Lysis In Patients Research Articles

Thrombin generation, fibrin clot permeation and lysis in patients with severe mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair: mitral fibrin study

Abstract Background/Introduction The management of heart failure (HF), particularly in the context of reduced ejection fraction, is further complicated by an increased risk of thromboembolic events. Structural alterations of both left ventricle and mitral valve contribute to mitral regurgitation (MR). However, the body of evidence provides inconclusive insights into the relationship between MR and thromboembolic risk. Purpose This study aimed to investigate the impact of transcatheter edge-to-edge repair (TEER) on thrombin generation, clot permeation and clot lysis time in HF patients with severe MR eligible for mitral TEER. Methods A cohort of 31 HF patients with severe MR undergoing TEER underwent systematic evaluation at three time points. Coagulation parameters, including fibrinogen concentration, thrombin generation, fibrin clot permeability (Ks), and clot lysis time (CLT), were assessed. Comprehensive evaluations also covered echocardiographic, laboratory, and clinical parameters. Results TEER induced changes in fibrinogen levels (p=0.009, visit 3 vs. visit 2) and improved fibrin clot properties over a 50-day follow-up (Ks, p=0.005, visit 3 vs. visit 2). No significant differences were observed among time points in analyzed blood clot parameters. Linear regression, incorporating thrombin generation variables, Ks, and CLT for delta NT-proBNP, highlighted CLT as the sole predictor of NT-proBNP change between visit 2 and visit 1 (p=0.03; R2=0.18). Conclusions MR reduction through TEER led to transient alterations in fibrinogen concentration and improved fibrin clot characteristics. Additionally, baseline CLT emerged as a significant predictor of early NT-proBNP reduction, emphasizing its role as a key indicator of the hemodynamic response to TEER.

Thrombin generation, fibrin clot permeation and lysis in patients with severe mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair: Mitral Fibrin Study.

Intricate management of heart failure (HF), especially in the context of reduced ejection fraction, is further complicated by an elevated risk of thromboembolic events. Studies published so far offer inconclusive insight into the interplay between mitral regurgitation (MR) and the coagulation system. This study aimed to investigate the impact of transcatheter edge‑to‑edge repair (TEER) on specific coagulation parameters in HF patients. A cohort of 31 HF patients with severe MR treated with TEER underwent a systematic evaluation at 3 visits (V1, V2, and V3). Coagulation parameters, including fibrinogen concentration, thrombin generation, fibrin clot permeability, and clot lysis time (CLT) were assessed (n = 27 at V2; n = 25 at V3). TEER induced changes in fibrinogen levels (P = 0.01; V3 vs V2) and improved fibrin clot properties over 50‑day follow‑up (P = 0.01; V3 vs V2). No significant differences were observed between time points in the analyzed blood clot parameters. Correlation analysis showed that baseline CLT was associated with ΔN‑terminal pro-B‑type natriuretic peptide (NT‑proBNP) level (P = 0.049; r = 0.4). Multivariable analysis identified baseline CLT as an independent predictor of early post‑TEER NT‑proBNP change (R2 = 0.55; P = 0.02). We found decreased level of fibrinogen and increased permeation coefficient over a median 50 (interquartile range, 32.5-75.5)-day post‑TEER follow‑up, as compared with early postprocedural assessments. Other blood coagulation parameters remained unchanged from baseline at both follow‑up time points after TEER. Finally, CLT was an independent predictor of early NT‑proBNP increase, emphasizing its role as an indicator of hemodynamic response to TEER.

Observation on the Effect of Shentong Zhuyu Decoction Combined with Acupotomy Lysis in the Treatment of Sciatica Caused by Lumbar Disc Herniation

Objective: This paper aims to observe the curative effect of Shentong Zhuyu Decoction combined with acupotomy lysis in patients with lumbar disc herniation and sciatica. Methods: 72 patients with lumbar disc herniation and sciatica who were treated from March 2022 to March 2023 were randomly divided into two groups. The study group was treated with Shentong Zhuyu Decoction combined with acupotomy lysis, and the control group was treated with acupotomy lysis. The patients’ walking ability, lumbar pain, lumbar function, quality of life, and complications were compared. Results: The walking ability indexes of the study group were better than those of the control group (P < 0.05). The visual analogue scale (VAS) and Oswestry disability index (ODI) of the study group were lower than those of the control group, and the Japanese orthopedic association score (JOA) was higher than that of the control group (P < 0.05). The quality of life scale using 36-item short-form (SF-36) survey in the study group was higher than that in the control group (P < 0.05). The complication rate of lumbar disc herniation in the study group was lower than that in the control group (P < 0.05). Conclusion: Shentong Zhuyu Decoction combined with acupotomy lysis can improve lumbar function, relieve pain, and restore walking ability in patients with lumbar disc herniation and sciatica, which is a highly effective and feasible treatment with great clinical value.

Inhibition of thrombin-activatable fibrinolysis inhibitor via DS-1040 to accelerate clot lysis in patients with acute pulmonary embolism: a randomized phase 1b study

BackgroundThe optimal treatment of intermediate-risk pulmonary embolism (PE) in hemodynamically stable patients remains unknown. Fibrinolytics reduce the risk of hemodynamic deterioration but increase bleeding risk. DS-1040, an inhibitor of thrombin-activatable fibrinolysis inhibitor, enhanced endogenous fibrinolytic activity without increasing bleeding risk in preclinical studies. ObjectivesTo evaluate the tolerability and explore the efficacy of DS-1040 in patients with acute PE. MethodsIn this multicenter, randomized, double-blind, placebo-controlled study, ascending doses of intravenous DS-1040 (20-80 mg) or placebo were added to enoxaparin (1 mg/kg twice daily) in patients with intermediate-risk PE. The primary endpoint was the number of patients with major or clinically relevant nonmajor bleeding. The percentage change in thrombus volume and right-to-left ventricular dimensions, assessed using quantitative computed tomography pulmonary angiography, at baseline and after 12 to 72 hours were used to explore the efficacy of DS-1040. ResultsOf 125 patients with all available data, 38 were randomized to placebo and 87 to DS-1040. The primary endpoint occurred in 1 patient in the placebo group (2.6%) and 4 patients who received DS-1040 (4.6%). One subject experienced major bleeding (DS-1040 80 mg group); no fatal or intracranial bleeding occurred. Thrombus volume was 25% to 45% lower after infusion, with no differences between the DS-1040 and placebo groups. There was no difference in the change from baseline right-to-left ventricular dimensions between the DS-1040 and placebo groups. ConclusionIn patients with acute PE, adding DS-1040 to standard anticoagulation was not associated with an increase in bleeding but did not improve thrombus resolution or right ventricular dilation.

Peculiarities of hemostasis in patients with COVID-19

Analysis of the dynamics of different stages of clot formation and its lysis in patients with different COVID-19 severity. We prospectively included 58 patients with COVID-19 (39 patients with moderate disease severity and 18 patients with severe disease) and 47 healthy volunteers as a control group. All participants underwent the assessment of flow-mediated dilation (FMD) of brachial artery, impedance aggregometry, rotational thromboelastometry and thrombodynamics. Von Willebrand factor antigen (vWF:Ag) quantification was also performed in patients with COVID-19. Measurements were repeated on the 3rd and 9th day of hospitalization. Compared to the control group, patients with COVID-19 showed reduced values of platelet aggregation and greater values of the clot growth rate, as well as its size and density. On the first day of hospitalization, we found no differences in the activity of plasma hemostasis and endogenous fibrinolysis between subgroups of patients. With the progression of the disease, the growth rate and size of the clot were higher in the severe subgroup, even despite higher doses of anticoagulants in this subgroup. An increase in platelet aggregation was noted during the progression of the disease, especially in the severe subgroup. There were no differences in the results of the FMD test by subgroups of patients. The vWF:Ag level was significantly higher in the severe subgroup. Thus, plasma hemostasis followed by secondary platelet activation correlates with the severity of COVID-19. Patients with moderate to severe coronavirus infection have predominantly local rather than generalized endothelial dysfunction.

Tumor Lysis Syndrome in Pediatric Patients with Hematological Malignancies

BACKGROUND: Tumor lysis syndrome (TLS) is a common complication of hematological malignancies and consists of either hyperkalemia, hyperphosphatemia, hyperuricemia, or hypocalcemia. These metabolic derangements may result in clinical tumor lysis syndrome in the form of acute kidney injury (AKI), arrhythmias, seizures, and sudden death. OBJECTIVES: This study was conducted to determine the incidence and outcome of TLS and to identify local risk factors in children with hematological malignancies. PATIENTS AND METHODS: This was a retrospective chart review of children ≤18 years diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia, or non-Hodgkin lymphoma between 2014 and 2018. TLS was diagnosed and stratified according to the risk of developing tumor lysis using the Cairo and Bishop definition and Cairo stratification. RESULTS: Among 180 patients, only 11 patients (6%) developed TLS. Four patients had laboratory TLS (LTLS) (36.3%) and six had CLTS (54.5%). The male-to-female ratio was high (2.4:1 in the TLS group). Hyperphosphatemia and hypocalcemia were the most frequently occurring criteria for LTLS (81.8%). The strongest predictors for TLS were hyperuricemia and hypocalcemia at presentation (P < 0.001) followed by diagnosis of T-cell ALL, preceding AKI splenomegaly, high initial white blood cell, and lactate dehydrogenase, with P < 0.05. AKI secondary to tumor lysis occurred in six patients (54.5%), of which five needed dialysis. One patient had seizures secondary to tumor lysis (9.1%) and no patient died from TLS. CONCLUSION: There is a wide variation in reported incidence of TLS from 6% to 45%, likely due to different TLS definitions applied, diverse cohorts and duration. A universal definition and risk-stratified approach to prevent tumor lysis in patients with hematologic malignancies is needed to help in proper comparison between studies.

The association of anticoagulation therapy characteristics with left atrial thrombus lysis in patients with nonvalvular persistent atrial fibrillation

Purpose. The aim of this study was to reveal the effect of the duration and characteristics of anticoagulant therapy on the clot dissolution in the left atrial appendage (LAA) in patients with persistent atrial fibrillation (AF).Material and methods. The repeat transesophageal echocardiography was performed in 68 patients with persistent AF, because the thrombus was detected in the LAA during the first examination. Of these, 37 (54.4%) patients started or continued to receive warfarin and 31 (45.6%) patients continued to receive the direct oral anticoagulants. Transesophageal echocardiography was repeated after 3-5 weeks. One follow-up examination was for 53 patients, two follow-up examination was for 11 patients and three follow-up examination was for 4 patients. Cox regression analysis was performed to identify factors affecting the likelihood of clot dissolution and Kaplan-Meier survival analyses with log-rank tests were used to compare the clot dissolution time.Results. The chance of the LAA thrombus lysis is 50% after 35.0 ± 3.7 days of receiving anticoagulants. This time is reduced to 30.0 ± 1.4 days for small thrombus (no more than 18 mm), and it increases to 45.0 ± 7.4 days (p = 0.038) for large thrombus. The dissolution time of small thrombus depends on the characteristics of the treatment: the median of the dissolution curve is 24.0 ± 3.7 days when the patients received the direct oral anticoagulants, and the median of the dissolution curve is 40.0 ± 7.2 days (p = 0.009), if the patients received warfarin. The dependence of the dissolution time of large thrombus on the characteristics of treatment did not found.Conclusion. The LAA thrombus dissolution time in patients with atrial fibrillation depends on their size, and the dissolution time of small thrombi depends on the characteristics of anticoagulant therapy.

Safety aspect of intraoperative, local urokinase lysis in patients with acute lower limb ischemia.

Acute lower limb ischemia (ALI) is associated with a high risk of limb loss and death. The present study evaluates the safety of intraoperative, local urokinase lysis in patients with ALI and crural artery occlusion. A total of 107 patients (115 legs) were treated surgically for ALI with additional intraoperative urokinase lysis to improve the outflow tract. Minor and major bleeding as well as efficacy of treatment and amputation-free survival were investigated. Complete restoration of at least one run-off vessel was achieved in 64%. Collateralization was improved in 34%. Lysis failed in 2%. Major amputation rate was 27% overall (12% within 30 days) and depended on Rutherford class of ALI (overall/30 day: IIa 11%/6%; IIb 20%/17%; III 37%/15%). Amputation-free survival turned out to be 82% after 30 days, 58% after one, and 41% after five years. Minor bleeding occurred in 21% (24/115) and major bleeding in 3.5% (4/115). One of these patients died of haemorrhage. No patient experienced intracranial bleeding. Intraoperative urokinase lysis improves limb perfusion and causes low major and intracranial bleeding. It can be safely applied to patients with severe ischaemia when surgical restoration of the outflow tract fails.

Time dependent changes in red blood cells during storage in the local blood banks of Khyber Pakhtunkhwa.

This project aimed at determining time-dependent ultrastructural and haematological changes taking place in blood stored in local blood banks of Khyber Pakhtunkhwa. It was a longitudinal study with repeated measures design. Twenty healthy blood donors participated in this study. An amount of 250ml blood was collected from each donor and stored in Citrate Phosphate Dextrose Adenine-1 (CPDA-1)- containing blood bags. Within first four hours, baseline samples were taken while subsequent samples were obtained at 5 days interval till day 20th. Structural changes in RBCs were observed under light and scanning electron microscope (SEM) at different intervals. Furthermore, haematological parameters and osmotic fragility were also determined. Remarkable alterations were seen in RBCs morphology. From 5th day onwards, multiple visible spicules were observed on the RBC's outer membrane and more than 2/3rd cells were abnormal at day 20. There was a significant reduction in RBCs count and haemoglobin concentration while the remaining parameters remained unchanged. Osmotic fragility increased significantly over time, with <1% haemolysis noted in baseline samples as compared to 2.4% haemolysis on day 20th (p≤0.0001). Prolonged storage of blood results in distorted RBCs morphology and increased fragility. Transfusion of such cells would potentially result in rapid lysis in patients with hepatosplenomegaly and conditions requiring multiple blood transfusions.

Intracardiac thrombosis: frequency, risk factors and place of oral anticoagulants in treatment

This review systematizes the currently known data on intracardiac thrombosis. The main nosology leading to left atrial thrombosis is atrial fibrillation, with up to 90% of all trombi forming in the left atrial appendage. The optimal method to diagnose thrombosis is the transesophageal echocardiography. The detection rate of left atrial appendage thrombosis in early studies ranged from 2.5 to 74.7% and dropped to 1-15.2% in the era of oral anticoagulants. However, there is no basis for performing transesophageal echocardiography as a screening examination for all patients with atrial fibrillation, and the CHA2DS2-VASc clinical scale is the guideline for prescribing and selecting antithrombotic therapy. The article presents data on the possibility of lysis of the left atrial appendage thrombosis against the background of oral anticoagulants therapy, which is of practical importance for patients before cardioversion and pulmonary vein ablation. The results of published studies and observations of patients receiving vitamin К antagonists show that 46.3-85% of thrombi are dissolved. The only prospective study to investigate the possibility of left atrial thrombosis lysis in patients with atrial fibrillation or fluttering while taking direct oral anticoagulants was X-TRA, which studied rivaroxaban therapy and showed thrombi dissolution in 41.5% of patients. The frequency of left ventricular thrombosis in patients with acute coronary syndrome with ST segment elevation in the age of reperfusion therapy is about 6-7%, reaching 19.2% in patients with anterior myocardial infarction and reduction of left ventricular ejection fraction. These recommendations indicate that only vitamin К antagonists may be prescribed in patients with left ventricular thrombosis. However, the results of the COMMANDER HF study showing the potential of rivaroxaban to prevent thromboembolic complications in patients with chronic heart failure have laid the foundation for the use of direct oral anticoagulants in left ventricular thrombosis. At present the study of efficacy and safety of apixaban and rivaroxaban in this category of patients is ongoing, but there are no results at present. In most cases, right ventricular thrombosis is part of the development of a pulmonary embolism, and much less often it accompanies right ventricular arrhythmogenic dysplasia or is associated with implantable devices. Anticoagulants are the basis for the treatment of these patients, and the present guidelines allow for moderate and low risk thromboembolism in patients with pulmonary artery thromboembolism, along with parenteral anticoagulants, prescribing immediate oral anticoagulants, giving preference to Xa-factor antagonists or direct thrombin inhibitors.

Bispecific T-Cell Engager (BiTE) Antibody Based Immunotherapy for Treatment of Relapsed Refractory Multiple Myeloma (RRMM): A Systematic Review of Preclinical and Clinical Trials

Introduction Bispecific T-cell engager (BiTE) antibodies represent a novel therapeutic option for patients with multiple myeloma (MM). BiTE antibodies lack Fc region, and have variable domain only, they can simultaneously bind to two different epitopes i.e. cluster of differentiation 3 (CD3) molecules on tumor-specific T cells, and a specific antigen on myeloma cells, which leads to T-cell dependent destruction of myeloma cells. Currently, blinatumomab, specific for CD3 and CD19 is the only Food and Drug Administration FDA approved BiTE antibody for clinical use in patients with relapsed/refractory (RR) B-cell acute lymphoblastic leukemia, several similar BiTE antibodies are under development. Methods Following PRISMA guidelines, we performed comprehensive literature on 4/15/19 cross-referencing the terms "bispecific antibodies" and "multiple myeloma" using PubMed, Embase, Web of Science, Cochrane Library, Clinicaltrials.gov and review of international medical meeting abstracts. Initially, 256 articles were identified and after detailed scrutiny, one phase 1 clinical trial with prelim results, 4 preclinical and 4 ongoing clinical trials were included. Results Preclinical trials: Anti-BCMA x Anti-CD3 Bispecific Antibody: BiTE antibodies are still in early development in MM, and most of the published data is about the pre-clinical phase. In preclinical trials, Hipp et al. 2017 and Cho et al. 2018 reported that AMG 420 (BI 836909) and AMG 701, which are anti CD3 and B-cell maturation antigen (BCMA), are highly efficacious in vitro in the killing of myeloma cells and potently induces autologous tumor cell lysis in patients with both newly diagnosed and RRMM regardless of their disease status. In mouse xenograft models reconstituted with human T cells, in vivo efficacy of AMG 420 was reported with an overall response in 6 of 10 animals, with all 6 responders became tumor-free at the end of the study. In an orthotopic L-363 xenograft model, treatment with AMG 420 resulted in prolonged median survival of 43-43.5 days. Dilillo et al. 2018 and Ji Li et al. 2017 reported similar in vivo results for REGN5458 and BFCR4350A respectively. Clinical trials: Currently, there are 5 phase 1 ongoing clinical trials (Table 1). Updated results of only first in human phase I AMG 420 are available. Forty-two MM patients with a high tumor burden and four prior lines of therapy were given 2.5 treatment cycles with AMG 420. Overall thirteen (31%) patients responded to AMG 420 therapy, with complete response (CR) in 6 (14.2%) patients, very good partial response (VGPR) in 2 (5%) patients and partial response (PR) in 2(5%) patients. Eleven of these patients responded in the first treatment cycle, with a median response time of 1 month. Twenty-five (57.1%) patients discontinued treatment due to progressive disease. Four deaths were reported; 2 from disease progression and 2 due to adverse events; neither of them was treatment-related. Serious adverse events were reported in twenty-one (50%) patients, the infection was reported in twelve (29%) and polyneuropathy in three (7%), eighteen (43%) required hospitalization. Treatment-related serious adverse events included three (7%) patients with grade 2-3 cytokine release syndrome, three (7%) with polyneuropathy and one (2.3%) with edema. Conclusion After the success of naked antibodies like daratumumab and elotuzumab for MM, there is a need to develop immunotherapy using conjugated antibodies and BiTE antibodies to overcome the challenge of MM resistance and relapse to prior therapies. Preclinical data with BiTE antibodies are promising; AMG 420 anti-CD3/BCMA BiTE has already been granted fast track status by the FDA. We anticipate that drug will enter phase 2 clinical trials for drug development against RRMM Other BiTE antibodies with strong preclinical efficacy are under development and data from larger prospective clinical trials is needed to explore their efficacy in the treatment of multiple myeloma. Table 1 Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Thrombin‐generating potential, plasma clot formation, and clot lysis are impaired in patients with bleeding of unknown cause

BackgroundIn a large proportion of patients with a mild to moderate bleeding tendency no diagnosis can be established (bleeding of unknown cause, BUC). ObjectivesTo investigate possible dysfunctions in thrombin generation and plasma clot formation and lysis in patients with BUC from the Vienna Bleeding Biobank (VIBB). Patients and MethodsThrombin generation and plasma clot properties of 382 BUC patients were compared to those of 100 healthy controls and 16 patients with factor VIII (FVIII) activity ≤50%. ResultsThrombin generation was significantly impaired in BUC patients compared to healthy controls, exhibiting a prolonged lag time and time to peak and decreased maximum thrombin generation, velocity index, and area under the curve (AUC). The assessment of clot formation and lysis in BUC patients revealed a lower clot formation rate (Vmax), resulting in a longer TTP, increased absorbance (ΔAbs), and a shorter clot lysis time (CLT) than in healthy controls. Comparing patients with FVIII activity ≤ 50% to those with BUC, parameters of thrombin generation and clot formation and lysis were either stronger or comparably impaired. Bleeding severity did not correlate with parameters of thrombin generation, clot formation, or clot lysis. ConclusionPatients with BUC have an impaired hemostatic capacity reflected by a lower thrombin‐generation potential, a lower clot formation rate, increased clot turbidity, and shorter clot lysis time, which might contribute to their increased bleeding tendency. Assays monitoring these parameters can alert physicians of hemostatic impairment and should be considered in situations where traditional hemostatic lab tests fail to reveal the clinical bleeding tendency.

Ex vivo properties of plasma clot formation and lysis in patients with cancer at risk for venous thromboembolism, arterial thrombosis, and death

A prothrombotic state is frequently observed in patients with cancer and contributes to the risks of venous thromboembolism (VTE), arterial thromboembolism (ATE), tumor progression, and death. Altered ex vivo properties of plasma clot formation and lysis have been observed in patients with cancer. The aim of this prospective study was to comprehensively characterize the relationship between plasma clot properties, inflammation, hypercoagulability, thrombotic complications, and mortality in patients with cancer using a tissue-factor-based turbidimetric assay of clot formation and lysis. Turbidity parameters were determined in 815 patients with newly-diagnosed or recurrent cancer and 97 healthy controls. Patients were followed-up for 2 years and rates of VTE (n = 72 events), ATE (n = 21 events), and death (n = 304 events) were assessed. Compared to controls, cancer patients' turbidity profiles showed an increased clot formation potential and higher resistance toward fibrinolysis. Elevated biomarkers of inflammation and hemostasis, such as C-reactive protein, FVIII, and thrombin generation explained substantial amounts of variation in turbidity parameters. In a prospective analysis, altered parameters of clot formation identified cancer patients at high risk of ATE (Hazard ratio [HR] per doubling of peak absorbance: 4.43, 95% CI: 1.50-13.07, P = 0.007) and death (HR per doubling of peak absorbance: 2.73, 2.00-3.72, P< 0.0001); these findings were independent of other prognostic covariates. Contrarily, turbidity parameters were not associated with risk of VTE (HR per doubling of peak absorbance: 1.15, 0.66-2.01, P = 0.62). We conclude that patients with cancer have altered ex vivo properties of clot formation which predict risks of ATE and mortality but not VTE.

SUN-085 Assessing the Impact of Disease Activity on Clot Formation and Lysis in Patients with Acromegaly

Introduction: Data from previous studies suggest increased thrombogenic potential in patients with acromegaly, with higher levels of fibrinogen and a degree of impaired fibrinolysis, which may be contributing to the increased cardiovascular risk associated with acromegaly. However, it remains unclear whether these hemostatic abnormalities reverse in patients with disease remission. Patients and Methods: We conducted a cross-sectional study in 40 patients with acromegaly. The patients were divided into two groups based on the Endocrine Society criteria for disease remission (GH<1mcg/L and IGF-1 within the reference range) at the time of the study. We measured fibrinogen using the Clauss method and also analyzed clot formation and lysis using a validated turbidimetric assay. Results: Twenty-two patients with active acromegaly (Group 1; mean age 51±13 years) and 18 with disease remission (Group 2; mean age 55±13 years) were assessed. There was no difference in the two groups with regards to age, gender distribution, BMI, fat mass (as measured by bioimpedance), skinfold thickness, total cholesterol and HbA1c. Mean GH and IGF-1 values were significantly higher in the group with active acromegaly (2.6±2.4 vs. 0.5±0.5 mcg/L, p<0.001 and 163±105% vs. 73±23% of upper limit of normal, p<0.001 respectively). Mean duration of disease remission in Group 2 was 9.4±6 years. Patients in remission had more prolonged lag time for the initiation of clot formation (571±68 vs. 514±72 sec, p=0.02), however maximum clot optic density was similar in the two groups (Group 1: 0.40±0.12 vs. Group 2: 0.35±0.14 arbitrary units, p=0.26). Additionally, no statistical difference was found in the lysis times in the two groups (mean time from maximum clot formation to 50% lysis was 24.5±18.7 min in Group 1, compared with 34.4±25.3 min in Group 2; p=0.16). Fibrinogen levels were also similar (Group 1: 3.9±1.6 mg/ml vs. Group 2: 3.2±1.5 mg/ml; p=0.2). Duration of active disease was associated with higher fibrinogen levels (coefficient 0.06, p=0.03), while duration of disease remission was associated with longer lag time for clot formation (coefficient 5.0, p=0.015). Disease status was another predictor of lag time for clot formation, with active acromegaly being associated with shorter lag time (coefficient -56.5, p=0.016). Conclusions: We were not able to demonstrate any significant differences in the clot structure properties between patients with active acromegaly and those with disease remission. This may be due to a type II statistical error due to the relatively small sample size or suggest that hemostatic abnormalities described in other studies persist, despite biochemical control of acromegaly. The presence of active disease and the overall duration of this, appear to be associated with increased potential for clot formation in patients with acromegaly.

Разработка и апробация нового метода определения параметров гемостаза у больных с психической патологией

Introduction: hemostasis is one of the most important protective systems of the organism, and its deviations from the norm can lead to fatal results. Changes in hemostasis are observed in many diseases, including mental pathology. In addition, parameters of this system may also change during antipsychotic therapy. Objective: Development and testing of a new method and device for estimating plasma hemostasis parameters in patients with mental pathologies in order to optimize treatment and eliminate fatal outcomes. Materials and methods: in the study we used frozen (-80 °C) platelet-free blood plasma (PFP) samples from patients with schizophrenia (16 patients), taken at admission to the clinic FSBSI «Mental Health Research Centre». Plasma coagulation of patients and healthy donors was assessed with the device of our design. Hemostasis assessment is based on the determination of the clot size in proportion to the brightness of the image, which changes as a result of clot formation and lysis. Results: optimal concentrations of coagulation and fibrinolysis activators, as well as concentrations of calcium ions were determined during the first stage of testing the method and device. The median values of all parameters of coagulation and fibrinolysis except «time before the formation of a clot» in patients upon admission to the clinic were reduced relative with combined plasma donors. The rates of clot formation and lysis in patients are significantly reduced at discharge compared with these parameters at admission. Consequently, these parameters can serve as an estimate of the change in the state of the coagulation and fibrinolysis systems during treatment. Conclusion: during approbation of the device and method in the process of coagulation and fibrinolysis research in patients with schizophrenia, lower levels of parameters were detected compared to donors, and a decrease in the activity of plasma coagulation and fibrinolysis during treatment with antipsychotics was shown.

Redirected T cell lysis in patients with metastatic uveal melanoma with gp100-directed TCR IMCgp100: Overall survival findings.

9521Background: IMCgp100 is a bispecific biologic comprised of a soluble T cell receptor recognizing the gp100 antigen fused to a scFV anti-CD3 and redirects T cell lysis of melanoma cells expressi...

PATHOGENETIC SUBSTANTIATION OF COMPREHENSIVE TREATMENT OF PATIENTS WITH CHRONIC PANCREATITIS COMBINED WITH OSTEOARTHROSIS AND OBESITY CONCERNING THE CORRECTION OF THE DISORDERS IN THE PROTEINASE INHIBITOR SYSTEM AND METABOLISM OF THE CONNECTIVE TISSUE COM

Introduction. The incidence of the co-morbid course of chronic pancreatitis (CP) and obesity has recently increased significantly both in Ukraine and all over the world, especially in individuals being in the second half of their adulthood and in the elderly ones. This combination of interdependent diseases is often complemented by osteoarthrosis (OA) of the large joints, which is characterized by severe, rapidly progressing course. The basis CP and OA progression, among various mechanisms of pathogenesis, is the proteinase-inhibitor imbalance, which leads to proteolytic damage and destruction of acinar epithelium and cartilage tissue, polymorphocyte infiltration of the tissue of the pancreas and synovial epithelium (reactive synovitis) under the influence of increased expression and activation of cellular adhesion factors, hyperproduction of proinflammatory cytokines, growth factors of anabolic action, acidosis, hypoxia, etc.Objective. Тo identify the mechanisms of mutual aggravation of chronic pancreatitis and osteoarthrosis of large joints in obese patients on the basis of the study of protein and carbohydrate-protein components of the extracellular matrix of the proteinase inhibitor system, to increase the efficiency of comprehensive treatment for this polymorbidity.Materials and methods. Тhe study involved 90 patients with CP, aged 45 to 63 years old , 22 of whom had normal body weight (1group 1), 27 patients with CP suffered from the first degree obesity (group 2), 41 patients had CP with comorbid first degree obesity and І-ІІ stage osteoarthritis of the of the hip and knee joints (group 3).To evaluate the effectiveness of the proposed treatment, the patients of group 3 were divided into two subgroups: 3A and 3B. Group 3А (21 individuals) received basic treatment of CP exacerbation: a hypocaloric diet with elimination of extractive foods, antisecretory (proton pump inhibitor), antispasmodic (mebeverine hydrochloride) for 1 month, multienzyme (kreon10-20 thousand units) preparations, L-carnitine (solution) 1.0 (10 ml) twice a day for 90 days. Group 3B (20 people), in addition to the above therapy, received the drinking form of L-carnitine 1.0 (10 ml) twice a day and L-glutathione (hepaval) 250 mg twice a day for 90 days.Results. Тhe proposed therapy contributed to the normalization of proteinase inhibitor homeostasis. Without proteinase inhibitors in the basic therapy the complex application of L-carnitine and L-glutathione contributed to a reliable decrease in the intensity of azole albumin lysis in patients of both groups: 1.2 and 1.6 times, respectively (p &lt;0.05), due to significant inhibition of hyperproduction of proteinase inhibitors: the content of α2- macroglobulins in the blood dropped by 1.6 and 2.2 times (p &lt;0.05) with normalization of the values.Conclusions. Patients with chronic pancreatitis, comorbid obesity and osteoarthrosis of large joints were studied during their therapy, the mechanisms of mutual aggravation were identified: hyperproduction of the extracellular matrix components, acute phase proteins, an increased degradation of fucoglycoproteins and proteinase-inhibitor imbalance.The integrated therapy of patients with CP and obesity which includes antioxidant (L-glutathione) and a metabolism stabilizer (L-carnitine) against the basic treatment resulted in the balance of the processes of synthesis and decomposition of collagen and glycoproteins, proteinase-inhibitor system homeostasis, collagenolysis enhancement with the achievement of the balance in the metabolism of the connective tissue components, homeostasis of hydrogen sulfide, which underlies the achievement of stable remission of CP and OA, reducing the risk of their progression.

Conventional trabeculectomy versus trabeculectomy with the Ex-PRESS® mini-glaucoma shunt: differences in postoperative interventions.

PurposeTo compare the postoperative interventions and outcomes between conventional trabeculectomy and trabeculectomy with the Ex-PRESS® mini-glaucoma shunt device (Ex-Press).MethodsThis was a retrospective, comparative, single-facility study. We analyzed the cases of 108 glaucoma patients who underwent trabeculectomy and were followed for >1 year. Thirty-nine eyes underwent a conventional trabeculectomy (conventional group) and 69 eyes underwent a trabeculectomy with an Ex-Press (Ex-Press group). As evaluation items, we examined postoperative intraocular pressure (IOP), the surgical success rate, postoperative complications, the number of days to laser suture lysis, and needling.ResultsTrabeculectomy significantly decreased the patients’ IOP values from 27.8±7.9 to 11.1±3.9 mmHg in the conventional group (p<0.001) and from 27.7±9.2 to 11.5±3.7 mmHg in the Ex-Press group (p<0.001) after 1 year. The success rate was not significantly different between the groups. The timing of the first laser suture lysis was significantly sooner in the Ex-Press group, and the Ex-Press group showed significantly less choroidal detachment due to low IOP.ConclusionEarlier laser suture lysis in patients whose trabeculectomy treatment includes an Ex-Press is required to obtain the outcomes comparable to those of conventional trabeculectomy.

Abnormal populations and functions of natural killer cells in patients with myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by ineffective hematopoiesis that lead to leukemia. Disorders of the immune system serve important functions in the pathophysiology and progression of this disease. Different levels or mechanisms of natural killer (NK) cells in patients with MDS have been measured in previous studies, making it challenging to understand the pathogenesis of NK cytotoxicity. The present study investigated the frequency of NK cell-mediated antibody-dependent cellular cytotoxicity and explored the function of NK cells by their activating receptors, inhibition signals, degranulation and cytotoxicity factors. In the present study, levels of cluster of differentiation (CD)3−CD56+ NK cells, CD16+-expressing NK cells and subset CD56dim NK cells were decreased in the peripheral blood of patients with MDS. Altered expression of NK protein 44, NK group 2 member D, killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) and KIR2DL3 on NK cell effector signaling pathways may trigger tumor cell lysis in patients with MDS. The weak cellular adhesion and decreased cytotoxicity of NK cells may lead to ineffective antitumor activity in MDS. These observations suggested that NK cells may serve as immunological determinants in MDS and may permit the development of NK cell-based immunotherapy for the treatment of patients with MDS.

Role of coexisting contralateral primary venous disease in development of post-thrombotic syndrome following catheter-based treatment of iliofemoral deep venous thrombosis.

It has been reported that early clot removal benefits patients with iliofemoral deep venous thrombosis (DVT) by removing obstruction and preserving valve function. However, a substantial number of patients who had successful clot removal develop post-thrombotic syndrome (PTS). Residual thrombus and rethrombosis play a part in this phenomenon, but the role of coexisting primary chronic venous disease (PCVD) in these patients has not been studied. All patients who underwent catheter-based techniques of thrombus removal for symptomatic acute iliofemoral DVT during a 5-year period compose the study group. These patients were assessed for PTS by the Villalta scale, the Venous Clinical Severity Score (VCSS), and the Venous Insufficiency Epidemiological and Economic Study on Quality of Life (VEINES-QOL) questionnaire. The presence of coexisting PCVD was determined by clinical and duplex ultrasound findings in the contralateral leg at the time of the initial DVT diagnosis. Patients who had coexisting PCVD were compared with those without PCVD. Forty patients (40 limbs) were included in the study group. At initial diagnosis, 15 patients (38%) had coexisting symptomatic primary valve reflux in the unaffected limb. After thrombolysis, 9 of 40 limbs (22%) had complete lysis, 29 (73%) had ≥ 50% to 99% lysis, and 2 (5%) had <50% lysis. The mean percentage of lysis in patients with or without PCVD was similar (78% vs 86%; P = .13). Patients without coexisting PCVD had significantly better Villalta score and VCSS compared with those with coexisting PCVD (Villalta score, 2.52 vs 3.27, P = .014; VCSS, 2.96 vs 3.29, P = .005). Forty-five percent of patients (18 of 40) developed PTS. Patients who developed PTS had less clot lysis than those without PTS. This was true for patients with coexisting PCVD (60% vs 85%; P = .025) and in patients without PCVD (75% vs 89%; P = .013). There was no significant difference in the VEINES-QOL score between those with or without PCVD (79.5 vs 80.5; P = .9). Patients who had reflux in the treated limb after lysis had a five times greater chance for development of PTS compared with those who retained normal valve function during follow-up (odds ratio, 5.3; 95% confidence interval, 1.6-17.045). However, in patients with normal veins in the contralateral leg, the chance of development of PTS was 1.5 times higher if reflux was present in the treated limb (odds ratio, 1.49; 95% confidence interval, 0.043-10.253). Coexisting PCVD is a contributing factor to development of PTS after treatment of iliofemoral DVT with thrombus removal techniques.