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Background: The coronavirus disease 19 (COVID-19) recently became one of the leading causes of death worldwide, similar to cardiovascular disease (CVD). Coexisting CVD may influence the prognosis of patients with COVID-19. Aims: We analyzed the impact of CVD and the use of cardiovascular drugs on the in-hospital course and mortality of patients with COVID-19. Methods: We retrospectively studied data for consecutive patients admitted to our hospital, with COVID-19 between March 6th and October 15th, 2020. Results: 1729 patients (median interquartile range age 63 [50–75] years; women 48.8%) were included. Overall, in-hospital mortality was 12.9%. The most prevalent CVD was arterial hypertension (56.1%), followed by hyperlipidemia (27.4%), diabetes mellitus (DM) (25.7%), coronary artery disease (16.8%), heart failure (HF) (10.3%), atrial fibrillation (13.5%), and stroke (8%). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) were used in 25.0% of patients, β-blockers in 40.7%, statins in 15.6%, and antiplatelet therapy in 19.9%. Age over 65 years (odds ratio [OR], 6.4; 95% CI, 4.3–9.6), male sex (OR, 1.4; 95% CI, 1.1–2.0), pre-existing DM (OR, 1.5; 95% CI, 1.1–2.1), and HF (OR, 2.3; 95% CI, 1.5–3.5) were independent predictors of in-hospital death, whereas treatment with ACEIs/ARBs (OR, 0.4; 95% CI, 0.3–0.6), β-blockers (OR, 0.6; 95% CI, 0.4–0.9), statins (OR, 0.5; 95% CI, 0.3–0.8), or antiplatelet therapy (OR, 0.6; 95% CI: 0.4–0.9) was associated with lower risk of death. Conclusions: Among cardiovascular risk factors and diseases, HF and DM appeared to increase in-hospital COVID-19 mortality, whereas the use of cardiovascular drugs was associated with lower mortality.

Background: Cardiovascular diseases including arterial hypertension are common comorbidities among patients hospitalized due to COVID-19. We assessed the influence of preexisting hypertension and its pharmacological treatment on in-hospital mortality in patients hospitalized with COVID-19. Methods: We studied all consecutive patients who were admitted to the University Hospital in Krakow, Poland, due to COVID-19 between March 2020 and May 2021. Data of 5191 patients (mean age 61.9±16.7 years, 45.2% female) were analyzed. Results: The median hospitalization time was 14 days, and the mortality rate was 18.4%. About a quarter of patients had an established cardiovascular disease including coronary artery disease (16.6%) or stroke (7.6%). Patients with hypertension (58.3%) were older and had more comorbidities than patients without hypertension. In multivariable logistic regression analysis, age above median (64 years), male gender, history of heart failure or chronic kidney disease, and higher C-reactive protein level, but not preexisting hypertension, were independent risk factors for in-hospital death in the whole study group. Patients with hypertension already treated (n=1723) with any first-line antihypertensive drug (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, or thiazide/thiazide-like diuretics) had a significantly lower risk of in-hospital death (odds ratio, 0.25 [95% CI, 0.2–0.3]; P Conclusions: Although the diagnosis of preexisting hypertension per se had no significant impact on in-hospital mortality among patients with COVID-19, treatment with any first-line blood pressure–lowering drug had a profound beneficial effect on survival in patients with hypertension. These data support the need for antihypertensive pharmacological treatment during the COVID-19 pandemic.

The course of consecutive COVID‑19 waves was influenced by medical and organizational factors.We aimed to assess the outcomes of patients hospitalized for COVID‑19 during the first 3 waves of the pandemic.We performed a retrospective analysis of medical records of all COVID‑19 patients admitted to the University Hospital in Kraków, Poland, a designated COVID‑19 hospital in Małopolska province, between March 1, 2020 and May 31, 2021. The waves were defined as 1, 2, and 3, and covered the periods of March 2020 to July 2020, August 2020 to January 2021, and February 2021 to May 2021, respectively. Patients' characteristics and outcomes for waves 1 through 3 were compared.Data analyses included 5191 patients with COVID‑19. We found differences in age (mean [SD], 60.2 [17.3] years vs 62.4 [16.8] years vs 61.9 [16.1] years, respectively, for waves 1, 2, and 3; P = 0.003), sex distribution (proportion of women, 51.4% vs 44.2% vs 43.6%; P = 0.003), as well as concentrations of inflammatory markers and oxygen saturation (the lowest and the highest for wave 1, respectively; P0.001). Hospital death rates in subsequent waves were 10.4%, 19.8%, and 20.3% (P0.001). Despite similarities in patients' characteristics, the length of hospital and intensive care unit stay was shorter for wave 3 than for wave 2. The risk factors for in‑hospital death were: advanced age, male sex, cardiovascular or chronic kidney disease, higher C‑reactive protein level, and hospitalization during the second or third wave.We identified differences in patients' clinical characteristics and outcomes between consecutive pandemic waves, which probably reflect changes in terms of COVID‑19 isolation policy, hospitalization and treatment indications, and treatment strategies.

BACKGROUND AND AIMS Chemerin is an adipokine and novel biomarker of cardiovascular disease in patients with chronic kidney disease, which has been associated with renal, metabolic and inflammatory parameters. Data on chemerin in transplant patients are scarce. METHOD One hundred twenty-seven kidney transplant recipients were enrolled in the present study. Biochemical testing of serum samples was performed at baseline, and subsequent follow-up of kidney function was performed. Subjects were followed for a median of 58 months (Q1, Q3; 32, 63) during which a composite primary endpoint of hemodialysis or all-cause death was assessed. RESULTS Patients were stratified according to low or high chemerin concentrations based on median values of 94.43 ng/mL (Q1, Q3; 83.4, 122.2). In patients with high chemerin, estimated mean glomerular filtration (eGFR) was significantly reduced (50.7 versus 62.7, P = 0.004), while mean hemoglobin concentrations were significantly lower (12.63 versus 14.78, P CONCLUSION The findings of the present study are in line with earlier reports in chronic kidney disease cohorts. Serum chemerin concentrations remain significantly tied not only to kidney function but also, surprisingly, hemoglobin levels. It remains to be established whether pathogenic pathways that lead to anemia are tied to chemerin concentrations and may translate into poor outcome following kidney transplant.

Introduction: Although filters are still preferred during carotid stenting, proximal protection systems (PPS) are increasingly used during these procedures. PPS seem to be safer than distal systems, especially in symptomatic patients, but evidence supporting their use is limited. Aim: This was a post hoc survey with 30-day mid-term and long-term follow up, which was aimed at assessment of the safety and efficacy of stenting of the internal carotid artery under PPS in symptomatic patients. Material and methods: We analysed the results of stenting in 120 symptomatic patients presenting with at least 60% stenosis. Patients were aged 67.9 ±9.8 years, and 12 patients were older than 80 years. An occlusion of contralateral artery was found in 5 patients and bilateral stenosis in 26 patients. The primary endpoint of this study was the proportion of patients who had new neurological events, including transient ischemic attack and minor or major stroke in 30-day follow-up. The secondary endpoint was a composite of technical and clinical success. During longterm follow-up we assessed new neurological events and stenoses of implanted stents. Results: The incidence of new neurological events during 30-day follow-up was 0.8%. The rate of technical success defined by secondary endpoint was 100%. Mean internal carotid artery stenosis before and after stent implantation was 93.8 ±9% and 8.4 ±6.3%, respectively (p < 0.001). Procedural success was achieved in all cases. During longterm follow-up there were two (1.7%) asymptomatic in-stent stenoses and no (0%) new neurological events. Conclusions: Endovascular management of symptomatic carotid stenosis under PPS is safe, feasible, and appears to be a good alternative to surgical endarterectomy.

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 and Aims The aim of the study was to analyse the utility of retinol binding protein (RBP) in case of renal impairment in MM patients and investigate its relationship with acclaimed parameters of renal failure and markers of MM stages. Method We recruited 73 patients (35 women, 38 men, in age range of 29-90 years, mean 70 ± 10 years) with multiple myeloma (MM), including 6 (8%) with smoldering MM, 40 (55%) with International Staging System (ISS) stage I, 15 (21%) with ISS II and 12 (16%) with ISS III. The majority of patients (65, 89%) received at least one treatment scheme. Thirty patients (41%) received maintenance treatment at recruitment. Median eGFR based on serum creatinine (CKD-EPICr) equaled 67 (range 9 – 117) ml/min/1.73 m2. Results Significant correlation was observed between RBP and the ordered variable describing MM stage from smoldering myeloma to ISS III (R=0.36; p=0.002). There were no differences between patients in CR, PR, SD and PD at the time of samples’ collection. Patients who were on maintenance treatment at recruitment tended to have higher serum RBP (median 42.6 versus 37.7 mg/l), however, the difference was not statistically significant (p=0.068). The patients who received steroid treatment had significantly higher RBP concentrations. There were no such association with other medications. There was no association between RBP and the number of previous treatment lines (p=0.8). Serum RBP did not differ between men and women (p=0.7) and did not correlate with age (p=0.6). Significant correlations were found between RBP and serum creatinine, cystatin C and eGFR values calculated based on creatinine and/or cystatin C (Table 1). In multiple regression, serum creatinine or cystatin C and the treatment with steroids were associated with RBP independently of ISS stage (Table 2). Moreover, RBP correlated with β2-microglobulin, LDH, leukocyte count, α-klotho, FGF-23, GDF-15, uNGAL and uIGFBP-7, however, only the associations with β2-microglobulin and sTfR were independent of serum creatinine in multiple regression (Table 1). Baseline serum RBP concentration was significantly correlated with eGFR after a median of 19 months follow-up (range 1-24 months) (R=-0.35; p=0.003), however, the correlation was not independent of baseline serum creatinine ((beta ± SE: 0.06 ± 0.10; p=0.5). To the contrary, baseline serum cystatin C (beta ± SE: -0.36 ± 0.13; p=0.009) predicted final eGFR independently of baseline serum creatinine. Conclusion RBP may be useful marker in renal damage in patients with chronic kidney injury among patients with MM. This can lead to noninvasive biomarker-targeted diagnostic interventions and contribute to early beginning of treatment that may improve life expectancy quality of life in MM.

We aimed to describe the clinical presentation, treatment, outcome and report on factors associated with mortality over a 90-day period in Clostridioides difficile infection (CDI). Descriptive, univariate, and multivariate regression analyses were performed on data collected in a retrospective case-control study conducted in nine hospitals from seven European countries. A total of 624 patients were included, of which 415 were deceased (cases) and 209 were still alive 90 days after a CDI diagnosis (controls). The most common antibiotics used previously in both groups were β-lactams; previous exposure to fluoroquinolones was significantly (p = 0.0004) greater in deceased patients. Multivariate logistic regression showed that the factors independently related with death during CDI were older age, inadequate CDI therapy, cachexia, malignancy, Charlson Index, long-term care, elevated white blood cell count (WBC), C-reactive protein (CRP), bacteraemia, complications, and cognitive impairment. In addition, older age, higher levels of WBC, neutrophil, CRP or creatinine, the presence of malignancy, cognitive impairment, and complications were strongly correlated with shortening the time from CDI diagnosis to death. CDI prevention should be primarily focused on hospitalised elderly people receiving antibiotics. WBC, neutrophil count, CRP, creatinine, albumin and lactate levels should be tested in every hospitalised patient treated for CDI to assess the risk of a fatal outcome.

OBJECTIVE Introduction: Index of microcirculatory resistance assessment is an invasive method of measuring coronary microcirculation function. Association between impaired microcirculatory function and higher rate of cardiovascular events was proven. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio seem to be a promising parameters to predict coronary microcirculatory disease in patients with chronic coronary syndrome. The aim: To determine neutrophil-lymphocyte ratio and platelet-lymphocyte ratio levels in patients with coronary microcirculatory disease and potential association with clinical outcome. PATIENTS AND METHODS Material and methods: 82 consecutive patients with mean age of 67 years, 67% male, were tested for presence of coronary microcirculatory disease using index of microcirculatory resistance. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were calculated based on admission full blood count. Follow-up with major adverse cardiac and cardiovascular events registration was performed (median 24 months). RESULTS Results: The study showed significantly higher neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with coronary microcirculatory disease compared to control group (3.58±2.61 vs 2.54±1.09 and 164±87.9 vs 124±36.6 respectively). Higher level of platelet-lymphocyte ratio in patients with coronary microcirculatory disease results in worse MACCE-free survival. Optimal cut-off values of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio to detect coronary microcirculatory disease were 3.2 and 181.3, respectively. CONCLUSION Conclusions: Higher neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are associated with increased index of microcirculatory resistance value. Platelet-lymphocyte ratio may be used as a predictor of worse outcome in patients with coronary microcirculatory disease.

Background and Aims Zonulin is a haptoglobin 2 precursor, that regulates the intestinal permeability. As a double-chain form it takes part in scavenging haemoglobin. Chronic inflammation is common complication of chronic kidney disease which affects iron metabolism. The most frequent manifestation of multiple myeloma is anaemia in up to 73% of patients. Serum concentrations of zonulin are associated with inflammation process, age, kidney failure and iron status and anaemia. The aim of the study was to analyse zonulin as a marker of anaemia in MM patients and investigate its relationship with acclaimed parameters of renal failure, inflammation, bone metabolism and stages of MM. Method The studied group of seventy-three patients with MM (67 symptomatic, 6 smoldering) included 35 women and 38 man, with mean age 69 ± 10 years. Median (IQR) of time from initial MM diagnosis was 36 (17; 69) months. Forty patients were in ISS stage 1, 15 in stage 2, and 12 in stage 3 at the time of blood collection. Remission of MM was diagnosed in 52 patients and stable or progressive disease in 21. Twenty-six patients had eGFR Results Median (IQR) serum zonulin in the studied group was 23.9 (19.9; 27.4) ng/ml. There were no differences in zonulin concentrations between patients with smoldering versus symptomatic MM (p=0.4), with ISS 1 to 3 (p=0.7), with remission versus stable or progressive MM (p=0.9), or with eGFR Conclusion Zonulin as a biomarker may promote diagnosis of etiology and management of MM-associated anaemia, which can contribute to biomarker-targeted therapeutic interventions. Early treatment may result in improved life expectancy in patients with MM and increase their quality of life.

Background and Aims Transgelin (SM22) is a cytoskeletal actin-binding protein involved in differentiation of smooth muscle cells, osteoblasts and adipocytes. It is present in fibroblasts, some epithelium, immune cells and acts as a tumor suppressor. It was found as a marker of interstitial fibrosis and glomerulosclerosis. Transgelin upregulation depends on the etiology of the disease in various cells (glomerular parietal or visceral, or tubular interstitial cells). Elevated SM22 expression was detected in glomerular and in tubulointerstitial injury. Among patients with multiple myeloma (MM) up to 50% suffer from renal insufficiency (RI) in early stages. Free light chains (FLCs), potential nephrotoxic substances, where lambda light chains are more commonly associated with renal damage, appear to have a prognostic value in MM and indicate the stages of MM. The aim of the study was to analyse the utility of transgelin in case of renal impairment in MM patients and investigate its relationship with acclaimed parameters of renal failure and markers of MM stages. Method The analysis included 126 patients (73 women and 53 men) in mean age 66 ± 10 years. Symptomatic MM was diagnosed in 119 patients, including 84 (67%) with ISS stage 1, 20 (16%) with stage 2 and 15 (12%) with stage 3; 7 (6%) patients had smoldering MM. Mean baseline eGFR (CKD-EPICr) was 74 ± 24 ml/min/1.73 m2 and 31 (25%) patients had eGFR Results Median serum transgelin in the whole studied group was 84.1 (IQR: 65.4; 116.4) ng/ml. Transgelin concentrations were higher in men (median 96.2 versus 78.8 ng/ml; p=0.022) and in patients with smoldering MM (median 149.2 versus 82.4 ng/ml; p=0.003). Transgelin did not differ according to ISS stage (p=0.3) or disease state (regression, stable disease or progression) (p=0.3). Significant correlations were detected between transgelin and serum creatinine (R=0.29; p=0.001), eGFR (CKD-EPICr) (R=-0.25; p=0.007), uric acid (R=0.19; p=0.036), alanine (R=0.18; p=0.048) and aspartate (R=0.26; p=0.003) aminotransferases, ferritin (R=-0.22; p=0.049), hepcidin (R=-0.25; p=0.033), and urine cystatin C (R=0.19; p=0.042). Moreover, after exclusion of patients with smoldering MM, transgelin significantly correlated with serum FLC lambda (R=0.18; p=0.047) and serum periostin (R=-0.22; p=0.013). After median follow-up of 21 (IQR: 15; 24) months, eGFR decreased in 47 (37%) of patients and increased in 71 (56%) patients (no follow-up data were available in 8, i.e. 6% of patients). Patients in whom eGFR decreased had higher transgelin (median 106.6 versus 83.9 ng/ml), although the difference was marginally significant (p=0.05). However, baseline transgelin positively correlated with serum creatinine after follow-up (R=0.37; p Conclusion Transgelin may be useful in investigating renal damage because of its proven role in regulation of fibrosis, especially in kidney. As a biomarker it may indicate diagnosis and etiology of MM-related chronic kidney disease, which can lead to beginning of early therapeutic interventions and improved overall survival and quality of life in patients with MM. Moreover, elevated transgelin at the beginning of the disease may induce future development of chronic kidney disease.

Background and Aims Urine tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) seem to be novel kidney injury related biomarkers, especially in tubular cells damage. Free light chains (FLCs) are associated with renal failure in multiple myeloma (MM) and appear to have a prognostic value and indicate stages in MM. The aim of the study was to investigate the correlation between new biomarkers and acclaimed parameters of renal failure and markers of MM stages and prognosis. Method The study included 124 patients with MM in the mean age of 66 +/- 10 years, with median time from MM diagnosis of 30 (lower; upper quartile 14; 63) months. There were 7(6%) patients with smoldering MM, 80(65%) with ISS stage 1, 22 (18%)with stage 2 and 15 (12%) with stage 3 MM. Mean eGFR was 71 +/- 25 ml/min/1.73 m2 and 30 (24%) patients had eGFR Results Except for urine cystatin C and urine TIMP-2, all the studied markers were higher among patients with eGFR Serum and urine IGFBP-7 and urine NGAL were also higher among patients with ISS grade 3 comparing to the rest of the group (p=0.008, p Conclusion Urine TIMP-2 and IGFBP-7 may be useful in investigating tubular renal damage in patients with chronic kidney injury among patients with MM. This can lead to noninvasive biomarker-targeted diagnostic interventions and contribute to early beginning of treatment that may improve life expectancy quality of life in MM.

We studied the correlations between circulating osteoprotegerin (OPG) level and radial artery calcification (RAC) assessed histologically and carotid artery intima-media thickness (CCA-IMT). Moreover, we studied the relationship between OPG levels and all-cause and cardiovascular (CV) mortality during a 5-year observation period. The study comprised 59 CKD patients (36 hemodialyzed (HD), 23 predialysis). The biochemical parameters included: creatinine, calcium, phosphate, intact parathormone, C-reactive protein, interleukin-6, tumor necrosis factor receptor II (TNFRII), transforming growth factor-β, hepatocyte growth factor, fibroblast growth factor 23, osteonectin (ON), osteopontin, osteoprotegerin, and osteocalcin. CCA-IMT and the presence of atherosclerotic plaques was assessed by ultrasound. Fragments of radial artery obtained during creation of HD access were prepared for microscopy and stained for calcifications with alizarin red. RAC was detected in 34 patients (58%). In multiple regression adjusted for dialysis status, TNFRII, ON and Framingham risk score (FRS) were identified as the independent predictors of OPG. Serum OPG above the median value of 7.55 pmol/L significantly predicted the presence of RAC in simple logistic regression (OR 5.33; 95%CI 1.39-20.4; P = 0.012) and in multiple logistic regression adjusted for FRS, dialysis status and CCA-IMT values (OR 6.56; 95%CI 1.06-40.6; P = 0.036). OPG levels above the median were associated with higher CCA-IMT values (1.02 ± 0.10 vs. 0.86 ± 0.13; P < 0.001) and predicted the presence of atherosclerotic plaques in carotid artery (OR 14.4; 95%CI 2.84-72.9; P < 0.001), independently of FRS, dialysis status and RAC. In this study, elevated serum OPG levels correlated with higher CCA-IMT, the presence of atherosclerotic plaques and the severity of the RAC independently of each other. During follow-up, 25 patients (42%) died, including 21 due to CV causes. In multiple Cox regression, OPG above the median predicted overall survival independently of dialysis status, Framingham risk score, CCA-IMT above the median value, and the presence of atherosclerotic plaques in CCA, but not independently of RAC. We postulate that circulating OPG may play a dual role as a marker for both medial arterial calcification and atherosclerosis, hence it seems to be a valuable tool for assessing CV risk in patients with CKD. OPG might be an early indicator of all-cause mortality in CKD patients with advanced medial arterial calcification.

A high neutrophil-to-lymphocyte ratio (NLR) has been reported to be a strong biomarker of inflammation.We sought to evaluate the impact of NLR on long-term all-cause and cardio-vascular (CV) mortality in hemodialysis (HD) patients.total of 84 chronic kidney disease (CKD) stage 5 patients with 54 of them on HD, with a median age of 61.5 (51.3-74.8) years were enrolled. e association between NLR and clinical biomarkers was investigated. Multivariable Cox regression analysis was used to find significant predictors of all-cause and CV mortality at follow-up.the median NLR (interquartile range) was 3.0 (2.1-4.1). Patients with NLR ≥3.9 (the highest tertile) had higher five-year all-cause mortality then remaining patients (53.6% vs. 30.4%; p = 0.039). On the contrary, only a trend towards increased CV mortality was observed (25.0% vs. 42.9%; p = 0.10). NLR ≥3.9 was a significant predictor of all-cause mortality at five years [hazard ratio (95%CI): 2.23 (1.10-4.50); p = 0.025] in Cox regression model adjusted for age, gender, and diabetes status. Similarly, while using NLR as continuous variable a significant association between NLR and all-cause mortality was confirmed even a er adjustment for covariates [hazard ratio per 1 unit increase (95%CI): 1.26 (1.06-1.51); p = 0.009] with the area under the receiver operating characteristic (ROC) curve of 0.64. Correlations between NLR and WBC, concentration of fibrinogen, albumin were observed.Asymptomatic inflammation measured by NLR showed an association with long-term all-cause mortality in stage 5 CKD patients, even while white blood cell count was in the normal range.

Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor-β superfamily, participates in processes associated with myeloma development and its end-organ complications. It plays a significant role in both physiological and abnormal erythropoiesis and regulates iron homeostasis through modulation of hepcidin. It is abnormally secreted in marrow stromal cells of patients with multiple myeloma (MM), which may reflect the tumor microenvironment. We analyzed the associations of serum GDF-15 with clinical characteristics of 73 MM patients (including asymptomatic MM) and the laboratory indices of renal function, anemia, and inflammation. Baseline serum GDF-15 was studied as the predictor of two-year survival. We defined five clinically relevant subgroups of patients (symptomatic MM only, patients with and without remission, patients on chemotherapy, and without treatment). Increased GDF-15 concentrations were associated with more advanced MM stage, anemia, renal impairment (lower glomerular filtration and higher markers of tubular injury), and inflammation. Most of the results were confirmed in the subgroup analysis. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin were associated with GDF-15 independently of other variables. In the studied MM patients, GDF-15 did not significantly predict survival ( p = 0.06 ). Our results suggest that serum GDF-15 reflects myeloma burden and shares a relationship with several markers of prognostic significance, as well as major manifestations.

Introduction Survival after heart transplantation (HTX) is extended due to continuous improvement of medical care, allowing enough time for coronary artery vasculopathy to develop. Data on the clinical outcome of cardiac transplantation patients after percutaneous coronary intervention (PCI) are still not extensively explored. The aim of our study was to assess whether heart transplantation itself compromises the outcome in patients undergoing percutaneous coronary intervention and to assess survival rates as well as major cardiovascular complications in heart transplant recipients who had undergone PCI. Material and methods Thirty-three heart transplant recipients who had undergone PCI in the years 2005 to 2015 in a single center were matched by age, sex and main risk factors of arteriosclerosis with 33 controls without heart transplant history. Mean age of patients was 54.6 ±11.4 years in the HTX group and 58.8 ±10.8 years in controls. Median time from heart transplant to PCI was 13 years (4.4-22 years). Case and control groups did not differ in terms of standard risk factors of coronary artery disease, apart from chronic kidney disease, which was present in 70% of patients after heart transplantation, and dyslipidemia, which was present in 91% of control subjects. Results Patients after HTX had worse survival compared to controls (p = 0.04). When adjusted for comorbidities in the Cox regression model, there was no significant difference in survival between cardiac transplant recipients and the control group (HR = 1.06; 95% CI: 0.10-11.24). Chronic renal disease was a significant predictor of all-cause mortality (HR = 29.9; 95% CI: 2.3-393). Considering other endpoints, HTX patients had considerably higher incidence of severe bleeding compared to the control group (27% vs. 3%, p < 0.05). Conclusions There was no significant difference in myocardial infarction rate, revascularization or hospitalization rates.

Multiple myeloma (MM) is a common plasma cell malignancy, which is responsible for significant mortality, often related to severe renal impairment (RI). Kidney injury can limit therapeutic choices and may often translate into poor outcomes, but it remains potentially reversible in a proportion of patients. The most accessible, conventional markers of RI are subject to several shortfalls, among which are the delayed onset following kidney insult, multiple interfering factors, and lesser sensitivity to mild changes in glomerular filtration. Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C have accumulated large interest in MM-RI due to being very sensitive markers of renal injury, as well as indicators of tubular-glomerular axis impairment. Of interest, recent data suggest that prediction of acute kidney injury may be aided by urinary tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), which both act to induce G1 cell cycle arrest, reflective of a state of pre-injury, and thus may be superior to other measures of kidney insult (NGAL, kidney injury molecule ((KIM-1)). Moreover, TIMP-2 seems to be a biomarker dedicated to distal tubular cells, whereas insulin-like growth factor-binding protein 7 (IGFBP7) secretion has been found in proximal tubule cells. IGFBP7 can also identify a subsection of the normal proximal nephron, even, maybe the one that is responding to insult. They may be adopted into a conceptual screening panel for MM-RI. Unfortunately, no biomarker is ideal (influence of non-renal, biologic factors), and novel measures are limited by economic constraints, availability, lack of standardization. With the emergence of more advanced diagnostic and prognostic MM models, markers reflective of disease processes (including RI) are of high interest. Candidate molecules also include peptidome markers.

Introduction: The prevalence of cardiovascular (CV) comorbidity in patients with chronic kidney disease (CKD) is high, particularly in end-stage renal disease (ESRD). There is an ongoing search for novel biomarkers of CV disease in this population. Objectives: We aimed to investigate the associations of matrix proteoglycans (PGs) and glycosaminoglycans (GAGs), collagen, and arterial calcifications with selected serum and plasma markers of endothelial dysfunction, inflammation, oxidative stress, and bone turnover in patients with ESRD. Patients and methods: We enrolled 47 adult patients (32 men) with stage 5 CKD. The following parameters were investigated: fibrinogen, soluble thrombomodulin (sTM), plasminogen activator inhibitor 1 (PAI-1), stromal cell-derived factor 1α (SDF-1α), calcium (Ca), phosphate (Pi), intact parathormone, interleukin 6, high-sensitivity C-reactive protein (hs-CRP), ferric reducing ability of plasma, 2,2-diphenyl-1-picrylhydrazyl scavenging, ferric reducing ability of ascorbate in plasma, fetuin-A, fibroblast growth factor 23, osteopontin, osteoprotegerin, osteocalcin, transforming growth factor β (TGF-β), hepatocyte growth factor, secreted protein acidic and rich in cysteine, as well as matrix metalloproteinase 2. Radial artery specimens were stained with alizarin red for calcifications, alcian blue for PGs and GAGs, and sirius red for collagen. Results: We observed positive correlations between PG and GAG, collagen, and calcification staining. The most intense (grade 3) alcian blue staining was significantly correlated with diabetes as well as higher levels of Ca×Pi product, hs-CRP, fibrinogen, SDF-1α, PAI-1, and sTM. However, PAI-1 was the only significant predictor of grade 3 alcian blue staining in a multiple logistic regression model adjusted for hemodialysis, Ca×Pi product, and hs-CRP levels. Conclusions: Coagulation disorders and endothelial dysfunction are the hallmarks of ESRD. The levels of SDF-1α, PAI-1, sTM, and fibrinogen may be novel predictors of early vascular wall alterations and may serve as CV risk markers. biomarkers end‑stage renal disease glycosaminoglycans plasminogen activator inhibitor 1 proteoglycans

Principles of treat-to-target (T2T) have been widely adopted in both multinational and regional guidelines for rheumatoid arthritis (RA). Several questionnaire studies among physicians and real-world data have suggested that an evidence–practice gap exists in RA management. Investigating physician adherence to T2T, which requires a process measure, is difficult. Different practice patterns among physicians are observed, while adherence to protocolized treatment declines over time. Rheumatologist awareness, agreement, and claims of adherence to T2T guidelines are not always consistent with medical records. Comorbidities, a difficult disease course, communication barriers, and individual preferences may hinder an intensive, proactive treatment stance. Interpreting deviations from protocolized treatment/T2T guidelines requires sufficient clinical context, though higher adherence seems to improve clinical outcomes. Nonmedical constraints in routine care may consist of barriers in healthcare structure and socioeconomic factors. Therefore, strategies to improve the institution of T2T should be tailored to local healthcare. Educational interventions to improve T2T adherence among physicians may show a moderate, although beneficial effect. Meanwhile, a proportion of patients with inadequately controlled RA exists, while management decisions may not be in accordance with T2T. Physicians tend to be aware of current guidelines, but their institution in routine practice seems challenging, which warrants attention and further study.

Multiple myeloma (MM) is a malignancy of clonal plasma cells accounting for approximately 10% of haematological malignancies. MM mainly affects older patients, more often males and is more frequently seen in African Americans. The most frequent manifestations of MM are anaemia, osteolytic bone lesions, kidney failure and hypercalcemia. The anaemia develops secondary to suppression of erythropoiesis by cytokine networks, similarly to the mechanism of anaemia of chronic disease. The concomitant presence of kidney failure, especially chronic kidney disease (CKD) and MM per se, leading to anaemia of chronic disease (ACD) in combination, provoked us to pose the question about their reciprocal dependence and relationship with specific biomarkers; namely, soluble transferrin receptor (sTfR), growth differentiation factor 15 (GDF15), hepcidin 25 and zonulin. One or more of these are new biomarkers of ferric management may be utilized in the near future as prognostic predictors for patients with MM and kidney failure.

INTRODUCTION Medial arterial calcification is common in patients with chronic kidney disease (CKD) and is considered a risk factor for morbidity and mortality. OBJECTIVES We aimed to evaluate the correlation between asymmetric dimethylarginine (ADMA) levels, radial artery calcification, and common carotid artery intima-media thickness (CCA‑IMT). PATIENTS AND METHODS The study included 51 patients with CKD, in whom an arteriovenous fistula for hemodialysis access was created to collect radial artery samples for a histological examination, and 33 healthy volunteers, in whom the reference concentrations of ADMA were assessed. The concentrations of creatinine, albumin, calcium, phosphate, fibroblast growth factor 23, osteoprotegerin (OPG), osteopontin (OPN), osteocalcin, secreted protein acidic and rich in cysteine, interleukin 6, interleukin 18, pentraxin 3, stromal cell‑derived factor 1α (SDF1α), thrombomodulin, soluble tumor necrosis factor receptor II (sTNFRII), and matrix metalloproteinase 2 (MMP‑2) were determined. Radial artery fragments were stained for calcifications using alizarin red. The CCA‑IMT was assessed by ultrasonography. RESULTS Patients with CKD had higher ADMA levels than controls. Patients with ADMA levels above the median were older, had higher levels of phosphate, fibroblast growth factor 23, OPG, OPN, PTX3, sTNFRII, MMP‑2, thrombomodulin, and they had more atherosclerotic plaques in the carotid artery. In multiple regression, log‑transformed (log)sTNFRII, MMP‑2, and SDF1α levels were independent predictors of log(ADMA). Patients with calcifications had higher ADMA levels. A similar correlation was observed between SDF1α and alizarin red staining grades 1 to 3. In logistic regression, ADMA levels positively predicted the presence of calcifications independently of age, hemodialysis status, Framingham risk score, and PTX3. CONCLUSIONS Circulating ADMA levels indicate medial arterial calcification in patients with CKD.

Monoclonal gammopathy of renal significance (MGRS) has introduced a new perspective to several well-known disease entities impacting nephrology, haematology and pathology. Given the constantly changing disease spectrum of these entities, it is clinically imperative to establish diagnostic and treatment pathways supported by evidence-based medicine. MGRS is a disease of the kidney, secondary to plasma cell clonal proliferation or immune dysfunction, requiring therapeutic intervention to eradicate the offending clone. To fully understand the disease(s), it is prerequisite to determine the significance of the findings. The diagnostic work up should be extensive due to the wide heterogeneity of clinical presentation, ultimately necessitating kidney biopsy. Particular patient profiles such as AL amyloidosis, which may be diagnosed through biopsies of other tissues/organs, may be an exception. Treatment decisions should be formulated by multi-disciplinary consensus: nephrologists, haematologists and pathologists. The ultimate goal in managing MGRS is eradication of the offending plasma cell clone which requires targeted chemotherapy and, in eligible cases, haematopoietic stem cell transplantation. We present a review of diagnostic procedures, treatment options and advances in the last few years in the management of MGRS in an effort to acquaint specialists with this new face of several older diseases.

INTRODUCTION Medial arterial calcification is common in patients with chronic kidney disease (CKD) and is considered a risk factor for morbidity and mortality. OBJECTIVES We aimed to evaluate the correlation between asymmetric dimethylarginine (ADMA) levels, radial artery calcification, and common carotid artery intima-media thickness (CCA‑IMT). PATIENTS AND METHODS The study included 51 patients with CKD, in whom an arteriovenous fistula for hemodialysis access was created to collect radial artery samples for a histological examination, and 33 healthy volunteers, in whom the reference concentrations of ADMA were assessed. The concentrations of creatinine, albumin, calcium, phosphate, fibroblast growth factor 23, osteoprotegerin (OPG), osteopontin (OPN), osteocalcin, secreted protein acidic and rich in cysteine, interleukin 6, interleukin 18, pentraxin 3, stromal cell‑derived factor 1α (SDF1α), thrombomodulin, soluble tumor necrosis factor receptor II (sTNFRII), and matrix metalloproteinase 2 (MMP‑2) were determined. Radial artery fragments were stained for calcifications using alizarin red. The CCA‑IMT was assessed by ultrasonography. RESULTS Patients with CKD had higher ADMA levels than controls. Patients with ADMA levels above the median were older, had higher levels of phosphate, fibroblast growth factor 23, OPG, OPN, PTX3, sTNFRII, MMP‑2, thrombomodulin, and they had more atherosclerotic plaques in the carotid artery. In multiple regression, log‑transformed (log)sTNFRII, MMP‑2, and SDF1α levels were independent predictors of log(ADMA). Patients with calcifications had higher ADMA levels. A similar correlation was observed between SDF1α and alizarin red staining grades 1 to 3. In logistic regression, ADMA levels positively predicted the presence of calcifications independently of age, hemodialysis status, Framingham risk score, and PTX3. CONCLUSIONS Circulating ADMA levels indicate medial arterial calcification in patients with CKD.

Background: The survival rate of elderly hemodialyzed (HD) patients is commonly thought to be poor. In a prospective, single center, non-interventional, observational study, the cause of all-cause and cardiovascular (CV) and heart failure (HF) mortality in this patient group were examined and compared with a younger cohort (below 60 years). Material/Methods: The study included 223 patients (90 women and 133 men) with age ranging from 34.5 to 75.0 years treated with HD. Median duration of HD was 70.0 months (24.0-120.0). Mortality data was collected over a period of six years. We divided patients into groups

We studied the correlations between circulating osteoprotegerin (OPG) level and radial artery calcification (RAC) assessed histologically and carotid artery intima-media thickness (CCA-IMT). Moreover, we studied the relationship between OPG levels and all-cause and cardiovascular (CV) mortality during a 5-year observation period. The study comprised 59 CKD patients (36 hemodialyzed (HD), 23 predialysis). The biochemical parameters included: creatinine, calcium, phosphate, intact parathormone, C-reactive protein, interleukin-6, tumor necrosis factor receptor II (TNFRII), transforming growth factor-β, hepatocyte growth factor, fibroblast growth factor 23, osteonectin (ON), osteopontin, osteoprotegerin, and osteocalcin. CCA-IMT and the presence of atherosclerotic plaques was assessed by ultrasound. Fragments of radial artery obtained during creation of HD access were prepared for microscopy and stained for calcifications with alizarin red. RAC was detected in 34 patients (58%). In multiple regression adjusted for dialysis status, TNFRII, ON and Framingham risk score (FRS) were identified as the independent predictors of OPG. Serum OPG above the median value of 7.55 pmol/L significantly predicted the presence of RAC in simple logistic regression (OR 5.33; 95%CI 1.39-20.4; P = 0.012) and in multiple logistic regression adjusted for FRS, dialysis status and CCA-IMT values (OR 6.56; 95%CI 1.06-40.6; P = 0.036). OPG levels above the median were associated with higher CCA-IMT values (1.02 ± 0.10 vs. 0.86 ± 0.13; P 0.001) and predicted the presence of atherosclerotic plaques in carotid artery (OR 14.4; 95%CI 2.84-72.9; P 0.001), independently of FRS, dialysis status and RAC. In this study, elevated serum OPG levels correlated with higher CCA-IMT, the presence of atherosclerotic plaques and the severity of the RAC independently of each other. During follow-up, 25 patients (42%) died, including 21 due to CV causes. In multiple Cox regression, OPG above the median predicted overall survival independently of dialysis status, Framingham risk score, CCA-IMT above the median value, and the presence of atherosclerotic plaques in CCA, but not independently of RAC. We postulate that circulating OPG may play a dual role as a marker for both medial arterial calcification and atherosclerosis, hence it seems to be a valuable tool for assessing CV risk in patients with CKD. OPG might be an early indicator of all-cause mortality in CKD patients with advanced medial arterial calcification.