Hydroxychloroquine as an important immunomodulator: a novel insight into an old drug.

Hydroxychloroquine (HCQ) is an increasingly popular drug owing to its efficacy, long­term safety, and a wide range of therapeutic effects. Currently, due to the numerous benefits it provides, the use of the drug goes beyond the treatment of rheumatic and dermatologic diseases. As HCQ shows anti­inflammatory, immunomodulatory, antiproliferative, and photoprotective action, it has a great potential to be applied also in the treatment of oncologic diseases, multiple sclerosis, diabetes, cardiovascular diseases, or recurrent miscarriages. Nevertheless, antimalarial drugs are still most widely used in the long­term treatment of systemic rheumatic disorders, such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and primary Sjögren syndrome, as they continue to offer satisfactory outcomes. They reduce the need for glucocorticoids and immunosuppressants and increase their effectiveness. In addition, they reduce the risk of possible side effects and complications. This paper presents the latest data on HCQ, its mechanisms of action, its therapeutic potential in current clinical practice as well as future perspectives. It also discusses the correct dosing regimen and long­term monitoring, with consideration of possible rare complications. Finally, it focuses on the enormous benefits for patients with rheumatic diseases in terms of reducing the disease activity and organ damage, preventing flares and pregnancy­related complications, and, most importantly, lowering mortality rates in SLE patients.

Identification of Clinical Response Predictors of Tocilizumab Treatment in Patients with Severe COVID-19 Based on Single-Center Experience.

Hyperinflammation in COVID-19 plays a crucial role in pathogenesis and severity; thus, many immunomodulatory agents are applied in its treatment. We aimed to identify good clinical response predictors of tocilizumab (TCZ) treatment in severe COVID-19, among clinical, laboratory, and radiological variables. We conducted a prospective, observational study with 120 patients with severe COVID-19 not improving despite dexamethasone (DEX) treatment. We used parametric and non-parametric statistics, univariate logistic regression, receiver operating characteristic (ROC) curves, and nonlinear factors tertile analysis. In total, 86 (71.7%) patients achieved the primary outcome of a good clinical response to TCZ. We identified forty-nine predictive factors with potential utility in patient selection and treatment monitoring. The strongest included time from symptom onset between 9 and 12 days, less than 70% of estimated radiological lung involvement, and lower activity of lactate dehydrogenase. Additional predictors were associated with respiratory function, vitamin D concentration, comorbidities, and inflammatory/organ damage biomarkers. Adverse events analysis proved the safety of such a regimen. Our study confirmed that using TCZ early in the hyperinflammatory phase, before severe respiratory failure development, is most beneficial. Considering the described predictive factors, employing simple and widely available laboratory, radiological, and clinical tools can optimize patient selection for immunomodulatory treatment with TCZ.

Study of Degradation Kinetics and Structural Analysis of Related Substances of Ceftobiprole by HPLC with UV and MS/MS Detection.

Ceftobiprole is a novel ß-lactam antibiotic, active against methicillin-resistant Staphylococcus aureus, vancomycin-resistant S. aureus and penicillin-resistant Streptococcus pneumoniae. To artificially generate potential degradation products (DPs) of ceftobiprole that may be formed under relevant storage conditions, acidic, alkaline, oxidative, photolytic and thermolytic stress tests were performed in both solution and solid state. A novel selective HPLC method was developed for the separation of ceftobiprole from its DPs and synthesis by-products (SBPs) using Kinetex Biphenyl column, ammonium acetate buffer pH 5.8 and acetonitrile. The kinetic studies demonstrated the low stability of ceftobiprole in alkaline solution, in the presence of an oxidising agent and under irradiation with near UV. In the solid state, ceftobiprole underwent oxidation when the powder was irradiated with visible light and UV. Based on mass spectroscopic analysis, 13 new structural formulas of SBPs and DPs were proposed, along with molecular formulas for three other DPs obtained in solution and four oxidative DPs characteristic of solid-state degradation.

Phytochemical screening and effect of Viscum album L. on monoamine oxidase A and B activity and serotonin, dopamine and serotonin receptor 5-HTR1A levels in Galleria mellonealla (Lepidoptera).

ETHNOPHARMACOLOGICAL RELEVANCE: Viscum album L. (European mistletoe), a member of the Santalaceae, is a hemiparasitic, evergreen shrub growing on deciduous and coniferous trees. In traditional and folk medicine, mistletoe was used for the treatment of central nervous system disorders such as epilepsy, hysteria, insomnia, nervous excitability, neuralgia, headache, dizziness and fatigue. However, relatively little is known of its neuropharmacological activity. AIM OF THE STUDY: The aim of the present study was to evaluate the effect of treatment with aqueous and hydroethanolic extracts from Viscum album L. parasitizing birch, linden and pine, on MAO-A and MAO-B activity as well as serotonin, dopamine and serotonin receptor 5-HTR1A levels in Galleria mellonella (Lepidoptera) larvae. MATERIALS AND METHODS: The phytochemical composition of the extracts was characterised using UPLC-DAD-ESI-MS/MS. To investigate the neuropharmacological activity of Viscum album L. extracts, Galleria mellonella (Lepidoptera) larvae were used as a model organism. The inhibitory potential of the extracts against MAO-A and MAO-B was determined by fluorometry. The serotonin, dopamine and serotonin receptor 5-HTR1A levels in larvae hemolymph after treatment were quantified by ELISA. RESULTS: UPLC-DAD-ESI-MS/MS analysis allowed the identification of 88 compounds, either full or in part. Most of the characterised phytochemicals were flavonoids, hydroxycinnamic acids and lignans. Screening found that aqueous and hydroethanolic mistletoe extracts inhibited the enzymatic activity of either MAO-A or MAO-B or both. Additionally, mistletoe extract administration increased the levels of serotonin and serotonin receptor 5-HTR1A. None of the tested extracts had any significant effect on dopamine level. CONCLUSIONS: A key novel finding was that the aqueous and hydroethanolic extracts from Viscum album L. inhibited monoamine oxidase activity and increased the levels of serotonin and serotonin receptor 5-HTR1A in Galleria mellonella (Lepidoptera) larvae. These properties may be due to the presence of phenolic constituents, particularly flavonoids. Further research based on bioassay-guided fractionation of mistletoe is needed to identify CNS-active molecules.

Neuropsychiatric manifestations and their attribution to systemic lupus erythematosus: a retrospective single-center study in a Polish population.

INTRODUCTION: Neuropsychiatric (NP) manifestations occur in patients with systemic lupus erythematosus (SLE), and it is challenging to distinguish these manifestations from other neuropsychiatric conditions. OBJECTIVES: We aimed to assess the prevalence of primary neuropsychiatric SLE (NPSLE) in a Polish cohort of SLE patients. PATIENTS AND METHODS: This retrospective, cross­sectional study evaluated 164 patients with SLE. NP manifestations were attributed to SLE using the Italian model. Demographic and clinical data, including disease activity (measured by the Systemic Lupus Erythematosus Disease Activity Index version 2000 [SLEDAI­2K] and the Physician Global Assessment) and organ damage (measured by the Systemic Lupus International Collaborating Clinics / American College of Rheumatology Damage Index), were obtained in patients with and without NP manifestations attributed to SLE. RESULTS: The final analysis set included 143 patients, 34 of whom (23.8%) had NP manifestations attributed to SLE. The age of the patients with NPSLE and the age of disease onset were significantly lower in comparison with those without NP symptoms attributed to SLE (median [interquartile range], 38 [29-45] vs 45 [32-55] years; P = 0.009, and 35 [24-38] vs 40 [25-48] years; P = 0.03, respectively). The disease activity and proportion of patients with active disease (SLEDAI­2K ≥6) was significantly higher in the NPSLE patients than in those without NP symptoms attributed to SLE (P <0.005; 100% vs 85.3%; P = 0.01, respectively). NP manifestations in the central nervous system were the most frequent (91.5%). In the patients with NPSLE, cerebrovascular disease, seizures, cognitive dysfunction, psychosis, and cranial neuropathy occurred most often. CONCLUSIONS: NP manifestations occurred mainly in young patients with high disease activity. Cerebrovascular disease, seizures, psychosis, cognitive dysfunction, and cranial neuropathy were the most frequent manifestations of NPSLE.

Tocilizumab as a first-line biologic treatment in rheumatoid arthritis patients - the impact of concomitant methotrexate treatment and Rheumatic Disease Comorbidity Index on the clinical response - results from the multicenter observational ACT-POL study.

Objectives: According to the EULAR recommendations, remission or low disease activity (LDA) in rheumatoid arthritis should be achieved by a maximum of 6 months (M6) of treatment. Data on the use of tocilizumab (TCZ) as first-line biologic treatment in rheumatoid arthritis (RA) in routine clinical practice in Poland are lacking. Material and methods: This multicenter, non-interventional, prospective, observational study recruited adults, presenting with moderate-to-severe RA, showing an inadequate response or intolerance to disease-modifying antirheumatic drugs, where TCZ was the first-line biologic treatment. The effectiveness of TCZ was assessed by the proportion of patients achieving remission and low disease activity following 6 months of treatment with intravenous TCZ. The impact of comorbidities on treatment outcomes was measured using the Rheumatic Disease Comorbidity Index (RDCI). Results: Total remission rates at months 3 and 6 were 6% and 31%, respectively. Low disease activity was reported in 10% and 92% of the patients at 3 and 6 months, respectively. The response was comparable between TCZ as monotherapy and in combination with methotrexate. Mean DAS28 decreased from 6.61 at baseline to 4.27 at the scheduled time of the assessment (3 and 6 months). The Rheumatic Disease Comorbidity Index was not correlated with the number of patients achieving LDA at M3 and M6 or remission rates at M6. Remission rates correlated with RDCI at M3. A total of 114 adverse events were reported in 61 patients, among which five were considered as serious. Conclusions: The study confirms the effectiveness and safety of TCZ in real-world settings as a first-line biologic treatment in patients with moderate-to-severe RA. Importantly, comorbidities do not affect the results of 6-month treatment with TCZ, that is, the optimal time to achieve at least LDA. Our results may improve the effects of RA therapy in Poland, especially in patients with comorbidities and those who, for various reasons, cannot receive optimal treatment with methotrexate.

2022 Systemic lupus erythematosus remission in clinical practice. Message for Polish rheumatologists.

Systemic lupus erythematosus (SLE) is a complicated multiorgan disease and can lead to organ damage and increased risk of morbidity and mortality. The strategy of management while avoiding complications, especially caused by chronic glucocorticoid therapy, improves outcomes. Different definitions of the treatment goal in different configurations of lupus activity indexes have appeared over the years. In 2021 the definition of remission and recommendations for its achievement were published and it become a way to implement a treat-to-target strategy. The main goal of treatment has become DORIS (definition of remission in SLE) remission and the alternative LLDAS (low lupus disease activity state). Prolonging remission with clinical and immunological lupus activity restrictions and minimizing or stopping steroid doses reduced flares and damage accrual. The analysis and neutralization of poor prognosis predictive factors in lupus could be the most beneficial for less morbidity and mortality and better quality of life.

On-admission laboratory predictors for developing critical COVID-19 during hospitalization - a multivariable logistic regression model.

INTRODUCTION AND OBJECTIVE: Recognition of patients with COVID-19 who will progress clinically and need respiratory support remains challenging. The aim of the study was to identify abnormalities in on-admission laboratory results that can precede progression from moderate or severe to critical COVID-19. MATERIAL AND METHODS: Laboratory data analyzed of 190 patients admitted with moderate or severe COVID-19 to our ward. Laboratory results taken into analysis were obtained during the first 48 hours of hospitalization. Multivariate logistic regression was performed using risk factors obtained in the univariate analysis as dependent variables. RESULTS: 42 patients were identified who developed critical COVID-19. In univariate analysis, 22 laboratory risk factors were detected that were used in logistic regression and in building model with following predictors: high-sensitive troponin I concentration (hs-TnI) >26 ng/mL (OR 13.45; 95%CI 3.28-55.11; P 15 (OR 5.67; 95%CI 1.97-16.36, P 50 pg/mL (OR 5.52; 95%CI 1.86-16.37; P = 0.001), fasting glycaemia >6.8 mmol/L (OR 4.74; 95%CI 1.65-13.66; P = 0.002), immature neutrophils count >0.06/µL (OR 4.06; 95%CI 1.35-12.2; P = 0.012) and urine protein concentration >500 mg/L (OR 2.94; 95%CI 1.04-8.31; P = 0.043). CONCLUSIONS: The most significant risk factors of developing critical COVID-19 during hospitalization are: elevated hs-TnI, IL-6, and glucose serum concentrations, increased immature neutrophil count, neutrophils to monocytes ratio, and proteinuria during the first 48 hours after admission. The model built with these predictors achieved better predictive performance than any other univariately analysed laboratory markers in predicting the critical development COVID-19.

Different blood-brain-barrier disruption profiles in multiple sclerosis, neuromyelitis optica spectrum disorders, and neuropsychiatric systemic lupus erythematosus.

AIM OF THE STUDY: To assess differences in BBB damage profiles by measuring serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and S100 calcium-binding protein B (S100B) in relapsing-remitting multiple sclerosis (RRMS), neuromyelitis optica spectrum disorders (NMOsd), and neuropsychiatric systemic lupus erythematosus (NPSLE) patients. CLINICAL RATIONALE FOR THE STUDY: Blood-brain-barrier (BBB) disruption is one of the key pathological processes involved in various demyelinating diseases of the central nervous system (CNS) and is associated with shedding of cell adhesion molecules and S100B into the serum compartment. Therefore, making an assessment of serum levels of the above-mentioned molecules could provide information about disease pathogenesis, severity of BBB disruption, and disease activity. MATERIAL AND METHODS: We recruited 42 RRMS, 19 NMOsd and 35 NPSLE patients. Subjects were treated with beta-interferons or glatiramer acetate (RRMS), oral steroids and/or azathioprine (NMOsd, NPSLE), other immunosuppressants (NPSLE), or antimalarials (NPSLE). The clinical condition of the patients was assessed using the Kurtzke Expanded Disability Status Scale for MS and NMOsd, and the Systemic Lupus Erythematosus Disease Activity Index for NPSLE. Serum levels of sVCAM-1, sPECAM-1, sICAM-1 and S100B were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: We found the lowest levels of sPECAM-1, sICAM-1 and S100B in sera from NMOsd patients. The highest levels of sPECAM-1 and sICAM-1 were observed in NPSLE, and in NPSLE and MS, respectively. There were no statistically significant differences in sVCAM-1 levels between the examined groups. In MS and NMOsd, there was a negative correlation between the EDSS score and the following molecules: sPECAM-1, sICAM-1 and S100B. CONCLUSIONS AND CLINICAL IMPLICATIONS: We conclude that there is a different profile of blood-brain-barrier disruption reflected by cell adhesion molecules shedding in the spectrum of autoimmune CNS disorders with disseminated white matter lesions. These molecules could become new biomarkers to be used in CNS demyelinating diseases differential diagnoses and monitoring disease activity, but further studies on larger groups of patients are necessary.

Separation of menaquinone-7 geometric isomers by semipreparative high-performance liquid chromatography with silver complexation and identification by nuclear magnetic resonance.

Dietary supplements containing vitamin K2 are often used to prevent osteoporosis, vascular calcification and coronary heart disease. It has been shown that some of these products contain a mixture of menaquinone-7 geometric isomers. Since the geometric shape may influence biological activity, there was a need for a semipreparative method to isolate single compounds for further studies. Here, we present an argentation chromatographic method for the separation of menaquinone-7 isomers and an nuclear magnetic resonance (NMR) methodology for the configuration assignment of isoprenoid side chain. The DFT calculations were performed to determine more energetically favorable complexes between the cis or trans menaquinone-7 isomers and the silver cation. Seventeen components were resolved, and fractions were collected and subjected to NMR study. Structures and chemical shifts for thirteen new compounds were assigned, and the identity of three known compounds was confirmed.

Relationship between Structure and Biological Activity of Various Vitamin K Forms.

Vitamin K is involved many biological processes, such as the regulation of blood coagulation, prevention of vascular calcification, bone metabolism and modulation of cell proliferation. Menaquinones (MK) and phylloquinone vary in biological activity, showing different bioavailability, half-life and transport mechanisms. Vitamin K1 and MK-4 remain present in the plasma for 8-24 h, whereas long-chain menaquinones can be detected up to 96 h after administration. Geometric structure is also an important factor that conditions their properties. Cis-phylloquinone shows nearly no biological activity. An equivalent study for menaquinone is not available. The effective dose to decrease uncarboxylated osteocalcin was six times lower for MK-7 than for MK-4. Similarly, MK-7 affected blood coagulation system at dose three to four times lower than vitamin K1. Both vitamin K1 and MK-7 inhibited the decline in bone mineral density, however benefits for the occurrence of cardiovascular diseases have been observed only for long-chain menaquinones. There are currently no guidelines for the recommended doses and forms of vitamin K in the prevention of osteoporosis, atherosclerosis and other cardiovascular disorders. Due to the presence of isomers with unknown biological properties in some dietary supplements, quality and safety of that products may be questioned.

Synthesis of Oxidized 3ß,3'ß-Disteryl Ethers and Search after High-Temperature Treatment of Sterol-Rich Samples.

It was proven that sterols subjected to high-temperature treatment can be concatenated, which results in polymeric structures, e.g., 3ß,3'ß-disteryl ethers. However, it was also proven that due to increased temperature in oxygen-containing conditions, sterols can undergo various oxidation reactions. This study aimed to prove the existence and perform quantitative analysis of oxidized 3ß,3'ß-disteryl ethers, which could form during high-temperature treatment of sterol-rich samples. Samples were heated at 180, 200 and 220 °C for 0.5 to 4 h. Quantitative analyses of the oxidized 3ß,3'ß-disteryl ethers were performed with liquid extraction, solid-phase extraction and liquid chromatography coupled with mass spectrometry. Additionally, to perform this analysis, the appropriate standards of all oxidized 3ß,3'ß-disteryl ethers were prepared. Eighteen various oxidized 3ß,3'ß-disteryl ethers (derivatives of 3ß,3'ß-dicholesteryl ether, 3ß,3'ß-disitosteryl ether and 3ß,3'ß-distigmasteryl ether) were prepared. Additionally, the influence of metal compounds on the mechanism of ether formation at high temperatures was investigated.

Lack of Association between Serum Interleukin-23 and Interleukin-27 Levels and Disease Activity in Patients with Active Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the production of multiple autoantibodies, resulting in tissue and organ damage. Recent studies have revealed that interleukin-23 (IL-23) and interleukin-27 (IL-27) may be therapeutically relevant in selected SLE manifestations. This study aimed to identify associations between serum IL-27 and IL-23 levels and disease activity in Polish patients with different manifestations of SLE: neuropsychiatric lupus (NPSLE), and lupus nephritis (LN). Associations between interleukin levels and oligo-specific antibodies against double-stranded DNA (dsDNA), dose of glucocorticoids, and type of treatment were also analyzed. An enzyme-linked immunosorbent assay was used to assess anti-dsDNA antibodies and analyze the serum concentration of IL-27 and IL-23 from 72 patients aged 19-74 years with confirmed active SLE. Disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2-K). No significant correlations between interleukin levels and SLEDAI score, anti-dsDNA, corticosteroid dose, or type of treatment were noted. Patients with NPSLE and LN presented the highest median scores of SLEDAI.

TYK2 as a therapeutic target in the treatment of autoimmune and inflammatory diseases.

JAKs are intracellular protein tyrosine kinases that, through activation of STATs, are responsible for signal transduction pathways that regulate cellular responses to numerous cytokines, growth factors and hormones in many different cells. JAK-STAT signaling plays a key role in regulating immune function, and cytokines - such as IL-23, IL-12 and type I interferons - are central to the pathogenesis of autoimmune diseases, including psoriasis, inflammatory bowel disease and systemic lupus erythematosus. Here the authors review the evidence for targeting TYK2 as a more specific approach to treating these conditions. TYK2 inhibitors are clinically effective in autoimmune and inflammatory diseases and may avoid some of the complications reported with nonselective JAK inhibitors.

The solution and solid-state degradation study followed by identification of tedizolid related compounds in medicinal product by high performance liquid chromatography with diode array and tandem mass spectrometry detection.

The aim of the study was to investigate the intrinsic stability and to identify potential degradation products of tedizolid disodium phosphate (TED-OPO3Na2), which belongs to the antimicrobial agents of the oxazolidinone class. Tedizolid, as disodium phosphate (prodrug), is registered under the trade name SIVEXTRO®, at a dose of 200 mg, in the form of powder for injection or infusion. The stability-indicating assay method was optimised using HPLC with diode array detection and with electrospray ionisation time-of-flight mass spectrometry. In solution-state studies, the forced decomposition of TED-OPO3Na2 carried out under acidic, basic, oxidative, photocatalytic, and thermal conditions revealed the lability of TED-OPO3Na2 to acidic, basic, and photocatalytic (UV) conditions, while it was relatively stable in oxidative conditions and during thermolysis processes. The kinetics of degradation and shelf-life values in solution-state studies were determined, and activation energies were calculated for alkaline and thermolytic degradation. In contrast, in the solid state degradation study, TED-OPO3Na2 was stable under thermal conditions at high humidity and in visible light, while moderate degradation was observed under thermal conditions of low humidity and ultraviolet light. The developed method enabled the identification of 12 new degradation products and 3 new by-products.

Work instability and associated factors among patients with rheumatoid arthritis in Greater Poland.

OBJECTIVES: Rheumatoid arthritis (RA) affects patients' capacity to work. The Rheumatoid Arthritis Work Instability Scale (RA-WIS) is a reliable method to measure work instability (WI) (1-3). We lack data on the relationship between RA and work instability among Polish patients. Our study aimed to assess WI and associated factors among patients with RA. MATERIAL AND METHODS: The authors conducted a multi-centre cross-sectional observational study. 315 patients from three rheumatology centres were enrolled and filled in questionnaires, including demographic and self-reported clinical data, RA-WIS, and the Health Assessment Questionnaire (HAQ). Swollen and tender joint counts (SJC, TJC) were assessed by the attending physician, and current erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were collected. We excluded 41 patients due to an incorrectly filled in form and analysed questionnaires of 274 patients. DAS28 (Disease Activity Score in 28 joints) and DAS28-CRP were calculated. We performed statistical analysis with Statistica v. 13.3 using the Mann-Whitney U test, χ2 test, and Spearman's correlation. RESULTS: 140 (51%) patients were currently employed and their characteristics were analysed. In univariable analysis we identified the following risk factors for high risk WI: moderate-to-high disease activity (DAS28 ≥ 3.2 - OR 2.29, 95% CI 1.06-4.96, p = 0.033; DAS28-CRP ≥ 3.2 - OR 2.34, 95% CI 1.04-5.27, p = 0.038), ESR ≥ 30 mm/h in women and ≥ 20 mm/h in men (OR 2.65, 95% CI 1.20-5.89, p = 0.010), CRP ≥ 1 mg/dl (OR 4.02, 95% CI 1.78-9.10, p < 0.001), HAQ-DI > 1.0 (OR 2.23, 95% CI 1.04-4.81, p = 0.037) and at least moderate pain on the visual analogue scale (VAS p ≥ 4.5 cm - OR 5.31, 95% CI 2.36-11.96, p < 0.001).Correlations were moderate between RA-WIS and VASp (RS = 0.59, p < 0.001) and HAQ-DI (RS = 0.52, p < 0.001) but weak with disease activity indices (DAS28 [RS = 0.31, p < 0.001]; DAS28-CRP [RS = 0.28, p < 0.001]). CONCLUSIONS: Pain and disability are the main factors strongly associated with work instability among patients with RA.

Kikuchi-Fujimoto disease associated with primary Sjögren's syndrome - literature review based on a case report.

Primary Sjögren's syndrome (pSS) is a chronic, autoimmune disease predominantly involving exocrine glands. Lymphadenopathy is one of the possible symptoms of pSS. It may also suggest development of non-Hodgkin lymphoma (NHL), the most severe complication of pSS, or be a symptom of less common diseases, such as Kikuchi-Fujimoto disease (KFD), presented in this paper. Kikuchi-Fujimoto disease is an extremely rare, benign and self-limiting disorder, characterized by regional lymphadenopathy. This paper presents a case of previously unreported association of pSS, KFD and renal cancer in a patient with recurrent cervical lymphadenopathy, as well as a discussion on the coexistence of these diseases based on available literature searching for PubMed, Scopus and Google Scholar databases, particularly in this subject. These three clinical entities may manifest lymphadenopathy each, causing a diagnostic dilemma. The treatment is also challenging under such circumstances. In this particular situation, it was a combination of immunosuppressive therapy and surgery.

Synthesis and search for 3ß,3'ß-disteryl ethers after high-temperature treatment of sterol-rich samples.

It has been proven that at increased temperature, sterols can undergo various chemical reactions e.g., oxidation, dehydrogenation, dehydration and polymerisation. The objectives of this study are to prove the existence of dimers and to quantitatively analyse the dimers (3ß,3'ß-disteryl ethers). Sterol-rich samples were heated at 180 °C, 200 °C and 220 °C for 1 to 5 h. Quantitative analyses of the 3ß,3'ß-disteryl ethers were conducted using liquid extraction, solid-phase extraction and gas chromatography coupled with mass spectrometry. Additionally, for the analyses, suitable standards were synthetized from native sterols. To identify the mechanism of 3ß,3'ß-disteryl ether formation at high temperatures, an attempt was made to use the proposed synthesis method. Additionally, due to the association of sterols and sterol derivatives with atherosclerosis, preliminary studies with synthetized 3ß,3'ß-disteryl ethers on endothelial cells were conducted.

Factors associated with quality of life in systemic sclerosis: a cross-sectional study.

INTRODUCTION: Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive fibrosis of the skin and internal organs, leading to their failure and disturbances in the morphology and function of blood vessels. The disease affects people in different ways, and identifying how the difficulties and limitations are related to quality of life may contribute to designing helpful interventions. The aim of this study was to identify factors associated with quality of life in people with SSc. METHODS: This was a cross-sectional study conducted in 11 rheumatic centres in Poland. Patients diagnosed with SSc were included. Quality of life was measured using the SSc Quality of Life Questionnaire (SScQoL). The following candidate factors were entered in preliminary multivariable analysis: age, place of residence, marital status, occupational status, disease type, disease duration, pain, fatigue, intestinal problems, breathing problems, Raynaud's symptoms, finger ulcerations, disease severity, functional disability, anxiety and depression. Factors that achieved statistical significance at the 10% level were then entered into a final multivariable model. Factors achieving statistical significance at the 5% level in the final model were considered to be associated with quality of life in SSc. RESULTS: In total, 231 participants were included. Mean age (SD) was 55.82 (12.55) years, disease duration 8.39 (8.18) years and 198 (85.7%) were women. Factors associated with quality of life in SSc were functional disability (ß = 2.854, p < 0.001) and anxiety (ß = 0.404, p < 0.001). This model with two factors (functional disability and anxiety) explained 56.7% of the variance in patients with diffuse SSc and 73.2% in those with localized SSc. CONCLUSIONS: Functional disability and anxiety are significantly associated with quality of life in SSc. Interventions aimed at improving either of these factors may contribute towards improving the quality of life of people with SSc.

Autologous hematopoietic stem cell transplant for progressive diffuse systemic sclerosis: procedural success and clinical outcome in 5-year follow-up.

Systemic sclerosis is an autoimmune connective tissue disease affecting both skin and internal organs. Progressive disease with multiple organ involvement is considered to have a poor prognosis. Treatment possibilities are limited, but certain patients may benefit from autologous hematopoietic stem cell transplantation (auto-HSCT). We report a case of a 30-year-old woman with progressive diffuse systemic sclerosis treated with parenteral cyclophosphamide with unsatisfactory results. Due to progression of the disease and lack of alternative therapies auto-HSCT was performed. After instituting treatment with autologous hematopoietic stem cell transplantation no immunosuppressive therapy has been required during 5-year follow-up. Improvement in exertion tolerance, partial regression of skin lesions and stabilization of pulmonary and cardiovascular changes were observed. Currently therapeutic options in patients with progressive systemic sclerosis are limited. Hematopoietic stem cell transplantation might become an alternative therapeutic solution not only in the early phase of the disease but also among selected patients with progressive systemic sclerosis resistant to standard therapy.