiency. In the background of excessive vaginal bleeding and hypopituitarism, a diagnosis of SS was made. The presence of factor XI deficiency may have led to excessive bleeding and the development of SS. To the best of our knowledge, there is no reported association of factor XI deficiency with SS in the literature, and this is the first reported case.

Ferrate as a coagulant prior to sand filters treating secondary wastewater effluent for reuse.

Wastewater reuse is one of the crucial water resources in Egypt due to the ongoing need to increase water resources and close the supply-demand gap. In this study, a new coagulant has been investigated before sand filters as an advanced wastewater treatment method. The sand filter pilot was run at a hydraulic loading rate of 0.75 m/h and two different dosages of three coagulants (Alum, FeCl3, and Ferrate VI) were selected using the jar tests. The sand filter without coagulant removed 12% of BOD5 and 70% of turbidity. Applying in-line coagulation before the sand filter provided effluents with better quality, especially for turbidity, organics, and microorganisms. Ferrate provided the highest removal of turbidity (90%) and BOD5 (93%) at very low dosages and lower costs compared with other coagulants, however, it adversely impacted both conductivity and dissolved solids. A significant effect on reducing bacteria was obtained with 40.0 mg/L of alum. According to the study's findings, the ferrate coagulant enhanced the sand filter's performance producing effluents with high quality, enabling it to meet strict water reuse regulations as well as aquatic environmental and health preservations.

Salvianolic acid B inhibits thrombosis and directly blocks the thrombin catalytic site.

Background: Salvianolic acid B (SAB) is a major component of Salvia miltiorrhiza root (Danshen), widely used in East/Southeast Asia for centuries to treat cardiovascular diseases. Danshen depside salt, 85% of which is made up of SAB, is approved in China to treat chronic angina. Although clinical observations suggest that Danshen extracts inhibited arterial and venous thrombosis, the exact mechanism has not been adequately elucidated. Objective: To delineate the antithrombotic mechanisms of SAB. Methods: We applied platelet aggregation and coagulation assays, perfusion chambers, and intravital microscopy models. The inhibition kinetics and binding affinity of SAB to thrombin are measured by thrombin enzymatic assays, intrinsic fluorescence spectrophotometry, and isothermal titration calorimetry. We used molecular in silico docking models to predict the interactions of SAB with thrombin. Results: SAB dose-dependently inhibited platelet activation and aggregation induced by thrombin. SAB also reduced platelet aggregation induced by adenosine diphosphate and collagen. SAB attenuated blood coagulation by modifying fibrin network structures and significantly decreased thrombus formation in mouse cremaster arterioles and perfusion chambers. The direct SAB-thrombin interaction was confirmed by enzymatic assays, intrinsic fluorescence spectrophotometry, and isothermal titration calorimetry. Interestingly, SAB shares key structural similarities with the trisubstituted benzimidazole class of thrombin inhibitors, such as dabigatran. Molecular docking models predicted the binding of SAB to the thrombin active site. Conclusion: Our data established SAB as the first herb-derived direct thrombin catalytic site inhibitor, suppressing thrombosis through both thrombin-dependent and thrombin-independent pathways. Purified SAB may be a cost-effective agent for treating arterial and deep vein thrombosis.

Mass spectrometry-based proteomic profiling of extracellular vesicle proteins in diabetic and non-diabetic ischemic stroke patients: a case-control study.

Acute ischemic stroke is the most common cause of neurologic dysfunction caused by focal brain ischemia and tissue injury. Diabetes is a major risk factor of stroke, exacerbating disease management and prognosis. Therefore, discovering new diagnostic markers and therapeutic targets is critical for stroke prevention and treatment. Extracellular vesicles (EVs), with their distinctive properties, have emerged as promising candidates for biomarker discovery and therapeutic application. This case-control study utilized mass spectrometry-based proteomics to compare EVs from non-diabetic stroke (nDS = 14), diabetic stroke (DS = 13), and healthy control (HC = 12) subjects. Among 1288 identified proteins, 387 were statistically compared. Statistical comparisons using a general linear model (log2 foldchange ≥0.58 and FDR-p≤0.05) were performed for nDS vs HC, DS vs HC, and DS vs nDS. DS vs HC and DS vs nDS comparisons produced 123 and 149 differentially expressed proteins, respectively. Fibrinogen gamma chain (FIBG), Fibrinogen beta chain (FIBB), Tetratricopeptide repeat protein 16 (TTC16), Proline rich 14-like (PR14L), Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKKE), Biorientation of chromosomes in cell division protein 1-like 1 (BD1L1), and protein PR14L exhibited significant differences in the DS group. The pathway analysis revealed that the complement system pathways were activated, and blood coagulation and neuroprotection were inhibited in the DS group (z-score ≥2; p ≤ 0.05). These findings underscore the potential of EVs proteomics in identifying biomarkers for stroke management and prevention, warranting further clinical investigation.

Clinical significance, molecular characterization, and immune microenvironment analysis of coagulation-related genes in clear cell renal cell carcinoma.

Background: Numerous studies have revealed a tight connection between tumor development and the coagulation system. However, the effects of coagulation on the prognosis and tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) remain poorly understood. Methods: We employed the consensus clustering method to characterize distinct molecular subtypes associated with coagulation patterns. Subsequently, we examined variations in the overall survival (OS), genomic profiles, and TME characteristics between these subtypes. To develop a prognostic coagulation-related risk score (CRRS) model, we utilized the least absolute shrinkage and selection operator Cox regression and stepwise multivariate Cox regression analyses. We also created a nomogram to aid in the clinical application of the risk score, evaluating the relationships between the CRRS and the immune microenvironment, responsiveness to immunotherapy, and targeted treatment. The clinical significance of PLAUR and its biological function in ccRCC were also further analyzed. Results: There were significant differences in clinical features, prognostic stratification, genomic variation, and TME characteristics between the two coagulation-related subtypes. We established and validated a CRRS using six coagulation-related genes that can be employed as an effective indicator of risk stratification and prognosis estimation for ccRCC patients. Significant variations in survival outcomes were observed between the high- and low-risk groups. The nomogram was proficient in predicting the 1-, 3-, and 5-year OS. Additionally, the CRRS emerged as a novel tool for evaluating the clinical effectiveness of immunotherapy and targeted treatments in ccRCC. Moreover, we confirmed upregulated PLAUR expression in ccRCC samples that was significantly correlated with poor patient prognosis. PLAUR knockdown notably inhibited ccRCC cell proliferation and migration. Conclusion: Our data suggested that CRRS may be employed as a reliable predictive biomarker that can provide therapeutic benefits for immunotherapy and targeted therapy in ccRCC.

Quantification of the contribution of individual coagulation factors to haemostasis using a microchip flow chamber system and reconstituted blood from deficient plasma.

BACKGROUND AND OBJECTIVES: Quantifying the contribution of individual coagulation factors to haemostasis may aid our understanding of the haemostatic function in patients with rare coagulation deficiencies (RCDs) and the exploration of suitable treatments. MATERIALS AND METHODS: Reconstituted blood prepared from specific coagulation factor-deficient plasma (factor [F]II; prothrombin, FV, FVII, FVIII, FIX, FX, FXI or FXII) and red blood cell/platelet products were used to simulate the whole blood of patients with RCD. We prepared in vitro treatment models for patients with prothrombin deficiency using coagulation factor agents and fresh frozen plasma. Haemostatic function was measured using a microchip flow chamber system at 600 s-1. RESULTS: The haemostatic function was low, especially in blood samples reconstituted with prothrombin- and FX-deficient plasma. In a plasma transfusion model of prothrombin deficiency, haemostatic function recovered after 10% replacement with normal plasma and reached a plateau at ≧60% replacement. A treatment model of prothrombin deficiency with prothrombin complex concentrates revealed dose-dependent therapeutic effects in the range of 0-50 IU/kg. CONCLUSION: Microchip flow chamber system-based quantification of haemostatic function using reconstituted blood could predict haemostasis and therapeutic effects of treatments in patients with prothrombin deficiency.

The Prothrombin-Prothrombinase Interaction.

The hemostatic response to vascular injury entails a sequence of proteolytic events where several inactive zymogens of the trypsin family are converted to active proteases. The cascade starts with exposure of tissue factor from the damaged endothelium and culminates with conversion of prothrombin to thrombin in a reaction catalyzed by the prothrombinase complex composed of the enzyme factor Xa, cofactor Va, Ca2+, and phospholipids. This cofactor-dependent activation is paradigmatic of analogous reactions of the blood coagulation and complement cascades, which makes elucidation of its molecular mechanism of broad significance to the large class of trypsin-like zymogens to which prothrombin belongs. Because of its relevance as the most important reaction in the physiological response to vascular injury, as well as the main trigger of pathological thrombotic complications, the mechanism of prothrombin activation has been studied extensively. However, a molecular interpretation of this mechanism has become available only recently from important developments in structural biology. Here we review current knowledge on the prothrombin-prothrombinase interaction and outline future directions for the study of this key reaction of the coagulation cascade.

Identification and validation of a novel 17 coagulation-related genes signature for predicting prognostic risk in colorectal cancer.

Background: Patients with colorectal cancer commonly experience disturbances in coagulation homeostasis. Activation of the coagulation system contributes to cancer-associated thrombosis as the second risk factor for death in cancer patients. This study intended to discover coagulation-related genes and construct a risk model for colorectal cancer patients' prognosis. Methods: Coagulation-related genes were identified by searching coagulation-related pathways in the Molecular Signatures Database. Transcriptomic data and clinical data were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus datasets. Univariate Cox and backward stepwise regression were utilized to identify prognosis-related genes and construct a predictive risk model for the training cohort. Next, survival analysis determines the risk model's predictive power, correlation with clinicopathological characteristics, and nomogram. Additionally, we characterized the variances in immune cell infiltration, somatic mutations, immune checkpoint molecules, biological functions, and drug sensitivity between the high- and low-score patients. Result: Eight hundred forty-five genes were obtained by searching the theme term "coagulation" after de-duplication. After univariate regression analysis, 69 genes correlated with prognosis were obtained from the Cancer Genome Atlas dataset. A signature consisting of 17 coagulation-related genes was established through backward stepwise regression. The Kaplan-Meier curve indicated a worse prognosis for high-score patients. Time-dependent receiver operating characteristic curve analysis demonstrated high accuracy in predicting overall survival. Further, the results were validated by two independent datasets (GSE39582 and GSE17536). Combined with clinicopathological characteristics, the risk model was proven to be an independent prognostic factor to predict poor pathological status and worse prognosis. Furthermore, high-score patients had significantly higher stromal cell infiltration. Low-score patients were associated with high infiltration of resting memory CD4+ T cells, activated CD4+ T cells, and T follicular helper cells. The low-score patients exhibited increased expression of immune checkpoint genes, and this might be relevant to their better prognosis. High-score patients exhibited lower IC50 values of Paclitaxel, Rapamycin, Temozolomide, Cyclophosphamide, etc. The differential signaling pathways mainly involve the calcium signaling pathway and the neuroactive ligand-receptor interaction. Lastly, a nomogram was constructed and showed a good prediction. Conclusion: The prognostic signature of 17 coagulation-related genes had significant prognostic value for colorectal cancer patients. We expect to improve treatment modalities and benefit more patients through research on molecular features.

A Rare Cause of Septicemia After Pork Meat Ingestion.

Streptococcus suis infection in humans occurs due to consuming raw or undercooked pork meat and after contact with pigs. The highest prevalence occurs in Southeast Asian countries, which have the largest pork industry. We report the first case of a 50-year-old healthy male patient from a rural area of São Paulo, Brazil, with septicemia from undercooked pork meat ingestion. The patient was diagnosed at the emergency department with septicemia and multiple organ dysfunctions, including streptococcal toxic shock syndrome. Blood cultures yielded the growth of S. suis. The patient was treated with ceftriaxone and was maintained for two weeks, according to sensitivity tests. The outcome was favorable but developed deafness as a sequela. This report aims to give importance to recognizing this disease regarding typical signs and symptoms and occupational and epidemiological history.

Development and internal validation of a model for predicting cefoperazone/sulbactam-associated coagulation disorders in Chinese inpatients.

BACKGROUND AND AIM: The use of cefoperazone/sulbactam (CPZ/SAM) could commonly cause vitamin K-dependent coagulation disorders and even hemorrhage sometimes. However, there is a lack of prediction tools estimating the risk for this. This study aimed at developing and internally validating a model for predicting CPZ/SAM-associated coagulation disorders in Chinese inpatients. METHODS: A case-control study was conducted in 11,092 adult inpatients admitted to a Chinese general hospital between 2020 and 2021 and treated with CPZ/SAM. Patients with CPZ/SAM-associated coagulation disorders were identified through the Adverse Drug Events Active Surveillance and Assessment System-II and subsequent manual evaluation. Controls were selected from eligible patients who didn't develop coagulation disorders after CPZ/SAM therapy, with a 1:1 propensity score matching. The final predictors were obtained by univariable and multivariable logistic regression analyses. Internal validation and calibration for the model were performed using 1000 bootstrap resamplings. RESULTS: 258 patients were identified as CPZ/SAM-associated coagulation disorders in 2184 patients eligible for inclusions and exclusions and the incidence was 11.8%. A final population of 252 cases and 252 controls was included for model development and validation. Malnutrition (OR = 2.41 (1.56-3.77)), history of recent bleeding (OR = 1.95 (1.32-2.90)), treatment duration (OR = 1.10 (1.07-1.14)), combination with carbapenems (OR = 4.43 (1.85-11.88)), and serum creatinine (OR = 1.01 (1.00-1.01)) were identified as final predictors. The model showed good discrimination, calibration, and clinical practicality, with the validated area under the receiver operating characteristic curve being 0.723 (0.683-0.770). CONCLUSIONS: The model with good performance quantifies the risk for CPZ/SAM-associated coagulation disorders, and may support individual assessment and interventions to mitigate the risk after external validation.

Glycemia and coagulation in patients with glioblastomas.

Glioblastomas are among the most malignant tumors which, despite aggressive treatment, currently have an abysmal prognosis. These lesions are known to cause local and systemic perturbations in the coagulation system, leading to neo-angiogenesis and a high risk of venous thromboembolism. Indeed, there have been multiple proposals of the coagulation system being a possible target for future treatment of these patients. However, non-selective anticoagulant therapy has proven suboptimal and leads to a significant increase of intracranial hemorrhage. Thus, recognizing factors which lead to hyper-coagulation is considered paramount. Hyperglycemia is a well-known pro-thrombotic factor, a fact which has received little attention in neuro-oncology so-far. We previously hypothesized that patients with brain tumors could be highly susceptible to iatrogenic glycemia dysregulation. Here, we analyzed the connection between glycated hemoglobin (HbA1c) and the routine coagulation markers (D-dimers, prothrombin time (PT) and activated partial thromboplastin time (aPTT)) in patients with de novo intracranial glioblastomas. Included in this study were 74 patients, operated on in three hospitals, Clinical Hospital Dubrava, Zagreb, Croatia; University Hospital Center Split, Split, Croatia and University Hospital de la Princesa, Madrid, Spain. We found a significant inverse correlation between HbA1c and aPTT (ρ=-0.379; P=0.0009). We also found a significant inverse correlation between Ki67 immunoreactivity and aPTT (ρ=-0.211; P=0.0082). No connection was found between HbA1c and D-dimers or PT. Our results suggest that hyperglycemic patients, with a more proliferative glioblastoma, could in fact have their coagulation profile significantly disrupted, primarily through the intrinsic coagulation pathway. Such findings could have great clinical importance. Further research in this area could help elucidate the vicious connection between glioblastomas and coagulation, and help combat the deadly disease.

Admission Viscoelastic Hemostatic Assay Parameters Predict Poor Long-Term Intracerebral Hemorrhage Outcomes.

BACKGROUND: Viscoelastic hemostatic assays (VHAs) provide more comprehensive assessments of coagulation compared with conventional coagulation assays. Although VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. METHODS: Patients with spontaneous ICH enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with previous anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. RESULTS: Of 44 patients analyzed, the mean age was 64 years, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64% of patients. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted odds ratio for every second increase in clot formation time 1.04, 95% confidence interval 1.00-1.09, p = 0.04) and weaker clot strength (adjusted odds ratio for every millimeter increase of maximum clot firmness 0.84, 95% confidence interval 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. CONCLUSIONS: Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA-guided treatments should be incorporated into ICH care.

Analysis of coagulation alteration and its correlation with ß2-microglobulin in 371 patients with newly diagnosed multiple myeloma.

OBJECTIVES: To explore the changes in the coagulation function of patients newly diagnosed with multiple myeloma (MM) at different stages and with different M protein types, and to analyze the correlation between coagulation indexes and ß2-microglobulin (ß2-MG). METHODS: A total of 371 Patients with newly diagnosed MM (n = 371) and healthy controls (n = 48) were selected from January 2016 to December 2022. Baseline data, ß2-MG and coagulation index values were collected. Indexes included prothrombin time (PT), activated partial thromboplastin time (APPT), fibrinogen (FIB), thrombin time (TT), fibrinogen degradation products (FDP), and D-dimer(D-D). Patients were divided into different groups according to the Durie-Salmon staging system (DS), the International Staging System (ISS) and disease classification (M protein type). The levels of these six indexes were compared among the groups and the correlation between each index and ß2-MG was analyzed. RESULTS: Compared to the normal control group, the levels of PT, FIB, TT, FDP and D-D in the MM group were significantly higher (all P < 0.001). As DS and ISS staging increased, the levels of PT, TT, FDP and D-D also increased significantly (all P < 0.001). ß2-MG was positively correlated with PT, TT, and FDP levels (Spearman r = 0.157, 0.270, 0.108, respectively; all P < 0.05), and negatively correlated with FIB (r = -0.220, P < 0.001). Significant differences existed in the levels of these six indexes among different M protein types (all P < 0.001). Among them, PT and APTT increased significantly in the IgA-κ group, FIB increased in the λ light chain group, TT increased in the IgG-κ group, FDP increased in the κ light chain group, and D-D increased in the IgG-λ group. CONCLUSIONS: The degree of coagulation dysfunction in MM patients increases with disease stage and abnormal increases of various coagulation indicators occur in different M protein types and are closely related to ß2-MG.

[Haemophilia B therapy: impact of the reimbursability of a long-acting recombinant factor on pharmaceutical expenditure in Italy]. / Terapia dell'emofilia B: impatto dell'ammissione alla rimborsabilità di un fattore ricombinante long-acting sulla spesa farmaceutica in Italia.

OBJECTIVES: to assess the variability in expenditure compared to 2022 assuming different rates of shifting of therapy days from current active ingredients used for the treatment of haemophilia B to nonacog beta pegolDesign: descriptive cross-sectional study. SETTING AND PARTICIPANTS: consumption in the year 2022 (data source: Medicines Utilisation Monitoring Centre, Italian Medicines Agency) of all medicinal products available in Italy containing coagulation factor IX. MAIN OUTCOMES MEASURES: for each active ingredient, the total number of therapy days and the variability in expenditure compared to 2022 were estimated on the basis of a switch of therapy days, between 5% and 20%, to nonacog beta pegol. RESULTS: on the basis of considered scenarios, the analysis shows that the total annual expenditure for clotting factors used in the treatment of haemophilia B could remain at most unchanged or reduced. Particularly, the extent of the reduction in spending could vary from 0.11% to 2.26%. This trend would be in contrast to the stable increase seen in recent years, particularly in 2022. CONCLUSIONS: this predictive spending assessment may be useful in evaluating the economic impact from new treatment options, such as etranacogene dezaparvovec gene therapy already approved by the European Medicines Agency and the Food and Drug Administration, and to improve pharmaceutical governance.

Using microfluidic shear to assess transfusion requirements in trauma patients.

Background: Viscoelastic assays have widely been used for evaluating coagulopathies but lack the addition of shear stress important to in vivo clot formation. Stasys technology subjects whole blood to shear forces over factor-coated surfaces. Microclot formation is analyzed to determine clot area (CA) and platelet contractile forces (PCFs). We hypothesize the CA and PCF from this novel assay will provide information that correlates with trauma-induced coagulopathy and transfusion requirements. Methods: Blood samples were collected on adult trauma patients from a single-institution prospective cohort study of high-level activations. Patient and injury characteristics, transfusion data, and outcomes were collected. Thromboelastography, coagulation studies, and Stasys assays were run on paired samples collected at admission. Stasys CA and PCFs were quantified as area under the curve calculations and maximum values. Normal ranges for Stasys assays were determined using healthy donors. Data were compared using Kruskal-Wallis tests and simple linear regression. Results: From March 2021 to January 2023, 108 samples were obtained. Median age was 37.5 (IQR 27.5-52) years; patients were 77% male. 71% suffered blunt trauma, 26% had an Injury Severity Score of ≥25. An elevated international normalized ratio significantly correlated with decreased cumulative PCF (p=0.05), maximum PCF (p=0.05) and CA (p=0.02). Lower cumulative PCF significantly correlated with transfusion of any products at 6 and 24 hours (p=0.04 and p=0.05) as well as packed red blood cells (pRBCs) at 6 and 24 hours (p=0.04 and p=0.03). A decreased maximum PCF showed significant correlation with receiving any transfusion at 6 (p=0.04) and 24 hours (p=0.02) as well as transfusion of pRBCs, fresh frozen plasma, and platelets in the first 6 hours (p=0.03, p=0.03, p=0.03, respectively). Conclusions: Assessing coagulopathy in real time remains challenging in trauma patients. In this pilot study, we demonstrated that microfluidic approaches incorporating shear stress could predict transfusion requirements at time of admission as well as requirements in the first 24 hours. Level of evidence: Level II.