Haematological disorders following kidney transplantation.

Transplantation offers cure for some haematological cancers, end-stage organ failure, but at the cost of long-term complications. Renal transplantation is the best-known kidney replacement therapy and it can prolong end-stage renal disease patient lives for decades. However, patients after renal transplantation are at a higher risk of developing different complications connected not only with surgical procedure but also with immunosuppressive treatment, chronic kidney disease progression and rejection processes. Various blood disorders can develop in post-transplant patients ranging from relatively benign anaemia through cytopenias to therapy-related myelodysplasia and acute myeloid leukaemia (AML) and post-transplant lymphoproliferative disorders followed by a rare and fatal condition of thrombotic microangiopathy and haemophagocytic syndrome. So far literature mainly focused on the post-transplant lymphoproliferative disease. In this review, a variety of haematological problems after transplantation ranging from rare disorders such as myelodysplasia and AML to relatively common conditions such as anaemia and iron deficiency are presented with up-to-date diagnosis and management.

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.

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.

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.

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.

Endothelial injury is closely related to osteopontin and TNF receptor-mediated inflammation in end-stage renal disease.

BACKGROUND: Endothelial dysfunction, inflammation and active mineralization are key processes involved in cardiovascular burden in end stage renal disease (ESRD). Serum (soluble) thrombomodulin (sTM) is an established marker of endothelial injury. PATIENTS: 80 patients in ESRD were recruited consecutively. Baseline distribution of sex, age, main comorbidities and Framingham score was similar. A biochemical panel including sTM, intact PTH (iPTH), interleukin-6 (IL-6), pentraxin 3 (PTX3), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteonectin (ON), soluble tumor necrosis factor receptor type 2 (TNFR2), transforming growth factor-ß (TGF-ß), hepatocyte growth factor (HGF), vascular endothelial growth factor receptor type 2 (sVEGFR2) and stromal cell-derived factor 1α (SDF1α) was investigated in each patient. Samples obtained while establishing haemodialysis (HD) access were stained for radial artery calcifications (RACs) with Alizarin red and examined histologically. RESULTS: After adjustment for HD status, sTM showed a significant positive correlation with serum creatinine, TNFR2, OPN, HGF, SDF1α, sVEGFR2, Pi, iPTH, FGF-23, OPG, OC and ON. In forward stepwise multiple regression, serum creatinine, TNFR2, and OPN were identified as significant, independent predictors of sTM. Grades 1-3 of RACs correlated with sTM (R = 0.50, p = 0.017), while grade 3 RACs were significantly associated with higher sTM (p = 0.02) than less advanced lesions. CONCLUSION: Among novel renal and cardiovascular biomarkers, OPN and TNFR2 are closely related to sTM. This may link endothelial damage, vascular remodeling and inflammation. Progression of RAC parallels a presumed compensatory rise in sTM, reflecting endothelial injury. sTM has an intricate role in endothelial function and potential clinical and prognostic applications.

The clinical implication of monoclonal gammopathies: monoclonal gammopathy of undetermined significance and of renal significance.

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.

Neutrophil-to-lymphocyte ratio predicts long-term all-cause mortality in patients with chronic kidney disease stage 5.

INTRODUCTION: A high neutrophil-to-lymphocyte ratio (NLR) has been reported to be a strong biomarker of inflammation. AIM: We sought to evaluate the impact of NLR on long-term all-cause and cardio-vascular (CV) mortality in hemodialysis (HD) patients. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparison of the incidence of skin cancers in patients on dialysis and after kidney transplantation.

INTRODUCTION: Kidney transplant (KTx) patients on immunosuppressive therapy are predisposed to the development of infections and cancers. AIM: To compare the incidence and type of malignant skin lesions in kidney transplant patients and the dialyzed population based on the initiated dermatologic screening. MATERIAL AND METHODS: The study included 598 patients: 486 kidney transplant recipients and 112 patients on maintenance dialysis. All the patients underwent dermatological examination. Only histologically confirmed cancers were included in this study. Age, gender and immunosuppressive therapy administration were also considered. Patients were followed up by a dermatologist for a period of 5 years. RESULTS: Fifty-eight skin cancers; 39 basal cell carcinomas (BCC), 13 squamous cell carcinomas (SCC), 1 Bowen disease, 2 Kaposi sarcoma, 1 malignant melanoma, 1 Merkel cell carcinoma, and 1 fibrosarcoma protuberans were diagnosed in 30 (6.2%) kidney transplant patients, and 8 lesions (7 BCC and 1 SCC) were found in 4 (3.6%) patients on dialysis. CONCLUSIONS: The initiated dermatologic screening program indicates that the risk of skin cancer incidence in post kidney transplant patients receiving immunosuppressive therapy was significantly higher than in patients on dialysis.

Carboxylated and intact osteocalcin predict adiponectin concentration in hemodialyzed patients.

Purpose Disrupted bone metabolism in patients with chronic kidney disease (CKD) is associated with elevated concentrations of biochemical bone markers. Recently, animal studies show the role of osteocalcin in energy metabolism, which is partially confirmed in humans. The aim of our study was to evaluate the relationships between serum concentrations of bone markers and indices of energy metabolism in CKD patients on maintenance hemodialysis; in particular, the relationship between various forms of osteocalcin and adiponectin. Patients and methods The cross-sectional study included 155 hemodialyzed stage 5 CKD patients. Serum concentrations of glucose, insulin, adiponectin, bone alkaline phosphatase (bALP), tartrate resistant acid phosphatase (TRAP), carboxylated (cOC), undercarboxylated (ucOC), and intact osteocalcin (OC) were determined. Results In total cohort, bALP, TRAP, cOC, and ucOC negatively correlated with BMI. All analyzed bone markers positively correlated with adiponectin in total cohort and in men. In multiple linear regression analysis including all patients, log(cOC) and log(intact OC) were the only bone markers that predicted log(adiponectin) (beta = 0.22; p = 0.016 and beta = 0.26; p = 0.010) independently of sex, dialysis vintage, CRP, insulin, iPTH concentrations, BMI, and age. Conclusions Our data confirm the positive association between cOC, intact OC, and adiponectin concentrations in CKD patients on maintenance hemodialysis.

Prevalence of the stages of chronic kidney disease (CKD) according to simplified MDRD formula in patients from ambulatory settings.

BACKGROUND: The staging system of chronic kidney disease (CKD) classification plays an important role in patients stratification according to disease activity. The aim of the study was to evaluate the frequency of appearance of consecutive stages of chronic kidney disease based on simplified MDRD formula in patients with diagnosed CKD. Additionally, relationship between eGFR values and selected biochemical parameters and comorbidities were analyzed. METHODS: The study was performed retrospectively in the group of 1176 patients (636 males and 540 females) aged between 17-98 years (mean 64.7) with creatinine level > 120 µmol/l and/or creatinine clearance < 90 ml/min/1.73 m2. RESULTS: The highest percentage of patients were designated to the 3rd CKD stage. There were positive correlations between eGFR and Hb, Ht, Fe, LDL-Ch, AspAT, HbA1c and negative correlations between eGFR and age, mean and systolic blood pressure, as well as with P, K, iPTH, and uric acid concentration. Patients with cardiovascular diseases had significaintly lower eGFR values as compare with patients without such complications, respectively: atrial fibrillation, arterial hypertension, chronic heart failure, ischaemic heart disease (p < 0.01), and myocardial infarction (p < 0.04). CONCLUSIONS: The highest percentage of patients with diagnosed CKD belong to the 3rd stage of disease. Patients with cardiovascular complications have significantly lower eGFR as compared with those without such disturbances.

[Comparison of the iron metabolism and effectiveness of anemia treatment in patients on maintenance hemodialysis performed based on polysulfone and helixone dialyzers]. / Prównanie gospodarki zelazem i skutecznosc leczenia niedokrwistosci u chorych hemodializowanych w oparciu o dializatory polisulfonowe i helixonowe.

INTRODUCTION: Anemia is a common complication in patients with chronic renal failure (CRF) especially on maintenance hemodialysis. There are some data that the use of biocompatible high-flux dialyzers is more efficient than low-flux dialyzers in controlling some uremia related diseases including anemia. The aim of the study was to assess the iron metabolism and degree of anemia correction in patients on maintenance hemodialysis performed based on low-flux dialyzers (HD-LF), with polysulfone membrane and high- flux dialyzers (HD-HF), with helixone membrane. MATERIAL AND METHODS: The observation lasted 12 months and involved 60 patients (23 F and 37 M) aged from 24 to 84 years, mean 60.73 ± 15.75 treated on maintenance HD. RESULTS: It was demonstrated a higher mean Hb and Ht values during period of HD-HF as compared with the HD-LF (LF-Hb = 11.09 ± 0.89 vs. HF-Hb = 11.42 ± 0.98; p < 0.01 and LF- Ht = 33.7 ± 2.87% vs. HF-Ht = 34.45 ± 3.08%). Higher values of Hb and Ht during HD-HF were obtained at a comparable average doses of darbepoetin alfa (Aranesp) used in both periods (LF-Aranesp = 8.29 ± 4.17 µg vs. HF-Aranesp = 8.25 ± 3.92 µg; p ≤ 0.29) and statistically significantly lower average doses of intravenous iron administered during HD-HF (LF-iron iv = 17.59 ± 10.44 mg vs. HF-iron iv 12.16 ± 9.04 mg; p < 0.01). It was also shown a statistically significant higher mean corpuscular volume of red blood cells (MCV) in patients during HD-HF (LF-MCV = 91.15 ± 6.6 µm3 vs. HF- MCV = 95.03 ± 5.38 µm3; p ≤ 0.001) and lower mean ferritin values (LF-ferritin = 636.33 ± 704.57 ng/ml vs. HF-ferritin = 538 ± 475.92 ng/ml; p ≤ 0.001). CONCLUSIONS: Lower intravenous iron use during HD-HF, with higher Hb values in these period may indicate on may indicate an increased loss of folates during HD-HF and the necessity of its increased supplementation.

[Patient receiving peritoneal dialysis after treatment of ovarian cancer]. / Pacjentka dializowana otrzewnowo, po leczeniu nowotworu zlosliwego jajnika.

Peritoneal dialysis is one of the three available options for renal replacement therapy. This method of treatment of end-stage renal disease gives patients relatively high sense of independence and control over their disease, especially in comparison with hemodialysis, and therefore is often preferable method for young individuals wishing to lead an active lifestyle. We present a case of 22 year old female patient with stage 5 of chronic kidney disease, which is a consequence of multi-agent chemotherapy for endo-dermal sinus tumor of the right ovary (diagnosed at the age of 13). Particularly important in the context of treating our patient with peritoneal dialysis is the fact of confirmed metastases into the peritoneum, which was the reason for the use of chemotherapy reserved for high-risk patients (ifosfamide + etoposide + cisplatin). The selected program of chemotherapy provided effective eradication of cancer, but a side effect of treatment was renal tubular damage. In the period from 03.2006 to 05.2007 our patient required hemodialysis (with gradually reduce dose of dialysis), at a later time to 12.2011 patient did not require renal replacement therapy (stable renal function were observed at the stage 4 of chronic kidney disease), but in 12.2011 resumption of dialysis was necessary and the patient, in accordance with her selection, is receiving peritoneal dialysis. Qualification of our patient for treatment with peritoneal dialysis was associated with reasonable concern about the ability to provide acceptable adequacy of dialysis. Apprehensions proved to be unfounded, the clinical observation of the patient presents proper ratios of dialysis adequacy. Our patient was also qualified for renal transplantation.

Malposition of Central Venous Catheter into Coronary Sinus throughout the Persistent Left Superior Vena Cava and Other Complications Related to Catheterization.

This case concentrates on the persistent left superior vena cava (PLSVC), a rare vascular anomaly which contributes to central venous catheter (CVC) misplacement. A 72-year-old woman with renal insufficiency presented to the hospital with recurrent bleeding from her permanent CVC device placed in the right common jugular vein. An initial attempt to replace the device was unsuccessful, necessitating the placement of a secondary catheter in the left jugular vein. Shortly after the procedure, the patient developed swelling of the face and neck. Further diagnostic imaging, including a chest radiograph and computed tomography (CT), revealed CVC misplacement in the PLSVC and coronary sinus, thrombosis of the common jugular vein, and a posterior mediastinal hematoma. Conservative therapy of the mediastinal hematoma was implemented and proved effective in this case. A temporary CVC was inserted into the left femoral vein. Two months later, the catheter underwent further dysfunction and a decision was made to place a long-term permanent CVC via the right femoral vein. The patient is currently awaiting an arteriovenous fistula for dialysis use. This case emphasizes the importance of radiological techniques for CVC procedural placement, as well as the detection of congenital abnormalities. Providers regularly placing CVCs should have an in-depth knowledge of the possible complications and potential anatomical variations, especially as seen in high-risk patients.

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.

Presence of retained calcified fibrin sheath after central venous catheter removal: A systematic literature review.

Central venous catheters (CVC) are used in many clinical settings for a variety of indications. We performed a systematic literature review concerning case reports of retained calcified fibrin sheaths after dialysis CVC removal. The aim of our study was to systematize the knowledge regarding clinical management of this phenomenon, placing special emphasis on diagnostic radiological features in different imaging modalities, including chest radiography, echocardiography, computed tomography, and magnetic resonance imaging. We discuss the most common risk factors associated with this CVC complication. In our review, we found eight cases of hemodialysis patients. The most common risk factors associated with calcified fibrin sheath formation in the analyzed cases were pro-thrombotic and pro-calcification factors related to patient comorbidities, and prolonged catheter dwell time. Differentiating between a calcified fibrin sheath (present in about 6% of patients with long-term indwelling CVC as diagnosed by computed tomography) and a retained catheter tip can be challenging. The initial diagnosis based on imaging methods was incorrect in most of the analyzed cases. This suggests that some cases of retained fibrin sheaths may remain undetected or misinterpreted. This is important in patients with known pro-thrombotic and pro-calcification risk factors and prolonged catheter dwell time. Therefore, implementation of preventive strategies, familiarity with radiological findings of this phenomenon, comparison with previous imaging studies, and an overall comprehensive assessment with clinical data is imperative.

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.

POEMS Syndrome: Real World Experience in Diagnosis and Systemic Therapy - 108 Patients Multicenter Analysis.

POEMS syndrome, a rare plasma cell disorder, is challenging both in the diagnostic and therapeutic management. We present real word retrospective analysis of 108 cases analyzing clinical features and therapeutic modes. We compare our results with the available literature. This is the first description with such wide use of proteasome inhibitors in first line treatment. POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare and challenging plasma cell disorder, both in the diagnostic and therapeutic management of the disease. Currently, the literature on POEMS is sparse with most evidence being case reports and small case studies. We present a retrospective real world experience of 108 patients with POEMS. We analyzed the clinical features and therapeutic interventions. Regarding clinical features, our findings demonstrated that skin lesions, thrombocythemia and polycythemia were present less frequently than reported previously. Regarding clinical interventions, this is one of the largest analyses of front line treatment in POEMS and the first one to include frequent utilization of proteasome inhibitors (37%). Bortezomib monotherapy was the most effective therapy achieving complete remission/very good partial remissions (CR/VGPR) in 69% of patients. Thirty percent of patients proceeded to planned autologous stem cell transplant (ASCT) as part of the front-line treatment resulting in statistically superior progression-free (PFS) and overall survival (OS) compared to non-ASCT treated patients (P= .003). In multivariate analysis, anemia, thrombocytopenia, and as age over 60 were associated with a negative impact on patient outcomes.

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.