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Introduction: Invariably, the search for an “ideal drug” in psychiatry has been going for years, one that is safe and effective, prevents relapse and shows the least possible side effects. Material and methods: The aim of this study authors is to draw attention to new drugs used in psychiatry- cariprazine, lurazidone and esketamine, their mechanism of action, dosage, the most common side effects and metabolism. The article reviews the research and works on these drugs available in Google Scholar and PubMed databases and the characteristics of medical products on years 2010-2021. Results: Cariprazine is a drug registered in Poland for the treatment of schizophrenia in adults since July,13 2017. In the world, it is additionally used in the treatment of manic and mixed episodes in the course of bipolar disorder, depression in the course of bipolar disorder and unipolar depression. Lurasidone in Poland is indicated for the treatment of schizophrenia in adult patients and adolescents from 13 years of age. In the world it is also used to treat depression in bipolar disorder, in some cases off-label in the treatment of mania in bipolar disorder and irritability and anger in autism spectrum disorders. Esketamine in nasal spray in combination with an oral antidepressant has been approved in the US for the treatment of depression in adults for whom other antidepressants have not benefited, in Poland, it is also used in such an indication. Conclusions: The action profile of these drugs, the research to date and the results of treatment with these drugs are very promising. The drugs are safe and well tolerated. However, it is clinical practice that will verify the usefulness and effectiveness of treatment with them and show the effects of long-term therapies with their use.

We apply a vector autoregression (VAR) model to investigate the market cycles of Initial Coin Offerings (ICOs) as well as their relationships with bitcoin and ether. Our sample covers 104 weekly observations between January 2017 and December 2018. Our results show that ICO market cycles exist and that shocks to the growth rates of ICO volumes are persistent. In addition, shocks in cryptocurrency returns have a substantial and positive effect on ICO volumes. In contrast, the volatility of cryptocurrency returns does not significantly affect ICO volumes. Our results are robust to using (i) the number of successfully completed ICO campaigns instead of ICO volumes and (ii) ICO data from a different data source. Our study has implications for financial practice, in particular for cryptocurrency investors and entrepreneurial firms conducting ICOs.

Rheumatoid meningitis (RM) is a rare central nervous system (CNS) manifestation of rheumatoid arthritis (RA) with a wide spectrum of symptoms. We present a review of the literature with a rare illustrative case of a 61-year-old man with a history of seropositive rheumatoid arthritis (RA) who presented headaches, stroke-like symptoms and seizures. MRI revealed the leptomeningeal enhancement in the right hemisphere. As cerebromeningeal fluid showed increased level of protein and was positive for Candida mannan, the initial clinical diagnosis was fungal meningitis. Despite the antifungal treatment the patient’s clinical condition did not improve. Detailed laboratory, radiologic and histopathological diagnostics enabled the diagnosis of RM. In conclusion is worth to highlight that presentation of RM is variable and complex, diagnosing it is a big dilemma which is why it must be considered in the differential in a patient with long-standing seropositive RA.

Sjögren’s syndrome (SS) is a chronic autoimmune disease with a wide spectrum of possible organ involvement. Peripheral (PNS) and central nervous system (CNS)-related symptoms may occur in the course of the disease. The aim of this study was to compare the health-related quality of life (HR-QOL) in SS patients with and without peripheral neuropathy. The study involved 50 patients with primary Sjögren’s syndrome (pSS). All patients underwent neurological clinical examination followed by nerve conduction studies (NCS) and rheumatological examination. Thirty-six-item Short Form Health Survey (SF-36) was used for evaluating HR-QOL. To assess pSS activity, the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) were used. For the assessment of clinical disability due to peripheral neuropathy, the Overall Disability Sum Score scale (ODSS) was used. Additional evaluation of pain was performed with the use of the Visual Analogue Scale (VAS) and a semistructured interview. Twenty-three (46%) patients were diagnosed with peripheral neuropathy. The most common PNS manifestation was sensorimotor neuropathy (47%). Neurological symptoms preceded the diagnosis of pSS in eight patients. The following domains of the SF-36 form were significantly lower scored by patients with peripheral nervous system involvement: role-physical [0 (0–100) vs. 75 (0–100)], role-emotional [67 (0–100) vs. 100 (0–100)], vitality [40 (10–70) vs. 50 (20–75)], bodily pain [45 (10–75) vs. 55 (0–100)], and general health [20 (5–50) vs. 30 (0–50)] (p ≤ 0.05). Our study showed that peripheral neuropathy was a common organ-specific complication in SS patients. In pSS patients, coexisting neurological involvement with symptoms such as pain and physical disability may be responsible for diminished HR-QOL.

ObjectivesSpecific systemic autoimmune syndrome characterized by inflammatory myopathy, arthritis or arthralgias, interstitial lung disease (ILD), fever, Raynaud’s phenomenon, and mechanic’s hands is called antisynthetase syndrome (AS). The aim of this study was to assess the clinical spectrum associated with presence of aminoacyl-transfer RNA synthetase autoantibodies (ASA).Material and methodsA total of 305 patients with presence of myositis-specific autoantibodies were identified in the database of immunological tests performed in the Clinical Immunology and Transplantology Unit, Medical University of Gdansk between January 2011 and March 2016. In 110 patients (36%) ASA were detected. The detailed analysis included 50 patients with ASA for whom full clinical data were available.ResultsThe incidence of specific ASA in the analyzed group was: Jo-1 46% (23 patients), PL-12 32% (16 patients), PL-7 16% (8 patients), OJ 12% (6 patients), EJ 6% (3 patients). In 10% (5 patients) there was coexistence of at least one ASA, and in another 5 patients there was coexistence of ASA with other antibodies specific for myositis (MSA). In the analyzed group of patients 11 (22%) satisfied the Bohan and Peter criteria for dermatomyositis, 1 for polymyositis. In 5 patients (10%) based on clinical presentation and ASA presence the AS was recognized. Another 3 patients met the criteria of the overlap syndrome polymyositis respectively with systemic lupus, rheumatoid arthritis, and scleroderma. In 5 patients undifferentiated connective tissue disease was diagnosed, and 14 consecutive patients were diagnosed with other connective tissue diseases, while 12 patients did not receive a definitive diagnosis.ConclusionsThe clinical presentation of patients with the presence of ASA is varied. Their presence indicates not only idiopathic inflammatory myopathies, but also non-specifically other disease entities. These patients require observation for the development of idiopathic inflammatory myopathy, and ILD.

Objective: Antipsychotic compounds are known to induce sedation somnolence and have expanded clinical indications beyond schizophrenia to regulatory approval in bipolar disorder, treatment-resistant depression, and is being repurposed in infectious diseases and oncology. However, the medical sciences literature lacks a comprehensive association between sedation and somnolence among a wide-range of antipsychotic compounds. The objective of this study is to assess the disproportionality of sedation and somnolence among thirty-seven typical and atypical antipsychotics.Materials and Methods: Patient adverse drug reactions (ADR) cases were obtained from the United States Food and Drug Administration Adverse Events Reporting System (FAERS) between January 01, 2004 and September 30, 2020 for a wide-array of clinical indications and off-label use of antipsychotics. An assessment of disproportionality were based on cases of sedation and somnolence and calculated using the case/non-case methodology. Statistical analysis resulting in the reporting odds-ratio (ROR) with corresponding 95% confidence intervals (95% CI) were conducted using the R statistical programming language.Results: Throughout the reporting period, there were a total of 9,373,236 cases with 99,251 specific ADRs reporting sedation and somnolence. Zuclopenthixol (n = 224) ROR = 13.3 (95% CI, 11.6–15.3) was most strongly associated of sedation and somnolence and haloperidol decanoate long-acting injection (LAI) was not statistically associated sedation and somnolence. Further, among atypical antipsychotic compounds, tiapride and asenapine were the top two compounds most strongly associated with sedation and somnolence. Comprehensively, the typical antipsychotics ROR = 5.05 (95%CI, 4.97–5.12) had a stronger association with sedation and somnolence when compared to atypical antipsychotics ROR = 4.65 (95%CI, 4.47–4.84).Conclusion: We conducted a head-to-head comparison of thirty-seven antipsychotics and ranked the compounds based on the association of sedation and somnolence from ADR data collected throughout 16 years from the FAERS. The results are informative and with recent interests in repurposing phenothiazine antipsychotics in infectious disease and oncology provides an informative assessment of the compounds during repurposing and in psychopharmacology.

Background: There has been a noticeable and systematic growth of the use of psychoactive substances over the past few decades. Dual diagnosis is a clinical term referring to the occurrence of psychoactive substance use disorder comorbid with another psychiatric disorder in the same person. The most common type of dual diagnosis is the co-occurrence of alcohol use disorder and mood disorders in the form of a depressive episode. Co-occurrent substance use disorders are frequently influenced by genetic factors. In selecting our area of research, we focused on dopamine and the DRD4 (Dopamine Receptor D4) gene polymorphism as well as associations with personality features. The aim of the study: The aim of the study was to compare DRD4 exon 3 (DRD4 Ex3) gene polymorphisms in patients diagnosed with polysubstance use disorder and co-occurrence of a depressive episode to DRD4 exon 3 gene polymorphisms in patients diagnosed with polysubstance use disorder and without co-occurrence of a depressive episode and a group of healthy volunteers. The study also aimed at establishing associations between personality features and DRD4 exon 3 gene polymorphisms of male patients diagnosed with polysubstance use disorder with co-occurrence of a depressive episode which may present a specific endophenotype of this group of patients. Methods: The study group comprised 602 male volunteers: patients diagnosed with polysubstance use disorder comorbid with a depressive episode (PUD MDD) (n = 95, mean age = 28.29, standard deviation (SD) = 7.40), patients diagnosed with polysubstance use disorder (PUD) (n = 206, mean age = 28.13, SD = 5.97), and controls (n = 301, mean age = 22.13, SD = 4.57). The patients and control subjects were diagnosed by a psychiatrist using the Mini International Neuropsychiatric Interview (MINI), the NEO Five-Factor Personality Inventory (NEO-FFI), and the State-Trait Anxiety Inventory (STAI) questionnaires. An analysis of the DRD4 exon 3 polymorphism was performed. Results: The patients diagnosed with PUD MDD compared to the control group of healthy volunteers showed significantly higher scores on both the STAI status and features scale and the NEO-FFI Neuroticism and Openness Scale, as well as lower scores on the Extraversion, Agreeableness, and Conscientiousness NEO-FFI scales. In the DRD4 exon 3 gene polymorphism, the s allele was more frequent in the PUD MDD compared to the l allele, which was less frequent. The results of the 2 × 3 factor analysis of variance (ANOVA) in patients and controls and the variant DRD4 exon 3 interaction were found on the Extraversion Scale and the Conscientiousness Scale of the NEO-FFI. Conclusions: The associations show that psychological factors combined with genetic data create a new area of research on addiction, including the problem of dual diagnosis. However, we want to be careful and draw no definite conclusions at this stage of our research.

Objectives: The aim of the study was the assessment of lung ultrasound (LUS) as a screening of pulmonary interstitial involvement secondary to systemic connective tissue diseases. Methods: A prospective study was conducted on the study group comprising 180 patients diagnosed with different systemic connective tissue diseases. Each patient underwent lung ultrasound (LUS), high-resolution chest computed tomography (HRCT), and echocardiography (ECHO). Each imaging examination was blinded and performed by an independent operator. LUS was conducted with convex and linear transducers. Results: The sensitivity and specificity of LUS as compared to HRCT in detecting pulmonary interstitial involvement in the study group were 99.3% and 96.4%, respectively, positive predictive value (PPV) 0.7, negative predictive value (NPV) 3.6. Abnormalities indicating interstitial lung disease (ILD) with fibrosis were most frequently localized bilaterally in the lower fields of the lungs, assessed in the dorsal view. Conclusions: LUS is an efficient imaging modality that can detect pulmonary interstitial involvement in patients with systemic connective tissue disease with a high sensitivity and specificity. Further prospective studies conducted on a larger population are deemed necessary.

Musculo-skeletal complaints in a patient suffering from systemic lupus, with co-existing chronic renal failure, undergoing immunosuppressive treatment after kidney transplantation, can have a varied etiology. The aim of this work was to present a case based review of differential diagnosis of knee pain in such a patient. A literature search was carried out using MEDLINE/PubMed, Google Scholar and EBSCO, with no time limit. We undertook a systematic review of the literature published in English, limited to full-text publications of original articles, letters to the editor, and case reports in peer-reviewed journals, for a discussion and analysis of studies reporting arthralgia in patients with lupus after kidney transplantation. We present a case report of a 45-year-old woman with lupus nephritis, after kidney transplantation, who started to complain of increasing pain in the knees, most pronounced at night and after physical activity approximately 2 years after transplantation. Extensive causal diagnostics were carried out, which revealed bilateral extensive regions of bone infarction in the femur and tibia, chondropathy, degenerative changes of medial meniscuses in the body and posterior horn as well as chondromalacia of the patella. Establishing the right diagnosis is crucial for implementing appropriate treatment.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease that leads to a chronic inflammatory process in tissues and organs. The neuropsychiatric systemic lupus erythematosus (NPSLE) is a set of neuropsychiatric symptoms that derive from the central and peripheral nervous system and are observed in the course of SLE.Case Report and Final Diagnostic and Therapeutic Results: A diagnostic and therapeutic process in a patient with the signs and symptoms of SLE and bipolar disorder (BD) has been described. Bipolar disorder has been diagnosed as a primary disorder while SLE as a comorbid disease.Discussion: Common immunological mechanisms in BD and SLE are the reason for difficulties in diagnosing BD with co-occurring SLE. It should be determined whether BD is a primary disorder or a secondary component of a clinical picture of SLE (NPSLE) or whether mood and/or psychotic disorders are the result of steroid therapy in the course of SLE (steroid-induced mood and psychotic disorders, SIMPD).Conclusion and the Patient's Perspective: The presented case report is a unique description of a patient with a primary diagnosis of BD with comorbid SLE.

The COVID-19 pandemic induced by the SARS-CoV-2 virus causes huge health burden. It influences physical and mental state of both, people who are infected and those who take care of them. The particularly exposed are healthcare professionals who have direct contact with patients infected with the SARS- CoV-2 virus. Workers belonging to this group especially often report anxiety, fear, mood disorders, frustration, loneliness, low quality of sleep, somatization disorders and phobias. Current efforts of the authorities are focused on preventing and limiting the spread of infection. What is missing, are specific interventions aimed at mental health care of the whole society, including healthcare professionals – doctors, nurses, paramedics, especially exposed to infection due to performed profession.

Introduction. The illness acceptance is one of the most effective strategies to cope with a chronic illness. Aim. The purpose of this study is to recognize which factors determine and favor acceptance of a chronic illness, in regard to the personal resources of alcohol-dependent patients. Material and methods. The study was conducted on 60 alcohol-dependent patients. During the study, the following research tools were used: Rosenberg’s SES questionnaire and AIS scale questionnaire. Results and conclusions. The study group is characterized by an average level of acceptance of the disease. The level of self-esteem is an important factor in determining the level of acceptance of the disease in patients.

Prostate adenocarcinoma, remaining among top most common cancers, is a heterogeneous group of tumors with a diverse morphological structure. Basing on the histological architecture of cancer tissue, individual cases can be classified into different therapeutic groups. Current diagnosis of prostate cancer brings many challenges. The major problem is the lack of effective and accessible diagnostic methods that would eliminate incidences of overdiagnosis and prevent unnecessary treatments of many patients. There are many efforts to determine favorable and unfavorable molecular prognostic factors. The basic marker currently used in this field is prostate-specific antigen (PSA). Increased level of PSA may suggest the presence of prostate cancer although its level is not specific for the disease and can be elevated also in certain benign hyperplastic or inflammatory conditions as well as after irritation or rectal examination. Clinical symptoms such as dysuria or hematuria are often uncharacteristic and benign prostatic diseases which cannot be confirmed on the basis of physical examination alone. Also, we often deal with the situation of false negative results of prostate needle biopsy, which require many tests to determine the final correct diagnosis. Moreover, prostate cancer can also be present in patients with non-elevated serum PSA level. Due to such difficulties, the search for new molecular markers that could be used for diagnostic purposes is underway. Evaluation of survivin level in prostate cancer tissue may serve as a new diagnostic indicator of prostate cancer progression. Other useful molecular biomarkers with good potential in prostate cancer diagnosis are AMACR (Alpha Methyl Acyl Coenzyme A Racemase), p-63 or Ki-67 or microRNAs present in body fluids.

Research on initial coin offerings (ICOs) is nascent and assesses ICOs from the perspectives of ventures and regulators. Little is known about the equally important group of investors who provide their capital to ventures in ICOs. Using a primary dataset of 517 ICO investors, we identify and categorize the motivations to invest in ICOs using factor analysis. We find that investors are driven by ideological, technological, and financial motives. Regarding the relative importance of the motives, we find that technological motives are the most important motives to ICO investors, followed by financial and ideological motives. To further profile investors, we conduct a regression analysis to distinguish investors across different motives. For example, we show significant differences across motives with regard to investors' risk perception, sources of information, and demand for strict regulation. The implications of this study for both theory and practice are considerable.

Objectives Sjögren's syndrome (SS) is a chronic inflammatory disease with an autoimmune background with possible complications from peripheral (PNS) and central nervous system (CNS). The aim of this study was to assess the prevalence and to describe the phenotype of peripheral neuropathies in patients with SS. Materials & Methods We studied fifty patients with primary Sjögren's syndrome for peripheral nervous system involvement. All patients underwent neurological and rheumatological examination followed by nerve conduction studies (NCS) of nine peripheral nerves. Results Thirty‐six patients (72%) fulfilled the criteria for the diagnosis of neuropathy. Carpal tunnel syndrome (54%) and axonal sensorimotor neuropathy (22%) were the most common. Neurological symptoms preceded the diagnosis of SS in eight patients. Conclusions Peripheral neuropathies are frequent in SS patients. Neurologists should be aware of possible autoimmune causes of neuropathies because clinical manifestations of neuropathy may precede the development of other symptoms of the autoimmune disease., Our study shows that peripheral neuropathies are frequent among patients with primary Sjögren's syndrome. Neurologists should be aware of possible autoimmune causes of neuropathies because clinical manifestations of neuropathy may precede the development of other symptoms of the autoimmune disease.

INTRODUCTION ANCA-associated vasculitides (AAV) is a group of rare disorders where inflammation and damage of the small blood vessels lead to dysfunction of the supplied organs. In severe flares of the disease patients may require intensive care unit (ICU) admission and treatment. The study aims to characterize Polish patients with AAV who were admitted to the ICU and compare them to the others. MATERIAL AND METHODS An observational, retrospective study based on the POLVAS - registry of Polish adult patients with AAV was carried out. Patients admitted to the ICU (ICU group) were identified and compared with the patients who did not require ICU admission (non-ICU group). Characteristics and comparison between groups were made using standard statistic descriptive methods. RESULTS 30 patients admitted to the ICU were identified among 573 cases included in the registry. All patients in the ICU group with available data were ANCA positive. The clinical manifestations related to the ICU admission were respiratory, renal and central nervous system involvement. The treatment regimen for remission induction was similar in both groups. Almost half of the patients in the ICU-group (48.3%) required dialysis, whereas in the non-ICU group it was 21.8% (P = 0.01). Infections were also more frequent in the ICU group (72.4% vs. 36.9% P < 0.001). The mortality rate among patients who needed ICU treatment was significantly higher when compared to the rest of the patients (53.6% vs. 7.8%; P < 0.001). CONCLUSIONS In the Polish AAV cohort one in twenty patients required ICU admission. This group was characterized by multiple organ involvement and high mortality.

We report the case of a 57-year-old Caucasian man who presented with dry cough, haemoptysis, fever, lung nodules, erythrocyturia, and acute hepatitis. After a lung biopsy, the patient was diagnosed with granulomatosis with polyangiitis. The diagnosis was supported by the presence of antiproteinase-3 anti-neutrophil cytoplasmic antibodies. The most common causes of liver damage are excluded. The patient was treated with prednisone and cyclophosphamide, which resulted in remission of chest CT findings and improvement in liver function tests. During the flare, new lung infiltrations as well as elevation of liver enzymes were present. Treatment with rituximab resulted in complete clinical and radiological remission and normalisation of liver function tests. What makes this case worth reporting is the rare liver involvement in the GPA. After exclusion of coexistence of autoimmune liver disease and drug-induced liver lesion, organ involvement was supported by the reversion of abnormal LFT after the immunosuppression of GPA.

Background: Endometriosis is a chronic inflammatory condition characterized by the presence of endometrial-like tissue outside of the uterine cavity. It affects approximately 6–12% among reproductive-age women. Laparoscopy is still the gold standard for diagnosing it. Since an average of couple of years elapses from the onset of symptoms to the definitive diagnosis, analysis of symptoms could serve as a non-invasive diagnostic tool. Methods: An anonymous survey was distributed online in November 2019. It contained 23 closed questions, which covered two areas: knowledge and awareness of endometriosis symptoms and its presence among respondents. Results: A total of 3319 women completed the survey, of which 328 were diagnosed with endometriosis (9.9%). The symptoms of endometriosis most often indicated by the general population were infertility and dysmenorrhea. In contrast, those least frequently indicated were painful defecation and dysuria. Respondents suffering from endometriosis indicated that they often or sometimes experienced dysmenorrhea (83%, n = 273), pelvic pain not related to menstruation (72%, n = 235), dyspareunia (68%, n = 223) and painful defecation or dysuria (40%, n = 132). Conclusions: Since the search for a non-invasive diagnostic endometriosis marker has been conducted for many years without success so far, it seems that awareness of the clinical presentation and reported symptoms may help to provide earlier diagnoses.

Granulomatosis with polyangiitis (GPA) is a chronic, relapsing, primary systemic small vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies. The disease is characterised by the involvement of various organs. The relapse rate rises from about 20% at 12 months to about 60% at 5 years. The combination of glucocorticoids and cyclophosphamide remains the standard therapy for patients with generalised GPA; nevertheless, some patients do not respond satisfactorily to this treatment. According to EULAR-EDTA recommendations for the management of ANCA-associated vasculitis, RTX should be considered for remission-induction of new-onset as well as major relapse of organ-threatening or life-threatening GPA. Here we present a 35-year-old patient with relapsing GPA successfully treated with RTX. We also highlight the infectious complications of immunosuppressive treatment.

Diffuse alveolar haemorrhage (DAH) leads to acute respiratory failure. This is why it requires rapid diagnosis and implementation of appropriate treatment. The standard diagnosis of a patient with DAH includes laboratory tests, diagnostic imagining (X-ray of the chest, high-resolution computed tomography), and bronchoscopy with bronchoalveolar lavage. We present a description of 2 patients diagnosed with systemic connective tissue disease and DAH, monitored with the help of lung ultrasound. To our knowledge, this is the first description of the use of lung ultrasound in DAH in adult patients.

IntroductionGranulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are forms of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). AAV most commonly affects the upper and lower respiratory tract as well as the kidneys. The first symptoms are often nonspecific, requiring careful differential diagnosis with infections and malignancies.Materials and methodsWe analyzed the clinical and radiological data of 38 patients (20 females and 18 males) diagnosed with ANCA-associated vasculitis. Lung involvement was observed in 29 cases. Lung ultrasound (LUS) was performed on 21 patients from the study group and compared to chest CT. For 7 patients the examination was conducted repeatedly.ResultsIn total, 35 LUS and CT examinations were performed, revealing the following lesions: nodules, infiltrates with and without features of disintegration, caves (n = 17), diffuse alveolar hemorrhage (n = 3), and features of interstitial lung disease (ILD) with pulmonary fibrosis (PF) (n = 11). In 2 cases LUS and CT were negative. In 4 cases LUS was negative, despite a positive CT result.ConclusionsBoth in CT and LUS, images of pulmonary lesions were consistent though highly variable. Therefore, further studies are required for a larger group of patients.

This study investigates financing patterns of European SMEs by looking at a large number of different financing instruments and their complementary and substitutive effects, using the SAFE dataset collected in 2015. We develop an empirical taxonomy of SME financing patterns in Europe to analyse SME financing, applying cluster analyses. Our cluster analysis identifies seven distinct SME financing types based on the financing instruments used: mixed-financed SMEs with focus on other loans, mixed-financed SMEs with focus on retained earnings or sale of assets, state-subsidised SMEs, debt-financed SMEs, trade-financed SMEs, asset-based financed SMEs and internally financed SMEs. Moreover, the SME financing types can not only be profiled according to their firm-, product-, industry- and country-specific characteristics but also to macroeconomic variables. Our findings can support policy makers in assessing the impact of changes in policy measures for SME financing.

We analyze the distribution of venture capital (VC) investments across German regions and explore the geographical determinants of these investments. So far, little is known about the regional determinants of governmental (GVC), independent (IVC), and corporate (CVC) VC firms and about whether these types of VC firms invest in different regions. Combining a dataset of 402 German districts, our regressions show that regions with a higher supply of human capital and knowledge creators attract a significantly higher number of GVC investments. Moreover, we find a significant difference in economically weaker regions but do not find a metropolitan bias. Hence, GVC firms do not invest more frequently in rural regions per se and do not prevent regional disparities more often than other types of VC firms. The implications of these findings for high-tech firms and regional policy are discussed.

Background: Systemic manifestations are common in primary Sjogren’s syndrome (pSS) and play a major role in the prognosis. Neurological complications may affect both the peripheral (PNS) and central nervous system (CNS). The incidence varies from several to several dozen percent. The course of the disease and the severity of the symptoms may be mild and self-limiting or progressive, leading to permanent neurological deficits. It is worth remembering that the symptoms of nervous system involvement may precede the onset of symptoms of dryness, and diagnosis of pSS may be delayed after a certain duration of neurological symptoms. Objectives: The aim of the study was to determine the prevalence of PNS involvement among symptomatic and asymptomatic patients with the diagnosis of pSS in our University Clinical Centre. Methods: We studied a consecutive group of fifty unselected patients aged from 33 to 74 years (mean 55.8 years). All patients fulfilled the criteria for the diagnosis of pSS. Additional connective tissue diseases and diabetes were the exclusion criteria. Disease activity was evaluated according to the EULAR Sjogren’s syndrome disease activity index (ESSDAI). All patients underwent clinical neurological examination and nerve conduction studies (NCS) of nine peripheral nerves. For the classification of polyneuropathies the ESTEEM (European Standardized Telematic tool to Evaluate Electrodiagnostic Methods) guidelines were used. Clinical examination and nerve conduction study were performed and evaluated by one certified neurologist. Results: Of our 50 patients, 48 were female with a mean (±SD) age 53.6±10.5 years and mean disease duration 7.9±5.3 years. Two were male with mean age 43.7±25.8 years and mean disease duration 5.7±0.6 years. The mean age at diagnosis was 50.4±14 years. 23 (46%) patients fulfilled the criteria for the diagnosis of neuropathy. The most common PNS manifestation was sensorimotor neuropathy 11/23 (47%), mononeuropathy was present in 6/23 (26%) patients, pure axonal sensory neuropathy was present in 1/23 (4.3%) patient, axonal motor neuropathy in 1/23 (4.3%), SFN in 1/23 (4.3%) and cranial nerve involvement was present in 4/23 (17.4%) (one of the patients had both cranial and sensorimotor neuropathy). Neurological symptoms preceded the diagnosis of pSS in 8 (35%) of 23 PNS+ patients. The frequency of following symptoms and extraglandular manifestations was significantly higher in PNS+ compared to PNS- patients: salivary gland enlargement (74% vs 44% p Conclusion: We found that PNS involvement is a common extraglandular manifestation of pSS (46% in our group). Sensorimotor neuropathies were most frequent. Involvement of the PNS seems frequent but remains underestimated. NCS is a non-invasive test which might be useful at diagnosis and follow-up. Guidelines for the diagnosis and treatment of peripheral neuropathies in patients with pSS are needed. Disclosure of Interests: None declared

Background: Lung involvement is observed in 43% to 94% of patients with granulomatosis with polyangiitis (GPA) (1). In about 10% of cases, the lung is the only organ affected and in as many as 30% of patients without clinical symptoms of lower respiratory tract involvement, abnormalities in chest imaging examinations can be found (2). The efficacy of lung ultrasound (LUS) is very well documented in many pulmonary diseases (3,4). Single publications indicate its applicability also in diagnostics of complications secondary to systemic connective tissue disease, e.g., lung fibrosis or diffuse alveolar hemorrhage (5,6). The necessity of repeating chest imaging examinations increases the patient‘s exposure to ionizing radiation. Thus, the possibility of limiting such exposure through the application of LUS as the diagnostic modality appears extremely inviting. Objectives: The aim of this study was to assess lesions detected by ultrasound in patients with active granulomatosis with polyangiitis (GPA) in comparison to abnormalities found by computed tomography (CT). Methods: We analyzed the clinical and radiological data of 12 patients (5 women/7 men, mean age 47.9 years/range 18-80) with active PR3-ANCA-associated vasculitis with lung involvement (Birmingham Vasculitis activity Score, BVASv3 mean 5.7/range 1-12). LUS was performed in the sitting and lying positions, using the convex (2-6 MHz) and linear (4-12 MHz) transducers placed to each intercostal space over the chest wall (anterior, lateral and inferior). Chest CT was performed according to a standard protocol with the use of a 64-slice CT scanner made by GE. The images obtained in LUS were compared to changes detected in CT scans. The study protocol was approved by an independent local Bioethics Committee (NKBBN/474/2018). Results: In all patients with lungs infiltrations, changes were visible in the LUS, but the visualized infiltrates and caves include only these lesions that were adjacent to the line of pleura. LUS revealed infiltrates as well as infiltrates with features of disintegration and cavities. Subpleural infiltrates in ultrasound were visualized as hypoechoic round or oval consolidations, without central flow visible in color Doppler (CD) and power Doppler (PD) modes. Caves visualized in LUS were round and anechoic; flow in CD and PD modalities was also absent. In some cases, we observed hypoechoic round or oval infiltrates with features of disintegration, partly filled in with fluid content (anechoic). Conclusion: Due to the harmlessness of ultrasonography, LUS can be repeatedly performed. In addition, ultrasound examination can be performed during hospitalization at the patient‘s bedside as well as during a visit to the rheumatologist’s office. References [1] anderson, et al. Wegener’s granuloma. A series of 265 British cases seen between 1975 and 1985. A report by a sub-committee of the British Thoracic Society Research Committee. Q J Med. 1992; 83:427-438. [2] Brown. Pulmonary vasculitis. Proc am Thorac Soc. 2006; 3:48-57. [3] Volpicelli, et al. International evidence-based recommendations for point-of-care lung ultrasound. Intensive Care Med. 2012; 38:577-591. [4] Buda, et al. Polish recommendations for lung ultrasound in internal medicine (POLLUS-IM). J Ultrason.2018; 18:198-206. [5] Masiak, et al. Diffuse alveolar hemorrhage as an initial presentation of aNCA–associated vasculitis in an 80–year–old man. Pol arch intern Med.2017; 127:365-367. [6] Buda, et al. Serial Lung Ultrasonography to Monitor Patient with Diffuse alveolar Hemorrhage. Ultrasound Q. 2017; 33:86-89 Disclosure of interests: None declared

Purpose The aim of this study is to present the treatment modalities and associated side effects in a Polish nation-wide ANCA-associated vasculitides (AAV) patients’ cohort. Materials and methods Retrospective analysis of patients diagnosed with AAV between 1990 and 2016, included in the POLVAS registry was performed. Standard descriptive statistic methods were used with an emphasis on the treatment modalities. Results There were 625 patients diagnosed with AAV included in this study: 417 cases of granulomatosis with polyangiitis (GPA; 66.7%), 106 cases of microscopic polyangiitis (MPA; 17.0%) and 102 cases of eosinophilic granulomatosis with polyangiitis (EGPA; 16.3%). The mean age at the date of diagnosis was 50.4 (±15.7) years and the median observational period amounted to 4.0 (2.0–8.0) years. Glucocorticosteroids (GCs) were the medicaments most frequently used for remission induction (593/622; 95.3%), followed by cyclophosphamide (487/622; 78.3%), rituximab (44/622; 7.1%), and methotrexate (39/622; 6.3%). GCs were also most frequently administered for maintenance therapy (499/592; 84.3%), followed by azathioprine (224/592; 37.8%), methotrexate (136/592; 23.0%) and mycophenolate mofetil (99/592; 16.7%). The median cumulative doses of cyclophosphamide and rituximab equalled 7.99 g (4.18–14.0) and 2000 mg (1500–2800), respectively. The most commonly observed adverse events included: infections - 214/551 cases (38.8%), which were associated with the time of observation (OR = 1.05; 95% CI 1.01–1.10), the use of GCs intravenous pulses (OR = 2.76; 95% CI 1.68–4.54) and need for haemodialysis (OR = 1.73; 95% CI 1.10–2.71). Conclusions Polish patients with AAV were predominantly treated according to appropriate guidelines. The most frequent adverse events were typical for usually administered immunosuppressive treatment.

Industrial robots are often equipped with external sensors that help perform the required production tasks. These sensors may be optical, tactile or force-torque sensors. Depending on the sensor, the measuring range can cover a one-dimensional, two-dimensional or threedimensional space. More specifically, laser line sensors are often used for inspection and calibration of 3D objects. Implementing an intuitive calibration method of such sensors on the robot flange is a challenging task. This is due to the fact that robotic applications and measurements are usually implemented with the presence of noise. As a result, best-fit methods or filters are implemented in order to realize an effective usage of the sensors. This paper deals with the concept of calibrating laser line sensors in order to measure cylindrical components using a bestfit method. Moreover, a modular control system for configuration and operation of the station with a variety of interfaces is discussed.

The Event-Related Potentials were investigated on a group of 70 participants using the dense array electroencephalographic amplifier with photogrammetry geodesic station. The source localisation was computed for each participant. The activity of brodmann areas (BAs) involved in the brain cortical activity of each participant was measured. Then the mean electric charge flowing through particular areas was calculated. The five different machine learning tools (logistic regression, boosted decision tree, Bayes point machine, classic neural network and averaged perceptron classifier) from the Azure ecosystem were trained, and their accuracy was tested in the task of distinguishing standard and target responses in the experiment. The efficiency of each tool was compared, and it was found out that the best tool was logistic regression and the boosted decision tree in our task. Such an approach can be useful in eliminating somatosensory responses in experimental psychology or even in establishing new communication protocols with mildly mentally disabled subjects.

Objective Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). Methods We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). Results Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3–12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06–9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05–6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3–25.5), skin involvement (OR = 4.4; 95% CI = 1.02– 19.6), and age > 65 (OR = 6.3; 95% CI = 1.18–33.7). Conclusions In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease.

The increasing body of evidence implies that brain-derived neurotrophic factor (BDNF) is the most common neurotrophin in the nervous system, playing an important role as an effectiveness indicator for rehabilitation interventions in schizophrenia patients. Currently, with the modern laboratory and instrumental diagnostic methods it is possible to diagnose deficits influencing the level of patient's functioning and use them as a basis for establishing individual re-adaptation programs for schizophrenia patients considering various forms of the therapy in different environments. Based on the PubMed and Scopus search tools a review of the available literature was performed and the paper presents current results of studies analyzing a relationship between selected rehabilitation interventions used in schizophrenia patients and changes in BDNF levels (a correlation between BDNF levels and physical activity and EEG Biofeedback therapy). Out of 240 records identified in total, the ones concerning the subject matter of the paper were taken into account. Studies concerning use of the presented method appear to indicate usefulness of BDNF factor in evaluation of effectiveness of implemented rehabilitation interventions in this group of patients. Changes in neurotrophin levels may indicate a synergy of the central and the peripheral nervous system, and high BDNF levels depending on physical activity and a neuromodulating effect of the EEG Biofeedback therapy may indicate their effectiveness. Use of various neurorehabilitation methods may improve the social functioning in schizophrenia patients. Treating BDNF as a biological indicator of those processes may represent an interesting hypothesis.

Background: We sought to test the hypothesis that transcriptome-level gene signatures are differentially expressed between male and female bipolar patients, prior to lithium treatment, in a patient cohort who later were clinically classified as lithium treatment responders. Methods: Gene expression study data was obtained from the Lithium Treatment-Moderate dose Use Study data accessed from the National Center for Biotechnology Information’s Gene Expression Omnibus via accession number GSE4548. Differential gene expression analysis was conducted using the Linear Models for Microarray and RNA-Seq (limma) package and the Decision Tree and Random Forest machine learning algorithms in R. Results: Using quantitative gene expression values reported from patient blood samples, the RBPMS2 and LILRA5 genes classify male lithium responders with an area under the receiver operator characteristic curve (AUROC) of 0.92 and the ABRACL, FHL3, and NBPF14 genes classify female lithium responders AUROC of 1. A Decision Tree rule for establishing male versus female samples, using gene expression values were found to be: if RPS4Y1 ≥ 9.643, patient is a male and if RPS4Y1 < 9.643, patient is female with a probability=100%. Conclusions: We developed a pre-treatment gender- and gene-expression-based predictive model selective for classifying male lithium responders with a sensitivity of 96% using 2-genes and female lithium responders with sensitivity=92% using 3-genes.

Background:Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a group of systemic necrotizing small vessel vasculitides. Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are two most common types of AAV affecting mainly middle-aged and elderly people. Previous data indicated an increased occurrence of cancer in AAV patients [1], which has been mainly attributed to exposure to cyclophosphamide [2].Objectives:The purpose of this paper was to analyze cancer incidence in unselected patients with GPA and MPA treated in one academic center since 1988 with follow-up until 2020.Methods:With case record review, the baseline characteristics, outcomes and malignancy development in a cohort of 251 patients were assessed. Patients were followed up from time of diagnosis to their death or most recent hospital or outpatient’s assessment.Results:Twenty-eight of 251 patients with AAV (65 % cANCA, 26% pANCA, 9.0 % ANCA-negative) developed a total of 32 malignancies during a mean follow-up of 8.6 years. Patients characteristic is presented in table 1. Mean time since AAV onset to cancer diagnosis was 5.86±6.78 years. Of these malignancies, 2 melanoma, 6 were non-melanoma skin cancers, 4 gastrointestinal tract cancer (2 colon, 1 stomach, 1 liver), 3 bladder cancer, 2 breast cancer, 2 uterine cancer, 1 ovarian cancer, 2 prostate cancer, 1 testis cancer, 2 lung cancer, 6 haematological malignancies (1 lymphoma, 1 chronic myeloid leukemia, 4 monoclonal gammopathy of unknown significance), additionally 1 benign salivary gland tumor was found. Four of the 16 patients with renal transplants developed a total of 6 malignancies. There were no differences in the incidence of cancer by gender, age, severity and activity of the disease, ANCA status, smoking status, number of relapses and treatment. There was no association between cancer and cumulative dose of cyclophosphamide.Conclusion:In the AAV group, 11% of patients developed different type of cancer. The most common was non-melanoma skin cancer. The risk of developing malignancy increased with follow-up time. We found no association of tumor development and cumulative cyclophosphamide dose.References:[1]Rahmattulla et al. Incidence of malignancies in patients with antineutrophil cytoplasmic antibody-associated vasculitis diagnosed between 1991 and 2013. Arthritis Rheum. 2015;67(12):3270–3278.[2]Faurschou M et al. Prolonged risk of specific malignancies following cyclophosphamide therapy among patients with granulomatosis with polyangiitis. Rheumatology (Oxford) 2015; 54:1345–1350.Table 1.Characteristics of the AAV patients included in the study.Total sample (n=251)No malignancy occurrence (n=223)Malignancy occurrence (n=28)P valueAge at diagnosis, mean ± SD years53.0±15.952.4±16.457.9±9.45NSFemale, n (%)115 (45.8%)106 (47.5 %)9 (32.1 %)NSMean observation time (years)5.72±5.175.35±4.938.61±6.170.002BVASv318.9±8.4918.9±8.4618.6±8.90NSDEI7.03±2.867.04±2.906.96±2.62NSOrgan involvement, n (%) Upper respiratory tract170 (67.7 %)151 (67.7 %)19 (67.9 %)NS Lungs163 (64.9 %)142 (63.7 %)21 (75.0 %)NS Kidney171 (68.1 %)151 (67.7 %)20 (71.4 %)NS Skin62 (24.7 %)54 (21.5 %)55 (24.7 %)49 (22.0 %)7 (25.0 %)NS Eyes11 (4.4 %)11 (4.9 %)5 (17.9 %)NS Heart30 (12.0 %)24 (10.8 %)0 (0.0 %)NS Gastrointestinal tract34 (13.5 %)32 (14.3 %)6 (21.4 %)NSFollow-up 0–5 years145 (57.8 %)136 (61.0 %)9 (32.1 %)0.004 > 5–10 years62 (24.7 %)52 (23.3 %)10 (35.7 %)NS > 10 years44 (17.5 %)35 (15.7 %)9 (32.1 %)0.031Deaths, n(%)56 (23.0 %)45 (20.8 %)11 (39.3 %)0.029Renal transplantation, n(%)16 (6.4 %)12 (5.4 %)4 (14.3 %)NSCumulative Cyclophosphamide dose (g)14.7±30.014.5±30.816.6±23.6NSDisclosure of Interests:None declared

Objectives: Inflammatory myopathies are a group of idiopathic, heterogeneous systemic diseases affecting predominantly skeletal muscles, though they can also involve the skin and internal organs. The association between cancer and idiopathic inflammatory myopathies, particularly dermatomyositis, which is termed cancer-associated myositis (CAM), has been reported in the medical literature. A newly described autoantibody to a 155-kDa nuclear protein, identified as transcription intermediary factor 1-gamma (TIF1-γ), has proven useful for cancer screening in patients with dermatomyositis. Material and methods: Based on our database of laboratory results, between November 2014 and January 2016, we found 80 patients with a positive autoimmune inflammatory myopathy immunoblot profile. Results: Eleven of 80 patients revealed the presence of anti-TIF1-γ antibodies: 8 women and 3 men with average age 54.2 years. Dermatomyositis (DM) was diagnosed in 6 cases, polymyositis in 1 case, myositis limited to ocular muscles and rhabdomyolysis in 1 case each, and undifferentiated connective tissue disease in 2 cases. Neoplasm was found in 4 cases. All of those patients had DM. The average time between DM and diagnosis of neoplasm was 7.5 months (from 1 to 18 months). Conclusions: The association between cancer and idiopathic inflammatory myopathies, particularly DM, is well known, and cancer screening should be obligatory in such patients. So far there is no consensus as to the method or frequency with which patients with an idiopathic inflammatory myopathy should be tested to rule out neoplasm. Detection of anti-TIF1-γ antibodies in patients with DM gives the clinicians the very important suggestion of CAM. It seems reasonable that these patients should have more detailed and often repeated differential diagnostics.

Granulomatosis with polyangiitis (GPA) is a primary, systemic small vessel vasculitis. The respiratory tract is typically involved in the course of the disease. Abnormalities on the chest radiograph are noted in more than 70% patients at some point during their disease history. In some clinical situations it is difficult to distinguish whether symptoms result from the underlying disease or are a symptom of infection. In these clinical situations, chest computed tomography (CT) can be very useful. We present a patient with GPA localized mainly in the respiratory tract with sudden deterioration of the general state and new abnormalities revealed in the CT of the chest.

Background: Approximately 25–50% of people diagnosed with substance use disorder experience psychiatric disorders, and this percentage is even higher if subclinical psychopathological symptomatology is taken into consideration. ”Dual diagnosis” implies the comorbidity of two disorders (mental disorder and addiction), but in a clinical setting, numerous dual diagnoses involve multiple addictions (polysubstance use means the concurrent use of more than one psychoactive substance). Clinical observations and epidemiological studies showed that the use of stimulants in combination with other substances results in additional risks. Apart from the clinical significance of the specificity of stimulants used in combination with other substances, only non-exhaustive research on the specificity of this comorbidity has been performed to date. The aim of the study was to analyze polymorphisms of the genes (DRD4 VNTR in exon III Ex3, DRD2 rs1076560, rs1800498, rs1079597, rs6276, as well as in the PROM promoter region (rs1799732, ANKK1 Tag1A rs1800497, DAT) in a group of patients diagnosed with polysubstance use disorder, including addiction to stimulants, and the co-occurrence of specific mental disorders in a group of patients diagnosed with polysubstance use disorder, including addiction to stimulants, compared to the group of patients diagnosed with polysubstance use disorder. Methods: The study group consisted of 601 male volunteers with psychoactive substance dependence (n = 300) and non-dependent controls (n = 301). The genomic DNA was extracted from venous blood using standard procedures. Genotyping was conducted with the real-time PCR method. All computations were performed using STATISTICA 13. Results: Psychotic disorders were significantly more common in the group of males with polysubstance addiction, including addiction to stimulants, compared to the group of males with polysubstance addiction without addiction to stimulants. In our own research, different statistical significances were found in the frequency of the DRD4 Ex3 gene polymorphism: s/s was more common in the study group. Psychotic disorders were more common in people addicted to stimulants compared to people addicted to other substances. Conclusions: In our study, psychotic disorders occurred more frequently in the study group of patients with polysubstance addiction, including addiction to stimulants, compared to the control group of patients with polysubstance addiction, but with no addiction to stimulants. Different statistical significances were found in the frequency of the DRD4 Ex3 gene polymorphism: s/s was more common in the study group, while the l/l genotype was less frequent in the study group. In DRD2 PROM rs 1799732, the del allele occurred more often than the ins allele in the study group. In the DRD4 Ex3 gene polymorphism, the s allele was more common in the study group, and the l allele was less frequent. In the DRD4 Ex3 gene polymorphism for the s/s genotype, psychotic disorders and generalized anxiety were more common, while for the s/l and l/l genotype, they were less frequent. The DRD4 Ex3 polymorphism s alleles were more common for depressive episode, dysthymia, and psychotic disorders as well as generalized anxiety disorder. We see a clear genetic aspect here. However, we want to be careful and draw no definite conclusions.

Background:Rituximab (RTX) is a B cell depleting monoclonal antibody with proven efficacy in the treatment of ANCA-associated vasculitis (AAV). The infectious complications occur in 15-25%.Objectives:We aimed to assess the frequency and risk factors of infections in patients with AAV receiving RTX among Polish patients.Methods:7 tertiary referral centers experienced in the treatment of vasculitis completed a questionnaire regarding AAV patients treated with RTX.Results:Among 49 patients included in the analysis (47 with GPA, 2 with MPA; 36/73% men; mean age at diagnosis 42,45±14,9 yrs., mean age on RTX initiation 46,14±14,72 yrs.,) at least one infection occurred in 20 patients (40.82%) after mean time of 16,65±16,01 weeks since the administration of RTX. Patients were followed for a mean time of 26,88±21,94 months. There were no differences in the incidence of infectious complications by gender, age, BMI, smoking status, severity of the disease, activity of the disease (BVAS), time from diagnosis to RTX initiation, carriage of staphylococcus aureus in the upper respiratory tract, total dose of CYC before RTX treatment. We didn’t observe severe hypogammaglobulinemia or neutropenia after RTX treatment. 40% of the observed infections occurred during the first month, 35% between second and sixth month of follow-up, while 25% were observed between 6 and 12 months after the RTX initiation. Of the 20 patients who developed infection, 12 (24.5%) had further infections. Antibiotic prophylaxis with trimethoprim–sulfamethoxazole was administered in 40 out of 49 (81.63%). Upper respiratory tract infection was the most common infectious complication (n=11), followed by lower respiratory tract (n=4), soft tissues (n=4) and urinary tract infections (n=4), lacrimal gland abscess (n=2) and abdomen (n=1). In cases with a positive microbial result Staphylococcus aureus (n=4), Klebsiella pneumoniae (n=2), Pseudomonas aeruginosa (n=1), Candida (n=1) and others (n=6) were identified. No fatalities were recorded and only 3 patients had severe infection with the necessity of prolonged treatment.Conclusion:Despite the high number of infections in our group treated with RTX, most of them were not severe. Upper respiratory tract was the most common site of infection.Disclosure of Interests:None declared

Background:ANCA associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown etiology and the clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Thus there is an unmet need for phenotype identification especially among patients with granulomatosis with polyangiitis GPA, patients with microscopic polyangiitis MPA group seems to be more uniform. Recently, based on previous clustering analysis and clinical, histopathological, serological and prognostic aspects three subcategories of AAV have been proposed and named as: non-severe AAV, severe PR3-AAV and severe MPO-AAV [1].Objectives:In line with these attempts to subcategorize AAV we decided to use latent class analysis (LCA) on a large multicenter cohort of polish AAV patients from POLVAS [2] registry to identify potential new subphenotypes or confirm already proposed ones.Methods:Latent Class Analysis (LCA) approach was used as a model based clustering method of objects described by dichotomous (e.g., gender; ANCA status – cANCA, pANCA; organ involvement - skin, eye, ENT, respiratory, heart, GI, renal, urinary, CNS, peripheral nerves) and polytomous (number of relapses) variables supported by quantitative covariates (e.g., age at diagnosis, CRP at diagnosis, maximal serum creatinine concentration ever).Results:Results of LCA on our AAV group returned four class model of AAV subphenotypes, confirming existence of the previously proposed by Mahr at al. [1] and revealed fourth – previously not described clinically relevant subphenotype. To this fourth class - belong patients only with GPA, diagnosed at young age, with multiorgan involvement, high relapse rate and relatively high risk of death.Table 1.AAV subcategorization – summary of clinical characteristics and ANCA specificityLCA Class 1LCA Class 2LCA Class 3LCA Class 4No of patients13019410297AAV typeMainly GPAMainly GPAmainly MPAOnly GPAAge at diagnosisMiddle ageMiddle ageOldYoungMale/female ratio1:22:11:11:1Main organ involvementENT, respiratory, eyeRenal, respiratory, ENTRenal, respiratory, skinMultiorgan involvementRelapse rateintermediateintermediatelowhighModified class description (based on ref. [1])Non severe AAVSevere PR3 AAVSevere MPO AAVSevere non-renalPR3 AAVConclusion:Based on multiple clinical and serological variables LCA methodology identified 4-class subphenotypes model of AAV. Fourth-class is a new clinically important subphenotype including exclusively PR3-positive young AAV patients with multiorgan involvement, high risk of relapse and distinct mortality.References:[1]Mahr A, Specks U, Jayne D. Subclassifying ANCA-associated vasculitis: a unifying view of disease spectrum. Rheumatol Oxf Engl 2019;58:1707–9.https://doi.org/10.1093/rheumatology/kez148.[2]Wójcik K, Wawrzycka-Adamczyk K, Włudarczyk A, Sznajd J, Zdrojewski Z, Masiak A, i in. Clinical characteristics of Polish patients with ANCA-associated vasculitides—retrospective analysis of POLVAS registry. Clinical Rheumatology. 1 wrzesień 2019;38(9):2553–63.Disclosure of Interests:Krzysztof Wójcik: None declared, Adam Ćmiel: None declared, Anna Masiak: None declared, Zbigniew Zdrojewski: None declared, Radoslaw Jeleniewicz: None declared, Maria Majdan Consultant of: Roche, Amgen, Speakers bureau: Roche, Amgen, Iwona Brzosko: None declared, Marek Brzosko: None declared, Piotr Głuszko: None declared, Małgorzata Stasiek: None declared, Małgorzata Wisłowska: None declared, Joanna Kur-Zalewska: None declared, Marta Madej: None declared, Anna Hawrot-Kawecka: None declared, Hanna Storoniak: None declared, Barbara Bułło-Piontecka: None declared, Alicja Dębska-Ślizień: None declared, Eugeniusz Kucharz: None declared, Katarzyna Jakuszko: None declared, Jacek Musiał: None declared

Background:Orbital inflammatory masses have been described as the common manifestation of granulomatosis with polyangiitis (GPA) occuring in 7- 45% of patients.Objectives:Identification and characterization of patients with orbital pseudotumor among Polish patients based on the national vasculitis registry, POLVAS.Methods:Clinical presentation and management of all GPA patients fulfilling ACR criteria or Chapel Hill Consensus Conference definition included to the Polish registry POLVAS who developed orbital masses in the course of GPA were evaluated.Results:Ocular involvement was found in 114 (27%) of 417 GPA patients registered in POLVAS, 34 (8%) developed orbital masses. Mean patients’ age was 47.8 (range from 19-75) yrs., 23 (67%) were women. Forty four per cent of the patients developed tumor at the beginning of the disease, 56% during relapse. Patients’ characteristics on diagnosis of orbital mass: 24 cANCA, 2 pANCA, and 8 ANCA negative, 9% active smokers and 31% past smokers, 29% had localized disease, 21% early systemic and 50% systemic with organ involvement, 29% had other type of ophthalmological involvement before pseudotumor occurred, 88% had active paranasal sinus involvement, 41% lungs, 15% CNS, 15% skin and 6% heart manifestations. Thirty seven per cent of patients had positive nasal swabs cultures, 50% of which were positive for Staphylococcus aureus. In 65%, tumor occurred during steroid therapy (46% had prednisone more than 5mg/d) and 45% on immunosuppressive treatment (19% when treated with AZA, 16% MTX, 6,5% MMF and 3,5% CYC). Due to orbital mass 86.5% were treated with CYC and 13.5% with RTX. Twenty one per cent had complete remission of the pseudotumor, 76% partial remission and in 3% patients there was no response to the treatment; 43% developed visual impairment, 20% suffered from blindness.Conclusion:Orbital inflammatory mass was not common manifestation of GPA among our patients. The mass developed at the beginning or in the course of the disease, even during immunosuppressive treatment. Orbital masses have been resistant to therapeutic interventions and were accompanied by high risk of visual impairment.Disclosure of Interests:Anna Masiak: None declared, Marcin Ziętkiewicz: None declared, Krzysztof Wójcik: None declared, Katarzyna Wawrzycka-Adamczyk: None declared, Radoslaw Jeleniewicz: None declared, Marta Madej: None declared, Joanna Kur-Zalewska: None declared, Katarzyna Jakuszko: None declared, Małgorzata Wisłowska: None declared, Hanna Storoniak: None declared, Michał Komorniczak: None declared, Barbara Bułło-Piontecka: None declared, Iwona Brzosko: None declared, Małgorzata Stasiek: None declared, Eugeniusz Kucharz: None declared, Alicja Dębska-Ślizień: None declared, Maria Majdan Consultant of: Roche, Amgen, Speakers bureau: Roche, Amgen, Jacek Musiał: None declared, Zbigniew Zdrojewski: None declared

Periodontal diseases are multiperspective problems resulting from numerous and diverse exposures that influence the process of initiation or progression of disease. The negative influence of tobacco smoking on oral health is well documented. The aim of the study was to analyze three SNPs in vitamin D receptor gene&mdash, rs7975232 (ApaI), rs2228570 (FokI) and rs1544410 (BsmI)&mdash, combined with oral health assessment&mdash, pH, gingival index, dry mouth, periodontitis, dry socket, redness of oral cavity mucosa, leukoplakia&mdash, in a group of cigarette smokers and in non-smokers. Moreover, the possibility of interactions between these polymorphisms and smoking was examined. When comparing the smokers and non-smokers groups, we noticed that rs1544410 heterozygotes were significantly more frequent in the first group, and for the second, both homozygotes were more frequent. Additionally, we observed the impact of interaction between the rs7975232 genotype and smoking status on gingival index. Current smoking was also associated with all analyzed oral health measures except for leucoplakia. Correlation between pH and age in both smokers and non-smokers was also present. Results of our analysis indicate that in our study group lifestyle and aging were leading factors associated with worse oral health status. However, the impact of genetic variants, and also the impact of their interaction with smoking on analyzed parameters was also visible. These results show great possibilities for all levels of prevention of oral diseases by means of education based on evidence-based medicine, but also for incorporating genetic testing and early interventions into this process for predisposed individuals.

Brain-Computer Interfaces (BCI) constitute an alternative channel of communication between humans and environment. There are a number of different technologies which enable the recording of brain activity. One of these is electroencephalography (EEG). The most common EEG methods include interfaces whose operation is based on changes in the activity of Sensorimotor Rhythms (SMR) during imagery movement, so-called Motor Imagery BCI (MIBCI).The present article is a review of 131 articles published from 1997 to 2017 discussing various procedures of data processing in MIBCI. The experiments described in these publications have been compared in terms of the methods used for data registration and analysis. Some of the studies (76 reports) were subjected to meta-analysis which showed corrected average classification accuracy achieved in these studies at the level of 51.96%, a high degree of heterogeneity of results (Q = 1806577.61; df = 486; p < 0.001; I2 = 99.97%), as well as significant effects of number of channels, number of mental images, and method of spatial filtering. On the other hand the meta-regression failed to provide evidence that there was an increase in the effectiveness of the solutions proposed in the articles published in recent years. The authors have proposed a newly developed standard for presenting results acquired during MIBCI experiments, which is designed to facilitate communication and comparison of essential information regarding the effects observed. Also, based on the findings of descriptive analysis and meta-analysis, the authors formulated recommendations regarding practices applied in research on signal processing in MIBCIs.

There are still no good quantitative methods to be applied in psychiatric diagnosis. The interview is still the main and most important tool in the psychiatrist work. This paper presents the results of electroencephalographic research with the subjects of a group of 30 patients with psychiatric disorders compared to the control group of healthy volunteers. All subjects were solving working memory task. The digit-span working memory task test was chosen as one of the most popular tasks given to subjects with cognitive dysfunctions, especially for the patients with panic disorders, depression (including the depressive phase of bipolar disorder), phobias, and schizophrenia. Having such cohort of patients some results for the subjects with insomnia and Asperger syndrome are also presented. The cortical activity of their brains was registered by the dense array EEG amplifier. Source localization using the photogrammetry station and the sLORETA algorithm was then performed in five EEG frequency bands. The most active Brodmann Areas are indicated. Methodology for mapping the brain and research protocol are presented. The first results indicate that the presented technique can be useful in finding psychiatric disorder neurophysiological biomarkers. The first attempts were made to associate hyperactivity of selected Brodmann Areas with particular disorders.

Background Fatigue is a common symptom among patients with ANCA-associated vasculitis (AAV) identified as the greatest burden of their disease. 1 2 Research revealed associations between fatigue and bio-psychosocial factors but not with clinical factors. Objectives To assess fatigue and its correlates among patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Methods 37 patients (44% women; mean age 52.3 years; range 18–85) with GPA (27 patients) and MPA (10 patients) hospitalised in 3 clinical centres completed Multidimensional Fatigue Inventory-20 (MFI-20). 3 Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS). Socio-demographic data including age, sex, education, marital and occupational status were recorded. Disease characteristics included its’ duration, severity, activity, organ involvement and laboratory data. Results The mean age was 52.3 years (range 18–85 years), and the mean disease duration was 43.1 months (range 1–248). 4 patients had limited type of the disease, 13 – early systemic, 16 – systemic and 4 – severe type of the disease. 75% of patients had active disease as defined by Birmingham Vasculitis Activity Score, BVASv3 (mean BVASv3 in active patients 12.2). 8% of patients were not taking steroids. 40,5% of patients had CRP >5 mg/, 43% had anaemia, 10% – thrombocytosis and 43% had renal insufficiency. Mean score of MFI-20 was 57 points (range 31–100). There were no differences in MFI-20 overall score between groups according to sex, education, marital and occupational status. No significant associations between fatigue and disease-related factors as well as steroid dose were observed. Depression (r=0,79, p Conclusions Since fatigue was not related to clinical characteristics, tiredness declared by the patient should not be interpreted as a symptom of active disease. There were no connexions between fatigue and socio-demographic variables. The strong association between fatigue and depression and anxiety levels indicates the necessity to supplement the standard drug therapy and/or cognitive-behavioural therapy aimed at reducing anxiety and improving mood. References [1] Basu N, McClean A, Harper L, et al. Explaining fatigue in ANCA-associated vasculitis. Rheumatology2013;52:1680–1685. [2] Herlyn K, Hellmich B, Seo P, et al. Patient-reported outcome assessment in vasculitis provides important data and a unique perspective. Arthritis Care Res2010;62:1639–45. [3] Buss T, Kruk A, Wiśniewski P, et al. Psychometric Properties of the Polish Version of the Multidimensional Fatigue Inventory-20 in Cancer Patients. J Pain Symptom Manag2014;48:730–737 Disclosure of Interest None declared

Background Vascultides are a heterogeneous group of rare diseases with unknown etiology and the clinical spectrum ranging from life–threatening systemic disease to minor isolated skin changes. Present nomenclature and definitions of systemic vasculitides have been proposed in 2012 at the International Chapel Hill Consensus Conference. 1 Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) belong to the small to medium-size vessel systemic diseases comprising granulomatosis with polyangitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Objectives We decided to retrospectively analyse a large cohort of Polish AAV patients coming from referral centres – members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). 2,3 Methods We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 Patients were enrolled to the study by 9 referral centres (14 clinical wards: – rheumatology – 10, nephrology – 2, metabolic diseases – 1, clinical immunology −1) from 7 Voivodships populated by 22,3 mln inhabitants (58,2% of the Polish population). Patient data have been collected according to the uniform protocol in the POLVAS registry. Results Distribution of AAV in the Polish population resembles that of north European cohorts. 4 In POLVAS registry 417 (66.7%) patients were diagnosed with GPA, 106 (17.0%) with MPA and 102 (16,3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA wasd twice more frequent among women (34/68). Clinical manifestations and organ involvement were analysed both by clinical phenotype (GPA, MPA, EGPA) and ANCA specificity (anti-PR3+, and anti-MPO+)Analysis by ANCA specificity showed no apparent difference as compared to phenotype analysis. Clinical manifestations of different AAV in the polish population seems very similar to other European countries. Conclusions This is the first multicenter retrospective study of the Polish patients sufferng from with AAV. Demographic characteristics and disease manifestations of AAV patients in POLVAS registry follow the same pattern as those from other European countries. 4 References [1] Jennette JC, et al. Arthritis Rheum2013Jan;65(1):1–11. [2] Padjas A, et al. Pol Arch Med Wewn2014;124(3):143–4. [3] Musiax J, Wojcik K. Pol Arch Intern Med2017Jan 31;127(1):71–72. [4] Bajema, et al. Kidney Int Rep2017;1018–1031. Disclosure of Interest None declared

Background Illness perception (IP) is one of the most important factors related to health related quality of life, psychological and physical functioning and medical adherence.1,2 Objectives To explore illness perception and its relationship with chosen clinical, socio-demographic and psychological variables in patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Methods 38 patients (57.9% women; median age 57 years; range 18–85; median disease duration: 11.5, range: 1–248 months) with GPA (28 patients) and MPA (10 patients). Inpatients recruited in 3 clinical centres were asked to complete Brief-Illness Perception Questionnaire (B-IPQ),3 Hospital Anxiety and Depression Scale-Modified (HADS-M) and Multidimensional Fatigue Inventory-20 (MFI-20). Socio-demographic variables included age, sex, education and marital status. Medical files were reviewed to gather data on disease duration and its activity (assessed using Birmingham Vasculitis Activity Score version 3, BVASv3). p≤0.05 was considered significant. Results 63% of patients had active disease as defined by BVASv3. Median total score of B-IPQ was 48.5 points (range 24–64). There were no significant differences in illness perception (B-IPQ total score) between groups according to sex, education and marital status. No significant relationships between IP and age, disease duration and its activity were noted. Significant positive correlations were observed between B-IPQ total score and MFI-20 total score, general, physical and mental fatigue as well as depression, anxiety and irritability (table 1). Conclusions In the studied group illness perception was not related to clinical and socio-demographic factors. More negative illness perception was related to higher levels of fatigue, depression, anxiety and irritability. The results suggest that psychotherapeutic interventions seem vital for improving illness perception in this population. References [1] Hagger MS, Orbell S. A meta-analytic review of the common-sense model of illness representation. Psych Health2003;18:141–84. [2] Morgan C, McBeth J, Cordingley L, et al. The influence of behavioral and psychological factors on medication adherence over time in rheumatoid arthritis patients: a study in the biologics era. Rheumatology2015;54:1780–91. [3] Nowicka-Sauer K, Banaszkiewicz D, Staskiewicz I, et al. Illness perception in Polish patients with chronic diseases: Psychometric properties of the Brief Illness Perception Questionnaire. J Health Psychol2015;21:1739–49. Disclosure of Interest None declared

The only way to cure the patient with adenocarcinoma of the pancreas (RT) is surgical excision of the tumor. The standard surgical treatment of resectable pancreatic carcinoma is considered the classic pancreatoduodenectomy (PD) with the Kausch- Whipple procedure, or the pylorus-preserving PD with the Traverso-Longmire method. The most difficult technically and at the same time the most important PD stage from an oncological point of view is the separation of the head of the pancreas from the superior mesenteric artery. Over the last decades several PD modifications have been developed, focusing on this maneuver in the early phase of the operation, i.e. before the pancreas is cut (an irreversible stage of the procedure). These procedures in the English literature are called “artery-first approach” or “SMA-first approach”. The term “mesopancreas” was created. Complete removal of the mesopancreas together with the proximal part of the jejunum is considered an R0 resection in the case of a tumor of the head of the pancreas with direct or indirect vascular invasion, or metastases to regional lymph nodes, and in English literature it is referred to as pancreatoduodenectomy with systematic mesopancreas dissection (SMDPD). Distal resection of the pancreas (DRT) due to cancer, is associated with a high percentage of positive margins, insufficient number of removed lymph nodes, low survival rates. A new technique was developed - a radical proximal-distal modular pancreatosplenectomy (RAMPS). In RAMPS, surgical operations proceed from the side of the pancreas head towards the tail, the pancreas is cut early, and the splenectomy is performed at the final stages of the procedure. Currently, following the PD model, attempts are made to further modify the original RAMPS technique, especially in the direction of SMA-first approach. In patients with borderline resectable pancreatic tumors or locally advanced tumors, after neoadjuvant treatment, a technique of radical resection with preservance of arterial vessels - “the TRIANGLE operation” has been elaborated. Despite the tremendous progress of surgical techniques, RT is still detected too late in the phase preventing effective resection.

The interview is still the main and most important tool in psychiatrist's work. The neuroimaging methods such as CT or MRI are widely used in other fields of medicine, for instance neurology. However, psychiatry lacks effective quantitative methods to support of diagnosis. A novel neuroinformatic approach to help clinical patients by means of electroencephalographic technology in order to build foundations for finding neurophysiological biomarkers of psychiatric disorders is proposed. A cohort of 30 right-handed patients (21 males, 9 females) with psychiatric disorders (mainly with panic and anxiety disorder, Asperger syndrome as well as with phobic anxiety disorders, schizophrenia, bipolar affective disorder, obsessive-compulsive disorder, nonorganic hypersomnia, and moderate depressive episode) were examined using the dense array EEG amplifier in the P300 experiment. The results were compared with the control group of 30 healthy, right-handed male volunteers. The quantitative analysis of cortical activity was conducted using the sLORETA source localization algorithm. The most active Brodmann Areas were pointed out and a new quantitative observable of electrical charge flowing through the selected Brodmann Area is proposed. The precise methodology and research protocol for collecting EEG data as well as the roadmap of future investigations in this area are presented. The essential result of this study is the idea proven by the initial results of our experiments that it is possible to determine quantitatively biomarkers of particular psychiatric disorders in order to support the process of diagnosis and hopefully choose most appropriate medical treatment later.

Research on initial coin offerings (ICOs) is nascent and assesses ICOs from ventures’ and regulators’ perspectives. Little is known about the equally important group of investors who provide their capital to ventures in ICOs. Using a primary dataset of 517 ICO investors collected in 2018, we perform a factor analysis to identify and categorize the motivations to invest in ICOs. We find that investors are driven by ideological motives, technological motives, and financial motives. To profile investors according to these motives, we then conduct a regression analysis to distinguish investors with high scores across the different motives. For example, we show significant differences across motives with regard to investors’ risk perception and the demand for a strict regulation. The implications of this study for theory and practice are considerable and discussed in detail.