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Background: Asthma is associated with low-grade systemic inflammation, prothrombotic state, and premature atherosclerosis. Objective: To evaluate the relationships between asthma, inflammatory biomarkers, and parameters of endothelial dysfunction. Material and Methods: We analyzed flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasound in 92 clinically stable adult asthmatics and 62 well-matched controls. We also measured blood levels of selected inflammatory and asthma-specific biomarkers, including interleukin (IL) 4, IL-5, IL-6, IL-10, IL-12 (p70), IL-17A, IL-23, and interferon γ, as well as a disintegrin and metalloproteinase domain–containing protein 33 (ADAM-33). In addition, we assessed endothelial damage using 2 laboratory biomarkers: circulating von Willebrand factor (vWF) and pentraxin-3. We analyzed relationships between the study variables and asthma severity, lung function abnormalities, airway remodeling indices on computed tomography, and transthoracic echocardiography parameters. Results: Asthmatics had higher IL-6, IL-10, and ADAM-33 levels. They were also characterized by 23% lower FMD% and 15% thicker IMT, as compared with controls (P

Colorectal cancer is one of the most frequent malignant tumours in Poland, making up the third cause of cancer deaths both in women and in men with regards to the frequency of occurrence. The therapy of patients with high-stage colorectal cancer is palliative and should be conducted in a continual manner until the disease progression or unacceptable toxicity of treatment. By definition, palliative care aims at prolongation of the period to the exacerbation of the disease and of the overall survival with simultaneous guarantee of appropriate quality of life to the patients. A long-term use of a multidrug chemotherapy is often connected with the presence of clinically significant toxicity, therefore, de-escalation of systemic treatment is currently the subject of numerous analyses. The studies evaluating the effect of maintenance therapy on patient survival, prove that this kind of treatment makes up a valuable option in the case of patients in whom a good clinical effect is maintained with a concurrent reduction of toxicity of treatment. Especially in the context of the ongoing SARS-CoV-2 pandemic, monotherapy or less aggressive therapy should be discussed with patients.

Aim: To evaluate treatment results in advanced/metastatic melanoma patients treated with anti-PD-1 immunotherapy in routine practice in oncology centers in Poland. Methods: Multicenter retrospective analysis included 499 patients with unresectable/metastatic (stage IIIC–IV) melanoma treated with anti-PD-1 in first-line therapy. Results: Estimated median overall survival (OS) and progression-free survival (PFS) were 19.9 and 7.9 months, respectively. Multivariate analysis confirmed that ECOG 0, no brain metastases, normal lactate dehydrogenase level and occurrence of immune-related adverse events (irAEs) were statistically significantly associated with improved OS and PFS. Any irAE occurred in 24% of patients. Grade 3 or Grade 4 irAEs occurred in 6% of patients. Conclusion: Analysis revealed a slightly worse OS in real-world treatment in comparison to clinical trials (KEYNOTE-006 and CheckMate 066). Polish population treatment results are similar to other studies of real-world data. PFS and ORR are similar in our research and clinical trials.

In cancer, immune checkpoint inhibitors (ICIs) improve patient survival but may lead to severe immune-related adverse events (irAEs). Rheumatic irAEs are a distinct entity that are much more common in a real-life than in clinical trial reports due to their unspecific symptoms and them being a rare cause of hospitalization. This review focuses on an interdisciplinary approach to the management of rheumatic irAEs, including cooperation between oncologists, rheumatologists, and immunologists. We discuss the immunological background of rheumatic irAEs, as well as their unique clinical characteristics, differentiation from other irAEs, and treatment strategies. Importantly, steroids are not the basis of therapy, and nonsteroidal anti-inflammatory drugs should be administered in the front line with other antirheumatic agents. We also address whether patients with pre-existing rheumatic autoimmune diseases can receive ICIs and how antirheumatic agents can interfere with ICIs. Interestingly, there is a preclinical rationale for combining ICIs with immunosuppressants, particularly tumor necrosis factor α and interleukin 6 inhibitors. Regardless of the data, the mainstay in managing irAEs is interdisciplinary cooperation between oncologists and other medical specialties.

Dermatomyositis and polymyositis (DM/PM) are rare autoimmune inflammatory myopathies, characterized by an increased risk of cardiovascular and thromboembolic events, likely related to the prothrombotic plasma properties. The aim of this study was to assess the in vitro thrombin generation profile as a biomarker of plasma procoagulant properties in DM/PM patients.In 58 clinically stable DM/PM patients and 67 controls matched for sex, age, body mass index, we measured plasma thrombin generation potential using the Calibrated Automated Thrombinography (CAT) and analyzed its relationship with clinical disease characteristics, including autoantibodies profile.Patients with DM/PM had a 21% increase in endogenous thrombin potential (ETP), 36% higher peak thrombin concentration, and 11% faster thrombin generation, compared to controls (p ​ ​0.001, all, also after adjustment for potential confounders). Interestingly, although both diseases did not differ in thrombin generation potential, heterogenous variables predicted elevated ETPs in both of them. In DM, that was higher fibrinogen, C-reactive protein, and total cholesterol, whereas in PM, presence of arthritis and increased blood platelet count. Surprisingly, thrombin formation capacity remained in a robust inverse relationship with serum troponin (r ​= ​-0.67, p ​ ​0.001) in the patient group.DM/PM patients are characterized by an increased thrombin generation potential, suggesting prothrombotic plasma properties in both diseases. However, more studies are needed to verify its rationale and role in DM/PM clinical course and unfavorable clinical outcomes.

Introduction Patients with systemic sclerosis experience endothelial dysfunction and damage even in the absence of clinical manifestations. Aim To evaluate various methods for assessing the endothelial function for their applicability to clinical practice. Material and methods Forty-two patients (7 men and 35 women) with systemic sclerosis and 36 controls (11 men and 25 women) matched for age, sex, body mass index, smoking habit, and comorbidities were enrolled in the study. We assessed each participant for typical risk factors for cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1) and thrombomodulin together with flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography. Results Patients with systemic sclerosis did not differ from controls in serum levels of VCAM-1 and thrombomodulin, however, the statistical analysis with adjustment for potential confounders revealed increased levels of thrombomodulin in the patients (p = 0.03). They also had a 45% lower relative increase of FMD (FMD%), and 13% higher IMT (p < 0.01, both, also after adjustment for potential confounders). In a simple regression model, lower FMD% was determined by age (β = –0.57, 95% confidence interval (CI): –0.72 to –0.43) and C-reactive protein levels (β = –0.38, 95% CI: –0.55 to –0.22). Thicker IMT was related to age (β = 0.64, 95% CI: 0.52–0.67), glomerular filtration rate (β = –0.34, 95% CI: –0.5 to –0.18), and blood thrombomodulin levels (β = 0.45, 95% CI: 0.13–0.76). Conclusions Patients with systemic sclerosis present with endothelial dysfunction which may be detected using ultrasonographic methods. The exact mechanism of observed abnormalities is unknown, but it is possibly related to the chronic inflammation and ischemia-reperfusion injury.

Introduction. One of the most important achievements of contemporary oncology is the discovery of new therapeutic possibilities: targeted therapy and immunotherapy associated with checkpoint inhibitors. It has not been unequivocally determined so far which therapy should be used as first-line treatment in patients with advanced/metastatic melanoma with the BRAF mutation. Material and methods. 137 patients with advanced/metastatic melanoma with the BRAF mutation were analyzed. They received anti-PD1-1 therapy (IT) or molecularly targeted therapy iBRAF ± iMEK (TT) as first-line treatment in the scope of the national drug program. IT and TT therapies used as first-line treatment were compared. Results. Median OS and PFS in the group were 14.0 and 7.3 months. Unfavorable prognostic factors for OS and PFS were metastases to the central nervous system, increased LDH levels and performance status > 1. Metastatic sites in > 2 locations were only unfavorable prognostic factors for OS. A statistically significant difference was found between TT and IT for OS (p = 0.0011; median for TT was 12.6 months and was not reached for IT). It should be noted that the group treated with TT was characterized by a worse prognostic factors. No differences in PFS were observed (p = 0.292, medians 7.2 and 9.0 months, respectively). Conclusion. In patients with advanced/metastatic melanoma with a BRAF mutation without rapid progression, IT should be considered as first-line therapy.

Introduction The treatment outcomes of patients with advanced/metastatic melanoma were poor before the use of new therapeutic options. Material and methods A retrospective analysis was conducted among 287 patients with unresectable stage III and stage IV melanoma treated at the Maria Sklodowska-Curie National Research Institute of Oncology Cracow Branch, from 2013 to 2019. All enrolled patients were treated with immunotherapy (IT; consisting of pembrolizumab/nivolumab, or ipilimumab) or target therapy (TT; consisting of vemurafenib ±cobimetinib or dabrafenib ±trametinib) in at least one treatment line. Results mutation was detected in 152 (55%) patients. In general, the majority of patients (92%) were in very good or good condition (Eastern Cooperative Oncology Group [ECOG] 0 or 1). Brain metastasis was detected in 64 (22%) patients. Median OS and PFS in the experimental group from the beginning of the first-line treatment were 14.9 and 6.7 months, respectively. Across the study population, as a first-line treatment patients received IT, TT as well as CHT, and the median OS was 19.2, 12.6 and 15.9 months, respectively. Multivariate analysis confirmed that normal LDH levels, no brain metastases, ECOG 0, and objective response to the treatment were strong predictors of longer OS. For PFS, absence of brain metastases, ECOG 0, and treatment response were found to be predictive factors on multivariate analysis. Conclusions The administration of new therapies for the treatment of patients with advanced/disseminated melanoma significantly prolonged survival in this group of patients. Nevertheless, further studies should be conducted to assess the effectiveness of various sequences of treatment.

Recently, the prognosis of patients with HER2‑positive breast cancer (BC) has improved significantly owing to the use of combined treatment modalities. However, systemic treatment is as-sociated with increased risk of cardiotoxicity.We aimed to assess subclinical cardiac alterations during the final stage of adjuvant com-bined therapy, that is, trastuzumab therapy (TT), as potential predictors of late cardiac complications in patients with HER2‑positive BC.We enrolled 251 patients with HER2‑positive BC treated with a radical local therapy, adjuvant chemotherapy (anthracyclines or anthracyclines + taxanes), and immunotherapy (trastuzumab). Patients underwent 6 echocardiographic examinations: at baseline, during TT, and after TT, with assessment of left ventricular ejection fraction (LVEF), degree of valvular regurgitation, and cardiac chamber diameters.Valvular fibrosis (28.4% of patients) was associated with older age, hypertension at baseline, and a higher degree of regurgitation during TT. Reduced LVEF, greater regurgitation, and larger cardiac chamber diameters were noted during TT. The patients who received higher anthracycline doses showed a greater degree of aortic insufficiency and a larger right ventricular diameter. Reduced LVEF during TT was associated with radiotherapy or chemotherapy and the degree of valvular regurgitation. Significantly larger diameters were observed in older patients and in those with comorbidities at baseline, high body mass index, and regurgitation.Asymptomatic subclinical cardiac alterations during TT may predict late cardiac complica-tions; however, longer follow‑up is necessary to confirm this hypothesis. Patients with HER2‑positive BC should be closely monitored for possible cardiac alterations during and after therapy to ensure optimal care and guide therapeutic decision‑making.

Trastuzumab-induced cardiotoxicity (TIC) can lead to early treatment discontinuation. The aim of this study was to evaluate: N-terminal brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), myoglobin, and selected biochemical and clinical factors as predictors of TIC. One hundred and thirty patients with HER2-positive BC receiving adjuvant trastuzumab therapy (TT) were enrolled. Measurement of cardiac markers and biochemical tests as well as echocardiography were performed prior to TT initiation and every three months thereafter. Cardiotoxicity leading to treatment interruption occurred in 24 patients (18.5%). While cardiotoxicity caused early treatment discontinuation in 14 patients (10.8%), the TIC resolved in 10 (7.7%) and TT was resumed. The most common complication was a decrease in left ventricular ejection fraction of more than 10% from baseline or below 50% (7.7%). In patients with TIC, there was no increase in the levels of NT-proBNP, myoglobin, and CK-MB. BMI, hypertension, ischemic heart disease, diabetes, age, cancer stage, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were shown to not have an effect on TIC occurrence. NT-proBNP, myoglobin, and CK-MB are not predictors of TIC. There is an ongoing need to identify biomarkers for TIC.

Recent advances in oncology have improved the treatment outcomes and life expectancy of cancer patients; therefore, late effects of oncological treatment are of high clinical importance. Recent studies have shown that cardiovascular events are among the leading causes of premature morbidity in cancer survivors. Cardiotoxicity of some chemotherapeutic agents have been already confirmed; however, this issue seems to be more complex. Endothelium dysfunction is one of the first recognisable signs of atherosclerosis, which occurs long before the development of overt cardiovascular disease. Thus, it could be considered as an initial step, leading to increased risk of cardiovascular events. This process is not easy to recognise; however, there are some laboratory tests and imagining techniques that provide an insight into the progression of endothelial dysfunction. In this review we discuss the influence of oncological treatment on endothelium, according to the hypothesis that it increases cardiovascular morbidity and mortality in cancer survivors. Additionally, we present diagnostic and therapeutic measures that could reduce cardiovascular risk in cancer patients.

Background Atrial fibrillation (AF) is a frequent comorbidity in malignant patients. Anticancer therapies complicate anticoagulant strategy. We evaluated the safety and efficacy of long-term use of direct oral anticoagulants (DOACs) in breast cancer women. Methods In a prospective cohort study we enrolled 48 consecutive radically treated breast cancer women with AF (median age 63 [interquartile range 56–69] years, CHA2DS2–VASc 2 [2,3]) score) and adjuvant hormonal therapy. Thromboembolic complications (stroke, transient ischemic attack [TIA], venous thromboembolism [VTE]) and bleeding events (major and clinically relevant non-major bleeding [CRNMB]) were recorded in follow-up. Results During a median follow-up of 40 (interquartile range 28–50.5) months 13 (27%) patients received apixaban, 22 (46%) rivaroxaban, and 13 (27%) dabigatran. One stroke (2.3%/year) and two CRNMBs (4.6%/year) were observed on apixaban. One TIA (1.3%/year), three major bleedings and two CRNMBs (6.7%/year, combined) were reported on rivaroxaban. Three VTE were documented in dabigatran treated individuals (7.8%/year), without any bleeding or cerebrovascular events. Women with thromboembolic events had higher body mass index (32 [29–33]) vs. 26 [24–29]) kg/m2, p = 0.02) and CHA2DS2–VASc score (3 [3]) vs. 2 [1–3]), p = 0.02). Most thromboembolic complications (n = 4, 80%) and all three major bleedings were observed in tamoxifen users, while three of four CRNMBs occurred on aromatase inhibitors. Mortality rates were low (apixaban, n = 1 [2.3%/year], rivaroxaban, n = 3 [5.22%/ year], and dabigatran, n = 2 [4%/ year]). No death was related to bleeding. Conclusions This study suggests that DOACs are an effective and safe therapeutic option in breast cancer patients with AF during adjuvant hormonal therapy.

Systemic sclerosis (SSc) is a rare immune-mediated heterogenous entity characterised by excessive tissue fibrosis and vascular injury. Recently, increased risk of thromboembolic events has been documented in that disease. Our aim was to investigate prothrombotic plasma properties together with selected laboratory biomarkers of endothelial injury in SSc.In 56 clinically stable SSc patients and 67 well-matched controls we assessed plasma thrombin generation profile and measured circulating vascular cell adhesion molecule-1 (VCAM-1), cellular fibronectin (cFN), and thrombomodulin, as well as analysed their relationships with disease clinical parameters and autoimmune antibodies profile.SSc was characterised by 18.3% increased endogenous thrombin potential (ETP), 14.5% higher thrombin peak (p0.001 both, also after adjustment for potential confounders), and similar endothelial damage biomarkers, as compared to controls. Surprisingly, raised thrombin generation was related to the lower thrombomodulin and VCAM-1. Inflammatory markers, factor VIII activity, and blood eosinophilia predicted positively ETP, whereas platelet count and thrombomodulin had negative impact on that parameter in a multiple regression model. Intriguingly, patient group had also 6.7% extended lag-time (p=0.01 after adjustment for confounders) which was independently determined by higher thrombomodulin and cFN, as well as lower VCAM-1. Former cyclophosphamide therapy, thus more severe type of the disease was referred to the increased thrombin generation.SSc is characterised by enhanced thrombin generation potential which might contribute to the higher risk of thromboembolic events in that disease. Endothelium may play hereby an additional role, although large observational and experimental studies are needed to verify this hypothesis.

Background Granulomatosis with polyangiitis (GPA) is a rare granulomatous vasculitis affecting small- and medium-sized blood vessels. In optimally treated patients with long-standing disease, the common cause of death is atherosclerosis even in the absence of typical risk factors. Objective To evaluate endothelial dysfunction in GPA patients. Methods 44 patients (21 men and 23 women) diagnosed with GPA and 53 controls matched for age, sex, BMI and typical risk factors for cardiovascular diseases (22 men and 31 women) were enrolled in the study. We measured each participant’s serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also studied flow-mediated dilatation (FMD) of the brachial artery, intima-media thickness (IMT) of the common carotid artery and aortic stiffness using echocardiography. Results Patients with GPA showed a 15.9% increase in serum levels of VCAM-1 (p = 0.01), 66% of IL-6 (p

Acquired haemophilia A (AHA) is a rare autoimmune disease caused by antibodies directed against clotting factor VIII. About half of cases are idiopathic, but AHA may also be secondary to autoimmune, dermatologic, or oncologic diseases. In approximately 10% of non-idiopathic cases, the disease occurs after or with the diagnosis of cancer as an extremely rare paraneoplastic syndrome. We describe the case of a 73-year-old male patient diagnosed with AHA and successfully treated with recombinant human activated factor VIIa and immunosuppression. Two and a half years later, however, the disease relapsed and a routine ultrasound revealed a liver tumour that was then diagnosed as hepatocellular carcinoma. We present this case to increase awareness that this life-threatening condition may develop years prior to the diagnosis of cancer.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of vasculitis associated with asthma and eosinophilia. Endothelial dysfunction has been well documented in other types of vasculitis but not in EGPA. Thirty patients (10 men and 20 women) diagnosed with EGPA and remaining in a remission, and 58 controls (24 men and 34 women) matched for age, sex, and body mass index, were enrolled in the study. We assessed each participants for typical risk factors of cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also measured flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography. Patients with EGPA had 20% higher serum level of VCAM-1 (p

During a routine dissection at the Department of Anatomy, Collegium Medicum, Jagiellonian University, one cadaver was found to have multiple variations of the arteries of the upper limbs. The variations pertained to the course of the brachial artery as well as to its distribution. An unusual formation of the superficial palmar arch was observed in both upper limbs. The anatomical peculiarities encountered included: in the left upper limb-the brachioradial artery, which formed the superficial palmar arch by turning to the palmar side of the hand and connecting with the ulnar artery and in the right upper limb-a subscapular-circumflex humeral-deep brachial trunk that correlated with a high division of the brachial artery (in the upper third of the biceps brachii muscle), a large anastomosis between the radial and the ulnar artery, the presence of a persistent median artery, and the unusual formation of the superficial palmar arch, which was created by the median, ulnar, and radial arteries. In this report, we will trace the path of the axillary artery and its branches in detail and emphasize its embryological significance.

During a routine dissection at the Department of Anatomy, Collegium Medicum, Jagiellonian University, one cadaver was found to have multiple variations of the arteries of the upper limbs. The variations pertained to the course of the brachial artery as well as to its distribution. An unusual formation of the superficial palmar arch was observed in both upper limbs. The anatomical peculiarities encountered included: in the left upper limb-the brachioradial artery, which formed the superficial palmar arch by turning to the palmar side of the hand and connecting with the ulnar artery and in the right upper limb-a subscapular-circumflex humeral-deep brachial trunk that correlated with a high division of the brachial artery (in the upper third of the biceps brachii muscle), a large anastomosis between the radial and the ulnar artery, the presence of a persistent median artery, and the unusual formation of the superficial palmar arch, which was created by the median, ulnar, and radial arteries. In this report, we will trace the path of the axillary artery and its branches in detail and emphasize its embryological significance.