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The complex course of the COVID-19 and the distant complications of the SARS-CoV-2 infection still remain an unfaded challenge for modern medicine. The care of patients with the symptomatic course of COVID-19 exceeds the competence of a single specialty, often requiring a multispecialist approach. The CRACoV-HHS (CRAcow in CoVid pandemic - Home, Hospital and Staff) project has been developed by a team of scientists and clinicians with the aim of optimizing medical care at hospital and ambulatory settings and treatment of patients with SARS-CoV-2 infection. The CRACoV project integrates 26 basic and clinical research from multiple medical disciplines, involving different populations infected with SARS-CoV-2 virus and exposed to infection. Between January 2021 and April 2022 we plan to recruit subjects among patients diagnosed and treated in the University Hospital in Cracow, the largest public hospital in Poland, i.e. 1) patients admitted to the hospital due to COVID-19 [main module: 'Hospital']; 2) patients with signs of infection who have been confirmed as having SARS-CoV-2 infection and have been referred to home isolation due to their mild course (module: 'Home isolation'); 3) patients with symptoms of infection and high exposure to SARS- CoV-2 who have a negative RT-PCR test result. In addition, survey in various professional groups of hospital employees, both medical and non-medical, and final-fifth year medical students (module: 'Staff') is planned. The project carries both scientific and practical dimension and is expected to develop a multidisciplinary model of care of COVID-19 patients as well as recommendations for the management of particular groups of patients including: asymptomatic patient or with mild symptoms of COVID-19; symptomatic patients requiring hospitalization due to more severe clinical course of disease and organ complications; patient requiring surgery; patient with diabetes; patient requiring psychological support; patient with undesirable consequences of pharmacological treatment.

Background: Knowledge of occupational health is crucial to the safety of healthcare workers in the pandemic period. The aim of our study was the rating of SARS-CoV-2 seroprevalence in connection with selected demographic, social, and organizational factors, as well as the identification of key elements determining the safety of HCWs and patients of the University Hospital in Krakow. Methods: This was a non-interventional, uncontrolled, open, single-center, cross-sectional online survey on the preparedness for the COVID-19 epidemic and the seroprevalence of medical and non-medical HCWs and students. Serum specimens from 1221 persons were tested using an immunoassay analyzer based on the ECLIA technique for the anti-SARS-CoV-2 antibodies IgM + IgG. Results: The total seroprevalence was 42.7%. In medical students it was 25.2%, while in physicians it was 43.4% and in nurses/midwives it was 48.1%. Of those who tested positive, 21.5% did not know their serological status. The use of personal protective equipment did not have any significant impact on the result of testing for anti-SARS-CoV-2 antibodies. The risk of developing the disease was not influenced by sex, professional work experience, workplace, or intensity of contact with the patient. Among the studied elements, only care of COVID-19 patients significantly increased the risk. The protective factor was starting work between the waves of the epidemic (June–September 2020). Conclusions: PPE is only one element of infection prevention and control—without other components, such as hand hygiene, it can be dangerous and contribute to self-infection. It is also very important to test healthcare workers. Not being aware of the COVID-19 status of HCWs poses a threat to other staff members, as well as patients and the family and friends of the infected. Thus, extreme caution should be applied when employing respirators with exhalation valves during the COVID-19 pandemic.

Backgrounds Health care workers’ (HCWs) knowledge of and compliance with personal protective procedures is a key for patients’ and personnel safety. The aim of this study was to assess which factors are associated with higher self-evaluations of training on infection prevention and control (IPC) and higher self-assessment of IPC practices used by HCWs regarding COVID-19 in University Hospital in Krakow, Poland, in January 2021. Material and methods This was an online survey on the preparedness for COVID-19 epidemic of medical/non-medical staff and medical students. Questions included in the survey concerned participants’ socio-demographic characteristics, hospital staff involvement in the training, knowledge about the hand hygiene, and adherence to IPC measures. Knowledge and Performance Index (K&amp, PI) based on selected questions was constructed for to reflect both subjective (self-evaluation) of preparedness and objective IPC knowledge and skills of HCWs participated in the IPC training. Results A total of 1412 health care workers, including 129 medical students, participated in the study. The largest group, 53.6%, was made up of nurses and paramedics. Age of respondents significantly correlated with knowledge of IPC and with K&amp, PI. The mean age of workers with high K&amp, PI was 42.39 ± 12.53, and among those with low, 39.71 ± 13.10, p &lt, 0.001. 51% UHK workers participated in IPC training, but 11.3% of physicians, 28.8% of other HCWs, and 55.8% of students did not know the IPC standard precaution. Most participants, 72.3%, felt that they had received sufficient training, however, 45.8% of students declined this. There was no correlation between self-reported preparedness and the K&amp, PI, indicating that self-reported preparedness was inadequate for knowledge and skills. Nurses and paramedics assessed their knowledge most accurately. Participants with low K&amp, PI and high subjective evaluation constituted a substantial group in all categories. Students least often overestimated (23.8%) and most often (9.6%) underestimated their knowledge and skills. Conclusions Our study revealed inadequate IPC practice, especially as it refers to the training programme. We confirmed the urgent need of including theory and practice of IPC in curricula of health professions’ training in order to provide students with knowledge and skills necessary not only for future pandemic situations but also for everyday work.

Although venous thromboembolism (VTE) is quite common in patients suffering from different stages of cancer, it is still an underestimated problem. Oncological treatment, surgeries, and advanced-stage cancer are only some risk factors for VTE, which is one of the most common causes of death in cancer patients. Differences in the risk of deep-venous thrombosis and its complications, including risk of bleeding, between particular onco­logical patient groups suggests that there is a need for individual risk assessment and prophylaxis dedicated to specific clinical situations and patients. They also give grounds for constant update of guidelines on prophylaxis in cancer patients. This document contains venous thromboembolism prophylaxis guidelines in oncology patients with focus on surgical cancer.

At present, secondary immune deficiencies have become a clinical problem, recognized in different specialties. The aim of this paper was to increase awareness and support the need for screening at-risk populations. Secondary immune deficiencies result in variety of conditions, but not all of them require immunoglobulin replacement therapy, as specific antibody response might be preserved. Moreover, the management of secondary immune deficiencies vary between countries and different medical disciplines. This literature review presents the most common causes and clinical presentation of secondary immunodeficiencies with predominant impaired antibody production. We present diagnostic guidelines for patients at-risk, with an emphasis on the role of prophylactic vaccination as a treatment and diagnostic tool. This review considers the specificity and disparities of the Polish healthcare system and ultimately, suggests that management teams should include a clinical immunologist experienced in the treatment of humoral immunodeficiencies.

Congenital fibrinogen disorders are poorly explored in Slavic populations. The aim of this study was to characterize the genetic background and clinical manifestations of fibrinogen disorders in the Polish case series.In 27 unrelated patients (mean [SD] age, 30.4 [19.2] years, 30% men) with fibrinogen concentration (von Clauss method) 1.8 g/L, exons and intron-exon junctions of the fibrinogen alpha chain (FGA), fibrinogen beta chain (FGB), and fibrinogen gamma chain (FGG) genes were analyzed using polymerase chain reaction (PCR) amplification followed by sequencing.At enrollment, 15 (55.6%) and 2 (7.4%) of patients experienced bleeding and thrombotic events, respectively, and the remainder were asymptomatic. The following congenital fibrinogen disorders were identified: 1A. afibrinogenemia, n = 1; 2A. severe hypofibrinogenemia, n = 2; 2B. moderate hypofibrinogenemia, n = 4; 2C. mild hypofibrinogenemia, n = 6; 3A. dysfibrinogenemia, n = 12; 3B. thrombotic related-dysfibrinogenemia, n = 1; 4C. mild hypodysfibrinogenemia, n = 1. Eight dysfibrinogenemic patients (62%) were carriers of hotspot mutations. Fifteen patients were heterozygous and one (afibrinogenemia) homozygous for known causative mutations. Three new heterozygous mutations were detected, all affecting splicing in FGG: fibrinogen Poznan II, a 177 bp deletion eliminating parts of intron 6 and exon 7 in a dysfibrinogenemic woman with recurrent bleeding; fibrinogen Zakopane, (intron 2 acceptor splice site) and fibrinogen Belchatow (intron 1 donor splice site), found in hypofibrinogenemic patients. During follow-up (median 60, interquartile range 10-60 months), bleeding episodes, mainly menorrhagia and easy bruising were reported in 15 (55.6%) patients. One thromboembolic event was observed.This study of the largest cohort of Slavic patients with congenital fibrinogen disorders has enabled the identification of 3 new FGG mutations and shows a high prevalence of bleeding manifestations with recurrences.

Plasmapheresis is a therapeutic method based on removal of high molecular weight particles from blood. It is used in a variety of clinical entities in which pathogenic role of such particles has been proven e.g. ANCA-associated vasculitides (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]). Efficacy of plasmapheresis in ANCA antibodies removal and its impact on disease activity has not been adequately investigated so far. Influence of antibodies levels on disease activity also remains unknown.Analysis of plasmapheresis effect on serum ANCA levels in patients with ANCA-associated vasculitides.Seven patients with diagnoses of ANCA-associated vasculitides were enrolled in the study between November 2015 and April 2016. All of them underwent plasmapheresis procedures. Serum ANCA levels were measured before and after plasmaphereses using fluoroimmunoenzymatic assay (FEIA). Disease activity was assessed using Birmingham Activity Vasculitis Score; BVAS ver. 3 before first plasma exchange procedure.Patients in disease exacerbation (BVAS 5-10) with positive ANCA antibodies were enrolled in the study: 2 patients with GPA and 5 patients with MPA. Number of performed plasmapheresis procedures ranged from 5 to 7 (median=7). Decrease of serum antibodies concentration was observed in all patients (mean decrease of 88.3% (±10.1%)) with statistically significant difference in mean antibodies concentration before and after plasmapheresis procedures (113.0 vs 15.4; p=0.014).Plasmapheresis is an effective method of ANCA antibodies removal in patients in disease exacerbation.

INTRODUCTION Inherited deficiencies of natural anticoagulants such as antithrombin (AT; gene: SERPINC1), protein C (PC; PROC), and protein S (PS; PROS1), with the prevalence in the general European population of 0.02% to 0.17%, 0.2% to 0.3%, and 0.5%, respectively, are associated with increased risk of thromboembolic events. Only a few case reports of Polish deficient patients with known causal mutations have been published so far. OBJECTIVES The aim of the study was to characterize the frequency of SERPINC1, PROC, and PROS1 mutations and their thromboembolic manifestations in patients with AT, PC, or PS deficiencies, inhabiting southern Poland. PATIENTS AND METHODS Ninety unrelated patients (mean [SD] age, 40.1 [13.2] years) with AT (n = 35), PC (n = 28), or PS (n = 27) deficiencies, with a history of venous 73 (81%) or arterial 17 (19%) thromboembolism, were screened for mutations using the Sanger sequencing or multiplex ligation‑dependent probe amplification. RESULTS Twenty mutations (29%) described here were new, mostly in the SERPINC1 and PROC genes. Missense mutations accounted for 84% of all mutations in the PROC gene and approximately 50% of those in the SERPINC1 and PROS1 genes. In all 3 genes, the ratio of nonsense and splice-site mutations was 8% to 31% and 8% to 23%, respectively. The mutation detection rate was 90% for AT or PC when anticoagulant activity was below 70%, while for the PROS1 gene, the rate reached 80% at the free PS levels below 40%. CONCLUSIONS To our knowledge, this is the largest cohort of Polish patients deficient in natural anticoagulants and evaluated for the causal genetic background. Several new Polish detrimental mutations were detected, mostly in AT- and PC‑deficient patients.

Introduction Venous thromboembolism (VTE) is the most common preventable cause of in-hospital death. However, the risk of VTE and prophylaxis practices in Polish hospitals are not known. Objectives The ENDORSE study in Poland was part of the global cross-sectional Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting survey with the objective to assess the prevalence of VTE risk in acutely ill medical and surgical patients and to determine the proportion of at-risk patients who receive recommended prophylaxis. Patients and methods In 10 non-academic Polish hospitals, a chart review was performed in all inpatients aged 40 or older admitted to medical wards, and in patients at the age of > or = 18 admitted to surgical wards. The VTE risk and recommended prophylaxis were assessed according to the 2004 American College of Chest Physicians (ACCP) guidelines. Results The study enrolled 2673 patients (1092 in surgical wards, 1581 in medical wards). Out of these, 1111 were judged to be at risk for VTE (597 surgical patients, 514 medical patients). Only 51.8% of all at-risk patients received ACCP-recommended VTE prophylaxis (54.7% of surgical patients, 32.5% of medical patients). Conclusions In Polish hospitals more than 40% of patients hospitalized for acute illness are at risk of VTE, but only a small proportion of them receives appropriate prophylaxis. These results call for decisive actions to ensure that at-risk patients receive recommended VTE prophylaxis.

Background— The mechanism underlying decreased risk for myocardial infarction in carriers of the Leu34 polymorphism of the factor (F) XIII A-subunit is unclear. Given that acetylation of fibrinogen by aspirin can alter its clotting properties and the presence of fibrin stimulates thrombin-mediated activation of FXIII, we have tested the hypothesis that treatment with aspirin differentially modulates the influence of the FXIII Val34Leu polymorphism on its activation in vivo. Methods and Results— The rates of the disappearance of FXIIIA chain and the appearance of its activated form (FXIIIAa) in sequential 30-second blood samples collected at the site of microvascular injury were compared in 14 healthy carriers of the Leu34 allele and 23 Val34 homozygotes both before and after a 7-day aspirin ingestion (75 mg/d), with the use of quantitative Western blotting. The presence of the Leu34 allele was associated with a significant increase in the maximum rate of FXIII activation by thrombin. Although the Leu34-positive and -negative subjects were similar with respect to aspirin-related impairment of thrombin generation, aspirin led to a more pronounced inhibition of the activation of FXIII in the Leu34 carriers as compared with the Val34 homozygotes. Conclusions— Inhibition of FXIII activation by aspirin is enhanced in the Leu34 carriers in vivo, suggesting that these subjects might benefit more than the Leu34-negative subjects from the reduction in risk for myocardial infarction with low-dose aspirin.

Homocysteine, an intermediate of methionine metabolism, has been found to be an independent risk factor for thromboembolism [1]. Various mechanisms have been proposed to explain possible homocysteine-induced thrombogenicity, including endothelial damage, enhanced lipid peroxidation, impaired activity of the anticoagulant protein C system and increased expression of tissue factor [1–5]. Relevance of these findings in vivo remains controversial. Much less is known on the effects of homocysteine on platelet function [6]. In patients with homocystinuria, homocysteine might increase thromboxane A2 production [7] and stimulate platelet aggregation [8], though the effect of homocysteine on platelet survival is less evident [6]. Oxidative stress might lead to homocysteine oxidation, enhanced platelet activation and increased prothrombotic potential in hyperhomocysteinemia [9]. Methionine loading test is recognized as a method to induce a transient acute hyperhomocysteinemia and helps to identify individuals with abnormal methionine metabolism [10,11]. It remains to be determined whether in mild hyperhomocysteinemia platelet-mediated prothrombotic effects might be of importance. The aim of the study was to evaluate potential alterations in thrombin formation in platelet-rich plasma after oral methionine loading in healthy subjects. 2. Materials and methods

Hemophagocytic syndrome (HPS), also known as hemophagocytic lymphohistiocytosis (HLH) encompasses an infrequent group of non-malignant, yet potentially life-threatening disorders caused by massive cytokine release from activated lymphocytes and macrophages (Filipovich, 2009; Henter et al., 1998, 2007; Janka et al., 1998; Janka, 2009). This multisystem inflammatory syndrome is associated with a range of genetic and acquired factors. Hectic and persistent fever, cytopenias, hepatitis, jaundice, edema, splenomegaly, neurological symptoms and hemophagocytosis in bone marrow (BM), liver or lymph nodes are common clinicopathological features of HLH.

Aims: Beneficial effects of statins in preventing cardiovascular events may depend, at least in part, on their anti-inflammatory action. The aim of the study was to assess the influence of simvastatin and aspirin on serum levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in hypercholesterolemic subjects. Methods and results: In 33 asymptomatic men with total cholesterol (TC) >6.5 mmol l −1 and in 25 men with coronary heart disease and borderline-high cholesterol levels (between 5.2 and 6.5 mmol l −1 ) chronically treated with low-dose aspirin (75 mg/d), serum levels of CRP, TNF-α, IL-6, and IL-8 were determined before and after a 3-month simvastatin therapy (20–40 mg daily). In the former group, these markers of inflammation were also measured before and after a 2-week treatment with aspirin (300 mg/d), implemented prior to and in combination with simvastatin. A distinct reduction of CRP and TNF-α was found in both groups; IL-6 levels were decreased only in subjects with marked hypercholesterolemia. Aspirin had no effect on the anti-inflammatory action of simvastatin. Conclusions: In men with hypercholesterolemia simvastatin treatment lowers serum levels of CRP and proinflammatory cytokines. Low-dose aspirin does not add to the anti-inflammatory action of simvastatin.