Age-Related Changes in Clinical and Analytical Variables in Chronic Hemodialyzed Patients.

Worldwide, the number of elderly individuals receiving chronic hemodialysis is rising. The aim of our study was to evaluate several clinical and analytical biomarkers in chronically dialyzed patients and analyze how they change with age. A cross-sectional study was performed by evaluating 289 end-stage renal disease patients undergoing dialysis. We evaluated the hemogram, adipokines, the lipid profile, and several markers related to inflammation, endothelial function/fibrinolysis, nutrition, iron metabolism, and cardiac and renal fibrosis. Clinical data and dialysis efficacy parameters were obtained from all patients. The relationships between studied biomarkers and age were assessed by a statistical comparison between younger (adults with age < 65 years) and older (age ≥ 65 years) patients and by performing regression analysis. Participants presented a mean age of 68.7 years (±13.6), with 66.8% (n = 193) being classified as older. Compared to younger patients, older patients presented the following: (a) significantly lower values of diastolic blood pressure (DBP) and ultrafiltration volume; (b) lower levels of phosphorus, uric acid, creatinine, and albumin; and (c) higher circulating concentrations of tissue-type plasminogen activator (tPA), D-dimer, interleukin-6, leptin, N-terminal pro B-type natriuretic peptide, and tissue inhibitor of metalloproteinase-1. In the multiple linear regression analysis, DBP values, tPA, phosphorus, and D-dimer levels were independently associated with the age of patients (standardized betas: -0.407, 0.272, -0.230, and 0.197, respectively; p < 0.001 for all), demonstrating relevant changes in biomarkers with increasing age at cardiovascular and nutritional levels. These findings seem to result from crosstalk mechanisms between aging and chronic kidney disease.

Hepcidin in chronic kidney disease anemia.

Chronic kidney disease (CKD) is associated with several complications that worsen with progression of disease; anemia, disturbances in iron metabolism and inflammation are common features. Inflammatory response starts early, releasing pro-inflammatory cytokines, acute phase reactants and hepcidin. Hepcidin production is modulated by several factors, as hypoxia/anemia, erythropoietin and erythropoiesis products, transferrin saturation (TSAT) and liver iron levels, which are altered in CKD. Treatment of CKD anemia is based on pharmaceutical intervention, with erythropoietic stimulating agents and/or iron supplementation; however, in spite of the erythropoietic benefits, this therapy, on a regular basis, involves risks, namely iron overload. To overcome these risks, some therapeutic approaches are under study to target CKD anemia. Considering the actual alerts about risk of iron overload in dialysis patients, inhibition of hepcidin, the central key player in iron homeostasis, could be a pivotal strategy in the management of CKD anemia.

Terapia de ressincronização cardíaca após implante por cateter debioprótese valvar aórtica / Cardiac resynchronization therapy after transcatheter aortic valve implantation

O tratamento da estenose aórtica com implante por cateter de bioprótese valvar aórtica é sabidamente eficaz. Contudo, os distúrbios de condução são complicações frequentes e associam-se a elevada taxa de implante de marcapasso definitivo. Questões referentes ao melhor modo de estimulação, ao papel do cardiodesfibrilador na profilaxia de morte súbita e ao prognóstico ainda não apresentam consenso. Relata-se, portanto, um caso de paciente que, após o implante valvar, evoluiu com bloqueio completo de ramo esquerdo agudo e bradiarritmia, insuficiência cardíaca refratária ao tratamento medicamentoso, com fração de ejeção gravemente comprometida e intolerância ao betabloqueador por bradiarritmia. Optou-se, então, pela terapia de ressincronização ao invésdo marcapasso convencional, com boa resposta clínica. A associação com cardiodesfibrilador foi descartada paraprofilaxia de morte súbita após o estudo eletrofisiológico, o qual não evidenciou instabilidade elétrica ventricular...

Treatment of aortic stenosis with valve of transcatheter implant is known to be effective. However, conduction disorders are common complications and are associated with a high permanent pacemaker implantation rate. Questions regarding the best pacing mode, the role of the defibrillator in sudden death prevention and prognosis, do not have consensus yet. We report, therefore, the case of a patient who developed complete blockage of acute left bundle branch and bradyarrhythmia, heart failure refractory to drug therapy, poor ejection fraction and intolerance to betablocker due bradyarrhythmias after valve implant. Thus, we chose resynchronizationtherapy instead of conventional pacemakers and obtained a good clinical response. The association with adefibrillator was ruled out for sudden death prevention after the electrophysiological study, which did not show ventricular electrical instability...

Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia.

This study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO) therapy in a rat model of chronic kidney disease (CKD)-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks) high dose of rHuEPO (200 UI/kg bw/week) treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue (kidney, liver and/or duodenum) protein and/or gene expression of mediators of erythropoiesis, iron metabolism and tissue hypoxia, inflammation, and fibrosis. Long-term treatment with a high rHuEPO dose is associated with development of resistance to therapy as a result of antibodies formation. In this condition, serum EPO levels are not deficient and iron availability is recovered by increased duodenal absorption. However, erythropoiesis is not stimulated, and the resistance to endogenous EPO effect and to rHuEPO therapy results from the development of a hypoxic, inflammatory and fibrotic milieu in the kidney tissue. This study provides new insights that could be important to ameliorate the current therapeutic strategies used to treat patients with CKD-associated anemia, in particular those that become resistant to rHuEPO therapy.

Principal determinants of the length of remission of psoriasis vulgaris after topical, NB-UVB, and PUVA therapy: a follow-up study.

BACKGROUND: Periods of remission and of exacerbation of psoriatic lesions are common in psoriasis. We recently reported C-reactive protein (CRP) as a marker of psoriasis severity and that some patients still presented with a residual inflammation after treatment. We wondered if this residual inflammation could underlie an earlier exacerbation of psoriasis. OBJECTIVE: The purpose of our study was to evaluate if there is a relationship between CRP levels, Psoriasis Area and Severity Index (PASI), and body mass index (BMI), at the end of psoriasis treatment, with the length of psoriasis remission. METHODS: We followed 46 patients studied at the end of treatment, to record the length of remission; 9 of the patients were treated with topical agents, 17 with narrow-band UVB (NB-UVB), and 20 with psoralen plus UVA (PUVA). RESULTS: We found that the length of remission correlated with the values for PASI and CRP at the end of therapy. By performing a multiple linear regression analysis, CRP, PASI, and BMI were each significantly associated with length of remission. Patients with residual inflammation at the end of treatment presented with a significantly shorter length of remission. When considering patients grouped according to the used therapies, CRP and PASI also emerged as potential determinants of length of remission, especially in the case of patients treated with NB-UVB and topical therapy. CONCLUSION: Our data suggest that CRP and PASI are important determinants of length of psoriasis remission for patients treated with phototherapy or topical therapy. Further studies with larger groups of patients are warranted to test this hypothesis. Moreover, we propose that, by the end of the treatment, the evaluation of CRP and PASI could be important to decide, when possible, if the treatment should be continued to achieve lower CRP values and longer periods of remission.

Complementary markers for the clinical severity classification of hereditary spherocytosis in unsplenectomized patients.

Hereditary spherocytosis (HS) is usually classified as mild, moderate or severe using conventional features, namely, hemoglobin (Hb) concentration, reticulocyte count and bilirubin levels, which do not always contribute to an adequate clinical classification. The aim of our study was to establish the importance of some laboratory routine parameters, as markers of HS clinical outcome, by studying a control group (n=26) and unsplenectomized HS patients (n=82) presenting mild, moderate or severe HS. We performed a basic hematologic study and evaluated the reticulocyte count, bilirubin, erythropoietin (EPO) and soluble transferrin receptor (sTfR) levels; the osmotic fragility (OFT) and criohemolysis tests (CHT); the ratios Hb/MCHC (mean cell hemoglobin concentration), Hb/RDW (red cell distribution width) and MCHC/RDW, were calculated. Hb changed significantly in accordance with HS severity, but not reticulocytes or bilirubin. We found that MCHC, RDW, EPO, sTfR, OFT, CHT and the calculated ratios were significantly changed in patients, and, therefore, were valuable as complementary diagnostic tools for HS. Moreover, RDW, Hb/MCHC, Hb/RDW and MCHC/RDW changed significantly with worsening of HS; thus, they are also good markers for the clinical outcome of HS. In conclusion, we propose the use of these routine parameters as useful to complement the analysis of HS severity.

Psoriasis therapy and cardiovascular risk factors: a 12-week follow-up study.

BACKGROUND: Psoriatic patients present with an increased frequency of cardiovascular events. OBJECTIVE: To study the impact of psoriasis duration and therapy on traditional and new cardiovascular risk factors. STUDY DESIGN: A longitudinal study performed between 2005 and the first trimester of 2008. Each patient was followed up for 12 weeks, and was observed before and 3, 6, and 12 weeks after starting therapy. SETTING: Patients attending the Dermatology Service, University Hospital of Coimbra, Coimbra, Portugal were enrolled. SUBJECTS: Thirty-four patients with psoriasis vulgaris and 37 healthy volunteers as controls. MAIN OUTCOME MEASURES: Psoriasis Area and Severity Index (PASI); lipid profile, oxidized low-density lipoprotein (oxLDL), oxLDL/low-density lipoprotein (LDL), total antioxidant status, lipid peroxidation, C-reactive protein (CRP), and circulating levels of adiponectin. INTERVENTION: Ten patients started therapy with topical treatment, 11 with narrow-band UVB radiation (NB-UVB), and 13 with psolaren plus UVA (PUVA). RESULTS: Before starting therapy, psoriatic patients presented with several risk changes in their lipid profiles, and significantly higher CRP, oxLDL, and oxLDL/LDL, and lower adiponectin levels (vs control subjects), which may further contribute to inflammation and atherogenesis. After treatment of the patients, although no significant differences were observed in the lipid profile compared with baseline, some changes suggested that the treatment could somehow alter lipid metabolism, as the reduction in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A and the increase in the atherogenic index cholesterol/HDL-C maintained an even higher significance (as shown by p-values) when compared with the control group. After topical therapy, there was a significant reduction in thiobarbituric acid reactivity only, suggesting that the reduction in the hyperproliferative process within the lesions is important for lipid peroxidation. After NB-UVB therapy, oxLDL/LDL, cholesterol/HDL-C, lipoprotein (a) [Lp(a)], and CRP remained higher than in the control subjects, reflecting persistent inflammation and atherogenic risk. After PUVA treatment, there was a significant reduction in Lp(a), associated with an almost significant increase in apolipoprotein-B (p = 0.054); these changes were not observed after NB-UVB treatment. However, after PUVA and NB-UVB treatment, CRP and, in the NB-UVB group, oxLDL/LDL were persistently higher than controls. CONCLUSION: Our data show that psoriatic patients present with several lipid profile changes that seem to be related to the severity of the disease and/or the treatment used. Mild psoriasis patients receiving topical treatment presented before starting therapy with a lipid profile similar to controls, whereas those undergoing NB-UVB and PUVA, who had higher PASI scores, presented with several risk factors. Moreover, PUVA therapy seems to interact in a different way with lipids that might result from an interaction of psoralen with plasma lipids, namely Lp(a). Inflammation, a hallmark of psoriasis, also seems to be related to psoriasis severity. Both NB-UVB and PUVA were effective, as shown by the reduction in PASI score, as well as in the oxidative and inflammatory stress markers. However, after NB-UVB and PUVA, a low-grade inflammatory process still persisted, which might be related to the duration of remission of the disease.

Powerful protective role of 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde against erythrocyte oxidative-induced hemolysis.

The present work studied and compared the capacity of four important olive oil polyphenolic compounds, oleuropein, hydroxytyrosol, and the oleuropein aglycones 3,4-dihydroxyphenylethanol-elenolic acid (3,4-DHPEA-EA) and 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde (3,4-DHPEA-EDA), to protect red blood cells (RBCs) from oxidative hemolysis induced by the physiological initiator H2O2. The amount of hemolysis was evaluated spectrophotometrically. The compounds were also tested in the presence and absence of the naturally occurring antioxidant ascorbic acid. All compounds were revealed to significantly protect RBCs from oxidative hemolysis induced by H2O2 at 40 and 80 microM, with the order of activity being 3,4-DHPEA-EDA>3,4-DHPEA-EA>hydroxytyrosol=oleuropein. At 20, 10, and 5 microM, only 3,4-DHPEA-EDA showed a significant protection against the oxidative injury. In the presence of ascorbic acid at physiological concentration, the addition of individual compounds at 40 microM increased the stability of erythrocytes. The addition of phenolic compounds at 20 and 10 microM did not produce further protection when compared with the protection given by ascorbic acid alone, except for 3,4-DHPEA-EDA. This compound was shown to produce further protection even at 5 microM. In summary, 3,4-DHPEA-EDA plays an important protective role against reactive oxygen species-induced oxidative injury in RBCs, and this effect is more potent than the one evidenced by hydroxytyrosol or oleuropein.

Effects of olive oil polyphenols on erythrocyte oxidative damage.

Many studies have investigated the protective effects of oleuropein and hydroxytyrosol against cell injury, but few have investigated the protective effects of oleuropein aglycones 3,4-dihydroxyphenylethanol-elenolic acid (3,4-DHPEA-EA) and 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde (3,4-DHPEA-EDA). The present work studied and compared the capacity of these four compounds, found at high concentrations in olive oil, to protect red blood cells (RBCs) from oxidative injury. The in vitro oxidative stress of RBCs was induced by the water-soluble radical initiator 2,2'-azo-bis(2-amidinopropane) dihydrochloride. RBC changes were evaluated either by optical microscopy or by the amount of hemolysis. All compounds were shown to significantly protect RBCs from oxidative damage in a dose-dependent manner. The order of activity at 20 microM was: 3,4-DHPEA-EDA > hydroxytyrosol > oleuropein > 3,4-DHPEA-EA. Even at 3 microM, 3,4-DHPEA-EDA and hydroxytyrosol still had an important protective activity. However, deleterious morphological RBC changes were much more evident in the presence of hydroxytyrosol than with 3,4-DHPEA-EDA. For the first time it was demonstrated that 3,4-DHPEA-EDA, one of most important olive oil polyphenols, may play a noteworthy protective role against ROS-induced oxidative injury in human cells since lower doses of this compound were needed to protect RBCs in vitro from oxidative mediated hemolysis.

Intra-His bundle block. Clinical, electrocardiographic, and electrophysiologic characteristics.

OBJECTIVE: To assess the clinical, electrocardiographic, and electrophysiologic characteristics of patients (pt) with intra-His bundle block undergoing an electrophysiologic study (EPS). METHODS: We analyzed the characteristics of 16 pt with second-degree atrioventricular block and symptoms of syncope or dyspnea, or both, undergoing conventional EPS. RESULTS: Intra-His bundle block was documented in 16 pt during an EPS. In 15 (94%) pt, the atrioventricular block was recorded in sinus rhythm; 4 (25%) pt had intra-His Wenckebach phenomenon, which correlated with Mobitz I (MI) atrioventricular block on the electrocardiogram. Seven (44%) pt had 2:1 atrioventricular block, 2 of whom were asymptomatic (12.5%). One (6%) pt had intra- and infra-His bundle block. Clinically, 11 (68%) pt had syncope or presyncope, 3 (18%) had dyspnea on exertion, and 2 (12.5%) were asymptomatic. Eight (50%) pt had bundle-branch block as follows: 4 (25%) pt had left bundle-branch block, and 4 (25%) had right bundle-branch block. Left anterosuperior divisional block was observed in 3 pt (19%), 2 of whom with associated right bundle-branch block. CONCLUSION: Intra-His bundle block was observed in 11% of the pt with second-degree atrioventricular block, syncope or presyncope, or both, it being the most frequent clinical presentation. Intra-His bundle block was more common in the elderly (> 60 years) and among females. The most frequent electrocardiographic presentations were second-degree Mobitz I or type 2:1 atrioventricular block.

Bloqueio intra-his. Características clínicas, eletrocardiográficas e eletrofisiológicas / Intra-His bundle block. Clinical, electrocardiographic, and electrophysiologic characteristics

OBJECTIVE - To assess the clinical, electrocardiographic, and electrophysiologic characteristics of patients (pt) with intra-His bundle block undergoing an electrophysiologic study (EPS). METHODS - We analyzed the characteristics of 16 pt with second-degree atrioventricular block and symptoms of syncope or dyspnea, or both, undergoing conventional EPS. RESULTS - Intra-His bundle block was documented in 16 pt during an EPS. In 15 (94 percent) pt, the atrioventricular block was recorded in sinus rhythm; 4 (25 percent) pt had intra-His Wenckebach phenomenon, which correlated with Mobitz I (MI) atrioventricular block on the electrocardiogram. Seven (44 percent) pt had 2:1 atrioventricular block, 2 of whom were asymptomatic (12.5 percent). One (6 percent) pt had intra- and infra-His bundle block. Clinically, 11 (68 percent) pt had syncope or presyncope, 3 (18 percent) had dyspnea on exertion, and 2 (12.5 percent) were asymptomatic. Eight (50 percent) pt had bundle-branch block as follows: 4 (25 percent) pt had left bundle-branch block, and 4 (25 percent) had right bundle-branch block. Left anterosuperior divisional block was observed in 3 pt (19 percent), 2 of whom with associated right bundle-branch block. CONCLUSION - Intra-His bundle block was observed in 11 percent of the pt with second-degree atrioventricular block, syncope or presyncope, or both, it being the most frequent clinical presentation. Intra-His bundle block was more common in the elderly (> 60 years) and among females. The most frequent electrocardiographic presentations were second-degree Mobitz I or type 2:1 atrioventricular block