Risk factors of acute kidney injury during hospitalization in acute ischaemic stroke patients undergoing mechanical thrombectomy.

Introduction: Acute kidney injury (AKI) seems to worsen the prognosis of acute ischaemic stroke (AIS) patients treated with mechanical thrombectomy (MT). At the same time, the procedure of MT increases AKI risk by iodinated contrast use. Identification of factors predisposing to AKI after MT is important for recognizing vulnerable patients and successful prevention. Aim: To identify factors associated with the occurrence of AKI during hospitalization in MT-treated AIS patients. Material and methods: The study included all AIS patients treated with MT in the University Hospital in Krakow from 2019 to 2021. The diagnosis of AKI during hospitalisation was based on serum creatinine concentration levels, according to the Kidney Disease Improving Global Outcomes guidelines. We compared patients with and without AKI in terms of age, sex, comorbidities, stroke course and laboratory test results at admission. We identified factors associated with the occurrence of AKI using univariate logistic regression analysis, with significant variables subsequently added to the multivariate analyses. Results: Among 593 MT-treated AIS patients the incidence of AKI during hospitalisation was 12.6%. AKI development was associated with diabetes, chronic kidney disease, total volume of iodinated contrast obtained during hospitalisation, posterior circulation stroke, lack of intravenous thrombolysis, and laboratory test results at admission: haemoglobin, glucose, urea, potassium, and creatinine. Total contrast volume and urea level were the most important independent risk factors associated with occurrence of AKI. Conclusions: AKI is common in MT-treated AIS patients. There is a need to establish a protocol for decreasing the risk of AKI in AIS patients undergoing MT and, in case it occurs, a procedure for its treatment.

Predicting acute kidney injury onset with a random forest algorithm using electronic medical records of COVID-19 patients: the CRACoV-AKI model.

INTRODUCTION: Acute kidney injury (AKI) is a serious and common complication of SARS­CoV­2 infection. Most risk assessment tools for AKI have been developed in the intensive care unit or in elderly populations. As the COVID­19 pandemic is transitioning into an endemic phase, there is an unmet need for prognostic scores tailored to the population of patients hospitalized for this disease. OBJECTIVES: We aimed to develop a robust predictive model for the occurrence of AKI in hospitalized patients with COVID­19. PATIENTS AND METHODS: Electronic medical records of all adult inpatients admitted between March 2020 and January 2022 were extracted from the database of a large, tertiary care center with a reference status in Lesser Poland. We screened 5806 patients with SARS­CoV­2 infection confirmed with a polymerase chain reaction test. After excluding individuals with lacking data on serum creatinine levels and those with a mild disease course (<7 days of inpatient care), a total of 4630 records were considered. Data were randomly split into training (n = 3462) and test (n = 1168) sets. A random forest model was tuned with feature engineering based on expert advice and metrics evaluated in nested cross­validation to reduce bias. RESULTS: Nested cross­validation yielded an area under the curve ranging between 0.793 and 0.807, and an average performance of 0.798. Model explanation techniques from a global perspective suggested that a need for respiratory support, chronic kidney disease, and procalcitonin concentration were among the most important variables in permutation tests. CONCLUSIONS: The CRACoV­AKI model enables AKI risk stratification among hospitalized patients with COVID­19. Machine learning-based tools may thus offer additional decision­making support for specialist providers.

Serial echocardiographic evaluation of COVID-19 patients without prior history of structural heart disease: a 1-year follow-up CRACoV-HHS study.

Background: It is a well-known fact that COVID-19 affects the cardiovascular system by exacerbating heart failure in patients with preexisting conditions. However, there is a poor insight into the cardiovascular involvement and sequelae in patients without preexisting conditions. The aim of the study is to analyse the influence of COVID-19 on cardiac performance in patients without prior history of structural heart disease. The study is part of the CRACoV project, which includes a prospective design and a 12-month follow-up period. Material and methods: The study included 229 patients hospitalised with a diagnosis of COVID-19 (median age of 59 years, 81 were women). A standard clinical assessment and laboratory tests were performed in all participants. An extended echocardiographic image acquisition was performed at baseline and at a 3-, 6-, and 12-month follow-up. All analyses were performed off-line. A series of echocardiographic parameters was compared using repeated measures or Friedman analysis of variance. Results: In all subjects, the left ventricular (LV) ejection fraction at baseline was preserved [63.0%; Q1:Q3 (60.0-66.0)]. Elevated levels of high-sensitivity cardiac troponin T were detected in 21.3% of the patients, and elevated NT-proBNP levels were detected in 55.8%. At the 1-year follow-up, no significant changes were observed in the LV diameter and volume (LV 48.0 ± 5.2 vs. 47.8 ± 4.8 mm, p = 0.08), while a significant improvement of the parameters in the biventricular strain was observed (LV -19.1 ± 3.3% vs. -19.7 ± 2.5%, p = 0.01, and right ventricular -19.9 ± 4.5% vs. -23.2 ± 4.9%, p = 0.002). In addition, a decrease in the LV wall thickness was also observed (interventricular septum 10.4 ± 1.6 vs. 9.7 ± 2.0 mm, p < 0.001; LV posterior wall 9.8 ± 1.4 vs. 9.1 ± 1.5 mm, p < 0.001). Conclusions: In an acute phase of COVID-19, the elevation of cardiac biomarkers in patients with normal left ventricular ejection fraction is a frequent occurrence; however, it does not translate into clinically significant cardiac dysfunction after 1 year. The serial echocardiographic evaluations conducted in patients without preexisting structural heart disease demonstrate an overall trend towards an improved cardiac function and a reduced myocardial thickening at 1-year follow-up. This suggests that the acute cardiac consequences of COVID-19 are associated with systemic inflammation and haemodynamic stress in patients without preexisting conditions.

Short- and long-term survival of patients hospitalized for COVID-19 in relation to cardiovascular risk factors and established cardiovascular disease: the Cor-Cardio study.

INTRODUCTION: The clinical presentation of COVID­19 may range from asymptomatic infection to severe disease. Previous studies reported a relationship between the course of COVID­19 and a history of cardiovascular (CV) disease (CVD). OBJECTIVES: We aimed to analyze the influence of CV risk factors, established CVD, and treatment with CV drugs on short- and long­term survival in patients hospitalized for COVID­19. PATIENTS AND METHODS: We retrospectively analyzed data of patients hospitalized in 13 COVID­19 hospitals in Poland (between March and October 2020). Individual deaths during the follow­up were recorded until March 2021. RESULTS: Overall, 2346 patients with COVID­19 were included (mean age, 61 years; 50.2% women). A total of 341 patients (14.5%) died during the hospitalization, and 95 (4.7%) died during the follow­up. Independent predictors of in­hospital death were older age, a history of established CVD, heart failure, and chronic kidney disease (CKD), while treatment with renin­angiotensin­aldosterone system blockers or statins was associated with a lower risk of death during hospitalization. Factors that independently predicted death during the follow­up were older age, a history of established CVD, CKD, and a history of cancer. The presence of CV risk factors did not increase the odds of death either in the hospital or during the follow­up. Of note, higher systolic blood pressure and oxygen blood saturation on admission were associated with better short- and long­term prognosis. CONCLUSION: Established CVD and CKD were the main predictors of mortality during both the hospitalization and the follow­up in the patients hospitalized for COVID­19, while the use of CV drugs during the hospitalization was associated with better prognosis. The presence of CV risk factors did not increase the odds of in­hospital and postdischarge death.

Impact of Arterial Hypertension and Use of Antihypertensive Pharmacotherapy on Mortality in Patients Hospitalized due to COVID-19: The CRACoV-HHS Study.

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<0.001) compared to nontreated hypertensives (n=1305). 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.

Comparison between COVID­19 outcomes in the first 3 waves of the pandemic: a reference hospital report.

INTRODUCTION: The course of consecutive COVID­19 waves was influenced by medical and organizational factors. OBJECTIVES: We aimed to assess the outcomes of patients hospitalized for COVID­19 during the first 3 waves of the pandemic. PATIENTS AND METHODS: We performed a retrospective analysis of medical records of all COVID­19 patients admitted to the University Hospital in Kraków, Poland, a designated COVID­19 hospital in Malopolska 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. RESULTS: Data analyses included 5191 patients with COVID­19. 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; P <0.001). Hospital death rates in subsequent waves were 10.4%, 19.8%, and 20.3% (P <0.001). 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 in­hospital death were: advanced age, male sex, cardiovascular or chronic kidney disease, higher C­reactive protein level, and hospitalization during the second or third wave. CONCLUSIONS: We identified differences in patients' clinical characteristics and outcomes between consecutive pandemic waves, which probably reflect changes in terms of COVID­19 isolation policy, hospitalization and treatment indications, and treatment strategies.

The Key Role of Hepcidin-25 in Anemia in Multiple Myeloma Patients with Renal Impairment.

Background and objectives: Anemia is common in multiple myeloma (MM) and is caused by a complex pathomechanism, including impaired iron homeostasis. Our aim is to evaluate the biomarkers of iron turnover: serum soluble transferrin receptor (sTfR) and hepcidin-25 in patients at various stages of MM in relation with markers of anemia, iron status, inflammation, renal impairment and burden of the disease and as predictors of mortality. Materials and methods: Seventy-three MM patients (six with smoldering and 67 with symptomatic disease) were recruited and observed for up to 27 months. Control group included 21 healthy individuals. Serum sTfR and hepcidin were measured with immunoenzymatic assays. Results: MM patients with and without anemia had higher sTFR compared to controls, while only anemic patients had higher hepcidin-25. Both hepcidin-25 and sTfR were higher in anemic than non-anemic patients. Higher hepcidin-25 (but not sTfR) was associated with increasing MM advancement (from smoldering to International Staging System stage III disease) and with poor response to MM treatment, which was accompanied by lower blood hemoglobin and increased anisocytosis. Neither serum hepcidin-25 nor sTfR were correlated with markers of renal impairment. Hepcidin-25 predicted blood hemoglobin in MM patients independently of other predictors, including markers of renal impairment, inflammation and MM burden. Moreover, both blood hemoglobin and serum hepcidin-25 were independently associated with patients' 2-year survival. Conclusions: Our results suggest that hepcidin-25 is involved in anemia in MM and its concentrations are not affected by kidney impairment. Moreover, serum hepcidin-25 may be an early predictor of survival in this disease, independent of hemoglobin concentration. It should be further evaluated whether including hepcidin improves the early diagnosis of anemia in MM.

Renal Impairment Detectors: IGFBP-7 and NGAL as Tubular Injury Markers in Multiple Myeloma Patients.

Background and Objectives: Urine insulin-like growth factor-binding protein 7 (IGFBP-7), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and neutrophil gelatinase-associated lipocalin (NGAL) monomer are novel tubular kidney injury biomarkers. In multiple myeloma (MM), immunoglobulin free light chains (FLCs) play an integral role in renal impairment. This study aimed to investigate the correlation between new biomarkers and acclaimed parameters of renal failure, MM stage, and prognosis. Materials and Methods: The examined parameters included: urinary and serum cystatin-C, IGFBP-7, and TIMP-2, and urinary NGAL monomer in 124 enrolled patients. Results: Urinary and serum IGFBP-7 and urinary NGAL were higher among patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and positively correlated with urine light chains. Serum and urine IGFBP-7 and urine NGAL were greater among patients with a higher disease stage. In the whole study group, urinary concentrations of the studied markers were positively correlated with each other. In multiple linear regression, urinary IGFBP-7 and NGAL were associated with lower eGFR, independently of other urinary markers. Conclusions: Urinary IGFBP-7 and NGAL monomer may be useful markers of tubular renal damage in patients with MM. Biomarker-based diagnostics may contribute to earlier treatment that may improve renal outcomes and life expectancy in MM.

Mortality Following Clostridioides difficile Infection in Europe: A Retrospective Multicenter Case-Control Study.

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 ß-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.

Association between cardiovascular disease, cardiovascular drug therapy, and in-hospital outcomes in patients with COVID-19: data from a large single-center registry in Poland.

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, ß-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), ß-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.

Mid-term and late results of endovascular treatment for symptomatic carotid artery stenosis under proximal protection.

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 long-term 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 long-term 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.

Transgelin-2 in Multiple Myeloma: A New Marker of Renal Impairment?

Transgelin is a 22-kDa protein involved in cytoskeletal organization and expressed in smooth muscle tissue. According to animal studies, it is a potential mediator of kidney injury and fibrosis, and moreover, its role in tumorigenesis is emerging in a variety of cancers. The study included 126 ambulatory patients with multiple myeloma (MM). Serum transgelin-2 concentrations were measured by enzyme-linked immunoassay. We evaluated associations between baseline transgelin and kidney function (serum creatinine, estimated glomerular filtration rate-eGFR, urinary markers of tubular injury: cystatin-C, neutrophil gelatinase associated lipocalin-NGAL monomer, cell cycle arrest biomarkers IGFBP-7 and TIMP-2) and markers of MM burden. Baseline serum transgelin was also evaluated as a predictor of kidney function after a follow-up of 27 months from the start of the study. Significant correlations were detected between serum transgelin-2 and serum creatinine (R = 0.29; p = 0.001) and eGFR (R = -0.25; p = 0.007). Transgelin significantly correlated with serum free light chains lambda (R = 0.18; p = 0.047) and serum periostin (R = -0.22; p = 0.013), after exclusion of smoldering MM patients. Patients with decreasing eGFR had higher transgelin levels (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 the follow-up period (R = 0.37; p < 0.001) and negatively correlated with eGFR after the follow-up period (R = -0.33; p < 0.001). Moreover, higher baseline serum transgelin (beta = -0.11 ± 0.05; p = 0.032) significantly predicted lower eGFR values after the follow-up period, irrespective of baseline eGFR and follow-up duration. Our study shows for the first time that elevated serum transgelin is negatively associated with glomerular filtration in MM and predicts a decline in renal function over long-term follow-up.

CRACoV-HHS: an interdisciplinary project for multi-specialist hospital and non-hospital care for patients with SARS-CoV-2 infection as well hospital staff assessment for infection exposure.

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.

Evaluating the Relationship of GDF-15 with Clinical Characteristics, Cardinal Features, and Survival in Multiple Myeloma.

Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor-ß 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.