Maciej Pastuszczak

Prior simvastatin treatment is associated with reduced thrombin generation and platelet activation in patients with acute ST-segment elevation myocardial infarction

BACKGROUND It has been reported that statin therapy produces additional effects including impaired activation of blood coagulation. It is not clear whether statins can affect hemostasis in patients with acute coronary syndrome. The aim of this study was to investigate the effect of prior statin treatment on thrombin generation and platelet activation in patients with ST-segment elevation myocardial infarction (STEMI). METHODS We studied 53 consecutive STEMI patients admitted within 12 hours of pain onset, including 19 treated with simvastatin (40 mg/d) (simvastatin group) at least one month prior to STEMI, and 34 not receiving any statins (no-statin group) on admission. Thrombin-antithrombin (TAT) complexes generation and soluble CD40 ligand (sCD40L) release were determined in 60-second blood samples collected at the site of microvascular injury. RESULTS There were no significant intergroup differences with respect to clinical and laboratory variables, including plasma TAT and sCD40L levels, except lower total cholesterol and low-density lipoprotein cholesterol in the simvastatin group. The mean maximum rate of TAT generation was 47.5% lower (p=0.0002) and sCD40L release 33.3% lower (p=0.0006) in the simvastatin group. Total amounts of TAT (p<0.0001) and sCD40L (p=0.002) collected within 5 minutes of bleeding were lower in simvastatin-pretreated patients. By multivariate regression analysis, variables describing local TAT and sCD40L profiles in the whole group were independently associated with simvastatin pretreatment (p<0.0001), but not with cholesterol, platelet count or troponin levels. CONCLUSIONS Prior simvastatin use is associated with lower thrombin generation and platelet activation following vascular injury in the early phase of STEMI.

Current standards for diagnosis and treatment of syphilis: selection of some practical issues, based on the European (IUSTI) and U.S. (CDC) guidelines

Syphilis continues to be an important epidemiologic problem. For a few years a steady increase in the incidence of this sexually transmitted disease has been observed. Advances in medical science obligate the doctor to use only such diagnostic and therapeutic approaches that are scientifically proven. Based on the European (IUSTI) and U.S. (CDC) guidelines, in this manuscript, we present some selected practical issues concerning diagnosis and treatment of syphilis. We truly hope that the present review will help all doctors taking care of syphilitic patients to systematize the current knowledge.

The effect of chronic kidney disease on fibrin clot properties in patients with acute coronary syndrome.

Chronic kidney disease (CKD), defined as a decreased estimated glomerular filtration rate (eGFR < 60 ml/min), is an independent risk factor for cardiovascular events. Both acute coronary syndrome (ACS) and end-stage renal disease have been shown to be associated with formation of compact fibrin clots relatively resistant to lysis. The aim of the current study was to evaluate the effect of CKD on fibrin clot properties in patients with ACS. In 30 ACS patients, aged 48–72 years, with CKD and 30 ACS patients with eGFR more than 60 ml/min, we investigated plasma fibrin clot properties using permeation and turbidity assays, including three different clot lysis assays. The ACS patients with eGFR less than 60 ml/min and those with normal filtration rate did not differ with regard to demographics, risk factors, medications and routine laboratory tests, including fibrinogen. The former group had higher plasminogen activator inhibitor-1 (P = 0.002) and tissue-type plasminogen activator (tPA) (P = 0.008). Compared with ACS patients with eGFR more than 60 ml/min, the ACS patients with CKD formed less porous fibrin clots (P = 0.004) and susceptible to fibrinolysis (P < 0.001), had thicker overall fibrin fibers (P = 0.007), earlier onset of fibrin clot formation (P = 0.004) and increased clot mass (P < 0.001). By multiple regression analysis, clot permeability was independently predicted by eGFR (P = 0.0005) and fibrinogen (P = 0.001), whereas the only predictors of lysis time were eGFR (P = 0.006) and tPA (P = 0.002). This study indicates that ACS patients with CKD display unfavorable fibrin clot properties including impaired fibrinolysis, which might contribute to worse outcome in this population.

Elevated cerebrospinal fluid interleukin-17A and interferon-γ levels in early asymptomatic neurosyphilis.

Background The mechanisms underlying the process of Treponema pallidum clearance from the central nervous system have not yet been established. Considering that neurosyphilis is associated with mild cerebrospinal fluid (CSF) pleocytosis with a lymphocytic predominance, it has been suggested that cells involved in the adaptive immune response may play a role in this process. In the current study, we assessed the cytokine production profile of T-helper cells in the serum and CSF of patients with early syphilis, with and without CSF abnormalities. Methods Cerebrospinal fluid and blood samples were collected from 33 patients with secondary and early latent syphilis. Five patients (15%) had a reactive CSF Venereal Disease Research Laboratory test without any accompanying neurological symptoms. According to the Centers of Disease Control and Prevention classification, they were diagnosed with asymptomatic neurosyphilis. Serum and CSF levels of interferon-&ggr; (IFN-&ggr;; Th1-type cytokine), interleukin-4 (IL-4; Th2-type cytokine), and interleukin-17A (IL-17A; Th17-type cytokine) were determined by enzyme-linked immunosorbent assay. Results Patients with asymptomatic neurosyphilis had significantly higher levels of IL-17A (8-fold) and IFN-&ggr; (7.8-fold) in the CSF compared with patients in the no-neurosyphilis group. Six individuals had CSF pleocytosis but a negative CSF Venereal Disease Research Laboratory test result (presumptive neurosyphilis group). In this group, CSF IFN-&ggr; and CSF IL-17A levels were also significantly elevated when compared with no-neurosyphilis group. There was no correlation between serum and CSF concentrations of IL-17A. However, CSF pleocytosis correlated positively with both CSF IL-17A (r = 0.4, P = 0.01) and IFN-&ggr; (r = 0.42, P = 0.01). Conclusions Increased CSF levels of IFN-&ggr; and IL-17A in syphilitic patients with CSF abnormalities suggest that cells of adaptive immunity (probably T-helper cells producing IFN-&ggr; and IL-17) may contribute to the inflammatory response associated with neurosyphilis. In addition, the lack of correlation between serum and CSF IL-17A levels suggests intrathecal production of this cytokine. Further studies are needed to establish the exact nature of the immune response accompanying neurosyphilis and its clinical significance.

Robust pro-inflammatory immune response is associated with serological cure in patients with syphilis: an observational study

Objectives Approximately 15% of adequately treated patients with early syphilis remain serofast. Pathogenesis and clinical significance of this phenomenon is unclear. The objective of this study was to determine whether there is any association between host immune response and treatment outcome (serofast state or proper serological response). Methods Forty-four patients with secondary syphilis were enrolled to this study. Levels of pro-inflammatory cytokines such as interferon-γ, tumour necrosis factor-α and interleukin-6 were measured before treatment and 8 hours after injection of antibiotic. Results After 1 year, based on the serological response patients were stratified into two groups: (1) proper serological response (n=31) and (2) serofast state (n=9). The serological cure rate was 77.5% at 12 months after treatment. Patients with proper serological response had significantly higher levels of analysed cytokines (at baseline and 8 hours after treatment) compared with the serofast state group (p<0.05). Conclusions We showed that robust host pro-inflammatory immune response to infection may be the predictive factor of serological cure. The treatment outcome may be also associated with the magnitude of immune reaction occurring during the treatment.

Functional characterisation of plasma fibrin clots in Polish carriers of fibrinogen γArg275His mutation (fibrinogen Zabrze)

Functional characterisation of plasma fibrin clots in Polish carriers of fibrinogen γArg275His mutation (fibrinogen Zabrze) -

Association of Interleukin-10 promoter polymorphisms with neurosyphilis

Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine. Increased production of IL-10 has been found in late syphilis, presumably creating favorable conditions for bacteria persistence. Single-nucleotide polymorphisms (SNPs) within the promoter of IL-10 gene have been found to influence IL-10 production. We investigated whether SNPs in the IL-10 gene promoter are associated with cerebrospinal fluid (CSF) levels of IL-10 and neurosyphilis. Polymorphisms in the gene for IL-10 (G→A mutation at the position -1084 and C→A mutation at the position -592) were sought in 35 patients with syphilis and 24 healthy volunteers. CSF examination (i.e. routine laboratory tests and IL-10 levels) was performed in all syphilis patients. Neurosyphilis was defined as reactive CSF VDRL test or CSF white blood cells⩾5/μL and CSF protein concentration⩾45mg/dL. Overall, 31% of patients with syphilis had neurosyphilis. CSF IL-10 levels were significantly higher in patients with neurosyphilis when compared to those with syphilis but not neurosyphilis. -1082 GG and -592 CC genotypes were significantly associated with higher CSF IL-10 levels. Moreover, these genotypes were found to be more frequent in individuals with neurosyphilis in comparison to those without neurosyphilis. Anti-inflammatory immune response seems to be important in pathogenesis of neurosyphilis. Our data suggest that host-related factors, such as SNPs of immune regulatory genes may influence the susceptibility to neurosyphilis.

Drug-induced linear IgA bullous dermatosis after discontinuation of cefuroxime axetil treatment

BACKGROUND Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is a rare autoimmune blistering disorder. The disease may be either idiopathic or druginduced. Over the past 30 years, approximately one hundred LABD cases have been described as induced by a wide range of drugs, chiefly antibiotics. MAIN OBSERVATIONS We report the case of 37-year-old woman who developed pruritic bullous lesions spread all over the body three weeks after her last dose of cefuroxime axetil. Antibiotic therapy was started due to rhino-sinusitis. CONCLUSIONS In most reported cases of drug-induced LABD, skin lesions occur within the time of drug administration. However, the onset of disease may be even after discontinuation of treatment. It seems that in such cases, other clinical conditions (like infection) act, as cofactors of immunologic response.

Pityriasis lichenoides-like secondary syphilis and neurosyphilis in a HIV-infected patient.

Papulo- and vesiculo-necrotic lesions are rare manifestations of secondary syphilis. Until now it has been described only in HIV-infected patients with advanced stages of immunosuppression. This case report describes an unusual case of PLEVA-like syphilis in a 33-year-old man with newly diagnosed HIV infection. Despite that the CD4 cells level and viral load did not indicate the advance stage of immunosuppression, the unusual manifestation of syphilis and neurosyphilis occurred. The presented case indicates the need for HIV screening in every patient with syphilis especially when the clinical manifestation is unusual. Importance of syphilis testing in every case with atypical rashes should be also highlighted.

Cerebrospinal Fluid Abnormalities in HIV-Negative Patients with Secondary and Early Latent Syphilis and Serum VDRL ≥ 1:32.

Background: Syphilis is caused by a spirochete Treponema pallidum. Invasion of the central nervous system (CNS) by T. pallidum may appear early during the course of disease. The diagnosis of confirmed neurosyphilis is based on the reactive Venereal Disease Research Laboratory (VDRL) in cerebrospinal fluid (CSF). Recent studies indicated that serum RPR ≥ 1:32 are associated with higher risk of reactivity of CSF VDRL. Aims: The main aim of the current study was to assess cerebrospinal fluid serological and biochemical abnormalities in HIV negative subjects with secondary and early latent syphilis and serum VDRL ≥ 1:32. Materials and Methods: Clinical and laboratory data of 33 HIV-negative patients with secondary and early latent syphilis, with the serum VDRL titer ≥ 1:32, who underwent a lumbar puncture and were treated in Department of Dermatology at Jagiellonian University School of Medicine in Cracow, were collected. Results: Clinical examination revealed no symptoms of CNS involvement in all patients. 18% (n = 6) of patients met the criteria of confirmed neurosyphilis (reactive CSF-VDRL). In 14 (42%) patients CSF WBC count ≥ 5/ul was found, and in 13 (39%) subjects there was elevated CSF protein concentration (≥ 45 mg/dL). 10 patients had CSF WBC count ≥ 5/ul and/or elevated CSF protein concentration (≥ 45 mg/dL) but CSF-VDRL was not reactive. Conclusions: Indications for CSF examination in HIV-negative patients with early syphilis are the subject of discussion. It seems that all patients with syphilis and with CSF abnormalities (reactive serological tests, elevated CSF WBC count, elevated protein concentration) should be treated according to protocols for neurosyphilis. But there is a need for identification of biomarkes in order to identify a group of patients with syphilis, in whom risk of such abnormalities is high.