ASPIRIN RESISTANCE IN NEUROVASCULAR DISEASES.

INTRODUCTION: The issue of resistance to antiplatelet therapy has raised many questions in the area of neurovascular diseases. The first objective of this work was to determine the prevalence of aspirin resistance in neurovascular patients with clinical non-responsiveness to aspirin treatment and a high-risk of atherothrombotic complications using two interpretable and independent methods (aggregation and PFA 100). The second objective was to find the correlation between both assays and to evaluate the results in groups at risk for various cerebrovascular diseases. MATERIAL AND METHODS: Laboratory tests of aspirin resistance were performed in 79 patients with clinical non-responsiveness to aspirin treatment suffering from neurovascular diseases. Patients were divided into the two groups: expected low risk for aspirin resistance due to the first manifestation of a neurovascular disease (n = 34) and expected high risk due to the second clinical manifestation of a neurovascular disease (n = 45). RESULTS: The prevalence of aspirin resistance in both groups combined as determined by the PFA-100 and CPG techniques were 50.6% and 17.7%, respectively. No correlation was found between the two techniques. CONCLUSIONS: No significant prevalence of aspirin resistance was demonstrated by either method despite the heterogeneous pathophysiological mechanisms. However, we are presently unable to provide an accurate opinion on the value of laboratory test result or routine monitoring in clinical neurology.

Sysmex-derived COVID-19 prognostic score as an early prognostic marker for severity of the COVID-19 disease.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a life-threatening disease with a heterogeneous course. Even some young patients are at increased risk of severe course or death, as they can face severe complications. It would be very useful to have a cheap and easily available marker to predict COVID-19 course in the early stages of the disease. The COVID-19 prognostic score could be a very useful clinical indicator available at the time of primary contact with the patient. METHODS: The COVID-19 prognostic score and the clinical condition together with selected laboratory parameters were evaluated in patients with respiratory tract infection and a positive PCR test for the SARS-CoV-2 during the first contact with the patient. Prognostic significance was evaluated using receiver operating characteristic curves (ROC) and area under the curve (AUC). Selected parameters of the blood count and hemostasis, as well as selected biochemical indicators, were examined too. RESULTS: Thirty-seven of 164 patients developed serious symptoms. The COVID-19 score had one of the highest AUC values (0.855) of all markers. The highest combination of sensitivity (91.9%) and specificity (71.7%) for identifying patients with a subsequent moderate and severe course of the disease was achieved at the threshold 1.5. The predictive value of a negative test is beneficial too (0.968). CONCLUSIONS: The COVID-19 prognostic score is a promising indicator stratifying patients with COVID-19 into prognostic groups at the time of the first contact, thus allowing the timely provision of increased care in patients at high risk of severe development.

MonoMAC syndrome with GATA2 novel mutation: A case report.

GATA2 deficiency was first identified in 2011 and have been reported over 500 individuals with GATA2 mutations. The onset of symptoms ranges from early childhood to late adulthood but very often the diagnosis is made between adolescence and early adulthood. These patients can be relatively asymptomatic or have life threatening diseaseas (myelodysplastic syndrome, acute leukemia). We describe case of 30-years old women with GATA2 novel mutation who present by primary lymphedema, myelodysplastic changes in bone marrow, monocytopenia and history of several recurrent infections (bacterial, mycobacterial). The case illustrates the diagnostic difficulties in identifying GATA2 deficiencies.

Intensive Care Infection Score (ICIS) is elevated in patients with moderate and severe COVID-19 in the early stages of disease.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus is still a very dangerous and life-threatening disease with an extremely heterogeneous course. Older patients and those with comorbidities are at increased risk of death from the disease but young patients can develop potentially lethal complications too. For those reasons, numerous recent studies focus on the analysis of markers associated with early assessment of COVID-19 prognosis. Previous publications provided evidence for the Intensive Care Infection Score (ICIS) as an easy to use tool to assess the risk for bacterial infection in ICU patients based on a combination of haematologic parameters. This study evaluated the performance of ICIS as a prognostic marker of stages of disease in COVID-19 patients. METHODS: A total of 205 COVID-19 patients admitted to the University Hospital Hradec Kralove, Czech Republic, with symptoms of respiratory tract infection and a positive RT-PCR test for SARS-CoV-2 virus were enrolled in this study. Forty-nine patients developed mild COVID-19 symptoms (no oxygen therapy needed), 156 patients developed moderate or severe symptoms (supplemental oxygen therapy or death). RESULTS: ICIS predicted the mild or moderate/severe course with the highest AUC (0.773). The cut-off value (ICIS = 3.5) was selected as the value with the highest Youden index (0.423). The cut-off value could predict a mild or moderate/severe course of the disease with the highest specificity (77.6%) and positive predictive value (90.2%) of all markers used in this study. Sensitivity was 64.7%. CONCLUSION: ICIS is a reliable, cheap, fast and simply interpretable score for the early identification of moderate/severe course of COVID-19 in an early stage of the disease. ICIS> 3 predicts a severe course of the disease with high specificity and positive predictive value.

High on-treatment platelet reactivity: risk factors and 5-year outcomes in patients with acute myocardial infarction.

OBJECTIVE: The aim of the present study was to assess long-term prognostic value of high on-treatment platelet reactivity (HTPR) in patients after acute myocardial infarction (MI) and its association with possible risk factors. METHODS: This prospective, case-control study was an observation of 198 patients who had acute MI. Response to aspirin and clopidogrel was assessed using impedance aggregometry. Patients were divided into groups of adequate response, dual poor responsiveness (DPR), poor responsiveness to aspirin (PRA), and poor responsiveness to clopidogrel (PRC). Simultaneously, potential risk factors of HTPR development were recorded. After 5 years, MI recurrence and overall mortality were assessed. RESULTS: HTPR was more frequent in New York Heart Association Class III and IV patients, and in patients with left ventricle systolic dysfunction. Five-year mortality rate was higher in all groups of patients with HTPR compared to patients with sufficient response to antiplatelet treatment: in PRA patients, 38.1% vs. 19.2%, p<0.01; in PRC patients, 45.2% vs. 17.3%, p<0.001; and in DPR patients, 50.0% vs. 19.9%, p<0.05. Risk of repeat MI also increased (hazard ratio [HR] 4.0, p<0.05 for DPR group; HR 4.37, p<0.01 for PRA group; and HR 3.25, p<0.05 for PRC group). CONCLUSION: PRA, PRC, and DPR are independent predictors of increased 5-year mortality and risk of repeat non-fatal MI. The study has demonstrated that HTPR is frequently observed in patients with severe heart failure and left ventricle systolic dysfunction.

Analysis of circulating miRNAs in patients with familial hypercholesterolaemia treated by LDL/Lp(a) apheresis.

BACKGROUND: LDL/Lp(a) apheresis therapy is a well-established method of aggressively lowering LDL and Lp(a). Recently, miRNAs have been discussed as markers of vascular status including atherosclerosis. MiRNAs inhibit post-transcriptional processes through RNA duplex formation resulting in gene silencing or regulation of gene expression. MATERIALS AND METHODS: We measured a profile of 175 plasma-circulating miRNAs using pre-defined Serum/Plasma Focus Human microRNA PCR Panels in pooled samples of 11 subjects with familial hypercholesterolaemia under long-term apheresis treatment. Subsequently we analysed expressions of ten pre-selected miRNAs potentially involved in lipid homeostasis in the same group of subjects. We compared plasma-circulating miRNA levels isolated from peripheral blood collected immediately before and after apheresis. RESULTS: The greatest differences in plasma levels were found in miR-451a, miR-16, miR-19a/b, miR-223 and miR-185. In subsequent individual miRNA assay we detected a significant increase in miR-33b levels after apheresis (P < 0.05). Additionally, correlations between plasma lipids and miR-33a (P < 0.04) and miR-122 (P < 0.01) have been determined. Moreover, miR-122 levels in LDLR homozygotes were higher compared to heterozygotes after, but not before, apheresis treatment (P < 0.04). CONCLUSIONS: LDL/Lp(a) apheresis has an impact on miRNAs associated with lipid homeostasis and vascular status.

Epidermal Growth Factor Attenuates Delayed Ionizing Radiation-Induced Tissue Damage in Bone Marrow Transplanted Mice.

We examined the effect of epidermal growth factor (EGF) treatment in mice that received bone marrow transplantation (BMT) after 11 Gy whole-body irradiation. C57Bl/6 mice were divided into three treatment groups: 0 Gy; 11 Gy ((60)Co, single dose, 0.51 Gy/min) with BMT (5 × 10(6) bone marrow cells isolated from green fluorescent protein syngeneic mice, 3-4 h postirradiation); and 11 Gy with BMT and EGF (2 mg/kg applied subcutaneously 1, 3 and 5 days postirradiation). Survival data were collected. Bone marrow, peripheral blood count and cytokines, gastrointestine and liver parameters and migration of green fluorescent protein-positive cells were evaluated at 63 days postirradiation. Epidermal growth factor increased survival of irradiated animals that received BMT from 10.7 to 85.7% at 180 days postirradiation. In the BMT group, we found changes in differential bone marrow and blood count, plasma cytokine levels, gastrointestinal tissues and liver at 63 days postirradiation. These alterations were completely or in some parameters at least partially restored by epidermal growth factor. These findings indicate that epidermal growth factor, administered 1, 3 and 5 days postirradiation in combination with bone marrow transplantation, significantly improves long-term prognosis.

Prothrombotic changes due to an increase in thyroid hormone levels.

OBJECTIVE: With increasing free thyroxine levels, a gradually rising risk of venous thromboembolism has been described in case-control studies. However, reports on the influence of thyroid hormones on haemostasis, while suggesting a hypercoagulable state in thyrotoxicosis, have often been inconclusive. This study evaluates multiple markers of haemostasis and fibrinolysis in a paired design, making it more sensitive to changes in thyroid hormone levels. DESIGN: We analysed multiple variables in patients who shifted from severe hypothyroidism to mild hyperthyroidism during thyroid cancer treatment. Those with possible residual disease were excluded. METHODS: Ninety patients following total thyroidectomy were tested on two occasions: i) before radioiodine remnant ablation and ii) 6 weeks later, on levothyroxine (lT4) suppression treatment, and the results were compared using the Wilcoxon's test for paired data. RESULTS: During lT4 treatment, significant increases (all P<0.001) in fibrinogen (from median 3.4 to 3.8 g/l), von Willebrand factor (from 85 to 127%), factor VIII (from 111 to 148%) and plasminogen activator inhibitor 1 (from 6.5 to 13.9 µg/l) were observed. In addition, the activation times of platelet adhesion and aggregation stimulated with collagen and epinephrine (EPI)/ADP, i.e. closure times in platelet function analyser (PFA-100), were significantly shortened (P<0.001): for EPI from median 148 to 117 s and for ADP from 95 to 80 s. Changes in other tests were less prominent or insignificant. CONCLUSIONS: An increase in thyroid hormone levels shifts the haemostatic balance towards a hypercoagulable, hypofibrinolytic state. This may contribute to the increased cardiovascular morbidity and mortality observed even in mild thyrotoxicosis.

Good short-term but not long-term reproducibility of the antiplatelet efficacy laboratory assessment.

BACKGROUND: The antiplatelet effect of acetylsalicylic acid (ASA) varies among individual patients. We assessed the short-term reproducibility (STR) and long-term reproducibility (LTR) of light transmission aggregometry (LTA). METHODS: Residual platelet reactivity was measured twice using LTA in a group of 207 consecutive patients (56 females, mean age 67 ± 9 years) on ASA therapy in 10 ± 6 months interval. The STR was assessed in 15 patients (6 females, mean age 61 ± 7 years) with 10 measurements on 2 consecutive days. RESULTS: There was no correlation between both measurements in the long-term part of the study, and also Bland-Altman plot showed a diverging pattern. However, LTA STR was good with a correlation coefficient of .800 (P < .05) confirmed by Bland-Altman plot. CONCLUSIONS: Although short-term intraindividual reproducibility of LTA assessment of platelet reactivity is very good, in the long-term perspective the antiplatelet ASA effectivity may be influenced by additional variables and repeated measurements are warranted.

The importance of rheological parameters in the therapy of the dry form of age-related macular degeneration with rheohaemapheresis.

To date, rheological treatment is the only chance to control the advanced dry form of age-related macular degeneration and arrest its progression to legal blindness. Rheohaemapheresis can change the main rheological parameters, blood and plasma viscosity, as well as change erythrocyte aggregability, improve erythrocyte flexibility and lead to substantial improvement when other methods of therapy fail. In this study, we describe changes in the levels of rheological efficacy indicators after rheohaemapheresis and their clinical significance in the dry form of age-related macular degeneration (AMD). Seventy-two patients with AMD were randomised; 34 controls, and 38 patients were treated with rheohaemapheresis (separator Cobe Spectra + Evaflux filter). After the procedures, α2-macroglobulin levels decreased by approximately 58%, fibrinogen by approximately 65%, IgM by approximately 67%, LDL cholesterol by approximately 71%, apolipoprotein B by approximately 65%, and lipoprotein (a) by approximately 42%. These decreases correspond with a decrease in blood and plasma viscosity (14/12%), clinical improvement (arrest of disease progression, even visual improvement in some cases), and heretofore-unreported improvement (even reattachment) of drusen retinal pigment epithelium detachment. Our modification of rheohaemapheresis is safe (5.4% of patients experienced clinically insignificant side effects).