Frequency of Deleterious Germline Variants in HER2-Low Breast Cancer Patients Using a Hereditary Multipanel Gene Testing.

HER2-Low is defined as low levels of HER2 expression, based on a score of 1+ on immunohistochemical (IHC) assay or as an IHC score of 2+ and negative results on in situ hybridization (ISH or FISH). They are a heterogeneous population of breast cancers that vary in prognosis and sensitivity to systemic treatments. The frequency and clinical characteristics of pathogenic germline variants (PGVs) in HER2-Low breast cancer (BC) patients is not defined. We analyzed results from patients with BC who underwent multi-gene panel testing (MGPT) (maximum 145 genes) between 2018-2019. We reclassified HER-2 status accordingly. Relationships between the variables of interest were assessed by adopting the proportional regression Cox models. Of a total of 167 BC patients who underwent MGPT, half were hormone-receptor-positive. The median age was 45 years. About two thirds of the patients were in the earlier stage of BC. A total of 57% of the cases were reclassified as HER-2-negative or -Low. PGVs were found in 19% of the patients overall, as follows: seven BRCA1, four BRCA2, two ATM, one ATR, two CFTR, three CHEK2, one FANCA, one MERTK, one MLH1, three MUTYH, one RAD50, three RAD51C, one RECQL4, and two TP53 mutations. In HER2-Low, 26.5% of the patients had PGVs, and in the overall cohort, this was 19.8%. In conclusion, differences in the prevalence of deleterious germline mutations in HER2-Low BC patients compared to non-HER2-Low BC patients were identified. Similar alterations in BRCA were observed in this group of patients compared to the overall cohort. Germline genetic tests should be evaluated in larger cohorts of patients with HER2-Low status to better address the findings.

Chronic kidney disease induces inflammation by increasing Toll-like receptor-4, cytokine and cathelicidin expression in neutrophils and monocytes.

TLR expression in neutrophils and monocytes is associated with increased cytokine synthesis, resulting in increased inflammation. However, the inflammatory pathway related to TLR and cathelicidin expression in these cells from CKD patients is unclear. To evaluate TLR4, cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 expression in neutrophils and monocytes from HD and CKD patients. Blood samples were drawn from 47 CKD and 43 HD patients and 71 age and gender-matched healthy volunteers (CONT). TLR4 was analyzed using flow cytometry. Cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 were analyzed via ELISA.TLR4 expression in neutrophils was higher in HD patients than in stage 3 and 4 CKD patients. In these cells, we observed a positive correlation between TLR4 and cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 levels. In monocytes, TLR4 expression was significantly higher in CKD 3 and 4 groups than in the control and HD groups and positively and negatively correlated with IL-6 and MCP-1 and cathelicidin, respectively. TNF-α, IL-6 and MCP-1 serum levels were higher in HD and CKD patients than in control. Cathelicidin and IL-10 levels were only higher in HD patients. IL-6 serum levels were positively correlated with all cytokines, and cathelicidin was negatively correlated with MCP-1 (r = - 0.35; p < 0.01) and positively correlated with IL-10 (r = 0.37; p = 0.001). These results suggest that a uremic environment induces high TLR4, cathelicidin and cytokine expression and may increase inflammation. Thus, future studies should be conducted to evaluate whether TLR4 and cathelicidin should be targets for anti-inflammatory therapeutic strategies.

Cholecalciferol Supplementation Did Not Change Interleukin-7 and B cell-Activating Factor Levels and CD95 Expression in B lymphocytes in Patients on Dialysis: A Randomized Pilot-Controlled Trial.

BACKGROUND: End-stage renal disease results in B cell lymphopenia and low levels of vitamin D. Since the link between vitamin D deficiency and B lymphocytes dysfunction are not clear in patients with end-stage renal disease, we suggest that vitamin D adequacy and factors related to the homeostasis of these cells should be investigated. B lymphocytes homeostasis is a process mainly regulated signals of grown and death as interleukin (IL)-7, B cell-activating factor (BAFF)/BAFF-receptor and CD95 expression. OBJECTIVE: As vitamin D serum levels were reduced in patients with end stage renal disease and it is associated with human B homeostasis, we evaluated the effect of cholecalciferol supplementation on dialysis. DESIGN: Randomized, double blind clinical trial in dialysis patients with 25OH Vitamin D deficiency for a period of 12 weeks. MAIN OUTCOME MEASURE: In a pilot study, we investigated the effect of cholecalciferol supplementation (100,000 UI once per week or placebo. In vitro, peripheral blood mononuclear cells isolated by Ficoll-Hypaque centrifugation from 12 healthy volunteers were incubated with healthy or uremic serum in the presence or absence of 25 (OH)DC with 5% CO. RESULTS: There was an increase in the serum 25(OH)D level in the cholecalciferol group. No differences were found in BAFF and IL7 levels and CD95 and BAFF-R expression in B lymphocytes from patients on dialysis after cholecalciferol supplementation. Uremic serum induced an increase in the IL-7, BAFF, BAFF-R and CD95 expression compared with the control. However, we observed no effect of incubation of 25(OH)D3 and 1,25(OH)2D3 on the expression of IL-7, BAFF, BAFF-R and CD95 when incubated in the presence of normal or uremic serum. CONCLUSION: Our results suggest that vitamin D is not involved in mechanisms of regulation of differentiation and survival in B lymphocytes. In conclusion, further studies are needed to explore the effects of vitamin D on B lymphocytes to better evaluate the possible impact of vitamin D on humoral response in the CKD population.

Serum Soluble-Fas, Inflammation, and Anemia in Acute Kidney Injury.

Anemia is a common feature in critically ill patients. Serum soluble-Fas (sFas) levels are associated with anemia in chronic kidney disease. It is possible that sFas levels are also associated with anemia in acute kidney injury (AKI) patients. The study aims to investigate the relationship between serum levels of sFas, erythropoietin (Epo), inflammatory cytokines, and hemoglobin (Hb) concentration in critically ill patients with AKI. We studied 72 critically ill patients with AKI (AKI group; n = 53) or without AKI (non-AKI group; n = 19), and 18 healthy volunteers. Serum sFas, Epo, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-10, iron status, and Hb concentration were analyzed in all groups. We also investigated the correlation between these variables in the AKI group. Critically ill patients (AKI and non-AKI groups) had higher serum levels of Epo than healthy volunteers. Hb concentration was lower in the AKI group than in the other groups. Serum sFas, IL-6, TNF-α, and ferritin levels were higher in the AKI group. Hb concentration correlated negatively with serum IL-6 (r = -0.37, P = 0.008), sFas (r = -0.35, P = 0.01), and Epo (r = -0.27, P = 0.04), while serum sFas correlated positively with iron levels (r = 0.36, P = 0.008) and IL-6 (r = 0.28, P = 0.04) in the AKI group. In multivariate analysis, after adjusting for markers of inflammation and iron stores, only serum sFas levels (P = 0.03) correlated negatively with Hb concentration in the AKI group. Serum Epo and inflammatory cytokine levels are elevated in critically ill patients with or without AKI. Serum levels of sFas are elevated and independently associated with anemia in critically ill patients with AKI.

Second opinion for degenerative spinal conditions: an option or a necessity? A prospective observational study.

BACKGROUND: Second opinions may improve quality of patient care. The primary objective of this study was to determine the concordance between first and second diagnoses and opinions regarding need for spinal surgery among patients with back or neck pain that have been recommended spinal surgery. METHODS: We performed a prospective observational study of patients who had been recommended for spinal surgery and received a second opinion between May 2011 and May 2012 at the Hospital Israelita Albert Einstein on the advice of their health insurance company. A physiatrist and orthopaedic surgeon independently performed the second assessment. If both agreed surgery was indicated, or consensus could not be reached, participants attended a spine review panel for a final recommendation. Descriptive analyses compared diagnoses and management plans of the first and second opinions. RESULTS: Of 544 referred patients, 16 (2.9%) did not meet inclusion criteria, 43 (7.9%) refused participation and 485 were included. Diagnoses differed from the first opinion for 290 (59.8%). Diagnoses of cervical and lumbar radiculopathy were concordant in 36/99 (36.4%) and 116/234 (49.6%) respectively. The second opinion was for conservative treatment for 168 (34.6%) participants, 27 (5.6%) were not considered to have a spine condition, and 290 (59.8%) were referred to the review board. 60 participants did not attend the board review and therefore did not receive a final recommendation. Board review was conservative treatment for an additional 67 participants, 20 were not considered to have a spine condition and 143 participants were recommended surgery. Overall, 33.6% received a final opinion of surgery (143/425) although only 66 (15.5%) received the same surgical recommendation, 235 (55.3%) were advised to have conservative treatment, and 47 (11.1%) were not considered to have a spinal diagnosis. CONCLUSIONS: We found a large discordance between first and second opinions regarding diagnosis and need for spinal surgery. This suggests that obtaining a second opinion could reduce potentially unnecessary surgery. TRIAL REGISTRATION: Current Controlled Trials ISRCTN07143259 . Registered 21 November 2011.

TNF-α depuration is a predictor of mortality in critically ill patients under continuous veno-venous hemodiafiltration treatment.

INTRODUCTION: Critically ill patients with acute kidney injury (AKI) present high mortality rates. The magnitude of inflammatory response could determine the prognosis of such patients. Continuous renal replacement therapy (CRRT) may play an important role in removing inflammatory mediators in patients with AKI. AIM: To investigate whether the magnitude of inflammatory mediator's removal is associated with mortality among critically ill patients on CVVHDF, a CRRT modality. METHODS: This study consisted of 64 critically ill patients requiring CVVHDF. Plasma levels of C3a, TNF-α, IL-10, IL-6, IL-1ß, sTNFRI and sTNFRII were determined by enzyme-linked immunosorbent assay (ELISA) at the beginning of CVVHDF and after 24h (outlet). Clearance of cytokines during the first 24h of CVVHDF was calculated. Clinical and laboratory data were acquired from patient's records data. RESULTS: Mean age of patients requiring CVVHDF was 63years, 67.2% were men and 87.3% were Caucasian. Thirty-five (35) patients (54.7%) died. Comparing non-survivors with the group of survivors we observed higher incidence of sepsis (68.6 versus 37.9%, p<0.05), higher APACHE II score (34.8±7.6 versus 29.2±7.1, p<0.05) and higher lactate levels (23.2±17.6 versus 16.4±6.6, p<0.05). According to the inter-tertile range of TNF-α clearance (ITR1 (<0.54); ITR2 (0.54-2.93); ITR3 (>2.93)) we found that those patients with higher TNF-α removal by RRT (ITR3) had a better survival. Multivariable analysis showed that lower clearance of TNF-α remained independently associated with high mortality after adjustment for sex, age, use of vasoactive drugs, APACHE II score sepsis, creatinine and lactate before CVVHDF (HR: 0.179, 95% IC: 0.049-0.661, p<0.01). CONCLUSION: The attenuation of inflammatory response may be related to the lower mortality observed on those patients with higher TNF-α removal by CVVHDF.

A retrospective view of the relationship of soluble Fas with anemia and outcomes in chronic kidney disease.

BACKGROUND: Anemia is common in chronic kidney disease (CKD) and is associated with outcomes. In addition, serum soluble Fas (sFas) levels are related to anemia and erythropoietin (EPO) resistance. OBJECTIVES: Firstly, to compare clinical data and serum levels of sFas, EPO, and pro-inflammatory markers between patients with non-dialytic CKD (NDD-CKD) and healthy subjects. Subsequently, to compare and evaluate the relationship of serum EPO, sFas levels with anemia, and outcomes in patients with NDD-CKD over a long follow-up period. METHODS: We performed a retrospective study in 58 NDD-CKD patients compared with 20 healthy subjects on complete blood count, kidney function, serum EPO, sFas, and inflammatory markers (CRP, IL- 6, and IFN-γ) at baseline. We then compared the same baseline data between patients with NDD-CKD who evolved to anemia and those who did not have anemia over the follow-up. We also evaluated the frequency of outcomes in patients with CKD with higher sFas levels. Finally, we performed a multivariate analysis of factors associated with CKD anemia. RESULTS: There were lower eGFR and Hb but higher serum inflammatory markers, sFas levels, sFas/eGFR, and EPO/Hb ratios in patients with NDD-CKD. Comparatively, on the other hand, NDD-CKD patients with anemia had lower eGFR but were older, had more diabetes, and had higher sFas/ eGFR, EPO/Hb ratios, and serum levels of IL-6 and sFas than NDD-CKD without anemia for an extended period. In addition, there was an association in a multivariate analysis of diabetes, age, and sFas levels with kidney anemia. Furthermore, there were higher frequencies of outcomes in increased serum sFas levels. CONCLUSION: As an elective risk factor, serum sFas levels, in addition to age and diabetes, were independently associated with kidney anemia for an extended period. Thus, more studies are necessary to analyze the proper relationship of sFas with kidney anemia and its outcomes and therapy in CKD.

Effects of spermidine and p-cresol on polymorphonuclear cell apoptosis and function.

Polymorphonuclear leukocytes (PMNs) from chronic kidney disease (CKD) patients display accelerated apoptosis and dysfunction, which may predispose CKD patients to infections. In this study, we investigated the effect of spermidine and p-cresol on apoptosis and function on PMN from healthy subjects. We measured the effect of spermidine and p-cresol on apoptosis, ROS production unstimulated and stimulated (S. aureus and PMA) and expression of CD95, caspase 3, and CD11b on PMN. After incubation with p-cresol and spermidine, we did not observe any changes in apoptosis, viability or expression of caspase 3 and CD95 in PMN from healthy subjects. PMN incubated for 10 minutes with spermidine demonstrated a significant reduction in spontaneous, S. aureus and PMA-stimulated ROS production. p-cresol induced a decrease in PMA-stimulated ROS production. Spermidine and p-cresol also induced a decrease in the expression of CD11b on PMN. Spermidine and p-cresol decreased the expression of CD11b and oxidative burst of PMN from healthy subjects and had no effect on PMN apoptosis and viability.

The use of regional citrate anticoagulation for continuous venovenous hemodiafiltration in acute kidney injury.

OBJECTIVE: Continuous renal replacement therapy is commonly used in the treatment of acute kidney injury. Although the optimal anticoagulation system is not well defined, citrate has emerged as the most promising method. We evaluated the data of 143 patients with acute kidney injury subjected to citrate-based continuous venovenous hemodiafiltration. DESIGN: Retrospective cohort study. SETTING: Intensive care unit of tertiary care private hospital. PATIENTS: Patients with acute kidney injury treated from February 2004 to July 2006. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main cause of acute kidney injury was sepsis (58%). The mean dialysis dose was 36.6 mL/kg/hr allowing for excellent metabolic control (last tests: creatinine, 1.1 mg/dL; urea, 46 mg/dL). No significant bleeding, severe electrolyte, or calcium disorders were observed. Of the 418 filters used, almost 28,000 hrs of treatment, hemofilter patency was 68% at 72 hrs. Hospital mortality was 59%, and 22% of survivors were dialysis-dependent at the time of discharge. Within our sample, we identified 21 patients with liver failure (mean prothrombin time index, 21% vs. 67%, p < 0.001). This group presented with a lesser median systemic ionized calcium level (1.06 vs. 1.12 mmol/L, p < 0.001) and similar mean total calcium level (8.5 vs. 8.6 mg/dL, not significant), compared with patients without liver failure. These subjects also showed acidemia (median pH, 7.31 vs. 7.40, p < 0.001); however, they exhibited higher levels of lactate (median 29 vs. 16 mg/dL, p < 0.001), chloride (mean 109 vs. 107 mEq/L, p = 0.045) and had a trend to higher mortality rate (76% vs. 56%). CONCLUSIONS: Besides a trend toward higher mortality rate observed in the group with liver failure, we found that citrate-based continuous venovenous hemodiafiltration allowed an effective dialysis dose and reasonable filter patency.

Timing of renal replacement therapy initiation in acute renal failure: a meta-analysis.

BACKGROUND: Some studies have suggested that early institution of renal replacement therapy (RRT) might be associated with improved outcomes in patients with acute renal failure (ARF). STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials and cohort comparative studies to assess the effect of early RRT on mortality in patients with ARF. SETTING & POPULATION: Hospitalized adult patients with ARF. SELECTION CRITERIA FOR STUDIES: We searched several databases for studies that compared the effect of "early" and "late" RRT initiation on mortality in patients with ARF. We included studies of various designs. INTERVENTION: Early RRT as defined in the individual studies. OUTCOMES: The primary outcome measure was the effect of early RRT on mortality stratified by study design. The pooled risk ratio (RR) for mortality was compiled using a random-effects model. Heterogeneity was evaluated by means of subgroup analysis and meta-regression. RESULTS: We identified 23 studies (5 randomized or quasi-randomized controlled trials, 1 prospective and 16 retrospective comparative cohort studies, and 1 single-arm study with a historic control group). By using meta-analysis of randomized trials, early RRT was associated with a nonsignificant 36% mortality risk reduction (RR, 0.64; 95% confidence interval, 0.40 to 1.05; P = 0.08). Conversely, in cohort studies, early RRT was associated with a statistically significant 28% mortality risk reduction (RR, 0.72; 95% confidence interval, 0.64 to 0.82; P < 0.001). The overall test for heterogeneity among cohort studies was significant (P = 0.005). Meta-regression yielded no significant associations; however, early dialysis therapy was associated more strongly with lower mortality in smaller studies (n < 100) by means of subgroup analysis. LIMITATIONS: Paucity of randomized controlled trials, use of variable definitions of early RRT, and publication bias preclude definitive conclusions. CONCLUSION: This hypothesis-generating meta-analysis suggests that early initiation of RRT in patients with ARF might be associated with improved survival, calling for an adequately powered randomized controlled trial to address this question.

Impact of dialyzer membrane on apoptosis and function of polymorphonuclear cells and cytokine synthesis by peripheral blood mononuclear cells in hemodialysis patients.

In an in vivo crossover trial, we compared a cellulosic with a synthetic dialyzer with respect to polymorphonuclear cells (PMN) function and apoptosis, cytokine serum levels and synthesis by peripheral blood mononuclear cells (PBMC), and complement activation. Twenty hemodialysis (HD) patients were assigned in alternate order to HD with cellulose acetate (CA) or polysulfone (PS) dialyzer. After 2 weeks, patients were crossed over to the second dialyzer and treated for another 2 weeks. Apoptosis was assessed by flow cytometry in freshly isolated PMN. Phagocytosis and production of peroxide by PMN were studied by flow cytometry in whole blood. PBMC were isolated from blood samples and incubated for 24 h with or without lipopolysaccharide (LPS). There was no impact of dialyzer biocompatibility on PMN apoptosis and function, cytokine synthesis by PBMC or on their serum levels, serum levels of C3a, and terminal complement complex (TCC). Nevertheless, after HD, serum levels of complement correlated negatively with PMN phagocytosis and peroxide production, and positively with PMN apoptosis and cytokine production by PBMC. Although the results did not show a dialyzer advantage on the immunologic parameters, complement activation may have modulated cell function and apoptosis after HD.

The progression and impact of vascular calcification in peritoneal dialysis patients.

BACKGROUND: Progression of coronary artery calcification (CAC) has been described in hemodialysis patients, and severe CAC has been associated with the occurrence of cardiovascular events in this population. Little information is available regarding peritoneal patients. AIM: To prospectively evaluate peritoneal dialysis patients in order to identify the variables associated with the rate of CAC progression, as well as to determine the impact that baseline CAC has on clinical outcomes over a 1-year follow-up period. METHODS: Using multislice coronary tomography, calcium scores were estimated at baseline and after 12 months in 49 peritoneal dialysis patients. Patients with and without CAC progression were compared with respect to clinical characteristics and biochemical variables, including lipid profile, parameters of mineral metabolism, and markers of inflammation. Cardiovascular events, hospitalizations, and all-cause mortality were recorded. RESULTS: At baseline, 29 patients (59%) presented CAC and a median calcium score of 234.7 (range 10.3-2351) Agatston units. Progression of CAC was observed in 13 patients (43%) who, in comparison with those presenting no CAC progression, were older, presented higher baseline calcium scores, and had higher mean glucose levels, lower mean high density lipoprotein cholesterol levels, and more months using low calcium peritoneal solution. We also observed a trend toward more often presenting with a history of hypertension, exhibiting more hyperphosphatemic and hyperglycemic events, and having lower albumin levels. In multiple logistic regression, only baseline calcium score was independently associated with progression of CAC. A shorter cardiovascular event-free time and a trend toward lower survival rates were observed in the group with CAC. Hospitalization event-free time did not differ between the groups. CONCLUSION: Determining CAC provides important prognostic data in peritoneal dialysis patients. Baseline calcium score and disturbances in glucose, mineral, and lipid metabolism were indicative of higher risk of CAC progression in this population.

Cholecalciferol decreases inflammation and improves vitamin D regulatory enzymes in lymphocytes in the uremic environment: A randomized controlled pilot trial.

It has been reported that vitamin D regulates the immune system. However, whether vitamin D repletion modulates inflammatory responses in lymphocytes from dialysis patients is unclear. In the clinical trial, thirty-two (32) dialysis patients with 25 vitamin D ≤ 20ng/mL were randomized to receive either supplementation of cholecalciferol 100,000 UI/week/3 months (16 patients) or placebo (16 patients). In the in vitro study, B and T lymphocytes from 12 healthy volunteers (HV) were incubated with or without uremic serum in the presence or absence of 25 or 1,25 vitamin D. We evaluated the intracellular expression of IL-6, IFN-γ TLR7, TLR9, VDR, CYP27b1 and CYP24a1 by flow cytometry. We observed a reduction in the expression of TLR7, TLR9, INF-γ and CYP24a1 and an increase in VDR and CYP27b1 expression in patients which were supplemented with cholecalciferol, whereas no differences were found in the placebo group. Uremic serum increased the intracellular expression of IL-6, IFN-γ, TLR7, TLR9, VDR, CYP27b1 and CYP24a1. Treatment with 25 or 1,25 vitamin D decreased IL-6 and TLR9. CYP24a1 silencing plus treatment with 25 and/or 1,25 vitamin D had an additional reduction effect on IL-6, IFN-γ, TLR7 and TLR9 expression. This is the first study showing that cholecalciferol repletion has an anti-inflammatory effect and improves vitamin D intracellular regulatory enzymes on lymphocytes from dialysis patients.

Effect of microcystin on leukocyte viability and function.

Microcystin (MC) has been found in several areas of the world. In addition to its hepatotoxicity, microcystin may have an immunomodulatory effect. Considering that patients receiving hemodialysis may be chronically exposed to variable concentrations of MC, and that they present important changes in this immune response, we have assessed the effect of MC on the function of leukocytes. Polymorphonuclear leukocytes isolated from healthy volunteers (HV) and patients receiving hemodialysis (HD) were incubated with microcystin (10 microg/L) for 24h and evaluated for reactive oxygen species production (ROS), phagocytosis and apoptosis. Monocytes incubated with and without LPS (100 ng/mL) and microcystin for 24h were assessed for TNFalpha and IL-10 production. Leukocytes of HV presented an increase in apoptosis rates and leukocytes from HD exhibited a lower production of oxygen-reactive species, both spontaneously and after stimulus with S. aureus, when compared with leukocytes incubated without toxin. Monocytes presented an increase in cytokine production after stimulation by LPS in both groups, but there was no difference between the groups with and without MC that were incubated with or without LPS. Low concentrations of microcystin can induce mild changes in leukocyte function of HV and HDP, particularly in the ability to produce ROS.

Coronary artery calcification, systemic inflammation markers and mineral metabolism in a peritoneal dialysis population.

AIMS: To assess the prevalence of coronary artery calcification (CAC) in peritoneal dialysis (PD) patients and to determine whether comorbidities such as inflammation, dyslipidemia and mineral metabolism disorders correlate with its development. METHODS: Forty-nine PD patients (45% male; median age, 52 years) were submitted to multislice computed tomography. Inflammatory markers, anti-oxidized LDL antibody, calcium-phosphate balance and lipid profiles were assessed. RESULTS: Twenty-nine patients (59.2%) presented CAC (median calcium score, 234.7 Agatston units). Patients with CAC were older than those without, more frequently presented a history of coronary artery disease or hypertension and had lower HDL cholesterol levels, as well as presenting higher levels of osteoprotegerin and LDL oxidation. The logistic regression revealed that the independent determinants of CAC were age (odds ratio = 1.12; p = 0.006) and number of prescribed anti-hypertensive drugs (odds ratio = 2.38; p = 0.048). When the population was stratified by calcium score quartile, soluble Fas levels were significantly higher in patients with severe calcification. In patients younger than 45, CAC correlated positively with phosphorus levels (r = 0.52; p = 0.04). CONCLUSION: In PD patients, CAC is highly prevalent. Our results indicate that conditions such as inflammation and mineral disturbances are associated with its development.

Erythropoietin resistance in end-stage renal disease patient with gastric antral vascular ectasia.

We observed a case of recombinant human erythropoietin resistance caused by Gastric Antral Vascular Ectasia in a 40-year-old female with ESRD on hemodialysis. Some associated factors such as autoimmune disease, hemolysis, heart and liver disease were discarded on physical examination and complementary tests. The diagnosis is based on the clinical history and endoscopic appearance of watermelon stomach. The histologic findings are fibromuscular proliferation and capillary ectasia with microvascular thrombosis of the lamina propria. However, these histologic findings are not necessary to confirm the diagnosis. Gastric Antral Vascular Ectasia is a serious condition and should be considered in ESRD patients on hemodialysis with anemia and resistance to recombinant human erythropoietin because GAVE is potentially curable with specific endoscopic treatment method or through surgical procedure.

Erythropoietin resistance in end-stage renal disease patient with gastric antral vascular ectasia.

We observed a case of recombinant human erythropoietin resistance caused by Gastric Antral Vascular Ectasia in a 40-year-old female with ESRD on hemodialysis. Some associated factors such as autoimmune disease, hemolysis, heart and liver disease were discarded on physical examination and complementary tests. The diagnosis is based on the clinical history and endoscopic appearance of watermelon stomach. The histologic findings are fibromuscular proliferation and capillary ectasia with microvascular thrombosis of the lamina propria. However, these histologic findings are not necessary to confirm the diagnosis. Gastric Antral Vascular Ectasia is a serious condition and should be considered in ESRD patients on hemodialysis with anemia and resistance to recombinant human erythropoietin because GAVE is potentially curable with specific endoscopic treatment method or through surgical procedure.

Evaluation of the prevalence and risk factors for colonization by vancomycin-resistant Enterococcus among patients on dialysis.

BACKGROUND: Vancomycin-resistant Enterococcus (VRE) has been reported among long-term dialysis patients, although risk factors for VRE colonization are not well defined. This study aims to appraise the prevalence and risk factors for VRE colonization among patients on long-term dialysis therapy, as well as the mechanisms for dissemination of vancomycin resistance. METHODS: This is a cross-sectional survey of 320 patients on long-term dialysis therapy at 2 hospitals of the Federal University of São Paulo from June 2001 to March 2003. Fecal samples were collected from each patient once a week for 1 month. Samples with positive test results for VRE were submitted to molecular typing through automated ribotyping. RESULTS: VRE prevalence was 14.4%. There were significant associations between VRE and dialysis type (hemodialysis, P = 0.04), number of hospitalizations (P = 0.03), low hemoglobin level (P = 0.03), and leukocytosis (P = 0.05). Among samples with VRE (n = 56), 25% were Enterococcus faecium; 10.7%, Enterococcus casseliflavus; 57.1%, Enterococcus gallinarum; and 3.6%, Enterococcus faecalis. All samples isolated were sensitive to teicoplanin, except for E faecium samples, which were strongly resistant, although 9 of 14 patients with this isolate presented the same ribogroup (111-S-4). Typing of 6 samples from 8 dialysis patients with E gallinarum was performed, showing a predominant ribogroup (112-S-4). CONCLUSION: Hospital environment, hemodialysis, anemia, and leukocytosis appear to be associated with VRE colonization. These results suggest that dissemination of these bacteria among patients on long-term dialysis therapy may be taking place.

A model for improving quality in nephrology settings.

Continuous quality improvement (CQI) programs have been instituted in many health care organizations over the last decade. PDCA, a tool composed of planning (P), doing (D), checking (C), and acting (A), has proved to be very useful in the CQI problem-solving process. The use of the PDCA tool described in this article resulted in the successful resolution of a hepatitis B outbreak in a Brazilian hemodialysis population and can serve as a model methodology for improving care in nephrology settings.

Frequency of TGF- ß and IFN- γ genotype as risk factors for acute kidney injury and death in intensive care unit patients.

Genetic variations in TGF-ß and IFN-γ may interfere with proinflammatory cytokine production and, consequently, may be involved with inflammatory diseases, as acute kidney injury (AKI). We considered that genetic polymorphisms of these cytokines may have a crucial role in the outcome of critically ill patients. To investigate whether the genetic polymorphisms of rs1800470 (codon 10 T/C), rs1800471 (codon 25 C/G) from the TGF-ß, and rs2430561 (+874 T/A) from IFN-γ may be a risk factor for ICU patients to the development of AKI and/or death. In a prospective nested case-control study, were included 139 ICU patients who developed AKI, 164 ICU patients without AKI, and 244 healthy individuals. We observed a higher frequency to T/A genotype for IFN-γ (intermediate producer phenotype) and higher frequency of TT GG and TC GG genotype (high producer) for TGF-ß polymorphism in overall population. However, these polymorphisms have not been shown as a predictor of risk for AKI and death. We found an increased prevalence of high and intermediate producer phenotypes from TGF-ß and IFN-γ, respectively, in patients in ICU setting. However, the studied genetic polymorphism of the TGF-ß and IFN-γ was not associated as a risk factor for AKI or death in our population.