The effect of transfusion on immune responses in thalassemia.

BACKGROUND: Regular transfusions are the gold standard therapy for ß-thalassemia and are often complicated by secondary-iron overload and alloimmunization. We assessed the frequency of regulatory T cells (Tregs) and the levels of cytokines implicated in Th-responses in 49 patients 33 TDT and 16 NTDT in order to investigate the contribution of transfusion and its complications on immune responses. MATERIALS AND METHODS: Tregs were characterized with flow cytometry. Soluble IL-4, IL-6, IL-10, IL-17A, and TGF-ß1 were assessed by ELISA. Clinical data including alloimmunization, age of onset of transfusion splenectomy hepatitis B and C infection, iron overload assessment with MRI T2* (liver and heart) were recorded from the patients' files. RESULTS: Tregs levels, IL-6, IL-10, TGFß and serum ferritin were higher in the TDT compared to the NTDT group (all p < 0.05). There was no difference of Tregs and circulating cytokines in patients in correlation with the extend of iron overload (assessed by T2*liver), the type of chelator or the development of alloantibodies. DISCUSSION: Tregs levels are higher in TDT patients compared to NTDT, a difference which could be ascribed to transfusion. Tregs levels and the cytokines analyzed may play little role in alloimmunization and are not impacted by the extend of iron overload.

Comparison between Nageotte and flow cytometric counting of residual leucocytes in freshly prepared leucocyte-reduced red blood cell components.

BACKGROUND: Flow cytometry (FC) and Nageotte hemocytometry represent the most widely accepted methods for counting residual white blood cells (rWBCs) in leucocyte-reduced (LR) blood components. Our aim was to study the agreement between the two methods, under real working blood bank conditions. MATERIALS AND METHODS: 94 freshly produced LR red blood cell (RBC) units were tested for rWBC concentrations by FC and Nageotte. To assess the precision of each method, we calculated the intra-assay coefficients of variation (CV), and followed the Bland-Altman methodology to study the agreement between the two methods. RESULTS: CV was 18.5% and 26.2% for the Nageotte and the FC, respectively. However, the agreement between the duplicate observations, using the binary cut-off threshold of 1 × 106 WBCs per unit to define the results as "pass/fail", was 71.9% for the Nageotte and 93.3% for the FC. Linear regression analysis did not show any correlation (R-squared = 0.01, p = 0.35) between the two methods, while the Bland-Altman analysis for the measuring agreement showed a bias toward a higher Nageotte count of 0.77 × 106 leucocytes per unit (p < 0.001) with the 95% limits of agreement (d ± 2 sd) ranging from -0.40 × 106 to 1.94 × 106 leucocytes per unit. CONCLUSION: The absence of agreement between Nageotte and FC method, with the differences within d ± 2 sd being of high clinical importance, suggests that the two methods cannot be used for clinical purposes interchangeably. The Nageotte seems unsuitable for quality control even with a pass-fail criterion, under real working blood bank conditions.

Thromboelastometry for diagnosis of neonatal sepsis-associated coagulopathy: an observational study.

Our aim was to evaluate the potential role of standard extrinsically activated thromboelastometry (EXTEM) assay in the early detection of neonatal sepsis. We studied 91 hospitalized neonates categorized in two groups: group A included 35 neonates with confirmed sepsis, while group B included 56 neonates with suspected sepsis; 274 healthy neonates served as controls. Whenever sepsis was suspected, EXTEM assay was performed, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE) and Tοllner score were calculated, and clinical findings and laboratory results were recorded. Septic neonates had significantly prolonged clotting time (CT) and clot formation time (CFT), and reduced maximum clot firmness (MCF), compared to neonates with suspected sepsis (p values 0.001, 0.001, and 0.009, respectively) or healthy neonates (p values 0.001, 0.001, and 0.021, respectively). EXTEM parameters (CT, CFT, MCF) demonstrated a more intense hypocoagulable profile in septic neonates with hemorrhagic diathesis than those without (p values 0.021, 0.007, and 0.033, respectively). In septic neonates, CFT was correlated with platelet count, SNAPPE, Tollner score, and day of full enteral feeding (p values 0.01, 0.02, 0.05, and 0.03, respectively). CONCLUSIONS: A ROTEM hypocoagulable profile at admission seems promising for the early detection of sepsis in neonates while the degree of hypocoagulation may be associated with sepsis severity. What is Known: • The early phase of septicemia might be difficult to be recognized in neonates. In adult septic patients, the diagnostic and prognostic role of thromboelastometry (ROTEM) have been extensively investigated. • Limited data are available on the role of ROTEM as an indicator of early neonatal sepsis. What is New: • ROTEM measurements indicate an early appearance of hypocoagulability in neonatal sepsis, while the degree of hypocoagulation might be associated with severity of sepsis. • ROTEM could be a useful tool in the early detection of sepsis in neonates.

Juvenile Adamantiades-Behçet Disease.

Adamantiades-Behçet disease (ABD) is a chronic, multisystemic, recurrent, inflammatory vascular disorder of unknown etiology. Patients with symptoms initially appearing at the age of 16 or less are considered as cases of juvenile-onset ABD (JABD). JABD is relatively rare compared to ABD of adults, and only case reports and case studies have been published regarding this subtype of the disease. Epidemiology, clinical features, diagnosis and treatment of JABD are discussed in this review.

Seroprevalence of hepatitis E in HIV infected patients in Greece.

HEV infection is an emerging public health problem worldwide Data concerning HEV infection in HIV+ patients in Greece is scare. The aim of the study was to determine HEV seroprevalence in patients with HIV infection in Greece. We studied 243 HIV(+) patients 214 men (88%) and 29 women (12%) with a median age of 45 years (range 19-83) who attended the HIV unit of Pathophysiology Department of Laikon General Hospital in Athens for the presence of anti-HEV IgG antibodies with (EIA) (EIA HEV IgG, Adaltis, Rome, Italy Eighteen/243 patients (7.3%) were positive for HEV IgG antibodies, a seroprevalence that was not different from that described for the blood donors group from Greece There was no difference of the presence of HbsAg, hepatitis C and hepatitis A between the HEV(+) and HEV(-) patients. There was no statistically significant difference between the HEV(+) and HEV(-) group in terms of HIV acquisition, sexual orientation, median duration of HIV infection, ART treatment, or duration of ART. Only the median age of HEV(+) was 52 years (35-78) while that of HEV(-) was 44 years (19-83)(P = 0.03). Only 2/18(11.1%) HEV(+) HIV(+) patients had abnormal ALT and AST values. The seroprevalence of hepatitis E in HIV(+) patients in Greece seems to be the same with that of the general population thus implying that HIV infection is not a risk factor for HEV infection and only age shows a positive correlation with seropositivity.

The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G/5G polymorphism, and myocardial infarction: a Mendelian randomization meta-analysis.

BACKGROUND: The circulating levels of plasminogen activator inhibitor type 1 (PAI-1) are increased in individuals carrying the 4G allele at position -675 of the PAI-1 gene. In turn, overexpression of PAI-1 has been found to affect both atheroma and thrombosis. However, the association between PAI-1 levels and the incidence of myocardial infarction (MI) is complicated by the potentially confounding effects of well-known cardiovascular risk factors. The current study tried to investigate in parallel the association of PAI-1 activity with the PAI-1 4G/5G polymorphism, with MI, and some components of metabolic syndrome (MetS). METHODS: Using meta-analytical Mendelian randomization approaches, genotype-disease and genotype-phenotype associations were modeled simultaneously. RESULTS: According to an additive model of inheritance and the Mendelian randomization approach, the MI-related odd ratio for individuals carrying the 4G allele was 1.088 with 95% confidence interval (CI) 1.007, 1.175. Moreover, the 4G carriers had, on average, higher PAI-1 activity than 5G carriers by 1.136 units (95% CI 0.738, 1.533). The meta-regression analyses showed that the levels of triglycerides (p=0.005), cholesterol (p=0.037) and PAI-1 (p=0.021) in controls were associated with the MI risk conferred by the 4G carriers. CONCLUSIONS: The Mendelian randomization meta-analysis confirmed previous knowledge that the PAI-1 4G allele slightly increases the risk for MI. In addition, it supports the notion that PAI-1 activity and established cardiovascular determinants, such as cholesterol and triglyceride levels, could lie in the etiological pathway from PAI-1 4G allele to the occurrence of MI. Further research is warranted to elucidate these interactions.

The lung in the spectrum of antiphospholipid syndrome.

Patients with antiphospholipid syndrome may develop various lung manifestations. The lung complications that have been described so far are pulmonary thromboembolic disease, pulmonary hypertension, acute respiratory distress syndrome, primary thrombosis of large and small lung vessels, diffuse alveolar haemorrhage, fibrosing alveolitis and postpartum syndrome. Clinicians should be aware of these conditions as in most of these cases, timely diagnosis and treatment is needed.

The role of procalcitonin and IL-6 in discriminating between septic and non-septic causes of ALI/ARDS: a prospective observational study.

BACKGROUND: The aim was to evaluate the clinical usefulness of a single plasma and bronchoalveolar lavage fluid (BALF) PCT and IL-6 measurement in discriminating septic from non-septic causes of acute respiratory distress syndrome (ARDS) and forecasting clinical outcomes. METHODS: One hundred patients were enrolled within 48 h of ALI/ARDS recognition. Demographic, clinical data, severity indices were recorded and PCT and IL-6 concentrations were measured in plasma and BALF. RESULTS: Plasma PCT and IL-6 values were significantly higher in septic compared to non-septic individuals (p=0.001 and 0.0005, respectively), while there were no differences in their respective BALF values. As far as identification of septic vs. non-septic ARDS is concerned, the comparison of the areas under the curves favored PCT vs. IL-6 [0.88, (95% CI 0.81-0.95) vs. 0.71, (95% CI 0.60-0.81); χ(2)=9.04, p=0.003]. A plasma PCT level of 0.815 ng/mL was associated with 74.1% sensitivity and 97.6% specificity in identifying septic ARDS cases; this corresponded to a diagnostic odds ratio value of 116. Linear regression multivariable analysis disclosed a significant relation of plasma PCT with SOFA score in septic ARDS patients (p<0.001), while neither BALF PCT nor IL-6 levels were associated with clinical outcome. CONCLUSIONS: Early plasma - but not BALF - PCT concentrations can discriminate between septic and non-septic ARDS causes and are associated with the severity of multiple organ dysfunction syndrome in septic ARDS patients. However, neither plasma or BALF IL-6 levels nor BALF PCT levels carry any prognostic potential. A single plasma PCT value higher than 0.815 ng/mL makes a non-septic cause of ARDS highly unlikely.

Evaluation of the role of the new INNOVANCE PFA P2Y test cartridge in detection of clopidogrel resistance.

Light transmittance aggregometry (LTA) has been extensively used in monitoring clopidogrel therapy. However, the availability of simple and rapid point-of-care platelet function assays is of great clinical importance. Thus, the manufacturer of the Platelet Function Analyzer (PFA)-100 System has recently produced the INNOVANCE PFA P2Y test cartridge. We assessed the ability of this new test to reliably detect clopidogrel resistance. We enrolled 90 consecutive patients with coronary artery disease receiving chronic clopidogrel maintenance therapy in combination with aspirin. Twenty healthy volunteers served as controls. Clopidogrel resistance was simultaneously analysed by the INNOVANCE PFA P2Y test cartridge, ADP-induced LTA, the flow-cytometric vasodilator-stimulated phosphoprotein (VASP)-phosphorylation assay and the multiple electrode aggregometry (Multiplate). Agreement among the four platelet function methods by two was assessed using Cohen's kappa coefficient. According to the cut-off points for clopidogrel resistance proposed by the literature, agreement was fair between INNOVANCE PFA-100 P2Y and LTA (74.4%) and Multiplate (75.6%), while poor agreement was noticed in VASP assay (63.3%). Based on cut-off points indicating a higher thrombotic risk, agreement between the PFA-100 System and the other three methods did not significantly differ compared to the previous cut-offs (72.2%, 71.1% and 55.1%, respectively). The INNOVANCE PFA-100 P2Y test seems to be comparable to other established platelet function assays in detecting clopidogrel resistance. However, the modest agreement among platelet function methods makes the performance of platelet function testing crucial with more than one technique in order to reliably identify poor responders to clopidogrel treatment.

Angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism and circulating ACE levels are not associated with outcome in critically ill septic patients.

BACKGROUND: In critically ill patients independent studies have shown contradictory findings regarding the prognostic significance of the D/D genotype of the I/D angiotensin converting enzyme (ACE) polymorphism. The study aim was to evaluate the effect of both ACE I/D polymorphism and ACE serum levels on the clinical outcomes of critically ill septic patients. METHODS: This study recruited 186 Caucasian patients with sepsis, severe sepsis or septic shock. Epidemiological, clinical data, co-morbidities and severity scores were recorded. Measurements of serum ACE activity and genotyping for ACE I/D polymorphism were carried out. Primary outcomes were the 28- and the 90-day mortality; secondary outcomes included the number of days without renal or cardiovascular failure and ventilation-free days over the 28-day period following study enrolment. RESULTS: Neither 28- nor 90-day mortality were associated with ACE I/D polymorphism (p=0.59 and 0.34, respectively) or circulating ACE levels (p=0.17 and 0.25, respectively). Similarly, ACE polymorphism and levels were not related to ventilation-free days (p=0.14 and 0.25, respectively), days without cardiovascular failure (p=0.14 and 0.81, respectively) and days without renal failure (p=0.64 and 0.27, respectively). CONCLUSIONS: Neither ACE I/D polymorphism nor serum ACE levels seem to be significant prognostic factors of clinical outcomes in septic, critically ill patients.

Cell cycle and apoptosis regulatory gene expression in the bone marrow of patients with de novo myelodysplastic syndromes (MDS).

Deregulation of cell cycle and apoptosis pathways are known contributors to the pathogenesis of myelodysplastic syndromes (MDS). However, the underlying mechanisms are not fully clarified. The aim of our study was to examine mRNA expression levels of cell cycle and apoptosis regulatory genes, as well as the percentage of apoptotic and S phase cells and to correlate the findings with clinical characteristics and prognosis. Sixty patients with MDS, classified according to FAB (17 RA, five RARS, 19 RAEB, nine RAEBT, ten CMML) and WHO (ten RA, three RARS, seven RCMD, two RCMD-RS, 11 RAEBI, eight RAEBII, ten CMML, and nine AML) were included in the study. We found increased expression of anti-apoptotic bclxL and mcl1 genes and decreased expression of p21 gene in MDS patients. Moreover, we found increased expression of anti-apoptotic mcl1 gene in patients with higher than Intermediate-1 IPSS group. Multivariate analysis confirmed that combined expression of apoptotic caspases 8, 3, 6, 5, 2, 7, and Granzyme B was decreased in MDS patients. Regarding cell cycle regulatory genes expression, we demonstrated increased expression of cyclin D1 in patients with CMML Increased combined expression of cyclins B, C, D1, and D2 was found in patients with cytogenetic abnormalities. The two pathways seem to be interconnected as shown by the positive correlation between CDKs 1, 2, 4, p21 and the level of apoptosis and positive correlation between apoptotic caspase 3 expression and the percentage of S phase cells. In conclusion, our study showed altered expression of genes involved in apoptosis and cell cycle in MDS and increased expression of cyclin D1 in patients with CMML.

Regulatory T Cell Counts and Development of Malignancy in Patients with HIV Infection.

BACKGROUND: T-regulatory cells (Tregs) play an important role in maintaining homeostasis by attenuating the cytokine response to T-cell receptor (TCR) stimulation and by suppressing the functioning of neighboring immune cells. In Human Immunodeficiency Virus (HIV) infection, Tregs can be either beneficial, by suppressing generalized T-cell activation, or detrimental, by suppressing protective anti-HIV cell-mediated immunity. An imbalance of Tregs and effector T-cells can blunt immune responses to malignant cells or facilitate inflammation-mediated pathologies. OBJECTIVE: The purpose of our study was to explore the possible correlation between Tregs' concentration and HIV infection's parameters as well as the development of hematological and solid malignancies. METHODS: In a longitudinal prospective study, ex vivo phenotyping of fresh peripheral blood mononuclear cells from patients with primary HIV infection was performed at baseline. All patients were then followed up every 3 months and the development of solid or hematological malignancies was noted. RESULTS: A total of 155 patients were included in the study and the median follow-up period was 64 months. Treg counts were significantly higher among males, patients with high viral load (>350 copies/ml) and patients with virological failure to antiretroviral treatment (ART). Linear regression analysis showed a significant negative correlation between Treg levels and CD4 (+) T-cell counts. Patients with neoplasia had lower levels of Tregs while increasing levels showed a negative correlation with the development of neoplasia. CONCLUSION: In our population of HIV-infected patients, high levels of Tregs were associated with disease progression, and low baseline levels were associated with a higher probability of developing neoplasia.

Superiority of synovial membrane mesenchymal stem cells in chondrogenesis, osteogenesis, myogenesis and tenogenesis in a rabbit model.

Engineering complex tissues is perhaps the most ambitious goal of all tissue engineers. Despite significant advances in tissue engineering, which have resulted in successful engineering of simple tissues such as skin and cartilage, there are a number of challenges that remain in engineering of complex, hybrid tissue structures, such as osteochondral tissue. Mesenchymal stem cells (MSCs) have the capacity to highly proliferate in an undifferentiated state and the potential to differentiate into a variety of different lineages, providing a promising single cell source to produce multiple cell types. MSC obtained from adult human contribute to the regeneration of mesenchymal tissues such as bone, cartilage, fat, muscle, tendon and marrow stroma. In the present study, the regeneration capacity of multipotent MSCs derived from different tissues in the rabbit were compared. Specifically the aim of this study was to isolate and characterize rabbit adult stem cell populations from bone marrow, adipose, synovial membrane, rotator cuff, ligament and tendon and assess their cell morphology, growth rate, cell surface markers and differentiation capacity. MSCs derived from synovial membrane showed superiority in terms of chondrogenesis, osteogenesis, myogenesis and tenogenesis, suggesting that synovial membrane-derived MSCs would be a good candidate for efforts to regenerate musculoskeletal tissues.

Reemergence of West Nile Virus Infections in Southern Greece, 2017.

Greece experienced the largest European West Nile virus (WNV) outbreak in 2010 since the 1996 Romania epidemic. West Nile virus reemerged in southern Greece during 2017, after a 2-year hiatus of recorded human cases, and herein laboratory findings, clinical features, and geographic distribution of WNV cases are presented. Clinical specimens from patients with clinically suspected WNV infection were sent from local hospitals to the Microbiology Department of Medical School, National and Kapodistrian University of Athens, and were tested for the presence of specific anti-WNV antibodies and WNV RNA. From July to September 2017, 45 confirmed or probable WNV infection cases were identified; 43 of them with an acute/recent infection, of which 24 (55.8%) experienced WNV neuroinvasive disease (WNND). Risk factors for developing WNND included advanced age, hypertension, and diabetes mellitus. A total of four deaths (16.7%) occurred, all in elderly patients aged > 70 years. Thirty-nine cases were identified in regional units that had not been affected before (36 in Argolis and two in Corinth, northeastern Peloponnese, and one in Rethymno, Crete). The remaining four cases were reported from previously affected regional units of northwestern Peloponnese. The reemergence of WNV after a 2-year hiatus of recorded human cases and the spread of the virus in newly affected regions of the country suggests that WNV has been established in Greece and disease transmission will continue in the future. Epidemiological surveillance, intensive mosquito management programs, and public awareness campaigns about personal protective measures are crucial to the prevention of WNV transmission.

Immunophenotypic Profile of CD34+ Subpopulations and Their Role in the Diagnosis and Prognosis of Patients with De-Novo, Particularly Low-Grade Myelodysplastic Syndromes.

BACKGROUND: Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders with unknown aetiology. Multiparameter flow cytometry (MFC) is being evaluated for the diagnosis and prognosis of MDS. METHODS: In the present study, five-color MFC was performed on bone marrow aspirates of 50 untreated patients, newly diagnosed with MDS and 27 age matched control samples. Patients were classified according to World Health Organization 2016, International Prognostic Scoring System (IPSS), and Revised IPSS (IPSS-R). RESULTS: Significantly higher CD133+/CD90-CD45weak, CD117+/TdT-CD45weak, and CD33+/MPO-neutrophil precursor percentages on CD34+ cells, as well as a significant decrease of lymphoid and erythroid precursors were observed in the group of MDS patients in comparison to controls. A new scoring system was based on these findings, which can be helpful in discriminating lower risk MDS patients, including those with normal karyotype (a subgroup of MDS with diagnostic challenges). In addition, an increased level of apoptosis of CD34+/CD117+ cells was identified as an independent favorable prognostic factor both for the risk of transformation to acute myeloid leukemia and for overall survival. CONCLUSIONS: A new scoring system based on the expression of immature cell antigens on CD34+ cells (by itself or in combination with the Ogata score) can discriminate lower risk MDS patients, including those with normal karyotype, from the normal control group. © 2018 International Clinical Cytometry Society.

Evaluation of a convenient vaccination schedule against hepatitis B in HIV-patients with undetectable HIV viral load.

Vaccination against hepatitis B virus (HBV) is recommended for all HIV-positive individuals but the standard schedule is not satisfactory. High or more doses have also been studied with variable results. We compared a vaccination schedule with a higher dose but fewer shots to the standard scheme (HBVaxPro 40 µg versus Engerix 20 µg at 0, 1, and 6 months). Of the 63 patients vaccinated with HBVaxPro 79%, 65% and 47% seroconverted at month 1, 12 and 24 after vaccination, respectively. A total of 137 patients received Engerix and showed lower response rates (68%, 53% and 38%, respectively). Anti-HBs titers in the Engerix group were also lower with a statistically significant difference. In patients younger than 55 years HBVaxPro was 3 times more likely to provoke a response compared with Engerix (OR = 3, p = 0.006). In conclusion, HBVaxPro 40 µg at 3 doses could be proposed as a more robust and acceptable alternative.

Laboratory Assessment of the Anticoagulant Activity of Apixaban in Patients With Nonvalvular Atrial Fibrillation.

Our aim is to determine the most appropriate laboratory tests, besides anti-factor Xa (anti-FXa) chromogenic assays, to estimate the degree of anticoagulation with apixaban and compare it with that of rivaroxaban in real-world patients. Twenty patients with nonvalvular atrial fibrillation treated with apixaban 5 mg twice daily and 20 patients on rivaroxaban 20 mg once daily were studied. Conventional coagulation tests, thrombin generation assay (TGA), and thromboelastometry (nonactivated TEM [NATEM] assay) were performed in the 40 patients and 20 controls. The anti-FXa chromogenic assays were used to measure apixaban and rivaroxaban plasma levels. The NATEM measurements showed no significant difference between the 2 groups of patients. Concerning TGA, endogenous thrombin potential (ETP) was significantly decreased in patients on rivaroxaban as compared to those treated with apixaban (P < .003). A statistically significant, strong inverse correlation between apixaban plasma concentrations and ETP (P < .001) was observed. Apixaban significantly reduces ETP compared to controls, but to a lesser extent than rivaroxaban. Thrombin generation assay might provide additional information on apixaban exposure, which is required in order to individualize treatment especially for patients with a high bleeding risk. Our findings have to be further investigated in studies with larger sample sizes, in the entire range of apixaban exposure, with other direct oral anticoagulants, and in relation to clinical outcomes.

Grouping of patients with common variable immunodeficiency based on immunoglobulin biosynthesis: comparison with a classification system on CD4-naïve cells.

The present study compared two different systems of classification of patients with common variable immunodeficiency (CVID); one based on in vitro immunoglobulin biosynthesis; and another on CD4-naïve cell counts. Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with CVID and 20 healthy controls. They were stimulated for the secretion of IgM and IgG after stimulation with Staphylococcus aureus Cowan I (SAC) upon supplementation of interleukin-2 (IL-2) or with pokeweed mitogen. T cell subsets were estimated by flow cytometry. By the first system, patients were classified into group A (n=18) with secretion of neither IgG nor IgM; into group B (n=12) with detectable IgM but no IgG secretion; and into group C (n=5) with IgM and IgG secretion similar to controls. By the second system, patients were classified into group I (n=12) with less than 109 CD4-naïve cells/mul; into group II (n=12) with CD4-naïve cells within 109-225microl(-1); and into group III (n=11) with more than 225 CD4-naïve cells/mul. All groups I-III were defective for in vitro release of IgG and IgM. The likelihood ratio for splenomegaly in patients with <225 CD4-naïve cells/mul was 5.08 (p: 0.024). CD4-naïve cell counts of patients were positively correlated to serum levels of IgG and IgA of patients. The presented results revealed that the former system described adequately the function of B cells and the latter the clinical status of the patient. Our proposal is that both should be used for the characterization of patients with CVID.

Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of ischemic stroke: a meta-analysis.

This study investigated the hypothesis that the insertion/deletion (4G/5G) polymorphism of the plasminogen activator inhibitor type-1 gene affects the risk for ischemic stroke, since results concerning this association have been controversial. We therefore performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out until January 2006. The analysis was performed using random-effects models and meta-regression. Eighteen eligible studies were retrieved (15 case-control studies and three cohort studies). The case-control studies included 3104 cases and 4870 control individuals concerning the contrast of 4G/4G versus remaining genotypes. The 4G pooled allele frequencies in cases and controls were 54.21 and 54.75%, respectively. Overall, the per-allele odds ratio of the 4G allele was 0.98 (95% confidence interval, 0.858-1.121). Regarding genotypes, we derived nonsignificant odds ratios in all contrasts. The subanalysis including the three studies with a prospective design in the 4G/4G versus 5G/5G contrast derived a significant result (relative risk, 0.523; 95% confidence interval, 0.353-0.775), but the estimated effect size was insignificant when cohort and case-control studies were analyzed together (relative risk, 0.848; 95% confidence interval, 0.662-1.087). We failed to demonstrate a significant association between the 4G/5G polymorphism and ischemic stroke under basal conditions. Determination of plasminogen activator inhibitor type-1 function seems of much higher clinical value than determination of the 4G/5G polymorphism. The effect of this genotype on risk of ischemic stroke in acute stressful diseases and the role of cohort studies in genetic epidemiology, however, warrant further investigation.

Early syphilis affects markers of HIV infection.

The objective of this study was to investigate if early syphilis infection affects markers of HIV infection; CD4 T cells and viral load (VL). A retrospective study was performed on 160 HIV-positive patients (111 receiving antiretroviral therapy [ART] and 49 without ART). Early syphilis diagnosis was made in HIV patients during their follow-up at the HIV/AIDS Unit at a Greek Dermatology and Venereology Unit. The patients' blood tests were available at the time of diagnosis, as well as before and 12 weeks after early syphilis diagnosis. CD4 T cell counts and VL levels were measured. It was found that syphilis infection had a negative impact on the CD4 T cell counts in both groups, with reduced CD4 T cell counts observed in 84.6% (99/111) and 79.5% (39/49) of patients receiving and not receiving ART, respectively. After treatment for syphilis, CD4 T cell counts returned to pre-treatment levels in most patients, especially those receiving ART. There was a slight and transient VL increase. Patients receiving ART had a 27% increase in VL, compared to 71.4% among patients not receiving ART. Although the VL increase was slight (41-14,000 copies/ml) in the group under treatment, 4-5% (5/111) patients did not return to pre-treatment levels. Moreover, viral mutations associated with treatment resistance were identified in these patients. Early syphilis accelerates and complicates the progression of HIV infection. Early diagnosis and treatment of syphilis may prevent infection-associated complications in most instances. Consequently, prevention of syphilis and other sexually transmitted infections is of great importance for patients infected with HIV.