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Objective: To assess survival of ALS patients in general and in selected demographic and clinical subgroups comparing two periods (1998–2000 vs. 2008–2010). Methods: Newly diagnosed adults resident of Lombardy, Northern Italy from a population-based registry were included. Data were collected on age at diagnosis, sex, site of onset, diagnostic delay, and El-Escorial diagnostic category. Patients were followed until death or last observation. Survival was evaluated using Kaplan–Meier curves and Cox’s proportional hazards models. Results: In 2008–2010 (267 patients), median survival was 2.4 years and 1-year, 2-year, 3-year and 5-year survival rates were 79%, 56%, 41% and 24%. Longer survival was associated with male sex, younger age, spinal onset, and longer diagnostic delay. Multivariable analysis confirmed higher death in 65–69yr (HR 2.8; 95% CI 1.4-5.6), 70–74yr (HR 3.2; 95% CI 1.6-6.3) and 75 + yr (HR 6.9; 95% CI 3.5-13.8) categories, compared to ≤49yr, in females (HR 1.4; 95% CI 1.02-1.8), compared to males, and in patients diagnosed after 6–12 months (HR 1.9; 95% CI 1.4-2.7), compared with longer diagnostic delay. In 1998–2000 (235 patients), median survival was 2.2 years. The 1-year, 2-year, 3-year and 5-year survival rates were 77%, 53%, 38% and 20%. When adjusting for demographic and clinical variables, the HR for death in 2008–2010 versus 1998–2000 was 0.80 (95% CI 0.66–0.98). A significant increase of survival in 2008–2010 was found only in patients aged 50–59yr and 70–74yr at diagnosis. Conclusions: Survival of ALS has increased over time in the last decades, especially in middle aged and elderly patients. The benefits of comprehensive care in selected age groups might explain our findings.

Purpose The purpose of this study was to assess the priorities of patients with epilepsy and caring physicians and the correspondence between these priorities. Methods In this multicenter cross-sectional study, patients with epilepsy attending 21 Italian epilepsy centers and their caring physicians filled anonymously questionnaires on the needs and priorities in the management of the disease. Included were questions on patients' demographics, diagnosis, treatment, and outcome of epilepsy. The concordance between patients and their physicians was assessed on various aspects of the diagnosis and care of the disease. Patients' satisfaction with communication, services, and patient–doctor relationship was also assessed. Results Included were 432 women and 355 men aged 15 to 88 years (median: 41 years). Disease duration ranged from 6 months to 75 years. A structural/metabolic etiology predominated (52.7%), followed by a (presumed) genetic etiology (33.0%). Seizure remission was present in 56.5% of cases. Comorbidities requiring chronic treatment were present in 27.5%, and comorbidities affecting self-sufficiency in 9.5%. Psychiatric comorbidity was present in 35.0%. Patients' priorities included discovery of the cause (89.1%), use of right drug (98.7%), use of a drug without chronic side effects (94.0%), and a life without restrictions (90.4%). Physicians' priorities included choice of right drug (83.5%) and use of drugs without chronic side effects (86.8%). Priorities varied with patients' age, sex, education, and occupation. Patient–doctor relationships were at least good in most cases. The information imparted was considered unsatisfactory by 21–44% of cases on seizure circumstances and complications, side effects of drugs, limitations of daily activities, and management of physiologic or pathologic conditions. Patients declared overall satisfaction, except for appointments (21.5%) and emergencies (30.8%). Conclusion Patients and physicians' priorities in the management of epilepsy overlap only in part. Patients are satisfied with their caring physicians and less satisfied with communication and management of routine and emergency problems.

There is still a need to analyze the factors that enhance navigation accuracy. This study aims to examine how success in environment learning relates to task goals and WM. A total of 90 undergraduates (46 females) learned a route from a virtual navigation experience after being given a goal that involved tracing the route (a route-based goal) or finding a shortcut (a survey-based goal). The two groups thus formed were each divided into three subgroups according to the dual-task paradigm: one only navigated (control condition); the other two did so while simultaneously performing a visuo-spatial or verbal secondary task. Afterwards, participants traced the previously seen route and found a shortcut. Several visuo-spatial and verbal WM tasks were also administered. The results showed that participants given a route-based goal performed better in the route-tracing task; and those given a survey-based goal were better at finding shortcuts. An influence of WM was also shown: higher WM (visuo-spatial and verbal) ability significantly reduced the number of route-tracing errors made while performing a secondary visuo-spatial task, regardless of the goal, whereas no such effects emerged for shortcut finding. These results offer new insight on how task goals and WM support successful navigation.

Objectives To determine whether the generic and branded warfarins used as anticoagulants in Brazil are therapeutic equivalents based on their international normalized ratio (INR) results. Methods This crossover randomized controlled trial had four periods. We used the branded Marevan and two generic versions of warfarin sodium tablets, manufactured by União Química and Teuto laboratories, all purchased from retail drugstores. Eligible participants were outpatients from an anticoagulation clinic at a university hospital in São Paulo, Brazil. They had atrial fibrillation or flutter and had been using warfarin for at least 2 months with an INR therapeutic range of 2.0–3.0. Randomization was by numbered, opaque, sealed envelopes. Healthcare personnel and outcome assessors were blinded to treatments, but patients were not. The primary outcome was the variability in the INR (ΔINR) and secondary outcomes included mean INR. We accepted formulations as equivalent if the 95% confidence interval (CI) of the comparison of ΔINR between branded and generic formulations was within the limit of ±0.49. Results One hundred patients were recruited and randomized to six sequences of treatment (four sequences with n = 17 and two sequences with n = 16). União Química generic warfarin had equivalent variability in the INR to Marevan (ΔINR +0.09 [95% CI -0.29 to +0.46], n = 84). Comparison between Teuto generic warfarin and Marevan was inconclusive (ΔINR +0.29 [95% CI -0.09 to +0.68], n = 84). Conclusions Marevan and União Química warfarin had equivalent therapeutic effectiveness and both could be confidently used for anticoagulation. The comparison between Marevan and TW was inconclusive and does not warrant a statement of equivalence. Our methods are especially important for comparing generic and branded drugs that raise concerns and may be subject of future investigations by regulatory agents. Trial registration ClinicalTrials.gov NCT02017197.

Objective The objective of this study was to assess the priorities of patients with epilepsy and their caring physicians with reference to the timing and severity of the disease. Methods This is a national survey in which patients with epilepsy followed in 21 Italian epilepsy centers, and their caring physicians were asked to fill anonymous questionnaires to collect data on different aspects of the disease and their needs and priorities in its management. The collected information included demographics, clinical profile and diagnosis, treatment and outcome of epilepsy. The questions were designed to understand the expectations of the patients and their caring physicians and verify the degree of concordance between patient and doctor. The study population was divided in six prognostic categories: (1) Newly diagnosed epilepsy; (2) Absence of seizures for at least 2 years; (3) Absence of seizures for at least 1 year or occasional seizures; (4) Nondrug-resistant recurrent seizures; (5) drug-resistant seizures; (6) surgical candidate. Results Of the 787 patients enrolled, 432 were women and 355 men aged 15 to 88 years (median 41 years). Disease duration ranged from 6 months to 75 years. The sample included 53 patients with newly diagnosed epilepsy, 283 without seizures for at least 2 years, 162 seizure-free for at least 1 year or with occasional seizures, 123 with nondrug-resistant recurrent seizures, 128 with drug-resistant seizures, and 38 surgical candidates. Significant differences were found between patients and physicians in terms of priorities and needs with reference to the management of the disease. While physicians tend to prioritize the information on the diagnosis and treatment of epilepsy depending on timing and severity, patients focus on the search of the cause, the side effects of drugs, and the effects of any new treatment on the control of seizures regardless of the prognostic category. In addition, physicians tend to undervalue the communication of specific information, like the risk of sudden unexpected death in epilepsy (SUDEP) or the existence of lay associations, which might be of special interest for selected categories of patients. Significance Differences between patients with epilepsy and their caring physicians in terms of needs and priorities and suboptimal communication call for the implementation of programs aimed at addressing the factors deemed most relevant by patients and caregivers for the management of the disease.

OBJECTIVE: An increased cardiovascular mortality and morbidity has been widely reported in patients with atrial fibrillation (AF). In this study, a subanalysis of the AntiThrombotic Agents Atrial Fibrillation (ATA‐AF) is performed with the aim to evaluate estimated glomerular filtration rate (eGFR) as an independent prognostic marker of cardiovascular mortality and morbidity in patients with AF. METHODS AND RESULTS: The ATA‐AF study enrolled 7148 patients with AF, in 360 Italian centers. The eGFR was calculated from data reported in patient notes or hospital database. This post‐hoc analysis included 1097 AF patients with eGFR data available and 1‐year clinical follow‐up. The endpoint was assessed as cardiovascular mortality and/or hospital admission for cardiovascular causes at follow‐up. Patients were also divided in two groups according to the eGFR (

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Some evidence shows that gastroesophageal reflux disease (GERD) may be a trigger for paroxysmal AF (PAF). Most of the previous studies that correlated GERD and AF used questionnaires to diagnose GERD, not an objective evaluation. This study aims to evaluate in patients with PAF: (a) accuracy of symptoms to diagnose GERD; (b) prevalence of GERD; and (c) temporal correlation between cardiac arrhythmia and reflux. Twenty-two patients (59% females, mean age 68 years) with PAF underwent esophageal manometry followed by ambulatory pH monitoring and concurrent Holter. Eight (36%) patients had GERD symptoms. Patients were grouped as GERD+ or GERD− based on the DeMeester score. Temporal correlation between arrhythmia and reflux was recorded. Six (27%) patients were GERD+. Symptoms had sensitivity and specificity of 50 and 70%, respectively, for the diagnosis of GERD. Episodic AF occurred in one patient only (GERD−). There were 23 episodes of AF during the test with 14% correlation with reflux. Persistent AF during the period of the test was found in five patients (60% GERD+). Our results show: (a) Symptoms have a low accuracy for the diagnosis of GERD; (b) the prevalence of GERD in patients with PAF is low; and (c) temporal correlation between episodes of reflux and cardiac arrhythmia is low.

Background The independent prognostic impact of diabetes mellitus ( DM ) and prediabetes mellitus (pre‐ DM ) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐ DM on survival outcomes in the GISSI ‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial. Methods and Results We assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI ‐ HF trial, who were stratified by presence of DM (n=2852), pre‐ DM (n=2013), and non‐ DM (n=2070) at baseline. Compared with non‐ DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐ DM patients and those with pre‐ DM . Cox regression analysis showed that DM , but not pre‐ DM , was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI , 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI , 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI , 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI , 1.01–1.29, respectively). Conclusions Presence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00336336.

Objectives Observational studies on early surgery in infective endocarditis have conflicting results. This study aims to compare the treatment strategies for early surgery (within 2 weeks of diagnosis) and late surgery/medical therapy in terms of survival among patients with the left-sided infective endocarditis. Methods This study included patients with the left-sided infective endocarditis registered between 2006 and 2010 in the Italian Registry of Infective Endocarditis (RIEI). A Cox proportional hazards model was used to estimate the effect of these treatment strategies on overall survival and included sociodemographic and clinical characteristics associated with treatment, risk factors for mortality and early surgery as a time-dependent covariate to avoid indication and immortal time biases. Results Among the 502 patients included, 184 (36.7%) underwent early surgery. Of the remaining 318 patients, 138 underwent late surgery. The early surgery group had fewer patients with comorbidities and with enterococcus as the causative microorganism, but this group had more complicated cardiac conditions. No difference in mortality risk was estimated between the treatment groups including early surgery as time-dependent variables (adjusted hazard ratio = 0.95, 95% confidence interval 0.55-1.63), while a distorted and overestimated beneficial effect of surgery was estimated considering surgery as a non-time-dependent variable (adjusted hazard ratio 0.41, 95% confidence interval 0.25-0.70). Conclusions Our study did not confirm a better overall survival in patients undergoing early surgery. However, even with the use of statistical techniques to control biases, we could not draw definitive conclusions that early surgery is not beneficial. Our results need to be assessed by randomized trials before any changes in clinical practice can be recommended.

Introduction The epidemiology of infective endocarditis (IE) is changing due to a number of factors, including aging and health related comorbidities and medical procedures. The aim of this study is to describe the main clinical, epidemiologic and etiologic changes of IE from a large database in Italy. Methods We prospectively collected episodes of IE in 17 Italian centers from July 2007 to December 2010. Results We enrolled 677 patients with definite IE, of which 24% health-care associated. Patients were male (73%) with a median age of 62years (IQR: 49–74) and 61% had several comorbidities. One hundred and twenty-eight (19%) patients had prosthetic left side IE, 391 (58%) native left side IE, 94 (14%) device-related IE and 54 (8%) right side IE. A predisposing cardiopathy was present in 50%, while odontoiatric and non odontoiatric procedures were reported in 5% and 21% of patients respectively. Symptoms were usually atypical and precocious. The prevalent etiology was represented by Staphylococcus aureus (27%) followed by coagulase-negative staphylococci (CNS, 21%), Streptococcus viridans (15%) and enterococci (14%). CNS and enterococci were relatively more frequent in patients with intravascular devices and prosthesis and S. viridans in left native valve. Diagnosis was made by transthoracic and transesophageal echocardiography in 62% and 94% of cases, respectively. The in-hospital mortality was 14% and 1-year mortality was 21%. Conclusion The epidemiology is changing in Italy, where IE more often affects older patients with comorbidities and intravascular devices, with an acute onset and including a high frequency of enterococci. There were few preceding odontoiatric procedures.

Udgivelsesdato: 2010 AIMS: To assess the association between circulating levels of chromogranin A (CgA) and outcome in a large population of patients with chronic heart failure (HF). METHODS AND RESULTS: Plasma CgA levels were measured at randomization and after 3 months in 1233 patients (median age 68 years, 80% male) with chronic, stable HF from the GISSI-HF trial. Circulating CgA levels were associated with several established risk markers in HF, including increased age, diabetes, reduced renal function, and heart rate variability. During a median follow-up of 3.9 years, 333 patients (27%) died. By univariable analysis, plasma CgA levels at baseline were strongly associated with all-cause mortality during follow-up; 2nd vs. 1st tertile: HR 1.58 (1.17-2.11), P = 0.002; and 3rd vs. 1st tertile: HR 2.35 (1.78-3.10), P < 0.0001. After adjustment for established risk factors of mortality, this association was attenuated and no longer significant. Randomized treatments with n-3 polyunsaturated fatty acid or rosuvastatin did not significantly change plasma CgA concentration over 3 months. CONCLUSION: Measurement of circulating CgA levels in patients with chronic, stable HF does not provide incremental prognostic information to that obtained from physical examination, routine biochemical analysis, and contemporary HF biomarkers.

Introduction: Emerging diseases are of great interest, especially those associated with high mortality rates such as hantaviruses. We aimed to conduct a seroepidemiological survey to determine the levels of hantavirus infection. Methods: In-house enzyme-linked immunosorbent assay (ELISA) was used to detect specific antibodies. Results: Of the 429 samples collected, seropositivity of 3.9% to anti-hantavirus immunoglobulin G (IgG) was observed (CI 95%: 2.3-5.7). Moreover, in three cases, immunoglobulin M (IgM) was detected, of which two were diagnosed as hantavirus cardiopulmonary syndrome (HCPS). Conclusions: Our data indicate the considerable occurrence of previous hantavirus infections, highlighting occurrences from sub-clinical cases to HCPS. Keywords: Hantavirus. Zoonosis. Hantavirus cardiopulmonary syndrome.Hantaviruses are an emerging zoonosis transmitted mainly by the inhalation of aerosols from the excreta of infected wild rodents. Following the inhalation, viral particles may invade endothelial cells and platelets through tropism by β-integrin receptors. Subsequently, a heightened immune response can lead to pulmonary edema and cardiogenic shock as observed in hantavirus cardiopulmonary syndrome (HCPS). The evolution to this clinical picture reflects in a high case fatality rate ranging from 35 to 50% in several American countries

Summary Background Oral anticoagulation is underused in patients with atrial fibrillation. We assessed the impact of a multifaceted educational intervention, versus usual care, on oral anticoagulant use in patients with atrial fibrillation. Methods This study was a two-arm, prospective, international, cluster-randomised, controlled trial. Patients were included who had atrial fibrillation and an indication for oral anticoagulation. Clusters were randomised (1:1) to receive a quality improvement educational intervention (intervention group) or usual care (control group). Randomisation was carried out centrally, using the eClinicalOS electronic data capture system. The intervention involved education of providers and patients, with regular monitoring and feedback. The primary outcome was the change in the proportion of patients treated with oral anticoagulants from baseline assessment to evaluation at 1 year. The trial is registered at ClinicalTrials.gov, number NCT02082548. Findings 2281 patients from five countries (Argentina, n=343; Brazil, n=360; China, n=586; India, n=493; and Romania, n=499) were enrolled from 48 clusters between June 11, 2014, and Nov 13, 2016. Follow-up was at a median of 12·0 months (IQR 11·8–12·2). Oral anticoagulant use increased in the intervention group from 68% (804 of 1184 patients) at baseline to 80% (943 of 1184 patients) at 1 year (difference 12%), whereas in the control group it increased from 64% (703 of 1092 patients) at baseline to 67% (732 of 1092 patients) at 1 year (difference 3%). Absolute difference in the change between groups was 9·1% (95% CI 3·8–14·4); odds ratio of change in the use of oral anticoagulation between groups was 3·28 (95% CI 1·67–6·44; adjusted p value=0·0002). Kaplan-Meier estimates showed a reduction in the secondary outcome of stroke in the intervention versus control groups (HR 0·48, 95% CI 0·23–0·99; log-rank p value=0·0434). Interpretation A multifaceted and multilevel educational intervention, aimed to improve use of oral anticoagulation in patients with atrial fibrillation and at risk for stroke, resulted in a significant increase in the proportion of patients treated with oral anticoagulants. Such an intervention has the potential to improve stroke prevention around the world for patients with atrial fibrillation. Funding Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer.

Summary Background and objectives Poorphysical performanceiscommoninpatients with kidneyfailureondialysis (CKD5D). Whether lung congestion, a predictable consequence of cardiomyopathy and fluid overload, may contribute to the low physical performance of CKD-5D patients has not been investigated in hemodialysis patients. Design, setting, participants, & measurements This study investigated the relationship between the physical functioning scale of the Kidney Disease Quality of Life Short Form and a validated ultrasonographic measure of lung water in a multicenter survey of 270 hemodialysis patients studied between 2009 and 2010. ResultsModerate to severe lung congestion by lung ultrasonography was observed in 156 (58%) patients; among these, 60 (38%) were asymptomatic (New York Heart Association [NYHA] class I). On univariate analysis, physical functioning was inversely associated with lung water in the whole group (r=20.22; P,0.001) and in the subgroup of asymptomatic patients (r=20.40; P=0.002). Age (r=20.45; P,0.001) and past cardiovascular events (r=20.22; P=0.002) were also inversely associated with physical functioning, whereas albumin (r=0.23;P,0.001) was directly associated with the same parameter. NYHA class correlated strongly with physical functioning (r=20.52; P,0.001). In a multiple regression analysis, both NYHA class and lung water maintained an independentassociationwithphysical functioning,whereasalbuminandbackgroundcardiovascularevents failed to independently relate with the same outcome. Conclusions Symptomatic and asymptomatic lung congestion is associated with poor physical functioning in hemodialysis patients. This association is independent of NYHA, suggesting that this measurement and NYHA may have complementary value to explain the variability in physical performance in hemodialysis patients. Clin J Am Soc Nephrol 8: 1343–1348, 2013. doi: 10.2215/CJN.11111012

Background: Studies have shown the impact of atrial fibrillation (AF) on the patients' quality of life. Specific questionnaires enable the evaluation of relevant events. We previously developed a questionnaire to assess the quality of life of patients with AF (AFQLQ version 1), which was reviewed in this study, and new domains were added. Objective: To demonstrate the reproducibility of the AFQLQ version 2 (AFQLQ v.2), which included the domains of fatigue, illness perception and well-being. Methods: We applied 160 questionnaires (AFQLQ v.2 and SF-36) to 40 patients, at baseline and 15 days after, to measure inter- and intraobserver reproducibility. The analysis of quality of life stability was determined by test-retest, applying the Bartko intraclass correlation coefficient (ICC). Internal consistency was assessed by Cronbach's alpha test. Results: The total score of the test-retest (n = 40) had an ICC of 0.98 in the AFQLQ v.2, and of 0.94 in the SF36. In assessing the intra- and interobserver reproducibility of the AFQLQ v.2, the ICC reliability was 0.98 and 0.97, respectively. The internal consistency had a Cronbach's alpha coefficient of 0.82, compatible with good agreement of the AFQLQ v.2. Conclusion: The AFQLQ v.2 performed better than its previous version. Similarly, the domains added contributed to make it more comprehensive and robust to assess the quality of life of patients with AF. Resumo Fundamento: Estudos demonstraram o impacto da fibrilação atrial (FA) na qualidade de vida dos pacientes. Questionários específicos permitem avaliar manifestações pertinentes. Desenvolvemos anteriormente questionário de qualidade de vida para FA (QVFA versão 1) e, neste estudo, apresentamos reanálise e adições de novos domínios. Objetivo: Demonstrar a reprodutibilidade do QVFA na versão 2 (QVFA v.2) com a inclusão dos domínios fadiga, percepção da doença e bem-estar. Métodos: Foram aplicados 160 questionários (QVFA v.2 e SF-36) em 40 pacientes com intervalos de 15 dias para mensuração da reprodutibilidade inter- e intra-observador. A análise de estabilidade da qualidade de vida foi determinada pelo teste-reteste, aplicando o coeficiente de correlação intraclasse (CCI) de Bartko. A consistência interna foi avaliada pelo teste alfa de Cronbach. Resultados: O escore total do teste-reteste (n=40) apresentou CCI de 0,98 no QVFA v.2 e de 0,94 no SF36. Na avaliação intra-observador e inter-observador do QVFA v.2, a confiabilidade do CCI foi de 0,98 e 0,97, respectivamente. Para a análise da consistência interna, obteve-se um coeficiente alfa de Cronbach de 0,82, compatível com boa concordância do QFVA v.2. Conclusão: O QVFA v.2 apresentou melhor desempenho em relação à versão anterior. No mesmo sentido, os domínios acrescentados contribuíram para torná-lo mais abrangente e robusto para avaliar a qualidade de vida de pacientes com FA.

Background. Polymorphisms in the FTO (fat-mass and obesity-associated) gene have been associated with the body mass index, cancer, type 2 diabetes and hypertension. Methods. We investigated the relationship between 17 tag single-nucleotide polymorphisms (SNPs) and all-cause mortality in three cohorts of dialysis patients (CREED-1, North Apulian and CREED-2 cohorts; n=783) and in one cohort of stage 2–5 CKD patients (n= 757). Results. We first explored the association between the 17 tag SNPs and all-cause mortality in the CREED-1 cohort and found that patients with the A allele of the FTO rs708259 polymorphism had an elevated risk of mortality (hazard ratio, HR: 1.52, 95% confidence interval (CI) 1.11–2.08; P = 0.008). Similarly, the A allele was associated with an increased risk of death also in the other two dialysis cohorts (North Apulian cohort, risk: +23%; CREED-2 cohort, risk: +21%). The elevated risk portended by this allele was even higher in the stage 2–5 CKD cohort (+97%). However, the risk of mortality associated with the A allele in the three confirmatory cohorts failed to achieve formal statistical significance. In a meta-analysis including the four cohorts (n= 1540; total deaths, n= 381), individuals with the A allele had a 42% excess risk of death (HR: 1.42, 95% CI 1.14–1.76, P = 0.002). Conclusion. The A allele of the FTO rs708259 polymorphism is an independent predictor of all-cause mortality in patients with CKD of various severity. These data support our hypothesis that the FTO gene may be a relevant genetic risk factor for mortality in this population.

Background. Chest ultrasound (US) is a non-invasive wellvalidated technique for estimating extravascular lung water (LW) in patients with heart diseases and in end-stage renal disease. We systematically applied this technique to the whole peritoneal dialysis (PD) population of five dialysis units. Methods. We studied the cross-sectional association between LW, echocardiographic parameters, clinical [pedal oedema, New York Heart Association (NYHA) class] and bioelectrical impedance analysis (BIA) markers of volume status in 88 PD patients. Results. Moderate to severe lung congestion was evident in 41 (46%) patients. Ejection fraction was the echocardiographic parameter with the strongest independent association with LW (r ¼� 0.40 P ¼ 0.002). Oedema did not associate with LW on univariate and multivariate analysis. NYHA class was slightly associated with LW (r ¼ 0.21 P ¼ 0.05). Among patients with severe lung congestion, only 27% had pedal oedema and the majority (57%) had no dyspnoea (NYHA Class I). Similarly, the prevalence of patients with BIA, evidence of volume excess was small (11%) and not significantly different (P ¼ 0.79) from that observed in patients with mild or no congestion (9%). Conclusions. In PD patients, LW by chest US reveals moderate to severe lung congestion in a significant proportion of asymptomatic patients. Intervention studies are necessary to prove the usefulness of chest US for optimizing the control of fluid excess in PD patients.

Background and methods: Since heart rate (HR) is a cardiovascular risk factor and a marker of sympa- thetic activity, we tested the predictive value of HR for progression to kidney failure in a well characterized cohort of 759 patients with stage 2-5 CKD followed up for 29 ± 11 months. Results: Overall, a total of 244 patients had renal events. In an unadjusted analysis by age tertiles the predictive value of HR for renal events was appar- ent only in patients in the third age tertile (older than 68 years) but not in those in the first two tertiles indi- cating effect modification by age of the HR - progres- sion to kidney failure relationship. In a multiple Cox regression model adjusting for potential confounders, a 5 beats/min increase in HR entailed a 16% risk ex- cess (Hazard Ratio = 1.16, P = .004) for renal events in patients in the third age tertile but no excess risk for the same events in patients in the first two tertiles. A statistically significant interaction (P

BACKGROUND The aim of the present study was the detection of asymptomatic coronary re-stenosis after percutaneous coronary intervention (PCI). METHODS We studied 26 subjects who had been recently implanted with a paclitaxel-eluting coronary stent by both a conventional exercise test and the determination of plasma B-type natriuretic peptide (BNP) levels. RESULTS At control coronary angiography, nine months after initial PCI, six patients had re-stenosis and 20 were re-stenosis free. We found that re-stenosis was best predicted by the combination of a basal plasma BNP level > or = 50 pg/ml and a positive or uncertain conventional exercise test (positive likelihood ratio of the combination = 10). The best predictor of absence of re-stenosis was a low (< 50 pg/ml) plasma BNP level (negative likelihood ratio = 0.26). CONCLUSIONS Accordingly, basal BNP level testing can be recommended in the follow-up evaluation of coronary patients after PCI, to improve both the detection and the exclusion of asymptomatic re-stenosis.

Background and methods. The endogenous inhibitor of nitric oxide synthase (NOs) asymmetrical dimethylarginine (ADMA) has been implicated as a possible modulator of inducible NOs during acute inflammation. We examined the evolution in the plasma concentration of ADMA measured at the clinical outset of acute inflammation and after its resolution in a series of 17 patients with acute bacterial infections. Results. During the acute phase of inflammation/ infection, patients displayed very high levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin and nitrotyrosine. Simultaneous plasma ADMA concentration was similar to that in healthy subjects while symmetric dimethyl-arginine (SDMA) levels were substantially increased and directly related with creatinine. When infection resolved, ADMA rose from 0.62 � 0.23 to 0.80 � 0.18mmol/l (þ29%, P ¼ 0.01) while SDMA remained unmodified. ADMA changes were independent on concomitant risk factor changes and inversely related with baseline systolic and diastolic pressure. Changes in the ADMA/SDMA ratio were compatible with the hypothesis that inflammatory cytokines activate ADMA degradation. Conclusions. Resolution of acute inflammation is characterized by an increase in the plasma concentration of ADMA. The results imply that ADMA suppression may actually serve to stimulate NO synthesis or that in this situation plasma ADMA levels may not reflect the inhibitory potential of this methylarginine at the cellular level.

This study examines the involvement of spatial and visual working memory (WM) in the construction of flexible spatial models derived from survey and route descriptions. Sixty young adults listened to environment descriptions, 30 from a survey perspective and the other 30 from a route perspective, while they performed spatial (spatial tapping [ST]) and visual (dynamic visual noise [DVN]) secondary tasks – believed to overload the spatial and visual working memory (WM) components, respectively – or no secondary task (control, C). Their mental representations of the environment were tested by free recall and a verification test with both route and survey statements. Results showed that, for both recall tasks, accuracy was worse in the ST than in the C or DVN conditions. In the verification test, the effect of both ST and DVN was a decreasing accuracy for sentences testing spatial relations from the opposite perspective to the one learnt than if the perspective was the same; only ST had a stronger interference effect than the C condition for sentences from the opposite perspective from the one learnt. Overall, these findings indicate that both visual and spatial WM, and especially the latter, are involved in the construction of perspective-flexible spatial models.

Long-term visit-to-visit blood pressure (BP) variability predicts a high risk for cardiovascular events in patients with essential hypertension. Whether long-term visit-to-visit BP variability holds the same predictive power in predialysis patients with chronic kidney disease (CKD) is unknown. Here we tested the relationship between long-term visit-to-visit office BP variability and a composite end point (death and incident cardiovascular events) in a cohort of 1618 patients with stage 2–5 CKD. Visit-to-visit systolic BP variability was significantly and independently related to baseline office, maximal, and average systolic BPs, age, glucose, estimated glomerular filtration rate, and albumin, and to the number of visits during the follow-up. Both the standard deviation of systolic BP (hazard ratio: 1.11, 95% confidence interval: 1.01–1.20) and the coefficient of variation of systolic BP (hazard ratio: 1.15, 95% confidence interval: 1.02–1.29) were significant predictors of the combined end point independent of peak and average systolic BP, cardiovascular comorbidities, Framingham risk factors, and CKD-related risk factors. Antihypertensive treatment (β-blockers and sympatholytic drugs) significantly abrogated the excess risk associated with high systolic BP variability. Thus, large visit-to-visit systolic BP variability in patients with CKD predicts a higher risk of death and nonfatal cardiovascular events independent of underlying BP levels.

Background— Moderate, regular alcohol consumption is generally associated with a lower risk of cardiovascular events but data in patients with chronic heart failure are scarce. We evaluated the relations between wine consumption, health status, circulating biomarkers, and clinical outcomes in a large Italian population of patients with chronic heart failure enrolled in a multicenter clinical trial. Methods and Results— A brief questionnaire on dietary habits was administered at baseline to 6973 patients enrolled in the Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza Cardiaca-Heart Failure (GISSI-HF) trial. The relations between wine consumption, fatal and nonfatal clinical end points, quality of life, symptoms of depression, and circulating biomarkers of cardiac function and inflammation (in subsets of patients) were evaluated with simple and multivariable-adjusted statistical models. Almost 56% of the patients reported drinking at least 1 glass of wine per day. After adjustment, clinical outcomes were not significantly different in the predefined 4 groups of wine consumption. However, patients with more frequent wine consumption had a significantly better perception of health status (Kansas City Cardiomyopathy Questionnaire score, adjusted P P =0.01), and lower plasma levels of biomarkers of vascular inflammation (osteoprotegerin and C-terminal proendothelin-1, adjusted P P =0.01) after adjusting for possible confounders. Conclusions— We show for the first time in a large cohort of patients with chronic heart failure that moderate wine consumption is associated with a better perceived and objective health status, lower prevalence of depression, and less vascular inflammation, but does not translate into more favorable clinical 4-year outcomes. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT0033633.

Cystatin C (Cys C) is a cysteine protease inhibitor produced at a constant rate by nucleated cells, filtered through the glomerular membrane and reabsorbed by kidney tubular cells. Aim of this cross-sectional and longitudinal study was to assess serum Cys C and creatinine (Crea) concentrations in thyroid dysfunction. One hundred and eighty-one patients, 26 with untreated non-toxic nodular goiter, 58 with hyperthyroidism, 31 on L-T4 suppressive therapy for non-toxic nodular goiter, 35 with short-term hypothyroidism after L-T4 withdrawal to perform whole body scan for thyroid cancer, 11 with long-term hypothyroidism due to chronic autoimmune thyroiditis and 20 patients with mild hypothyroidism were enrolled in the study. Fifty-seven age- and sex-matched normal subjects served as controls. Serum Cys C, Crea, free T4 (FT4), FT3 and TSH were assessed. Thirty hyperthyroid patients and 35 short-term hypothyroid patients were followed prospectively until euthyroidism was reached by methimazole or L-T4 therapy. The cross-sectional study showed that mean serum Crea concentrations were significantly reduced in overt hyperthyroid or subclinical hyperthyroid patients, while it was increased in overt hypothyroid patients, but not in mild hypothyroidism. Conversely, serum Cys C levels were significantly increased in overt hyperthyroid patients compared to controls (p

BACKGROUND Whether hypertension and left ventricular hypertrophy (LVH) are more prevalent in CAPD than in haemodialysis (HD) patients is still under discussion. METHODS To examine this problem we compared a group of 51 CAPD patients, with a group of 201 HD patients. The evaluation included the measurement of atrial natriuretic peptide (atrial natriuretic factor (ANF)), taken as indicator of volume status, and echocardiographic measurements. RESULTS CAPD patients were older, had been treated for a shorter time, and had lower serum albumin and phosphate than HD patients. Plasma ANF was higher (P

Background The choice of the imaging modality (transthoracic [TTE] vs. transesophageal echocardiography [TEE]) for the diagnosis of infective endocarditis (IE) depends on different variables. Aim of the present study is to provide updated data on the diagnostic sensitivity and the clinical usefulness of TTE vs. TEE from the Italian Registry on IE (RIEI). Methods The RIEI has enrolled consecutive cases of IE in every participating centre, evaluating diagnostic and therapeutic data from a real world practice perspective. Results From July 2007 to October 2010, 658 consecutive cases with definite IE according to Duke criteria have been enrolled in the RIEI (483 males). The following diagnostic echocardiographic exams were performed: 616 TTE (94%) and 476 TEE (72%). A positive TTE was recorded in 399 cases (65%), an uncertain TTE in 108 cases (17%), and a negative TTE in 109 cases (18%). For TEE, a positive study was reported in 451 cases (95%), uncertain in 13 cases (2.7%), and negative in 12 cases (2.5%) (P

The inotropic effect of isoproterenol, as well as the β-adrenoceptor population, was measured in pregnant uterine tissue from female spontaneous hypertensive rats (SHR) (control group: C) and female SHR that were grafted with skin from Holtzman male rats (eclamptic group: E). The K d value of the concentration response curve of isoproterenol was higher for uteri from E rats than C rats. This phenomenon was not accompanied by a modification in the expression of β-adrenoceptors. Inhibition of the synthesis of prostaglandins prevented the hyporeactivity to isoproterenol during eclampsia. Moreover, uteri from E rats generated and released greater amounts of prostaglandin E 2 (PGE 2 ) than uteri from C rats, even in the presence or absence of isoproterenol. In addition, whereas isoproterenol administered alone increased basal cyclic AMP (cAMP) production from C uteri, PGE 2 administered alone enhanced cAMP production in E uterine tissue. These results suggest that the decrease in β-adrenergic response to the agonist in E rats is ascribed to PGE 2 production. The abnormal reactivity to the β-agonist could be associated with a heterologous desensitization of uterine β-adrenoceptors exerted by PGE 2 overload in uteri from E rats. These results bear directly on the regulation of uterine motility during pregnancy, since an impaired response to β-adrenergic innervation could lead to increased uterine motility, impairing the maintenance of pregnancy.

Background: The Multiple Intervention and Audit in Renal Diseases to Optimize Care (MAURO) study was a cluster randomized controlled trial in 22 renal clin- ics which aimed to assess the efficacy of a multimodal quality improvement intervention to increase compli- ance with guideline recommendations for prevention of chronic kidney disease (CKD) progression and car- diovascular (CV) complications. The trial aimed to test whether this multimodal intervention improved adher- ence to recommended targets for a series of surro- gate indicators relevant to blood pressure (BP) control, sodium intake, proteinuria, dyslipidemia, anemia and calcium-phosphate alterations. The trial also tested whether the same intervention slowed CKD progres- sion and prevented CV complications in CKD patients. Method: Twenty-two renal clinics were randomized to 2 arms: an intervention arm applying a multimethod quality improvement intervention and a control arm providing standard care. Surrogate indicators were measured to evaluate blood pressure (BP) control, sodium intake, proteinuria, dyslipidemia, anemia and calcium-phosphate alterations. Results: Notwithstanding the fact that the vast major- ity of patients enrolled in this study (95%) were being treated with antihypertensive drugs, BP goals at base- line (specific for proteinuria level and diabetes) were met only in 45% of nonproteinuric patients and in just 14% and 18% of proteinuric and diabetic patients, respectively. The use of diuretics in hypertensive pa- tients was less than what was needed, and about 80% of patients showed a salt excretion >100 mmol/ 24 hours. Total and low-density lipoprotein cholesterol levels were out of target in over 40% of patients, but only about 60% of these were on statins. A large ma- jority of CKD patients were obese or overweight. The proportion of smokers was relatively small (13%), and 37% of patients had quit smoking, indicating patients' awareness of the health risks of smoking. Conclusions: In our cohort, management of modifiable risk factors for CKD progression and CV disease could be substantially improved.

Purpose Decline in physical function is commonly observed in patients with kidney failure on dialysis. Whether lung congestion, a predictable consequence of cardiomyopathy and fluid overload, may contribute to the low physical functioning of these patients has not been investigated. Methods In 51 peritoneal dialysis (PD) patients, we investigated the cross-sectional association between the physical functioning scale of the Kidney Disease Quality of Life Short Form (KDQOL-SF: Rand Corporation, Santa Monica, CA, USA) and an ultrasonographic measure of lung water recently validated in dialysis patients. The relationship between physical functioning and lung water was also analyzed taking into account the severity of dyspnea measured using the New York Heart Association (NYHA) classification currently used to grade the severity of heart failure. Results Evidence of moderate-to-severe lung congestion was evident in 20 patients, and this alteration was asymptomatic (that is, NHYHA class I) in 11 patients (55%). On univariate analysis, physical functioning was inversely associated with lung water ( r = –0.48, p < 0.001), age ( r = –0.44, p = 0.001), previous cardiovascular events ( r = –0.46, p = 0.001), and fibrinogen ( r = –0.34, p = 0.02). Physical functioning was directly associated with blood pressure, the strongest association being with diastolic blood pressure ( r = 0.38, p = 0.006). The NYHA class correlated inversely with physical functioning ( r = –0.51, p < 0.001). In multiple regression analysis, only lung water and fibrinogen remained independent correlates of physical functioning. The NYHA class failed to maintain its independent association. Conclusions This cross-sectional study supports the hypothesis that symptomatic and asymptomatic lung congestion is a relevant factor in the poor physical functioning of patients on PD.

Background Pro-inflammatory cytokines play a key role in bone remodeling. Inflammation is highly prevalent in CKD-5D patients, but the relationship between pro-inflammatory cytokines and fractures in CKD-5D patients is unclear. We studied the relationship between inflammatory cytokines and incident bone fractures in a cohort of CKD-5D patients. Methods In 100 CKD-5D patients (66 on HD, 34 on CAPD; males:63, females:37; mean age: 61 ± 15; median dialysis vintage: 43 months) belonging to a single renal Unit, we measured at enrolment bone metabolic parameters (intact PTH, bone and total alkaline phosphatase, calcium, phosphate) and inflammatory cytokines (TNF-α, IL-6, CRP). Patients were followed-up until the first non traumatic fracture. Results During follow-up (median: 74 months; range 0.5 -84.0) 18 patients experienced fractures. On categorical analysis these patients compared to those without fractures had significantly higher intact PTH (median: 319 pg/ml IQ range: 95–741 vs 135 pg/ml IQ: 53–346; p = 0.04) and TNF-α levels (median: 12 pg/ml IQ: 6.4-13.4 vs 7.8 pg/ml IQ: 4.6-11; p = 0.02). Both TNF-α (HR for 5 pg/ml increase in TNF-α: 1.62 95% CI: 1.05-2.50; p = 0.03) and intact PTH (HR for 100 pg/ml increase in PTH: 1.15 95% CI: 1.04-1.27; p = 0.005) predicted bone fractures on univariate Cox’s regression analysis. In restricted (bivariate) models adjusting for previous fractures, age, sex and other risk factors both PTH and TNF-α maintained an independent association with incident fractures. Conclusions In our bivariate analyses TNF-α was significantly associated with incident fractures. Analyses in larger cohorts and with adequate number of events are needed to firmly establish the TNF α -fracture link emerged in the present study.

This study was aimed to identify the knowledge and attitudes of dentists regarding ageing and the elderly.As the population ages, there is a greater demand for differentiated care from health professionals. However, the treatment needs of the elderly population are not sufficiently addressed, particularly in developing countries.An official list of all dentists registered in the city of Belo Horizonte, Brazil, was obtained from the Regional Dentistry Council. A questionnaire was delivered to 276 randomly selected dentists; the survey contained questions designed to characterise the sample and identify dentists' conduct towards elderly patients. A Likert scale was used to identify knowledge regarding care for the elderly and attitudes towards ageing.Women demonstrated more positive attitudes towards the elderly. Graduates who worked in the public sector demonstrated a greater knowledge of geriatric dentistry (p0.05). Attending specific continuing education courses had no influence over the dentists' willingness to treat the elderly population. Significant associations were not found between attitudes and knowledge regarding the elderly.Dentists who worked in the public sector demonstrated a greater knowledge regarding the elderly. This knowledge did not influence attitudes towards ageing. Women demonstrated a more positive attitude regarding ageing and dental care.

The objective of this study was to understand the coping mechanisms of men living with HIV/AIDS in terms of their work environment. A qualitative study was carried out at a specialized outpatient clinic in Fortaleza-Ceará between March and June 2010, involving eleven men infected with the virus. Semi-structured and audio-recorded interviews were used. The statements were categorized through content analysis into the following categories: absence from work due to the infection; subterfuges used to hide the disease; disrespect for confidentiality in the work environment; suffering associated with the fear of rejection and prejudice; ways of coping after diagnosis of the disease; and the importance of work for personal accomplishment. In conclusion, men infected with HIV face counterproductive situations in the work environment, mainly evidenced by fear of discovery of the infection and prejudice. Associated with coping, absences for health monitoring purposes interfered with performance at work and increased the risk of losing their job.

The authors report a 29-year-old kidney transplant patient who presented, four episodes of severe hyponatraemia associated with sepsis from 2006 to 2010. He was a long-term user of marijuana. The association between severe recurrent hyponatraemia during sepsis and marijuana addiction might not be casual, since experimental data show that vasopressin release induced by sepsis is modulated by the endocannabinoid system.

An updated review of cases of reactivated visceral leishmaniasis (VL) in transplant patients is presented, with a new report of a kidney transplant patient who had VL caused by reactivation of a dormant infection contracted 21 years previously. Close to the time of disease reactivation, the patient had a primary varicella-zoster infection.

This study was performed with the purpose to analyze the communication between nursing students and patients with AIDS during peripheral venous puncture. Video recordings were made of six pairs (student-patient) while performing the venous puncture procedure in May 2009 at a day-hospital in Fortaleza-Ceará. As a group, four judges evaluated the interactions established between the pairs. The analyses were categorized in: Valuing technique over communication; Mask: a barriers to communication; Private space invasion; Interference of the environment in the communication. It was concluded that different factors increase the difficulty establishing an effective communication, especially the need for students to be trained about the importance of establishing communication during care, so as to promote humanized and individual care, in which sensitivity and empathy overlap fear and insecurity.

This study assessed the oral health of the institutionalized elderly in Belo Horizonte, Minas Gerais State, Brazil. A sample of 335 individuals over 60 years of age was randomly selected. Data were collected through interviews, review of medical records, and clinical examination by a single researcher. Oral health was evaluated in terms of oral hygiene, caries, and periodontal disease. Bacterial plaque was present on 76% of the dental surfaces, and 57% of the elderly using upper dentures presented plaque on at least one of its surfaces. DMF-T index was 30.8, with the missing component representing 94.2%. Missing sextant was the worst periodontal finding in 78.2% of the elderly. Among the valid sextants, there was a higher prevalence of 4 to 5mm periodontal pocket and attachment loss from 4 to 5mm (47%). According to the findings, institutionalized elderly suffer from precarious oral health, with deficient oral hygiene, high caries rate, tooth loss, and periodontal pocket.

Extracellular matrix accumulation, epithelial-to-mesenchymal transition, tubular atrophy and loss of peritubular capillary network are hallmarks of tubulointerstitial injury in progressive renal diseases. In this study, we analyzed endostatin expression in kidneys subjected to unilateral ureteral obstruction (UUO).Collagen XVIII mRNA expression was evaluated by real-time polymerase chain reaction (PCR). Endostatin and CD31 protein levels were analyzed by Western blot and immunohistochemistry. In vitro quantification of collagen XVIII and fibrosis-related genes in HK2 cells was performed by real-time PCR.UUO significantly increased collagen XVIII mRNA expression and released a 30-kDa endostatin fragment. Immunohistochemistry revealed endostatin expression increased in injured tissue, mainly on tubular cells. Of interest, expression of CD31 was significantly reduced by UUO. Endostatin administration in vitro did not modify the expression of genes related to fibrosis development. However, in vitro TGF-beta1 administration induced expression of collagen XVIII/endostatin mRNA in human tubular cells.Endostatin is expressed during the progression of renal fibrosis in vitro and in vivo, suggesting a role for endostatin in development of tubulointerstitial injury.

A number of reports on dialysis and transplantation for diabetic patients in the UK and USA are available. The aim of the present survey was to assess the prevalence, main characteristics and complications of diabetic patients treated by dialysis and transplantation in Italy. On 31 December 1987 in Italy, 1605 diabetic patients were being treated by dialysis or transplantation. The prevalence was 28 per million compared with the UK and the USA where the corresponding figures were 17 and 78 per million respectively. The annual incidence in 1987 was 9 per million (UK: 4 per million; USA: 33 per million). The mean age of the Italian diabetic patients was 59 years whereas that for British diabetic patients similarly evaluated was 48 years. Of the Italian diabetic patients 67% had NIDDM (UK: 22%; USA: 50%). Haemodialysis was used in 81% of the Italian patients, peritoneal dialysis in 14%, and only 5% were transplanted. This is in contrast to the UK where only 18% of the patients were treated by haemodialysis and 39% were transplanted. Amongst Italian patients who started RRT in 1987, 9% died within the year, and of the remainder 38% had severe bilateral visual impairment (UK 35%), 3% had had amputations (UK 6%), 7% had suffered from disabling strokes (UK 6%) and 7% had had a myocardial infarction (UK 17%). Before 31 December 1987 another 2.2% developed severe bilateral visual impairment, 0.6% underwent amputations, 1.0% had a disabling stroke and 0.6% suffered from a myocardial infarction. The proportion of diabetic patients treated by RRT in Italy is twice that of the UK but only half that of the USA.(ABSTRACT TRUNCATED AT 250 WORDS)

We investigated whether transfer of the gene encoding the angiogenesis inhibitor endostatin into the NIH/3T3 fibroblast cell line could inhibit renal tumor growth in vivo. NIH/3T3 cells were transduced with retroviral vectors containing the murine endostatin (ES) gene. SCID mice bearing CaKi-1 derived tumors were given a subcutaneous injection of either ES-transduced cells or control cells and were monitored for tumor growth. At the end of the in vivo experiment, the mean tumor volume of treated mice was 51.6 +/- 2.4 mm(3), while the tumor volume of control was 234.5 +/- 14.8 mm(3). Microvascular density was significantly decreased on treatment (control 9.79 vs. ES 2.53%, < 0.001) accompanied by a 23-fold increase in intraturmoral necrotic area and a 2.94-fold increase in the apoptotic index, determined by immunohistochemistry with anti- activated caspase-3. Apoptotic cells were found in foci enriched in infiltrating leukocytes. in conclusion, retroviral endostatin gene transfer led to secretion of functional endostatin that was sufficiently active to inhibit tumor angiogenesis and tumor growth. A second mechanism may also be implied in endostatin-dependent tumor regression, associated with tumor infiltration of leukocytes. Besides its antiangiogenic properties, endostatin may be a promising adjuvant to immunotherapy. IPEN CNEN SP, BR-05508900 São Paulo, Brazil Universidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, Brazil CEPID FAPESP, Ctr Terapia Celular, São Paulo, Brazil Univ São Paulo, Fac Med, Dept Radiol, Expt Oncol Lab, São Paulo, Brazil Universidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, Brazil Web of Science

Renal cell carcinoma (RCC) accounts for approximately 3% of new cancer incidence and mortality in the United States. Unfortunately many RCC masses remain asymptomatic and nonpalpable until they are advanced. Diagnosis and localization of early carcinoma play an important role in the prevention and curative treatment of RCC. The autofluorescence of blood porphyrin of healthy and tumor induced in male SCID mice was analyzed using fluorescence and excitation spectroscopy. A significant contrast between normal and tumor blood could be established. Blood porphyrin fluorophore showed enhanced fluorescence band (around 630 nm) in function of the tumor growth. This indicates that either the autofluorescence intensity of the blood fluorescence may provide a good parameter for the “first approximation” characterization of the tumor stage.

Background. Low T3 is a frequent alteration in patients with ESRD. This derangement has been recently linked to inflammation in haemodialysis patients. Whether this association holds true in peritoneal dialysis patients has not been studied. Methods. We investigated the relationship between low-grade inflammation [IL-6, C-reactive protein (CRP) and serum albumin levels] and free triiodothyronine (fT3) in a cohort of 41 CAPD patients (mean age, 66 years; M, 26; F, 15) without heart failure and inter-current illnesses. Results. CAPD patients had lower fT3 levels (2.7 � 0.8 pg/ml) than healthy subjects (3.7 � 1.0 pg/ml, P < 0.001) of similar age. Free T3 levels were directly related to those of serum albumin (r ¼ 0.52, P ¼ 0.001) and inversely to IL-6 (r ¼� 0.30, P ¼ 0.05) and CRP (r ¼� 0.54, P < 0.001). Age (r ¼� 0.61, P < 0.001), haemoglobin levels (r ¼ 0.32, P ¼ 0.05) and diastolic blood pressure (r ¼ 0.50, P ¼ 0.001) were also related to fT3. In multiple regression models adjusting for all variables related to fT3, CRP and albumin were retained as independent correlates of fT3. During the follow-up (2.8 � 1.7 years) 27 patients died. Plasma fT3 levels were lower in patients who died (2.5 � 0.8 pg/ml) compared with survivors (3.3 � 0.5 pg/ml P ¼ 0.001). In Cox analyses, fT3 was a significant predictor of mortality independent of the main traditional as well as non-traditional risk factors. Conclusions. The relationship between fT3, CRP and serum albumin suggests that inflammation– malnutrition might be involved in the low T3 syndrome in CAPD patients. Thyroid dysfunction might be implicated in the pathogenic pathway which links micro-inflammation to survival in PD patients.

Plasma fibrinogen (Fib) and calcium x phosphate product have emerged as cardiovascular (CV) event predictors in hemodialysis (HD) patients, but their role in peritoneal dialysis (PD) is less studied.We investigated whether Fib and calcium x phosphate product predict CV events in a prospective cohort study of 47 continuous ambulatory PD (CAPD) patients (mean follow-up 34.6 months).During the follow-up, 29 patients experienced CV events, which were fatal in 11 of them. Plasma Fib was markedly elevated in the entire population studied (median 612 mg/dL inter-quartile range (IQ): 566-718 mg/dL). On univariate analysis, Fib was higher (p=0.02) in those patients who had fatal or non-fatal CV events (median 654 mg/dL, IQ: 577-801) than in event-free patients (median 579 mg/dL, IQ: 532-629). Patients with incident CV events also tended to have higher calcium x phosphate product (51.6 +/- 12.8 vs. 43.8 +/- 13.9 mg2/dL2, p=0.06). On multivariate Cox's regression analyses, including traditional risk factors and history of previous CV events, Fib (hazard ratio (HR) associated with 100 mg/dL increase in plasma Fib 1.29 95% confidence interval (CI) 1.03-1.63 (p=0.03)) and calcium x phosphate product (HR associated with a 5 mg2/dL2 increase 1.25 95% CI 1.05-1.49 (p=0.01)) emerged as independent CV event predictors.Calcium x phosphate product and Fib are CV event predictors in CAPD patients.

Before introducing a wrist device (NAIS-Matsushita) for blood pressure (BP) measurement in our Unit, we formally tested its validity. Since the wrist position is critical and BP in the clinical setting is often measured with patients lying in bed, we also estimated the error introduced by allowing the wrist to lay flat at the bed level. Ten normal subjects and 20 hypertensive patients took part in two consecutive studies. In the first study the subjects were sitting and the blood pressure was simultaneously taken with the auscultatory mercury sphygmomanometer on the left arm and with the NAIS on the right wrist. The wrist was kept at the heart level. In the second study two NAIS devices were used with the subjects lying in bed; the left wrist was allowed to stay at the bed level, while the right one was kept at the heart level. The diastolic BP was consistently underestimated (P0.001) by the wrist device (79 mmHg 95%CI: 75-83) as compared to the values obtained with the standard mercury sphygmomanometer (85 CI: 79-88). No significant difference was found in systolic BP (mercury: 135 CI: 127-143; wrist 134 CI: 126-141). In the second study the BP (systolic and diastolic) was markedly higher (P0.001) when the wrist was kept at the bed level (systolic bed level: 144 CI: 135-152; systolic heart level: 135 CI:126-141; diastolic bed level: 83 CI:78-88; diastolic heart level: 76 CI:71-79).

C-reactive protein (CRP) levels have not been routinely used to diagnose thyroid disease, although many thyroid conditions involve inflammation. This study was intended to determine whether CRP levels could differentiate between inflammatory and noninflammatory thyroid conditions, especially between type II inflammatory amiodarone-induced thyrotoxicosis (AIT) and type I iodine-induced AIT. Serum high-sensitivity CRP levels were measured in 100 euthyroid controls (7 taking amiodarone) and 353 patients with one of the following thyroid conditions: AIT, subacute thyroiditis, toxic diffuse goiter, nodular goiter, Hashimoto's thyroiditis, shortterm hypothyroidism, or postpartum thyroiditis. No patients with nontoxic multinodular goiter (n = 34), toxic nodular goiter (n = 23), or toxic diffuse goiter, either untreated (n = 49) or euthyroid while taking methimazole (n = 33), had positive CRP levels (>10 mg/L). The occurrence of positive CRP levels among patients with Hashimoto's thyroiditis (n = 35), short-term hypothyroidism (n = 38), and postpartum thyroiditis (n = 70) did not differ significantly from controls. The occurrence of positive CRP values did not differ significantly between patients with type I and type II AIT and controls. Six of 7 patients (86%) with untreated subacute thyroiditis had positive CRP levels (p < 0.00001). These results indicate that there is only a limited role for measurement of CRP levels in the diagnosis of thyroid diseases other than subacute thyroiditis.

Summary Background The plasma concentration of asymmetrical dimethylarginine (ADMA), an inhibitor of nitric-oxide synthase, which has been linked to endothelial dysfunction and atherosclerosis in the general population, is raised in patients with end-stage renal disease and could contribute to the high cardiovascular risk in patients with chronic renal failure. We investigated the relation between cardiovascular risk factors and plasma ADMA concentration in a cohort of haemodialysis patients (n=225), and tested the predictive power of ADMA for mortality and cardiovascular outcomes. Methods Patients had standard dialysis three times a week. We accurately recorded cardiovascular events over a mean follow-up of 33·4 months (SD 14·6); these events were reviewed by a panel of physicians. We identified correlates of plasma ADMA by univariate and multivariate analyses. Findings On univariate analysis, ADMA concentration in plasma was directly related to concentrations of fibrinogen and L-arginine in plasma, duration of dialysis treatment, and serum cholesterol concentration, and was inversely related to serum albumin concentration. On multivariate analysis, only plasma fibrinogen (p=0·0001) and serum albumin (p=0·04) concentrations were independently related to plasma ADMA concentration (multiple r =0·44, p=0·0001). 83 patients died, 53 (64%) by cardiovascular causes. In a Cox's proportional-hazards model, plasma ADMA ranked as the second factor predicting overall mortality (hazard ratio 1·26, 95% Cl 1·11–1·41, p=0·0001) and cardiovascular events (1·17, 1·04–1·33, p=0·008). Interpretation In haemodialysis patients, plasma ADMA is a strong and independent predictor of overall mortality and cardiovascular outcome. These findings lend support to the hypothesis that accumulation of ADMA is an important risk factor for cardiovascular disease in chronic renal failure.

The DOQI initiative produced 32 guidelines for peritoneal dialysis. The guidelines on adequate dose of peritoneal dialysis and criteria for starting dialysis treatment constitute the core of the document and are expected to have the most important impact on clinical practice. These guidelines are based mainly on circumstantial evidence and observational studies, thus they must be considered for what they are, i.e. useful operational tools open to discussion and not absolute truth. The potential impact of the DOQI guidelines in a dialysis programme is shown using the anthropometric data of 1061 adult patients on file in the Calabrian Registry of Uremia, Dialysis and Transplantation.

Nocturnal hypoxemia, night-day arterial pressure changes and left ventricular geometry in dialysis patients. It is well established that nocturnal hypoxemia in sleep apnea causes an inversion of the circadian arterial pressure rhythm and triggers nocturnal hypertension. Since sleep apnea is very frequent in dialysis patients, we hypothesized that nocturnal hypoxemia may be a factor that contributes to alter the 24-hour arterial pressure profile in these patients. To test the hypothesis 32 dialysis patients underwent 24-hour blood pressure (BP) monitoring and contin- uous monitoring of arterial O2 saturation during the night-time. Hemo- dialysis patients were studied during the non-dialysis day. All patients underwent an echocardiographic study. Thirteen patients had no episode of nocturnal hypoxemia (group I), 7 had at least one episode overnight but less than 2 episodes/hr (group II) and 12 had $ 2 episodes/hr (group III). The average daytime systolic pressure was similar in the three groups. However, the average nocturnal systolic pressure fell in the first group (22.5 6 4.2%) and rose in the second (12.0 6 3.6%) and in the third (13.9 6 2.2%) group (one way ANOVA, P , 0.005). The relative wall thickness of the left ventricle (RWT) was significantly (P , 0.05) higher in group III than in group I, and in the aggregate (N 5 32) there was an inverse relationship between average nocturnal SaO2 and RWT (r 5 20.43, P 5 0.015). The proportion of patients with concentric remodeling or concentric hypertrophy was higher (P 5 0.05) in the group with a more severe degree of nocturnal hypoxemia (group III, 8 of 12) than in the other two groups (group I, 3 of 13; group II, 2 of 7). Nocturnal hypoxemia is associated with the "non-dipping" arterial pressure profile in dialysis patients. Disturbed respiratory control during the night may represent an important cardiovascular risk factor in dialysis patients. The inability to maintain the circadian profile is an important feature of the altered arterial pressure control in patients with chronic renal failure. Indeed, these patients very frequently fail to show the physiological decrease during night-time ("non-dipping" profile) (1-12). Various hypotheses have been proposed to explain such alteration (2, 4, 5) (see Discussion). We thought that episodes of oxygen desaturation, triggered by sleep apnea, which is very frequent in the dialysis population (13-24; reviewed in 19), could be a contributory factor. Sleep apnea in the general population represents a well established cause of nocturnal hy- pertension (25, 26), and it is frequently associated with primary hypertension (reviewed in 27, 28), as well as with severe cardio- vascular complications (29 -31). Therefore, in this study we sought whether nocturnal hypoxemia is related with altered night-day arterial pressure changes as well as with deranged left ventricular geometry in uremic patients.

Although malnutrition is not uncommon in continuous ambulatory peritoneal dialysis (CAPD) and maintenance hemodialysis (MHD) patients, there has never been a large-scale comparison study of nutritional status with these two dialysis modalities. We therefore assessed protein-calorie nutrition in 224 CAPD patients and 263 MHD patients who were treated in eight centers in Italy. The CAPD patients were slightly older than the MHD patients (60.2 +/- 14.2 years v 56.3 +/- 15.1 years; P < 0.01), had undergone dialysis for less time (2.32 +/- 2.10 years v 3.66 +/- 2.66 years; P < 0.0001), and had higher residual renal function (1.83 +/- 2.29 mL/min v 0.27 +/- 0.91 mL/min; P < 0.0001). Protein nitrogen appearance was 60.5 +/- 16.6 g/d and 61.9 +/- 16.5 g/d in the CAPD and MHD patients, respectively. In CAPD versus MHD patients, serum total protein and albumin tended to be lower; serum transferrin and midarm muscle circumference were similar; and relative body weight, skinfold thickness, and estimated percent body fat tended to be greater. These greater values in CAPD patients were particularly evident in those who were 65 years of age or older. Serum glucose, total cholesterol, and triglycerides also were greater in CAPD patients. The subjective global nutritional assessment indicated a significantly greater proportion of malnourished CAPD patients than MHD patients (42.3% v 30.8%). The greater prevalence of malnutrition in CAPD patients diminished with age. Maintenance hemodialysis patients older than 76 years were more likely to be malnourished than CAPD patients. In patients less than 65 years of age, protein-calorie malnutrition was more likely to be present in CAPD patients than in MHD patients.

We describe a case of prolonged sinus arrest resolved by external cardiac massage following intravenous infusion of dipyridamole, during a thallium myocardial perfusion test. The arrhythmia, presumably due to an acute drug adverse effect, had not been previously described (to our knowledge) as a complication of dipyridamole stress testing.