Assessing the risk of venous thromboembolism in patients with haematological cancers using three prediction models.

PURPOSE: Assessment of individual VTE risk in cancer patients prior to chemotherapy is critical for determining necessity of interventions. Risk assessment models (RAM) are available but have not been validated for haematological malignancy. We aimed to assess the validity of the Vienna Cancer and Thrombosis Study (V-CATS) score in prediction of VTE in a variety of haematological malignancies. METHODS: This is a prospective cohort study conducted on 81 newly diagnosed cancer patients undergoing chemotherapy. Demographic, clinical and cancer related data were collected, patients were followed up for 6 months, and VTE events were recorded. Khorana score (KS) was calculated. Plasma D-dimer and sP-selectin were measured, and then, V-CATS score was calculated. Receiver operator curve (ROC) was used to assess the sensitivity and specificity of RAMs. A modified V-CATS was generated and subsequently assessed by using new cut-off levels of d-dimer and sP-selectin based on ROC curve of the patients' results and compared the probability of VTE occurrence using all three RAMs. RESULTS: Among the 81 patients included in this study, a total of 2.7% were diagnosed with advanced metastatic cancer. The most frequent cancer was non-Hodgkin lymphoma (39.5%), and 8 patients (9.8%) developed VTE events. The calculated probability of VTE occurrence using KS, V-CATS and modified V-CATS scores at cut-off levels ≥ 3 was 87.5%, 87.5% and 100%, respectively. The AUC in ROC curve of modified Vienna CATS score showed significant difference when compared to that of V-CATS and KS (P = 0.047 and 0.029, respectively). CONCLUSION: The findings of our study highlight the value of three VTE risk assessment models in haematological malignancies. The modified V-CATS score demonstrated higher specificity compared to both V-CATS and KS, while all three scores exhibited similar sensitivity. We encourage the implementation of RAMs in haematological cancers for an appropriate use of thromboprophylaxis.

Preparation, Characterization, and Anticancer Effects of Capsaicin-Loaded Nanoliposomes.

BACKGROUND: Medicinal plants have proven their value as a source of molecules with therapeutic potential, and recent studies have shown that capsaicin has profound anticancer effects in several types of human cancers. However, its clinical use is handicapped due to its poor pharmacokinetics. This study aims to enhance capsaicin's pharmacokinetic properties by loading the molecule into nanoliposomes model and testing its anticancer activity. METHODS: Nanoliposomes were prepared using the thin-film method, and characteristics were examined followed by qualitative and quantitative analyses of encapsulation efficiency and drug loading using HPLC at different lipid/capsaicin ratios. Cell viability assay (MTT) was used to determine IC50. RESULTS: Capsaicin-loaded nanoliposomes showed optimum characteristics of morphology, particle size, zeta potential, and stability. In vitro anticancer activity of capsaicin and capsaicin-loaded nanoliposomes were compared against MCF7, MDA-MB-231, K562, PANC1, and A375 cell lines. Capsaicin-loaded nanoliposomes showed significant improvement in anticancer activity against cancers cell lines studied (p < 0.001), with increased selectivity against cancer cells compared to capsaicin. CONCLUSION: The encapsulated capsaicin nanoliposomes produced an improvement in pharmacokinetics properties, enhancing the anticancer activity and selectivity compared with capsaicin. This model seems to offer a potential for developing capsaicin formulations for the prevention and treatment of cancer.

Loading of capsaicin-in-cyclodextrin inclusion complexes into PEGylated liposomes and the inhibitory effect on IL-8 production by MDA-MB-231 and A549 cancer cell lines.

Capsaicin (CAP) is an active component in Capsicum annuum L. known to have anti inflammatory and anticancer activity. CAP is highly lipophilic and suffers low bioavailability. Therefore, developing delivery systems that enhance solubility and bioavailability can provide more promising therapeutic applications for CAP. In the current work, CAP was complexed with ß-cyclodextrin (ßCD) to form capsaicin-in-ß-cyclodextrin (CAP-in-ßCD) inclusion complexes. Then, the CAP-in-ßCD inclusion complexes were characterized and loaded into PEGylated liposomes using the thin-film hydration extrusion method. The size, charge, and polydispersity index (PDI) of the PEGylated liposomes were characterized. The levels of IL-8 production were quantified after treatment using array beads. The results of this work showed that the successful formation of inclusion complexes at 1:5 M ratio of CAP to ßCD respectively. PEGylated liposomes loaded with ßCD/CAP inclusion complexes (CAP-in-ßCD-in-liposomes) have a hydrodynamic diameter of (181 ± 36) nm, zeta potential of (-2.63 ± 4.00) mV, encapsulation efficiency (EE) of (38.65 ± 3.70)%, drug loading (DL) of (1.65 ± 0.16)%, and a stable release profile. Both free CAP and liposomal CAP showed a significant reduction in the IL-8 production by the MDA-MB-231 and A549 cancer cell lines after treatment. In conclusion, a liposomal-based drug delivery system for CAP was achieved.

Aptamer-functionalized pH-sensitive liposomes for a selective delivery of echinomycin into cancer cells.

Echinomycin (quinomycin A) is a peptide antibiotic from the quinoxaline family, which has a DNA bifunctional intercalating activity and an inhibitor of hypoxia-inducible factor (HIF1α). Echinomycin was discovered in 1957 as a potent antitumor agent; however, it was not successful in clinical use due to its low water solubility and short half-life. To revitalize this potent drug, it is important to increase its aqueous solubility and bioavailability. In this study, echinomycin was loaded into PEGylated pH-sensitive liposomes (PEGLippH) and functionalized with anti-nucleolin aptamer (AptNCL) for selective targeting and pH-responsive release of echinomycin into cancer cells. Echinomycin was complexed with γ-cyclodextrin (ECγCD) to enhance its water solubility and then encapsulated into pH-sensitive liposomes (PEGLippH-ECγCD). Then, liposomes were functionalized with AptNCL (AptNCL-PEGLippH-ECγCD) and the successful functionalization was confirmed by dynamic light scattering (DLS) measurements and gel electrophoresis. Cellular uptake for AptNCL-PEGLippH was evaluated by flow cytometry analysis using MDA-MB-231, MCF7, A549 cancer cell lines with respect to the normal fibroblast cells. The results showed a higher uptake and selectivity for AptNCL-PEGLippH compared to PEGLippH. The anti-proliferative effects of AptNCL-PEGLippH-ECγCD were more potent than PEGLippH-ECγCD by 3.5, 4, and 5 folds for A549, MDA-MB-231, and MCF7, respectively. Selectivity indices (SI) for AptNCL-PEGLippH-ECγCD for the tumor cell lines compared to the normal cell line after 72 h were MDA-MB-231 (43.3), MCF7 (16.9), and A549 (8.5). Furthermore, SI after 3 h for the three cancer cell lines were 4.7, 2.5, 2.8, respectively.

Co-encapsulation of thymoquinone with docetaxel enhances the encapsulation efficiency into PEGylated liposomes and the chemosensitivity of MCF7 breast cancer cells to docetaxel.

Combinatorial therapeutic strategies to eradicate tumors can be superior to a single therapeutic modality. Docetaxel (DT) has been approved for the treatment of local or metastasized breast cancer alone or in combination with other chemotherapeutic agents. Thymoquinone (TQ) originated from the seeds of Nigella Sativa plant has been reported to possess in vitro and in vivo antitumor activity against variety of tumors. In the current study, we have investigated the synergistic anticancer efficacy of a novel combination of DT and TQ on MCF7 breast cancer cell line using MTT cell viability assay. Moreover, this study describes for the first time the co-encapsulation of DT and TQ into PEGylated liposomes. The results showed that the combination of DT and TQ resulted in significant synergistic cytotoxicity compared to DT and TQ alone. Moreover, DT and TQ have been successfully co-encapsulated into PEGylated liposomes with higher encapsulation efficiency compared to DT and TQ alone. In conclusion, DT and TQ combination poses a synergistic effect and may aid in decreasing the required doses of DT. Also, the co-encapsulation of DT and TQ into PEGylated liposomes can provide a promising DT and TQ delivery system into cancer cells.

Soluble E-selectin, platelet count and mean platelet volume as biomarkers for pre-eclampsia.

OBJECTIVES: Preeclampsia remains a major cause of maternal mortality and morbidity worldwide with increased risk for cardiovascular disease later in life. Many previous studies have examined several biomarkers including E-selectin. We aimed to assess the role of sE-selectin together with platelet count and mean platelet volume (MPV) as biomarkers for the prediction of preeclampsia. STUDY DESIGN AND MAJOR OUTCOME MEASURES: This case-control study included 85 pregnant women; 40 healthy (mean age 27.1 ±â€¯4.8 years) and 45 with preeclampsia (mean age 26.8 ±â€¯6.7 years), recruited at the third trimester of pregnancy and subjected to full clinical and laboratory testing. This included complete blood picture, urine analysis and plasma sE-selectin using ELISA. RESULTS: A significant decrease in platelet count (P = 0.003), and a significant increase in MPV (P < 0.001) were seen in patients versus controls. Plasma sE-selectin levels were significantly higher in patients versus control (P = 0.002). ROC curve showed the best cut-off values for sE-selectin was 64.3 ng/mL, with 58% sensitivity 80.0% specificity. Positive predictive value was 76.5; negative predictive value was 62.7 and accuracy was 68.2 with a statically significant area under curve (P = 0.002). Platelet count, MPV and sE-selectin were significantly associated with PE in univariate analysis. In multivariate analysis, only MPV and sE-selectin were independent risk factors for PE development. Higher MPV or sE-selectin were associated with PE development (P < 0.001). CONCLUSION: The simultaneous use of sE-selectin and platelet count and volume may help earlier recognition of preeclampsia and thus appropriate and more efficient therapy. Larger studies are likely to help verify data and justify wider application of these markers.

Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients.

BACKGROUND/AIMS: Data from previous reports, addressing the significance of genotype-guided dosing of warfarin in Egyptian patients, are infrequent and controversial. This study is aimed at demonstrating the validity of genetic dosing algorithms in Egyptian patients on warfarin therapy. METHODS: A total of 100 Egyptian patients on a stable maintenance daily dose of warfarin were enrolled. The predicted warfarin dose for each patient was calculated using the warfarin dosing table, the Gage and the International Warfarin Pharmacogenetics Consortium (IWPC) clinical algorithms and the Gage and the IWPC genetic algorithms and compared to the actual dose. The accuracy of warfarin dosing algorithms was assessed by using the linear regression analysis. RESULTS: The most accurate model in predicting the ideal dose was the Gage genetic algorithm by R2 of 50.4% and the IWPC genetic algorithm by R2 of 42.3%, followed by the warfarin dosing table by R2 of 19.1%, and the Gage clinical algorithm by R2 of 18.9% and the least accurate was the IWPC clinical algorithm by R2 of 9.4%. CONCLUSIONS: The Gage -genetic warfarin dosing algorithm is the best model that could be implemented in Egyptian patients starting warfarin therapy.

Reduced Protein C Global Assay Levels in Infertile Women with in vitro Fertilization Failure: A Pilot Study.

Protein C global is a global dotting assay that evaluates abnormalities in the protein C anticoagulant pathway. A few studies have examined this assay in relation to assisted reproductive technology (ART), but its role in infertile women with in vitro fertilization (IVF) failure remains unclear. In this study, we assessed protein C in infertile women with a history of IVF failure who were undergoing ART. We examined 45 healthy fertile women who conceived naturally, and 45 infertile women with 2 or more implantation failures undergoing ART. Both protein C and activated protein C resistance (APC-R) were evaluated. The results showed that mean protein C expressed as a normalized ratio (PCAT-NR) was significantly lower in the study group compared to the control group (0.76 ± 0.15 vs. 0.91 ± 0.14, respectively; p = 0.0001). Follow-up on ART outcomes showed that women who failed ART had significantly lower PCAT-NR compared to successful cases. PCAT-NR did not correlate with APC-R levels in the study (r = 0.125, p < 0.5) or failed ART subgroups. Using logistic regression analysis, patients with lower PCAT-NR levels showed an elevated risk of implantation failure (p = 0.04, OR 0.50, 95% CI 0.26-0.84). In conclusion, protein C global assay may play a role in the etiology of IVF failure, which might be independent of APC-R. Larger studies are encouraged to validate these findings and explore the underlying pathophysiological mechanisms.

Antipsychotic Polypharmacy and Its Relation to Metabolic Syndrome in Patients With Schizophrenia: An Egyptian Study.

PURPOSE/BACKGROUND: Few studies have examined the relationship between antipsychotic polypharmacy and metabolic syndrome in schizophrenia. Some studies suggest that antipsychotic polypharmacy may be associated with greater metabolic risk, whereas other studies suggest that this is uncertain. To date, there have been no studies in Egypt or the Arab world that have investigated this relationship. We sought to compare subjects with schizophrenia receiving antipsychotic polypharmacy and monotherapy as regards metabolic outcomes and to investigate medication-related factors associated with metabolic syndrome. METHODS/PROCEDURES: We recruited 118 subjects with schizophrenia and compared between those receiving antipsychotic polypharmacy (86 subjects) and monotherapy (32 subjects) as regards demographic, clinical, metabolic, and antipsychotic medication characteristics. We examined the effect of antipsychotic-related factors an outcome of metabolic syndrome. FINDINGS/RESULTS: The prevalence of metabolic syndrome in our sample was 38.1%. Except for gender, there was no statistically significant difference as regards demographic and clinical characteristics, rates of metabolic syndrome, or for individual metabolic parameters. We found a statistically significant difference (P < 0.05) between the 2 groups as regards the number, dose, and duration of intake and for the number of subjects receiving typical antipsychotics (oral and depot) and a number of individual antipsychotic medications. Using logistic regression, receiving haloperidol depot was the only antipsychotic-related factor predictive for metabolic syndrome. IMPLICATIONS/CONCLUSIONS: The prevalence of metabolic syndrome does not differ in schizophrenia whether patients are receiving polypharmacy and monotherapy nor do they differ for individual metabolic parameters. Most antipsychotic-related characteristics did not predict for metabolic syndrome.

Assessment of annexin A5 and annexin A2 levels as biomarkers for pre-eclampsia: A pilot study.

Deficient anticoagulant activity of annexin A5 and deficient profibrinolytic activity of annexin A2 have been linked to increased risk of thrombotic events. Placental dysfunction due to fibrin deposition/microthrombi has been implicated in the pathogenesis of pre-eclampsia (PE). In this study, we aimed to assess serum levels of annexin A5 and annexin A2 in a cohort of PE patients and investigate their role as biomarkers for the development of the disease. We examined 80 women in total; 40 healthy pregnant women and 40 pregnant women with PE after 20weeks of pregnancy. Women were subjected to full clinical assessment, ultrasonography, and laboratory testing including complete blood picture, liver and kidney function tests and assessment of serum and urine proteins. Annexin A5 and annexin A2 were analyzed using enzyme-linked immunosorbent assay. The study showed serum annexin A2 but not annexin A5 was significantly reduced (P=0.029) in women with PE (total and severe cases) compared to those with normal pregnancy. The ROC analysis of annexin A2 level for the prediction of development of PE showed an area under the curve of 0.64 (P=0.029), and the best cut-off value was 0.89ng/ml with a sensitivity of 70.0% and a specificity of 70.0%. Univariate analysis showed annexin A2 of <0.89ng/ml, proteinuria, lower platelet count and higher BP were associated with significantly higher risk to develop PE. Based on this pilot study, serum annexin A2 levels may be a useful biomarker for pre-eclampsia. However, a larger study is required before a final conclusion is made.

The utility of International Society on Thrombosis and Haemostasis-Bleeding Assessment Tool and other bleeding questionnaires in assessing the bleeding phenotype in two platelet function defects.

The main objective of this study is to investigate the utility of International Society on Thrombosis and Haemostasis-Bleeding Assessment Tool (ISTH-BAT) in comparison with the condensed form of Molecular and Clinical Markers for the Diagnosis and Management of type 1 and WHO BATs, in assessing bleeding in two well known and clinically significant platelet function defects. Thirty-eight patients previously diagnosed with Glanzmann's thrombasthenia and 10 with Bernard-Soulier syndrome (BSS) were analyzed. Bleeding scores were significantly higher than that of controls using both electronic bleeding questionnaire (eBQ) and ISTH-BAT with no significant difference between both tools. ISTH-BAT had a sensitivity, specificity, positive predictive value and negative predictive value of 100%, 76.2%, 0.9 and 1. This was closely similar to eBQ. Both ISTH-BAT and eBQ are efficient in BSS and Glanzmann's thrombasthenia. However, given the ISTH recommendation, ISTH-BAT should be adopted. Larger study including other platelet defects will enhance its utility and support the integration of bleeding scores with standardized laboratory testing to allow for a universal diagnostic approach to patients with suspected bleeding disorders.

VKORC1 and CYP2C9 genotypes in Egyptian patients with warfarin resistance.

Warfarin is the most commonly prescribed anticoagulant drug; however, a narrow therapeutic range and a high risk of bleeding or stroke complicate its clinical use. Warfarin resistance was defined as prolonged warfarin requirements of more than 15 mg/day to achieve therapeutic anticoagulation or failure to achieve therapeutic anticoagulation with more than 20 mg/day. The resistance is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex (VKORC1) and cytochrome P450-2C9 (CYP2C9) genes, which affect warfarin pharmacodynamics and pharmacokinetics, respectively. Identification of the VKORC1 -1639 (A/G) and CYP2C9 (*1/*2/*3) allelic variants was performed using the PGX-Thrombo Strip in 41 patients with warfarin resistance compared with 30 patients with normal warfarin response out of 352 diagnosed cases of deep vein thrombosis. In warfarin-resistant patients, the VKORC1-1639 genotype frequencies were GG 0.756, GA 0.244 and AA 0.0, whereas in warfarin responder patients, they were: GG 0.333, GA 0.400 and AA 0.276 with P ≤ 0.001. The CYP2C9 genotype frequencies showed nonsignificant difference in both group of patients (P = 0.31). Our results suggest that the VKORC1-1639 GG and the wild type CYP2C9*1*1genotypes are associated with the high-dose requirement for warfarin therapy, and that VKORC1-1639 GG is responsible for warfarin resistance and failure in Egyptian patients.

Association of Hemostatic Gene Polymorphisms With Early-Onset Ischemic Heart Disease in Egyptian Patients.

The association between hereditary thrombophilia and venous thrombosis is well established but controversial data exist with respect to arterial thrombosis. We performed a pilot study on 31 patients with acute myocardial infarction (AMI), 21 patients with unstable angina (UA), and 20 healthy volunteers to investigate the role of various hemostatic gene polymorphisms in young Egyptian patients, who survived their first ischemic heart disease (IHD). Thrombophilic gene polymorphisms were tested using multiplex polymerase chain reaction and reverse-hybridization technique. We showed an increased risk of AMI with factor V (FV) Leiden and prothrombin G20210A heterozygosity. The increased risks of UA was associated with GA and A allele of fibrinogen ß-455G→A polymorphism. Conversely, factor XIII (FXIII) Val34Leu GT and T allele were protective in the UA group. Nevertheless, the prevalence of FV H1299R, plasminogen activator inhibitor 1 4G/5G, glycoprotein IIIa C1565T, 5,10-methylenetetrahydrofolate reductase C677T, and A1298C mutations did not differ between patients with IHD and controls. The data have clinical implications regarding screening and thromboprophylaxis in high-risk individuals younger than 40 years.

Role of traditional healers in the pathway to care of patients with bipolar disorder in Egypt.

BACKGROUND: A large number of mentally ill patients prefer to visit non-medical practitioners such as traditional healers because of the confidence in the system, affordability and accessibility of the service. This may lead to delay in seeking psychiatric services and has prognostic impact. AIM: To assess the rate of bipolar affective disorder (BAD) patients seeking traditional healers, the sociodemographic and clinical correlates of those patients. METHODS: We assessed 350 patients with BAD after confirmation of diagnosis with Structured Clinical Interview for DSM-IV Axis I Disorder (SCID-I) research version and assessment of functioning with Global Assessment of Functioning scale. They were assessed for percent, rate and timing of seeking traditional healers. RESULTS: In all, 40.8% sought traditional healers, with 34.9% more than four times. Of those, 62.2% were before seeking psychiatric services and 37.8% after. Lower educational level, less impairment of functioning and presence of hallucinations were significant correlates. CONCLUSION: This study shows that most of the patients suffering from mental illness prefer to approach faith healers first, which may delay entry to psychiatric care and thereby negatively impact the prognosis of BAD. This highlights the importance of mental health education and developing a positive collaborative relationship with traditional healers.

Atherosclerotic effects of long-term old and new antiepileptic drugs monotherapy: a cross-sectional comparative study.

This work aimed to evaluate the metabolic and atherogenic effects of long-term antiepileptic drugs in a group of Egyptian epileptic patients. Sixty-nine epileptic patients on antiepileptic drug monotherapy for at least 2 years and 34 control subjects were recruited in this study. Patients were divided into 5 subgroups according to antiepileptic drugs used (valproate, carbamazepine, lamotrigine, topiramate, and levetiracetam). Fasting lipid profile (total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), lipoprotein(a), homocysteine, free thyroxine, thyroid-stimulating hormone, and common carotid artery intima-media thickness were measured for all subjects. Significant higher mean values of low-density lipoprotein cholesterol, low-density lipoprotein / high-density lipoprotein ratio, lipoprotein(a), homocysteine, significantly lower mean value of high-density lipoprotein cholesterol, and significantly larger diameter of common carotid artery intima-media thickness were observed in each drug-treated group versus control group. Our study supports that long-term monotherapy treatment with valproate, carbamazepine, lamotrigine, and topiramate had altered markers of vascular risk that might enhance atherosclerosis, whereas levetiracetam exerted minimal effect.

Correlates of psychiatric co-morbidity in a sample of Egyptian patients with bipolar disorder.

BACKGROUND AND OBJECTIVES: Bipolar disorder (BD) is a complex, chronic mood disorder involving repeated episodes of depression and mania/hypomania. Two thirds of patients with bipolar disorder have a comorbid psychiatric condition. This study aims to assess the prevalence of Axis I diagnosis with its socio-demographic and clinical correlates among a sample of Egyptian patients with bipolar disorder. METHODS: Out of the 400 patients who were enrolled in the study from number of governmental and private psychiatric hospitals in Cairo, Egypt, 350 patients diagnosed with bipolar affective disorders (157 females and 193 males) with age ranging from 18 to 55years were selected. Patients were assessed using the Structured Clinical Interview for DSM-IV Axis I disorder (Research Version) (SCID-I). RESULTS: Prevalence of psychiatric comorbidity among BD patients was 20.3% (71 patients) among which 63 patients (18%) had comorbid substance abuse and 8 patients (2.3%) had comorbid anxiety disorders. LIMITATIONS: The study was limited by its cross sectional design with some patients having florid symptoms during assessment, not having a well representative community sample. This might have decreased the reliability and prevalence of lifetime psychiatric comorbidity due to uncooperativeness or memory bias. The study group was composed of bipolar patients attending tertiary care service which limits the possibility of generalizing these results on different treatment settings. CONCLUSIONS: Substance abuse followed by anxiety disorders was found to be the most common psychiatric comorbidity. Family history of psychiatric disorders and substance abuse as well as current psychotic features were highly correlated with comorbidity.

Clinical significance of minimal residual disease in young adults with standard-risk/Ph-negative precursor B-acute lymphoblastic leukemia: results of prospective study.

Clinical risk classification is inaccurate in predicting outcome in adult patients with acute lymphoblastic leukemia (ALL), sometimes resulting in patients receiving inappropriate chemotherapy or stem cell transplantation. To identify complementary markers suitable for further treatment stratification in patients with standard-risk (SR)/philadelphia-negative (Ph-negative) precursor B-ALL, we evaluated the predictive value of minimal residual disease (MRD) after induction and consolidation chemotherapy in strictly defined SR/Ph-negative precursor B-ALL patients who were treated with a standard protocol using quantitative real-time polymerase chain reaction with the rearranged immunoglobulin heavy chain gene as a molecular marker. The cytologic complete response (CR) rate was 92.3 % after induction. At this time point, the molecular CR rate was 73.9%. Patients with molecular CR (MolCR) after induction had a significantly higher probability of disease-free survival (DFS; 78.8 vs 30.8%; P = .001) and of overall survival (OS; 82.4 vs 41.7%; P < .0001) compared to patients with molecular failure (MolFail). MRD at end consolidation had the same significance. Quantitative MRD assessment identified patients with MolFail after induction and/or consolidation as a high-risk group, with 3-year DFS and OS rates of 28.6 and 35.7%, respectively. Patients with MolCR after induction and consolidation were classified as low-risk and had 3-year DFS rate of 89.7% and OS rate of 93.3%. Thus, MRD quantification during treatment identified prognostic subgroups within the otherwise homogeneous SR/Ph-negative precursor B-ALL population who may benefit from individualized treatment.

Upregulation of CD40/CD40L system in rheumatic mitral stenosis with or without atrial fibrillation.

Platelet activation occurs in peripheral blood of patients with rheumatic mitral stenosis (MS) and atrial fibrillation (AF) and could be related to abnormal thrombogenesis. The CD40/CD40 ligand (CD40L) which reflects platelet activation, mediate a central role in thrombotic diseases. However, the role of CD40/CD40L system in rheumatic MS with or without AF remains unclear. Expressions of CD40 on monocytes and CD40L on platelets were determined by whole blood flow cytometry and serum levels of soluble CD40L were measured by enzyme-linked immunosorbent assay in group 1 (19 patients with MS) and group 2 (20 patients with MS and AF) compared to group 3 (10 controls). Patients with groups 1 and 2 had a significant increase in expression of CD40 on monocytes (P1 and P2 = 0.000) and serum levels of sCD40L (P1 = 0.014 and P2 = 0.033, respectively), but nonsignificant increase in expression of CD40L on platelets (P1 = 0.109 and P2 = 0.060, respectively) as compared to controls. There were no significant difference in all the parameters in group 1 compared to group 2. Correlation analysis demonstrated that there was a significant direct relationship between the severity of MS and serum levels of sCD40L (r = -0.469, p = 0.043). In conclusion, rheumatic MS patients with or without AF had upregulation of the CD40/CD40L system as well as elevated sCD40L levels. The levels of sCD40L had a significantly direct relationship with the severity of MS and it was the stenotic mitral valve, not AF, that had a significant impact on platelet activation.

The expression and concentration of CD40 ligand in normal pregnancy, preeclampsia, and hemolytic anemia, elevated liver enzymes and low platelet count (HELLP) syndrome.

Preeclampsia has been associated with increased platelet activation detected before disease onset. Inappropriate activation of platelets may be involved in pathogenesis in preeclampsia by promoting coagulation and thrombosis and also as a mediator of inflammation. The exaggerated platelet activation and inflammation leading to endothelial damage in preeclampsia can be explained by the CD40-CD40 ligand (CD40L) system. Expression of CD40L on platelets was determined by whole-blood flow cytometry, and serum levels of soluble CD40L (sCD40L) were measured by enzyme-linked immunosorbent assay in 11 women with mild preeclampsia, 11 women with severe preeclampsia, and six women with hemolytic anemia, elevated liver enzymes and low platelet count (HELLP) syndrome compared with 13 normotensive pregnant women as a control group. The platelet surface expression of CD40L was significantly higher in women with mild and severe preeclampsia and HELLP compared with normal pregnancy group (P = 0.001; P ≤ 0.001; P = 0.003, respectively), with no significant difference being found between women with mild preeclampsia compared with HELLP and severe preeclampsia compared with HELLP (P = 0.2; P = 0.8, respectively). The serum concentration of sCD40L was significantly higher in women with mild and severe preeclampsia and HELLP compared with the normal pregnancy group (P = 0.001; P ≤ 0.001; P = 0.022, respectively), with no significant difference being found between women with mild compared with severe preeclampsia or HELLP and severe preeclampsia compared with HELLP (P = 0.7; P = 0.6; P = 0.6, respectively). In conclusion, the higher expression and concentration of CD40L in women with preeclampsia and HELLP syndrome compared with normal pregnant women may indicate an exaggerated activation of platelets and endothelial cells in the disorder.

Clinical and biochemical aspirin resistance in patients with recurrent cerebral ischemia.

BACKGROUND AND AIM: Stroke recurrence is an important public health concern. One half of survivors remain disabled, and one seventh requires institutional care. Aspirin remains the cornerstone of primary and secondary stroke prevention; meanwhile, aspirin resistance is one of the possible causes of stroke recurrence. We aimed to evaluate the clinical and biochemical aspirin resistance in patients with recurrent ischemic stroke. PATIENTS AND METHODS: We studied demographic characteristics, vascular risk factors, stroke subtypes, radiologic findings and biochemical aspirin resistance tests using both arachidonic acid (AA) and adenosine diphosphate (ADP)-induced light transmittance aggregometry (LTA) on admission and 24 h after observed aspirin ingestion. RESULTS: Of the 82 patients with recurrent cerebral ischemia included in this study, 37 (45%) patients were poor compliant with aspirin. There were no statistically significant differences between the two groups regarding the demographic characteristics, stroke severity, laboratory tests, radiological findings or vascular risk factors. On admission, 19.6% and 4.8% of patients showed aspirin resistance, while 24 h after supervised 300 mg single aspirin dose ingestion, it was 9.8% and 2.4% using ADP and AA-induced LTA respectively. Of the eight aspirin resistant patients, two only showed resistance using both AA and ADP. Aspirin resistance was statistically significantly higher in the male gender, older age, hyperlipidemia, smokers and in all lacunar strokes using AA. CONCLUSION: Biochemical aspirin resistance in one's series was rather rare (2.4%) and was more prevalent in patients with lacunar strokes. Clinical aspirin failure may often be contributed to poor compliance with aspirin intake.