Newly developed cardiovascular risk factors in rheumatoid arthritis patients initiating biologic treatment.

Introduction: Rheumatoid arthritis (RA) is a risk factor (RF) for cardiovascular (CV) disease, a leading cause of mortality in RA patients. Material and methods: Consecutive records of RA patients with high disease activity screened upon biologic therapy initiation were reviewed between January 2001 and 2018. Patients with at least 6-month follow-up and baseline disease activity scores were enrolled (n = 353) and stratified into manifest CV disorder ("overt CVD"), any traditional CV risk factor ("atCVrisk") and no CV risk factor ("vlCVrisk") groups. Results: Overall, mean (SD) patient age was 51.4 (±12.2) years, and 291 (82.4%) subjects were female. Median follow-up was 41.9 (IQR 18.6, 80) months. Overall, 89 (25.2%) individuals developed at least one new CV RF, of which 65 (18.4%) acquired one and 24 (6.8%) two or more. Incident lipid disorders (42, 11.9%), followed by hypertension (14, 4%), atrial fibrillation (17, 4.8%) and venous thromboembolism (VTE) (16, 4.5%), were common. Incident major adverse cardiac events (MACE) were not reported in the vlCVrisk group, in contrast to atCVrisk (n = 8, 4.2%) or overt CVD (n = 4, 18.2%). Age was a significant predictor of incident CV risk factor (HR 1.04, 95% CI: 1.02-1.07; p < 0.01). In age-adjusted analyses, only baseline body mass index (BMI) (HR 1.11, 95% CI: 1.04-1.18; p < 0.01), but not ever smoking (p = 0.93), male sex (p = 0.26), positive RF (p = 0.24), positive ACPA (p = 0.90), or baseline disease activity (p = 0.19), were independent predictor of incident CV risk factors. Conclusions: Patients with RA initiating biologics should be screened for cardiometabolic risk factors, especially at an older age. The presence of at least one risk factor may be linked to a worse long-term prognosis.

Multicenter evaluation of tofacitinib retention and safety in rheumatoid arthritis - why cardiovascular risk factors do not equate to overt risk.

Introduction: This multicenter, real-world, retrospective cohort study aimed to assess the effectiveness and safety of tofacitinib (TOFA) in rheumatoid arthritis (RA). Material and methods: Two hundred nine patients with active RA treated with TOFA, unresponsive to at least 2 conventional synthetic disease-modifying drugs, were recruited. Clinical characteristics were extracted from an electronic registry and supplemented with manual chart review and data linkage with ambulatory care. Drug retention and reasons for discontinuation were evaluated. Results: Median (interquartile range) follow-up in the whole sample was 16.9 (5.93-31.7) months. Mean (standard deviation) age was 51.44 (±11.84) years, with female predominance (n = 168, 80.4%). Only 30 patients (14.4%) had no pre-existing traditional cardiovascular (CV) risk factor at TOFA initiation. Tofacitinib retention rates were high, with median survival estimated at 89.3% at 6 months, 82.4% at 12 months, and 60.4% at 24 months. Ineffectiveness was the primary cause of discontinuation (n = 50). The rate of adverse events (AEs) was relatively low, with lipid abnormalities, blood count alterations, and infectious events among the most common. No major adverse CV event was reported. The incidence rate of AEs necessitating treatment switch was 60.34 (95% CI: 37-92) per 1,000 person-years of follow-up. Presence of multiple (> 3) CV risk factors was associated with lower odds of TOFA retention and treatment effectiveness. Conclusions: Tofacitinib demonstrated high retention rates and a favorable safety profile in RA patients, including those with traditional CV risk factors. Tofacitinib may be a valuable treatment option for RA patients when combined with individualized CV risk management. Further studies are warranted to explore the long-term effects of TOFA and its CV impact in larger populations.

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.

Charting the Etanercept Journey: Tracing Cost Dynamics in Poland's Off-Patent Market from Reference Drug Rivalry to Biosimilar Monopoly.

OBJECTIVES: To evaluate the pricing of etanercept (ETN) reference and biosimilar drugs in a changing competitive to monopolized market. METHODS: We conducted a comprehensive, retrospective analysis of ETN market competition, specifically changes in tender price based on shifts in market monopoly, including the effects on cost evolution, in the off-patent market in Poland. We included a total of 473 tenders for ETN purchase in dedicated biologic drug reimbursement programs, covering both pre-filled syringes and automatic injectors. This study covers the timeframe from November 2017 to December 2023, throughout which we evaluated a unique setting of ETN market re-monopolization from the perspective of payer, hospital and patient benefits resulting from changing cost calculations. RESULTS: Between 2017 and 2022, Erelzi was recorded as having the largest total tender volume (59%), with a mean price [per ETN daily defined dose (DDD)] of €7.28, followed by Enbrel (31%, €8.34) and Benepali (10%, €9.45), respectively. Over the last 6 months of waning market competition, the mean price for winning bids was estimated at €5.69. After market re-monopolization by an ETN biosimilar, the mean price of winning bids increased to €8.09, and continued to increase (€9.71) in the last 6 months of available follow-up. In contrast to the competitive era, no significant relationship between tender volume and winning price was recorded after re-monopolization. In the most recent tenders, mean ETN prices increased up to €15.82, nearly tripling the lowest prices of the competitive market period. In the early re-monopolization market, mean annual treatment cost per patient is estimated at over €3800, which exceeds therapy costs in the prior competitive market years, and is expected to increase to over €6200 based on the most recent tenders. On a healthcare system level, this corresponds to over €3.42 million excess costs due to market monopoly. Higher ETN prices resulted in downstream failure of regulatory incentives to promote affordable biologics. Due to higher pricing, hospitals lost over an estimated €2.52 million, with possible risk of treatment restrictions. For the same reason, the public payer achieved comparable savings, allowing for partial coverage of higher reimbursement expenses. CONCLUSIONS: This nation-level scenario of market re-monopolization by a biosimilar drug confirms net loss and excess costs for the healthcare payer, as can be expected from economic theory. The upwards drug repricing and restriction of treatment availability occurs much more rapidly than the decrement in a period of market competition.

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.

Learned Irrelevance, Perseveration, and Cognitive Aging: A Cross-Sectional Study of Cognitively Unimpaired Older Adults.

The effect of natural aging on physiologic mechanisms that regulate attentional set-shifting represents an area of high interest in the study of cognitive function. In visual discrimination learning, reward contingency changes in categorization tasks impact individual performance, which is constrained by attention-shifting costs. Perseveration (PE) and learned irrelevance (LI) are viewed as two different mechanisms that shape responses to stimuli, which are predicated on the shift in stimulus form. To date, only studies examining patients with Parkinson's disease have provided some insight into the relationship between individual age and performance in PE and LI tasks. We enrolled 60 healthy individuals (mean [SD] age, 63.0 [12.6]) without a history of dementia, a cerebrovascular incident, or a neurodegenerative disease. No association was observed between crystallized intelligence or verbal fluency scores and reaction time in both PE (r = 0.074, p = 0.603; r = -0.124, p = 0.346) and LI (r = -0.076, p = 0.562; r = -0.081, p = 0.536) task conditions, respectively. In contrast, a statistically significant linear relationship was observed between age and reaction time (RT) for PE (r = 0.259, p = 0.046) but not for LI (r = 0.226, p = 0.083). No significant linear relationship was observed for changing RTs in PE and LI (r = 0.209, p = 0.110). The present study is the first report that provides a descriptive overview of age-related differences in PE and LI in a sample of cognitively unimpaired middle- to older-aged adults.

Circulating Angiogenic Factors and Ischemic Diabetic Foot Syndrome Advancement-A Pilot Study.

Despite clear evidence of inadequate angiogenesis in ischemic diabetic foot syndrome (DFS) pathogenesis, angiogenic factor level changes in patients with ischemic DFS remain inconsistent. This study aimed to assess circulating angiogenic factors concerning ischemic DFS advancement and describe their relationships with patients' clinical characteristics, microvascular parameters, and diabetic control. The study included 41 patients with ischemic DFS (67.3 (8.84) years; 82.9% males). Angiogenic processes were assessed by identifying circulating concentrations of five pro- and two anti-angiogenic factors. We found that penetrating ulcers were related to a significantly higher FGF-2 level (8.86 (5.29) vs. 5.23 (4.17) pg/mL, p = 0.02). Moreover, plasma FGF-2 showed a significant correlation with the SINBAD score (r = 0.32, p = 0.04), platelet count (r = 0.43, p < 0.01), white cell count (r = 0.42, p < 0.01), and age (r = -0.35, p = 0.03). We did not observe any significant linear relationship between the studied biomarkers and microcirculatory parameters, nor for glycemic control. In a univariate analysis using logistic regression, an increase in plasma FGF-2 was tied to greater odds of high-grade ulcers (OR 1.16; 95% CI 1.02-1.38, p = 0.043). This suggests that circulating FGF-2 may serve as a potential biomarker for predicting DFU advancement and progression. It is necessary to conduct further studies with follow-up observations to confirm this hypothesis.

Impact of Blood-Flow-Restricted Training on Arterial Functions and Angiogenesis-A Systematic Review with Meta-Analysis.

Despite growing evidence of the significant influence of blood-flow-restricted (BFR) training on different body functions, its impact on the vascular system, especially the arteries, is controversial. Therefore, the objective of our study was to analyze how BFR exercise, compared to other types of exercise without the restriction of blood flow, influences arterial functions and angiogenesis in adults. Studies comparing the effect of BFR versus non-BFR training on arterial parameters were divided into three categories: endothelial function, angiogenesis, and other vasculature functions. The search was based on Cochrane Library, PubMed®, and Embase, and 38 studies were included. The meta-analysis revealed a more significant improvement in flow-mediated dilatation (FMD) (p = 0.002) and the production of the primary angiogenesis biomarker vascular endothelial growth factor (VEGF) (p = 0.009) after BFR compared to non-BFR training (p = 0.002). The analysis of the pulse wave velocity, ankle-brachial index, systolic blood pressure, and heart rate did not show significant differences in changes between BFR and non-BFR training. The other parameters examined did not have sufficient data to be included in the meta-analysis. The results obtained present trends that suggest significant impacts of BFR training on endothelial functions and angiogenesis. There is still a lack of multicenter randomized clinical trials including many participants, and such studies are necessary to confirm the advantage of BFR over non-BFR activity.

Angiogenic and Microvascular Status Alterations after Endovascular Revascularization of Lower Limb Arteries among Patients with Diabetic Foot Syndrome: A Prospective 12-Month Follow-Up Study.

Peripheral arterial disease (PAD)-induced ischemia is an important component of diabetic foot syndrome (DFS). The results of revascularization of the lower extremity arteries (including percutaneous transluminal angioplasty [PTA]) do not always give satisfactory long-term results, which is due to many factors. The aim of the study was to investigate the alterations in selected circulating angiogenic factors and microcirculation parameters in 41 patients with DFS following PTA and analyze their relationships with clinical outcomes during 1-year follow-up. Our study revealed a general decrease in pro-angiogenic factor levels after PTA and their subsequent stabilization during subsequent observation. The results indicated a significant association between plasma circulating FGF-2 level and poor outcomes (including the incidence of restenosis/reocclusion of treated arteries) during 12 months of observation. The perioperative changes in FGF-2 showed a significant association with LDF alterations after PTA. Follow-up 1-3 months post-intervention showed a tendency towards elevated TcpO2, VEGF-A, and VEGF-R2 levels in patients free from adverse events. These results may provide a basis for further research on the potential use of selected circulating angiogenic factors for monitoring the treatment of patients with DFS following PTA.

Drug Retention and Safety of Secukinumab in a Real-World Cohort of Ankylosing Spondylitis and Psoriatic Arthritis Patients.

Real-life data that support effectiveness of secukinumab (SEC), an interleukin 17A inhibitor, in Poland are few. We aimed to evaluate SEC effectiveness based on drug retention and safety measures reported in electronic medical records (EMRs) of patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS) from two tertiary-care centers in the region of Lesser Poland. A total one-hundred eighty seven (127 PsA and 60 AS) first (n = 112), second (n = 59) and third-line SEC users were enrolled. The mean (SD) age of the sample was 45.7 (12.9), and 48% were male. All patients were classified with active and severe disease prior to initiation. Administrative delays for SEC users last a median 2 weeks. Median delay from symptom onset to diagnosis was 4 years (IQR 8), and differed by predominant disease subtype. The inefficacy rate was 10.7% and 18.6% for first and second-line users with median (IQR) drug maintenance estimated at 1.22 years (1.46) and 1.51 (1.38), respectively. First-year drug loss defined as drug switch due to inefficacy or adverse event was rare, with median estimates of 0.91 (95% CI; 0.85, 0.97) and 0.86 (95% CI; 0.77, 0.95) for first and second-line, respectively.

New Markers of Renal Failure in Multiple Myeloma and Monoclonal Gammopathies.

* Correspondence: kasiajanda@op [...].

Interplay of nitric oxide metabolites and markers of endothelial injury, inflammation, and vascular disease in the spectrum of advanced chronic kidney disease.

BACKGROUND: Chronic kidney disease is linked to cardiovascular morbidity; therefore, relevant biomarkers are widely investigated. AIMS: We aimed to assess the relationship between nitric oxide (as measured by its metabolites, NOx), a key endothelial molecule, with markers of endothelial dysfunction, inflammation, antioxidant status, and mineral disorders as well as histologically assessed vascular calcification in uremic and hemodialysis patients with chronic kidney disease. METHODS: Plasma and serum samples were obtained from 62 patients with renal failure. NOx was assessed by the Griess method, while the other biomarkers were measured by the immunoenzymatic assay. Morphological analysis of arterial calcification was performed in a blinded, semiquantitative manner. Common carotid intima­media thickness and atherosclerotic plaques were assessed by ultrasonography. RESULTS: In the simple analysis, NOx levels correlated positively with the parameters of renal function, mineral metabolism, endothelial injury, and inflammation. NOx predicted carotid intima­media thickness in simple (P = 0.014) and multiple analysis (P = 0.036) adjusted for the Framingham risk score, C­reactive protein, serum creatinine, and parathormone. The occurrence of atherosclerotic plaques in the common carotid artery was correlated with higher NOx concentrations (P = 0.021). CONCLUSIONS: In chronic renal failure, NOx is associated with surrogate markers of atherosclerosis, even after adjustment for traditional cardiovascular risk factors, inflammation, and renal function, but not with the presence or grade of medial arterial calcification. Endothelial injury, inflammation, and mineral metabolism markers are associated with NOx levels, though a causal link requires further study.

Physician Adherence to Treat-to-Target and Practice Guidelines in Rheumatoid Arthritis.

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.