Correction to: A prospective, longitudinal monocentric study on laser Doppler imaging of microcirculation: comparison with macrovascular pathophysiology and effect of adalimumab treatment in early rheumatoid arthritis.

In the Original article, the legend of Figures 3 and 4 are interchanged and line number 387 is incomplete.

A prospective, longitudinal monocentric study on laser Doppler imaging of microcirculation: comparison with macrovascular pathophysiology and effect of adalimumab treatment in early rheumatoid arthritis.

Increased cardiovascular (CV) morbidity and mortality have been found in rheumatoid arthritis (RA). Tumour necrosis factor α (TNF-α) inhibitors may improve vascular function. In the first part of this study, we determined microcirculation during postoocclusive reactive hyperemia (PORH) representing endothelial function. In a nonselected population (n = 46) we measured flow-mediated vasodilation (FMD) of the brachial artery and laser Doppler flow (LDF) by ultrasound. Among LDF parameters, we determined TH1 (time to half before hyperemia), TH2 (time to half after hyperemia), Tmax (time to maximum) and total hyperemic area (AH). We measured von Willebrand antigen (vWF:Ag) by ELISA. In the second part of the study, we assessed the effects of adalimumab treatment on microcirculatory parameters in 8 early RA patients at 0, 2, 4, 8 and 12 weeks. We found significant positive correlations between FMD and LDF Tmax (R = 0.456, p = 0.002), FMD and TH2 (R = 0.435, p = 0.004), and negative correlation between vWF:Ag and Tmax (R = - 0.4, p = 0.009) and between vWF:Ag and TH2 (R = - 0.446, p = 0.003). Upon adalimumab therapy in early RA, TH2 times improved in comparison to baseline (TH2baseline = 26.9 s vs. TH24weeks = 34.7 s, p = 0,032), and this effect prolonged until the end of treatment (TH28weeks = 40.5, p = 0.026; TH212weeks = 32.1, p = 0.013). After 8 weeks of treatment, significant improvement was found in AHa (AHbaseline = 1599 Perfusion Units [PU] vs. AH8weeks = 2724 PU, p = 0.045). The PORH test carried out with LDF is a sensitive option to measure endothelial dysfunction. TH1 and TH2 may be acceptable and reproducible markers. In our pilot study, treatment with adalimumab exerted favorable effects on disease activity, endothelial dysfunction and microcirculation in early RA patients.

[Immunoadsorption in a patient with dilated cardiomyopathy. The first case in Hungary]. / Dilatatív cardiomyopathia immunadszorpciós kezelése. Az elso magyarországi eset kapcsán.

Dilated cardiomyopathy is the main cause of heart transplantation. The etiology is unknown in almost half of the cases. Many cardiac specific antibodies have been identified till now which can cause decreased cardiac function, ventricular tachycardia or sudden heart death. The prognosis of DCM is poor despite the development of medical treatment. Immunoadsorption is hopeful since, with the removal of antibodies, cardiac function and NYHA class can improve and LVAD/heart transplantation-free survival can be prolonged. At the University of Debrecen, Faculty of Medicine, Department of Internal Medicine, Division of Angiology, Intensive Care and Therapeutic Apheresis Unit we performed the first immunoadsorption. Our patient was a 43-year-old man with idiopathic dilated cardiomyopathy, NYHA class IV, a heart transplantation candidate, whose cardiac specific antibody, type IgG was indentified by Western blot. Before the treatment he had ejection fraction of 18%. Discussing with his cardiologists we decided for immunoadsorption therapy. We performed 5 cycles on consecutive days in Intensive Care Unit. After 1 month we detected improvement in exercise capacity. We detected improvement in isovolemic contraction (from 465 mmHg/s to 575 mmHg/s), increased stroke volume (from 49 ml to 66 ml). After 3 months we repeated SPECT investigation which showed improvement in ejection fraction, from 18% to 32%. Orv Hetil. 2018; 159(13): 532-536.

[Favourable effects of kidney transplantation on vascular condition of patients: Potential prognostic significance of non-invasive measurement of arterial stiffness]. / A vesetranszplantáció pozitív hatásai a betegek angiológiai státuszára: Az artériás funkció (stiffness) noninvazív mérésének lehetséges szerepe az elorejelzésben.

INTRODUCTION: Development of atherosclerosis is accelerated in kidney transplant patients. Impaired metabolic pathways have complex effect on the arterial wall which can be measured by non-invasive techniques. Only few data are available on the change of stiffness parameters in the postoperative course. Therefore, in this study the authors analysed the stiffness parameters of kidney transplant recipients during the perioperative period. AIM: Non-invasive clinical trial of the arterial functional parameters in the early postoperative period. METHOD: Seventeen successful primary kidney transplant patients with uneventful postoperative period (8 females, 9 males; age, 46.16 ± 12.19 years) were involved in this short-term prospective longitudinal study. The authors analysed correlations between non-in vasively assessed stiffness parameters (pulse wave velocity PWV, augmentation index - AIx). Stiffness parameters were measured with a TensioMed Arteriograph. These parameters were assessed before the transplantation, as well as 24 hours, 1 and 2 weeks after surgery under standard conditions. RESULTS: It was found that PWV (p = 0.0075) and AIx (p = 0.013) improved significantly. There was no significant change in case of PP and the other monitored parameters. Serum creatinine decreased (p = 0.0008) and glomerular filtration rate increased significantly (p = 0.0005). CONCLUSIONS: Along with the available data in the literature, the findings suggest that kidney transplantation has a positive effect on the arterial function. Improvement can be detected non-invasively with Arteriograph in the early postoperative period.

Impaired endothelial function in patients with undifferentiated connective tissue disease: a follow-up study.

OBJECTIVE: In this study the alteration of endothelial function, arterial stiffness and autoantibodies was investigated in patients with UCTD. METHODS: Thirty-one patients with UCTD were included in this prospective study. All the patients remained in the UCTD stage during the average 3.8 years follow-up period. The onset of UCTD was denoted as UCTD1, while the end of the follow-up period was called UCTD2. Flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT), autoantibodies [such as anti-SSA, anti-SSB, anti-DNA, anti-RNP, anti-CCP, aCL, anti-oxidized low-density lipoprotein (oxLDL) and AECA], von Willebrand factor antigen, thrombomodulin (TM), endothelin 1 (ET-1) and lipid parameters were measured. RESULTS: In the UCTD1 stage, high-sensitivity CRP (hsCRP) and endothelial cell activation and/or damage markers such as TM, ET-1 and AECA levels were significantly higher compared with controls (controls vs UCTD1: hsCRP, P < 0.0001; TM, P = 0.001; ET-1, P < 0.0001). In the UCTD2 stage, the carotid IMT increased (UCTD1 vs UCTD2, P = 0.01) and FMD further deteriorated (UCTD1 and UCTD2, P = 0.001). In UCTD2 there was a close correlation between the carotid IMT, and duration of the disease (r = 0.612, P < 0.001), the level of TM (r = 0.673, P < 0.001) and anti-oxLDL (r = 0.800, P < 0.001). CONCLUSION: Our data suggest that the presence of inflammation and autoantibodies provoke endothelial cell activation and/or injury in UCTD patients. The persistent endothelial dysfunction may provoke the development of atherosclerosis. FMD was found to be the most sensitive marker for arterial stiffness, and the increase of IMT clearly indicated the existence of preclinical atherosclerosis in UCTD patients.

Role of Altered Metabolism of Triglyceride-Rich Lipoprotein Particles in the Development of Vascular Dysfunction in Systemic Lupus Erythematosus.

BACKGROUND: Impaired lipid metabolism contributes to accelerated inflammatory responses in addition to promoting the formation of atherosclerosis in systemic lupus erythematosus (SLE). We aimed to evaluate the lipid profile, inflammatory markers, and vascular diagnostic tests in active SLE patients to clarify the association between dyslipidemia and early vascular damage. PATIENTS AND METHODS: 51 clinically active SLE patients and 41 age- and gender-matched control subjects were enrolled in the study. Lipoprotein subfractions were detected by Lipoprint. Brachial artery flow-mediated dilation and common carotid intima-media thickness were detected by ultrasonography. Arterial stiffness indicated by augmentation index (Aix) and pulse wave velocity was measured by arteriography. RESULTS: We found significantly higher Aix, higher VLDL ratio, plasma triglyceride, ApoB100, and small HDL, as well as lower HDL-C, large HDL, and ApoA1 in patients with SLE. There was a significant positive correlation of Aix with triglyceride, VLDL, IDL-C, IDL-B, and LDL1. A backward stepwise multiple regression analysis showed IDL-C subfraction to be the best predictor of Aix. CONCLUSIONS: Our results indicate that in young patients with SLE, triglyceride-rich lipoproteins influence vascular function detected by Aix. These parameters may be assessed and integrated into the management plan for screening cardiovascular risk in patients with SLE.

One Step Back from Bedside to the Bench-How Do Different Arterial Stiffness Parameters Behave in Relation to Peripheral Resistance?

The investigation of arterial stiffening is a promising approach to estimating cardiovascular risk. Despite the widespread use of different methods, the dynamic nature of measured and calculated stiffness parameters is marginally investigated. We aimed to determine the stability of large artery elasticity parameters assessed via commonly used, ultrasound-based and oscillometric methods in relation to peripheral resistance modulation. A human experimental environment was composed, and fifteen young males were investigated at rest after extremity heating and external compression. Functional vascular parameters were monitored in each session, and several arterial stiffness parameters were analysed. The distensibility coefficient (DC) did not show significant changes during heat provocation and extremity compression, while DC's stability seemed to be acceptable. The same stability of carotid-femoral pulse wave velocity (PWV) was detected with ultrasound measurement (5.43 ± 0.79, 5.32 ± 0.86 and 5.28 ± 0.77, with p = 0.38, p = 0.27 and p = 0.76, respectively) with excellent intersession variability (intraclass correlation coefficient of 0.90, 0.88 and 0.91, respectively). However, the oscillometric PWV (oPWV) did change significantly between the heating and outer compression phase of the study (7.46 ± 1.37, 7.10 ± 1.18 and 7.60 ± 1.21, with p = 0.05, p = 0.68 and p < 0.001, respectively), the alteration of which is closely related to wave reflection, represented by the changes in reflection time. Our results indicate the good stability of directly measured elastic parameters such as DC and PWV, despite the extreme modulation of peripheral resistance. However, the oscillometric, indirectly detected PWV might be altered by physical interventions, which depend on wave reflection. The effective modulation of wave reflection was characterized by changes in the augmentation index, detected using both oscillometry and applanation tonometry. Thus, the environment during oscillometric measurement should be rigorously standardized. Furthermore, our results suggest the dynamic nature of the reflection point, rather than being a fixed anatomical point, proposed previously as aortic bifurcation.

The effect of rheopheresis treatment on the cytokine profile in diabetic foot syndrome with hyperviscosity in the aspect of clinical changes: A preliminary study.

BACKGROUND: Rheopheresis is a selective extracorporal double cascade filtration treatment, which can extract high molecular weight proteins being responsible for hyperviscosity. As the whole blood and plasma viscosity decrease microcirculation improves. OBJECTIVE: In this preliminary study we aimed to analyze additional beneficial effects of rheopheresis treatment with changes of pro-inflammantory cytokine levels in diabetic foot syndrome patients. METHODS: Two rheopheresis treatments were performed for 6 patients with diabetic foot ulcer and/or neuropathy on consecutive days. Before and after the treatments whole blood and plasma viscosity, as well as IL-6, IL-8, and TNF-alpha serum levels were determined, and complex angiological and ENG examinations were performed. RESULTS: Rheopheresis decreased the whole blood and plasma viscosity, and the serum levels of IL-6, IL-8, and TNF-alpha were markedly reduced. The life quality of the patients improved, the ulcers healed, the pain decreased. Daily dose of analgesics decreased in the follow-up period (6 months). The ENG showed improving amplitude and/or normalizing conduction speed. CONCLUSION: Application of rheopheresis in patients with diabetic foot syndrome has a beneficial effect, providing favorable rheological condition, normalizing cytokine profile and reducing the sensorineural symptoms.

Monitoring and recovery of hyperglycaemia-induced endothelial dysfunction with rheopheresis in diabetic lower extremity ulceration with hyperviscosity.

AIMS: Rheopheresis is an extracorporeal haematotherapy that improves haemorheological status by filtering proteins that enhance blood viscosity. It also has anti-inflammatory effects by removing inflammatory cytokines. Our study aims to examine the effects of rheopheresis on the endothelial status in diabetic lower extremity ulceration. METHODS: In vitro experiments were performed in a HUVEC model to mimic hyperglycaemic stress. We determined the changes in gene expression levels of IL-6, IL-8, TNF-alpha, endothelin convertase enzyme, ET-1, and NO synthase, as well as the ROS and intracellular GSH levels upon hyperglycaemia. In in vivo studies, two rheopheresis procedures were performed on seven patients with diabetic lower extremity ulceration with hyperviscosity, and we measured the changes in plasma concentrations of ET-1, TXB2, SOD enzyme activity, and extracellular components of the glutathione pool depending on treatments. RESULTS: Our results showed that hyperglycaemia increases endothelial expression of inflammatory cytokines, ET-1, and endothelin convertase enzyme, while NO synthase was decreased. As a result of rheopheresis, we observed decreased ET-1 and TXB2 concentrations in the plasma and beneficial changes in the parameters of the glutathione pool. CONCLUSION: To summarize our results, hyperglycaemia-induced oxidative stress and endothelial inflammation can be moderated by rheopheresis in diabetic lower extremity ulceration with hyperviscosity.

Effects of adalimumab treatment on vascular disease associated with early rheumatoid arthritis.

BACKGROUND: Increased cardiovascular morbidity has become a leading cause of mortality in rheumatoid arthritis (RA). Tumor necrosis factor-alpha (TNFa) inhibitors may influence flow-mediated vasodilation (FMD) of the brachial artery, common carotid intima-media thickness (ccIMT) and arterial stiffness indicated by pulse-wave velocity (PWV) in RA. OBJECTIVES: To assess the effects of adalimumab treatment on FMD, ccIMT and PWV in early RA. METHODS: Eight RA patients with a disease duration < or =1 year received 40 mg adalimumab subcutaneously every 2 weeks. Ultrasound was used to assess brachial FMD and ccIMT. PWV was determined by arteriograph. These parameters were correlated with C-reactive protein, vonWillebrand factor (vWF), immunoglobulin M (IgM)-rheumatoid factor (RF), anti-CCP levels and 28-joint disease activity score (DAS28). RESULTS: Adalimumab therapy successfully ameliorated arthritis as it decreased CRP levels (P = 0.04) and DAS28 (P < 0.0001). Endothelial function (FMD) improved in comparison to baseline (P < 0.05). ccIMT decreased after 24 weeks, indicating a mean 11.9% significant improvement (P = 0.002). Adalimumab relieved arterial stiffness (PWV) after 24 weeks. Although plasma vWF levels decreased only non-significantly after 12 weeks of treatment, an inverse correlation was found between FMD and vWF (R = -0.643, P = 0.007). FMD also inversely correlated with CRP (R = -0.596, P= 0.015). CRP and vWF also correlated with each other (R = 0.598, P = 0.014). PWV and ccIMT showed a positive correlation (R = 0.735, P = 0.038). CONCLUSIONS: Treatment with adalimumab exerted favorable effects on disease activity and endothelial dysfunction. It also ameliorated carotid atherosclerosis and arterial stiffness in patients with early RA. Early adalimumab therapy may have an important role in the prevention and management of vascular comorbidity in RA.

Anti-ß2-glycoprotein I autoantibodies influence thrombin generation parameters via various mechanisms.

INTRODUCTION: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by recurrent thrombotic events, pregnancy loss and thrombocytopenia and the presence of antiphospholipid antibodies (APL). The exact pathomechanism of APS is still unknown, thus we investigated the effect of anti-ß2-glycoprotein I (anti-ß2GPI) on thrombin generation in different plasma samples. METHODS: For the separation of anti-ß2GPI IgG, overall 12 APS patients were selected. The criteria were the existence of lupus anticoagulant, and the presence of anti-CL and anti-ß2GPI, the latter exceeding at least 25 times the upper reference limit. We purified anti-ß2GPI IgG antibodies from APS patients by affinity chromatography and added the antibodies to normal pooled, and heterozygous forms of inherited thrombophilia plasma samples (prothrombin G20210A, factor V Leiden). To further specify the mechanism of the effect, we also used factor deficient plasmas in the thrombin generation assay. RESULTS: In normal pooled plasma, the anti-ß2GPI significantly prolonged Lag Time according to the lupus anticoagulant effect, in contrast, it also elevated Peak Thrombin significantly, which suggests a procoagulant effect. The antibody was also able to exert this multi-faceted effect both in FVLeiden heterozygous plasma and prothrombin G20210A heterozygous polymorphism, however, the prolonging effect was more remarkable in the latter. By using factor deficient plasmas, it was found that FVII is required for the prolongation, while intrinsic factors are needed for the elevation of the Peak Thrombin. CONCLUSION: The anti-ß2GPI autoantibodies exert their effect in both normal and thrombophilic plasmas via various mechanisms.

The first local experiences with rheopheresis treatment / A rheopheresiskezeléssel szerzett elso hazai tapasztalatok.

Összefoglaló. Háttér: A rheopheresis egy szelektív, extracorporalis, kettos kaszkádfiltrációs eljárás, mely elozetes plazmaszeparációt követoen egy speciális filter segítségével kivonja a vérplazmából a hiperviszkozitásért felelos komponenseket, úgymint alacsony suruségu lipoprotein, lipoprotein(a), triglicerid, koleszterin, fibrinogén, α2-makroglobulin, Von Willebrand-faktor, immunglobulin-M. Módszer és Betegek: Klinikánkon az elmúlt 5 évben MONET filter alkalmazásával összesen 80 kezelést végeztünk hiperviszkozitással összefüggo, idoskori száraz maculadegeneratióban, diabeteses alsó végtagi fekélyben, illetve neuropathiában. Eredmények: A dolgozatban beszámolunk kedvezo klinikai tapasztalatainkról, a viszkozitás, a klinikai tünetek és az elektroneurográfiai paraméterek tükrében. Orv Hetil. 2021; 162(10): 375-382. BACKGROUND: Rheopheresis is a selective, extracorporeal, double cascade filtration method. After a previous plasma separation, with the help of a special filter it extracts compounds from blood plasma which are responsible for hyperviscosity such as low-density lipoprotein, lipoprotein(a), triglyceride, cholesterine, fibrinogen, α2-macroglobulin, Von Willebrand factor, immunoglobulin M. METHOD AND PATIENTS: In the past 5 years, with the application of MONET filter we performed 80 therapies to treat age-related macula degeneration, diabetic foot ulcers and neuropathy which are complicated with hyperviscosity. RESULTS: The review describes our benefical clinical experiences in consideration of viscosity, clinical symptoms and electroneurography parameters. Orv Hetil. 2021; 162(10): 375-382.

Distinct and overlapping effects of ß2-glycoprotein I conformational variants in ligand interactions and functional assays.

One of the most abundant coagulation proteins is ß2-glycoprotein I (ß2GPI) that is present in humans at a concentration of around 200 mg/L. Its physiological role is only partially understood, but it adopts several different structural forms the majority of which are the open and closed forms. We isolated native (circular) ß2GPI and converted it into an open conformation. The effectiveness of these procedures was assessed by Western blot and negative-staining electron microscopy. We found that in coagulation assays the open form of ß2GPI had a significant prolonging effect on fibrin formation in a dilute prothrombin time test (p < 0.001). In the dilute activated partial thromboplastin time test, both conformations had a significant prolonging effect (p < 0.001) but the open conformation was more effective. In a fluorescent thrombin generation assay both conformations slightly delayed thrombin generation with no significant effect on the quantity of formed thrombin. By using surface plasmon resonance assays, the equilibrium dissociation constants of both the open and closed conformations of ß2GPI showed a similar and strong affinity to isolated anti-ß2GPI autoantibodies (Kd closed ß2GPI = 5.17 × 10-8 M, Kd open ß2GPI = 5.56 × 10-8 M) and the open form had one order of magnitude stronger affinity to heparin (Kd = 0.30 × 10-6 M) compared to the closed conformation (Kd = 3.50 × 10-6 M). The two different forms of ß2GPI have distinct effects in functional tests and in ligand binding, which may considerably affect the intravascular events related to this abundant plasma protein in health and disease.

Increased platelet glycoprotein Ib receptor number, enhanced platelet adhesion and severe cerebral ischaemia in a patient with polycythaemia vera.

The present study describes severe multiplex cerebral ischaemic laesions in a male patient being diagnosed with polycythaemia vera (PV). In contrast to previous publications, unique platelet receptor pattern with normal platelet count was identified. Glycoprotein Ib receptor number on the surface of resting platelets was increased two-fold and almost three-fold in case of activated platelets compared to the controls. More over, in an in vitro study when whole blood was circulated both at venous and arterial shear conditions and shear rate was adjusted according to the blood viscosity, platelet aggregate/thrombus formation was characteristic on surfaces covered with purified von Willebrand factor while in case of controls the surface was covered with single platelets or platelet monolayer. Similar results with pathological findings have not been published in PV until now. Our result undersigns the necessity of antiplatelet therapy of PV patients, even at normal platelet count.

[National survey of the therapeutic apheresis in Hungary, 2013-2017]. / A terápiás apheresisek számának és indikációjának változása, valamint új eljárások megjelenése Magyarországon 2013 és 2017 között.

Therapeutic apheresis is a treatment option for several subspecialities. It is a relatively expensive intervention, which can only be done by dedicated centers based on specific indications. The Therapeutic Apheresis Committee and the National Health Insurance Fund of Hungary jointly control the number of interventions to be made, the introduction of new diagnoses and the application of new apheresis procedures in Hungary. In this work, we review the therapeutic practice of the period between 2013 and 2017 in Hungary, describing also the new modalities under implementation. Orv Hetil. 2019; 160(19): 727-738.

[Staphylococcus-induced immunglobulin E-dependent allergic anaphylaxis in Crohn's disease. First description of an association of symptoms]. / Staphylococcus által kiváltott, immunglobulin-E-alapú anafilaxiás reakciók Crohn-betegségben. Egy tünetegyüttes elso leírása.

Immunglobulin E (IgE)-based, irregularly recurring, severe anaphylactic reactions occurred in a 50-year-old European white male patient suffering also from Crohn's disease. On the base of immunologic laboratory tests concerning the mechanism of the phenomenon, the idea arose whether molecules derived for certain microbial derivatives could enter the blood circulation via the damaged bowel walls in the patient with Crohn's disease and they might act as allergens. The microbial analysis diagnosed atypical Staphylococcus in the stool. The serum level of IgE was very high. The concomitant use of targeted antibiotics and anti-allergy and immunosuppressive agents resulted in a complete remission during a couple of months. Not only Crohn's disease has improved, but also the total serum IgE level has decreased significantly, and the unpredictable anaphylactic attacks have been completely eliminated. In Crohn's disease, the anaphylactic complications induced by atypical microbial allergens (e.g., derivatives of Staphylococcus) can be effectively treated after the recognition of this pathological mechanism. This is the first description of such a pathologic state. Orv Hetil. 2019; 160(38): 1514-1518.

Hypertension-induced subclinical vascular and cognitive changes are reversible-An observational cohort study.

Beside the well-known complications of poorly controlled, long-standing hypertension, milder abnormalities induced by early-stage hypertension have also been described. In our study, the authors examined the reversibility of changes induced by early-stage hypertension. The authors performed laboratory testing, ambulatory blood pressure monitoring, carotid intima-media thickness (IMT) measurement, evaluation of stiffness parameters, assessment of various cardiac and cerebral hemodynamic parameters during head-up tilt table (HUTT) testing, and neuropsychological examinations in 49 recently diagnosed hypertensive patients. Following baseline assessment, antihypertensive therapy was commenced. After one year of therapy, lower IMT values were found. Pulse wave velocity showed a borderline significant decrease. During HUTT, several hemodynamic parameters improved. The patients performed better on neuropsychological testing and reached significantly lower scores on questionnaires evaluating anxiety. The present study shows that early vascular changes and altered cognitive function observed in newly diagnosed hypertensive patients may improve with promptly initiated antihypertensive management.

Association of HELLP syndrome with primary antiphospholipid syndrome--a case report.

Authors present the first Hungarian case of a young pregnant woman with the association of antiphospholipid syndrome (APS) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. After the onset of severe preeclampsia, the pregnancy was terminated but the patient's condition continued to worsen. New symptoms of APS, including deep vein thrombosis and ischemic nervus opticus lesion, developed in the patient followed by the onset of acute respiratory distress syndrome, which required respiratory therapy. Intensive treatment with plasmapheresis, high-dose intravenous immunoglobulin, high-dose corticosteroids, cyclophosphamide, and anticoagulants eventually led to full recovery. There have been only few scattered reports in the literature on the association of HELLP syndrome and APS, which was successfully managed with the combination of various immunosuppressive and immunomodulatory treatment modalities.

[Multiple obliterative vascular disease. Challenge in diagnosis and in treatment]. / Multiplex obliteratív érbetegség. Kihívás a diagnosztikában és a kezelésben.

UNLABELLED: Currently, peripheral arterial disease is an underdiagnosed disorder. Several modifiable and non-modifiable risk factors have role in its development and progression. As system disorder it might be a part and an important predictor of fatal cardio- and cerebrovascular events. CASE REPORT: The authors describe the case of a 73-year-old male with multilocational vascular disorder, with simultaneously occurring carotid disease, critical limb ischaemia with aorto-bifemoral bypass, multiple infarction with mechanical complication, inoperable coronary disease and with implantable cardioverter defibrillator for ventricular arrhythmia. CONCLUSION: Peripheral arterial disease affects the whole vascular system and can progress into serious cardiac and cerebral manifestations causing the patient's death inspite of comprehensive treatment.

[High-dose chemotherapy followed by autologous CD34+ stem cell transplantation in the treatment of severe refractory multisystem autoimmune diseases of adults--first experiences in Hungary]. / Nagy dózisú kemoterápia és autológ CD34+ ossejt-transzplantáció alkalmazása súlyos felnottkori terápiarefrakter poliszisztémás autoimmun kórképek kezelésében - az elso hazai tapasztalatok.

UNLABELLED: High dose chemotherapy followed by autologous stem cell support is a promising therapeutical approach in the treatment of severe refractory multisystem autoimmune diseases. The aim of this study was to perform the authors' first experiences in this field. RESULTS: Between August 2006 and November 2007 autologous stem cell transplantation was performed for seven patients: two of them had systemic lupus erythematosus, four of them had rheumatoid arthritis and one of them had systemic sclerosis. Cyclophosphamide plus colony stimulating factor were administered to mobilize stem cells. The conditioning protocol included high dose cyclophosphamide (200 mg/kg) and anti-thymocyte globulin (9 mg/kg). The re-infused stem cells were successfully engrafted by all patients. One of the lupus patients died on the 46th day due to a lethal cytomegalovirus infection, but the rest of them had no severe complications. Complete remission of their diseases and significant improvement in their quality of life were observed during a mean follow-up period of 10 months. CONCLUSIONS: Autologous stem cell therapy can be effectively administered in special cases of severe autoimmune disorders.