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Slavic populations, such as those in Poland, are considered to have a low prevalence of giant cell arteritis (GCA), although epidemiological data are sparse. The study aimed to compare the reported frequency of GCA in various regions of Poland and analyze the differences between them. We conducted a multicenter, retrospective study of all GCA patients included in the POLVAS registry—the first large multicenter database of patients with vasculitis in Poland. The data from the POLVAS registry were compared with the reported prevalence provided by national insurers from the corresponding regions. A 10-fold increase in the diagnostic rates of GCA was observed in Poland between 2008 and 2019, reaching 8.38 per 100,000 population > 50 years old. It may be attributed to increased interest accompanied by improved diagnostic modalities with the introduction of ultrasound-based, fast-track diagnostic pathways in some centers. However, regional inequities are present, resulting in 10-fold differences (from 2.57 to 24.92) in reported prevalence between different regions. Corticosteroid (CS) monotherapy was the main stem of treatment. Further cooperation and education are needed to minimize regional inequities. This observational study suggests some potential for further increase of the recognizability of GCA and wider use of other than CS monotherapy treatment regimens. We hope that the Polish experience might be interesting and serve as some guidance for the populations where GCA is underdiagnosed.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of rare diseases with a chronic and relapsing course. Recent treatment guidelines offer many therapeutic options depending mainly on the type of diagnosis and disease manifestations. Areas that remain under discussion include whether all patients diagnosed with AAV belong to a homogeneous group with a similar prognosis at baseline or if the type and duration of remission-inducing treatment should depend on factors other than just diagnosis and disease severity. The aim of this review is to present the recent literature on the tools available to use while evaluating the risk of relapse in patients upon presentation as well as potential biomarkers of proceeding flare in patients upon remission.

Objective. To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/μl) (GPA HE) to develop a differentiating strategy. Methods. A retrospective analysis of the POLVAS registry. Results. The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p

IntroductionGranulomatosis with polyangiitis (GPA) is a small vessel vasculitis with a complex pathomechanism. Organ damage in GPA is also mediated by extracellular trap formation (NETosis). We analyzed the functional status of phosphoproteins modulating NETosis in neutrophils by the mammalian target of rapamycin (mTOR) pathway in GPA along with NETosis biomarkers.MethodsPhosphoproteins levels measured in isolated neutrophils from 42 patients with GPA (exacerbation n=21; remission n=21) and 21 healthy controls were compared to serum biomarkers of the disease.ResultsNeutrophils in active disease manifested lowered levels of phosphorylated mTOR(Ser2448), PTEN(Ser380) and ULK1(Ser555), whereas phosphorylated GSK-3α/β(Ser21/Ser9) was elevated. Exacerbation of GPA was characterized by elevated neutrophil dsDNA in serum, circulating mitochondrial DNA, and DNA-MPO complexes. A significant negative correlation between mTOR or PTEN phosphoproteins and biomarkers of GPA activity was also present, reflecting the clinical activity score of GPA. Positive correlations between phosphorylated GSK-3 α/β and circulating mtDNA, DNA-MPO complexes, neutrophil-released dsDNA, or circulating proteins were also significant. Increased serum levels of IGFBP-2, TFF-3, CD147, and CHI3L1 accompanied GPA exacerbation, whereas DPP-IV levels were the lowest in active GPA. Using a principal component analysis basigin, PTEN and mTOR had the highest loadings on the discrimination function, allowing classification between active, remission, and control subjects with 98% performance.ConclusionsWe present evidence that inhibited mTOR signaling accompanies NETosis in patients with GPA. The functional status of phosphoproteins suggests simultaneous activation of NETosis and autophagy. These results give rise to the study of autophagy as a mechanism underlying granuloma formation in GPA.

Fibrosarcomas are placed among the most infrequent malignant tumors of the uterus. We present a case of a 38 years-old woman, whose benign looking uterine mass was primary diagnosed as a sclerosing leiomyoma. However, the tumor relapsed in two years with multisite metastases in the abdomen. The complex differential diagnosis excluded the most common mesenchymal tumors of the gynecological tract. Finally, we diagnosed the tumor as an epithelioid sclerosing fibrosarcoma arising from the uterine.

Tumor necrosis factor (TNF)-α is a proinflammatory cytokine that plays an important role in the pathogenesis of autoimmune diseases. The aim of the study was to establish an association between TNF-α promoter variability and systemic sclerosis (SSc). The study included 43 SSc patients and 74 controls. Four single nucleotide polymorphisms (rs361525, rs1800629, rs1799724, and rs1799964) located at the promoter of the TNFA gene were genotyped using commercially available TaqMan allelic discrimination assays with real-time PCR. The rs1799724 allele was associated with an increased SSc susceptibility (p = 0.028). In turn, none of the polymorphisms studied were related to the clinical and laboratory parameters of SSc patients, except for a higher prevalence of anti-Ro52 antibodies in the AG rs1800629 genotype in comparison to GG carriers (p = 0.04). Three of four cancer patients had both CT rs1799964 and AG rs361525 genotypes; thus, both of them were related to the increased risk of cancer, as compared to the TT (p = 0.03) and GG carriers (p = 0.0003), respectively. The TNFA C rs1799724 variant is associated with an increased risk of SSc, while the CT rs1799964 and AG rs361525 genotypes might enhance cancer susceptibility in SSc patients, although large observational and experimental studies are needed to verify the above hypothesis.

Nabyta hemofilia jest rzadkim, potencjalnie śmiertelnym, nabytymschorzeniem autoimmunologicznym, z wytworzeniem przeciwciałblokujących aktywność własnych czynników krzepnięcia. Toobniżenie aktywności prowadzi do rozwoju skazy krwotocznej.Najczęściej wytwarzane są przeciwciała przeciwko czynnikowi VIII– określane jako nabyta hemofilia A. W blisko połowie przypadkówma ona charakter pierwotny i nie towarzyszy żadnym innym zmia -nom patologicznym, w 35–40% jest wtórna do innych schorzeńautoimmunologicznych, nowotworowych lub reakcji polekowych,a w 10–15% dotyczy młodych kobiet w okresie połogu. Leczenienabytej hemofilii polega na opanowaniu czynnego krwawienia orazeliminacji z krążenia aktywnego inhibitora.Autorzy przedstawiają przypadek 55-letniej chorej na reumatoidalnezapalenie stawów z nabytą hemofilią typu A (ryc. 1 i 2). Objawy skazykrwotocznej ustąpiły po dożylnym podaniu rekombinowanegoaktyw nego czynnika VII oraz prednizonu i cyklofosfamidu. Celem pracyjest zwrócenie uwagi na występowanie tego schorzenia u pacjentówz chorobami reumatycznymi. Nagłe wystąpienie objawów skazykrwotocznej, a szczególnie krwawień podskórnych, połączonez wydłużeniem czasu częściowej tromboplastyny po aktywacjipowinno budzić podejrzenie nabytej hemofilii. Życie choremu możeuratować jedynie szybka diagnostyka i właściwe leczenie.

Abstract Objective: The main goal of our study was to assess the impact of vascular procedures on the activity of hemostatic and fibrinolytic pathways. Methods: We enrolled 38 patients with ≥ 45 years old undergoing surgery for abdominal aortic aneurysm or peripheral artery disease under general or regional anesthesia and who were hospitalized at least one night after the procedure. Patients undergoing carotid artery surgery and those who had acute bypass graft thrombosis, cancer, renal failure defined as estimated glomerular filtration rate < 30 ml/min/1.73m2, venous thromboembolism three months prior to surgery, or acute infection were excluded from the study. We measured levels of markers of hemostasis (factor VIII, von Willebrand factor:ristocetin cofactor [vWF:CoR], antithrombin), fibrinolysis (D-dimer, tissue plasminogen activator [tPA], plasmin-antiplasmin complexes), and soluble cluster of differentiation 40 ligand (sCD40L) before and 6-12h after vascular procedure. Results: Significant differences between preoperative and postoperative levels of factor VIII (158.0 vs. 103.3, P

Abstract Background Exacerbation‐prone asthma is a feature of severe disease. However, the basis for its persistency remains unclear. Objectives To determine the clinical and transcriptomic features of frequent exacerbators (FEs) and persistent FEs (PFEs) in the U‐BIOPRED cohort. Methods We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE,

Introduction Antiphospholipid antibodies (aPL) affect atherogenesis and may cause thromboembolism in systemic lupus erythematosus (SLE) and coronary artery disease (CAD). Intensive treatment with statins may reduce inflammation and decrease the number of thrombotic events. That may explain the beneficial effect of statin therapy in SLE and CAD. This study was established to investigate the influence of statin treatment on aPL antibody levels and selected endothelial dysfunction markers in CAD and SLE patients. Material and methods Fifty-eight patients – 40 after coronary revascularization (age 38.9 (27–46), 35 males) and 18 with clinically stable SLE (age 38.8 (18–62), 1 male) – were enrolled in the study. In both groups intensive atorvastatin treatment was administered. At baseline and after 1 year of follow-up serology tests were performed: anticardiolipin antibodies (aCL), anti-β2 glycoprotein I (aβ2GPI), lupus anticoagulant (LA), C-reactive protein (CRP), soluble form of intracellular adhesion molecule-1 (sICAM-1), vWF:Ag. Results Coronary artery disease patients in 1 year follow-up revealed a decrease of aβ2GPI IgG and CRP. There was a significant increase in aCL IgG, sICAM-1 and vWF:Ag. In SLE patients aPL levels showed no significant reduction after treatment. Conclusions In clinically stable patients IgM and IgG class aβ2GPI levels are higher in CAD than in SLE, whereas IgG class aCL levels are lower. Statin treatment decreases the CRP level in both SLE and CAD patients, while decreasing the aβ2GPI IgG level only in CAD patients.

Abstract Background Anticardiolipin (aCL) and anti‐β2 glycoprotein I (aβ2GPI) immunoglobulin (Ig) G/IgM antibodies are 2 of the 3 laboratory criteria for classification of antiphospholipid syndrome (APS). The threshold for clinically relevant levels of antiphospholipid antibodies (aPL) for the diagnosis of APS remains a matter of debate. The aim of this study was to evaluate the variation in cutoffs as determined in different clinical laboratories based on the results of a questionnaire as well as to determine the optimal method for cutoff establishment based on a clinical approach. Methods The study included samples from 114 patients with thrombotic APS, 138 patients with non‐APS thrombosis, 138 patients with autoimmune disease, and 183 healthy controls. aCL and aβ2GPI IgG/IgM antibodies were measured at 1 laboratory using 4 commercial assays. Assay‐specific cutoff values for aPL were obtained by determining 95th and 99th percentiles of 120 compared to 200 normal controls by different statistical methods. Results Normal reference value data showed a nonparametric distribution. Higher cutoff values were found when calculated as 99th rather than 95th percentiles. These values also showed a stronger association with thrombosis. The use of 99th percentile cutoffs reduced the chance of false positivity but at the same time reduced sensitivity. The decrease in sensitivity was higher than the gain in specificity when 99th percentiles were calculated by methods wherein no outliers were eliminated. Conclusions We present cutoff values for aPL determined by different statistical methods. The 99th percentile cutoff value seemed more specific. However, our findings indicate the need for standardized statistical criteria to calculate 99th percentile cutoff reference values.

Numerous in vitro experiments have confirmed that a dysfunctional endothelium is characterized by, inter alia, a higher affinity for binding of platelets and leukocytes. However, there is still no direct evidence for greater interaction between platelets and intact endothelium in in vivo animal models of diabetes. Therefore, the present study examines the pro-adhesive properties of endothelium change in vivo as an effect of streptozotocin (STZ)-induced diabetes and the role of two key platelet receptors: GPIb-IX-V and GPIIb/IIIa. Mice of C57BL strain with streptozotocin-induced diabetes were used in the study. Flow cytometry was used to assess basal activation and reactivity of platelets. Adhesion of platelets to the vascular wall was visualized with the use of intravital microscopy in mesentery. The contribution of GPIIb/IIIa and GPIb-IX-V was evaluated by the injection of Fab fragments of respective antibodies. The integrity of the endothelium and vWf expression were evaluated histochemically. Basal activation and reactivity of platelets in streptozotocin-diabetic mice were elevated. Blood platelets adhered more often to the vascular wall of diabetic mice than nondiabetic animals: 11.9 (6.4; 32.8) plt/min/mm2 (median [IQR]) vs 2.7 (1.3; 6.4) plt/min/mm2. The injection of anti-GPIbα antibodies decreased the number of adhering platelets from 89.5 (34.0; 113.1) plt/min/mm2 (median [IQR]) in mice treated with isotype antibodies to 3.1 (1.7; 5.6) plt/min/mm2 in mice treated with blocking antibodies. The effect of GPIIb/IIIa blockage was not significant. Immunohistochemistry revealed a higher expression of vWF in the endothelium of STZ mice, but no substantial changes in endothelial morphology were detected. To conclude, the study shows that the platelets interact more frequently with the mesenteric vascular bed in mice with 1-month STZ-induced diabetes than in healthy mice. These interactions are mediated via platelet GPIb-IX-V and are driven by increased expression of vWF in endothelial cells.

Noninvasive Raman imaging of non-fixed and unstained human colon tissues based on vibrational properties of noncancerous and cancerous samples can effectively enable the differentiation between noncancerous and tumor tissues. This work aimed to evaluate the biochemical characteristics of colon cancer and the clinical merits of multivariate Raman image and spectroscopy analysis. Tissue samples were collected during routine surgery. The non-fixed, fresh samples were used to prepare micrometer sections from the tumor mass and the tissue from the safety margins outside of the tumor mass. Adjacent sections were used for typical histological analysis. We have found that the chemical composition identified by Raman spectroscopy of the cancerous and the noncancerous colon samples is sufficiently different to distinguish pathologically changed tissue from noncancerous tissue. We present a detailed analysis of Raman spectra for the human noncancerous and cancerous colon tissue. The multivariate analysis of the intensities of lipids/proteins/carotenoids Raman peaks shows that these classes of compounds can statistically divide analyzed samples into noncancerous and pathological groups, reaffirming that Raman imaging is a powerful technique for the histochemical analysis of human tissues. Raman biomarkers based on ratios for lipids/proteins/carotenoids content were found to be the most useful biomarkers in spectroscopic diagnostics.

Impaired function of regulatory T-cells (Treg) leads to a failure in immune tolerance and triggers autoimmunity. We analyzed whether the deficiency in Treg in systemic lupus erythematosus (SLE) is accompanied by an increase in effector T-cell responses. We studied the frequencies of IL-17A (Th17) and IFNg (Th1) producing CD4+ T-cells by flow cytometric detection of intracellular cytokines in PMA/ionomycin stimulated blood lymphocytes from seven patients with active SLE, eight with SLE in remission, and 11 healthy controls. Circulating Treg were evaluated as CD4+CD25+ lymphocytes expressing FoxP3. There was no difference in the percentage of Treg cells between the groups, but their absolute counts were decreased in active SLE (5 [1–7] cells/μL) compared to inactive SLE (11 [6–15]; p = 0.05) and healthy controls (16 [10–20]; p < 0.01). Both the frequency and numbers of Th1 cells were decreased in SLE compared to controls. No difference was observed in the number of Th17 cells, which resulted in a decreased Th1/Th17 ratio. In parallel, a higher Treg/Th17 ratio in healthy controls (2.2 [1.8–3.6]) compared to active SLE (1.1 [1.0–2.1]; p < 0.05) was observed. There was a correlation between the number of Treg cells and disease activity status (SLEDAI, r = –0.59). SLE patients in the active phase of the disease are characterized by a deficiency in Treg cells and decreased Treg/Th17 ratio. This suggests that the imbalance between major T-cells subsets might be responsible for an increased proinflammatory response in the exacerbation of SLE. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 646–653)