Lactate level is an independent predictor of mortality in patients with hematologic malignancy receiving urgent chemotherapy in intensive care unit.

BACKGROUND: Intensive care unit (ICU) survival of cancer patients has improved. Urgent chemotherapy has become feasible in critically ill patients with specific organ dysfunction due to hematological malignancies. OBJECTIVE: The aim of the study was to assess ICU mortality rates and the factors associated with mortality in patients with hematologic malignancies receiving urgent chemotherapy in the ICU. METHODS: We retrospectively included all patients admitted to the ICU who received chemotherapy due to hematologic malignancy in 2012-2022. RESULTS: Of the 129 patients undergoing chemotherapy in the ICU, 50 (38.7 %) died during the ICU follow-up. The following conditions were significantly more common among nonsurvivors: presence of infection at the time of ICU admission (p < 0.001), the requirement for mechanical ventilation during ICU stay (p < 0.001), the need for noninvasive mechanical ventilation during ICU stay (p = 0.014), vasopressor support (p < 0.001), and sepsis (p < 0.001). Logistic regression analysis revealed that among laboratory parameters on ICU admission, lactate (p = 0.008), albumin (p = 0.022), C-reactive protein (p = 0.046), baseline sequential organ failure assessment (SOFA) score (p < 0.001), newly developed heart failure (p = 0.006), and the requirement for vasopressor agents during ICU stay (p < 0.001) significantly influenced the risk of mortality in the univariate analysis. The multivariate analysis revealed lactate levels (p = 0.047) on ICU admission as an independent predictor of mortality. CONCLUSION: The development of heart failure and lactate levels on admission were the main predictors of mortality. Additionally, higher SOFA scores revealed that illness severity was closely associated with mortality. Future studies should focus on strategies to further reduce these risks and achieve the best outcomes for these patients.

Evaluation of sarcopenia and phase angle in elderly patients with Parkinson's Disease.

PURPOSE: To investigate sarcopenia and related factors and to determine the disease-specific phase angle (PhA) cut-off score in detecting sarcopenia in elderly patients with Parkinson's Disease (PD). METHODS: This cross-sectional study was conducted with 89 participants. The Mini-Nutritional Assessment (MNA), the Eating Attitude Test-10 (EAT-10), the Physical Activity Scale for The Elderly (PASE) questionnaire and the Hoehn-Yahr scale have been used. Additionally, anthropometric measurements were performed. The diagnosis of sarcopenia was based on the new consensus published by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). PhA has been performed by Bioelectrical Impedance Analysis (BIA) with Tanita MC 780®. RESULTS: The mean age was of the participants 68.9 ± 6.4 years, and 57.3% were male. The prevalence of sarcopenia was 12.3%. PhA, malnutrition, age, disease severity, low calf circumference (CC), low body mass index (BMI), the difference between the pre-diagnosis and current weight loss, dopaminergic treatment, and low PASE score were associated with sarcopenia. The cut-off value of the PhA in terms of the ability to identify sarcopenia was <4.5o with a sensitivity of 53.3% and a specificity of 93.2% (p = 0.001). When we grouped the PhA of the patients according to this cut-off score, it was seen that 14.6% of them were sarcopenic. Age, disease severity, PASE score and hand grip strength were significantly related to both sarcopenia and PhA. CONCLUSION: It is important to be aware of sarcopenia and related factors at an early stage in Parkinson's patients. Because of disease-related symptoms, it may be more appropriate to use a disease-specific PhA cut-off score in the definition of sarcopenia.

Impact of the empirical therapy timing on the clinical progress of septic shock patients.

AIM: To evaluate the effect of timing of antimicrobial therapy on clinical progress of patients with septic shock. MATERIALS AND METHOD: We included 204 adult patients diagnosed with septic shock according to Sepsis-3 criteria between March 2016 and April 2021. One-month survival was evaluated using univariate and logistic regression analysis. RESULTS: Antibiotic treatment was initiated within 1 h of the vasopressors in 26.4 % of patients. One-month mortality did not differ significantly between patients with and without empirical therapy coverage on etiological agents. Univariate factors that significantly affected one-month survival were starting antibiotics at the first hour, the unit where the case was diagnosed with septic shock, SOFA scores, qSOFA scores, and lactate level. In multivariate analysis, diagnosis of septic shock in the Emergency Service, SOFA score ≥11, qSOFA score of three and lactate level ≥4 were significantly associated with one-month mortality. CONCLUSION: Training programs should be designed to increase the awareness of septic shock diagnosis and treatment in the Emergency Service and other hospital units. Additionally, electronic patient files should have warning systems for earlier diagnosis and consultation.

Association between vitamin D receptor gene FokI polymorphism and mortality in patients with sepsis.

BACKGROUND: Sepsis is life-threatening organ dysfunction as a result of the host's dysregulated immune response to infection. The vitamin D receptor (VDR) gene FokI polymorphism influences immune cell behavior. In the present study, we aimed to investigate the association between VDR FokI polymorphism and mortality in sepsis and non-sepsis patients in the intensive care unit (ICU). METHODS AND RESULTS: This is a prospective observational study involving 96 sepsis and 96 non-sepsis patients admitted to the Ege University ICU. VDR FokI polymorphisms were investigated, as well as the relationship between the identified polymorphisms and mortality.  In-hospital mortality was 27.1% in the sepsis group and 8.33% in the non-sepsis group (p = 0.001). The frequencies of VDR FokI TT, TC, and CC genotypes were 8 (8.33%), 48 (50.0%), and 40 (41.7%) in the sepsis group, and 11 (11.5%), 42 (43.8%), and 43 (44.8%) in the non-sepsis group, respectively (p = 0.612). In the sepsis group, the frequencies of Fokl TT, TC, and CC genotypes did not differ significantly between survivors and non-survivors. However, homozygous C allele carriers had lower overall mortality (p = 0.047). CONCLUSION: The VDR FokI polymorphism, particularly the CC genotype, appears to be associated with lower mortality in ICU patients.

Performance Evaluation of Machine Learning Algorithms for Sarcopenia Diagnosis in Older Adults.

BACKGROUND: Sarcopenia is a progressive and generalized skeletal muscle disorder. Early diagnosis is necessary to reduce the adverse effects and consequences of sarcopenia, which can help prevent and manage it in a timely manner. The aim of this study was to identify the important risk factors for sarcopenia diagnosis and compare the performance of machine learning (ML) algorithms in the early detection of potential sarcopenia. METHODS: A cross-sectional design was employed for this study, involving 160 participants aged 65 years and over who resided in a community. ML algorithms were applied by selecting 11 features-sex, age, BMI, presence of hypertension, presence of diabetes mellitus, SARC-F score, MNA score, calf circumference (CC), gait speed, handgrip strength (HS), and mid-upper arm circumference (MUAC)-from a pool of 107 clinical variables. The results of the three best-performing algorithms were presented. RESULTS: The highest accuracy values were achieved by the ALL (male + female) model using LightGBM (0.931), random forest (RF; 0.927), and XGBoost (0.922) algorithms. In the female model, the support vector machine (SVM; 0.939), RF (0.923), and k-nearest neighbors (KNN; 0.917) algorithms performed the best. Regarding variable importance in the ALL model, the last HS, sex, BMI, and MUAC variables had the highest values. In the female model, these variables were HS, age, MUAC, and BMI, respectively. CONCLUSIONS: Machine learning algorithms have the ability to extract valuable insights from data structures, enabling accurate predictions for the early detection of sarcopenia. These predictions can assist clinicians in the context of predictive, preventive, and personalized medicine (PPPM).

Ertapenem plus meropenem combination treatment in carbapenem-resistant Klebsiella pneumoniae bacteremia: an analysis of 53 cases.

Herein, we aimed to describe the outcomes of patients with blood stream infections due to carbapenem-resistant Klebsiella pneumoniae (CR-Kp) who received ertapenem plus meropenem combination treatment (EMCT). A total of 53 patients with culture proven CR-Kp bacteremia treated with ertapenem + meropenem were included. The patients with secondary bacteremia due to urinary tract infection exhibited a significantly lower 1-month mortality (OMM), particularly in those with microbiological eradication and those with end-of-treatment success. Salvage EMCT resulted in 49% 1-month survival.

Biomarker diversity in increased inflammation: Secondary hemophagocytic syndrome vs. systemic inflammatory response syndrome.

INTRODUCTION: Secondary hemophagocytic syndrome (HPS) and systemic inflammatory response syndrome (SIRS) share similar clinical findings as a result of hyperinflammation. Due to high mortality rates in HPS; it is critical to diagnose promptly. Thus, this study aimed to evaluate the diagnostic and prognostic significance of inflammatory markers in these two increased inflammatory states. METHODS: We conducted a prospective observational study including patients hospitalized in the intensive care unit of the Internal Medicine Department of Ege University Hospital. RESULTS: Thirty-three patients with HPS and 46 patients with SIRS were evaluated. Serum ferritin and sIL-2r levels were significantly higher in the HPS group than in the SIRS group, as expected. Receiver operating curve (ROC) analysis showed that the optimal cutoff for ferritin to distinguish HPS from SIRS was 1703 µg/L (sensitivity: 75%, specificity: 94.1%, area under the curve (AUC): 0.871, p < 0.001), and that for sIL-2r was 5888 U/ml (sensitivity: 45.5%, specificity: 89.1%, AUC: 0.698, and p = 0.001). Temporal changes (Δ) in ferritin were determined as a mortality predictor. When evaluated in terms of prognostic significance in ROC analysis, a decrease in ferritin of less than 38% was the cutoff value (sensitivity: 92.3%, specificity: 76.9%, AUC: 0.888, and p < 0.001), in mortality. Contrarily, neither baseline nor temporal change in sIL-2r did not achieve prognostic significance as a mortality predictor. CONCLUSION: In this single-center study, serum ferritin level was found to be a particularly more valuable diagnostic and prognostic marker than sIL-2r in patients with HPS.

Serum estradiol level predicts acute kidney injury in medical intensive care unit patients.

Previous studies have shown that serum estradiol (E2) levels can predict mortality in intensive care unit patients. Our study investigated the predictive role of admission estradiol level on patient mortality and development of acute kidney injury in medical intensive care unit patients with a wide range of diagnoses. We conducted a prospective cohort study using serum samples from hospitalized patients in medical, cardiac, and pulmonary intensive care units at the Ege University Hospital within 6 months. Serum estradiol levels from 118 adult patients were collected within 48 h of hospitalization. Receiver operating curves and multiple logistic regression analyses were performed to investigate its relationship with acute kidney injury development and mortality. Serum estradiol levels were significantly higher in non-survivor patients than in survivor patients [85 (19-560) pg/mL vs. 32 (3-262) pg/mL, p < 0.001]. Admission estradiol levels were significantly higher in patients with AKI on admission than in patients with chronic kidney disease (p = 0.002) and normal renal function (p = 0.017). Serum E2 levels were higher in patients with renal deterioration during follow-up than patients with stable renal functions [62 (11-560) pg/mL vs. 38 (3-456) pg/mL, p = 0.004]. An admission estradiol level of 52.5 pg/mL predicted follow-up renal deterioration with 63% sensitivity and 74% specificity. A combined (APACHE II-E) score using APACHE II and serum estradiol level predicted overall mortality with 66% sensitivity and 82% specificity. Admission estradiol level is a good marker to predict the development of acute kidney injury and mortality in medical intensive care unit patients.

Carbapenem-resistant Gram-negative pathogens associated with septic shock: a review of 120 cases.

This study aimed to evaluate the influencing variables for outcomes in patients with septic shock having culture-proven carbapenem-resistant Gram-negative pathogens. It included 120 patients (mean age 64.29 ± 1.35 years and 58.3% female). The mean Sequential Organ Failure Assessment score during septic shock diagnosis was found to be 11.22 ± 0.43 and 9 ± 0.79 among the patients with mortality and among the survivors, respectively (P = 0.017). The logistic regression analysis showed that empirical treatment as mono Gram-negative bacteria-oriented antibiotic therapy (P = 0.016, odds ratio (OR) = 17.730, 95% confidence interval (CI): 1.728-182.691), Charlson Comorbidity Index >2 (P = 0.032, OR = 7.312, 95% CI: 5.7-18.3), and systemic inflammatory response syndrome score 3 or 4 during septic shock diagnosis (P = 0.014, OR = 5.675, 95% CI: 1.424-22.619) were found as independent risk factors for day 30 mortality. Despite early diagnosis and effective management of patients with septic shock, the mortality rates are quite high in CRGNP-infected patients.

Mortal Interaction Between Hemophagocytic Syndrome and Newly Developed Heart Failure. / Interação Letal entre Síndrome Hemofagocítica e Insuficiência Cardíaca Recentemente Desenvolvida.

BACKGROUND: Hemophagocytic syndrome (HPS) ia s devastating hyperinflammatory syndrome. Heart failure (HF) with preserved ejection fraction (HFpEF) status is closely correlated with increased inflammation, both systemic and intramyocardial. OBJECTIVES: This study sought to determine mortality predictors and reliable follow-up parameters in HPS that developed HFpEF during the clinical course. METHOD: Thirty-nine patients, diagnosed as HPS, according to HLH 2004 diagnostic criteria, with an HScore of ≥169 and proven bone marrow aspiration or biopsy, were recruited retrospectively. Both traditional, serum C-reactive protein, albumin and ferritin levels with lymphocyte, and platelet counts, as well as non-traditional risk factors, neutrophil-to-lymphocyte count (NLR), monocyte-to-lymphocyte count (MLR), mean platelet volume (MPV), and N-Terminal pro-brain natriuretic peptide (NTproBNP), were investigated retrospectively. The relationship between time-changed laboratory values both among themselves and with mortality. The overall significance level was set at 5%. RESULTS: This study showed that temporal change of cardiothoracic ratio (CTR), serum NTproBNP, ferritin, CRP, and albumin levels were detected as mortality predictors (p<0.05, for all) in the univariate analysis. Lymphocyte and platelet counts with NLR and MPV values were also significant (p<0.05). The relationship between NT-proBNP and increased systemic inflammatory markers proved to be significant. In addition to traditional risk factors, serum ferritin levels, NLR, MLR, and MPV levels also proved to be significantly correlated with each other. CONCLUSION: Accompanied by reliable follow-up parameters, rapid diagnosis and aggressive anti-inflammatory treatment with tight volume control can be life-saving in HPS patients who suffer from HFpEF. Close monitoring of inflammation may predict the outcome of patients suffering from HFpEF.

FUNDAMENTO: A síndrome hemofagocítica (SHF) é uma síndrome hiperinflamatória debilitante. O status da insuficiência cardíaca (IC) com fração de ejeção preservada (ICFEP) está intimamente relacionado ao aumento da inflamação sistêmica e intramiocárdica. OBJETIVOS: este estudo pretende determinar os preditores de mortalidade e os parâmetros de monitoramento confiáveis nos casos de SHF que desenvolveram a ICFEP durante seu curso clínico. MÉTODOS: Trinta e nove pacientes, diagnosticados com SHF de acordo com os critérios diagnósticos do estudo HLH 2004 com Hscore ≥169, e com aspiração ou biópsia de medula óssea comprovada, foram recrutados retrospectivamente. Foram investigados retrospectivamente os fatores de risco tradicionais, como proteína C reativa sérica, níveis de albumina e ferritina com contagens de linfócitos e plaquetas, e fatores não tradicionais, como relação neutrófilolinfócito (NLR), relação linfócito-monócito (MLR), volume plaquetário médio (MPV) e pró-peptídeo natriurético cerebral N-terminal (NTproBNP). Analisou-se a relação entre os valores laboratoriais alterados ao longo do tempo entre si e com a mortalidade. O nível de significância geral foi de 5%. RESULTADOS: Foi demonstrado que a alteração temporal dos níveis de índice cardiotorácico (ICT), NTproBNP sérico, ferritina, PCR e albumina foram detectados como sendo preditores de mortalidade (p<0,05, para todos) em análise univariada. As contagens de linfócitos e plaquetas com valores de NLR e MPV também foram significativos (p<0,05). A relação entre NT-proBNP e o aumento dos marcadores inflamatórios sistêmicos também foi considerada significativa. Além de fatores de risco tradicionais, os níveis de ferritina sérica, e os níveis de NLR, MLR e MPV foram considerados significativamente correlacionados entre si. CONCLUSÃO: Acompanhado de parâmetros de monitoramento confiáveis, o diagnóstico rápido e o tratamento antiinflamatório agressivo com controle rígido de volume podem salvar vidas de pacientes com SHF que sofrem de complicações por ICFEP. O monitoramento rígido da inflamação pode prever o resultado do paciente que sofre de ICFEP.

Interação Letal entre Síndrome Hemofagocítica e Insuficiência Cardíaca Recentemente Desenvolvida / Mortal Interaction Between Hemophagocytic Syndrome and Newly Developed Heart Failure

Resumo Fundamento: A síndrome hemofagocítica (SHF) é uma síndrome hiperinflamatória debilitante. O status da insuficiência cardíaca (IC) com fração de ejeção preservada (ICFEP) está intimamente relacionado ao aumento da inflamação sistêmica e intramiocárdica. Objetivos: este estudo pretende determinar os preditores de mortalidade e os parâmetros de monitoramento confiáveis nos casos de SHF que desenvolveram a ICFEP durante seu curso clínico. Métodos: Trinta e nove pacientes, diagnosticados com SHF de acordo com os critérios diagnósticos do estudo HLH 2004 com Hscore ≥169, e com aspiração ou biópsia de medula óssea comprovada, foram recrutados retrospectivamente. Foram investigados retrospectivamente os fatores de risco tradicionais, como proteína C reativa sérica, níveis de albumina e ferritina com contagens de linfócitos e plaquetas, e fatores não tradicionais, como relação neutrófilolinfócito (NLR), relação linfócito-monócito (MLR), volume plaquetário médio (MPV) e pró-peptídeo natriurético cerebral N-terminal (NTproBNP). Analisou-se a relação entre os valores laboratoriais alterados ao longo do tempo entre si e com a mortalidade. O nível de significância geral foi de 5%. Resultados: Foi demonstrado que a alteração temporal dos níveis de índice cardiotorácico (ICT), NTproBNP sérico, ferritina, PCR e albumina foram detectados como sendo preditores de mortalidade (p<0,05, para todos) em análise univariada. As contagens de linfócitos e plaquetas com valores de NLR e MPV também foram significativos (p<0,05). A relação entre NT-proBNP e o aumento dos marcadores inflamatórios sistêmicos também foi considerada significativa. Além de fatores de risco tradicionais, os níveis de ferritina sérica, e os níveis de NLR, MLR e MPV foram considerados significativamente correlacionados entre si. Conclusão: Acompanhado de parâmetros de monitoramento confiáveis, o diagnóstico rápido e o tratamento antiinflamatório agressivo com controle rígido de volume podem salvar vidas de pacientes com SHF que sofrem de complicações por ICFEP. O monitoramento rígido da inflamação pode prever o resultado do paciente que sofre de ICFEP.

Abstract Background: Hemophagocytic syndrome (HPS) ia s devastating hyperinflammatory syndrome. Heart failure (HF) with preserved ejection fraction (HFpEF) status is closely correlated with increased inflammation, both systemic and intramyocardial. Objectives: This study sought to determine mortality predictors and reliable follow-up parameters in HPS that developed HFpEF during the clinical course. Method: Thirty-nine patients, diagnosed as HPS, according to HLH 2004 diagnostic criteria, with an HScore of ≥169 and proven bone marrow aspiration or biopsy, were recruited retrospectively. Both traditional, serum C-reactive protein, albumin and ferritin levels with lymphocyte, and platelet counts, as well as non-traditional risk factors, neutrophil-to-lymphocyte count (NLR), monocyte-to-lymphocyte count (MLR), mean platelet volume (MPV), and N-Terminal pro-brain natriuretic peptide (NTproBNP), were investigated retrospectively. The relationship between time-changed laboratory values both among themselves and with mortality. The overall significance level was set at 5%. Results: This study showed that temporal change of cardiothoracic ratio (CTR), serum NTproBNP, ferritin, CRP, and albumin levels were detected as mortality predictors (p<0.05, for all) in the univariate analysis. Lymphocyte and platelet counts with NLR and MPV values were also significant (p<0.05). The relationship between NT-proBNP and increased systemic inflammatory markers proved to be significant. In addition to traditional risk factors, serum ferritin levels, NLR, MLR, and MPV levels also proved to be significantly correlated with each other. Conclusion: Accompanied by reliable follow-up parameters, rapid diagnosis and aggressive anti-inflammatory treatment with tight volume control can be life-saving in HPS patients who suffer from HFpEF. Close monitoring of inflammation may predict the outcome of patients suffering from HFpEF.

Prediction of Lipoprotein-Associated Phospholipase A2 and Inflammatory Markers in Subclinical Atherosclerosis in Premature Ovarian Failure Patients.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has been associated with the risk of clinical cardiovascular events. OBJECTIVES: In this study, we aimed to investigate whether the activity of Lp-PLA2 presents a risk for subclinical atherosclerosis in young patients with premature ovarian failure (POF). METHODS: Consecutive patients with clinical and biochemical evidence of naïve POF (n = 66) in January and February 2018 and age-matched healthy controls (n = 73) were enrolled. Lp-PLA2 activity, fibrinogen concentrations, high- sensitivity C-reactive protein (Hs-CRP) levels, and carotid intima-media thickness (CIMT) were measured in all participants. RESULTS: Plasma Lp-PLA2 activity (24.6 ± 3.2 nmol/mL vs. 18.6 ± 1.6 nmol/mL; p < 0.001), mean Hs-CRP (0.620 ± 0.26 mg/dL vs. 0.450 ± 0.28 mg/dL; p < 0.001) and fibrinogen (0.310 ± 0.12 g/dL vs. 0.24 ± 0.11 g/dL; p < 0.001) levels were significantly higher in the patients with POF than control subjects. Mean CIMT was significantly higher in the POF patients than in controls (0.499 ± 0.122 mm vs. 0.323 ± 0.079 mm; p < 0.001). There was a possitive and strong correlation between CIMT and Lp-PLA2 activity (r = 0.548; 95% CI 0.445-0.644; p < 0.001) and a weak correlation Hs-CRP (r = 0.228, 95% CI 0.060-0.398; p = 0.007). In multivariate analysis, Lp-PLA2 activity (B = 1.456, 95% CI 0.908-2.003; p < 0.001) and 17ß-E2 (B = -0.077, 95% CI -0.131 - -0.023; p = 0.006) were found to be independently associated with CIMT (R2 = 0.46). CONCLUSIONS: The present study showed that mean CIMT and Lp-PLA2 activity were significantly higher in POF subjects than control subjects. Moreover, Lp-PLA2 activity and 17ß-E2 levels were independently associated with CIMT in young POF patients.

Glycated hemoglobin predicts overall and cardiovascular mortality in non-diabetic hemodialysis patients.

AIMS: Besides diabetic patients, glycated hemoglobin (HbA1c) levels have been reported to predict mortality in non-diabetics patients. However, the importance of HbA1c levels in non-diabetic hemodialysis patients still remains unknown. Thus, we aimed to prospectively investigate the impact of HbA1c on all-cause and cardiovascular mortality in a large group of prevalent non-diabetic hemodialysis patients. METHODS: HbA1c was measured quarterly in 489 non-diabetic prevalent hemodialysis patients. Overall and cardiovascular mortality were evaluated over a 3 year follow-up. RESULTS: Mean HbA1c level was 4.88 ± 0.46% (3.5 - 6.9%). During the 28.3 ± 10.6 months follow-up period, 67 patients (13.7%) died; 31 from cardiovascular causes. In Kaplan-Meier analysis, patients in the lowest (< 4.69%) and highest HbA1c (> 5.04%) tertiles had poorer overall survival compared to the middle HbA1c tertile (p < 0.001). Adjusted Cox-regression analysis revealed that the highest HbA1c tertile was associated with both overall (HR = 3.60, 95% CI 1.57 - 8.27, p = 0.002) and cardiovascular (HR = 6.66, 95% CI 1.51 - 29.4; p = 0.01) mortality. Also, low HbA1c levels tended to be associated with overall mortality (HR = 2.26, 95% CI 0.96 - 5.29, p = 0.06). CONCLUSION: Upper normal HbA1c levels are independently associated with cardiovascular and overall mortality in non-diabetic hemodialysis patients, whereas lower HbA1c levels are not.

The impact of membrane permeability and dialysate purity on cardiovascular outcomes.

The effects of high-flux dialysis and ultrapure dialysate on survival of hemodialysis patients are incompletely understood. We conducted a randomized controlled trial to investigate the effects of both membrane permeability and dialysate purity on cardiovascular outcomes. We randomly assigned 704 patients on three times per week hemodialysis to either high- or low-flux dialyzers and either ultrapure or standard dialysate using a two-by-two factorial design. The primary outcome was a composite of fatal and nonfatal cardiovascular events during a minimum 3 years follow-up. We did not detect statistically significant differences in the primary outcome between high- and low-flux (HR=0.73, 95% CI=0.49 to 1.08, P=0.12) and between ultrapure and standard dialysate (HR=0.90, 95% CI=0.61 to 1.32, P=0.60). Posthoc analyses suggested that cardiovascular event-free survival was significantly better in the high-flux group compared with the low-flux group for the subgroup with arteriovenous fistulas, which constituted 82% of the study population (adjusted HR=0.61, 95% CI=0.38 to 0.97, P=0.03). Furthermore, high-flux dialysis associated with a lower risk for cardiovascular events among diabetic subjects (adjusted HR=0.49, 95% CI=0.25 to 0.94, P=0.03), and ultrapure dialysate associated with a lower risk for cardiovascular events among subjects with more than 3 years of dialysis (adjusted HR=0.55, 95% CI=0.31 to 0.97, P=0.04). In conclusion, this trial did not detect a difference in cardiovascular event-free survival between flux and dialysate groups. Posthoc analyses suggest that high-flux hemodialysis may benefit patients with an arteriovenous fistula and patients with diabetes and that ultrapure dialysate may benefit patients with longer dialysis vintage.

Neither oxidized nor anti-oxidized low-density lipoprotein level is associated with atherosclerosis or mortality in hemodialysis patients.

It is anticipated that oxidized low-density lipoprotein (oxLDL) and anti-oxLDL are associated with atherosclerosis and mortality. However, data on this issue are controversial and limited. We aimed to investigate the effect of these two markers on the extent and progression of atherosclerosis and mortality in a group of hemodialysis patients. In this prospective observational study with a follow-up of 36 months, 124 hemodialysis patients were studied. Ninety-five patients underwent carotid intima media thickness (CA-IMT) measurement by B-Mode ultrasonography both at baseline and at the end of the study. oxLDL and anti-oxLDL were measured by enzyme-linked immunosorbent assay. The extent and progression of CA-IMT, along with overall and cardiovascular mortality, were assessed. The mean age at baseline was 54.0 ± 14.8 years, 57.3% male and 20% diabetic. The mean oxLDL and anti-oxLDL levels were 8.11 ± 3.16 mU/L and 1.30 ± 0.31, respectively. Baseline mean CA-IMT was 0.82 ± 0.20 mm. Fifteen patients died during a follow-up period of 28.5 ± 6.6 months, 11 from cardiovascular causes. Only oxLDL, not anti-oxLDL, was correlated with the extent of atherosclerosis at baseline. However, both had no role in the progression of atherosclerosis. Also, in unadjusted and adjusted models, both parameters were not associated with overall or cardiovascular mortality. Neither oxLDL nor anti-oxLDL level is associated with the progression of atherosclerosis or mortality in hemodialysis patients.

The effects of mycophenolate mofetil on encapsulated peritoneal sclerosis model in rats.

INTRODUCTION: Encapsulated peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis. We aimed to investigate the effects of mycophenolate mofetil (MMF) treatment in experimental EPS in rats. METHODS: 40 nonuremic Wistar albino rats were divided equally into 4 groups: control rats received 2 ml isotonic saline intraperitoneally daily for 3 weeks without any other treatment. The chlorhexidine gluconate group received intraperitoneally 2 ml/200 g injection of chlorhexidine gluconate and ethanol dissolved in saline for 3 weeks. The resting group received chlorhexidine gluconate (0 - 3rd week) + peritoneal resting (4th - 6th week). The MMF group received chlorhexidine gluconate (0 - 3rd week) + 125 mg/l MMF in drinking water (4th - 6th week). Dialysate cytokine levels, leukocyte count, peritoneal thickness, inflammation and fibroblast activities were evaluated. RESULTS: Although the MMF and resting groups showed beneficial effects on ultrafiltration and D1/D0 glucose compared to the chlorhexidine gluconate group, only MMF treatment improved dialysate TGFß1, VEGF and MCP-1 levels compared to the resting group. Inflammatory activity and vascularity observed in a tissue biopsy, including capillaries number per mm2 of submesothelial area, decreased in the treatment group. CONCLUSIONS: MMF treatment has beneficial effects on EPS via inhibiting inflammation and neovascularisation by reducing dialysate VEGF overexpression.

What does the dialysate level of matrix metalloproteinase 2 tell us?

Long-term peritoneal dialysis leads to encapsulating peritoneal sclerosis (EPS), which is a rare but often fatal complication. The pathogenesis of EPS is characterized by increased inflammation, neoangiogenesis, epithelial-mesenchymal transition (EMT), and fibrosis. Matrix metalloproteinase 2 (MMP-2), which degrades type IV collagen, plays an important role in pathogenesis. Clinical trials report that dialysate levels of MMP-2 can be used as an early marker of peritoneal sclerosis. We aimed to determine the association of MMP-2 with peritoneal function, histology, and effluent cytokine levels in an experimental EPS model in rats. We evaluated data for 71 rats from our various studies using an experimental EPS model. Functional assessment was performed using a 1-hour peritoneal equilibration test with peritoneal dialysis fluid containing 3.86% glucose. Specimens of parietal peritoneum were examined with light microscopy for histologic evaluation. Parietal peritoneum thickness and submesothelial area were measured. Fibrosis, number of vessels, neovascularization, and cellular infiltration were evaluated by one pathologist. The relationships between MMP-2 and other parameters were analyzed using Pearson correlation analysis. Dialysate levels of MMP-2 reflect both functional and histologic change in peritoneum. Levels of MMP-2 were negatively correlated with net ultrafiltration, effluent protein levels, and end (1-hour)-to-initial dialysate concentration ratio of glucose. Cytokines such as vascular endothelial growth factor transforming growth factor beta, monocyte chemotactic protein 1, and osteopontin-which are known to play important roles in neovascularization, inflammation, and EMT leading to fibrosis-were correlated with MMP-2. In peritoneal dialysis patients, MMP-2 levels may be an early marker of EPS and EMT

Body composition monitor measurement technique for the detection of volume status in peritoneal dialysis patients: the effect of abdominal fullness.

BACKGROUND: Bioimpedance spectroscopy (BIS) is used to assess volume status in peritoneal dialysis (PD) patients. However, it is proposed that it may be troubling in patients with abnormal fluid distribution and body geometry. It is not clear whether having an empty abdomen or not interferes with the BIS results and its relation with echocardiographic findings in PD patients. METHODS: Twenty-five prevalent PD patients were enrolled. Echocardiography and body composition analysis using BIS technique (50 frequencies, the Body Composition Monitor, BCM) were performed. Overhydration (OH), extracellular water (ECW) in liters and OH/ECW ratio were used as volume status indices. Differences in volume and echocardiographic findings, in patients with empty and with full abdomen, and their correlations with echocardiographic parameters were investigated. RESULTS: Mean age and PD duration were 61 ± 2.5 years and 42 ± 33 months, respectively. Sixty-four percent were male and 24% were diabetic. Mean left ventricular mass index (LVMi) was 131 ± 43 g/m (,) (2) mean left atrium diameter (LA) was 4.1 ± 0.1 cm, mean left ventricular ejection fraction (EF) was 64 ± 10%. Mean OH in patients with full abdomen were 1.67 ± 1.51 L and 1.68 ± 1.48 L, depending on the inclusion or exclusion of the dialysate volume, respectively. In patients with an empty abdomen, mean OHs were 2.12 ± 1.76 L and 1.91 ± 1.56 L, depending on the inclusion or exclusion of the dialysate volume. BIS measurements with an empty, but not with a full abdomen, was related to the echocardiographic parameters. CONCLUSION: BIS is a reliable method to evaluate volume status in PD patients. BIS performed after peritoneal equilibration test with an empty abdomen, better reflects overhydration and is related to echocardiographic parameters.